Molecular basis of structural make-up of feeds in relation to nutrient absorption in ruminants, revealed with advanced molecular spectroscopy: A review on techniques and models

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

Rahman, Md. Mostafizar; Yu, Peiqiang

Progress in ruminant feed research is no more feasible only based on wet chemical analysis, which is merely able to provide information on chemical composition of feeds regardless of their digestive features and nutritive value in ruminants. Studying internal structural make-up of functional groups/feed nutrients is often vital for understanding the digestive behaviors and nutritive values of feeds in ruminant because the intrinsic structure of feed nutrients is more related to its overall absorption. In this article, the detail information on the recent developments in molecular spectroscopic techniques to reveal microstructural information of feed nutrients and the use of nutritionmore » models in regards to ruminant feed research was reviewed. The emphasis of this review was on (1) the technological progress in the use of molecular spectroscopic techniques in ruminant feed research; (2) revealing spectral analysis of functional groups of biomolecules/feed nutrients; (3) the use of advanced nutrition models for better prediction of nutrient availability in ruminant systems; and (4) the application of these molecular techniques and combination of nutrient models in cereals, co-products and pulse crop research. The information described in this article will promote better insight in the progress of research on molecular structural make-up of feed nutrients in ruminants.« less

Postpartum Patient Teaching Success: Implications from Nursing and Patient Perspectives

ERIC Educational Resources Information Center

Day, Dawn

2014-01-01

A recent examination of postpartum patient satisfaction scores in an inner-city hospital revealed decreased satisfaction of discharge teaching practices. Guided by Knowles' model of andragogy and Donabedian's model of structure-process-outcome, the purpose of this study was to gain an understanding of how the structure and process of discharge…

A Structural Model for a Self-Assembled Nanotube Provides Insight into Its Exciton Dynamics

PubMed Central

2016-01-01

The design and synthesis of functional self-assembled nanostructures is frequently an empirical process fraught with critical knowledge gaps about atomic-level structure in these noncovalent systems. Here, we report a structural model for a semiconductor nanotube formed via the self-assembly of naphthalenediimide-lysine (NDI-Lys) building blocks determined using experimental 13C–13C and 13C–15N distance restraints from solid-state nuclear magnetic resonance supplemented by electron microscopy and X-ray powder diffraction data. The structural model reveals a two-dimensional-crystal-like architecture of stacked monolayer rings each containing ∼50 NDI-Lys molecules, with significant π-stacking interactions occurring both within the confines of the ring and along the long axis of the tube. Excited-state delocalization and energy transfer are simulated for the nanotube based on time-dependent density functional theory and an incoherent hopping model. Remarkably, these calculations reveal efficient energy migration from the excitonic bright state, which is in agreement with the rapid energy transfer within NDI-Lys nanotubes observed previously using fluorescence spectroscopy. PMID:26120375

Crustal modeling of the central part of the Northern Western Desert, Egypt using gravity data

NASA Astrophysics Data System (ADS)

Alrefaee, H. A.

2017-05-01

The Bouguer anomaly map of the central part of the Northern Western Desert, Egypt was used to construct six 2D gravity models to investigate the nature, physical properties and structures of the crust and upper mantle. The crustal models were constrained and constructed by integrating results from different geophysical techniques and available geological information. The depth to the basement surface, from eight wells existed across the study area, and the depth to the Conrad and Moho interfaces as well as physical properties of sediments, basement, crust and upper mantle from previous petrophysical and crustal studies were used to establish the gravity models. Euler deconvolution technique was carried on the Bouguer anomaly map to detect the subsurface fault trends. Edge detection techniques were calculated to outlines the boundaries of subsurface structural features. Basement structural map was interpreted to reveal the subsurface structural setting of the area. The crustal models reveals increasing of gravity field from the south to the north due to northward thinning of the crust. The models reveals also deformed and rugged basement surface with northward depth increasing from 1.6 km to 6 km. In contrast to the basement, the Conrad and Moho interfaces are nearly flat and get shallower northward where the depth to the Conrad or the thickness of the upper crust ranges from 18 km to 21 km while the depth to the Moho (crustal thickness) ranges from 31.5 km to 34 km. The crust beneath the study area is normal continental crust with obvious thinning toward the continental margin at the Mediterranean coast.

Diverse binding site structures revealed in homology models of polyreactive immunoglobulins

NASA Astrophysics Data System (ADS)

Ramsland, Paul A.; Guddat, Luke W.; Edmundson, Allen B.; Raison, Robert L.

1997-09-01

We describe here computer-assisted homology models of the combiningsite structure of three polyreactive immunoglobulins. Template-based modelsof Fv (VL-VH) fragments were derived forthe surface IgM expressed by the malignant CD5 positive B cells from threepatients with chronic lymphocytic leukaemia (CLL). The conserved frameworkregions were constructed using crystal coordinates taken from highlyhomologous human variable domain structures (Pot and Hil). Complementaritydetermining regions (CDRs) were predicted by grafting loops, taken fromknown immunoglobulin structures, onto the Fv framework models. The CDRtemplates were chosen, where possible, to be of the same length and of highresidue identity or similarity. LCDR1, 2 and 3 as well as HCDR1 and 2 forthe Fv were constructed using this strategy. For HCDR3 prediction, adatabase containing the Cartesian coordinates of 30 of these loops wascompiled from unliganded antibody X-ray crystallographic structures and anHCDR3 of the same length as that of the B CLL Fv was selected as a template.In one case (Yar), the resulting HCDR3 model gave unfavourable interactionswhen incorporated into the Fv model. This HCDR3 was therefore modelled usingan alternative strategy of construction of the loop stems, using apreviously described HCDR3 conformation (Pot), followed by chain closurewith a β-turn. The template models were subjected to positionalrefinement using energy minimisation and molecular dynamics simulations(X-PLOR). An electrostatic surface description (GRASP) did not reveal acommon structural feature within the binding sites of the three polyreactiveFv. Thus, polyreactive immunoglobulins may recognise similar and multipleantigens through a diverse array of binding site structures.

Structure-function insights of membrane and soluble proteins revealed by electron crystallography.

PubMed

Dreaden, Tina M; Devarajan, Bharanidharan; Barry, Bridgette A; Schmidt-Krey, Ingeborg

2013-01-01

Electron crystallography is emerging as an important method in solving protein structures. While it has found extensive applications in the understanding of membrane protein structure and function at a wide range of resolutions, from revealing oligomeric arrangements to atomic models, electron crystallography has also provided invaluable information on the soluble α/β-tubulin which could not be obtained by any other method to date. Examples of critical insights from selected structures of membrane proteins as well as α/β-tubulin are described here, demonstrating the vast potential of electron crystallography that is first beginning to unfold.

Transcriptome mining and in silico structural and functional analysis of ascorbic acid and tartaric acid biosynthesis pathway enzymes in rose-scanted geranium.

PubMed

Narnoliya, Lokesh K; Sangwan, Rajender S; Singh, Sudhir P

2018-06-01

Rose-scented geranium (Pelargonium sp.) is widely known as aromatic and medicinal herb, accumulating specialized metabolites of high economic importance, such as essential oils, ascorbic acid, and tartaric acid. Ascorbic acid and tartaric acid are multifunctional metabolites of human value to be used as vital antioxidants and flavor enhancing agents in food products. No information is available related to the structural and functional properties of the enzymes involved in ascorbic acid and tartaric acid biosynthesis in rose-scented geranium. In the present study, transcriptome mining was done to identify full-length genes, followed by their bioinformatic and molecular modeling investigations and understanding of in silico structural and functional properties of these enzymes. Evolutionary conserved domains were identified in the pathway enzymes. In silico physicochemical characterization of the catalytic enzymes revealed isoelectric point (pI), instability index, aliphatic index, and grand average hydropathy (GRAVY) values of the enzymes. Secondary structural prediction revealed abundant proportion of alpha helix and random coil confirmations in the pathway enzymes. Three-dimensional homology models were developed for these enzymes. The predicted structures showed significant structural similarity with their respective templates in root mean square deviation analysis. Ramachandran plot analysis of the modeled enzymes revealed that more than 84% of the amino acid residues were within the favored regions. Further, functionally important residues were identified corresponding to catalytic sites located in the enzymes. To, our best knowledge, this is the first report which provides a foundation on functional annotation and structural determination of ascorbic acid and tartaric acid pathway enzymes in rose-scanted geranium.

Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering.

PubMed

Costenaro, Lionel; Grossmann, J Günter; Ebel, Christine; Maxwell, Anthony

2007-03-01

DNA gyrase, the only topoisomerase able to introduce negative supercoils into DNA, is essential for bacterial transcription and replication; absent from humans, it is a successful target for antibacterials. From biophysical experiments in solution, we report a structural model at approximately 12-15 A resolution of the full-length B subunit (GyrB). Analytical ultracentrifugation shows that GyrB is mainly a nonglobular monomer. Ab initio modeling of small-angle X-ray scattering data for GyrB consistently yields a "tadpole"-like envelope. It allows us to propose an organization of GyrB into three domains-ATPase, Toprim, and Tail-based on their crystallographic and modeled structures. Our study reveals the modular organization of GyrB and points out its potential flexibility, needed during the gyrase catalytic cycle. It provides important insights into the supercoiling mechanism by gyrase and suggests new lines of research.

Three-dimensional structure of basal body triplet revealed by electron cryo-tomography

PubMed Central

Li, Sam; Fernandez, Jose-Jesus; Marshall, Wallace F; Agard, David A

2012-01-01

Basal bodies and centrioles play central roles in microtubule (MT)-organizing centres within many eukaryotes. They share a barrel-shaped cylindrical structure composed of nine MT triplet blades. Here, we report the structure of the basal body triplet at 33 Å resolution obtained by electron cryo-tomography and 3D subtomogram averaging. By fitting the atomic structure of tubulin into the EM density, we built a pseudo-atomic model of the tubulin protofilaments at the core of the triplet. The 3D density map reveals additional densities that represent non-tubulin proteins attached to the triplet, including a large inner circular structure in the basal body lumen, which functions as a scaffold to stabilize the entire basal body barrel. We found clear longitudinal structural variations along the basal body, suggesting a sequential and coordinated assembly mechanism. We propose a model in which δ-tubulin and other components participate in the assembly of the basal body. PMID:22157822

The Internal Structure of Positive and Negative Affect: A Confirmatory Factor Analysis of the PANAS

ERIC Educational Resources Information Center

Tuccitto, Daniel E.; Giacobbi, Peter R., Jr.; Leite, Walter L.

2010-01-01

This study tested five confirmatory factor analytic (CFA) models of the Positive Affect Negative Affect Schedule (PANAS) to provide validity evidence based on its internal structure. A sample of 223 club sport athletes indicated their emotions during the past week. Results revealed that an orthogonal two-factor CFA model, specifying error…

Social coordination in animal vocal interactions. Is there any evidence of turn-taking? The starling as an animal model

PubMed Central

Henry, Laurence; Craig, Adrian J. F. K.; Lemasson, Alban; Hausberger, Martine

2015-01-01

Turn-taking in conversation appears to be a common feature in various human cultures and this universality raises questions about its biological basis and evolutionary trajectory. Functional convergence is a widespread phenomenon in evolution, revealing sometimes striking functional similarities between very distant species even though the mechanisms involved may be different. Studies on mammals (including non-human primates) and bird species with different levels of social coordination reveal that temporal and structural regularities in vocal interactions may depend on the species' social structure. Here we test the hypothesis that turn-taking and associated rules of conversations may be an adaptive response to the requirements of social life, by testing the applicability of turn-taking rules to an animal model, the European starling. Birdsong has for many decades been considered as one of the best models of human language and starling songs have been well described in terms of vocal production and perception. Starlings do have vocal interactions where alternating patterns predominate. Observational and experimental data on vocal interactions reveal that (1) there are indeed clear temporal and structural regularities, (2) the temporal and structural patterning is influenced by the immediate social context, the general social situation, the individual history, and the internal state of the emitter. Comparison of phylogenetically close species of Sturnids reveals that the alternating pattern of vocal interactions varies greatly according to the species' social structure, suggesting that interactional regularities may have evolved together with social systems. These findings lead to solid bases of discussion on the evolution of communication rules in relation to social evolution. They will be discussed also in terms of processes, at the light of recent neurobiological findings. PMID:26441787

Exploratory graphical models of functional and structural connectivity patterns for Alzheimer's Disease diagnosis.

PubMed

Ortiz, Andrés; Munilla, Jorge; Álvarez-Illán, Ignacio; Górriz, Juan M; Ramírez, Javier

2015-01-01

Alzheimer's Disease (AD) is the most common neurodegenerative disease in elderly people. Its development has been shown to be closely related to changes in the brain connectivity network and in the brain activation patterns along with structural changes caused by the neurodegenerative process. Methods to infer dependence between brain regions are usually derived from the analysis of covariance between activation levels in the different areas. However, these covariance-based methods are not able to estimate conditional independence between variables to factor out the influence of other regions. Conversely, models based on the inverse covariance, or precision matrix, such as Sparse Gaussian Graphical Models allow revealing conditional independence between regions by estimating the covariance between two variables given the rest as constant. This paper uses Sparse Inverse Covariance Estimation (SICE) methods to learn undirected graphs in order to derive functional and structural connectivity patterns from Fludeoxyglucose (18F-FDG) Position Emission Tomography (PET) data and segmented Magnetic Resonance images (MRI), drawn from the ADNI database, for Control, MCI (Mild Cognitive Impairment Subjects), and AD subjects. Sparse computation fits perfectly here as brain regions usually only interact with a few other areas. The models clearly show different metabolic covariation patters between subject groups, revealing the loss of strong connections in AD and MCI subjects when compared to Controls. Similarly, the variance between GM (Gray Matter) densities of different regions reveals different structural covariation patterns between the different groups. Thus, the different connectivity patterns for controls and AD are used in this paper to select regions of interest in PET and GM images with discriminative power for early AD diagnosis. Finally, functional an structural models are combined to leverage the classification accuracy. The results obtained in this work show the usefulness of the Sparse Gaussian Graphical models to reveal functional and structural connectivity patterns. This information provided by the sparse inverse covariance matrices is not only used in an exploratory way but we also propose a method to use it in a discriminative way. Regression coefficients are used to compute reconstruction errors for the different classes that are then introduced in a SVM for classification. Classification experiments performed using 68 Controls, 70 AD, and 111 MCI images and assessed by cross-validation show the effectiveness of the proposed method.

Statistical physics approaches to Alzheimer's disease

NASA Astrophysics Data System (ADS)

Peng, Shouyong

Alzheimer's disease (AD) is the most common cause of late life dementia. In the brain of an AD patient, neurons are lost and spatial neuronal organizations (microcolumns) are disrupted. An adequate quantitative analysis of microcolumns requires that we automate the neuron recognition stage in the analysis of microscopic images of human brain tissue. We propose a recognition method based on statistical physics. Specifically, Monte Carlo simulations of an inhomogeneous Potts model are applied for image segmentation. Unlike most traditional methods, this method improves the recognition of overlapped neurons, and thus improves the overall recognition percentage. Although the exact causes of AD are unknown, as experimental advances have revealed the molecular origin of AD, they have continued to support the amyloid cascade hypothesis, which states that early stages of aggregation of amyloid beta (Abeta) peptides lead to neurodegeneration and death. X-ray diffraction studies reveal the common cross-beta structural features of the final stable aggregates-amyloid fibrils. Solid-state NMR studies also reveal structural features for some well-ordered fibrils. But currently there is no feasible experimental technique that can reveal the exact structure or the precise dynamics of assembly and thus help us understand the aggregation mechanism. Computer simulation offers a way to understand the aggregation mechanism on the molecular level. Because traditional all-atom continuous molecular dynamics simulations are not fast enough to investigate the whole aggregation process, we apply coarse-grained models and discrete molecular dynamics methods to increase the simulation speed. First we use a coarse-grained two-bead (two beads per amino acid) model. Simulations show that peptides can aggregate into multilayer beta-sheet structures, which agree with X-ray diffraction experiments. To better represent the secondary structure transition happening during aggregation, we refine the model to four beads per amino acid. Typical essential interactions, such as backbone hydrogen bond, hydrophobic and electrostatic interactions, are incorporated into our model. We study the aggregation of Abeta16-22, a peptide that can aggregate into a well-ordered fibrillar structure in experiments. Our results show that randomly-oriented monomers can aggregate into fibrillar subunits, which agree not only with X-ray diffraction experiments but also with solid-state NMR studies. Our findings demonstrate that coarse-grained models and discrete molecular dynamics simulations can help researchers understand the aggregation mechanism of amyloid peptides.

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.

An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.

PubMed

Schur, Florian K M; Obr, Martin; Hagen, Wim J H; Wan, William; Jakobi, Arjen J; Kirkpatrick, Joanna M; Sachse, Carsten; Kräusslich, Hans-Georg; Briggs, John A G

2016-07-29

Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs. We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra- and intermolecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease. We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1. Copyright © 2016, American Association for the Advancement of Science.

The utility of the bifactor model in understanding unique components of anxiety sensitivity in a South Korean sample.

PubMed

Ebesutani, Chad; Kim, Mirihae; Park, Hee-Hoon

2016-08-01

The present study was the first to examine the applicability of the bifactor structure underlying the Anxiety Sensitivity Index-3 (ASI-3) in an East Asian (South Korean) sample and to determine which factors in the bifactor model were significantly associated with anxiety, depression, and negative affect. Using a sample of 289 South Korean university students, we compared (a) the original 3-factor AS model, (b) a 3-group bifactor AS model, and (c) a 2-group bifactor AS model (with only the physical and social concern group factors present). Results revealed that the 2-group bifactor AS model fit the ASI-3 data the best. Relatedly, although all ASI-3 items loaded on the general AS factor, the Cognitive Concern group factor was not defined in the bifactor model and may therefore need to be omitted in order to accurately model AS when conducting factor analysis and structural equation modeling (SEM) in cross cultural contexts. SEM results also revealed that the general AS factor was the only factor from the 2-group bifactor model that significantly predicted anxiety, depression, and negative affect. Implications and importance of this new bifactor structure of Anxiety Sensitivity in East Asian samples are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Connections between Concepts Revealed by the Electronic Structure of Carbon Monoxide

ERIC Educational Resources Information Center

Liu, Ying; Liu, Bihui; Liu, Yue; Drew, Michael G. B.

2012-01-01

Different models for the electronic structure of carbon monoxide are suggested in influential textbooks. Therefore, this electronic structure offers an interesting subject in teaching because it can be used as an example to relate seemingly conflicting concepts. Understanding the connections between ostensibly different methods and between…

Atomic structures of B20 FeGe thin films grown on the Si(111) surface

NASA Astrophysics Data System (ADS)

Kim, Wondong; Noh, Seungkyun; Yoon, Jisoo; Kim, Young Heon; Lee, Inho; Kim, Jae-Sung; Hwang, Chanyong

We investigated the growth and atomic structures of FeGe thin films on the Si (111) surface by using scanning tunneling microscopy (STM) and transmission electron microscopy (TEM). The 2 5nm- thick FeGe thin films were prepared on the clean Si(111) 7x7 surface by co-deposition of Fe and Ge from separated electron-beam evaporators. With direct deposition on the substrate at the temperature above 550 K, the surface of FeGe films was not smooth and consisted of coarse grains. By the combination of room-temperature annealing and post-annealing process around 800 K, the structure of FeGe thin films evolved into the well crystalized structures. Atom-resolved STM images revealed that there are at least four different surface terminations. We constructed atomic models for each surface terminations based on the bulk atomic arrangement of a B20 chiral structure and confirmed that the observed STM images are successfully reproduced by using computational simulations employing Vienna Ab Initio Simulation package (VASP) with a B20 chiral structure model. TEM cross-sectional images also support our atomic models by revealing clearly the characteristic zigzag features of B20 structures of FeGe(111) thin films.

Determinants of cation transport selectivity: Equilibrium binding and transport kinetics

PubMed Central

2015-01-01

The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport processes. However, these structures, in and of themselves, do not reveal equilibrium selectivity or transport preferences, which can be discerned only from various functional assays. In this Review, I explore the relationship between cation transport protein structures, equilibrium binding measurements, and ion transport selectivity. The primary focus is on K+-selective channels and nonselective cation channels because they have been extensively studied both functionally and structurally, but the principles discussed are relevant to other transport proteins and molecules. PMID:26078056

Northeastern Brazilian margin: Regional tectonic evolution based on integrated analysis of seismic reflection and potential field data and modelling

NASA Astrophysics Data System (ADS)

Blaich, Olav A.; Tsikalas, Filippos; Faleide, Jan Inge

2008-10-01

Integration of regional seismic reflection and potential field data along the northeastern Brazilian margin, complemented by crustal-scale gravity modelling, is used to reveal and illustrate onshore-offshore crustal structure correlation, the character of the continent-ocean boundary, and the relationship of crustal structure to regional variation of potential field anomalies. The study reveals distinct along-margin structural and magmatic changes that are spatially related to a number of conjugate Brazil-West Africa transfer systems, governing the margin segmentation and evolution. Several conceptual tectonic models are invoked to explain the structural evolution of the different margin segments in a conjugate margin context. Furthermore, the constructed transects, the observed and modelled Moho relief, and the potential field anomalies indicate that the Recôncavo, Tucano and Jatobá rift system may reflect a polyphase deformation rifting-mode associated with a complex time-dependent thermal structure of the lithosphere. The constructed transects and available seismic reflection profiles, indicate that the northern part of the study area lacks major breakup-related magmatic activity, suggesting a rifted non-volcanic margin affinity. In contrast, the southern part of the study area is characterized by abrupt crustal thinning and evidence for breakup magmatic activity, suggesting that this region evolved, partially, with a rifted volcanic margin affinity and character.

High School Students' Epistemological Beliefs, Conceptions of Learning, and Self-Efficacy for Learning Biology: A Study of Their Structural Models

ERIC Educational Resources Information Center

Sadi, Özlem; Dagyar, Miray

2015-01-01

The current work reveals the data of the study which examines the relationships among epistemological beliefs, conceptions of learning, and self-efficacy for biology learning with the help of the Structural Equation Modeling. Three questionnaires, the Epistemological Beliefs, the Conceptions of Learning Biology and the Self-efficacy for Learning…

Using discharge data to reduce structural deficits in a hydrological model with a Bayesian inference approach and the implications for the prediction of critical source areas

NASA Astrophysics Data System (ADS)

Frey, M. P.; Stamm, C.; Schneider, M. K.; Reichert, P.

2011-12-01

A distributed hydrological model was used to simulate the distribution of fast runoff formation as a proxy for critical source areas for herbicide pollution in a small agricultural catchment in Switzerland. We tested to what degree predictions based on prior knowledge without local measurements could be improved upon relying on observed discharge. This learning process consisted of five steps: For the prior prediction (step 1), knowledge of the model parameters was coarse and predictions were fairly uncertain. In the second step, discharge data were used to update the prior parameter distribution. Effects of uncertainty in input data and model structure were accounted for by an autoregressive error model. This step decreased the width of the marginal distributions of parameters describing the lower boundary (percolation rates) but hardly affected soil hydraulic parameters. Residual analysis (step 3) revealed model structure deficits. We modified the model, and in the subsequent Bayesian updating (step 4) the widths of the posterior marginal distributions were reduced for most parameters compared to those of the prior. This incremental procedure led to a strong reduction in the uncertainty of the spatial prediction. Thus, despite only using spatially integrated data (discharge), the spatially distributed effect of the improved model structure can be expected to improve the spatially distributed predictions also. The fifth step consisted of a test with independent spatial data on herbicide losses and revealed ambiguous results. The comparison depended critically on the ratio of event to preevent water that was discharged. This ratio cannot be estimated from hydrological data only. The results demonstrate that the value of local data is strongly dependent on a correct model structure. An iterative procedure of Bayesian updating, model testing, and model modification is suggested.

Modeling the full length HIV-1 Gag polyprotein reveals the role of its p6 subunit in viral maturation and the effect of non-cleavage site mutations in protease drug resistance.

PubMed

Su, Chinh Tran-To; Kwoh, Chee-Keong; Verma, Chandra Shekhar; Gan, Samuel Ken-En

2017-12-27

HIV polyprotein Gag is increasingly found to contribute to protease inhibitor resistance. Despite its role in viral maturation and in developing drug resistance, there remain gaps in the knowledge of the role of certain Gag subunits (e.g. p6), and that of non-cleavage mutations in drug resistance. As p6 is flexible, it poses a problem for structural experiments, and is hence often omitted in experimental Gag structural studies. Nonetheless, as p6 is an indispensable component for viral assembly and maturation, we have modeled the full length Gag structure based on several experimentally determined constraints and studied its structural dynamics. Our findings suggest that p6 can mechanistically modulate Gag conformations. In addition, the full length Gag model reveals that allosteric communication between the non-cleavage site mutations and the first Gag cleavage site could possibly result in protease drug resistance, particularly in the absence of mutations in Gag cleavage sites. Our study provides a mechanistic understanding to the structural dynamics of HIV-1 Gag, and also proposes p6 as a possible drug target in anti-HIV therapy.

Structure and organization of heteromeric AMPA-type glutamate receptors.

PubMed

Herguedas, Beatriz; García-Nafría, Javier; Cais, Ondrej; Fernández-Leiro, Rafael; Krieger, James; Ho, Hinze; Greger, Ingo H

2016-04-29

AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling. Copyright © 2016, American Association for the Advancement of Science.

Parallel Large-Scale Molecular Dynamics Simulation Opens New Perspective to Clarify the Effect of a Porous Structure on the Sintering Process of Ni/YSZ Multiparticles.

PubMed

Xu, Jingxiang; Higuchi, Yuji; Ozawa, Nobuki; Sato, Kazuhisa; Hashida, Toshiyuki; Kubo, Momoji

2017-09-20

Ni sintering in the Ni/YSZ porous anode of a solid oxide fuel cell changes the porous structure, leading to degradation. Preventing sintering and degradation during operation is a great challenge. Usually, a sintering molecular dynamics (MD) simulation model consisting of two particles on a substrate is used; however, the model cannot reflect the porous structure effect on sintering. In our previous study, a multi-nanoparticle sintering modeling method with tens of thousands of atoms revealed the effect of the particle framework and porosity on sintering. However, the method cannot reveal the effect of the particle size on sintering and the effect of sintering on the change in the porous structure. In the present study, we report a strategy to reveal them in the porous structure by using our multi-nanoparticle modeling method and a parallel large-scale multimillion-atom MD simulator. We used this method to investigate the effect of YSZ particle size and tortuosity on sintering and degradation in the Ni/YSZ anodes. Our parallel large-scale MD simulation showed that the sintering degree decreased as the YSZ particle size decreased. The gas fuel diffusion path, which reflects the overpotential, was blocked by pore coalescence during sintering. The degradation of gas diffusion performance increased as the YSZ particle size increased. Furthermore, the gas diffusion performance was quantified by a tortuosity parameter and an optimal YSZ particle size, which is equal to that of Ni, was found for good diffusion after sintering. These findings cannot be obtained by previous MD sintering studies with tens of thousands of atoms. The present parallel large-scale multimillion-atom MD simulation makes it possible to clarify the effects of the particle size and tortuosity on sintering and degradation.

Use of airborne lidar data to improve plant species richness and diversity monitoring in lowland and mountain forests

PubMed Central

Durrieu, Sylvie; Gosselin, Frédéric; Herpigny, Basile

2017-01-01

We explored the potential of airborne laser scanner (ALS) data to improve Bayesian models linking biodiversity indicators of the understory vegetation to environmental factors. Biodiversity was studied at plot level and models were built to investigate species abundance for the most abundant plants found on each study site, and for ecological group richness based on light preference. The usual abiotic explanatory factors related to climate, topography and soil properties were used in the models. ALS data, available for two contrasting study sites, were used to provide biotic factors related to forest structure, which was assumed to be a key driver of understory biodiversity. Several ALS variables were found to have significant effects on biodiversity indicators. However, the responses of biodiversity indicators to forest structure variables, as revealed by the Bayesian model outputs, were shown to be dependent on the abiotic environmental conditions characterizing the study areas. Lower responses were observed on the lowland site than on the mountainous site. In the latter, shade-tolerant and heliophilous species richness was impacted by vegetation structure indicators linked to light penetration through the canopy. However, to reveal the full effects of forest structure on biodiversity indicators, forest structure would need to be measured over much wider areas than the plot we assessed. It seems obvious that the forest structure surrounding the field plots can impact biodiversity indicators measured at plot level. Various scales were found to be relevant depending on: the biodiversity indicators that were modelled, and the ALS variable. Finally, our results underline the utility of lidar data in abundance and richness models to characterize forest structure with variables that are difficult to measure in the field, either due to their nature or to the size of the area they relate to. PMID:28902920

The dynamics of aloof baby Skyrmions

DOE PAGES

Salmi, Petja; Sutcliffe, Paul

2016-01-25

The aloof baby Skyrme model is a (2+1)-dimensional theory with solitons that are lightly bound. It is a low-dimensional analogue of a similar Skyrme model in (3+1)- dimensions, where the lightly bound solitons have binding energies comparable to nuclei. A previous study of static solitons in the aloof baby Skyrme model revealed that multi-soliton bound states have a cluster structure, with constituents that preserve their individual identities due to the short-range repulsion and long-range attraction between solitons. Furthermore, there are many different local energy minima that are all well-described by a simple binary species particle model. In this paper wemore » present the first results on soliton dynamics in the aloof baby Skyrme model. Numerical field theory simulations reveal that the lightly bound cluster structure results in a variety of exotic soliton scattering events that are novel in comparison to standard Skyrmion scattering. A dynamical version of the binary species point particle model is shown to provide a good qualitative description of the dynamics.« less

The dynamics of aloof baby Skyrmions

NASA Astrophysics Data System (ADS)

Salmi, Petja; Sutcliffe, Paul

2016-01-01

The aloof baby Skyrme model is a (2+1)-dimensional theory with solitons that are lightly bound. It is a low-dimensional analogue of a similar Skyrme model in (3+1)-dimensions, where the lightly bound solitons have binding energies comparable to nuclei. A previous study of static solitons in the aloof baby Skyrme model revealed that multi-soliton bound states have a cluster structure, with constituents that preserve their individual identities due to the short-range repulsion and long-range attraction between solitons. Furthermore, there are many different local energy minima that are all well-described by a simple binary species particle model. In this paper we present the first results on soliton dynamics in the aloof baby Skyrme model. Numerical field theory simulations reveal that the lightly bound cluster structure results in a variety of exotic soliton scattering events that are novel in comparison to standard Skyrmion scattering. A dynamical version of the binary species point particle model is shown to provide a good qualitative description of the dynamics.

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

Salmi, Petja; Sutcliffe, Paul

The aloof baby Skyrme model is a (2+1)-dimensional theory with solitons that are lightly bound. It is a low-dimensional analogue of a similar Skyrme model in (3+1)- dimensions, where the lightly bound solitons have binding energies comparable to nuclei. A previous study of static solitons in the aloof baby Skyrme model revealed that multi-soliton bound states have a cluster structure, with constituents that preserve their individual identities due to the short-range repulsion and long-range attraction between solitons. Furthermore, there are many different local energy minima that are all well-described by a simple binary species particle model. In this paper wemore » present the first results on soliton dynamics in the aloof baby Skyrme model. Numerical field theory simulations reveal that the lightly bound cluster structure results in a variety of exotic soliton scattering events that are novel in comparison to standard Skyrmion scattering. A dynamical version of the binary species point particle model is shown to provide a good qualitative description of the dynamics.« less

Identification of the Ah-Receptor Structural Determinants for Ligand Preferences

PubMed Central

Xing, Yongna

2012-01-01

The aryl hydrocarbon receptor (AHR) is a transcription factor that responds to diverse ligands and plays a critical role in toxicology, immune function, and cardiovascular physiology. The structural basis of the AHR for ligand promiscuity and preferences is critical for understanding AHR function. Based on the structure of a closely related protein HIF2α, we modeled the AHR ligand binding domain (LBD) bound to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzo(a)pyrene (BaP) and identified residues that control ligand preferences by shape and H-bond potential. Mutations to these residues, particularly Q377 and G298, resulted in robust and opposite changes in the potency of TCDD and BaP and up to a 20-fold change in the ratio of TCDD/BaP efficacy. The model also revealed a flexible “belt” structure; molecular dynamic (MD) simulation suggested that the “belt” and several other structural elements in the AHR-LBD are more flexible than HIF2α and likely contribute to ligand promiscuity. Molecular docking of TCDD congeners to a model of human AHR-LBD ranks their binding affinity similar to experimental ranking of their toxicity. Our study reveals key structural basis for prediction of toxicity and understanding the AHR signaling through diverse ligands. PMID:22659362

Complete protein-protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling

NASA Astrophysics Data System (ADS)

Plattner, Nuria; Doerr, Stefan; de Fabritiis, Gianni; Noé, Frank

2017-10-01

Protein-protein association is fundamental to many life processes. However, a microscopic model describing the structures and kinetics during association and dissociation is lacking on account of the long lifetimes of associated states, which have prevented efficient sampling by direct molecular dynamics (MD) simulations. Here we demonstrate protein-protein association and dissociation in atomistic resolution for the ribonuclease barnase and its inhibitor barstar by combining adaptive high-throughput MD simulations and hidden Markov modelling. The model reveals experimentally consistent intermediate structures, energetics and kinetics on timescales from microseconds to hours. A variety of flexibly attached intermediates and misbound states funnel down to a transition state and a native basin consisting of the loosely bound near-native state and the tightly bound crystallographic state. These results offer a deeper level of insight into macromolecular recognition and our approach opens the door for understanding and manipulating a wide range of macromolecular association processes.

Uncovering the influence of social skills and psychosociological factors on pain sensitivity using structural equation modeling.

PubMed

Tanaka, Yoichi; Nishi, Yuki; Nishi, Yuki; Osumi, Michihiro; Morioka, Shu

2017-01-01

Pain is a subjective emotional experience that is influenced by psychosociological factors such as social skills, which are defined as problem-solving abilities in social interactions. This study aimed to reveal the relationships among pain, social skills, and other psychosociological factors by using structural equation modeling. A total of 101 healthy volunteers (41 men and 60 women; mean age: 36.6±12.7 years) participated in this study. To evoke participants' sense of inner pain, we showed them images of painful scenes on a PC screen and asked them to evaluate the pain intensity by using the visual analog scale (VAS). We examined the correlation between social skills and VAS, constructed a hypothetical model based on results from previous studies and the current correlational analysis results, and verified the model's fit using structural equation modeling. We found significant positive correlations between VAS and total social skills values, as well as between VAS and the "start of relationships" subscales. Structural equation modeling revealed that the values for "start of relationships" had a direct effect on VAS values (path coefficient =0.32, p <0.01). In addition, the "start of relationships" had both a direct and an indirect effect on psychological factors via social support. The results indicated that extroverted people are more sensitive to inner pain and tend to get more social support and maintain a better psychological condition.

Analytical coupled-wave model for photonic crystal surface-emitting quantum cascade lasers.

PubMed

Wang, Zhixin; Liang, Yong; Yin, Xuefan; Peng, Chao; Hu, Weiwei; Faist, Jérôme

2017-05-15

An analytical coupled-wave model is developed for surface-emitting photonic-crystal quantum cascade lasers (PhC-QCLs). This model provides an accurate and efficient analysis of full three-dimensional device structure with large-area cavity size. Various laser properties of interest including the band structure, mode frequency, cavity loss, mode intensity profile, and far field pattern (FFP), as well as their dependence on PhC structures and cavity size, are investigated. Comparison with numerical simulations confirms the accuracy and validity of our model. The calculated FFP and polarization profile well explain the previously reported experimental results. In particular, we reveal the possibility of switching the lasing modes and generating single-lobed FFP by properly tuning PhC structures.

Transitional circuitry for studying the properties of DNA

NASA Astrophysics Data System (ADS)

Trubochkina, N.

2018-01-01

The article is devoted to a new view of the structure of DNA as an intellectual scheme possessing the properties of logic and memory. The theory of transient circuitry, developed by the author for optimal computer circuits, revealed an amazing structural similarity between mathematical models of transition silicon elements and logic and memory circuits of solid state transient circuitry and atomic models of parts of DNA.

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans.

PubMed

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C G; Benavente, Ricardo

2012-10-09

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans.

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans

PubMed Central

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C. G.; Benavente, Ricardo

2012-01-01

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans. PMID:23012415

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

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

Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko

2013-11-20

Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

Correlations in Scattered X-Ray Laser Pulses Reveal Nanoscale Structural Features of Viruses

NASA Astrophysics Data System (ADS)

Kurta, Ruslan P.; Donatelli, Jeffrey J.; Yoon, Chun Hong; Berntsen, Peter; Bielecki, Johan; Daurer, Benedikt J.; DeMirci, Hasan; Fromme, Petra; Hantke, Max Felix; Maia, Filipe R. N. C.; Munke, Anna; Nettelblad, Carl; Pande, Kanupriya; Reddy, Hemanth K. N.; Sellberg, Jonas A.; Sierra, Raymond G.; Svenda, Martin; van der Schot, Gijs; Vartanyants, Ivan A.; Williams, Garth J.; Xavier, P. Lourdu; Aquila, Andrew; Zwart, Peter H.; Mancuso, Adrian P.

2017-10-01

We use extremely bright and ultrashort pulses from an x-ray free-electron laser (XFEL) to measure correlations in x rays scattered from individual bioparticles. This allows us to go beyond the traditional crystallography and single-particle imaging approaches for structure investigations. We employ angular correlations to recover the three-dimensional (3D) structure of nanoscale viruses from x-ray diffraction data measured at the Linac Coherent Light Source. Correlations provide us with a comprehensive structural fingerprint of a 3D virus, which we use both for model-based and ab initio structure recovery. The analyses reveal a clear indication that the structure of the viruses deviates from the expected perfect icosahedral symmetry. Our results anticipate exciting opportunities for XFEL studies of the structure and dynamics of nanoscale objects by means of angular correlations.

Structural elucidation of transmembrane domain zero (TMD0) of EcdL: A multidrug resistance-associated protein (MRP) family of ATP-binding cassette transporter protein revealed by atomistic simulation.

PubMed

Bera, Krishnendu; Rani, Priyanka; Kishor, Gaurav; Agarwal, Shikha; Kumar, Antresh; Singh, Durg Vijay

2017-09-20

ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein of Aspergillus rugulosus are encoded by the same cluster of genes. Co-expression of EcdL and echinocandinB reflects tightly linked biological functions. EcdL belongs to Multidrug Resistance associated Protein (MRP) subfamily of ABC transporters with an extra transmembrane domain zero (TMD0). Complete structure of MRP subfamily comprising of TMD0 domain, at atomic resolution is not known. We hypothesized that the transportation of echonocandinB is mediated via EcdL protein. Henceforth, it is pertinent to know the topological arrangement of TMD0, with other domains of protein and its possible role in transportation of echinocandinB. Absence of effective template for TMD0 domain lead us to model by I-TASSER, further structure has been refined by multiple template modelling using homologous templates of remaining domains (TMD1, NBD1, TMD2, NBD2). The modelled structure has been validated for packing, folding and stereochemical properties. MD simulation for 0.1 μs has been carried out in the biphasic environment for refinement of modelled protein. Non-redundant structures have been excavated by clustering of MD trajectory. The structural alignment of modelled structure has shown Z-score -37.9; 31.6, 31.5 with RMSD; 2.4, 4.2, 4.8 with ABC transporters; PDB ID 4F4C, 4M1 M, 4M2T, respectively, reflecting the correctness of structure. EchinocandinB has been docked to the modelled as well as to the clustered structures, which reveals interaction of echinocandinB with TMD0 and other TM helices in the translocation path build of TMDs.

Geophysical data reveal the crustal structure of the Alaska Range orogen within the aftershock zone of the Mw 7.9 Denali fault earthquake

USGS Publications Warehouse

Fisher, M.A.; Ratchkovski, N.A.; Nokleberg, W.J.; Pellerin, L.; Glen, J.M.G.

2004-01-01

Geophysical information, including deep-crustal seismic reflection, magnetotelluric (MT), gravity, and magnetic data, cross the aftershock zone of the 3 November 2002 Mw 7.9 Denali fault earthquake. These data and aftershock seismicity, jointly interpreted, reveal the crustal structure of the right-lateral-slip Denali fault and the eastern Alaska Range orogen, as well as the relationship between this structure and seismicity. North of the Denali fault, strong seismic reflections from within the Alaska Range orogen show features that dip as steeply as 25?? north and extend downward to depths between 20 and 25 km. These reflections reveal crustal structures, probably ductile shear zones, that most likely formed during the Late Cretaceous, but these structures appear to be inactive, having produced little seismicity during the past 20 years. Furthermore, seismic reflections mainly dip north, whereas alignments in aftershock hypocenters dip south. The Denali fault is nonreflective, but modeling of MT, gravity, and magnetic data suggests that the Denali fault dips steeply to vertically. However, in an alternative structural model, the Denali fault is defined by one of the reflection bands that dips to the north and flattens into the middle crust of the Alaska Range orogen. Modeling of MT data indicates a rock body, having low electrical resistivity (>10 ??-m), that lies mainly at depths greater than 10 km, directly beneath aftershocks of the Denali fault earthquake. The maximum depth of aftershocks along the Denali fault is 10 km. This shallow depth may arise from a higher-than-normal geothermal gradient. Alternatively, the low electrical resistivity of deep rocks along the Denali fault may be associated with fluids that have weakened the lower crust and helped determine the depth extent of the after-shock zone.

Exploring the possibility of a common structural model measuring associations between safety climate factors and safety behaviour in health care and the petroleum sectors.

PubMed

Olsen, Espen

2010-09-01

The aim of the present study was to explore the possibility of identifying general safety climate concepts in health care and petroleum sectors, as well as develop and test the possibility of a common cross-industrial structural model. Self-completion questionnaire surveys were administered in two organisations and sectors: (1) a large regional hospital in Norway that offers a wide range of hospital services, and (2) a large petroleum company that produces oil and gas worldwide. In total, 1919 and 1806 questionnaires were returned from the hospital and petroleum organisation, with response rates of 55 percent and 52 percent, respectively. Using a split sample procedure principal factor analysis and confirmatory factor analysis revealed six identical cross-industrial measurement concepts in independent samples-five measures of safety climate and one of safety behaviour. The factors' psychometric properties were explored with satisfactory internal consistency and concept validity. Thus, a common cross-industrial structural model was developed and tested using structural equation modelling (SEM). SEM revealed that a cross-industrial structural model could be identified among health care workers and offshore workers in the North Sea. The most significant contributing variables in the model testing stemmed from organisational management support for safety and supervisor/manager expectations and actions promoting safety. These variables indirectly enhanced safety behaviour (stop working in dangerous situations) through transitions and teamwork across units, and teamwork within units as well as learning, feedback, and improvement. Two new safety climate instruments were validated as part of the study: (1) Short Safety Climate Survey (SSCS) and (2) Hospital Survey on Patient Safety Culture-short (HSOPSC-short). Based on development of measurements and structural model assessment, this study supports the possibility of a common safety climate structural model across health care and the offshore petroleum industry. 2010 Elsevier Ltd. All rights reserved.

Structural prediction of a novel chitinase from the psychrophilic Glaciozyma antarctica PI12 and an analysis of its structural properties and function

NASA Astrophysics Data System (ADS)

Ramli, Aizi Nor Mazila; Mahadi, Nor Muhammad; Shamsir, Mohd Shahir; Rabu, Amir; Joyce-Tan, Kwee Hong; Murad, Abdul Munir Abdul; Illias, Rosli Md.

2012-08-01

The structure of psychrophilic chitinase (CHI II) from Glaciozyma antarctica PI12 has yet to be studied in detail. Due to its low sequence identity (<30 %), the structural prediction of CHI II is a challenge. A 3D model of CHI II was built by first using a threading approach to search for a suitable template and to generate an optimum target-template alignment, followed by model building using MODELLER9v7. Analysis of the catalytic insertion domain structure in CHI II revealed an increase in the number of aromatic residues and longer loops compared to mesophilic and thermophilic chitinases. A molecular dynamics simulation was used to examine the stability of the CHI II structure at 273, 288 and 300 K. Structural analysis of the substrate-binding cleft revealed a few exposed aromatic residues. Substitutions of certain amino acids in the surface and loop regions of CHI II conferred an increased flexibility to the enzyme, allowing for an adaptation to cold temperatures. A substrate binding comparison of CHI II with the mesophilic chitinase from Coccidioides immitis, 1D2K, suggested that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through a reduction in the number of salt bridges, fewer hydrogen bonds and an increase in the exposure of the hydrophobic side chains to the solvent.

Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending

PubMed Central

Bebel, Aleksandra; Karaca, Ezgi; Kumar, Banushree; Stark, W Marshall; Barabas, Orsolya

2016-01-01

Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers, but their mechanism of action has remained structurally uncharacterized. Here, we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA difH, representing pre-cleavage and post-cleavage synaptic intermediates in the recombination pathway. The structures reveal that activation of DNA strand cleavage and rejoining involves large conformational changes and DNA bending, suggesting how interaction with the cell division protein FtsK may license recombination at the septum. Together with biochemical and in vivo analysis, our structures also reveal how a small sequence asymmetry in difH defines protein conformation in the synaptic complex and orchestrates the order of DNA strand exchanges. Our results provide insights into the catalytic mechanism of Xer recombination and a model for regulation of recombination activity during cell division. DOI: http://dx.doi.org/10.7554/eLife.19706.001 PMID:28009253

A Simplified Model of Local Structure in Aqueous Proline Amino Acid Revealed by First-Principles Molecular Dynamics Simulations

PubMed Central

Troitzsch, Raphael Z.; Tulip, Paul R.; Crain, Jason; Martyna, Glenn J.

2008-01-01

Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data. PMID:18790850

A simplified model of local structure in aqueous proline amino acid revealed by first-principles molecular dynamics simulations.

PubMed

Troitzsch, Raphael Z; Tulip, Paul R; Crain, Jason; Martyna, Glenn J

2008-12-01

Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data.

Fibrillation mechanism of a model intrinsically disordered protein revealed by 2D correlation deep UV resonance Raman spectroscopy.

PubMed

Sikirzhytski, Vitali; Topilina, Natalya I; Takor, Gaius A; Higashiya, Seiichiro; Welch, John T; Uversky, Vladimir N; Lednev, Igor K

2012-05-14

Understanding of numerous biological functions of intrinsically disordered proteins (IDPs) is of significant interest to modern life science research. A large variety of serious debilitating diseases are associated with the malfunction of IDPs including neurodegenerative disorders and systemic amyloidosis. Here we report on the molecular mechanism of amyloid fibrillation of a model IDP (YE8) using 2D correlation deep UV resonance Raman spectroscopy. YE8 is a genetically engineered polypeptide, which is completely unordered at neutral pH yet exhibits all properties of a fibrillogenic protein at low pH. The very first step of the fibrillation process involves structural rearrangements of YE8 at the global structure level without the detectable appearance of secondary structural elements. The formation of β-sheet species follows the global structural changes and proceeds via the simultaneous formation of turns and β-strands. The kinetic mechanism revealed is an important new contribution to understanding of the general fibrillation mechanism proposed for IDP.

Homotropic Cooperativity from the Activation Pathway of the Allosteric Ligand-Responsive Regulatory Protein TRAP†

PubMed Central

Kleckner, Ian R.; McElroy, Craig A.; Kuzmic, Petr; Gollnick, Paul; Foster, Mark P.

2014-01-01

The trp RNA-binding Attenuation Protein (TRAP) assembles into an 11-fold symmetric ring that regulates transcription and translation of trp-mRNA in bacilli via heterotropic allosteric activation by the amino acid tryptophan (Trp). Whereas nuclear magnetic resonance studies have revealed that Trp-induced activation coincides with both μs-ms rigidification and local structural changes in TRAP, the pathway of binding of the 11 Trp ligands to the TRAP ring remains unclear. Moreover, because each of eleven bound Trp molecules is completely surrounded by protein, its release requires flexibility of Trp-bound (holo) TRAP. Here, we used stopped-flow fluorescence to study the kinetics of Trp binding by Bacillus stearothermophilus TRAP over a range of temperatures and we observed well-separated kinetic steps. These data were analyzed using non-linear least-squares fitting of several two- and three-step models. We found that a model with two binding steps best describes the data, although the structural equivalence of the binding sites in TRAP implies a fundamental change in the time-dependent structure of the TRAP rings upon Trp binding. Application of the two binding step model reveals that Trp binding is much slower than the diffusion limit, suggesting a gating mechanism that depends on the dynamics of apo TRAP. These data also reveal that Trp dissociation from the second binding mode is much slower than after the first Trp binding mode, revealing insight into the mechanism for positive homotropic allostery, or cooperativity. Temperature dependent analyses reveal that both binding modes imbue increases in bondedness and order toward a more compressed active state. These results provide insight into mechanisms of cooperative TRAP activation, and underscore the importance of protein dynamics for ligand binding, ligand release, protein activation, and allostery. PMID:24224873

Disruption of River Networks in Nature and Models

NASA Astrophysics Data System (ADS)

Perron, J. T.; Black, B. A.; Stokes, M.; McCoy, S. W.; Goldberg, S. L.

2017-12-01

Many natural systems display especially informative behavior as they respond to perturbations. Landscapes are no exception. For example, longitudinal elevation profiles of rivers responding to changes in uplift rate can reveal differences among erosional mechanisms that are obscured while the profiles are in equilibrium. The responses of erosional river networks to perturbations, including disruption of their network structure by diversion, truncation, resurfacing, or river capture, may be equally revealing. In this presentation, we draw attention to features of disrupted erosional river networks that a general model of landscape evolution should be able to reproduce, including the consequences of different styles of planetary tectonics and the response to heterogeneous bedrock structure and deformation. A comparison of global drainage directions with long-wavelength topography on Earth, Mars, and Saturn's moon Titan reveals the extent to which persistent and relatively rapid crustal deformation has disrupted river networks on Earth. Motivated by this example and others, we ask whether current models of river network evolution adequately capture the disruption of river networks by tectonic, lithologic, or climatic perturbations. In some cases the answer appears to be no, and we suggest some processes that models may be missing.

Structure of the European upper mantle revealed by adjoint tomography

NASA Astrophysics Data System (ADS)

Zhu, Hejun; Bozdağ, Ebru; Peter, Daniel; Tromp, Jeroen

2012-07-01

Images of the European crust and upper mantle, created using seismic tomography, identify the Cenozoic Rift System and related volcanism in central and western Europe. They also reveal subduction and slab roll back in the Mediterranean-Carpathian region. However, existing tomographic models are either high in resolution, but cover only a limited area, or low in resolution, and thus miss the finer-scale details of mantle structure. Here we simultaneously fit frequency-dependent phase anomalies of body and surface waveforms in complete three-component seismograms with an iterative inversion strategy involving adjoint methods, to create a tomographic model of the European upper mantle. We find that many of the smaller-scale structures such as slabs, upwellings and delaminations that emerge naturally in our model are consistent with existing images. However, we also derive some hitherto unidentified structures. Specifically, we interpret fast seismic-wave speeds beneath the Dinarides Mountains, southern Europe, as a signature of northeastward subduction of the Adria plate; slow seismic-wave speeds beneath the northern part of the Rhine Graben as a reservoir connected to the Eifel hotspot; and fast wave-speed anomalies beneath Scandinavia as a lithospheric drip, where the lithosphere is delaminating and breaking away. Our model sheds new light on the enigmatic palaeotectonic history of Europe.

A periodic mixed gaussians-plane waves DFT study on simple thiols on Au(111): adsorbate species, surface reconstruction, and thiols functionalization.

PubMed

Rajaraman, Gopalan; Caneschi, Andrea; Gatteschi, Dante; Totti, Federico

2011-03-07

Here we present DFT calculations based on a periodic mixed gaussians/plane waves approach to study the energetics, structure, bonding of SAMs of simple thiols on Au(111). Several open issues such as structure, bonding and the nature of adsorbate are taken into account. We started with methyl thiols (MeSH) on Au(111) to establish the nature of the adsorbate. We have considered several structural models embracing the reconstructed surface scenario along with the MeS˙-Au(ad)-MeS˙ type motif put forward in recent years. Our calculations suggest a clear preference for the homolytic cleavage of the S-H bond leading to a stable MeS˙ on a gold surface. In agreement with the recent literature studies, the reconstructed models of the MeS˙ species are found to be energetically preferred over unreconstructed models. Besides, our calculations reveal that the model with 1:2 Au(ad)/thiols ratio, i.e. MeS˙-Au(ad)-MeS˙, is energetically preferred compared to the clean and 1:1 ratio models, in agreement with the experimental and theoretical evidences. We have also performed Molecular Orbital/Natural Bond Orbital, MO/NBO, analysis to understand the electronic structure and bonding in different structural motifs and many useful insights have been gained. Finally, the studies have then been extended to alkyl thiols of the RSR' (R, R' = Me, Et and Ph) type and here our calculations again reveal a preference for the RS˙ type species adsorption for clean as well as for reconstructed 1:2 Au(ad)/thiols ratio models.

The Quality and Validation of Structures from Structural Genomics

PubMed Central

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

2014-01-01

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

GCM studies on Jovian polar dynamics

NASA Astrophysics Data System (ADS)

Tabataba-Vakili, F.; Orton, G.; Li, C.; Young, R. M.; Read, P. L.; Ingersoll, A. P.

2017-12-01

The Juno spacecraft has produced unparalleled measurements of the polar regions of Jupiter. Observations from JunoCAM and JIRAM (Jupiter Infrared Auroral Mapper) have revealed a structure of cyclonic vortices near the poles. We report simulations of the observed polar dynamics using a hierarchy of models from shallow-water to general circulation models with increasing detail. An initialized, unforced shallow-water model of the polar region results in merging cyclones, producing a Saturn-like polar vortex. Further investigations with more detailed models aim to recreate the observed polar structures on Jupiter and investigate the difference between vortical structures on Saturn and Jupiter. Identifying this difference may shed light on the formation and maintenance mechanisms of the observed vortices.

Robust multi-model control of an autonomous wind power system

NASA Astrophysics Data System (ADS)

Cutululis, Nicolas Antonio; Ceanga, Emil; Hansen, Anca Daniela; Sørensen, Poul

2006-09-01

This article presents a robust multi-model control structure for a wind power system that uses a variable speed wind turbine (VSWT) driving a permanent magnet synchronous generator (PMSG) connected to a local grid. The control problem consists in maximizing the energy captured from the wind for varying wind speeds. The VSWT-PMSG linearized model analysis reveals the resonant nature of its dynamic at points on the optimal regimes characteristic (ORC). The natural frequency of the system and the damping factor are strongly dependent on the operating point on the ORC. Under these circumstances a robust multi-model control structure is designed. The simulation results prove the viability of the proposed control structure. Copyright

Modeling online social signed networks

NASA Astrophysics Data System (ADS)

Li, Le; Gu, Ke; Zeng, An; Fan, Ying; Di, Zengru

2018-04-01

People's online rating behavior can be modeled by user-object bipartite networks directly. However, few works have been devoted to reveal the hidden relations between users, especially from the perspective of signed networks. We analyze the signed monopartite networks projected by the signed user-object bipartite networks, finding that the networks are highly clustered with obvious community structure. Interestingly, the positive clustering coefficient is remarkably higher than the negative clustering coefficient. Then, a Signed Growing Network model (SGN) based on local preferential attachment is proposed to generate a user's signed network that has community structure and high positive clustering coefficient. Other structural properties of the modeled networks are also found to be similar to the empirical networks.

A Model Comparison for Characterizing Protein Motions from Structure

NASA Astrophysics Data System (ADS)

David, Charles; Jacobs, Donald

2011-10-01

A comparative study is made using three computational models that characterize native state dynamics starting from known protein structures taken from four distinct SCOP classifications. A geometrical simulation is performed, and the results are compared to the elastic network model and molecular dynamics. The essential dynamics is quantified by a direct analysis of a mode subspace constructed from ANM and a principal component analysis on both the FRODA and MD trajectories using root mean square inner product and principal angles. Relative subspace sizes and overlaps are visualized using the projection of displacement vectors on the model modes. Additionally, a mode subspace is constructed from PCA on an exemplar set of X-ray crystal structures in order to determine similarly with respect to the generated ensembles. Quantitative analysis reveals there is significant overlap across the three model subspaces and the model independent subspace. These results indicate that structure is the key determinant for native state dynamics.

Structure of T7 RNA polymerase complexed to the transcriptional inhibitor T7 lysozyme.

PubMed Central

Jeruzalmi, D; Steitz, T A

1998-01-01

The T7 RNA polymerase-T7 lysozyme complex regulates phage gene expression during infection of Escherichia coli. The 2.8 A crystal structure of the complex reveals that lysozyme binds at a site remote from the polymerase active site, suggesting an indirect mechanism of inhibition. Comparison of the T7 RNA polymerase structure with that of the homologous pol I family of DNA polymerases reveals identities in the catalytic site but also differences specific to RNA polymerase function. The structure of T7 RNA polymerase presented here differs significantly from a previously published structure. Sequence similarities between phage RNA polymerases and those from mitochondria and chloroplasts, when interpreted in the context of our revised model of T7 RNA polymerase, suggest a conserved fold. PMID:9670025

A bioinspired study on the compressive resistance of helicoidal fibre structures

NASA Astrophysics Data System (ADS)

Tan, Ting; Ribbans, Brian

2017-10-01

Helicoidal fibre structures are widely observed in natural materials. In this paper, an integrated experimental and analytical approach was used to investigate the compressive resistance of helicoidal fibre structures. First, helicoidal fibre-reinforced composites were created using three-dimensionally printed helicoids and polymeric matrices, including plain, ring-reinforced and helix-reinforced helicoids. Then, load-displacement curves under monotonic compression tests were collected to measure the compressive strengths of helicoidal fibre composites. Fractographic characterization was performed using an X-ray microtomographer and scanning electron microscope, through which crack propagations in helicoidal structures were illustrated. Finally, mathematical modelling was performed to reveal the essential fibre architectures in the compressive resistance of helicoidal fibre structures. This work reveals that fibre-matrix ratios, helix pitch angles and interlayer rotary angles are critical to the compressive resistance of helicoidal structures.

Moho topography, ranges and folds of Tibet by analysis of global gravity models and GOCE data

PubMed Central

Shin, Young Hong; Shum, C.K.; Braitenberg, Carla; Lee, Sang Mook; Na, Sung -Ho; Choi, Kwang Sun; Hsu, Houtse; Park, Young-Sue; Lim, Mutaek

2015-01-01

The determination of the crustal structure is essential in geophysics, as it gives insight into the geohistory, tectonic environment, geohazard mitigation, etc. Here we present the latest advance on three-dimensional modeling representing the Tibetan Mohorovičić discontinuity (topography and ranges) and its deformation (fold), revealed by analyzing gravity data from GOCE mission. Our study shows noticeable advances in estimated Tibetan Moho model which is superior to the results using the earlier gravity models prior to GOCE. The higher quality gravity field of GOCE is reflected in the Moho solution: we find that the Moho is deeper than 65 km, which is twice the normal continental crust beneath most of the Qinghai-Tibetan plateau, while the deepest Moho, up to 82 km, is located in western Tibet. The amplitude of the Moho fold is estimated to be ranging from −9 km to 9 km with a standard deviation of ~2 km. The improved GOCE gravity derived Moho signals reveal a clear directionality of the Moho ranges and Moho fold structure, orthogonal to deformation rates observed by GPS. This geophysical feature, clearly more evident than the ones estimated using earlier gravity models, reveals that it is the result of the large compressional tectonic process. PMID:26114224

Chromosome structure inside the nucleus.

PubMed

Swedlow, J R; Agard, D A; Sedat, J W

1993-06-01

Recent in situ three-dimensional structural studies have provided a new model for the 30 nm chromatin fiber. In addition, research during the past year has revealed some of the molecular complexity of non-histone chromosomal proteins. Still to come is the unification of molecular insights with chromosomal architecture.

MODIS-Aqua Reveals Evolving Phytoplankton Community Structure During the Arabian Sea Northeast Monsoon

NASA Technical Reports Server (NTRS)

Werdell, P. Jeremy; Roesler, Collin S.; Goes, Joaquim I.

2016-01-01

Applying a bio-optical model designed to identify the mixotrophic dinoflagellate Noctiluca miliaris to MODIS-Aqua revealed (1) patterns in its spatial distribution not previously seen (including its appearance in places not previously sampled), and (2) the surprising disassociation of total chlorophyll biomass with the presence of N. miliaris.

Structure of an E3:E2~Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases

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

Pruneda, Jonathan N.; Littlefield, Peter J.; Soss, Sarah E.

2012-09-28

Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanismby which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3:E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 side chain and an E2 backbone carbonyl, observed in all structures of active RING/ U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformationalmore » biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/ U-box E3:E2~Ub ligase complex and identify the long sought-after source of allostery for RING/UBox activation of E2~Ub conjugates.« less

Correlations in Scattered X-Ray Laser Pulses Reveal Nanoscale Structural Features of Viruses

DOE PAGES

Kurta, Ruslan P.; Donatelli, Jeffrey J.; Yoon, Chun Hong; ...

2017-10-12

We use extremely bright and ultrashort pulses from an x-ray free-electron laser (XFEL) to measure correlations in x rays scattered from individual bioparticles. This allows us to go beyond the traditional crystallography and single-particle imaging approaches for structure investigations. We employ angular correlations to recover the three-dimensional (3D) structure of nanoscale viruses from x-ray diffraction data measured at the Linac Coherent Light Source. Correlations provide us with a comprehensive structural fingerprint of a 3D virus, which we use both for model-based and ab initio structure recovery. The analyses reveal a clear indication that the structure of the viruses deviates frommore » the expected perfect icosahedral symmetry. Lastly, our results anticipate exciting opportunities for XFEL studies of the structure and dynamics of nanoscale objects by means of angular correlations.« less

Settlement Patterns and the Governing Structures of 19th Century School Systems.

ERIC Educational Resources Information Center

Richardson, John G.

Examination of state school governance structures in the late 19th century reveals three regional models, each springing from particular patterns of settlement and political administration. Historical explanations for school system origins have drawn mainly on the histories of northeastern cities and states. They have underemphasized regional…

Labor Market Structure and Salary Determination among Professional Basketball Players.

ERIC Educational Resources Information Center

Wallace, Michael

1988-01-01

The author investigates the labor market structure and determinants of salaries for professional basketball players. An expanded version of the resource perspective is used. A three-tiered model of labor market segmentation is revealed for professional basketball players, but other variables also are important in salary determination. (Author/CH)

Three-dimensional model of an ultramafic feeder system to the Nikolai Greenstone mafic large igneous province, central Alaska Range

USGS Publications Warehouse

Glen, J.M.G.; Schmidt, J.M.; Connard, G.G.

2011-01-01

The Amphitheater Mountains and southern central Alaska Range expose a thick sequence of Triassic Nikolai basalts that is underlain by several mafic-ultramafic complexes, the largest and best exposed being the Fish Lake and Tangle (FL-T) mafic-ultramafic sills that flank the Amphitheater Mountains synform. Three-dimensional (3-D) modeling of gravity and magnetic data reveals details of the structure of the Amphitheater Mountains, such as the orientation and thickness of Nikolai basalts, and the geometry of the FL-T intrusions. The 3-D model (50 ?? 70 km) includes the full geographic extent of the FL-T complexes and consists of 11 layers. Layer surfaces and properties (density and magnetic susceptibility) were modified by forward and inverse methods to reduce differences between the observed and calculated gravity and magnetic grids. The model suggests that the outcropping FL-T sills are apparently connected and traceable at depth and reveals variations in thickness, shape, and orientation of the ultramafic bodies that may identify paths of magma flow. The model shows that a significant volume (2000 km3) of ultramafic material occurs in the subsurface, gradually thickening and plunging westward to depths exceeding 4 km. This deep ultramafic material is interpreted as the top of a keel or root system that supplied magma to the Nikolai lavas and controlled emplacement of related magmatic intrusions. The presence of this deep, keel-like structure, and asymmetry of the synform, supports a sag basin model for development of the Amphitheater Mountains structure and reveals that the feeders to the Nikolai are much more extensive than previously known. Copyright 2011 by the American Geophysical Union.

Applying a Cognitive-Behavioral Model of HIV Risk to Youths in Psychiatric Care

ERIC Educational Resources Information Center

Donenberg, Geri R.; Schwartz, Rebecca Moss; Emerson, Erin; Wilson, Helen W.; Bryant, Fred B.; Coleman, Gloria

2005-01-01

This study examined the utility of cognitive and behavioral constructs (AIDS information, motivation, and behavioral skills) in explaining sexual risk taking among 172 12-20-year-old ethnically diverse urban youths in outpatient psychiatric care. Structural equation modeling revealed only moderate support for the model, explaining low to moderate…

Retrieving hydrological connectivity from empirical causality in karst systems

NASA Astrophysics Data System (ADS)

Delforge, Damien; Vanclooster, Marnik; Van Camp, Michel; Poulain, Amaël; Watlet, Arnaud; Hallet, Vincent; Kaufmann, Olivier; Francis, Olivier

2017-04-01

Because of their complexity, karst systems exhibit nonlinear dynamics. Moreover, if one attempts to model a karst, the hidden behavior complicates the choice of the most suitable model. Therefore, both intense investigation methods and nonlinear data analysis are needed to reveal the underlying hydrological connectivity as a prior for a consistent physically based modelling approach. Convergent Cross Mapping (CCM), a recent method, promises to identify causal relationships between time series belonging to the same dynamical systems. The method is based on phase space reconstruction and is suitable for nonlinear dynamics. As an empirical causation detection method, it could be used to highlight the hidden complexity of a karst system by revealing its inner hydrological and dynamical connectivity. Hence, if one can link causal relationships to physical processes, the method should show great potential to support physically based model structure selection. We present the results of numerical experiments using karst model blocks combined in different structures to generate time series from actual rainfall series. CCM is applied between the time series to investigate if the empirical causation detection is consistent with the hydrological connectivity suggested by the karst model.

CAD-Based Modeling of Advanced Rotary Wing Structures for Integrated 3-D Aeromechanics Analysis

NASA Astrophysics Data System (ADS)

Staruk, William

This dissertation describes the first comprehensive use of integrated 3-D aeromechanics modeling, defined as the coupling of 3-D solid finite element method (FEM) structural dynamics with 3-D computational fluid dynamics (CFD), for the analysis of a real helicopter rotor. The development of this new methodology (a departure from how rotor aeroelastic analysis has been performed for 40 years), its execution on a real rotor, and the fundamental understanding of aeromechanics gained from it, are the key contributions of this dissertation. This work also presents the first CFD/CSD analysis of a tiltrotor in edgewise flight, revealing many of its unique loading mechanisms. The use of 3-D FEM, integrated with a trim solver and aerodynamics modeling, has the potential to enhance the design of advanced rotors by overcoming fundamental limitations of current generation beam-based analysis tools and offering integrated internal dynamic stress and strain predictions for design. Two primary goals drove this research effort: 1) developing a methodology to create 3-D CAD-based brick finite element models of rotors including multibody joints, controls, and aerodynamic interfaces, and 2) refining X3D, the US Army's next generation rotor structural dynamics solver featuring 3-D FEM within a multibody formulation with integrated aerodynamics, to model a tiltrotor in the edgewise conversion flight regime, which drives critical proprotor structural loads. Prior tiltrotor analysis has primarily focused on hover aerodynamics with rigid blades or forward flight whirl-flutter stability with simplified aerodynamics. The first goal was met with the development of a detailed methodology for generating multibody 3-D structural models, starting from CAD geometry, continuing to higher-order hexahedral finite element meshing, to final assembly of the multibody model by creating joints, assigning material properties, and defining the aerodynamic interface. Several levels of verification and validation were carried out systematically, covering formulation, model accuracy, and accuracy of the physics of the problem and the many complex coupled aeromechanical phenomena that characterize the behavior of a tiltrotor in the conversion corridor. Compatibility of the new structural analysis models with X3D is demonstrated using analytical test cases, including 90° twisted beams and thick composite plates, and a notional bearingless rotor. Prediction of deformations and stresses in composite beams and plates is validated and verified against experimental measurements, theory, and state-of-the-art beam models. The second goal was met through integrated analysis of the Tilt Rotor Aeroacoustic Model (TRAM) proprotor using X3D coupled to Helios--the US Army's next generation CFD framework featuring a high fidelity Reynolds-average Navier-Stokes (RANS) structured/unstructured overset solver--as well as low order aerodynamic models. Although development of CFD was not part of this work, coupling X3D with Helios was, including establishing consistent interface definitions for blade deformations (for CFD mesh motion), aerodynamic interfaces (for loads transfer), and rotor control angles (for trim). It is expected that this method and solver will henceforth be an integral part of the Helios framework, providing an equal fidelity of representation for fluids and structures in the development of future advanced rotor systems. Structural dynamics analysis of the TRAM model show accurate prediction of the lower natural frequencies, demonstrating the ability to model advanced rotors from first principles using 3-D structural dynamics, and a study of how joint properties affect these frequencies reveals how X3D can be used as a detailed design tool. The CFD/CSD analysis reveals accurate prediction of rotor performance and airloads in edgewise flight when compared to wind tunnel test data. Structural blade loads trends are well predicted at low thrust, but a 3/rev component of flap and lag bending moment appearing in test data at high thrust remains a mystery. Efficiently simulating a gimbaled rotor is not trivial; a time-domain method with only a single blade model is proposed and tested. The internal stress in the blade, particularly at its root where the gimbal action has major influence, is carefully examined, revealing complex localized loading patterns.

Complex traffic flow that allows as well as hampers lane-changing intrinsically contains social-dilemma structures

NASA Astrophysics Data System (ADS)

Iwamura, Yoshiro; Tanimoto, Jun

2018-02-01

To investigate an interesting question as to whether or not social dilemma structures can be found in a realistic traffic flow reproduced by a model, we built a new microscopic model in which an intentional driver may try lane-changing to go in front of other vehicles and may hamper others’ lane-changes. Our model consists of twofold parts; cellular automaton emulating a real traffic flow and evolutionary game theory to implement a driver’s decision making-process. Numerical results reveal that a social dilemma like the multi-player chicken game or prisoner’s dilemma game emerges depending on the traffic phase. This finding implies that a social dilemma, which has been investigated by applied mathematics so far, hides behind a traffic flow, which has been explored by fluid dynamics. Highlight - Complex system of traffic flow with consideration of driver’s decision making process is concerned. - A new model dovetailing cellular automaton with game theory is established. - Statistical result from numerical simulations reveals a social dilemma structure underlying traffic flow. - The social dilemma is triggered by a driver’s egocentric actions of lane-changing and hampering other’s lane-change.

Analytical investigation of a three-dimensional FRP-retrofitted reinforced concrete structure's behaviour under earthquake load effect in ANSYS program

NASA Astrophysics Data System (ADS)

Altun, F.; Birdal, F.

2012-12-01

In this study, a 1:3 scaled, three-storey, FRP (Fiber Reinforced Polymer) retrofitted reinforced concrete model structure whose behaviour and crack development were identified experimentally in the laboratory was investigated analytically. Determination of structural behaviour under earthquake load is only possible in a laboratory environment with a specific scale, as carrying out structural experiments is difficult due to the evaluation of increased parameter numbers and because it requires an expensive laboratory setup. In an analytical study, structure was modelled using ANSYS Finite Element Package Program (2007), and its behaviour and crack development were revealed. When experimental difficulties are taken into consideration, analytical investigation of structure behaviour is more economic and much faster. At the end of the study, experimental results of structural behaviour and crack development were compared with analytical data. It was concluded that in a model structure retrofitted with FRP, the behaviour and cracking model can be determined without testing by determining the reasons for the points where analytical results are not converged with experimental data. Better understanding of structural behaviour is analytically enabled with the study.

Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear

PubMed Central

Drummond, Meghan C.; Barzik, Melanie; Bird, Jonathan E.; Zhang, Duan-Sun; Lechene, Claude P.; Corey, David P.; Cunningham, Lisa L.; Friedman, Thomas B.

2015-01-01

The maintenance of sensory hair cell stereocilia is critical for lifelong hearing; however, mechanisms of structural homeostasis remain poorly understood. Conflicting models propose that stereocilia F-actin cores are either continually renewed every 24–48 h via a treadmill or are stable, exceptionally long-lived structures. Here to distinguish between these models, we perform an unbiased survey of stereocilia actin dynamics in more than 500 utricle hair cells. Live-imaging EGFP-β-actin or dendra2-β-actin reveal stable F-actin cores with turnover and elongation restricted to stereocilia tips. Fixed-cell microscopy of wild-type and mutant β-actin demonstrates that incorporation of actin monomers into filaments is required for localization to stereocilia tips. Multi-isotope imaging mass spectrometry and live imaging of single differentiating hair cells capture stereociliogenesis and explain uniform incorporation of 15N-labelled protein and EGFP-β-actin into nascent stereocilia. Collectively, our analyses support a model in which stereocilia actin cores are stable structures that incorporate new F-actin only at the distal tips. PMID:25898120

Mapping nonlinear receptive field structure in primate retina at single cone resolution

PubMed Central

Li, Peter H; Greschner, Martin; Gunning, Deborah E; Mathieson, Keith; Sher, Alexander; Litke, Alan M; Paninski, Liam

2015-01-01

The function of a neural circuit is shaped by the computations performed by its interneurons, which in many cases are not easily accessible to experimental investigation. Here, we elucidate the transformation of visual signals flowing from the input to the output of the primate retina, using a combination of large-scale multi-electrode recordings from an identified ganglion cell type, visual stimulation targeted at individual cone photoreceptors, and a hierarchical computational model. The results reveal nonlinear subunits in the circuity of OFF midget ganglion cells, which subserve high-resolution vision. The model explains light responses to a variety of stimuli more accurately than a linear model, including stimuli targeted to cones within and across subunits. The recovered model components are consistent with known anatomical organization of midget bipolar interneurons. These results reveal the spatial structure of linear and nonlinear encoding, at the resolution of single cells and at the scale of complete circuits. DOI: http://dx.doi.org/10.7554/eLife.05241.001 PMID:26517879

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

DOE PAGES

Kim, Jeong Joo; Lorenz, Robin; Arold, Stefan T.; ...

2016-04-07

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Here, although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-raymore » scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG.« less

Multi-wavelength Observations and Modeling of Solar Flares: Magnetic Structures

NASA Astrophysics Data System (ADS)

Su, Y.

2017-12-01

We present a review of our recent investigations on multi-wavelength observations and magnetic field modeling of solar flares. High-resolution observations taken by NVST and BBSO/NST reveal unprecedented fine structures of the flaring regions. Observations by SDO, IRIS, and GOES provide the complementary information. The magnetic field models are constructed using either non-linear force free field extrapolations or flux rope insertion method. Our studies have shown that the flaring regions often consist of double or multiple flux ropes, which often exist at different heights. The fine flare ribbon structures may be due to the magnetic reconnection in the complex quasi separatrix layers. The magnetic field modeling of several large flares suggests that the so called hot-channel structure is corresponding to the erupting flux rope above the X-point in a magnetic configuration with Hyperbolic Flux Tube.

In silico local structure approach: a case study on outer membrane proteins.

PubMed

Martin, Juliette; de Brevern, Alexandre G; Camproux, Anne-Claude

2008-04-01

The detection of Outer Membrane Proteins (OMP) in whole genomes is an actual question, their sequence characteristics have thus been intensively studied. This class of protein displays a common beta-barrel architecture, formed by adjacent antiparallel strands. However, due to the lack of available structures, few structural studies have been made on this class of proteins. Here we propose a novel OMP local structure investigation, based on a structural alphabet approach, i.e., the decomposition of 3D structures using a library of four-residue protein fragments. The optimal decomposition of structures using hidden Markov model results in a specific structural alphabet of 20 fragments, six of them dedicated to the decomposition of beta-strands. This optimal alphabet, called SA20-OMP, is analyzed in details, in terms of local structures and transitions between fragments. It highlights a particular and strong organization of beta-strands as series of regular canonical structural fragments. The comparison with alphabets learned on globular structures indicates that the internal organization of OMP structures is more constrained than in globular structures. The analysis of OMP structures using SA20-OMP reveals some recurrent structural patterns. The preferred location of fragments in the distinct regions of the membrane is investigated. The study of pairwise specificity of fragments reveals that some contacts between structural fragments in beta-sheets are clearly favored whereas others are avoided. This contact specificity is stronger in OMP than in globular structures. Moreover, SA20-OMP also captured sequential information. This can be integrated in a scoring function for structural model ranking with very promising results. (c) 2007 Wiley-Liss, Inc.

Structural analyses for the modification and verification of the Viking aeroshell

NASA Technical Reports Server (NTRS)

Stephens, W. B.; Anderson, M. S.

1976-01-01

The Viking aeroshell is an extremely lightweight flexible shell structure that has undergone thorough buckling analyses in the course of its development. The analytical tools and modeling technique required to reveal the structural behavior are presented. Significant results are given which illustrate the complex failure modes not usually observed in simple models and analyses. Both shell-of-revolution analysis for the pressure loads and thermal loads during entry and a general shell analysis for concentrated tank loads during launch were used. In many cases fixes or alterations to the structure were required, and the role of the analytical results in determining these modifications is indicated.

Structural basis of respiratory syncytial virus neutralization by motavizumab

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

McLellan, Jason S.; Chen, Man; Kim, Albert

2010-04-13

Motavizumab is {approx}tenfold more potent than its predecessor, palivizumab (Synagis), the FDA-approved monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection. The structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the RSV fusion (F) glycoprotein reveals the structural basis for this greater potency. Modeling suggests that motavizumab recognizes a different quaternary configuration of the F glycoprotein than that observed in a homologous structure.

Integrating data from multiple sources for insights into demographic processes: Simulation studies and proof of concept for hierarchical change-in-ratio models.

PubMed

Nilsen, Erlend B; Strand, Olav

2018-01-01

We developed a model for estimating demographic rates and population abundance based on multiple data sets revealing information about population age- and sex structure. Such models have previously been described in the literature as change-in-ratio models, but we extend the applicability of the models by i) using time series data allowing the full temporal dynamics to be modelled, by ii) casting the model in an explicit hierarchical modelling framework, and by iii) estimating parameters based on Bayesian inference. Based on sensitivity analyses we conclude that the approach developed here is able to obtain estimates of demographic rate with high precision whenever unbiased data of population structure are available. Our simulations revealed that this was true also when data on population abundance are not available or not included in the modelling framework. Nevertheless, when data on population structure are biased due to different observability of different age- and sex categories this will affect estimates of all demographic rates. Estimates of population size is particularly sensitive to such biases, whereas demographic rates can be relatively precisely estimated even with biased observation data as long as the bias is not severe. We then use the models to estimate demographic rates and population abundance for two Norwegian reindeer (Rangifer tarandus) populations where age-sex data were available for all harvested animals, and where population structure surveys were carried out in early summer (after calving) and late fall (after hunting season), and population size is counted in winter. We found that demographic rates were similar regardless whether we include population count data in the modelling, but that the estimated population size is affected by this decision. This suggest that monitoring programs that focus on population age- and sex structure will benefit from collecting additional data that allow estimation of observability for different age- and sex classes. In addition, our sensitivity analysis suggests that focusing monitoring towards changes in demographic rates might be more feasible than monitoring abundance in many situations where data on population age- and sex structure can be collected.

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

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

Wong, Jaslyn E. M. M.; Midtgaard, Søren Roi; Gysel, Kira

The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of themore » Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.« less

Mapping temporal dynamics in social interactions with unified structural equation modeling: A description and demonstration revealing time-dependent sex differences in play behavior

PubMed Central

Beltz, Adriene M.; Beekman, Charles; Molenaar, Peter C. M.; Buss, Kristin A.

2013-01-01

Developmental science is rich with observations of social interactions, but few available methodological and statistical approaches take full advantage of the information provided by these data. The authors propose implementation of the unified structural equation model (uSEM), a network analysis technique, for observational data coded repeatedly across time; uSEM captures the temporal dynamics underlying changes in behavior at the individual level by revealing the ways in which a single person influences – concurrently and in the future – other people. To demonstrate the utility of uSEM, the authors applied it to ratings of positive affect and vigor of activity during children’s unstructured laboratory play with unfamiliar, same-sex peers. Results revealed the time-dependent nature of sex differences in play behavior. For girls more than boys, positive affect was dependent upon peers’ prior positive affect. For boys more than girls, vigor of activity was dependent upon peers’ current vigor of activity. PMID:24039386

Analysis of the dynamic behavior of structures using the high-rate GNSS-PPP method combined with a wavelet-neural model: Numerical simulation and experimental tests

NASA Astrophysics Data System (ADS)

Kaloop, Mosbeh R.; Yigit, Cemal O.; Hu, Jong W.

2018-03-01

Recently, the high rate global navigation satellite system-precise point positioning (GNSS-PPP) technique has been used to detect the dynamic behavior of structures. This study aimed to increase the accuracy of the extraction oscillation properties of structural movements based on the high-rate (10 Hz) GNSS-PPP monitoring technique. A developmental model based on the combination of wavelet package transformation (WPT) de-noising and neural network prediction (NN) was proposed to improve the dynamic behavior of structures for GNSS-PPP method. A complicated numerical simulation involving highly noisy data and 13 experimental cases with different loads were utilized to confirm the efficiency of the proposed model design and the monitoring technique in detecting the dynamic behavior of structures. The results revealed that, when combined with the proposed model, GNSS-PPP method can be used to accurately detect the dynamic behavior of engineering structures as an alternative to relative GNSS method.

A Markov model of the Indus script

PubMed Central

Rao, Rajesh P. N.; Yadav, Nisha; Vahia, Mayank N.; Joglekar, Hrishikesh; Adhikari, R.; Mahadevan, Iravatham

2009-01-01

Although no historical information exists about the Indus civilization (flourished ca. 2600–1900 B.C.), archaeologists have uncovered about 3,800 short samples of a script that was used throughout the civilization. The script remains undeciphered, despite a large number of attempts and claimed decipherments over the past 80 years. Here, we propose the use of probabilistic models to analyze the structure of the Indus script. The goal is to reveal, through probabilistic analysis, syntactic patterns that could point the way to eventual decipherment. We illustrate the approach using a simple Markov chain model to capture sequential dependencies between signs in the Indus script. The trained model allows new sample texts to be generated, revealing recurring patterns of signs that could potentially form functional subunits of a possible underlying language. The model also provides a quantitative way of testing whether a particular string belongs to the putative language as captured by the Markov model. Application of this test to Indus seals found in Mesopotamia and other sites in West Asia reveals that the script may have been used to express different content in these regions. Finally, we show how missing, ambiguous, or unreadable signs on damaged objects can be filled in with most likely predictions from the model. Taken together, our results indicate that the Indus script exhibits rich synactic structure and the ability to represent diverse content. both of which are suggestive of a linguistic writing system rather than a nonlinguistic symbol system. PMID:19666571

Crystal structure of a complex of HIV-1 protease with a dihydroxyethylene-containing inhibitor: comparisons with molecular modeling.

PubMed Central

Thanki, N.; Rao, J. K.; Foundling, S. I.; Howe, W. J.; Moon, J. B.; Hui, J. O.; Tomasselli, A. G.; Heinrikson, R. L.; Thaisrivongs, S.; Wlodawer, A.

1992-01-01

The structure of a crystal complex of recombinant human immunodeficiency virus type 1 (HIV-1) protease with a peptide-mimetic inhibitor containing a dihydroxyethylene isostere insert replacing the scissile bond has been determined. The inhibitor is Noa-His-Hch psi [CH(OH)CH(OH)]Vam-Ile-Amp (U-75875), and its Ki for inhibition of the HIV-1 protease is < 1.0 nM (Noa = 1-naphthoxyacetyl, Hch = a hydroxy-modified form of cyclohexylalanine, Vam = a hydroxy-modified form of valine, Amp = 2-pyridylmethylamine). The structure of the complex has been refined to a crystallographic R factor of 0.169 at 2.0 A resolution by using restrained least-squares procedures. Root mean square deviations from ideality are 0.02 A and 2.4 degrees, for bond lengths and angles, respectively. The bound inhibitor diastereomer has the R configurations at both of the hydroxyl chiral carbon atoms. One of the diol hydroxyl groups is positioned such that it forms hydrogen bonds with both the active site aspartates, whereas the other interacts with only one of them. Comparison of this X-ray structure with a model-built structure of the inhibitor, published earlier, reveals similar positioning of the backbone atoms and of the side-chain atoms in the P2-P2' region, where the interaction with the protein is strongest. However, the X-ray structure and the model differ considerably in the location of the P3 and P3' end groups, and also in the positioning of the second of the two central hydroxyl groups. Reconstruction of the central portion of the model revealed the source of the hydroxyl discrepancy, which, when corrected, provided a P1-P1' geometry very close to that seen in the X-ray structure. PMID:1304383

Structural Insights into High Density Lipoprotein: Old Models and New Facts

PubMed Central

Gogonea, Valentin

2016-01-01

The physiological link between circulating high density lipoprotein (HDL) levels and cardiovascular disease is well-documented, albeit its intricacies are not well-understood. An improved appreciation of HDL function and overall role in vascular health and disease requires at its foundation a better understanding of the lipoprotein's molecular structure, its formation, and its process of maturation through interactions with various plasma enzymes and cell receptors that intervene along the pathway of reverse cholesterol transport. This review focuses on summarizing recent developments in the field of lipid free apoA-I and HDL structure, with emphasis on new insights revealed by newly published nascent and spherical HDL models constructed by combining low resolution structures obtained from small angle neutron scattering (SANS) with contrast variation and geometrical constraints derived from hydrogen–deuterium exchange (HDX), crosslinking mass spectrometry, electron microscopy, Förster resonance energy transfer, and electron spin resonance. Recently published low resolution structures of nascent and spherical HDL obtained from SANS with contrast variation and isotopic labeling of apolipoprotein A-I (apoA-I) will be critically reviewed and discussed in terms of how they accommodate existing biophysical structural data from alternative approaches. The new low resolution structures revealed and also provided some answers to long standing questions concerning lipid organization and particle maturation of lipoproteins. The review will discuss the merits of newly proposed SANS based all atom models for nascent and spherical HDL, and compare them with accepted models. Finally, naturally occurring and bioengineered mutations in apoA-I, and their impact on HDL phenotype, are reviewed and discuss together with new therapeutics employed for restoring HDL function. PMID:26793109

Synchrotron IR microspectroscopy for protein structure analysis: Potential and questions

DOE PAGES

Yu, Peiqiang

2006-01-01

Synchrotron radiation-based Fourier transform infrared microspectroscopy (S-FTIR) has been developed as a rapid, direct, non-destructive, bioanalytical technique. This technique takes advantage of synchrotron light brightness and small effective source size and is capable of exploring the molecular chemical make-up within microstructures of a biological tissue without destruction of inherent structures at ultra-spatial resolutions within cellular dimension. To date there has been very little application of this advanced technique to the study of pure protein inherent structure at a cellular level in biological tissues. In this review, a novel approach was introduced to show the potential of the newly developed, advancedmore » synchrotron-based analytical technology, which can be used to localize relatively “pure“ protein in the plant tissues and relatively reveal protein inherent structure and protein molecular chemical make-up within intact tissue at cellular and subcellular levels. Several complex protein IR spectra data analytical techniques (Gaussian and Lorentzian multi-component peak modeling, univariate and multivariate analysis, principal component analysis (PCA), and hierarchical cluster analysis (CLA) are employed to relatively reveal features of protein inherent structure and distinguish protein inherent structure differences between varieties/species and treatments in plant tissues. By using a multi-peak modeling procedure, RELATIVE estimates (but not EXACT determinations) for protein secondary structure analysis can be made for comparison purpose. The issues of pro- and anti-multi-peaking modeling/fitting procedure for relative estimation of protein structure were discussed. By using the PCA and CLA analyses, the plant molecular structure can be qualitatively separate one group from another, statistically, even though the spectral assignments are not known. The synchrotron-based technology provides a new approach for protein structure research in biological tissues at ultraspatial resolutions.« less

From Voluntarism to Bureaucracy in American Education

ERIC Educational Resources Information Center

Katz, Michael B.

1971-01-01

Four models of public education conflicted during the first half of the 19th century; paternalistic and corporate voluntarism, democratic localism, and incipient bureaucracy. The models and underlying value conflicts are analyzed, revealing a growing role for schools--mediating between social change and social structure. (Author/DB)

Uncovering the influence of social skills and psychosociological factors on pain sensitivity using structural equation modeling

PubMed Central

Tanaka, Yoichi; Nishi, Yuki; Nishi, Yuki; Osumi, Michihiro; Morioka, Shu

2017-01-01

Pain is a subjective emotional experience that is influenced by psychosociological factors such as social skills, which are defined as problem-solving abilities in social interactions. This study aimed to reveal the relationships among pain, social skills, and other psychosociological factors by using structural equation modeling. A total of 101 healthy volunteers (41 men and 60 women; mean age: 36.6±12.7 years) participated in this study. To evoke participants’ sense of inner pain, we showed them images of painful scenes on a PC screen and asked them to evaluate the pain intensity by using the visual analog scale (VAS). We examined the correlation between social skills and VAS, constructed a hypothetical model based on results from previous studies and the current correlational analysis results, and verified the model’s fit using structural equation modeling. We found significant positive correlations between VAS and total social skills values, as well as between VAS and the “start of relationships” subscales. Structural equation modeling revealed that the values for “start of relationships” had a direct effect on VAS values (path coefficient =0.32, p<0.01). In addition, the “start of relationships” had both a direct and an indirect effect on psychological factors via social support. The results indicated that extroverted people are more sensitive to inner pain and tend to get more social support and maintain a better psychological condition. PMID:28979161

Localization of wood floor structure by infrared thermography

NASA Astrophysics Data System (ADS)

Cochior Plescanu, C.; Klein, M.; Ibarra-Castanedo, C.; Bendada, A.; Maldague, X.

2008-03-01

One of our industrial partners, Assek Technologie, is interested in developing a technique that would improve the drying process of wood floor in basements after flooding. In order to optimize the procedure, the floor structure and the damaged (wet) area extent must first be determined with minimum intrusion (minimum or no dismantling). The present study presents the use of infrared thermography to reveal the structure of (flooded) wood floors. The procedure involves opening holes in the floor. Injecting some hot air through those holes reveals the framing structure even if the floor is covered by vinyl or ceramic tiles. This study indicates that thermal imaging can also be used as a tool to validate the decontamination process after drying. Thermal images were obtained on small-scale models and in a demonstration room.

The mechanism of monomer transfer between two structurally distinct PrP oligomers

PubMed Central

Armiento, Aurora; Martin, Davy; Lepejova, Nad’a

2017-01-01

In mammals, Prion pathology refers to a class of infectious neuropathologies whose mechanism is based on the self-perpetuation of structural information stored in the pathological conformer. The characterisation of the PrP folding landscape has revealed the existence of a plethora of pathways conducing to the formation of structurally different assemblies with different biological properties. However, the biochemical interconnection between these diverse assemblies remains unclear. The PrP oligomerisation process leads to the formation of neurotoxic and soluble assemblies called O1 oligomers with a high size heterodispersity. By combining the measurements in time of size distribution and average size with kinetic models and data assimilation, we revealed the existence of at least two structurally distinct sets of assemblies, termed Oa and Ob, forming O1 assemblies. We propose a kinetic model representing the main processes in prion aggregation pathway: polymerisation, depolymerisation, and disintegration. The two groups interact by exchanging monomers through a disintegration process that increases the size of Oa. Our observations suggest that PrP oligomers constitute a highly dynamic population. PMID:28746342

The mechanism of monomer transfer between two structurally distinct PrP oligomers.

PubMed

Armiento, Aurora; Moireau, Philippe; Martin, Davy; Lepejova, Nad'a; Doumic, Marie; Rezaei, Human

2017-01-01

In mammals, Prion pathology refers to a class of infectious neuropathologies whose mechanism is based on the self-perpetuation of structural information stored in the pathological conformer. The characterisation of the PrP folding landscape has revealed the existence of a plethora of pathways conducing to the formation of structurally different assemblies with different biological properties. However, the biochemical interconnection between these diverse assemblies remains unclear. The PrP oligomerisation process leads to the formation of neurotoxic and soluble assemblies called O1 oligomers with a high size heterodispersity. By combining the measurements in time of size distribution and average size with kinetic models and data assimilation, we revealed the existence of at least two structurally distinct sets of assemblies, termed Oa and Ob, forming O1 assemblies. We propose a kinetic model representing the main processes in prion aggregation pathway: polymerisation, depolymerisation, and disintegration. The two groups interact by exchanging monomers through a disintegration process that increases the size of Oa. Our observations suggest that PrP oligomers constitute a highly dynamic population.

Polymer modeling of the E. coli genome reveals the involvement of locus positioning and macrodomain structuring for the control of chromosome conformation and segregation

PubMed Central

Junier, Ivan; Boccard, Frédéric; Espéli, Olivier

2014-01-01

The mechanisms that control chromosome conformation and segregation in bacteria have not yet been elucidated. In Escherichia coli, the mere presence of an active process remains an open question. Here, we investigate the conformation and segregation pattern of the E. coli genome by performing numerical simulations on a polymer model of the chromosome. We analyze the roles of the intrinsic structuring of chromosomes and the forced localization of specific loci, which are observed in vivo. Specifically, we examine the segregation pattern of a chromosome that is divided into four structured macrodomains (MDs) and two non-structured regions. We find that strong osmotic-like organizational forces, which stem from the differential condensation levels of the chromosome regions, dictate the cellular disposition of the chromosome. Strikingly, the comparison of our in silico results with fluorescent imaging of the chromosome choreography in vivo reveals that in the presence of MDs the targeting of the origin and terminus regions to specific positions are sufficient to generate a segregation pattern that is indistinguishable from experimentally observed patterns. PMID:24194594

A spatiotemporal structure: common to subatomic systems, biological processes, and economic cycles

NASA Astrophysics Data System (ADS)

Naitoh, Ken

2012-03-01

A theoretical model derived based on a quasi-stability concept applied to momentum conservation (Naitoh, JJIAM, 2001, Artificial Life Robotics, 2008, 2010) has revealed the spatial structure of various systems. This model explains the reason why particles such as biological cells, nitrogenous bases, and liquid droplets have bimodal size ratios of about 2:3 and 1:1. This paper shows that the same theory holds true for several levels of parcels from baryons to stars in the cosmos: specifically, at the levels of nuclear force, van der Waals force, surface tension, and the force of gravity. A higher order of analysis clarifies other asymmetric ratios related to the halo structure seen in atoms and amino acids. We will also show that our minimum hypercycle theory for explaining the morphogenetic cycle (Naitoh, Artificial Life Robotics, 2008) reveals other temporal cycles such as those of economic systems and the circadian clock as well as the fundamental neural network pattern (topological pattern). Finally, a universal equation describing the spatiotemporal structure of several systems will be derived, which also leads to a general concept of quasi-stability.

The strength study of the rotating device driver indexing spatial mechanism

NASA Astrophysics Data System (ADS)

Zakharenkov, N. V.; Kvasov, I. N.

2018-04-01

The indexing spatial mechanisms are widely used in automatic machines. The mechanisms maximum load-bearing capacity measurement is possible based on both the physical and numerical models tests results. The paper deals with the driven disk indexing spatial cam mechanism numerical model at the constant angular cam velocity. The presented mechanism kinematics and geometry parameters and finite element model are analyzed in the SolidWorks design environment. The calculation initial data and missing parameters having been found from the structure analysis were identified. The structure and kinematics analysis revealed the mechanism failures possible reasons. The numerical calculations results showing the structure performance at the contact and bending stresses are represented.

Risk Assessment of Alzheimer's Disease using the Information Diffusion Model from Structural Magnetic Resonance Imaging.

PubMed

Beheshti, Iman; Olya, Hossain G T; Demirel, Hasan

2016-04-05

Recently, automatic risk assessment methods have been a target for the detection of Alzheimer's disease (AD) risk. This study aims to develop an automatic computer-aided AD diagnosis technique for risk assessment of AD using information diffusion theory. Information diffusion is a fuzzy mathematics logic of set-value that is used for risk assessment of natural phenomena, which attaches fuzziness (uncertainty) and incompleteness. Data were obtained from voxel-based morphometry analysis of structural magnetic resonance imaging. The information diffusion model results revealed that the risk of AD increases with a reduction of the normalized gray matter ratio (p > 0.5, normalized gray matter ratio <40%). The information diffusion model results were evaluated by calculation of the correlation of two traditional risk assessments of AD, the Mini-Mental State Examination and the Clinical Dementia Rating. The correlation results revealed that the information diffusion model findings were in line with Mini-Mental State Examination and Clinical Dementia Rating results. Application of information diffusion model contributes to the computerization of risk assessment of AD, which has a practical implication for the early detection of AD.

Models for the a subunits of the Thermus thermophilus V/A-ATPase and Saccharomyces cerevisiae V-ATPase enzymes by cryo-EM and evolutionary covariance

PubMed Central

Schep, Daniel G.; Rubinstein, John L.

2016-01-01

Rotary ATPases couple ATP synthesis or hydrolysis to proton translocation across a membrane. However, understanding proton translocation has been hampered by a lack of structural information for the membrane-embedded a subunit. The V/A-ATPase from the eubacterium Thermus thermophilus is similar in structure to the eukaryotic V-ATPase but has a simpler subunit composition and functions in vivo to synthesize ATP rather than pump protons. We determined the T. thermophilus V/A-ATPase structure by cryo-EM at 6.4 Å resolution. Evolutionary covariance analysis allowed tracing of the a subunit sequence within the map, providing a complete model of the rotary ATPase. Comparing the membrane-embedded regions of the T. thermophilus V/A-ATPase and eukaryotic V-ATPase from Saccharomyces cerevisiae allowed identification of the α-helices that belong to the a subunit and revealed the existence of previously unknown subunits in the eukaryotic enzyme. Subsequent evolutionary covariance analysis enabled construction of a model of the a subunit in the S. cerevisae V-ATPase that explains numerous biochemical studies of that enzyme. Comparing the two a subunit structures determined here with a structure of the distantly related a subunit from the bovine F-type ATP synthase revealed a conserved pattern of residues, suggesting a common mechanism for proton transport in all rotary ATPases. PMID:26951669

Structural Models that Manage IT Portfolio Affecting Business Value of Enterprise Architecture

NASA Astrophysics Data System (ADS)

Kamogawa, Takaaki

This paper examines the structural relationships between Information Technology (IT) governance and Enterprise Architecture (EA), with the objective of enhancing business value in the enterprise society. Structural models consisting of four related hypotheses reveal the relationship between IT governance and EA in the improvement of business values. We statistically examined the hypotheses by analyzing validated questionnaire items from respondents within firms listed on the Japanese stock exchange who were qualified to answer them. We concluded that firms which have organizational ability controlled by IT governance are more likely to deliver business value based on IT portfolio management.

Gender differences in the factor structure of posttraumatic stress disorder symptoms in war-exposed adolescents.

PubMed

Armour, Cherie; Elhai, Jon D; Layne, Christopher M; Shevlin, Mark; Duraković-Belko, Elvira; Djapo, Nermin; Pynoos, Robert S

2011-05-01

DSM-IV's three-factor model of posttraumatic stress disorder (PTSD) is rarely empirically supported, whereas other four-factor models (King et al., 1998; Simms, Watson, & Doebbeling, 2002) have proven to be better representations of PTSD's latent structure. To date, a clear consensus as to which model provides the best representation of PTSD's underlying dimensions has yet to be reached. The current study investigated whether gender is associated with factor structure differences using the King et al. (1998) model of reexperiencing, avoidance, numbing, and hyperarousal PTSD symptoms. Participants were war-exposed Bosnian secondary/high school boys and girls (N=1572) assessed nearly two years after the 1992-1995 Bosnian conflict. Confirmatory factor analytic tests of measurement invariance across PTSD model parameters revealed many significant sex-linked differences. Implications regarding the potential role of gender as a moderator of the King et al. (1998) model's factor structure are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

A new method for constructing networks from binary data

NASA Astrophysics Data System (ADS)

van Borkulo, Claudia D.; Borsboom, Denny; Epskamp, Sacha; Blanken, Tessa F.; Boschloo, Lynn; Schoevers, Robert A.; Waldorp, Lourens J.

2014-08-01

Network analysis is entering fields where network structures are unknown, such as psychology and the educational sciences. A crucial step in the application of network models lies in the assessment of network structure. Current methods either have serious drawbacks or are only suitable for Gaussian data. In the present paper, we present a method for assessing network structures from binary data. Although models for binary data are infamous for their computational intractability, we present a computationally efficient model for estimating network structures. The approach, which is based on Ising models as used in physics, combines logistic regression with model selection based on a Goodness-of-Fit measure to identify relevant relationships between variables that define connections in a network. A validation study shows that this method succeeds in revealing the most relevant features of a network for realistic sample sizes. We apply our proposed method to estimate the network of depression and anxiety symptoms from symptom scores of 1108 subjects. Possible extensions of the model are discussed.

Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution

NASA Astrophysics Data System (ADS)

Schur, Florian K. M.; Hagen, Wim J. H.; Rumlová, Michaela; Ruml, Tomáš; Müller, Barbara; Kräusslich, Hans-Georg; Briggs, John A. G.

2015-01-01

Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all α-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.

The structure of Escherichia coli signal recognition particle revealed by scanning transmission electron microscopy.

PubMed

Mainprize, Iain L; Beniac, Daniel R; Falkovskaia, Elena; Cleverley, Robert M; Gierasch, Lila M; Ottensmeyer, F Peter; Andrews, David W

2006-12-01

Structural studies on various domains of the ribonucleoprotein signal recognition particle (SRP) have not converged on a single complete structure of bacterial SRP consistent with the biochemistry of the particle. We obtained a three-dimensional structure for Escherichia coli SRP by cryoscanning transmission electron microscopy and mapped the internal RNA by electron spectroscopic imaging. Crystallographic data were fit into the SRP reconstruction, and although the resulting model differed from previous models, they could be rationalized by movement through an interdomain linker of Ffh, the protein component of SRP. Fluorescence resonance energy transfer experiments determined interdomain distances that were consistent with our model of SRP. Docking our model onto the bacterial ribosome suggests a mechanism for signal recognition involving interdomain movement of Ffh into and out of the nascent chain exit site and suggests how SRP could interact and/or compete with the ribosome-bound chaperone, trigger factor, for a nascent chain during translation.

Does Attention-Deficit/Hyperactivity Disorder Have a Dimensional Latent Structure? A Taxometric Analysis

PubMed Central

Marcus, David K.; Barry, Tammy D.

2010-01-01

An understanding of the latent structure of attention-deficit/hyperactivity disorder (ADHD) is essential for developing causal models of this disorder. Although some researchers have presumed that ADHD is dimensional and others have assumed that it is taxonic, there has been relatively little research directly examining the latent structure of ADHD. The authors conducted a set of taxometric analyses using data from the NICHD Study of Early Child Care and Youth Development (ns between 667–1078). The results revealed a dimensional latent structure across a variety of different analyses and sets of indicators, for inattention, hyperactivity/impulsivity, and ADHD. Furthermore, analyses of correlations with associated features indicated that dimensional models demonstrated stronger validity coefficients with these criterion measures than dichotomous models. These findings jibe with recent research on the genetic basis of ADHD and with contemporary models of ADHD. PMID:20973595

Modeling structural change in spatial system dynamics: A Daisyworld example.

PubMed

Neuwirth, C; Peck, A; Simonović, S P

2015-03-01

System dynamics (SD) is an effective approach for helping reveal the temporal behavior of complex systems. Although there have been recent developments in expanding SD to include systems' spatial dependencies, most applications have been restricted to the simulation of diffusion processes; this is especially true for models on structural change (e.g. LULC modeling). To address this shortcoming, a Python program is proposed to tightly couple SD software to a Geographic Information System (GIS). The approach provides the required capacities for handling bidirectional and synchronized interactions of operations between SD and GIS. In order to illustrate the concept and the techniques proposed for simulating structural changes, a fictitious environment called Daisyworld has been recreated in a spatial system dynamics (SSD) environment. The comparison of spatial and non-spatial simulations emphasizes the importance of considering spatio-temporal feedbacks. Finally, practical applications of structural change models in agriculture and disaster management are proposed.

Does attention-deficit/hyperactivity disorder have a dimensional latent structure? A taxometric analysis.

PubMed

Marcus, David K; Barry, Tammy D

2011-05-01

An understanding of the latent structure of attention-deficit/hyperactivity disorder (ADHD) is essential for developing causal models of this disorder. Although some researchers have presumed that ADHD is dimensional and others have assumed that it is taxonic, there has been relatively little research directly examining the latent structure of ADHD. The authors conducted a set of taxometric analyses using data from the NICHD Study of Early Child Care and Youth Development (ns between 667 and 1,078). The results revealed a dimensional latent structure across a variety of different analyses and sets of indicators for inattention, hyperactivity/impulsivity, and ADHD. Furthermore, analyses of correlations with associated features indicated that dimensional models demonstrated stronger validity coefficients with these criterion measures than dichotomous models. These findings jibe with recent research on the genetic basis of ADHD and with contemporary models of ADHD.

Computational analysis of human and mouse CREB3L4 Protein

PubMed Central

Velpula, Kiran Kumar; Rehman, Azeem Abdul; Chigurupati, Soumya; Sanam, Ramadevi; Inampudi, Krishna Kishore; Akila, Chandra Sekhar

2012-01-01

CREB3L4 is a member of the CREB/ATF transcription factor family, characterized by their regulation of gene expression through the cAMP-responsive element. Previous studies identified this protein in mice and humans. Whereas CREB3L4 in mice (referred to as Tisp40) is found in the testes and functions in spermatogenesis, human CREB3L4 is primarily detected in the prostate and has been implicated in cancer. We conducted computational analyses to compare the structural homology between murine Tisp40α human CREB3L4. Our results reveal that the primary and secondary structures of the two proteins contain high similarity. Additionally, predicted helical transmembrane structure reveals that the proteins likely have similar structure and function. This study offers preliminary findings that support the translation of mouse Tisp40α findings into human models, based on structural homology. PMID:22829733

Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

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

Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance

2011-09-20

The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS-ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the {alpha}2 helix and in the conformation of the {alpha}3-{alpha}4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4-6.0). In contrast, at a highermore » pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS-ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS-ADP adopt different conformations depending upon the pH conditions of the crystallization solution.« less

3D Density Structure of Oceanic Lithosphere Affected by A Plume: A Case Study from the Greater Jan Mayen-East Greenland Region (NE Atlantic)

NASA Astrophysics Data System (ADS)

Tan, P.; Sippel, J.; Breivik, A. J.; Scheck-Wenderoth, M.; Meeßen, C.

2017-12-01

Unraveling the density structure of the oceanic lithosphere north of Iceland is key for understanding the effects of the Iceland Plume on the mid-ocean ridges of the greater Jan Mayen-East Greenland Region. We use a data-integrative approach for 3D gravity modeling to develop new insights into the crust and upper mantle density structure of this region. First, we obtain the 3D density structure of the sediments and crust from interpretations of regional reflection and refraction seismic lines. Then, the temperature and density structure of the mantle between 50 and 250 km are derived from a published shear-wave velocity (Vs) tomography model. To assess the density configuration between the Moho and 50 km depth, we follow a combined forward and inverse 3D gravity modeling approach. The Vs tomography and derived density of the deeper mantle (>50 km depth) reveal that the low-density anomaly related to the Iceland plume gets weaker with increasing distance from the plume, i.e. from the strongly influenced Middle Kolbeinsey Ridge (MKR) to the Mohn's Ridge. The West Jan Mayen Fracture Zone is identified as a main mantle density contrast, indicative of differences in the thermal evolution of the ridge systems it separates. Beneath the MKR region, the low-density anomaly at depths of >50 km continues upwards into the uppermost mantle, where its lateral dimensions narrow considerably. This elongated density anomaly is consistent with a basement high and indicates a channelization of the Iceland plume effects. The NE-SW elongated mantle anomaly does not, however, coincide with the topographical NNE-SSW striking ridge axis. Thus, the modelled plume-affected oceanic lithosphere reveals discrepancies with the half-space cooling model. We discuss the 3D density model in terms of such spatial relations between deeper mantle anomalies and the shallow crustal structure.

Gamma-Ray Pulsar Light Curves as Probes of Magnetospheric Structure

NASA Technical Reports Server (NTRS)

Harding, A. K.

2016-01-01

The large number of gamma-ray pulsars discovered by the Fermi Gamma-Ray Space Telescope since its launch in 2008 dwarfs the handful that were previously known. The variety of observed light curves makes possible a tomography of both the ensemble-averaged field structure and the high-energy emission regions of a pulsar magnetosphere. Fitting the gamma-ray pulsar light curves with model magnetospheres and emission models has revealed that most of the high-energy emission, and the particles acceleration, takes place near or beyond the light cylinder, near the current sheet. As pulsar magnetosphere models become more sophisticated, it is possible to probe magnetic field structure and emission that are self-consistently determined. Light curve modeling will continue to be a powerful tool for constraining the pulsar magnetosphere physics.

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

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

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

2007-01-01

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

Polymer Physics of the Large-Scale Structure of Chromatin.

PubMed

Bianco, Simona; Chiariello, Andrea Maria; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2016-01-01

We summarize the picture emerging from recently proposed models of polymer physics describing the general features of chromatin large scale spatial architecture, as revealed by microscopy and Hi-C experiments.

Structure of turbulent non-premixed flames modeled with two-step chemistry

NASA Technical Reports Server (NTRS)

Chen, J. H.; Mahalingam, S.; Puri, I. K.; Vervisch, L.

1992-01-01

Direct numerical simulations of turbulent diffusion flames modeled with finite-rate, two-step chemistry, A + B yields I, A + I yields P, were carried out. A detailed analysis of the turbulent flame structure reveals the complex nature of the penetration of various reactive species across two reaction zones in mixture fraction space. Due to this two zone structure, these flames were found to be robust, resisting extinction over the parameter ranges investigated. As in single-step computations, mixture fraction dissipation rate and the mixture fraction were found to be statistically correlated. Simulations involving unequal molecular diffusivities suggest that the small scale mixing process and, hence, the turbulent flame structure is sensitive to the Schmidt number.

Evaluating Individual Students' Perceptions of Instructional Quality: An Investigation of their Factor Structure, Measurement Invariance, and Relations to Educational Outcomes.

PubMed

Scherer, Ronny; Nilsen, Trude; Jansen, Malte

2016-01-01

Students' perceptions of instructional quality are among the most important criteria for evaluating teaching effectiveness. The present study evaluates different latent variable modeling approaches (confirmatory factor analysis, exploratory structural equation modeling, and bifactor modeling), which are used to describe these individual perceptions with respect to their factor structure, measurement invariance, and the relations to selected educational outcomes (achievement, self-concept, and motivation in mathematics). On the basis of the Programme for International Student Assessment (PISA) 2012 large-scale data sets of Australia, Canada, and the USA (N = 26,746 students), we find support for the distinction between three factors of individual students' perceptions and full measurement invariance across countries for all modeling approaches. In this regard, bifactor exploratory structural equation modeling outperformed alternative approaches with respect to model fit. Our findings reveal significant relations to the educational outcomes. This study synthesizes different modeling approaches of individual students' perceptions of instructional quality and provides insights into the nature of these perceptions from an individual differences perspective. Implications for the measurement and modeling of individually perceived instructional quality are discussed.

The CHIC Model: A Global Model for Coupled Binary Data

ERIC Educational Resources Information Center

Wilderjans, Tom; Ceulemans, Eva; Van Mechelen, Iven

2008-01-01

Often problems result in the collection of coupled data, which consist of different N-way N-mode data blocks that have one or more modes in common. To reveal the structure underlying such data, an integrated modeling strategy, with a single set of parameters for the common mode(s), that is estimated based on the information in all data blocks, may…

On vital aid: the why, what and how of validation

PubMed Central

Kleywegt, Gerard J.

2009-01-01

Limitations to the data and subjectivity in the structure-determination process may cause errors in macromolecular crystal structures. Appropriate validation techniques may be used to reveal problems in structures, ideally before they are analysed, published or deposited. Additionally, such tech­niques may be used a posteriori to assess the (relative) merits of a model by potential users. Weak validation methods and statistics assess how well a model reproduces the information that was used in its construction (i.e. experimental data and prior knowledge). Strong methods and statistics, on the other hand, test how well a model predicts data or information that were not used in the structure-determination process. These may be data that were excluded from the process on purpose, general knowledge about macromolecular structure, information about the biological role and biochemical activity of the molecule under study or its mutants or complexes and predictions that are based on the model and that can be tested experimentally. PMID:19171968

Three-Dimensional Electrical Resistivity Tomography of the Solfatara Crater (Italy): Implication for the Multiphase Flow Structure of the Shallow Hydrothermal System

NASA Astrophysics Data System (ADS)

Gresse, Marceau; Vandemeulebrouck, Jean; Byrdina, Svetlana; Chiodini, Giovanni; Revil, André; Johnson, Timothy C.; Ricci, Tullio; Vilardo, Giuseppe; Mangiacapra, Annarita; Lebourg, Thomas; Grangeon, Jacques; Bascou, Pascale; Metral, Laurent

2017-11-01

The Solfatara volcano is the main degassing area of the Campi Flegrei caldera, characterized by 60 years of unrest. Assessing such renewal activity is a challenging task because hydrothermal interactions with magmatic gases remain poorly understood. In this study, we decipher the complex structure of the shallow Solfatara hydrothermal system by performing the first 3-D, high-resolution, electrical resistivity tomography of the volcano. The 3-D resistivity model was obtained from the inversion of 43,432 resistance measurements performed on an area of 0.68 km2. The proposed interpretation of the multiphase hydrothermal structures is based on the resistivity model, a high-resolution infrared surface temperature image, and 1,136 soil CO2 flux measurements. In addition, we realized 27 soil cation exchange capacity and pH measurements demonstrating a negligible contribution of surface conductivity to the shallow bulk electrical conductivity. Hence, we show that the resistivity changes are mainly controlled by fluid content and temperature. The high-resolution tomograms identify for the first time the structure of the gas-dominated reservoir at 60 m depth that feeds the Bocca Grande fumarole through a 10 m thick channel. In addition, the resistivity model reveals a channel-like conductive structure where the liquid produced by steam condensation around the main fumaroles flows down to the Fangaia area within a buried fault. The model delineates the emplacement of the main geological structures: Mount Olibano, Solfatara cryptodome, and tephra deposits. It also reveals the anatomy of the hydrothermal system, especially two liquid-dominated plumes, the Fangaia mud pool and the Pisciarelli fumarole, respectively.

Sub-nanometer surface chemistry and orbital hybridization in lanthanum-doped ceria nano-catalysts revealed by 3D electron microscopy.

PubMed

Collins, Sean M; Fernandez-Garcia, Susana; Calvino, José J; Midgley, Paul A

2017-07-14

Surface chemical composition, electronic structure, and bonding characteristics determine catalytic activity but are not resolved for individual catalyst particles by conventional spectroscopy. In particular, the nano-scale three-dimensional distribution of aliovalent lanthanide dopants in ceria catalysts and their effect on the surface electronic structure remains unclear. Here, we reveal the surface segregation of dopant cations and oxygen vacancies and observe bonding changes in lanthanum-doped ceria catalyst particle aggregates with sub-nanometer precision using a new model-based spectroscopic tomography approach. These findings refine our understanding of the spatially varying electronic structure and bonding in ceria-based nanoparticle aggregates with aliovalent cation concentrations and identify new strategies for advancing high efficiency doped ceria nano-catalysts.

Fermi Research Alliance LLC

Science.gov Websites

dark matter structure in universe The findings - the most accurate made of the universe's present large -scale structure - support the dark matter/dark energy model. Read More Muon g-2 Muon magnet's moment has massive international experiment. Read More Dark Energy Camera DES reveals most accurate measurement of

Revealing driving factors of China's PM2.5 pollution

NASA Astrophysics Data System (ADS)

Zheng, Y.; Zhao, H.; Zhang, Q.; Geng, G.; Tong, D.; Peng, L.; He, K.

2017-12-01

China's rapid economic development and intensive energy consumption are deteriorating the air quality significantly. Understanding the key driving factors behind China's growing emissions of air pollutants and the accompanying PM2.5 pollution is critical for the development of China's clean air policies and also provides insight into how other emerging economies may develop a clear sky future. Here we reveal the socioeconomic drivers of the variations of China's PM2.5 concentrations during 2002-2012 by using an interdisciplinary framework that integrates an emission inventory model, an index decomposition analysis model, and a regional air quality model. The decomposition results demostrate that the improvements in emission efficiency and energy efficiency failed to offset the increased emissions of both primary PM2.5 and gaseous PM2.5 precursors (including SO2 NOx, and volatile organic compounds) triggered by the surging economic growth during 2002-2012. During the same time, the effects of energy structure, production structure and population growth were relatively less significant to all pollutants, which indicates the potential of large emission abatements through energy structure and production structure adjustment. Sensitivity simulations by the air quality model based on the provincial decomposition results also show that the economic growth have outpaced efficiency improvements in the increments of PM2.5 concentrations during the study years. As China continues to develop rapidly, future policies should promote further improvements in efficiency and accelerate the adjustments toward clean energy and production structures, which are critical for reducing China's emissions and alleviating the severe PM2.5 pollution.

Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure.

PubMed

Ishak, Siti Nor Hasmah; Aris, Sayangku Nor Ariati Mohamad; Halim, Khairul Bariyyah Abd; Ali, Mohd Shukuri Mohamad; Leow, Thean Chor; Kamarudin, Nor Hafizah Ahmad; Masomian, Malihe; Rahman, Raja Noor Zaliha Raja Abd

2017-09-25

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition.

Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

PubMed

Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

2009-12-01

The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

Images of Leadership and their Effect Upon School Principals' Performance

NASA Astrophysics Data System (ADS)

Gaziel, Haim

2003-09-01

The purpose of the present study is to identify how school principals perceive their world and how their perceptions influence their effectiveness as managers and leaders. The principals' views of their world were categorised into four different metaphorical ways of describing the workings of organisations: (1) the structural model (organisations as machines); (2) the human-resource model (organisations as organisms); (3) the political model (organisations as political systems); (4) the symbolic model (organisations as cultural patterns and clusters of myths and symbols). The results reveal that the best predictors of school principals' effectiveness as managers, according to their own assessments and teachers' reports, are the structural and human resource models, while the best predictors of effective leadership are the political and human-resource models.

The Minimum M3-M4 Loop Length of Neurotransmitter-activated Pentameric Receptors Is Critical for the Structural Integrity of Cytoplasmic Portals*

PubMed Central

Baptista-Hon, Daniel T.; Deeb, Tarek Z.; Lambert, Jeremy J.; Peters, John A.; Hales, Tim G.

2013-01-01

The 5-HT3A receptor homology model, based on the partial structure of the nicotinic acetylcholine receptor from Torpedo marmorata, reveals an asymmetric ion channel with five portals framed by adjacent helical amphipathic (HA) stretches within the 114-residue loop between the M3 and M4 membrane-spanning domains. The positive charge of Arg-436, located within the HA stretch, is a rate-limiting determinant of single channel conductance (γ). Further analysis reveals that positive charge and volume of residue 436 are determinants of 5-HT3A receptor inward rectification, exposing an additional role for portals. A structurally unresolved stretch of 85 residues constitutes the bulk of the M3-M4 loop, leaving a >45-Å gap in the model between M3 and the HA stretch. There are no additional structural data for this loop, which is vestigial in bacterial pentameric ligand-gated ion channels and was largely removed for crystallization of the Caenorhabditis elegans glutamate-activated pentameric ligand-gated ion channels. We created 5-HT3A subunit loop truncation mutants, in which sequences framing the putative portals were retained, to determine the minimum number of residues required to maintain their functional integrity. Truncation to between 90 and 75 amino acids produced 5-HT3A receptors with unaltered rectification. Truncation to 70 residues abolished rectification and increased γ. These findings reveal a critical M3-M4 loop length required for functions attributable to cytoplasmic portals. Examination of all 44 subunits of the human neurotransmitter-activated Cys-loop receptors reveals that, despite considerable variability in their sequences and lengths, all M3-M4 loops exceed 70 residues, suggesting a fundamental requirement for portal integrity. PMID:23740249

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation.

PubMed

Kim, Jeong Joo; Lorenz, Robin; Arold, Stefan T; Reger, Albert S; Sankaran, Banumathi; Casteel, Darren E; Herberg, Friedrich W; Kim, Choel

2016-05-03

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Nedelkoski, Zlatko; Kepaptsoglou, Demie; Lari, Leonardo

We compare the structural, chemical, and magnetic properties of magnetite nanoparticles. Aberration corrected scanning transmission electron microscopy reveals the prevalence of antiphase boundaries in nanoparticles that have significantly reduced magnetization, relative to the bulk. We show that atomistic magnetic modelling of nanoparticles with and without these defects reveal the origin of the reduced moment. Strong antiferromagnetic interactions across antiphase boundaries support multiple magnetic domains even in particles as small as 12–14 nm.

Computing by physical interaction in neurons.

PubMed

Aur, Dorian; Jog, Mandar; Poznanski, Roman R

2011-12-01

The electrodynamics of action potentials represents the fundamental level where information is integrated and processed in neurons. The Hodgkin-Huxley model cannot explain the non-stereotyped spatial charge density dynamics that occur during action potential propagation. Revealed in experiments as spike directivity, the non-uniform charge density dynamics within neurons carry meaningful information and suggest that fragments of information regarding our memories are endogenously stored in structural patterns at a molecular level and are revealed only during spiking activity. The main conceptual idea is that under the influence of electric fields, efficient computation by interaction occurs between charge densities embedded within molecular structures and the transient developed flow of electrical charges. This process of computation underlying electrical interactions and molecular mechanisms at the subcellular level is dissimilar from spiking neuron models that are completely devoid of physical interactions. Computation by interaction describes a more powerful continuous model of computation than the one that consists of discrete steps as represented in Turing machines.

Do sophisticated epistemic beliefs predict meaningful learning? Findings from a structural equation model of undergraduate biology learning

NASA Astrophysics Data System (ADS)

Lee, Silvia Wen-Yu; Liang, Jyh-Chong; Tsai, Chin-Chung

2016-10-01

This study investigated the relationships among college students' epistemic beliefs in biology (EBB), conceptions of learning biology (COLB), and strategies of learning biology (SLB). EBB includes four dimensions, namely 'multiple-source,' 'uncertainty,' 'development,' and 'justification.' COLB is further divided into 'constructivist' and 'reproductive' conceptions, while SLB represents deep strategies and surface learning strategies. Questionnaire responses were gathered from 303 college students. The results of the confirmatory factor analysis and structural equation modelling showed acceptable model fits. Mediation testing further revealed two paths with complete mediation. In sum, students' epistemic beliefs of 'uncertainty' and 'justification' in biology were statistically significant in explaining the constructivist and reproductive COLB, respectively; and 'uncertainty' was statistically significant in explaining the deep SLB as well. The results of mediation testing further revealed that 'uncertainty' predicted surface strategies through the mediation of 'reproductive' conceptions; and the relationship between 'justification' and deep strategies was mediated by 'constructivist' COLB. This study provides evidence for the essential roles some epistemic beliefs play in predicting students' learning.

Differential Relations of Depression and Social Anxiety Symptoms to the Facets of Extraversion/Positive Emotionality

PubMed Central

Naragon-Gainey, Kristin; Watson, David; Markon, Kristian E.

2009-01-01

Previous research has shown that depression and social anxiety—two “facets” of internalizing psychopathology— both are characterized by low levels of extraversion/positive emotionality (E/PE). However, little is known about the relations of the facets of E/PE with symptoms of depression and social anxiety. This study utilized multiple measures of each facet of E/PE, as well as depression and social anxiety symptoms. Self-report data were collected from large samples of college students and psychiatric outpatients. Separate factor analyses in each sample revealed a four-factor structure of E/PE, consisting of Sociability, Positive Emotionality, Ascendance, and Fun-Seeking. Structural equation modeling revealed that, after controlling for the higher-order internalizing factor and the overlap among the E/PE facets, social anxiety was broadly related to all four facets of E/PE, whereas depression was strongly related only to low positive emotionality. Implications for hierarchical models of personality and psychopathology, assessment and treatment, and etiological models are discussed. PMID:19413405

Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition

PubMed Central

Newman, Matthew; Murray-Rust, Judith; Lally, John; Rudolf, Jana; Fadden, Andrew; Knowles, Philip P; White, Malcolm F; McDonald, Neil Q

2005-01-01

The XPF/Mus81 structure-specific endonucleases cleave double-stranded DNA (dsDNA) within asymmetric branched DNA substrates and play an essential role in nucleotide excision repair, recombination and genome integrity. We report the structure of an archaeal XPF homodimer alone and bound to dsDNA. Superposition of these structures reveals a large domain movement upon binding DNA, indicating how the (HhH)2 domain and the nuclease domain are coupled to allow the recognition of double-stranded/single-stranded DNA junctions. We identify two nonequivalent DNA-binding sites and propose a model in which XPF distorts the 3′ flap substrate in order to engage both binding sites and promote strand cleavage. The model rationalises published biochemical data and implies a novel role for the ERCC1 subunit of eukaryotic XPF complexes. PMID:15719018

The effect of climatic forcing on population synchrony and genetic structuring of the Canadian lynx

PubMed Central

Stenseth, Nils Chr.; Ehrich, Dorothee; Rueness, Eli Knispel; Lingjærde, Ole Chr.; Chan, Kung-Sik; Boutin, Stan; O'Donoghue, Mark; Robinson, David A.; Viljugrein, Hildegunn; Jakobsen, Kjetill S.

2004-01-01

The abundance of Canadian lynx follows 10-year density fluctuations across the Canadian subcontinent. These cyclic fluctuations have earlier been shown to be geographically structured into three climatic regions: the Atlantic, Continental, and Pacific zones. Recent genetic evidence revealed an essentially similar spatial structuring. Introducing a new population model, the “climate forcing of ecological and evolutionary patterns” model, we link the observed ecological and evolutionary patterns. Specifically, we demonstrate that there is greater phase synchrony within climatic zones than between them and show that external climatic forcing may act as a synchronizer. We simulated genetic drift by using data on population dynamics generated by the climate forcing of ecological and evolutionary patterns model, and we demonstrate that the observed genetic structuring can be seen as an emerging property of the spatiotemporal ecological dynamics. PMID:15067131

Structural and functional analysis of a novel psychrophilic β-mannanase from Glaciozyma antarctica PI12

NASA Astrophysics Data System (ADS)

Parvizpour, Sepideh; Razmara, Jafar; Ramli, Aizi Nor Mazila; Md Illias, Rosli; Shamsir, Mohd Shahir

2014-06-01

The structure of a novel psychrophilic β-mannanase enzyme from Glaciozyma antarctica PI12 yeast has been modelled and analysed in detail. To our knowledge, this is the first attempt to model a psychrophilic β-mannanase from yeast. To this end, a 3D structure of the enzyme was first predicted using a threading method because of the low sequence identity (<30 %) using MODELLER9v12 and simulated using GROMACS at varying low temperatures for structure refinement. Comparisons with mesophilic and thermophilic mannanases revealed that the psychrophilic mannanase contains longer loops and shorter helices, increases in the number of aromatic and hydrophobic residues, reductions in the number of hydrogen bonds and salt bridges and numerous amino acid substitutions on the surface that increased the flexibility and its efficiency for catalytic reactions at low temperatures.

Application of viscous and Iwan modal damping models to experimental measurements from bolted structures

DOE PAGES

Deaner, Brandon J.; Allen, Matthew S.; Starr, Michael James; ...

2015-01-20

Measurements are presented from a two-beam structure with several bolted interfaces in order to characterize the nonlinear damping introduced by the joints. The measurements (all at force levels below macroslip) reveal that each underlying mode of the structure is well approximated by a single degree-of-freedom (SDOF) system with a nonlinear mechanical joint. At low enough force levels, the measurements show dissipation that scales as the second power of the applied force, agreeing with theory for a linear viscously damped system. This is attributed to linear viscous behavior of the material and/or damping provided by the support structure. At larger forcemore » levels, the damping is observed to behave nonlinearly, suggesting that damping from the mechanical joints is dominant. A model is presented that captures these effects, consisting of a spring and viscous damping element in parallel with a four-parameter Iwan model. As a result, the parameters of this model are identified for each mode of the structure and comparisons suggest that the model captures the stiffness and damping accurately over a range of forcing levels.« less

Identity Styles and Religiosity: Examining the Role of Identity Commitment

ERIC Educational Resources Information Center

Grajales, Tevni E.; Sommers, Brittany

2016-01-01

This study observed the role of identity styles, identity commitment, and identity statuses in predicting religiosity in a sample of undergraduate students attending a Seventh-day Adventist university (N = 138). Two structural models were evaluated via path analysis. Results revealed two strong models for the prediction of religiosity. Identity…

Demand for resident hunting in the southeastern United States

Treesearch

Neelam Poudyal; Seong Hoon Cho; J. Michael Bowker

2008-01-01

We modeled hunting demand among resident hunters in the Southeastern United States. Our model revealed that future hunting demand will likely decline in this region. Population growth in the region will increase demand but structural change in the region's demography (e.g., "browning" and "aging "), along with declining forestland access will...

A test of a linear model of glaucomatous structure-function loss reveals sources of variability in retinal nerve fiber and visual field measurements.

PubMed

Hood, Donald C; Anderson, Susan C; Wall, Michael; Raza, Ali S; Kardon, Randy H

2009-09-01

Retinal nerve fiber (RNFL) thickness and visual field loss data from patients with glaucoma were analyzed in the context of a model, to better understand individual variation in structure versus function. Optical coherence tomography (OCT) RNFL thickness and standard automated perimetry (SAP) visual field loss were measured in the arcuate regions of one eye of 140 patients with glaucoma and 82 normal control subjects. An estimate of within-individual (measurement) error was obtained by repeat measures made on different days within a short period in 34 patients and 22 control subjects. A linear model, previously shown to describe the general characteristics of the structure-function data, was extended to predict the variability in the data. For normal control subjects, between-individual error (individual differences) accounted for 87% and 71% of the total variance in OCT and SAP measures, respectively. SAP within-individual error increased and then decreased with increased SAP loss, whereas OCT error remained constant. The linear model with variability (LMV) described much of the variability in the data. However, 12.5% of the patients' points fell outside the 95% boundary. An examination of these points revealed factors that can contribute to the overall variability in the data. These factors include epiretinal membranes, edema, individual variation in field-to-disc mapping, and the location of blood vessels and degree to which they are included by the RNFL algorithm. The model and the partitioning of within- versus between-individual variability helped elucidate the factors contributing to the considerable variability in the structure-versus-function data.

The interplay between rheology and pre-existing structures in the lithosphere and its influence on intraplate tectonics: Insights from scaled physical analogue models.

NASA Astrophysics Data System (ADS)

Santimano, T. N.; Adiban, P.; Pysklywec, R.

2017-12-01

The primary controls of deformation in the lithosphere are related to its rheological properties. In addition, recent work reveals that inherited zones of weakness in the deep lithosphere are prevalent and can also define tectonic activity. To understand how deformation is genetically related to rheology and/or pre-existing structures, we compare a set of physical analogue models with the presence and absence of a fault in the deep lithosphere. The layered lithosphere scaled models of a brittle upper crust, viscous lower crust and viscous mantle lithosphere are deformed in a convergent setting. Deformation of the model is recorded using high spatial and temporal stereoscopic cameras. We use Particle Image Velocimetry (PIV) to acquire a time-series dataset and study the velocity field and subsequently strain in the model. The finished model is also cut into cross-section revealing the finite internal structures that are then compared to the topography of the model. Preliminary results show that deformation in models with an inherited fault in the mantle lithosphere is accommodated by displacement along the fault plane that propagates into the overlying viscous lower crust and brittle upper crust. Here, the majority of the deformation is localized along the fault in a brittle manner. This is in contrast to the model absent of a fault that also displays significant amounts of deformation. In this setting, ductile deformation is accommodated by folding and thickening of the viscous layers and flexural shearing of the brittle upper crust. In these preliminary experiments, the difference in the strength profile between the mantle lithosphere and the lower crust is within the same order of magnitude. Future experiments will include models where the strength difference is an order of magnitude. This systematic study aids in understanding the role of rheology and deep structures particularly in transferring stress over time to the surface and is therefore fundamental in understanding intraplate tectonics and orogenesis.

The High-Resolution Structure of Activated Opsin Reveals a Conserved Solvent Network in the Transmembrane Region Essential for Activation.

PubMed

Blankenship, Elise; Vahedi-Faridi, Ardeschir; Lodowski, David T

2015-12-01

Rhodopsin, a light-activated G protein coupled receptor (GPCR), has been the subject of numerous biochemical and structural investigations, serving as a model receptor for GPCRs and their activation. We present the 2.3-Å resolution structure of native source rhodopsin stabilized in a conformation competent for G protein binding. An extensive water-mediated hydrogen bond network linking the chromophore binding site to the site of G protein binding is observed, providing connections to conserved motifs essential for GPCR activation. Comparison of this extensive solvent-mediated hydrogen-bonding network with the positions of ordered solvent in earlier crystallographic structures of rhodopsin photointermediates reveals both static structural and dynamic functional water-protein interactions present during the activation process. When considered along with observations that solvent occupies similar positions in the structures of other GPCRs, these analyses strongly support an integral role for this dynamic ordered water network in both rhodopsin and GPCR activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles.

PubMed

Kudryashev, Mikhail; Castaño-Díez, Daniel; Deluz, Cédric; Hassaine, Gherici; Grasso, Luigino; Graf-Meyer, Alexandra; Vogel, Horst; Stahlberg, Henning

2016-01-05

The function of membrane proteins is best understood if their structure in the lipid membrane is known. Here, we determined the structure of the mouse serotonin 5-HT3 receptor inserted in lipid bilayers to a resolution of 12 Å without stabilizing antibodies by cryo electron tomography and subtomogram averaging. The reconstruction reveals protein secondary structure elements in the transmembrane region, the extracellular pore, and the transmembrane channel pathway, showing an overall similarity to the available X-ray model of the truncated 5-HT3 receptor determined in the presence of a stabilizing nanobody. Structural analysis of the 5-HT3 receptor embedded in a lipid bilayer allowed the position of the membrane to be determined. Interactions between the densely packed receptors in lipids were visualized, revealing that the interactions were maintained by the short horizontal helices. In combination with methodological improvements, our approach enables the structural analysis of membrane proteins in response to voltage and ligand gating. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sub-cellular force microscopy in single normal and cancer cells.

PubMed

Babahosseini, H; Carmichael, B; Strobl, J S; Mahmoodi, S N; Agah, M

2015-08-07

This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. Copyright © 2015 Elsevier Inc. All rights reserved.

Modeling of the relationship between dipeptide structure and dipeptide stability, permeability, and ACE inhibitory activity.

PubMed

Foltz, Martin; van Buren, Leo; Klaffke, Werner; Duchateau, Guus S M J E

2009-09-01

Selected di- and tripeptides exhibit angiotensin-I converting enzyme (ACE) inhibitory activity in vitro. However, the efficacy in vivo is most likely limited for most peptides due to low bioavailability. The purpose of this study was to identify descriptors of intestinal stability, permeability, and ACE inhibitory activity of dipeptides. A total of 228 dipeptides were synthesized; intestinal stability was obtained by in vitro digestion, intestinal permeability using Caco-2 cells and ACE inhibitory activity by an in vitro assay. Databases were constructed to study the relationship between structure and activity, permeability, and stability. Quantitative structure-activity relationship (QSAR) modeling was performed based on computed models using partial least squares regression based on 400 molecular descriptors. QSAR modeling of dipeptide stability revealed high correlation coefficients (R > 0.65) for models based on Z and X scales. However, amino acid (AA) clustering showed the best results in describing stability of dipeptides. The N-terminal AA residues Asp, Gly, and Pro as well as the C-terminal residues Pro, Ser, Thr, and Asp stabilize dipeptides toward luminal enzymatic peptide hydrolysis. QSAR modeling did not reveal significant correlation models for intestinal permeability. 2D-fingerprint models were identified describing ACE inhibitory activity of dipeptides. The intestinal stability of 12 peptides was predicted. Peptides were synthesized and stability was confirmed in simulated digestion experiments. Based on the results, specific dipeptides can be designed to meet both stability and activity criteria. However, postabsorptive ACE inhibitory activities of dipeptides in vivo are most likely limited due to the very low intestinal permeability of dipeptides.

Recursive formulae and performance comparisons for first mode dynamics of periodic structures

NASA Astrophysics Data System (ADS)

Hobeck, Jared D.; Inman, Daniel J.

2017-05-01

Periodic structures are growing in popularity especially in the energy harvesting and metastructures communities. Common types of these unique structures are referred to in the literature as zigzag, orthogonal spiral, fan-folded, and longitudinal zigzag structures. Many of these studies on periodic structures have two competing goals in common: (a) minimizing natural frequency, and (b) minimizing mass or volume. These goals suggest that no single design is best for all applications; therefore, there is a need for design optimization and comparison tools which first require efficient easy-to-implement models. All available structural dynamics models for these types of structures do provide exact analytical solutions; however, they are complex requiring tedious implementation and providing more information than necessary for practical applications making them computationally inefficient. This paper presents experimentally validated recursive models that are able to very accurately and efficiently predict the dynamics of the four most common types of periodic structures. The proposed modeling technique employs a combination of static deflection formulae and Rayleigh’s Quotient to estimate the first mode shape and natural frequency of periodic structures having any number of beams. Also included in this paper are the results of an extensive experimental validation study which show excellent agreement between model prediction and measurement. Lastly, the proposed models are used to evaluate the performance of each type of structure. Results of this performance evaluation reveal key advantages and disadvantages associated with each type of structure.

Dimensional Model for Estimating Factors influencing Childhood Obesity: Path Analysis Based Modeling

PubMed Central

Kheirollahpour, Maryam; Shohaimi, Shamarina

2014-01-01

The main objective of this study is to identify and develop a comprehensive model which estimates and evaluates the overall relations among the factors that lead to weight gain in children by using structural equation modeling. The proposed models in this study explore the connection among the socioeconomic status of the family, parental feeding practice, and physical activity. Six structural models were tested to identify the direct and indirect relationship between the socioeconomic status and parental feeding practice general level of physical activity, and weight status of children. Finally, a comprehensive model was devised to show how these factors relate to each other as well as to the body mass index (BMI) of the children simultaneously. Concerning the methodology of the current study, confirmatory factor analysis (CFA) was applied to reveal the hidden (secondary) effect of socioeconomic factors on feeding practice and ultimately on the weight status of the children and also to determine the degree of model fit. The comprehensive structural model tested in this study suggested that there are significant direct and indirect relationships among variables of interest. Moreover, the results suggest that parental feeding practice and physical activity are mediators in the structural model. PMID:25097878

Sound transmission through lightweight double-leaf partitions: theoretical modelling

NASA Astrophysics Data System (ADS)

Wang, J.; Lu, T. J.; Woodhouse, J.; Langley, R. S.; Evans, J.

2005-09-01

This paper presents theoretical modelling of the sound transmission loss through double-leaf lightweight partitions stiffened with periodically placed studs. First, by assuming that the effect of the studs can be replaced with elastic springs uniformly distributed between the sheathing panels, a simple smeared model is established. Second, periodic structure theory is used to develop a more accurate model taking account of the discrete placing of the studs. Both models treat incident sound waves in the horizontal plane only, for simplicity. The predictions of the two models are compared, to reveal the physical mechanisms determining sound transmission. The smeared model predicts relatively simple behaviour, in which the only conspicuous features are associated with coincidence effects with the two types of structural wave allowed by the partition model, and internal resonances of the air between the panels. In the periodic model, many more features are evident, associated with the structure of pass- and stop-bands for structural waves in the partition. The models are used to explain the effects of incidence angle and of the various system parameters. The predictions are compared with existing test data for steel plates with wooden stiffeners, and good agreement is obtained.

Is Small Still Beautiful for the Strengths and Difficulties Questionnaire? Novel Findings Using Exploratory Structural Equation Modeling.

PubMed

Garrido, Luis Eduardo; Barrada, Juan Ramón; Aguasvivas, José Armando; Martínez-Molina, Agustín; Arias, Víctor B; Golino, Hudson F; Legaz, Eva; Ferrís, Gloria; Rojo-Moreno, Luis

2018-06-01

During the present decade a large body of research has employed confirmatory factor analysis (CFA) to evaluate the factor structure of the Strengths and Difficulties Questionnaire (SDQ) across multiple languages and cultures. However, because CFA can produce strongly biased estimations when the population cross-loadings differ meaningfully from zero, it may not be the most appropriate framework to model the SDQ responses. With this in mind, the current study sought to assess the factorial structure of the SDQ using the more flexible exploratory structural equation modeling approach. Using a large-scale Spanish sample composed of 67,253 youths aged between 10 and 18 years ( M = 14.16, SD = 1.07), the results showed that CFA provided a severely biased and overly optimistic assessment of the underlying structure of the SDQ. In contrast, exploratory structural equation modeling revealed a generally weak factorial structure, including questionable indicators with large cross-loadings, multiple error correlations, and significant wording variance. A subsequent Monte Carlo study showed that sample sizes greater than 4,000 would be needed to adequately recover the SDQ loading structure. The findings from this study prevent recommending the SDQ as a screening tool and suggest caution when interpreting previous results in the literature based on CFA modeling.

Macro- and micro-chaotic structures in the Hindmarsh-Rose model of bursting neurons

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

Barrio, Roberto, E-mail: rbarrio@unizar.es; Serrano, Sergio; Angeles Martínez, M.

2014-06-01

We study a plethora of chaotic phenomena in the Hindmarsh-Rose neuron model with the use of several computational techniques including the bifurcation parameter continuation, spike-quantification, and evaluation of Lyapunov exponents in bi-parameter diagrams. Such an aggregated approach allows for detecting regions of simple and chaotic dynamics, and demarcating borderlines—exact bifurcation curves. We demonstrate how the organizing centers—points corresponding to codimension-two homoclinic bifurcations—along with fold and period-doubling bifurcation curves structure the biparametric plane, thus forming macro-chaotic regions of onion bulb shapes and revealing spike-adding cascades that generate micro-chaotic structures due to the hysteresis.

Chemical cross-linking of the urease complex from Helicobacter pylori and analysis by Fourier transform ion cyclotron resonance mass spectrometry and molecular modeling

NASA Astrophysics Data System (ADS)

Carlsohn, Elisabet; Ångström, Jonas; Emmett, Mark R.; Marshall, Alan G.; Nilsson, Carol L.

2004-05-01

Chemical cross-linking of proteins is a well-established method for structural mapping of small protein complexes. When combined with mass spectrometry, cross-linking can reveal protein topology and identify contact sites between the peptide surfaces. When applied to surface-exposed proteins from pathogenic organisms, the method can reveal structural details that are useful in vaccine design. In order to investigate the possibilities of applying cross-linking on larger protein complexes, we selected the urease enzyme from Helicobacter pylori as a model. This membrane-associated protein complex consists of two subunits: [alpha] (26.5 kDa) and [beta] (61.7 kDa). Three ([alpha][beta]) heterodimers form a trimeric ([alpha][beta])3 assembly which further associates into a unique dodecameric 1.1 MDa complex composed of four ([alpha][beta])3 units. Cross-linked peptides from trypsin-digested urease complex were analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and molecular modeling. Two potential cross-linked peptides (present in the cross-linked sample but undetectable in [alpha], [beta], and native complex) were assigned. Molecular modeling of urease [alpha][beta] complex and trimeric urease units ([alpha][beta])3 revealed a linkage site between the [alpha]-subunit and the [beta]-subunit, and an internal cross-linkage in the [beta]-subunit.

Cenozoic sedimentation in the Mumbai Offshore Basin: Implications for tectonic evolution of the western continental margin of India

NASA Astrophysics Data System (ADS)

Nair, Nisha; Pandey, Dhananjai K.

2018-02-01

Interpretation of multichannel seismic reflection data along the Mumbai Offshore Basin (MOB) revealed the tectonic processes that led to the development of sedimentary basins during Cenozoic evolution. Structural interpretation along three selected MCS profiles from MOB revealed seven major sedimentary sequences (∼3.0 s TWT, thick) and the associated complex fault patterns. These stratigraphic sequences are interpreted to host detritus of syn- to post rift events during rift-drift process. The acoustic basement appeared to be faulted with interspaced intrusive bodies. The sections also depicted the presence of slumping of sediments, subsidence, marginal basins, rollover anticlines, mud diapirs etc accompanied by normal to thrust faults related to recent tectonics. Presence of upthrusts in the slope region marks the locations of local compression during collision. Forward gravity modeling constrained with results from seismic and drill results, revealed that the crustal structure beneath the MOB has undergone an extensional type tectonics intruded with intrusive bodies. Results from the seismo-gravity modeling in association with litholog data from drilled wells from the western continental margin of India (WCMI) are presented here.

Experimental evidence and structural modeling of nonstoichiometric (010) surfaces coexisting in hydroxyapatite nano-crystals.

PubMed

Ospina, C A; Terra, J; Ramirez, A J; Farina, M; Ellis, D E; Rossi, A M

2012-01-01

High-resolution transmission electron microscopy (HRTEM) and ab initio quantum-mechanical calculations of electronic structure were combined to investigate the structure of the hydroxyapatite (HA) (010) surface, which plays an important role in HA interactions with biological media. HA was synthesized by in vitro precipitation at 37°C. HRTEM images revealed thin elongated rod nanoparticles with preferential growth along the [001] direction and terminations parallel to the (010) plane. The focal series reconstruction (FSR) technique was applied to develop an atomic-scale structural model of the high-resolution images. The HRTEM simulations identified the coexistence of two structurally distinct terminations for (010) surfaces: a rather flat Ca(II)-terminated surface and a zig-zag structure with open OH channels. Density functional theory (DFT) was applied in a periodic slab plane-wave pseudopotential approach to refine details of atomic coordination and bond lengths of Ca(I) and Ca(II) sites in hydrated HA (010) surfaces, starting from the HRTEM model. Copyright © 2011 Elsevier B.V. All rights reserved.

Vibration assessment and structural monitoring of the Basilica of Maxentius in Rome

NASA Astrophysics Data System (ADS)

Pau, Annamaria; Vestroni, Fabrizio

2013-12-01

The present paper addresses the analysis of the ambient vibrations of the Basilica of Maxentius in Rome. This monument, in the city centre and close to busy roads, was the largest vaulted structure in the Roman Empire. Today, only one aisle of the structure remains, suffering from a complex crack scenario. The ambient vibration response is used to investigate traffic induced vibration and compare this to values that could be a potential cause of structural damage according to international standards. Using output-only methods, natural frequencies and mode shapes are obtained from the response, allowing comparison with predictions made with a finite element model. Notwithstanding simplifications regarding material behavior and crack pattern in the finite element model, an agreement between numerical and experimental results is reached once selected mechanical parameters are adjusted. A knowledge of modal characteristics and the availability of an updated model may be a first step of a structural monitoring program that could reveal any decay over time in the structural integrity of the monument.

Discovering Structural Regularity in 3D Geometry

PubMed Central

Pauly, Mark; Mitra, Niloy J.; Wallner, Johannes; Pottmann, Helmut; Guibas, Leonidas J.

2010-01-01

We introduce a computational framework for discovering regular or repeated geometric structures in 3D shapes. We describe and classify possible regular structures and present an effective algorithm for detecting such repeated geometric patterns in point- or mesh-based models. Our method assumes no prior knowledge of the geometry or spatial location of the individual elements that define the pattern. Structure discovery is made possible by a careful analysis of pairwise similarity transformations that reveals prominent lattice structures in a suitable model of transformation space. We introduce an optimization method for detecting such uniform grids specifically designed to deal with outliers and missing elements. This yields a robust algorithm that successfully discovers complex regular structures amidst clutter, noise, and missing geometry. The accuracy of the extracted generating transformations is further improved using a novel simultaneous registration method in the spatial domain. We demonstrate the effectiveness of our algorithm on a variety of examples and show applications to compression, model repair, and geometry synthesis. PMID:21170292

Control Design Strategies to Enhance Long-Term Aircraft Structural Integrity

NASA Technical Reports Server (NTRS)

Newman, Brett A.

1999-01-01

Over the operational lifetime of both military and civil aircraft, structural components are exposed to hundreds of thousands of low-stress repetitive load cycles and less frequent but higher-stress transient loads originating from maneuvering flight and atmospheric gusts. Micro-material imperfections in the structure, such as cracks and debonded laminates, expand and grow in this environment, reducing the structural integrity and shortening the life of the airframe. Extreme costs associated with refurbishment of critical load-bearing structural components in a large fleet, or altogether reinventoring the fleet with newer models, indicate alternative solutions for life extension of the airframe structure are highly desirable. Increased levels of operational safety and reliability are also important factors influencing the desirability of such solutions. One area having significant potential for impacting crack growth/fatigue damage reduction and structural life extension is flight control. To modify the airframe response dynamics arising from command inputs and gust disturbances, feedback loops are routinely applied to vehicles. A dexterous flight control system architecture senses key vehicle motions and generates critical forces/moments at multiple points distributed throughout the airframe to elicit the desired motion characteristics. In principle, these same control loops can be utilized to influence the level of exposure to harmful loads during flight on structural components. Project objectives are to investigate and/or assess the leverage control has on reducing fatigue damage and enhancing long-term structural integrity, without degrading attitude control and trajectory guidance performance levels. In particular, efforts have focused on the effects inner loop control parameters and architectures have on fatigue damage rate. To complete this research, an actively controlled flexible aircraft model and a new state space modeling procedure for crack growth have been utilized. Analysis of the analytical state space model for crack growth revealed the critical mathematical factors, and hence the physical mechanism they represent, that influenced high rates of airframe crack growth. The crack model was then exercised with simple load inputs to uncover and expose key crack growth behavior. To characterize crack growth behavior, both "short-term" laboratory specimen test type inputs and "long-term" operational flight type inputs were considered. Harmonic loading with a single overload revealed typical exponential crack growth behavior until the overload application, after which time the crack growth was retarded for a period of time depending on the overload strength. An optimum overload strength was identified which leads to maximum retardation of crack growth. Harmonic loading with a repeated overload of varying strength and frequency again revealed an optimum overload trait for maximizing growth retardation. The optimum overload strength ratio lies near the range of 2 to 3 with dependency on frequency. Experimental data was found to correlate well with the analytical predictions.

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

PubMed

Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crustal structure beneath the Paleozoic Parnaíba Basin revealed by airborne gravity and magnetic data, Brazil

USGS Publications Warehouse

de Castroa, David L.; Fuck, Reinhardt A.; Phillips, Jeffrey D.; Vidotti, Roberta M.; Bezerra, Francisco H. R.; Dantas, Elton L.

2014-01-01

The Parnaíba Basin is a large Paleozoic syneclise in northeastern Brazil underlain by Precambrian crystalline basement, which comprises a complex lithostructural and tectonic framework formed during the Neoproterozoic–Eopaleozoic Brasiliano–Pan African orogenic collage. A sag basin up to 3.5 km thick and 1000 km long formed after the collage. The lithologic composition, structure, and role in the basin evolution of the underlying basement are the focus of this study. Airborne gravity and magnetic data were modeled to reveal the general crustal structure underneath the Parnaíba Basin. Results indicate that gravity and magnetic signatures delineate the main boundaries and structural trends of three cratonic areas and surrounding Neoproterozoic fold belts in the basement. Triangular-shaped basement inliers are geophysically defined in the central region of this continental-scale Neoproterozoic convergence zone. A 3-D gravity inversion constrained by seismological data reveals that basement inliers exhibit a 36–40.5 km deep crustal root, with borders defined by a high-density and thinner crust. Forward modeling of gravity and magnetic data indicates that lateral boundaries between crustal units are limited by Brasiliano shear zones, representing lithospheric sutures of the Amazonian and São Francisco Cratons, Tocantins Province and Parnaíba Block. In addition, coincident residual gravity, residual magnetic, and pseudo-gravity lows indicate two complex systems of Eopaleozoic rifts related to the initial phase of the sag deposition, which follow basement trends in several directions.

Corrected goodness-of-fit test in covariance structure analysis.

PubMed

Hayakawa, Kazuhiko

2018-05-17

Many previous studies report simulation evidence that the goodness-of-fit test in covariance structure analysis or structural equation modeling suffers from the overrejection problem when the number of manifest variables is large compared with the sample size. In this study, we demonstrate that one of the tests considered in Browne (1974) can address this long-standing problem. We also propose a simple modification of Satorra and Bentler's mean and variance adjusted test for non-normal data. A Monte Carlo simulation is carried out to investigate the performance of the corrected tests in the context of a confirmatory factor model, a panel autoregressive model, and a cross-lagged panel (panel vector autoregressive) model. The simulation results reveal that the corrected tests overcome the overrejection problem and outperform existing tests in most cases. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Ab Initio Structural Modeling of and Experimental Validation for Chlamydia trachomatis Protein CT296 Reveal Structural Similarity to Fe(II) 2-Oxoglutarate-Dependent Enzymes▿

PubMed Central

Kemege, Kyle E.; Hickey, John M.; Lovell, Scott; Battaile, Kevin P.; Zhang, Yang; Hefty, P. Scott

2011-01-01

Chlamydia trachomatis is a medically important pathogen that encodes a relatively high percentage of proteins with unknown function. The three-dimensional structure of a protein can be very informative regarding the protein's functional characteristics; however, determining protein structures experimentally can be very challenging. Computational methods that model protein structures with sufficient accuracy to facilitate functional studies have had notable successes. To evaluate the accuracy and potential impact of computational protein structure modeling of hypothetical proteins encoded by Chlamydia, a successful computational method termed I-TASSER was utilized to model the three-dimensional structure of a hypothetical protein encoded by open reading frame (ORF) CT296. CT296 has been reported to exhibit functional properties of a divalent cation transcription repressor (DcrA), with similarity to the Escherichia coli iron-responsive transcriptional repressor, Fur. Unexpectedly, the I-TASSER model of CT296 exhibited no structural similarity to any DNA-interacting proteins or motifs. To validate the I-TASSER-generated model, the structure of CT296 was solved experimentally using X-ray crystallography. Impressively, the ab initio I-TASSER-generated model closely matched (2.72-Å Cα root mean square deviation [RMSD]) the high-resolution (1.8-Å) crystal structure of CT296. Modeled and experimentally determined structures of CT296 share structural characteristics of non-heme Fe(II) 2-oxoglutarate-dependent enzymes, although key enzymatic residues are not conserved, suggesting a unique biochemical process is likely associated with CT296 function. Additionally, functional analyses did not support prior reports that CT296 has properties shared with divalent cation repressors such as Fur. PMID:21965559

Ab initio structural modeling of and experimental validation for Chlamydia trachomatis protein CT296 reveal structural similarity to Fe(II) 2-oxoglutarate-dependent enzymes

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

Kemege, Kyle E.; Hickey, John M.; Lovell, Scott

2012-02-13

Chlamydia trachomatis is a medically important pathogen that encodes a relatively high percentage of proteins with unknown function. The three-dimensional structure of a protein can be very informative regarding the protein's functional characteristics; however, determining protein structures experimentally can be very challenging. Computational methods that model protein structures with sufficient accuracy to facilitate functional studies have had notable successes. To evaluate the accuracy and potential impact of computational protein structure modeling of hypothetical proteins encoded by Chlamydia, a successful computational method termed I-TASSER was utilized to model the three-dimensional structure of a hypothetical protein encoded by open reading frame (ORF)more » CT296. CT296 has been reported to exhibit functional properties of a divalent cation transcription repressor (DcrA), with similarity to the Escherichia coli iron-responsive transcriptional repressor, Fur. Unexpectedly, the I-TASSER model of CT296 exhibited no structural similarity to any DNA-interacting proteins or motifs. To validate the I-TASSER-generated model, the structure of CT296 was solved experimentally using X-ray crystallography. Impressively, the ab initio I-TASSER-generated model closely matched (2.72-{angstrom} C{alpha} root mean square deviation [RMSD]) the high-resolution (1.8-{angstrom}) crystal structure of CT296. Modeled and experimentally determined structures of CT296 share structural characteristics of non-heme Fe(II) 2-oxoglutarate-dependent enzymes, although key enzymatic residues are not conserved, suggesting a unique biochemical process is likely associated with CT296 function. Additionally, functional analyses did not support prior reports that CT296 has properties shared with divalent cation repressors such as Fur.« less

Erbium ion implantation into diamond - measurement and modelling of the crystal structure.

PubMed

Cajzl, Jakub; Nekvindová, Pavla; Macková, Anna; Malinský, Petr; Sedmidubský, David; Hušák, Michal; Remeš, Zdeněk; Varga, Marián; Kromka, Alexander; Böttger, Roman; Oswald, Jiří

2017-02-22

Diamond is proposed as an extraordinary material usable in interdisciplinary fields, especially in optics and photonics. In this contribution we focus on the doping of diamond with erbium as an optically active centre. In the theoretical part of the study based on DFT simulations we have developed two Er-doped diamond structural models with 0 to 4 carbon vacancies in the vicinity of the Er atom and performed geometry optimizations by the calculation of cohesive energies and defect formation energies. The theoretical results showed an excellent agreement between the calculated and experimental cohesive energies for the parent diamond. The highest values of cohesive energies and the lowest values of defect formation energies were obtained for models with erbium in the substitutional carbon position with 1 or 3 vacancies in the vicinity of the erbium atom. From the geometry optimization the structural model with 1 vacancy had an octahedral symmetry whereas the model with 3 vacancies had a coordination of 10 forming a trigonal structure with a hexagonal ring. In the experimental part, erbium doped diamond crystal samples were prepared by ion implantation of Er + ions using ion implantation fluences ranging from 1 × 10 14 ions per cm 2 to 5 × 10 15 ions per cm 2 . The experimental results revealed a high degree of diamond structural damage after the ion implantation process reaching up to 69% of disordered atoms in the samples. The prepared Er-doped diamond samples annealed at the temperatures of 400, 600 and 800 °C in a vacuum revealed clear luminescence, where the 〈110〉 cut sample has approximately 6-7 times higher luminescence intensity than the 〈001〉 cut sample with the same ion implantation fluence. The reported results are the first demonstration of the Er luminescence in the single crystal diamond structure for the near-infrared spectral region.

Normalized Shape and Location of Perturbed Craniofacial Structures in the Xenopus Tadpole Reveal an Innate Ability to Achieve Correct Morphology

PubMed Central

Vandenberg, Laura N.; Adams, Dany S.; Levin, Michael

2012-01-01

Background Embryonic development can often adjust its morphogenetic processes to counteract external perturbation. The existence of self-monitoring responses during pattern formation is of considerable importance to the biomedicine of birth defects, but has not been quantitatively addressed. To understand the computational capabilities of biological tissues in a molecularly-tractable model system, we induced craniofacial defects in Xenopus embryos, then tracked tadpoles with craniofacial deformities and used geometric morphometric techniques to characterize changes in the shape and position of the craniofacial structures. Results Canonical variate analysis revealed that the shapes and relative positions of perturbed jaws and branchial arches were corrected during the first few months of tadpole development. Analysis of the relative movements of the anterior-most structures indicates that misplaced structures move along the anterior-posterior and left-right axes in ways that are significantly different from their normal movements. Conclusions Our data suggest a model in which craniofacial structures utilize a measuring mechanism to assess and adjust their location relative to other local organs. Understanding the correction mechanisms at work in this system could lead to the better understanding of the adaptive decision-making capabilities of living tissues and suggest new approaches to correct birth defects in humans. PMID:22411736

1H NMR study of the effect of variable ligand on heme oxygenase electronic and molecular structure

PubMed Central

Ma, Li-Hua; Liu, Yangzhong; Zhang, Xuhong; Yoshida, Tadashi; La Mar, Gerd N.

2009-01-01

Heme oxygenase carries out stereospecific catabolism of protohemin to yield iron, CO and biliverdin. Instability of the physiological oxy complex has necessitated the use of model ligands, of which cyanide and azide are amenable to solution NMR characterization. Since cyanide and azide are contrasting models for bound oxygen, it is of interest to characterize differences in their molecular and/or electronic structures. We report on detailed 2D NMR comparison of the azide and cyanide substrate complexes of heme oxygenase from Neisseria meningitidis, which reveals significant and widespread differences in chemical shifts between the two complexes. To differentiate molecular from electronic structural changes between the two complexes, the anisotropy and orientation of the paramagnetic susceptibility tensor were determined for the azide complex for comparison with those for the cyanide complex. Comparison of the predicted and observed dipolar shifts reveals that shift differences are strongly dominated by differences in electronic structure and do not provide any evidence for detectable differences in molecular structure or hydrogen bonding except in the immediate vicinity of the distal ligand. The readily cleaved C-terminus interacts with the active site and saturation-transfer allows difficult heme assignments in the high-spin aquo complex. PMID:18976815

Relationships between negative affect and academic achievement among secondary school students: the mediating effects of habituated exercise.

PubMed

Hashim, Hairul A; Freddy, Golok; Rosmatunisah, Ali

2012-09-01

The current study was undertaken to examine the associations between self-determination, exercise habit, anxiety, depression, stress, and academic achievement among adolescents aged 13 and 14 years in eastern Malaysia. The sample consisted of 750 secondary school students (mean age = 13.4 years, SD = 0.49). Participants completed self-report measures of exercise behavioral regulation, negative affect, and exercise habit strength. Midyear exam results were used as an indicator of academic performance. Structural equation modeling was used to analyze the data. The results of structural equation modeling revealed a close model fit for the hypothesized model, which indicates that higher levels of self-determination were positively associated with habituated exercise behavior. In turn, exercise habit strength fostered academic achievement and buffered the debilitative effect of stress, depression, and anxiety on student academic performance. The analysis of model invariance revealed a nonsignificant difference between male and female subjects. The findings support the notion that habituated exercise fosters academic performance. In addition, we found that habituated exercise buffers the combined effects of stress, anxiety and depression on academic performance. The finding also supports the roles of self-determination in promoting exercise habituation.

Crustal structure of the alaska range orogen and denali fault along the richardson highway

USGS Publications Warehouse

Fisher, M.A.; Pellerin, L.; Nokleberg, W.J.; Ratchkovski, N.A.; Glen, J.M.G.

2007-01-01

A suite of geophysical data obtained along the Richardson Highway crosses the eastern Alaska Range and Denali fault and reveals the crustal structure of the orogen. Strong seismic reflections from within the orogen north of the Denali fault dip as steeply as 25?? north and extend downward to depths between 20 and 25 km. These reflections reveal what is probably a shear zone that transects most of the crust and is part of a crustal-scale duplex structure that probably formed during the Late Cretaceous. These structures, however, appear to be relict because over the past 20 years, they have produced little or no seismicity despite the nearby Mw = 7.9 Denali fault earthquake that struck in 2002. The Denali fault is nonreflective, but we interpret modeled magnetotelluric (MT), gravity, and magnetic data to propose that the fault dips steeply to vertically. Modeling of MT data shows that aftershocks of the 2002 Denali fault earthquake occurred above a rock body that has low electrical resistivity (>10 ohm-m), which might signify the presence of fluids in the middle and lower crust. Copyright ?? 2007 The Geological Society of America.

Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

PubMed

Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

2017-02-22

Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

New generation of elastic network models.

PubMed

López-Blanco, José Ramón; Chacón, Pablo

2016-04-01

The intrinsic flexibility of proteins and nucleic acids can be grasped from remarkably simple mechanical models of particles connected by springs. In recent decades, Elastic Network Models (ENMs) combined with Normal Model Analysis widely confirmed their ability to predict biologically relevant motions of biomolecules and soon became a popular methodology to reveal large-scale dynamics in multiple structural biology scenarios. The simplicity, robustness, low computational cost, and relatively high accuracy are the reasons behind the success of ENMs. This review focuses on recent advances in the development and application of ENMs, paying particular attention to combinations with experimental data. Successful application scenarios include large macromolecular machines, structural refinement, docking, and evolutionary conservation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modification of the gravity model and application to the metropolitan Seoul subway system.

PubMed

Goh, Segun; Lee, Keumsook; Park, Jong Soo; Choi, M Y

2012-08-01

The Metropolitan Seoul Subway system is examined through the use of the gravity model. Exponents describing the power-law dependence on the time distance between stations are obtained, which reveals a universality for subway lines of the same topology. In the short (time) distance regime the number of passengers between stations does not grow with the decrease in the distance, thus deviating from the power-law behavior. It is found that such reduction in passengers is well described by the Hill function. Further, temporal fluctuations in the passenger flow data, fitted to the gravity model modified by the Hill function, are analyzed to reveal the Yule-type nature inherent in the structure of Seoul.

Solution Structures of Mycobacterium tuberculosis Thioredoxin C and Models of the Intact Thioredoxin System Suggest New Approaches to Inhibitor and Drug Design

PubMed Central

Olson, Andrew L.; Neumann, Terrence S.; Cai, Sheng; Sem, Daniel S.

2012-01-01

Here we report the NMR solution structures of Mycobacterium tuberculosis (M. tuberculosis) thioredoxin C in both oxidized and reduced states, with discussion of structural changes that occur in going between redox states. The NMR solution structure of the oxidized TrxC corresponds closely to that of the crystal structure, except in the C-terminal region. It appears that crystal packing effects have caused an artifactual shift in the α4 helix in the previously reported crystal structure, compared to the solution structure. Based on these TrxC structures, chemical shift mapping, a previously reported crystal structure of the M. tuberculosis thioredoxin reductase (not bound to a Trx) and structures for intermediates in the E. coli thioredoxin catalytic cycle, we have modeled the complete M. tuberculosis thioredoxin system for the various steps in the catalytic cycle. These structures and models reveal pockets at the TrxR/TrxC interface in various steps in the catalytic cycle, which can be targeted in the design of uncompetitive inhibitors as potential anti-mycobacterial agents, or as chemical genetic probes of function. PMID:23229911

Custodial grandmothers' psychological distress, dysfunctional parenting, and grandchildren's adjustment.

PubMed

Smith, Gregory C; Palmieri, Patrick A; Hancock, Gregory R; Richardson, Rhonda A

2008-01-01

An adaptation of the Family Stress Model (FSM) with hypothesized linkages between family contextual factors, custodial grandmothers' psychological distress, parenting practices, and grandchildren's adjustment was tested with structural equation modeling. Interview data from 733 custodial grandmothers of grandchildren between ages 4-17 revealed that the effect of grandmothers' distress on grandchildren's adjustment was mediated by dysfunctional parenting, especially regarding externalizing problems. The effects of contextual factors on grandchildren's adjustment were also indirect. The model's measurement and structural components were largely invariant across grandmothers' race and age, as well as grandchildren's gender and age. Group differences were more prevalent regarding the magnitude of latent means for model constructs. We conclude that parenting models like the FSM are useful for investigating custodial grandfamilies.

Custodial Grandmothers' Psychological Distress, Dysfunctional Parenting, and Grandchildren's Adjustment*ł

PubMed Central

Smith, Gregory C.; Palmieri, Patrick A.; Hancock, Gregory R.; Richardson, Rhonda A.

2009-01-01

An adaptation of the Family Stress Model (FSM) with hypothesized linkages between family contextual factors, custodial grandmothers' psychological distress, parenting practices, and grandchildren's adjustment was tested with structural equation modeling. Interview data from 733 custodial grandmothers of grandchildren between ages 4-17 revealed that the effect of grandmothers' distress on grandchildren's adjustment was mediated by dysfunctional parenting, especially regarding externalizing problems. The effects of contextual factors on grandchildren's adjustment were also indirect. The model's measurement and structural components were largely invariant across grandmothers' race and age, as well as grandchildren's gender and age. Group differences were more prevalent regarding the magnitude of latent means for model constructs. We conclude that parenting models like the FSM are useful for investigating custodial grandfamilies. PMID:19266869

Insights into the structural characteristics and substrate binding analysis of chondroitin AC lyase (PsPL8A) from Pedobacter saltans.

PubMed

Rani, Aruna; Dhillon, Arun; Sharma, Kedar; Goyal, Arun

2018-04-01

The structure of chondroitin AC lyase (PsPL8A) of family 8 polysaccharide lyase was characterized. Modeled PsPL8A structure showed, it contains N-terminal (α/α) 6 incomplete toroidal fold and a layered β sandwich structure at C-terminal. Ramchandran plot displayed 98.5% residues in favoured and 1.2% in generously allowed region. Secondary structure of PsPL8A by CD revealed 27.31% α helices 22.7% β sheets and 49.9% random coils. Protein melting study showed, PsPL8A completely unfolds at 60°C. SAXS analysis showed, PsPL8A is fully folded in solution form. The ab initio derived dummy model of PsPL8A superposed well with its modeled structure excluding some α-helices and loop region. Structural superposition and docking analysis showed, N153, W105, H203, Y208, Y212, R266 and E349 were involved in catalysis. Mutants N153A, H203A, Y212F, R266A and E349A created by SDM revealed no residual activity. Isothermal titration calorimetry analysis of Y212F and H203A with C4S polysaccharide, showed moderate binding by Y212F (Ka=9.56±3.81×10 5 ) and no binding with H203A, showing active contribution of Y212 in substrate binding. Residues Y212 and H203 or R266 might act as general base and general acid respectively. Residues N153 and E349 are likely contributing in charge neutralization and stabilizing enolate anion intermediate during β-elimination. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of Homology Templates and an Anesthetic Binding Site within the γ-Aminobutyric Acid Receptor

PubMed Central

Bertaccini, Edward J.; Yoluk, Ozge; Lindahl, Erik R.; Trudell, James R.

2013-01-01

Background Anesthetics mediate portions of their activity via modulation of the γ-aminobutyric acid receptor (GABAaR). While its molecular structure remains unknown, significant progress has been made towards understanding its interactions with anesthetics via molecular modeling. Methods The structure of the torpedo acetylcholine receptor (nAChRα), the structures of the α4 and β2 subunits of the human nAChR, the structures of the eukaryotic glutamate-gated chloride channel (GluCl), and the prokaryotic pH sensing channels, from Gloeobacter violaceus and Erwinia chrysanthemi, were aligned with the SAlign and 3DMA algorithms. A multiple sequence alignment from these structures and those of the GABAaR was performed with ClustalW. The Modeler and Rosetta algorithms independently created three-dimensional constructs of the GABAaR from the GluCl template. The CDocker algorithm docked a congeneric series of propofol derivatives into the binding pocket and scored calculated binding affinities for correlation with known GABAaR potentiation EC50’s. Results Multiple structure alignments of templates revealed a clear consensus of residue locations relevant to anesthetic effects except for torpedo nAChR. Within the GABAaR models generated from GluCl, the residues notable for modulating anesthetic action within transmembrane segments 1, 2, and 3 converged on the intersubunit interface between alpha and beta subunits. Docking scores of a propofol derivative series into this binding site showed strong linear correlation with GABAaR potentiation EC50. Conclusion Consensus structural alignment based on homologous templates revealed an intersubunit anesthetic binding cavity within the transmembrane domain of the GABAaR, which showed correlation of ligand docking scores with experimentally measured GABAaR potentiation. PMID:23770602

Assessment of homology templates and an anesthetic binding site within the γ-aminobutyric acid receptor.

PubMed

Bertaccini, Edward J; Yoluk, Ozge; Lindahl, Erik R; Trudell, James R

2013-11-01

Anesthetics mediate portions of their activity via modulation of the γ-aminobutyric acid receptor (GABAaR). Although its molecular structure remains unknown, significant progress has been made toward understanding its interactions with anesthetics via molecular modeling. The structure of the torpedo acetylcholine receptor (nAChRα), the structures of the α4 and β2 subunits of the human nAChR, the structures of the eukaryotic glutamate-gated chloride channel (GluCl), and the prokaryotic pH-sensing channels, from Gloeobacter violaceus and Erwinia chrysanthemi, were aligned with the SAlign and 3DMA algorithms. A multiple sequence alignment from these structures and those of the GABAaR was performed with ClustalW. The Modeler and Rosetta algorithms independently created three-dimensional constructs of the GABAaR from the GluCl template. The CDocker algorithm docked a congeneric series of propofol derivatives into the binding pocket and scored calculated binding affinities for correlation with known GABAaR potentiation EC50s. Multiple structure alignments of templates revealed a clear consensus of residue locations relevant to anesthetic effects except for torpedo nAChR. Within the GABAaR models generated from GluCl, the residues notable for modulating anesthetic action within transmembrane segments 1, 2, and 3 converged on the intersubunit interface between α and β subunits. Docking scores of a propofol derivative series into this binding site showed strong linear correlation with GABAaR potentiation EC50. Consensus structural alignment based on homologous templates revealed an intersubunit anesthetic binding cavity within the transmembrane domain of the GABAaR, which showed a correlation of ligand docking scores with experimentally measured GABAaR potentiation.

Protein homology model refinement by large-scale energy optimization.

PubMed

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

2018-03-20

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

Computer-assisted image analysis of human cilia and Chlamydomonas flagella reveals both similarities and differences in axoneme structure.

PubMed

O'Toole, Eileen T; Giddings, Thomas H; Porter, Mary E; Ostrowski, Lawrence E

2012-08-01

In the past decade, investigations from several different fields have revealed the critical role of cilia in human health and disease. Because of the highly conserved nature of the basic axonemal structure, many different model systems have proven useful for the study of ciliopathies, especially the unicellular, biflagellate green alga Chlamydomonas reinhardtii. Although the basic axonemal structure of cilia and flagella is highly conserved, these organelles often perform specialized functions unique to the cell or tissue in which they are found. These differences in function are likely reflected in differences in structural organization. In this work, we directly compare the structure of isolated axonemes from human cilia and Chlamydomonas flagella to identify similarities and differences that potentially play key roles in determining their functionality. Using transmission electron microscopy and 2D image averaging techniques, our analysis has confirmed the overall structural similarity between these two species, but also revealed clear differences in the structure of the outer dynein arms, the central pair projections, and the radial spokes. We also show how the application of 2D image averaging can clarify the underlying structural defects associated with primary ciliary dyskinesia (PCD). Overall, our results document the remarkable similarity between these two structures separated evolutionarily by over a billion years, while highlighting several significant differences, and demonstrate the potential of 2D image averaging to improve the diagnosis and understanding of PCD. Copyright © 2012 Wiley Periodicals, Inc.

Structural virology. Near-atomic cryo-EM structure of the helical measles virus nucleocapsid.

PubMed

Gutsche, Irina; Desfosses, Ambroise; Effantin, Grégory; Ling, Wai Li; Haupt, Melina; Ruigrok, Rob W H; Sachse, Carsten; Schoehn, Guy

2015-05-08

Measles is a highly contagious human disease. We used cryo-electron microscopy and single particle-based helical image analysis to determine the structure of the helical nucleocapsid formed by the folded domain of the measles virus nucleoprotein encapsidating an RNA at a resolution of 4.3 angstroms. The resulting pseudoatomic model of the measles virus nucleocapsid offers important insights into the mechanism of the helical polymerization of nucleocapsids of negative-strand RNA viruses, in particular via the exchange subdomains of the nucleoprotein. The structure reveals the mode of the nucleoprotein-RNA interaction and explains why each nucleoprotein of measles virus binds six nucleotides, whereas the respiratory syncytial virus nucleoprotein binds seven. It provides a rational basis for further analysis of measles virus replication and transcription, and reveals potential targets for drug design. Copyright © 2015, American Association for the Advancement of Science.

Topological structure dynamics revealing collective evolution in active nematics

PubMed Central

Shi, Xia-qing; Ma, Yu-qiang

2013-01-01

Topological defects frequently emerge in active matter like bacterial colonies, cytoskeleton extracts on substrates, self-propelled granular or colloidal layers and so on, but their dynamical properties and the relations to large-scale organization and fluctuations in these active systems are seldom touched. Here we reveal, through a simple model for active nematics using self-driven hard elliptic rods, that the excitation, annihilation and transportation of topological defects differ markedly from those in non-active media. These dynamical processes exhibit strong irreversibility in active nematics in the absence of detailed balance. Moreover, topological defects are the key factors in organizing large-scale dynamic structures and collective flows, resulting in multi-spatial temporal effects. These findings allow us to control the self-organization of active matter through topological structures. PMID:24346733

Computational Methods for Nonlinear Dynamic Problems in Solid and Structural Mechanics: Progress in the Theory and Modeling of Friction and in the Control of Dynamical Systems with Frictional Forces

DTIC Science & Technology

1989-03-31

present several numerical studies designed to reveal the effect that some of the governing parameters have on the behavior of the system and, whenever...Friction and in the Control of Dynamical Systems with Frictional Forces FINAL TECHNICAL REPORT March 31, 1989 _ -- I -.7: .-.- - : AFOSR Contract F49620...SOLID AND STRUCTURAL MECHANICS: Progress in the Theory and Modeling of Friction and in the Control of Dynamical Systems with Frictional Forces I I * FINAL

Vibrational behavior of adaptive aircraft wing structures modelled as composite thin-walled beams

NASA Technical Reports Server (NTRS)

Song, O.; Librescu, L.; Rogers, C. A.

1992-01-01

The vibrational behavior of cantilevered aircraft wings modeled as thin-walled beams and incorporating piezoelectric effects is studied. Based on the converse piezoelectric effect, the system of piezoelectric actuators conveniently located on the wing yield the control of its associated vertical and lateral bending eigenfrequencies. The possibility revealed by this study enabling one to increase adaptively the eigenfrequencies of thin-walled cantilevered beams could play a significant role in the control of the dynamic response and flutter of wing and rotor blade structures.

Validation of the Transient Structural Response of a Threaded Assembly: Phase I

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

Doebling, Scott W.; Hemez, Francois M.; Robertson, Amy N.

2004-04-01

This report explores the application of model validation techniques in structural dynamics. The problem of interest is the propagation of an explosive-driven mechanical shock through a complex threaded joint. The study serves the purpose of assessing whether validating a large-size computational model is feasible, which unit experiments are required, and where the main sources of uncertainty reside. The results documented here are preliminary, and the analyses are exploratory in nature. The results obtained to date reveal several deficiencies of the analysis, to be rectified in future work.

Unsupervised Structure Detection in Biomedical Data.

PubMed

Vogt, Julia E

2015-01-01

A major challenge in computational biology is to find simple representations of high-dimensional data that best reveal the underlying structure. In this work, we present an intuitive and easy-to-implement method based on ranked neighborhood comparisons that detects structure in unsupervised data. The method is based on ordering objects in terms of similarity and on the mutual overlap of nearest neighbors. This basic framework was originally introduced in the field of social network analysis to detect actor communities. We demonstrate that the same ideas can successfully be applied to biomedical data sets in order to reveal complex underlying structure. The algorithm is very efficient and works on distance data directly without requiring a vectorial embedding of data. Comprehensive experiments demonstrate the validity of this approach. Comparisons with state-of-the-art clustering methods show that the presented method outperforms hierarchical methods as well as density based clustering methods and model-based clustering. A further advantage of the method is that it simultaneously provides a visualization of the data. Especially in biomedical applications, the visualization of data can be used as a first pre-processing step when analyzing real world data sets to get an intuition of the underlying data structure. We apply this model to synthetic data as well as to various biomedical data sets which demonstrate the high quality and usefulness of the inferred structure.

Upper crustal structure of Madeira Island revealed from ambient noise tomography

NASA Astrophysics Data System (ADS)

Matos, Catarina; Silveira, Graça; Matias, Luís; Caldeira, Rita; Ribeiro, M. Luísa; Dias, Nuno A.; Krüger, Frank; Bento dos Santos, Telmo

2015-06-01

We present the first image of the Madeira upper crustal structure, using ambient seismic noise tomography. 16 months of ambient noise, recorded in a dense network of 26 seismometers deployed across Madeira, allowed reconstructing Rayleigh wave Green's functions between receivers. Dispersion analysis was performed in the short period band from 1.0 to 4.0 s. Group velocity measurements were regionalized to obtain 2D tomographic images, with a lateral resolution of 2.0 km in central Madeira. Afterwards, the dispersion curves, extracted from each cell of the 2D group velocity maps, were inverted as a function of depth to obtain a 3D shear wave velocity model of the upper crust, from the surface to a depth of 2.0 km. The obtained 3D velocity model reveals features throughout the island that correlates well with surface geology and island evolution.

Atomistic Model of Physical Ageing in Se-rich As-Se Glasses

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

Golovchak,R.; Shpotyuk, O.; Kozdras, A.

2007-01-01

Thermal, optical, X-ray excited and magnetic methods were used to develop a microstructural model of physical ageing in Se-rich glasses. The glass composition As10Se90, possessing a typical cross-linked chain structure, was chosen as a model object for the investigations. The effect of physical ageing in this glass was revealed by differential scanning calorimetry, whereas the corresponding changes in its atomic arrangement were studied by extended X-ray absorption fine structure, Raman and solid-state 77Se nuclear magnetic resonance spectroscopy. Straightening-shrinkage processes are shown to be responsible for the physical ageing in this Se-rich As-Se glass.

The School Counseling Program Implementation Survey: Initial Instrument Development and Exploratory Factor Analysis

ERIC Educational Resources Information Center

Clemens, Elysia V.; Carey, John C.; Harrington, Karen M.

2010-01-01

This article details the initial development of the School Counseling Program Implementation Survey and psychometric results including reliability and factor structure. An exploratory factor analysis revealed a three-factor model that accounted for 54% of the variance of the intercorrelation matrix and a two-factor model that accounted for 47% of…

Insights from Molecular Dynamics Simulations: Structural Basis for the V567D Mutation-Induced Instability of Zebrafish Alpha-Dystroglycan and Comparison with the Murine Model

PubMed Central

Pirolli, Davide; Sciandra, Francesca; Bozzi, Manuela; Giardina, Bruno; Brancaccio, Andrea; De Rosa, Maria Cristina

2014-01-01

A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D) C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD) simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies. PMID:25078606

Insights from molecular dynamics simulations: structural basis for the V567D mutation-induced instability of zebrafish alpha-dystroglycan and comparison with the murine model.

PubMed

Pirolli, Davide; Sciandra, Francesca; Bozzi, Manuela; Giardina, Bruno; Brancaccio, Andrea; De Rosa, Maria Cristina

2014-01-01

A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D) C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD) simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies.

Mass Spectrometry Based Identification of Geometric Isomers during Metabolic Stability Study of a New Cytotoxic Sulfonamide Derivatives Supported by Quantitative Structure-Retention Relationships

PubMed Central

Belka, Mariusz; Hewelt-Belka, Weronika; Sławiński, Jarosław; Bączek, Tomasz

2014-01-01

A set of 15 new sulphonamide derivatives, presenting antitumor activity have been subjected to a metabolic stability study. The results showed that besides products of biotransformation, some additional peaks occurred in chromatograms. Tandem mass spectrometry revealed the same mass and fragmentation pathway, suggesting that geometric isomerization occurred. Thus, to support this hypothesis, quantitative structure-retention relationships were applied. Human liver microsomes were used as an in vitro model of metabolism. The biotransformation reactions were tracked by liquid chromatography assay and additionally, fragmentation mass spectra were recorded. In silico molecular modeling at a semi-empirical level was conducted as a starting point for molecular descriptor calculations. A quantitative structure-retention relationship model was built applying multiple linear regression based on selected three-dimensional descriptors. The studied compounds revealed high metabolic stability, with a tendency to form hydroxylated biotransformation products. However, significant chemical instability in conditions simulating human body fluids was noticed. According to literature and MS data geometrical isomerization was suggested. The developed in sillico model was able to describe the relationship between the geometry of isomer pairs and their chromatographic retention properties, thus it supported the hypothesis that the observed pairs of peaks are most likely geometric isomers. However, extensive structural investigations are needed to fully identify isomers’ geometry. An effort to describe MS fragmentation pathways of novel chemical structures is often not enough to propose structures of potent metabolites and products of other chemical reactions that can be observed in compound solutions at early drug discovery studies. The results indicate that the relatively non-expensive and not time- and labor-consuming in sillico approach could be a good supportive tool assisting the identification of cis-trans isomers based on retention data. This methodology can be helpful during the structural identification of biotransformation and degradation products of new chemical entities - potential new drugs. PMID:24893169

Tertiary structure-based analysis of microRNA–target interactions

PubMed Central

Gan, Hin Hark; Gunsalus, Kristin C.

2013-01-01

Current computational analysis of microRNA interactions is based largely on primary and secondary structure analysis. Computationally efficient tertiary structure-based methods are needed to enable more realistic modeling of the molecular interactions underlying miRNA-mediated translational repression. We incorporate algorithms for predicting duplex RNA structures, ionic strength effects, duplex entropy and free energy, and docking of duplex–Argonaute protein complexes into a pipeline to model and predict miRNA–target duplex binding energies. To ensure modeling accuracy and computational efficiency, we use an all-atom description of RNA and a continuum description of ionic interactions using the Poisson–Boltzmann equation. Our method predicts the conformations of two constructs of Caenorhabditis elegans let-7 miRNA–target duplexes to an accuracy of ∼3.8 Å root mean square distance of their NMR structures. We also show that the computed duplex formation enthalpies, entropies, and free energies for eight miRNA–target duplexes agree with titration calorimetry data. Analysis of duplex–Argonaute docking shows that structural distortions arising from single-base-pair mismatches in the seed region influence the activity of the complex by destabilizing both duplex hybridization and its association with Argonaute. Collectively, these results demonstrate that tertiary structure-based modeling of miRNA interactions can reveal structural mechanisms not accessible with current secondary structure-based methods. PMID:23417009

Hubble space telescope observations and geometric models of compact multipolar planetary nebulae

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

Hsia, Chih-Hao; Chau, Wayne; Zhang, Yong

2014-05-20

We report high angular resolution Hubble Space Telescope observations of 10 compact planetary nebulae (PNs). Many interesting internal structures, including multipolar lobes, arcs, two-dimensional rings, tori, and halos, are revealed for the first time. These results suggest that multipolar structures are common among PNs, and these structures develop early in their evolution. From three-dimensional geometric models, we have determined the intrinsic dimensions of the lobes. Assuming the lobes are the result of interactions between later-developed fast winds and previously ejected asymptotic giant branch winds, the geometric structures of these PNs suggest that there are multiple phases of fast winds separatedmore » by temporal variations and/or directional changes. A scenario of evolution from lobe-dominated to cavity-dominated stages is presented. The results reported here will provide serious constraints on any dynamical models of PNs.« less

Quantitative Subsurface Atomic Structure Fingerprint for 2D Materials and Heterostructures by First-Principles-Calibrated Contact-Resonance Atomic Force Microscopy.

PubMed

Tu, Qing; Lange, Björn; Parlak, Zehra; Lopes, Joao Marcelo J; Blum, Volker; Zauscher, Stefan

2016-07-26

Interfaces and subsurface layers are critical for the performance of devices made of 2D materials and heterostructures. Facile, nondestructive, and quantitative ways to characterize the structure of atomically thin, layered materials are thus essential to ensure control of the resultant properties. Here, we show that contact-resonance atomic force microscopy-which is exquisitely sensitive to stiffness changes that arise from even a single atomic layer of a van der Waals-adhered material-is a powerful experimental tool to address this challenge. A combined density functional theory and continuum modeling approach is introduced that yields sub-surface-sensitive, nanomechanical fingerprints associated with specific, well-defined structure models of individual surface domains. Where such models are known, this information can be correlated with experimentally obtained contact-resonance frequency maps to reveal the (sub)surface structure of different domains on the sample.

A study of structural properties of gene network graphs for mathematical modeling of integrated mosaic gene networks.

PubMed

Petrovskaya, Olga V; Petrovskiy, Evgeny D; Lavrik, Inna N; Ivanisenko, Vladimir A

2017-04-01

Gene network modeling is one of the widely used approaches in systems biology. It allows for the study of complex genetic systems function, including so-called mosaic gene networks, which consist of functionally interacting subnetworks. We conducted a study of a mosaic gene networks modeling method based on integration of models of gene subnetworks by linear control functionals. An automatic modeling of 10,000 synthetic mosaic gene regulatory networks was carried out using computer experiments on gene knockdowns/knockouts. Structural analysis of graphs of generated mosaic gene regulatory networks has revealed that the most important factor for building accurate integrated mathematical models, among those analyzed in the study, is data on expression of genes corresponding to the vertices with high properties of centrality.

Personality and the latent structure of PTSD comorbidity

PubMed Central

Miller, Mark W.; Wolf, Erika J.

2012-01-01

This study examined the structure of PTSD comorbidity and its relationship to personality in a sample of 214 veterans using data from diagnostic interviews and the Multidimensional Personality Questionnaire-Brief Form (MPQ-BF; Patrick, Curtin, & Tellegen, 2002). Confirmatory factor analyses supported a three factor model composed of Externalizing, Fear and Distress factors. Analyses that examined the location of borderline personality disorder revealed significant cross-loadings for this disorder on both Externalizing and Distress. Structural equation models showed trait negative emotionality to be significantly related to all three comorbidity factors whereas positive emotionality and constraint evidenced specific associations with Distress and Externalizing, respectively. These results shed new light on the location of borderline personality disorder within the internalizing/externalizing model and clarify the relative influence of broad dimensions of personality on patterns of comorbidity. PMID:22480716

Evaluating Individual Students' Perceptions of Instructional Quality: An Investigation of their Factor Structure, Measurement Invariance, and Relations to Educational Outcomes

PubMed Central

Scherer, Ronny; Nilsen, Trude; Jansen, Malte

2016-01-01

Students' perceptions of instructional quality are among the most important criteria for evaluating teaching effectiveness. The present study evaluates different latent variable modeling approaches (confirmatory factor analysis, exploratory structural equation modeling, and bifactor modeling), which are used to describe these individual perceptions with respect to their factor structure, measurement invariance, and the relations to selected educational outcomes (achievement, self-concept, and motivation in mathematics). On the basis of the Programme for International Student Assessment (PISA) 2012 large-scale data sets of Australia, Canada, and the USA (N = 26,746 students), we find support for the distinction between three factors of individual students' perceptions and full measurement invariance across countries for all modeling approaches. In this regard, bifactor exploratory structural equation modeling outperformed alternative approaches with respect to model fit. Our findings reveal significant relations to the educational outcomes. This study synthesizes different modeling approaches of individual students' perceptions of instructional quality and provides insights into the nature of these perceptions from an individual differences perspective. Implications for the measurement and modeling of individually perceived instructional quality are discussed. PMID:26903917

Ligand Recognition by A-Class Eph Receptors: Crystal Structures of the EphA2 Ligand-Binding Domain and the EphA2/ephrin-A1 Complex

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

Himanen, J.; Goldgur, Y; Miao, H

2009-01-01

Ephrin (Eph) receptor tyrosine kinases fall into two subclasses (A and B) according to preferences for their ephrin ligands. All published structural studies of Eph receptor/ephrin complexes involve B-class receptors. Here, we present the crystal structures of an A-class complex between EphA2 and ephrin-A1 and of unbound EphA2. Although these structures are similar overall to their B-class counterparts, they reveal important differences that define subclass specificity. The structures suggest that the A-class Eph receptor/ephrin interactions involve smaller rearrangements in the interacting partners, better described by a 'lock-and-key'-type binding mechanism, in contrast to the 'induced fit' mechanism defining the B-class molecules.more » This model is supported by structure-based mutagenesis and by differential requirements for ligand oligomerization by the two subclasses in cell-based Eph receptor activation assays. Finally, the structure of the unligated receptor reveals a homodimer assembly that might represent EphA2-specific homotypic cell adhesion interactions.« less

Testing Envelope Models of Young Stellar Objects with Submillimeter Continuum and Molecular-Line Observations

NASA Astrophysics Data System (ADS)

Hogerheijde, Michiel R.; Sandell, Göran

2000-05-01

Theoretical models of star formation make predictions about the density and velocity structure of the envelopes surrounding isolated, low-mass young stars. This paper tests such models through high-quality submillimeter continuum imaging of four embedded young stellar objects in Taurus and previously obtained molecular-line data. Observations carried out with the Submillimeter Continuum Bolometer Array on the James Clerk Maxwell Telescope at 850 and 450 μm of L1489 IRS, L1535 IRS, L1527 IRS, and TMC 1 reveal ~2000 AU elongated structures embedded in extended envelopes. The density distribution in these envelopes is equally well fitted by a radial power-law of index p=1.0-2.0 or with a collapse model such as that of Shu. This inside-out collapse model predicts 13CO, C18O, HCO+, and H13CO+ line profiles that closely match observed spectra toward three of our four sources. This shows that the inside-out collapse model offers a good description of YSO envelopes, but also that reliable constraints on its parameters require independent measurements of the density and the velocity structure, e.g., through continuum and line observations. For the remaining source, L1489 IRS, we find that a model consisting of a 2000 AU radius, rotating, disklike structure better describes the data. Possibly, this source is in transition between the embedded class I and the optically revealed T Tauri phases. The spectral index of the dust emissivity decreases from β=1.5-2.0 in the extended envelope to 1.0+/-0.2 in the central peaks, indicating grain growth or high optical depth on small scales. The observations of L1527 IRS reveal warm (>~30 K) material outlining, and presumably heated by, its bipolar outflow. This material comprises <~0.2 Msolar, comparable to the amount of swept-up CO but only 10% of the total envelope mass. Two apparently starless cores are found at ~10,000 AU from L1489 IRS and L1535 IRS. They are cold, 10-15 K, contain 0.5-3.0 Msolar, and have flat density distributions characterized by a Gaussian of ~10,000 AU FWHM. The proximity of these cores shows that star formation in truly isolated cores is rare even in Taurus.

The structural approach to shared knowledge: an application to engineering design teams.

PubMed

Avnet, Mark S; Weigel, Annalisa L

2013-06-01

We propose a methodology for analyzing shared knowledge in engineering design teams. Whereas prior work has focused on shared knowledge in small teams at a specific point in time, the model presented here is both scalable and dynamic. By quantifying team members' common views of design drivers, we build a network of shared mental models to reveal the structure of shared knowledge at a snapshot in time. Based on a structural comparison of networks at different points in time, a metric of change in shared knowledge is computed. Analysis of survey data from 12 conceptual space mission design sessions reveals a correlation between change in shared knowledge and each of several system attributes, including system development time, system mass, and technological maturity. From these results, we conclude that an early period of learning and consensus building could be beneficial to the design of engineered systems. Although we do not examine team performance directly, we demonstrate that shared knowledge is related to the technical design and thus provide a foundation for improving design products by incorporating the knowledge and thoughts of the engineering design team into the process.

Model for the architecture of caveolae based on a flexible, net-like assembly of Cavin1 and Caveolin discs

PubMed Central

Stoeber, Miriam; Schellenberger, Pascale; Siebert, C. Alistair; Leyrat, Cedric; Helenius, Ari

2016-01-01

Caveolae are invaginated plasma membrane domains involved in mechanosensing, signaling, endocytosis, and membrane homeostasis. Oligomers of membrane-embedded caveolins and peripherally attached cavins form the caveolar coat whose structure has remained elusive. Here, purified Cavin1 60S complexes were analyzed structurally in solution and after liposome reconstitution by electron cryotomography. Cavin1 adopted a flexible, net-like protein mesh able to form polyhedral lattices on phosphatidylserine-containing vesicles. Mutating the two coiled-coil domains in Cavin1 revealed that they mediate distinct assembly steps during 60S complex formation. The organization of the cavin coat corresponded to a polyhedral nano-net held together by coiled-coil segments. Positive residues around the C-terminal coiled-coil domain were required for membrane binding. Purified caveolin 8S oligomers assumed disc-shaped arrangements of sizes that are consistent with the discs occupying the faces in the caveolar polyhedra. Polygonal caveolar membrane profiles were revealed in tomograms of native caveolae inside cells. We propose a model with a regular dodecahedron as structural basis for the caveolae architecture. PMID:27834731

Impact of structural and psychological empowerment on job strain in nursing work settings: expanding Kanter's model.

PubMed

Laschinger, H K; Finegan, J; Shamian, J; Wilk, P

2001-05-01

In this study, we tested an expanded model of Kanter's structural empowerment, which specified the relationships among structural and psychological empowerment, job strain, and work satisfaction. Strategies proposed in Kanter's empowerment theory have the potential to reduce job strain and improve employee work satisfaction and performance in current restructured healthcare settings. The addition to the model of psychological empowerment as an outcome of structural empowerment provides an understanding of the intervening mechanisms between structural work conditions and important organizational outcomes. A predictive, nonexperimental design was used to test the model in a random sample of 404 Canadian staff nurses. The Conditions of Work Effectiveness Questionnaire, the Psychological Empowerment Questionnaire, the Job Content Questionnaire, and the Global Satisfaction Scale were used to measure the major study variables. Structural equation modelling analyses revealed a good fit of the hypothesized model to the data based on various fit indices (chi 2 = 1140, df = 545, chi 2/df ratio = 2.09, CFI = 0.986, RMSEA = 0.050). The amount of variance accounted for in the model was 58%. Staff nurses felt that structural empowerment in their workplace resulted in higher levels of psychological empowerment. These heightened feelings of psychological empowerment in turn strongly influenced job strain and work satisfaction. However, job strain did not have a direct effect on work satisfaction. These results provide initial support for an expanded model of organizational empowerment and offer a broader understanding of the empowerment process.

Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

PubMed Central

Guaitoli, Giambattista; Raimondi, Francesco; Gilsbach, Bernd K.; Gómez-Llorente, Yacob; Deyaert, Egon; Renzi, Fabiana; Li, Xianting; Schaffner, Adam; Jagtap, Pravin Kumar Ankush; Boldt, Karsten; von Zweydorf, Felix; Gotthardt, Katja; Lorimer, Donald D.; Yue, Zhenyu; Burgin, Alex; Janjic, Nebojsa; Sattler, Michael; Versées, Wim; Ueffing, Marius; Ubarretxena-Belandia, Iban; Kortholt, Arjan; Gloeckner, Christian Johannes

2016-01-01

Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson’s disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity—together with the LRR domain—to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full-length LRRK2 in the pathogenesis of PD. PMID:27357661

Structures of mesophilic and extremophilic citrate synthases reveal rigidity and flexibility for function.

PubMed

Wells, Stephen A; Crennell, Susan J; Danson, Michael J

2014-10-01

Citrate synthase (CS) catalyses the entry of carbon into the citric acid cycle and is highly-conserved structurally across the tree of life. Crystal structures of dimeric CSs are known in both "open" and "closed" forms, which differ by a substantial domain motion that closes the substrate-binding clefts. We explore both the static rigidity and the dynamic flexibility of CS structures from mesophilic and extremophilic organisms from all three evolutionary domains. The computational expense of this wide-ranging exploration is kept to a minimum by the use of rigidity analysis and rapid all-atom simulations of flexible motion, combining geometric simulation and elastic network modeling. CS structures from thermophiles display increased structural rigidity compared with the mesophilic enzyme. A CS structure from a psychrophile, stabilized by strong ionic interactions, appears to display likewise increased rigidity in conventional rigidity analysis; however, a novel modified analysis, taking into account the weakening of the hydrophobic effect at low temperatures, shows a more appropriate decreased rigidity. These rigidity variations do not, however, affect the character of the flexible dynamics, which are well conserved across all the structures studied. Simulation trajectories not only duplicate the crystallographically observed symmetric open-to-closed transitions, but also identify motions describing a previously unidentified antisymmetric functional motion. This antisymmetric motion would not be directly observed in crystallography but is revealed as an intrinsic property of the CS structure by modeling of flexible motion. This suggests that the functional motion closing the binding clefts in CS may be independent rather than symmetric and cooperative. © 2014 Wiley Periodicals, Inc.

Improvement of the Processes of Liquid-Phase Epitaxial Growth of Nanoheteroepitaxial Structures

NASA Astrophysics Data System (ADS)

Maronchuk, I. I.; Sanikovich, D. D.; Potapkov, P. V.; Vel‧chenko, A. A.

2018-05-01

We have revealed the shortcomings of equipment and technological approaches in growing nanoheteroepitaxial structures with quantum dots by liquid-phase epitaxy. We have developed and fabricated a new vertical barreltype cassette for growing quantum dots and epitaxial layers of various thicknesses in one technological process. A physico-mathematical simulation has been carried out of the processes of liquid-phase epitaxial growth of quantumdimensional structures with the use of the program product SolidWorks (FlowSimulation program). Analysis has revealed the presence of negative factors influencing the growth process of the above structures. The mathematical model has been optimized, and the equipment has been modernized without additional experiments and measurements. The flow dynamics of the process gas in the reactor at various flow rates has been investigated. A method for tuning the thermal equipment has been developed. The calculated and experimental temperature distributions in the process of growing structures with high reproducibility are in good agreement, which confirms the validity of the modernization made.

Structure and Self-Assembly of the Calcium Binding Matrix Protein of Human Metapneumovirus

PubMed Central

Leyrat, Cedric; Renner, Max; Harlos, Karl; Huiskonen, Juha T.; Grimes, Jonathan M.

2014-01-01

Summary The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. Here, we report the crystal structure of the human metapneumovirus M at 2.8 Å resolution in its native dimeric state. The structure reveals the presence of a high-affinity Ca2+ binding site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity site that correlates well with data from fluorescence-based thermal shift assays. By combining small-angle X-ray scattering with MDS and ensemble analysis, we captured the structure and dynamics of M in solution. Our analysis reveals a large positively charged patch on the protein surface that is involved in membrane interaction. Structural analysis of DOPC-induced polymerization of M into helical filaments using electron microscopy leads to a model of M self-assembly. The conservation of the Ca2+ binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. PMID:24316400

Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A.

PubMed

Markovic-Mueller, Sandra; Stuttfeld, Edward; Asthana, Mayanka; Weinert, Tobias; Bliven, Spencer; Goldie, Kenneth N; Kisko, Kaisa; Capitani, Guido; Ballmer-Hofer, Kurt

2017-02-07

Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel development upon activation of three receptor tyrosine kinases: VEGFR-1, -2, and -3. Partial structures of VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, and X-ray crystallography revealed the location of VEGF binding and domain arrangement of individual receptor subdomains. Here, we describe the structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution. We combined X-ray crystallography, single-particle electron microscopy, and molecular modeling for structure determination and validation. The structure reveals the molecular details of ligand-induced receptor dimerization, in particular of homotypic receptor interactions in immunoglobulin homology domains 4, 5, and 7. Functional analyses of ligand binding and receptor activation confirm the relevance of these homotypic contacts and identify them as potential therapeutic sites to allosterically inhibit VEGFR-1 activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Dawn Topography Investigation

NASA Technical Reports Server (NTRS)

Raymond, C. A.; Jaumann, R.; Nathues, A.; Sierks, H.; Roatsch, T.; Preusker, E; Scholten, F.; Gaskell, R. W.; Jorda, L.; Keller, H.-U.;

Computational Identification of Genomic Features That Influence 3D Chromatin Domain Formation.

PubMed

Mourad, Raphaël; Cuvier, Olivier

2016-05-01

Recent advances in long-range Hi-C contact mapping have revealed the importance of the 3D structure of chromosomes in gene expression. A current challenge is to identify the key molecular drivers of this 3D structure. Several genomic features, such as architectural proteins and functional elements, were shown to be enriched at topological domain borders using classical enrichment tests. Here we propose multiple logistic regression to identify those genomic features that positively or negatively influence domain border establishment or maintenance. The model is flexible, and can account for statistical interactions among multiple genomic features. Using both simulated and real data, we show that our model outperforms enrichment test and non-parametric models, such as random forests, for the identification of genomic features that influence domain borders. Using Drosophila Hi-C data at a very high resolution of 1 kb, our model suggests that, among architectural proteins, BEAF-32 and CP190 are the main positive drivers of 3D domain borders. In humans, our model identifies well-known architectural proteins CTCF and cohesin, as well as ZNF143 and Polycomb group proteins as positive drivers of domain borders. The model also reveals the existence of several negative drivers that counteract the presence of domain borders including P300, RXRA, BCL11A and ELK1.

Computational Identification of Genomic Features That Influence 3D Chromatin Domain Formation

PubMed Central

Mourad, Raphaël; Cuvier, Olivier

2016-01-01

Recent advances in long-range Hi-C contact mapping have revealed the importance of the 3D structure of chromosomes in gene expression. A current challenge is to identify the key molecular drivers of this 3D structure. Several genomic features, such as architectural proteins and functional elements, were shown to be enriched at topological domain borders using classical enrichment tests. Here we propose multiple logistic regression to identify those genomic features that positively or negatively influence domain border establishment or maintenance. The model is flexible, and can account for statistical interactions among multiple genomic features. Using both simulated and real data, we show that our model outperforms enrichment test and non-parametric models, such as random forests, for the identification of genomic features that influence domain borders. Using Drosophila Hi-C data at a very high resolution of 1 kb, our model suggests that, among architectural proteins, BEAF-32 and CP190 are the main positive drivers of 3D domain borders. In humans, our model identifies well-known architectural proteins CTCF and cohesin, as well as ZNF143 and Polycomb group proteins as positive drivers of domain borders. The model also reveals the existence of several negative drivers that counteract the presence of domain borders including P300, RXRA, BCL11A and ELK1. PMID:27203237

In silico studies on tryparedoxin peroxidase of Leishmania infantum: structural aspects.

PubMed

Singh, Bishal Kumar; Dubey, Vikash Kumar

2009-09-01

Tryparedoxin peroxidase (TryP) is a key enzyme of the trypanothione-dependent metabolism for removal of oxidative stress in leishmania. These enzymes function as antioxidants through their peroxidase and peroxynitrite reductase activities. Inhibitors of this enzyme are presumed to be antilesihmania drugs and structural studies are prerequisite of rational drug design. We have constructed three dimensional structure of TryP of Leishmania infantum using comparative modeling. Structural analysis reveals several interesting features. Moreover, it shows remarkable structural difference with human host glutathione peroxidase, an enzyme involved in similar function and TryP from Leishmania major.

A generative spike train model with time-structured higher order correlations.

PubMed

Trousdale, James; Hu, Yu; Shea-Brown, Eric; Josić, Krešimir

2013-01-01

Emerging technologies are revealing the spiking activity in ever larger neural ensembles. Frequently, this spiking is far from independent, with correlations in the spike times of different cells. Understanding how such correlations impact the dynamics and function of neural ensembles remains an important open problem. Here we describe a new, generative model for correlated spike trains that can exhibit many of the features observed in data. Extending prior work in mathematical finance, this generalized thinning and shift (GTaS) model creates marginally Poisson spike trains with diverse temporal correlation structures. We give several examples which highlight the model's flexibility and utility. For instance, we use it to examine how a neural network responds to highly structured patterns of inputs. We then show that the GTaS model is analytically tractable, and derive cumulant densities of all orders in terms of model parameters. The GTaS framework can therefore be an important tool in the experimental and theoretical exploration of neural dynamics.

All-atom ensemble modeling to analyze small angle X-ray scattering of glycosylated proteins

PubMed Central

Guttman, Miklos; Weinkam, Patrick; Sali, Andrej; Lee, Kelly K.

2013-01-01

Summary The flexible and heterogeneous nature of carbohydrate chains often renders glycoproteins refractory to traditional structure determination methods. Small Angle X-ray scattering (SAXS) can be a useful tool for obtaining structural information of these systems. All-atom modeling of glycoproteins with flexible glycan chains was applied to interpret the solution SAXS data for a set of glycoproteins. For simpler systems (single glycan, with a well defined protein structure), all-atom modeling generates models in excellent agreement with the scattering pattern, and reveals the approximate spatial occupancy of the glycan chain in solution. For more complex systems (several glycan chains, or unknown protein substructure), the approach can still provide insightful models, though the orientations of glycans become poorly determined. Ab initio shape reconstructions appear to capture the global morphology of glycoproteins, but in most cases offer little information about glycan spatial occupancy. The all-atom modeling methodology is available as a webserver at http://modbase.compbio.ucsf.edu/allosmod-foxs. PMID:23473666

Benchmarking Inverse Statistical Approaches for Protein Structure and Design with Exactly Solvable Models.

PubMed

Jacquin, Hugo; Gilson, Amy; Shakhnovich, Eugene; Cocco, Simona; Monasson, Rémi

2016-05-01

Inverse statistical approaches to determine protein structure and function from Multiple Sequence Alignments (MSA) are emerging as powerful tools in computational biology. However the underlying assumptions of the relationship between the inferred effective Potts Hamiltonian and real protein structure and energetics remain untested so far. Here we use lattice protein model (LP) to benchmark those inverse statistical approaches. We build MSA of highly stable sequences in target LP structures, and infer the effective pairwise Potts Hamiltonians from those MSA. We find that inferred Potts Hamiltonians reproduce many important aspects of 'true' LP structures and energetics. Careful analysis reveals that effective pairwise couplings in inferred Potts Hamiltonians depend not only on the energetics of the native structure but also on competing folds; in particular, the coupling values reflect both positive design (stabilization of native conformation) and negative design (destabilization of competing folds). In addition to providing detailed structural information, the inferred Potts models used as protein Hamiltonian for design of new sequences are able to generate with high probability completely new sequences with the desired folds, which is not possible using independent-site models. Those are remarkable results as the effective LP Hamiltonians used to generate MSA are not simple pairwise models due to the competition between the folds. Our findings elucidate the reasons for the success of inverse approaches to the modelling of proteins from sequence data, and their limitations.

Structure of the mouse sex peptide pheromone ESP1 reveals a molecular basis for specific binding to the class C G-protein-coupled vomeronasal receptor.

PubMed

Yoshinaga, Sosuke; Sato, Toru; Hirakane, Makoto; Esaki, Kaori; Hamaguchi, Takashi; Haga-Yamanaka, Sachiko; Tsunoda, Mai; Kimoto, Hiroko; Shimada, Ichio; Touhara, Kazushige; Terasawa, Hiroaki

2013-05-31

Exocrine gland-secreting peptide 1 (ESP1) is a sex pheromone that is released in male mouse tear fluids and enhances female sexual receptive behavior. ESP1 is selectively recognized by a specific class C G-protein-coupled receptor (GPCR), V2Rp5, among the hundreds of receptors expressed in vomeronasal sensory neurons (VSNs). The specific sensing mechanism of the mammalian peptide pheromone by the class C GPCR remains to be elucidated. Here we identified the minimal functional region needed to retain VSN-stimulating activity in ESP1 and determined its three-dimensional structure, which adopts a helical fold stabilized by an intramolecular disulfide bridge with extensive charged patches. We then identified the amino acids involved in the activation of VSNs by a structure-based mutational analysis, revealing that the highly charged surface is crucial for the ESP1 activity. We also demonstrated that ESP1 specifically bound to an extracellular region of V2Rp5 by an in vitro pulldown assay. Based on homology modeling of V2Rp5 using the structure of the metabotropic glutamate receptor, we constructed a docking model of the ESP1-V2Rp5 complex in which the binding interface exhibited good electrostatic complementarity. These experimental results, supported by the molecular docking simulations, reveal that charge-charge interactions determine the specificity of ESP1 binding to V2Rp5 in the large extracellular region characteristic of class C GPCRs. The present study provides insights into the structural basis for the narrowly tuned sensing of mammalian peptide pheromones by class C GPCRs.

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.

Inferring Biological Structures from Super-Resolution Single Molecule Images Using Generative Models

PubMed Central

Maji, Suvrajit; Bruchez, Marcel P.

2012-01-01

Localization-based super resolution imaging is presently limited by sampling requirements for dynamic measurements of biological structures. Generating an image requires serial acquisition of individual molecular positions at sufficient density to define a biological structure, increasing the acquisition time. Efficient analysis of biological structures from sparse localization data could substantially improve the dynamic imaging capabilities of these methods. Using a feature extraction technique called the Hough Transform simple biological structures are identified from both simulated and real localization data. We demonstrate that these generative models can efficiently infer biological structures in the data from far fewer localizations than are required for complete spatial sampling. Analysis at partial data densities revealed efficient recovery of clathrin vesicle size distributions and microtubule orientation angles with as little as 10% of the localization data. This approach significantly increases the temporal resolution for dynamic imaging and provides quantitatively useful biological information. PMID:22629348

A combined computational and structural model of the full-length human prolactin receptor

PubMed Central

Bugge, Katrine; Papaleo, Elena; Haxholm, Gitte W.; Hopper, Jonathan T. S.; Robinson, Carol V.; Olsen, Johan G.; Lindorff-Larsen, Kresten; Kragelund, Birthe B.

2016-01-01

The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg. PMID:27174498

Physical Principles of Discrete Hierarchies Formation in Protein Macromolecules

NASA Astrophysics Data System (ADS)

Malyshko, E. V.; Tverdislov, V. A.

2017-11-01

A model for chiral periodicity with alternating chiral sense in hierarchies of protein and nucleic acid structures is proposed and substantiated. Regular alternation of the chirality sense is revealed in transitions from the lowest to higher levels of structural-functional organization in proteins where it is L-D-L-D. The stratification principle combines the ideas of biomacromolecules folding and molecular biological machines.

AIM for Allostery: Using the Ising Model to Understand Information Processing and Transmission in Allosteric Biomolecular Systems.

PubMed

LeVine, Michael V; Weinstein, Harel

2015-05-01

In performing their biological functions, molecular machines must process and transmit information with high fidelity. Information transmission requires dynamic coupling between the conformations of discrete structural components within the protein positioned far from one another on the molecular scale. This type of biomolecular "action at a distance" is termed allostery . Although allostery is ubiquitous in biological regulation and signal transduction, its treatment in theoretical models has mostly eschewed quantitative descriptions involving the system's underlying structural components and their interactions. Here, we show how Ising models can be used to formulate an approach to allostery in a structural context of interactions between the constitutive components by building simple allosteric constructs we termed Allosteric Ising Models (AIMs). We introduce the use of AIMs in analytical and numerical calculations that relate thermodynamic descriptions of allostery to the structural context, and then show that many fundamental properties of allostery, such as the multiplicative property of parallel allosteric channels, are revealed from the analysis of such models. The power of exploring mechanistic structural models of allosteric function in more complex systems by using AIMs is demonstrated by building a model of allosteric signaling for an experimentally well-characterized asymmetric homodimer of the dopamine D2 receptor.

The Electrical Structure of Discharges Modified by Electron Beams

NASA Astrophysics Data System (ADS)

Haas, F. A.; Braithwaite, N. St. J.

1997-10-01

Injection of an electron beam into a low pressure plasma modifies both the electrical structure and the distributions of charged particle energies. The electrical structure is investigated here in a one-dimensional model by representing the discharge as two collisionless sheaths with a monenergetic electron beam, linked by a quasi-neutral collisional region. The latter is modelled by fluid equations in which the beam current decreases with position. Since the electrodes are connected by an external conductor this implies through Kirchoff's laws that the thermal electron current must correspondingly increase with position. Given the boundary conditions and beam input at the first electrode then the rest of the system is uniquely described. The model reveals the dependence of the sheath potentials at the emitting and absorbing surfaces on the beam current. The model is relevant to externally injected beams and to electron beams originating from secondary processes on surfaces exposed to the plasma.

3D Nanoporous Anodic Alumina Structures for Sustained Drug Release

PubMed Central

Xifré-Pérez, Elisabet; Eckstein, Chris; Ferré-Borrull, Josep

2017-01-01

The use of nanoporous anodic alumina (NAA) for the development of drug delivery systems has gained much attention in recent years. The release of drugs loaded inside NAA pores is complex and depends on the morphology of the pores. In this study, NAA, with different three-dimensional (3D) pore structures (cylindrical pores with several pore diameters, multilayered nanofunnels, and multilayered inverted funnels) were fabricated, and their respective drug delivery rates were studied and modeled using doxorubicin as a model drug. The obtained results reveal optimal modeling of all 3D pore structures, differentiating two drug release stages. Thus, an initial short-term and a sustained long-term release were successfully modeled by the Higuchi and the Korsmeyer–Peppas equations, respectively. This study demonstrates the influence of pore geometries on drug release rates, and further presents a sustained long-term drug release that exceeds 60 days without an undesired initial burst. PMID:28825654

The structure of DSM-IV-TR personality disorder diagnoses in NESARC: a reanalysis.

PubMed

Trull, Timothy J; Vergés, Alvaro; Wood, Phillip K; Sher, Kenneth J

2013-12-01

Cox, Clara, Worobec, and Grant (2012) recently presented results from a series of analyses aimed at identifying the factor structure underlying the DSM-IV-TR (APA, 2000) personality diagnoses assessed in the large NESARC study. Cox et al. (2012) concluded that the best fitting model was one that modeled three lower-order factors (the three clusters of PDs as outlined by DSM-IV-TR), which in turn loaded on a single PD higher-order factor. Our reanalyses of the NESARC Wave 1 and Wave 2 data for personality disorder diagnoses revealed that the best fitting model was that of a general PD factor that spans each of the ten DSM-IV PD diagnoses, and our reanalyses do not support the three-cluster hierarchical structure outlined by Cox et al. (2012) and DSM-IV-TR. Finally, we note the importance of modeling the Wave 2 assessment method factor in analyses of NESARC PD data.

Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

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

Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance

2011-07-01

Bacterial acyl carrier protein synthase plays an essential role in the synthesis of fatty acids, nonribosomal peptides and polyketides. In Mycobacterium tuberculosis, AcpS or group I phosphopentatheine transferase exhibits two different structural conformations depending upon the pH. The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS–ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the α2 helix andmore » in the conformation of the α3–α4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4–6.0). In contrast, at a higher pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS–ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS–ADP adopt different conformations depending upon the pH conditions of the crystallization solution.« less

Representing Heterogeneity in Structural Relationships Among Multiple Choice Variables Using a Latent Segmentation Approach

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

Garikapati, Venu; Astroza, Sebastian; Pendyala, Ram M.

Travel model systems often adopt a single decision structure that links several activity-travel choices together. The single decision structure is then used to predict activity-travel choices, with those downstream in the decision-making chain influenced by those upstream in the sequence. The adoption of a singular sequential causal structure to depict relationships among activity-travel choices in travel demand model systems ignores the possibility that some choices are made jointly as a bundle as well as the possible presence of structural heterogeneity in the population with respect to decision-making processes. As different segments in the population may adopt and follow different causalmore » decision-making mechanisms when making selected choices jointly, it would be of value to develop simultaneous equations model systems relating multiple endogenous choice variables that are able to identify population subgroups following alternative causal decision structures. Because the segments are not known a priori, they are considered latent and determined endogenously within a joint modeling framework proposed in this paper. The methodology is applied to a national mobility survey data set to identify population segments that follow different causal structures relating residential location choice, vehicle ownership, and car-share and mobility service usage. It is found that the model revealing three distinct latent segments best describes the data, confirming the efficacy of the modeling approach and the existence of structural heterogeneity in decision-making in the population. Future versions of activity-travel model systems should strive to incorporate such structural heterogeneity to better reflect varying decision processes across population subgroups.« less

Refined structure of dimeric diphtheria toxin at 2.0 A resolution.

PubMed Central

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

1994-01-01

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

The Structure of Working Memory Abilities across the Adult Life Span

PubMed Central

Hale, Sandra; Rose, Nathan S.; Myerson, Joel; Strube, Michael J; Sommers, Mitchell; Tye-Murray, Nancy; Spehar, Brent

2010-01-01

The present study addresses three questions regarding age differences in working memory: (1) whether performance on complex span tasks decreases as a function of age at a faster rate than performance on simple span tasks; (2) whether spatial working memory decreases at a faster rate than verbal working memory; and (3) whether the structure of working memory abilities is different for different age groups. Adults, ages 20–89 (n=388), performed three simple and three complex verbal span tasks and three simple and three complex spatial memory tasks. Performance on the spatial tasks decreased at faster rates as a function of age than performance on the verbal tasks, but within each domain, performance on complex and simple span tasks decreased at the same rates. Confirmatory factor analyses revealed that domain-differentiated models yielded better fits than models involving domain-general constructs, providing further evidence of the need to distinguish verbal and spatial working memory abilities. Regardless of which domain-differentiated model was examined, and despite the faster rates of decrease in the spatial domain, age group comparisons revealed that the factor structure of working memory abilities was highly similar in younger and older adults and showed no evidence of age-related dedifferentiation. PMID:21299306

TreeNetViz: revealing patterns of networks over tree structures.

PubMed

Gou, Liang; Zhang, Xiaolong Luke

2011-12-01

Network data often contain important attributes from various dimensions such as social affiliations and areas of expertise in a social network. If such attributes exhibit a tree structure, visualizing a compound graph consisting of tree and network structures becomes complicated. How to visually reveal patterns of a network over a tree has not been fully studied. In this paper, we propose a compound graph model, TreeNet, to support visualization and analysis of a network at multiple levels of aggregation over a tree. We also present a visualization design, TreeNetViz, to offer the multiscale and cross-scale exploration and interaction of a TreeNet graph. TreeNetViz uses a Radial, Space-Filling (RSF) visualization to represent the tree structure, a circle layout with novel optimization to show aggregated networks derived from TreeNet, and an edge bundling technique to reduce visual complexity. Our circular layout algorithm reduces both total edge-crossings and edge length and also considers hierarchical structure constraints and edge weight in a TreeNet graph. These experiments illustrate that the algorithm can reduce visual cluttering in TreeNet graphs. Our case study also shows that TreeNetViz has the potential to support the analysis of a compound graph by revealing multiscale and cross-scale network patterns. © 2011 IEEE

Modelling dynamics in protein crystal structures by ensemble refinement

PubMed Central

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

2012-01-01

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

A Novel Information-Theoretic Approach for Variable Clustering and Predictive Modeling Using Dirichlet Process Mixtures

PubMed Central

Chen, Yun; Yang, Hui

2016-01-01

In the era of big data, there are increasing interests on clustering variables for the minimization of data redundancy and the maximization of variable relevancy. Existing clustering methods, however, depend on nontrivial assumptions about the data structure. Note that nonlinear interdependence among variables poses significant challenges on the traditional framework of predictive modeling. In the present work, we reformulate the problem of variable clustering from an information theoretic perspective that does not require the assumption of data structure for the identification of nonlinear interdependence among variables. Specifically, we propose the use of mutual information to characterize and measure nonlinear correlation structures among variables. Further, we develop Dirichlet process (DP) models to cluster variables based on the mutual-information measures among variables. Finally, orthonormalized variables in each cluster are integrated with group elastic-net model to improve the performance of predictive modeling. Both simulation and real-world case studies showed that the proposed methodology not only effectively reveals the nonlinear interdependence structures among variables but also outperforms traditional variable clustering algorithms such as hierarchical clustering. PMID:27966581

Modeling Protein Expression and Protein Signaling Pathways

PubMed Central

Telesca, Donatello; Müller, Peter; Kornblau, Steven M.; Suchard, Marc A.; Ji, Yuan

2015-01-01

High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case, inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The proposed approach exploits available expert knowledge about the target pathway to define an informative prior on the hidden conditional dependence structure. An important feature of this prior is that it provides an instrument to explicitly anchor the model space to a set of interactions of interest, favoring a local search approach to model determination. We apply our model to reverse-phase protein array data from a study on acute myeloid leukemia. Our inference identifies relevant subpathways in relation to the unfolding of the biological process under study. PMID:26246646

A Novel Information-Theoretic Approach for Variable Clustering and Predictive Modeling Using Dirichlet Process Mixtures.

PubMed

Chen, Yun; Yang, Hui

2016-12-14

In the era of big data, there are increasing interests on clustering variables for the minimization of data redundancy and the maximization of variable relevancy. Existing clustering methods, however, depend on nontrivial assumptions about the data structure. Note that nonlinear interdependence among variables poses significant challenges on the traditional framework of predictive modeling. In the present work, we reformulate the problem of variable clustering from an information theoretic perspective that does not require the assumption of data structure for the identification of nonlinear interdependence among variables. Specifically, we propose the use of mutual information to characterize and measure nonlinear correlation structures among variables. Further, we develop Dirichlet process (DP) models to cluster variables based on the mutual-information measures among variables. Finally, orthonormalized variables in each cluster are integrated with group elastic-net model to improve the performance of predictive modeling. Both simulation and real-world case studies showed that the proposed methodology not only effectively reveals the nonlinear interdependence structures among variables but also outperforms traditional variable clustering algorithms such as hierarchical clustering.

Conceptual finite element study for comparison among superior, anterior, and spiral clavicle plate fixations for midshaft clavicle fracture.

PubMed

Huang, Teng-Le; Chen, Wen-Chuan; Lin, Kun-Jhih; Tsai, Cheng-Lun; Lin, Kang-Ping; Wei, Hung-Wen

2016-10-01

Open reduction internal fixation technique has been generally accepted for treatment of midshaft clavicle fractures. Both superior and anterior clavicle plates have been reported in clinical or biomechanical researches, while presently the spiral clavicle plate design has been introduced improved biomechanical behavior over conventional designs. In order to objectively realize the multi-directional biomechanical performances among the three geometries for clavicle plate designs, a current conceptual finite element study has been conducted with identical cross-sectional features for clavicle plates. The conceptual superior, anterior, and spiral clavicle plate models were constructed for virtual reduction and fixation to an OTA 15-B1.3 midshaft transverse fracture of clavicle. Mechanical load cases including cantilever bending, axial compression, inferior bending, and axial torsion have been applied for confirming the multi-directional structural stability and implant safety in biomechanical perspective. Results revealed that the anterior clavicle plate model represented lowest plate stress under all loading cases. The superior clavicle plate model showed greater axial compressive stiffness, while the anterior clavicle plate model performed greater rigidity under cantilever bending load. Three model represented similar structural stiffness under axial torsion. Played as a transition structure between superior and anterior clavicle plate, the spiral clavicle plate model revealed comparable results with acceptable multi-directional biomechanical behavior. The concept of spiral clavicle plate design is worth considering in practical application in clinics. Implant safety should be further investigated by evidences in future mechanical tests and clinical observations. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly.

PubMed

Xu, Kai; Chan, Yee-Peng; Bradel-Tretheway, Birgit; Akyol-Ataman, Zeynep; Zhu, Yongqun; Dutta, Somnath; Yan, Lianying; Feng, YanRu; Wang, Lin-Fa; Skiniotis, Georgios; Lee, Benhur; Zhou, Z Hong; Broder, Christopher C; Aguilar, Hector C; Nikolov, Dimitar B

2015-12-01

Nipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein.

The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics.

PubMed

Liu, Xu; Shepherd, Tyson R; Murray, Ann M; Xu, Zhen; Fuentes, Ernesto J

2013-03-05

PDZ (PSD-95/Dlg/ZO-1) domains are protein-protein interaction modules often regulated by ligand phosphorylation. Here, we investigated the specificity, structure, and dynamics of Tiam1 PDZ domain/ligand interactions. We show that the PDZ domain specifically binds syndecan1 (SDC1), phosphorylated SDC1 (pSDC1), and SDC3 but not other syndecan isoforms. The crystal structure of the PDZ/SDC1 complex indicates that syndecan affinity is derived from amino acids beyond the four C-terminal residues. Remarkably, the crystal structure of the PDZ/pSDC1 complex reveals a binding pocket that accommodates the phosphoryl group. Methyl relaxation experiments of PDZ/SCD1 and PDZ/pSDC1 complexes reveal that PDZ-phosphoryl interactions dampen dynamic motions in a distal region of the PDZ domain by decoupling them from the ligand-binding site. Our data are consistent with a selection model by which specificity and phosphorylation regulate PDZ/syndecan interactions and signaling events. Importantly, our relaxation data demonstrate that PDZ/phospho-ligand interactions regulate protein dynamics and their coupling to distal sites. Copyright © 2013 Elsevier Ltd. All rights reserved.

Flexible Wing Model for Structural Sizing and Multidisciplinary Design Optimization of a Strut-Braced Wing

NASA Technical Reports Server (NTRS)

Gern, Frank H.; Naghshineh, Amir H.; Sulaeman, Erwin; Kapania, Rakesh K.; Haftka, Raphael T.

2000-01-01

This paper describes a structural and aeroelastic model for wing sizing and weight calculation of a strut-braced wing. The wing weight is calculated using a newly developed structural weight analysis module considering the special nature of strut-braced wings. A specially developed aeroelastic model enables one to consider wing flexibility and spanload redistribution during in-flight maneuvers. The structural model uses a hexagonal wing-box featuring skin panels, stringers, and spar caps, whereas the aerodynamics part employs a linearized transonic vortex lattice method. Thus, the wing weight may be calculated from the rigid or flexible wing spanload. The calculations reveal the significant influence of the strut on the bending material weight of the wing. The use of a strut enables one to design a wing with thin airfoils without weight penalty. The strut also influences wing spanload and deformations. Weight savings are not only possible by calculation and iterative resizing of the wing structure according to the actual design loads. Moreover, as an advantage over the cantilever wing, employment of the strut twist moment for further load alleviation leads to increased savings in structural weight.

Buckling analysis of carbon nanotube bundles under axial compressive, bending and torsional loadings via a structural mechanics model

NASA Astrophysics Data System (ADS)

Lashkari Zadeh, Ali; Shariati, Mahmoud; Torabi, Hamid

2012-11-01

A structural mechanics model is employed for the investigation of the buckling behavior of carbon nanotube bundles of three single-walled carbon nanotubes (SWCNTs) under axial compressive, bending and torsional loadings. The effects of van der Waals (vdW) forces are further modeled using a nonlinear spring element.The effects of different types of boundary conditions are studied for nanotubes with various aspect ratios. The results reveal that bundles comprising longer SWCNTs exhibit lower critical buckling load. Moreover, for the fixed-free boundary condition the rate of critical buckling load reduction is highest, while the lowest critical buckling load occurs. Simulations show good agreement between our model and molecular dynamics results.

QSAR modeling for anti-human African trypanosomiasis activity of substituted 2-Phenylimidazopyridines

NASA Astrophysics Data System (ADS)

Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.

2017-02-01

In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

Tools for Model Building and Optimization into Near-Atomic Resolution Electron Cryo-Microscopy Density Maps.

PubMed

DiMaio, F; Chiu, W

2016-01-01

Electron cryo-microscopy (cryoEM) has advanced dramatically to become a viable tool for high-resolution structural biology research. The ultimate outcome of a cryoEM study is an atomic model of a macromolecule or its complex with interacting partners. This chapter describes a variety of algorithms and software to build a de novo model based on the cryoEM 3D density map, to optimize the model with the best stereochemistry restraints and finally to validate the model with proper protocols. The full process of atomic structure determination from a cryoEM map is described. The tools outlined in this chapter should prove extremely valuable in revealing atomic interactions guided by cryoEM data. © 2016 Elsevier Inc. All rights reserved.

Factors Affecting Study-Related Burnout among Finnish University Students: Teaching-Learning Environment, Achievement Motivation and the Meaning of Life

ERIC Educational Resources Information Center

Meriläinen, Matti

2014-01-01

This study of a large sample (n = 3035) examined relationships between study-related burnout and components of the teaching-learning environment, achievement motivation and the perceived meaning of life. The overall model, tested with structural equation modelling, revealed that the factor of the teaching-learning environment correlated with both…

Toll-like receptor 4-related immunostimulatory polysaccharides: Primary structure, activity relationships, and possible interaction models.

PubMed

Zhang, Xiaorui; Qi, Chunhui; Guo, Yan; Zhou, Wenxia; Zhang, Yongxiang

2016-09-20

Toll-like receptor (TLR) 4 is an important polysaccharide receptor; however, the relationships between the structures and biological activities of TLR4 and polysaccharides remain unknown. Many recent findings have revealed the primary structure of TLR4/MD-2-related polysaccharides, and several three-dimensional structure models of polysaccharide-binding proteins have been reported; and these models provide insights into the mechanisms through which polysaccharides interact with TLR4. In this review, we first discuss the origins of polysaccharides related to TLR4, including polysaccharides from higher plants, fungi, bacteria, algae, and animals. We then briefly describe the glucosidic bond types of TLR4-related heteroglycans and homoglycans and describe the typical molecular weights of TLR4-related polysaccharides. The primary structures and activity relationships of polysaccharides with TLR4/MD-2 are also discussed. Finally, based on the existing interaction models of LPS with TLR4/MD-2 and linear polysaccharides with proteins, we provide insights into the possible interaction models of polysaccharide ligands with TLR4/MD-2. To our knowledge, this review is the first to summarize the primary structures and activity relationships of TLR4-related polysaccharides and the possible mechanisms of interaction for TLR4 and TLR4-related polysaccharides. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-pressure structural study of MnF 2

DOE PAGES

Stavrou, Elissaios; Yao, Yansun; Goncharov, Alexander F.; ...

2015-02-01

In this study, manganese fluoride (MnF 2) with the tetragonal rutile-type structure has been studied using a synchrotron angle-dispersive powder x-ray diffraction and Raman spectroscopy in a diamond anvil cell up to 60 GPa at room temperature combined with first-principles density functional calculations. The experimental data reveal two pressure-induced structural phase transitions with the following sequence: rutile → SrI 2 type (3 GPa)→ α–PbCl 2 type (13 GPa). Complete structural information, including interatomic distances, has been determined in the case of MnF 2 including the exact structure of the debated first high-pressure phase. First-principles density functional calculations confirm this phasemore » transition sequence, and the two calculated transition pressures are in excellent agreement with the experiment. Lattice dynamics calculations also reproduce the experimental Raman spectra measured for the ambient and high-pressure phases. The results are discussed in line with the possible practical use of rutile-type fluorides in general and specifically MnF 2 as a model compound to reveal the HP structural behavior of rutile-type SiO 2 (Stishovite).« less

Conductivity and local structure in LaNiO3

NASA Astrophysics Data System (ADS)

Fowlie, Jennifer; Gibert, Marta; Tieri, Giulio; Gloter, Alexandre; à+/-Iguez, Jorge; Filippetti, Alessio; Catalano, Sara; Gariglio, Stefano; StéPhan, Odile; Triscone, Jean-Marc

In this study we approach the thickness-dependence of the properties of LaNiO3 films along multiple, complementary avenues: sophisticated ab initio calculations, scanning transmission electron microscopy and electronic transport. Specifically, we find an unexpected maximum in conductivity in films of thickness 6 - 10 unit cells (3 nm) for several series of LaNiO3 films. Ab initio transport based on the detailed crystal structure also reveals a maximum in conductivity at the same thickness. In agreement with the structure obtained from scanning transmission electron microscopy (STEM), our simulated structures reveal that the substrate- and surface-induced distortions lead to three types of local structure (heterointerface, interior-layer, surface). Based on this observation, a 3-element parallel conductor model neatly reproduces the trend of conductivity with thickness. This study addresses the question of how structural distortions at the atomic scale evolve in a thin film under the influence of the substrate and the surface. This topic is key to the understanding of the physics of heterostructures and the design of functional oxides.

Structure of the Mtb CarD/RNAP β-lobes complex reveals the molecular basis of interaction and presents a distinct DNA-binding domain for Mtb CarD.

PubMed

Gulten, Gulcin; Sacchettini, James C

2013-10-08

CarD from Mycobacterium tuberculosis (Mtb) is an essential protein shown to be involved in stringent response through downregulation of rRNA and ribosomal protein genes. CarD interacts with the β-subunit of RNAP and this interaction is vital for Mtb's survival during the persistent infection state. We have determined the crystal structure of CarD in complex with the RNAP β-subunit β1 and β2 domains at 2.1 Å resolution. The structure reveals the molecular basis of CarD/RNAP interaction, providing a basis to further our understanding of RNAP regulation by CarD. The structural fold of the CarD N-terminal domain is conserved in RNAP interacting proteins such as TRCF-RID and CdnL, and displays similar interactions to the predicted homology model based on the TRCF/RNAP β1 structure. Interestingly, the structure of the C-terminal domain, which is required for complete CarD function in vivo, represents a distinct DNA-binding fold. Copyright © 2013 Elsevier Ltd. All rights reserved.

Crustal and uppermost mantle structures of the South China from joint analysis of receiver functions and Rayleigh wave dispersions

NASA Astrophysics Data System (ADS)

Guo, Zhi; Gao, Xing; Li, Tong; Wang, Wei

2018-05-01

We use P-wave receiver function H-k stacking and joint inversion of receiver functions and Rayleigh wave dispersions to investigate crustal and uppermost mantle structure beneath the South China. The obtained results reveal prominent crustal structure variations in the study area, Moho depth increases from ∼30 km in the Cathaysia Block to more than ∼60 km in the eastern Tibetan Plateau. A Moho undulation and Vp/Vs ratio variations can be observed from the Cathaysia Block to Yangtze Craton. These observations consistent with the crustal structures predict by the flat slab subduction model. We interpret these lateral crustal structure variations reflect the tectonic evolution of the Yangtze Craton and Cathaysia Block prior the Mesozoic and the post-orogenic magmatism due to the breaking up of the subducted flat slab and subsequent slab rollback in the South China. The observed variations of the crustal structures not only reveal the lateral crustal inhomogeneity, but also provide constraints on the geodynamic evolution of the South China.

Observing Consistency in Online Communication Patterns for User Re-Identification.

PubMed

Adeyemi, Ikuesan Richard; Razak, Shukor Abd; Salleh, Mazleena; Venter, Hein S

2016-01-01

Comprehension of the statistical and structural mechanisms governing human dynamics in online interaction plays a pivotal role in online user identification, online profile development, and recommender systems. However, building a characteristic model of human dynamics on the Internet involves a complete analysis of the variations in human activity patterns, which is a complex process. This complexity is inherent in human dynamics and has not been extensively studied to reveal the structural composition of human behavior. A typical method of anatomizing such a complex system is viewing all independent interconnectivity that constitutes the complexity. An examination of the various dimensions of human communication pattern in online interactions is presented in this paper. The study employed reliable server-side web data from 31 known users to explore characteristics of human-driven communications. Various machine-learning techniques were explored. The results revealed that each individual exhibited a relatively consistent, unique behavioral signature and that the logistic regression model and model tree can be used to accurately distinguish online users. These results are applicable to one-to-one online user identification processes, insider misuse investigation processes, and online profiling in various areas.

Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.

PubMed

Hudson, Nathan E; Ding, Feng; Bucay, Igal; O'Brien, E Timothy; Gorkun, Oleg V; Superfine, Richard; Lord, Susan T; Dokholyan, Nikolay V; Falvo, Michael R

2013-06-18

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics

PubMed Central

Hudson, Nathan E.; Ding, Feng; Bucay, Igal; O’Brien, E. Timothy; Gorkun, Oleg V.; Superfine, Richard; Lord, Susan T.; Dokholyan, Nikolay V.; Falvo, Michael R.

2013-01-01

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin’s elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin’s mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. PMID:23790375

Structural investigation of porcine stomach mucin by X-ray fiber diffraction and homology modeling

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

Veluraja, K., E-mail: veluraja@msuniv.ac.in; Vennila, K.N.; Umamakeshvari, K.

Research highlights: {yields} Techniques to get oriented mucin fibre. {yields} X-ray fibre diffraction pattern for mucin. {yields} Molecular modeling of mucin based on X-ray fibre diffraction pattern. -- Abstract: The basic understanding of the three dimensional structure of mucin is essential to understand its physiological function. Technology has been developed to achieve orientated porcine stomach mucin molecules. X-ray fiber diffraction of partially orientated porcine stomach mucin molecules show d-spacing signals at 2.99, 4.06, 4.22, 4.7, 5.37 and 6.5 A. The high intense d-spacing signal at 4.22 A is attributed to the antiparallel {beta}-sheet structure identified in the fraction of themore » homology modeled mucin molecule (amino acid residues 800-980) using Nidogen-Laminin complex structure as a template. The X-ray fiber diffraction signal at 6.5 A reveals partial organization of oligosaccharides in porcine stomach mucin. This partial structure of mucin will be helpful in establishing a three dimensional structure for the whole mucin molecule.« less

A computational model for epidural electrical stimulation of spinal sensorimotor circuits.

PubMed

Capogrosso, Marco; Wenger, Nikolaus; Raspopovic, Stanisa; Musienko, Pavel; Beauparlant, Janine; Bassi Luciani, Lorenzo; Courtine, Grégoire; Micera, Silvestro

2013-12-04

Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.

Differences in within- and between-person factor structure of positive and negative affect: analysis of two intensive measurement studies using multilevel structural equation modeling.

PubMed

Rush, Jonathan; Hofer, Scott M

2014-06-01

The Positive and Negative Affect Schedule (PANAS) is a widely used measure of emotional experience. The factor structure of the PANAS has been examined predominantly with cross-sectional designs, which fails to disaggregate within-person variation from between-person differences. There is still uncertainty as to the factor structure of positive and negative affect and whether they constitute 2 distinct independent factors. The present study examined the within-person and between-person factor structure of the PANAS in 2 independent samples that reported daily affect over 7 and 14 occasions, respectively. Results from multilevel confirmatory factor analyses revealed that a 2-factor structure at both the within-person and between-person levels, with correlated specific factors for overlapping items, provided good model fit. The best-fitting solution was one where within-person factors of positive and negative affect were inversely correlated, but between-person factors were independent. The structure was further validated through multilevel structural equation modeling examining the effects of cognitive interference, daily stress, physical symptoms, and physical activity on positive and negative affect factors.

Global industrial impact coefficient based on random walk process and inter-country input-output table

NASA Astrophysics Data System (ADS)

Xing, Lizhi; Dong, Xianlei; Guan, Jun

2017-04-01

Input-output table is very comprehensive and detailed in describing the national economic system with lots of economic relationships, which contains supply and demand information among industrial sectors. The complex network, a theory and method for measuring the structure of complex system, can describe the structural characteristics of the internal structure of the research object by measuring the structural indicators of the social and economic system, revealing the complex relationship between the inner hierarchy and the external economic function. This paper builds up GIVCN-WIOT models based on World Input-Output Database in order to depict the topological structure of Global Value Chain (GVC), and assumes the competitive advantage of nations is equal to the overall performance of its domestic sectors' impact on the GVC. Under the perspective of econophysics, Global Industrial Impact Coefficient (GIIC) is proposed to measure the national competitiveness in gaining information superiority and intermediate interests. Analysis of GIVCN-WIOT models yields several insights including the following: (1) sectors with higher Random Walk Centrality contribute more to transmitting value streams within the global economic system; (2) Half-Value Ratio can be used to measure robustness of open-economy macroeconomics in the process of globalization; (3) the positive correlation between GIIC and GDP indicates that one country's global industrial impact could reveal its international competitive advantage.

Self-expanding/shrinking structures by 4D printing

NASA Astrophysics Data System (ADS)

Bodaghi, M.; Damanpack, A. R.; Liao, W. H.

2016-10-01

The aim of this paper is to create adaptive structures capable of self-expanding and self-shrinking by means of four-dimensional printing technology. An actuator unit is designed and fabricated directly by printing fibers of shape memory polymers (SMPs) in flexible beams with different arrangements. Experiments are conducted to determine thermo-mechanical material properties of the fabricated part revealing that the printing process introduced a strong anisotropy into the printed parts. The feasibility of the actuator unit with self-expanding and self-shrinking features is demonstrated experimentally. A phenomenological constitutive model together with analytical closed-form solutions are developed to replicate thermo-mechanical behaviors of SMPs. Governing equations of equilibrium are developed for printed structures based on the non-linear Green-Lagrange strain tensor and solved implementing a finite element method along with an iterative incremental Newton-Raphson scheme. The material-structural model is then applied to digitally design and print SMP adaptive lattices in planar and tubular shapes comprising a periodic arrangement of SMP actuator units that expand and then recover their original shape automatically. Numerical and experimental results reveal that the proposed planar lattice as meta-materials can be employed for plane actuators with self-expanding/shrinking features or as structural switches providing two different dynamic characteristics. It is also shown that the proposed tubular lattice with a self-expanding/shrinking mechanism can serve as tubular stents and grippers for bio-medical or piping applications.

Modeling rises and falls in money addicted social hierarchies

NASA Astrophysics Data System (ADS)

Dybiec, Bartłomiej; Mitarai, Namiko; Sneppen, Kim

2014-08-01

The emergence of large communities is inherently associated with the creation of social structures. Connections between individuals are indispensable for cooperative action of agents building social groups. Moreover, social groups usually evolve and their structure changes over time. Consequently, an underlying network connecting individuals is not static, reflecting an ongoing adaptation to new conditions. The evolution of social connections is influenced by the relative position (hierarchy) of individuals building the system as well as by the availability of resources. We explore this aspect of human ambition by modeling the interplay of social networking and an uneven distribution of external resources. The model naturally generates social hierarchies. Remarkably, this social structure exhibits a rise-and-fall behavior. A well pronounced quasi-periodic dynamics, which is closely associated with the dissipation of resources that are needed to sustain the social links, is revealed.

Design and fabrication of plasmonic cavities for magneto-optical sensing

NASA Astrophysics Data System (ADS)

Loughran, T. H. J.; Roth, J.; Keatley, P. S.; Hendry, E.; Barnes, W. L.; Hicken, R. J.; Einsle, J. F.; Amy, A.; Hendren, W.; Bowman, R. M.; Dawson, P.

2018-05-01

The design and fabrication of a novel plasmonic cavity, intended to allow far-field recovery of signals arising from near field magneto-optical interactions, is presented. Finite element modeling is used to describe the interaction between a gold film, containing cross-shaped cavities, with a nearby magnetic under-layer. The modeling revealed strong electric field confinement near the center of the cross structure for certain optical wavelengths, which may be tuned by varying the length of the cross through a range that is compatible with available fabrication techniques. Furthermore, the magneto optical Kerr effect (MOKE) response of the composite structure can be enhanced with respect to that of the bare magnetic film. To confirm these findings, cavities were milled within gold films deposited upon a soluble film, allowing relocation to a ferromagnetic film using a float transfer technique. Cross cavity arrays were fabricated and characterized by optical transmission spectroscopy prior to floating, revealing resonances at optical wavelengths in good agreement with the finite element modeling. Following transfer to the magnetic film, circular test apertures within the gold film yielded clear magneto-optical signals even for diameters within the sub-wavelength regime. However, no magneto-optical signal was observed for the cross cavity arrays, since the FIB milling process was found to produce nanotube structures within the soluble under-layer that adhered to the gold. Further optimization of the fabrication process should allow recovery of magneto-optical signal from cross cavity structures.

Computational determination of the binding mode of α-conotoxin to nicotinic acetylcholine receptor

NASA Astrophysics Data System (ADS)

Tabassum, Nargis; Yu, Rilei; Jiang, Tao

2016-12-01

Conotoxins belong to the large families of disulfide-rich peptide toxins from cone snail venom, and can act on a broad spectrum of ion channels and receptors. They are classified into different subtypes based on their targets. The α-conotoxins selectively inhibit the current of the nicotinic acetylcholine receptors. Because of their unique selectivity towards distinct nAChR subtypes, α-conotoxins become valuable tools in nAChR study. In addition to the X-ray structures of α-conotoxins in complex with acetylcholine-binding protein, a homolog of the nAChR ligand-binding domain, the high-resolution crystal structures of the extracellular domain of the α1 and α9 subunits are also obtained. Such structures not only revealed the details of the configuration of nAChR, but also provided higher sequence identity templates for modeling the binding modes of α-conotoxins to nAChR. This mini-review summarizes recent modeling studies for the determination of the binding modes of α-conotoxins to nAChR. As there are not crystal structures of the nAChR in complex with conotoxins, computational modeling in combination of mutagenesis data is expected to reveal the molecular recognition mechanisms that govern the interactions between α-conotoxins and nAChR at molecular level. An accurate determination of the binding modes of α-conotoxins on AChRs allows rational design of α-conotoxin analogues with improved potency or selectivity to nAChRs.

Can role models boost entrepreneurial attitudes?

PubMed Central

Fellnhofer, Katharina; Puumalainen, Kaisu

2017-01-01

This multi-country study used role models to boost perceptions of entrepreneurial feasibility and desirability. The results of a structural equation model based on a sample comprising 426 individuals who were primarily from Austria, Finland and Greece revealed a significant positive influence on perceived entrepreneurial desirability and feasibility. These findings support the argument for embedding entrepreneurial role models in entrepreneurship education courses to promote entrepreneurial activities. This direction is not only relevant for the academic community but also essential for nascent entrepreneurs, policymakers and society at large. PMID:28458611

Can role models boost entrepreneurial attitudes?

PubMed

Fellnhofer, Katharina; Puumalainen, Kaisu

2017-01-01

This multi-country study used role models to boost perceptions of entrepreneurial feasibility and desirability. The results of a structural equation model based on a sample comprising 426 individuals who were primarily from Austria, Finland and Greece revealed a significant positive influence on perceived entrepreneurial desirability and feasibility. These findings support the argument for embedding entrepreneurial role models in entrepreneurship education courses to promote entrepreneurial activities. This direction is not only relevant for the academic community but also essential for nascent entrepreneurs, policymakers and society at large.

Near Infrared Spectroscopic Identification of Alkyl Aromatic Esters and Phenyl Ketones

NASA Astrophysics Data System (ADS)

Nelyubov, D. V.; Vazhenin, D. A.; Kudriavtsev, A. A.; Buzolina, A. Yu.

2018-03-01

Bands characterizing the content of carbon atoms in alkyl (7177-7205 cm-1) and phenyl structural fragments (9175-9192 cm-1) in organic molecules were revealed by studying the near infrared spectra of such compounds. The optical density at the maxima of these absorption bands was shown to depend strongly on the fraction of carbon atoms in the corresponding fragments. The developed models proved to be adequate for determining the fraction of carbon atoms in alkyl aromatic esters and phenyl ketones. The feasibility of modeling the molecular structure of alkyl aromatic esters using regression models was demonstrated for the product of the condensation of oleic acid and benzyl alcohol.

A contact angle hysteresis model based on the fractal structure of contact line.

PubMed

Wu, Shuai; Ma, Ming

2017-11-01

Contact angle is one of the most popular concept used in fields such as wetting, transport and microfludics. In practice, different contact angles such as equilibrium, receding and advancing contact angles are observed due to hysteresis. The connection among these contact angles is important in revealing the chemical and physical properties of surfaces related to wetting. Inspired by the fractal structure of contact line, we propose a single parameter model depicting the connection of the three angles. This parameter is decided by the fractal structure of the contact line. The results of this model agree with experimental observations. In certain cases, it can be reduced to other existing models. It also provides a new point of view in understanding the physical nature of the contact angle hysteresis. Interestingly, some counter-intuitive phenomena, such as the binary receding angles, are indicated in this model, which are waited to be validated by experiments. Copyright © 2017 Elsevier Inc. All rights reserved.

Modelling of AlAs/GaAs interfacial structures using high-angle annular dark field (HAADF) image simulations.

PubMed

Robb, Paul D; Finnie, Michael; Craven, Alan J

2012-07-01

High angle annular dark field (HAADF) image simulations were performed on a series of AlAs/GaAs interfacial models using the frozen-phonon multislice method. Three general types of models were considered-perfect, vicinal/sawtooth and diffusion. These were chosen to demonstrate how HAADF image measurements are influenced by different interfacial structures in the technologically important III-V semiconductor system. For each model, interfacial sharpness was calculated as a function of depth and compared to aberration-corrected HAADF experiments of two types of AlAs/GaAs interfaces. The results show that the sharpness measured from HAADF imaging changes in a complicated manner with thickness for complex interfacial structures. For vicinal structures, it was revealed that the type of material that the probe projects through first of all has a significant effect on the measured sharpness. An increase in the vicinal angle was also shown to generate a wider interface in the random step model. The Moison diffusion model produced an increase in the interface width with depth which closely matched the experimental results of the AlAs-on-GaAs interface. In contrast, the interface width decreased as a function of depth in the linear diffusion model. Only in the case of the perfect model was it possible to ascertain the underlying structure directly from HAADF image analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Instinct as interactive structure: Freud's psychoanalysis in historical and metatheoretical perspective.

PubMed

Jovanović, Gordana

2005-01-01

When Freud began formulating the basic postulates of psychoanalytic theory the concept of instinct was in widespread use. There are very different models of conceptualizing instincts in psychoanalysis: reflex arc, representation, interaction, subject and finally a regressive structure. Freud revised the traditional concept of instinct and his models formed a peculiar metatheoretical history of psychoanalysis. Defining human nature by reference to its determining instinctive essence and commitment to the ideal of natural science led Freud to a naturalistic fallacy. Yet at the same time the hermeneutics of instinct theory reveal a socio-historical meaning of naturalism.

Structure-Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors.

PubMed

Congdon, Molly D; Kharel, Yugesh; Brown, Anne M; Lewis, Stephanie N; Bevan, David R; Lynch, Kevin R; Santos, Webster L

2016-03-10

The two isoforms of sphingosine kinase (SphK1 and SphK2) are the only enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in a broad range of cellular processes including migration, proliferation, and inflammation. SphKs are targets for various diseases such as cancer, fibrosis, and Alzheimer's and sickle cell disease. Herein, we disclose the structure-activity profile of naphthalene-containing SphK inhibitors and molecular modeling studies that reveal a key molecular switch that controls SphK selectivity.

[Critical phenomena, phase equilibria, and the temperature and structural optimum of homeostasis, as revealed by a model system water-biopolymer-electrolyte].

PubMed

Rozhkov, S P

2005-01-01

Equations of spinodal and two quasispinodals corresponding to critical and supercritical phase transitions leading to a rise of different dynamic structures of solution in the phase diagram of a model system water-biopolymer-electrolyte were obtained. The section of the phase diagram was considered where there exists the probability of quasi-equilibrium monomer-cluster and the principle of water-ion homeostasis is realized. Based on these results, a possible mechanism of origination of unspecific adaptation reactions of a biomolecular system at the stage of chemical evolution was suggested.

Understanding metallic bonding: Structure, process and interaction by Rasch analysis

NASA Astrophysics Data System (ADS)

Cheng, Maurice M. W.; Oon, Pey-Tee

2016-08-01

This paper reports the results of a survey of 3006 Year 10-12 students on their understandings of metallic bonding. The instrument was developed based on Chi's ontological categories of scientific concepts and students' understanding of metallic bonding as reported in the literature. The instrument has two parts. Part one probed into students' understanding of metallic bonding as (a) a submicro structure of metals, (b) a process in which individual metal atoms lose their outermost shell electrons to form a 'sea of electrons' and octet metal cations or (c) an all-directional electrostatic force between delocalized electrons and metal cations, that is, an interaction. Part two assessed students' explanation of malleability of metals, for example (a) as a submicro structural rearrangement of metal atoms/cations or (b) based on all-directional electrostatic force. The instrument was validated by the Rasch Model. Psychometric assessment showed that the instrument possessed reasonably good properties of measurement. Results revealed that it was reliable and valid for measuring students' understanding of metallic bonding. Analysis revealed that the structure, process and interaction understandings were unidimensional and in an increasing order of difficulty. Implications for the teaching of metallic bonding, particular through the use of diagrams, critiques and model-based learning, are discussed.

The vibro-acoustic response and analysis of a full-scale aircraft fuselage section for interior noise reduction.

PubMed

Herdic, Peter C; Houston, Brian H; Marcus, Martin H; Williams, Earl G; Baz, Amr M

2005-06-01

The surface and interior response of a Cessna Citation fuselage section under three different forcing functions (10-1000 Hz) is evaluated through spatially dense scanning measurements. Spatial Fourier analysis reveals that a point force applied to the stiffener grid provides a rich wavenumber response over a broad frequency range. The surface motion data show global structural modes (approximately < 150 Hz), superposition of global and local intrapanel responses (approximately 150-450 Hz), and intrapanel motion alone (approximately > 450 Hz). Some evidence of Bloch wave motion is observed, revealing classical stop/pass bands associated with stiffener periodicity. The interior response (approximately < 150 Hz) is dominated by global structural modes that force the interior cavity. Local intrapanel responses (approximately > 150 Hz) of the fuselage provide a broadband volume velocity source that strongly excites a high density of interior modes. Mode coupling between the structural response and the interior modes appears to be negligible due to a lack of frequency proximity and mismatches in the spatial distribution. A high degree-of-freedom finite element model of the fuselage section was developed as a predictive tool. The calculated response is in good agreement with the experimental result, yielding a general model development methodology for accurate prediction of structures with moderate to high complexity.

Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography

PubMed Central

Han, Shen; Kollmer, Marius; Markx, Daniel; Claus, Stephanie; Walther, Paul; Fändrich, Marcus

2017-01-01

The deposition of amyloid fibrils as plaques is a key feature of several neurodegenerative diseases including in particular Alzheimer’s. This disease is characterized, if not provoked, by amyloid aggregates formed from Aβ peptide that deposit inside the brain or are toxic to neuronal cells. We here used scanning transmission electron microscopy (STEM) to determine the fibril network structure and interactions of Aβ fibrils within a cell culture model of Alzheimer’s disease. STEM images taken from the formed Aβ amyloid deposits revealed three main types of fibril network structures, termed amorphous meshwork, fibril bundle and amyloid star. All three were infiltrated by different types of lipid inclusions from small-sized exosome-like structures (50–100 nm diameter) to large-sized extracellular vesicles (up to 300 nm). The fibrils also presented strong interactions with the surrounding cells such that fibril bundles extended into tubular invaginations of the plasma membrane. Amyloid formation in the cell model was previously found to have an intracellular origin and we show here that it functionally destroys the integrity of the intracellular membranes as it leads to lysosomal leakage. These data provide a mechanistic link to explain why intracellular fibril formation is toxic to the cell. PMID:28240273

Generic Features of Tertiary Chromatin Structure as Detected in Natural Chromosomes

PubMed Central

Müller, Waltraud G.; Rieder, Dietmar; Kreth, Gregor; Cremer, Christoph; Trajanoski, Zlatko; McNally, James G.

2004-01-01

Knowledge of tertiary chromatin structure in mammalian interphase chromosomes is largely derived from artificial tandem arrays. In these model systems, light microscope images reveal fibers or beaded fibers after high-density targeting of transactivators to insertional domains spanning several megabases. These images of fibers have lent support to chromonema fiber models of tertiary structure. To assess the relevance of these studies to natural mammalian chromatin, we identified two different ∼400-kb regions on human chromosomes 6 and 22 and then examined light microscope images of interphase tertiary chromatin structure when the regions were transcriptionally active and inactive. When transcriptionally active, these natural chromosomal regions elongated, yielding images characterized by a series of adjacent puncta or “beads”, referred to hereafter as beaded images. These elongated structures required transcription for their maintenance. Thus, despite marked differences in the density and the mode of transactivation, the natural and artificial systems showed similarities, suggesting that beaded images are generic features of transcriptionally active tertiary chromatin. We show here, however, that these images do not necessarily favor chromonema fiber models but can also be explained by a radial-loop model or even a simple nucleosome affinity, random-chain model. Thus, light microscope images of tertiary structure cannot distinguish among competing models, although they do impose key constraints: chromatin must be clustered to yield beaded images and then packaged within each cluster to enable decondensation into adjacent clusters. PMID:15485905

Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar.

PubMed

Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F Javier

2010-12-01

Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar (Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

Nanoscale inhomogeneity and photoacid generation dynamics in extreme ultraviolet resist materials

NASA Astrophysics Data System (ADS)

Wu, Ping-Jui; Wang, Yu-Fu; Chen, Wei-Chi; Wang, Chien-Wei; Cheng, Joy; Chang, Vencent; Chang, Ching-Yu; Lin, John; Cheng, Yuan-Chung

2018-03-01

The development of extreme ultraviolet (EUV) lithography towards the 22 nm node and beyond depends critically on the availability of resist materials that meet stringent control requirements in resolution, line edge roughness, and sensitivity. However, the molecular mechanisms that govern the structure-function relationships in current EUV resist systems are not well understood. In particular, the nanoscale structures of the polymer base and the distributions of photoacid generators (PAGs) should play a critical roles in the performance of a resist system, yet currently available models for photochemical reactions in EUV resist systems are exclusively based on homogeneous bulk models that ignore molecular-level details of solid resist films. In this work, we investigate how microscopic molecular organizations in EUV resist affect photoacid generations in a bottom-up approach that describes structure-dependent electron-transfer dynamics in a solid film model. To this end, molecular dynamics simulations and stimulated annealing are used to obtain structures of a large simulation box containing poly(4-hydroxystyrene) (PHS) base polymers and triphenylsulfonium based PAGs. Our calculations reveal that ion-pair interactions govern the microscopic distributions of the polymer base and PAG molecules, resulting in a highly inhomogeneous system with nonuniform nanoscale chemical domains. Furthermore, the theoretical structures were used in combination of quantum chemical calculations and the Marcus theory to evaluate electron transfer rates between molecular sites, and then kinetic Monte Carlo simulations were carried out to model electron transfer dynamics with molecular structure details taken into consideration. As a result, the portion of thermalized electrons that are absorbed by the PAGs and the nanoscale spatial distribution of generated acids can be estimated. Our data reveal that the nanoscale inhomogeneous distributions of base polymers and PAGs strongly affect the electron transfer and the performance of the resist system. The implications to the performances of EUV resists and key engineering requirements for improved resist systems will also be discussed in this work. Our results shed light on the fundamental structure dependence of photoacid generation and the control of the nanoscale structures as well as base polymer-PAG interactions in EVU resist systems, and we expect these knowledge will be useful for the future development of improved EUV resist systems.

Structural basis of death domain signaling in the p75 neurotrophin receptor

PubMed Central

Lin, Zhi; Tann, Jason Y; Goh, Eddy TH; Kelly, Claire; Lim, Kim Buay; Gao, Jian Fang; Ibanez, Carlos F

2015-01-01

Death domains (DDs) mediate assembly of oligomeric complexes for activation of downstream signaling pathways through incompletely understood mechanisms. Here we report structures of complexes formed by the DD of p75 neurotrophin receptor (p75NTR) with RhoGDI, for activation of the RhoA pathway, with caspase recruitment domain (CARD) of RIP2 kinase, for activation of the NF-kB pathway, and with itself, revealing how DD dimerization controls access of intracellular effectors to the receptor. RIP2 CARD and RhoGDI bind to p75NTR DD at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. The p75NTR DD forms non-covalent, low-affinity symmetric dimers in solution. The dimer interface overlaps with RIP2 CARD but not RhoGDI binding sites, supporting a model of receptor activation triggered by separation of DDs. These structures reveal how competitive protein-protein interactions orchestrate the hierarchical activation of downstream pathways in non-catalytic receptors. DOI: http://dx.doi.org/10.7554/eLife.11692.001 PMID:26646181

Mechanistic Details of Glutathione Biosynthesis Revealed by Crystal Structures of Saccharomyces cerevisiae Glutamate Cysteine Ligase

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

Biterova, Ekaterina I.; Barycki, Joseph J.; UNL)

2009-12-01

Glutathione is a thiol-disulfide exchange peptide critical for buffering oxidative or chemical stress, and an essential cofactor in several biosynthesis and detoxification pathways. The rate-limiting step in its de novo biosynthesis is catalyzed by glutamate cysteine ligase, a broadly expressed enzyme for which limited structural information is available in higher eukaryotic species. Structural data are critical to the understanding of clinical glutathione deficiency, as well as rational design of enzyme modulators that could impact human disease progression. Here, we have determined the structures of Saccharomyces cerevisiae glutamate cysteine ligase (ScGCL) in the presence of glutamate and MgCl{sub 2} (2.1 {angstrom};more » R = 18.2%, R{sub free} = 21.9%), and in complex with glutamate, MgCl{sub 2}, and ADP (2.7 {angstrom}; R = 19.0%, R{sub free} = 24.2%). Inspection of these structures reveals an unusual binding pocket for the {alpha}-carboxylate of the glutamate substrate and an ATP-independent Mg{sup 2+} coordination site, clarifying the Mg{sup 2+} dependence of the enzymatic reaction. The ScGCL structures were further used to generate a credible homology model of the catalytic subunit of human glutamate cysteine ligase (hGCLC). Examination of the hGCLC model suggests that post-translational modifications of cysteine residues may be involved in the regulation of enzymatic activity, and elucidates the molecular basis of glutathione deficiency associated with patient hGCLC mutations.« less

Origin of reduced magnetization and domain formation in small magnetite nanoparticles

DOE PAGES

Nedelkoski, Zlatko; Kepaptsoglou, Demie; Lari, Leonardo; ...

2017-04-10

We compare the structural, chemical, and magnetic properties of magnetite nanoparticles. Aberration corrected scanning transmission electron microscopy reveals the prevalence of antiphase boundaries in nanoparticles that have significantly reduced magnetization, relative to the bulk. We show that atomistic magnetic modelling of nanoparticles with and without these defects reveal the origin of the reduced moment. Strong antiferromagnetic interactions across antiphase boundaries support multiple magnetic domains even in particles as small as 12–14 nm.

Revealing the nonadiabatic nature of dark energy perturbations from galaxy clustering data

NASA Astrophysics Data System (ADS)

Velten, Hermano; Fazolo, Raquel

2017-10-01

We study structure formation using relativistic cosmological linear perturbation theory in the presence of intrinsic and relative (with respect to matter) nonadiabatic dark energy perturbations. For different dark energy models we assess the impact of nonadiabaticity on the matter growth promoting a comparison with growth rate data. The dark energy models studied lead to peculiar signatures of the (non)adiabatic nature of dark energy perturbations in the evolution of the f σ8(z ) observable. We show that nonadiabatic dark energy models become close to be degenerated with respect to the Λ CDM model at first order in linear perturbations. This would avoid the identification of the nonadiabatic nature of dark energy using current available data. Therefore, such evidence indicates that new probes are necessary to reveal the nonadiabatic features in the dark energy sector.

β Lup, δ Lup, and τ^1 Lup observed by BRITE-Constellation

NASA Astrophysics Data System (ADS)

Cugier, H.; Pigulski, A.

2017-09-01

Time-series analysis of BRITE-Constellation photometry of β Lup, δ Lup and τ^1 Lup revealed 16, 22 and four pulsation modes, respectively. An attempt to constrain internal structure of these stars via seismic modelling was also made.

Sub-cellular force microscopy in single normal and cancer cells

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

Babahosseini, H.; Carmichael, B.; Strobl, J.S.

2015-08-07

This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer andmore » significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. - Highlights: • The cells are modeled as a triple-layered structure using Generalized Maxwell model. • The sub-domains include membrane/cortex, cytoplasm/nucleus, and nuclear/integrin. • Biomechanics of corresponding sub-domains are compared among normal and cancer cells. • Viscoelasticity of sub-domains show a decreasing trend from normal to cancer cells. • The decreasing trend becomes most significant in the deeper sub-domain.« less

Solution and Crystallographic Structures of the Central Region of the Phosphoprotein from Human Metapneumovirus

PubMed Central

Leyrat, Cedric; Renner, Max; Harlos, Karl; Grimes, Jonathan M.

2013-01-01

Human metapneumovirus (HMPV) of the family Paramyxoviridae is a major cause of respiratory illness worldwide. Phosphoproteins (P) from Paramyxoviridae are essential co-factors of the viral RNA polymerase that form tetramers and possess long intrinsically disordered regions (IDRs). We located the central region of HMPV P (Pced) which is involved in tetramerization using disorder analysis and modeled its 3D structure ab initio using Rosetta fold-and-dock. We characterized the solution-structure of Pced using small angle X-ray scattering (SAXS) and carried out direct fitting to the scattering data to filter out incorrect models. Molecular dynamics simulations (MDS) and ensemble optimization were employed to select correct models and capture the dynamic character of Pced. Our analysis revealed that oligomerization involves a compact central core located between residues 169-194 (Pcore), that is surrounded by flexible regions with α-helical propensity. We crystallized this fragment and solved its structure at 3.1 Å resolution by molecular replacement, using the folded core from our SAXS-validated ab initio model. The RMSD between modeled and experimental tetramers is as low as 0.9 Å, demonstrating the accuracy of the approach. A comparison of the structure of HMPV P to existing mononegavirales Pced structures suggests that Pced evolved under weak selective pressure. Finally, we discuss the advantages of using SAXS in combination with ab initio modeling and MDS to solve the structure of small, homo-oligomeric protein complexes. PMID:24224051

Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-terminal domain

PubMed Central

2011-01-01

Background The NIMA-related kinases (Neks) are widespread among eukaryotes. In mammalians they represent an evolutionarily conserved family of 11 serine/threonine kinases, with 40-45% amino acid sequence identity to the Aspergillus nidulans mitotic regulator NIMA within their catalytic domains. Neks have cell cycle-related functions and were recently described as related to pathologies, particularly cancer, consisting in potential chemotherapeutic targets. Human Nek6, -7 and -9 are involved in the control of mitotic spindle formation, acting together in a mitotic kinase cascade, but their mechanism of regulation remain elusive. Results In this study we performed a biophysical and structural characterization of human Nek6 with the aim of obtaining its low resolution and homology models. SAXS experiments showed that hNek6 is a monomer of a mostly globular, though slightly elongated shape. Comparative molecular modeling together with disorder prediction analysis also revealed a flexible disordered N-terminal domain for hNek6, which we found to be important to mediate interactions with diverse partners. SEC-MALS experiments showed that hNek6 conformation is dependent on its activation/phosphorylation status, a higher phosphorylation degree corresponding to a bigger Stokes radius. Circular dichroism spectroscopy confirmed our in silico predictions of secondary structure content and thermal stability shift assays revealed a slightly higher stability of wild-type hNek6 compared to the activation loop mutant hNek6(S206A). Conclusions Our data present the first low resolution 3D structure of hNek6 protein in solution. SAXS, comparative modeling and SEC-MALS analysis revealed that hNek6 is a monomeric kinase of slightly elongated shape and a short unfolded N-terminal domain. PMID:21320329

Structure of Insoluble Rat Sperm Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) via Heterotetramer Formation with Escherichia coli GAPDH Reveals Target for Contraceptive Design*

PubMed Central

Frayne, Jan; Taylor, Abby; Cameron, Gus; Hadfield, Andrea T.

2009-01-01

Sperm glyceraldehyde-3-phosphate dehydrogenase has been shown to be a successful target for a non-hormonal contraceptive approach, but the agents tested to date have had unacceptable side effects. Obtaining the structure of the sperm-specific isoform to allow rational inhibitor design has therefore been a goal for a number of years but has proved intractable because of the insoluble nature of both native and recombinant protein. We have obtained soluble recombinant sperm glyceraldehyde-3-phosphate dehydrogenase as a heterotetramer with the Escherichia coli glyceraldehyde-3-phosphate dehydrogenase in a ratio of 1:3 and have solved the structure of the heterotetramer which we believe represents a novel strategy for structure determination of an insoluble protein. A structure was also obtained where glyceraldehyde 3-phosphate binds in the Ps pocket in the active site of the sperm enzyme subunit in the presence of NAD. Modeling and comparison of the structures of human somatic and sperm-specific glyceraldehyde-3-phosphate dehydrogenase revealed few differences at the active site and hence rebut the long presumed structural specificity of 3-chlorolactaldehyde for the sperm isoform. The contraceptive activity of α-chlorohydrin and its apparent specificity for the sperm isoform in vivo are likely to be due to differences in metabolism to 3-chlorolactaldehyde in spermatozoa and somatic cells. However, further detailed analysis of the sperm glyceraldehyde-3-phosphate dehydrogenase structure revealed sites in the enzyme that do show significant difference compared with published somatic glyceraldehyde-3-phosphate dehydrogenase structures that could be exploited by structure-based drug design to identify leads for novel male contraceptives. PMID:19542219

Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers

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

Swanson, Kurt A.; Settembre, Ethan C.; Shaw, Christine A.

2012-02-07

Respiratory syncytial virus (RSV), the main cause of infant bronchiolitis, remains a major unmet vaccine need despite more than 40 years of vaccine research. Vaccine candidates based on a chief RSV neutralization antigen, the fusion (F) glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the prefusion and postfusion states, suggesting that postfusion F antigens might not efficiently elicit neutralizing antibodies. We have generated a homogeneous, stable, and reproducible postfusion RSV F immunogen that elicits high titers of neutralizing antibodies in immunized animals.more » The 3.2-{angstrom} X-ray crystal structure of this substantially complete RSV F reveals important differences from homology-based structural models. Specifically, the RSV F crystal structure demonstrates the exposure of key neutralizing antibody binding sites on the surface of the postfusion RSV F trimer. This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens.« less

Communication: Ion mobility of the radical cation dimers: (Naphthalene)2+• and naphthalene+•-benzene: Evidence for stacked sandwich and T-shape structures

NASA Astrophysics Data System (ADS)

Platt, Sean P.; Attah, Isaac K.; Aziz, Saadullah; El-Shall, M. Samy

2015-05-01

Dimer radical cations of aromatic and polycyclic aromatic molecules are good model systems for a fundamental understanding of photoconductivity and ferromagnetism in organic materials which depend on the degree of charge delocalization. The structures of the dimer radical cations are difficult to determine theoretically since the potential energy surface is often very flat with multiple shallow minima representing two major classes of isomers adopting the stacked parallel or the T-shape structure. We present experimental results, based on mass-selected ion mobility measurements, on the gas phase structures of the naphthalene+ṡ ṡ naphthalene homodimer and the naphthalene+ṡ ṡ benzene heterodimer radical cations at different temperatures. Ion mobility studies reveal a persistence of the stacked parallel structure of the naphthalene+ṡ ṡ naphthalene homodimer in the temperature range 230-300 K. On the other hand, the results reveal that the naphthalene+ṡ ṡ benzene heterodimer is able to exhibit both the stacked parallel and T-shape structural isomers depending on the experimental conditions. Exploitation of the unique structural motifs among charged homo- and heteroaromatic-aromatic interactions may lead to new opportunities for molecular design and recognition involving charged aromatic systems.

Use of Interactive Whiteboard in the Mathematics Classroom: Students' Perceptions within the Framework of the Technology Acceptance Model

ERIC Educational Resources Information Center

Önal, Nezih

2017-01-01

The purpose of the present research was to reveal students' perceptions regarding the use of the interactive whiteboard in the mathematics classroom within the framework of the Technology Acceptance Model. Semi-structured interviews were performed with 58 secondary school students (5th, 6th, 7th, and 8th grades) to collect data. The data obtained…

Disclosing Mental Illness Information to a Friend: Exploring How the Disclosure Decision-Making Model Informs Strategy Selection.

PubMed

Venetis, Maria K; Chernichky-Karcher, Skye; Gettings, Patricia E

2018-06-01

Within the context of mental illness disclosure between friends, this study tested the disclosure decision-making model (DD-MM; Greene, 2009) to comprehensively investigate factors that predict disclosure enactment strategies. The DD-MM describes how individuals determine whether they will reveal or conceal non-visible health information. Processes of revealing, called disclosures, take various forms including preparation and rehearsal, directness, third-party disclosure, incremental disclosures, entrapment, and indirect mediums (Afifi & Steuber, 2009). We explore the disclosure decision-making process to understand how college students select to disclose their mental illness information with a friend. Participants were 144 students at a Midwestern university who had disclosed their mental illness information to a friend. Structural equation modeling analyses revealed that college students choose strategies based on their evaluation of information assessment and closeness, and that for some strategies, efficacy mediates the relationship between information assessment and strategy. This manuscript discusses implications of findings and suggests direction for future research.

LeuT conformational sampling utilizing accelerated molecular dynamics and principal component analysis.

PubMed

Thomas, James R; Gedeon, Patrick C; Grant, Barry J; Madura, Jeffry D

2012-07-03

Monoamine transporters (MATs) function by coupling ion gradients to the transport of dopamine, norepinephrine, or serotonin. Despite their importance in regulating neurotransmission, the exact conformational mechanism by which MATs function remains elusive. To this end, we have performed seven 250 ns accelerated molecular dynamics simulations of the leucine transporter, a model for neurotransmitter MATs. By varying the presence of binding-pocket leucine substrate and sodium ions, we have sampled plausible conformational states representative of the substrate transport cycle. The resulting trajectories were analyzed using principal component analysis of transmembrane helices 1b and 6a. This analysis revealed seven unique structures: two of the obtained conformations are similar to the currently published crystallographic structures, one conformation is similar to a proposed open inward structure, and four conformations represent novel structures of potential importance to the transport cycle. Further analysis reveals that the presence of binding-pocket sodium ions is necessary to stabilize the locked-occluded and open-inward conformations. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

Wu, Huixian; Wacker, Daniel; Mileni, Mauro

Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and - in the case of {kappa}-opioid receptor ({kappa}-OR) - dysphoria and psychotomimesis. Here we report the crystal structure of the human {kappa}-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 {angstrom} resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human {kappa}-OR. Modelling of other important {kappa}-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5'-guanidinonaltrindole, and the diterpenemore » agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure-activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for {kappa}-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human {kappa}-OR.« less

Exploring the Electronic Structure and Chemical Homogeneity of Individual Bi2Te3 Nanowires by Nano-Angle-Resolved Photoemission Spectroscopy.

PubMed

Krieg, Janina; Chen, Chaoyu; Avila, José; Zhang, Zeying; Sigle, Wilfried; Zhang, Hongbin; Trautmann, Christina; Asensio, Maria Carmen; Toimil-Molares, Maria Eugenia

2016-07-13

Due to their high surface-to-volume ratio, cylindrical Bi2Te3 nanowires are employed as model systems to investigate the chemistry and the unique conductive surface states of topological insulator nanomaterials. We report on nanoangle-resolved photoemission spectroscopy (nano-ARPES) characterization of individual cylindrical Bi2Te3 nanowires with a diameter of 100 nm. The nanowires are synthesized by electrochemical deposition inside channels of ion-track etched polymer membranes. Core level spectra recorded with submicron resolution indicate a homogeneous chemical composition along individual nanowires, while nano-ARPES intensity maps reveal the valence band structure at the single nanowire level. First-principles electronic structure calculations for chosen crystallographic orientations are in good agreement with those revealed by nano-ARPES. The successful application of nano-ARPES on single one-dimensional nanostructures constitutes a new avenue to achieve a better understanding of the electronic structure of topological insulator nanomaterials.

Rheological properties in relation to molecular structure of quinoa starch.

PubMed

Li, Guantian; Zhu, Fan

2018-07-15

Quinoa starch granules are small (~0.5 - 3μm) with potentials for some food and other applications. To better exploit it as a new starch resource, this study investigates the steady shear and dynamic oscillatory properties of 9 quinoa starches varying in composition and structure. Steady shear analysis shows that the flow curves could be well described by 4 selected mathematic models. Temperature sweep analysis reveals that the quinoa starch encounters a 4-stage process including 2 phase transitions. Structure-function relationship analysis showed that composition as well as unit and internal chain length distribution of amylopectin have significant impact on the rheological properties (e.g., G' at 90°C) of quinoa starch. The roles of some individual unit chains and super-long unit chains of amylopectin in determining the rheological properties of quinoa starch were revealed. This study may stimulate further interest in understanding the structural basis of starch rheology. Copyright © 2018 Elsevier B.V. All rights reserved.

GdPtPb: A noncollinear antiferromagnet with distorted kagome lattice

DOE PAGES

Manni, S.; Bud'ko, Sergey L.; Canfield, Paul C.

2017-08-24

In the spirit of searching for Gd-based, frustrated, rare earth magnets, we have found antiferomagnetism (AF) in GdPtPb, which crystallizes in the ZrNiAl-type structure that has a distorted kagome lattice of Gd triangles. Single crystals were grown and investigated using structural, magnetic, transport, and thermodynamic measurements. GdPtPb orders antiferromagnetically at 15.5 K, arguably with a planar, noncollinear structure. The high temperature magnetic susceptibility data reveal an “anti-frustration” behavior having a frustration parameter, |f| = |Θ|/T N = 0.25, which can be explained by mean field theory within a two-sublattice model. Here, the study of the magnetic phase diagram down tomore » T = 1.8K reveals a change of magnetic structure through a metamagnetic transition at around 20 kOe and the disappearance of the AF ordering near 140 kOe. In total, our work indicates that GdPtPb can serve as an example of a planar, noncollinear AF with a distorted kagome magnetic sublattice.« less

Study on sand particles creep model and open pit mine landslide mechanism caused by sand fatigue liquefaction

NASA Astrophysics Data System (ADS)

Du, Dong-Ning; Wang, Lai-Gui; Zhang, Xiang-Dong; Zhang, Shu-Kun

2017-06-01

The sand particles in the sand - rock composite slope of the open pit mine occurs creep deformation and fatigue liquefaction under the action of vehicle load vibration and hydraulic gradient, which causes landslide geological disasters and it destroys the surface environment. To reveal the mechanism, a mechanics model based on the model considering the soil structural change with a new “plastic hinge” element is developed, to improve its constitutive and creep curve equations. Data from sand creep experiments are used to identify the parameters in the model and to validate the model. The results show that the mechanical model can describe the rotation progress between the sand particles, disclose the negative acceleration creep deformation stage during the third phase, and require fewer parameters while maintaining accuracy. It provides a new creep model considering rotation to analyze sand creep mechanism, which provides a theoretical basis for revealing the open pit mine landslide mechanism induced by creep deformation and fatigue liquefaction of sandy soil.

FRankenstein becomes a cyborg: the automatic recombination and realignment of fold recognition models in CASP6.

PubMed

Kosinski, Jan; Gajda, Michal J; Cymerman, Iwona A; Kurowski, Michal A; Pawlowski, Marcin; Boniecki, Michal; Obarska, Agnieszka; Papaj, Grzegorz; Sroczynska-Obuchowicz, Paulina; Tkaczuk, Karolina L; Sniezynska, Paulina; Sasin, Joanna M; Augustyn, Anna; Bujnicki, Janusz M; Feder, Marcin

2005-01-01

In the course of CASP6, we generated models for all targets using a new version of the "FRankenstein's monster approach." Previously (in CASP5) we were able to build many very accurate full-atom models by selection and recombination of well-folded fragments obtained from crude fold recognition (FR) results, followed by optimization of the sequence-structure fit and assessment of alternative alignments on the structural level. This procedure was however very arduous, as most of the steps required extensive visual and manual input from the human modeler. Now, we have automated the most tedious steps, such as superposition of alternative models, extraction of best-scoring fragments, and construction of a hybrid "monster" structure, as well as generation of alternative alignments in the regions that remain poorly scored in the refined hybrid model. We have also included the ROSETTA method to construct those parts of the target for which no reasonable structures were generated by FR methods (such as long insertions and terminal extensions). The analysis of successes and failures of the current version of the FRankenstein approach in modeling of CASP6 targets reveals that the considerably streamlined and automated method performs almost as well as the initial, mostly manual version, which suggests that it may be a useful tool for accurate protein structure prediction even in the hands of nonexperts. 2005 Wiley-Liss, Inc.

3-D Upper-Mantle Shear Velocity Model Beneath the Contiguous United States Based on Broadband Surface Wave from Ambient Seismic Noise

NASA Astrophysics Data System (ADS)

Xie, Jun; Chu, Risheng; Yang, Yingjie

2018-05-01

Ambient noise seismic tomography has been widely used to study crustal and upper-mantle shear velocity structures. Most studies, however, concentrate on short period (< 50 s) surface wave from ambient noise, while studies using long period surface wave from ambient noise are limited. In this paper, we demonstrate the feasibility of using long-period surface wave from ambient noise to study the lithospheric structure on a continental scale. We use broadband Rayleigh wave phase velocities to obtain a 3-D V S structures beneath the contiguous United States at period band of 10-150 s. During the inversion, 1-D shear wave velocity profile is parameterized using B-spline at each grid point and is inverted with nonlinear Markov Chain Monte Carlo method. Then, a 3-D shear velocity model is constructed by assembling all the 1-D shear velocity profiles. Our model is overall consistent with existing models which are based on multiple datasets or data from earthquakes. Our model along with the other post-USArray models reveal lithosphere structures in the upper mantle, which are consistent with the geological tectonic background (e.g., the craton root and regional upwelling provinces). The model has comparable resolution on lithosphere structures compared with many published results and can be used for future detailed regional or continental studies and analysis.

Subduction erosion and implication for evolution model of the Yap trench: new evidence from the latest geophysical survey

NASA Astrophysics Data System (ADS)

Zhang, Z.; Dong, D.; Bai, Y.; Zhang, G.

2017-12-01

The subduction of oceanic plateau, including the ridge and seamount, with buoyant feature will lead to the occurrence of subduction erosion. Yap Trench is a unique structure related to the Caroline Ridge subduction, but with lower research degree. Previous studies lacked the investigation of crustal structure and subduction erosion model based on integrated geophysical data in Yap Trench. In 2015, Institute of Oceanology, Chinese Academy of Sciences acquired swath bathymetric, multi-channel seismic and gravity data by research vessel "Kexue" in the Yap Trench and its adjacent area, providing the chance to further explore this subduction system. For this research, we mainly used the latest data to analyze the topography and crustal structure in Yap subduction system, which is significant for the construction of subduction erosion model. We reveal that, (1) The mean value of arc-ward slope is 8° according with bathymetric slope features in erosive margins(>3°). The increasing trend to dip angles in arc-ward slope shows the control of subducting plate with different elevation from north to south; (2) The horst and graben structures and different scales of seamounts display the rough features in the subducting plate, facilitating the overlying Yap Arc erosion. In the front of the Yap Arc, collision scars identified on the bathymetric map indicates the seamount subducting; (3) The horst and graben structures, with thinner crust of 2-4 km thick, in subducting plate, possibly eroded the Yap Arc basement and made it thinner during subduction. The subducted seamounts with high topography underplated the Yap Arc, which uplifted and thickened the overlying plate crust. Therefore, it is suggested that. subduction erosion model is varied in Yap subduction sysytem which is affected by topography and crust structure of subducting plate. The two types of subduction erosion models in Yap Trench exhibit a good case to reveal the process and mode of plate subducting in subduction zone. Acknowledge: This study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA11030102), the National Natural Science Foundation of China (No. 41476042, 41506055 )

Homology-based Modeling of Rhodopsin-like Family Members in the Inactive State: Structural Analysis and Deduction of Tips for Modeling and Optimization.

PubMed

Pappalardo, Matteo; Rayan, Mahmoud; Abu-Lafi, Saleh; Leonardi, Martha E; Milardi, Danilo; Guccione, Salvatore; Rayan, Anwar

2017-08-01

Modeling G-Protein Coupled Receptors (GPCRs) is an emergent field of research, since utility of high-quality models in receptor structure-based strategies might facilitate the discovery of interesting drug candidates. The findings from a quantitative analysis of eighteen resolved structures of rhodopsin family "A" receptors crystallized with antagonists and 153 pairs of structures are described. A strategy termed endeca-amino acids fragmentation was used to analyze the structures models aiming to detect the relationship between sequence identity and Root Mean Square Deviation (RMSD) at each trans-membrane-domain. Moreover, we have applied the leave-one-out strategy to study the shiftiness likelihood of the helices. The type of correlation between sequence identity and RMSD was studied using the aforementioned set receptors as representatives of membrane proteins and 98 serine proteases with 4753 pairs of structures as representatives of globular proteins. Data analysis using fragmentation strategy revealed that there is some extent of correlation between sequence identity and global RMSD of 11AA width windows. However, spatial conservation is not always close to the endoplasmic side as was reported before. A comparative study with globular proteins shows that GPCRs have higher standard deviation and higher slope in the graph with correlation between sequence identity and RMSD. The extracted information disclosed in this paper could be incorporated in the modeling protocols while using technique for model optimization and refinement. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cluster structure in the correlation coefficient matrix can be characterized by abnormal eigenvalues

NASA Astrophysics Data System (ADS)

Nie, Chun-Xiao

2018-02-01

In a large number of previous studies, the researchers found that some of the eigenvalues of the financial correlation matrix were greater than the predicted values of the random matrix theory (RMT). Here, we call these eigenvalues as abnormal eigenvalues. In order to reveal the hidden meaning of these abnormal eigenvalues, we study the toy model with cluster structure and find that these eigenvalues are related to the cluster structure of the correlation coefficient matrix. In this paper, model-based experiments show that in most cases, the number of abnormal eigenvalues of the correlation matrix is equal to the number of clusters. In addition, empirical studies show that the sum of the abnormal eigenvalues is related to the clarity of the cluster structure and is negatively correlated with the correlation dimension.

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

Kufareva, Irina; Gustavsson, Martin; Zheng, Yi

Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novelmore » epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.« less

Structure and application of antifreeze proteins from Antarctic bacteria.

PubMed

Muñoz, Patricio A; Márquez, Sebastián L; González-Nilo, Fernando D; Márquez-Miranda, Valeria; Blamey, Jenny M

2017-08-07

Antifreeze proteins (AFPs) production is a survival strategy of psychrophiles in ice. These proteins have potential in frozen food industry avoiding the damage in the structure of animal or vegetal foods. Moreover, there is not much information regarding the interaction of Antarctic bacterial AFPs with ice, and new determinations are needed to understand the behaviour of these proteins at the water/ice interface. Different Antarctic places were screened for antifreeze activity and microorganisms were selected for the presence of thermal hysteresis in their crude extracts. Isolates GU1.7.1, GU3.1.1, and AFP5.1 showed higher thermal hysteresis and were characterized using a polyphasic approach. Studies using cucumber and zucchini samples showed cellular protection when samples were treated with partially purified AFPs or a commercial AFP as was determined using toluidine blue O and neutral red staining. Additionally, genome analysis of these isolates revealed the presence of genes that encode for putative AFPs. Deduced amino acids sequences from GU3.1.1 (gu3A and gu3B) and AFP5.1 (afp5A) showed high similarity to reported AFPs which crystal structures are solved, allowing then generating homology models. Modelled proteins showed a triangular prism form similar to β-helix AFPs with a linear distribution of threonine residues at one side of the prism that could correspond to the putative ice binding side. The statistically best models were used to build a protein-water system. Molecular dynamics simulations were then performed to compare the antifreezing behaviour of these AFPs at the ice/water interface. Docking and molecular dynamics simulations revealed that gu3B could have the most efficient antifreezing behavior, but gu3A could have a higher affinity for ice. AFPs from Antarctic microorganisms GU1.7.1, GU3.1.1 and AFP5.1 protect cellular structures of frozen food showing a potential for frozen food industry. Modeled proteins possess a β-helix structure, and molecular docking analysis revealed the AFP gu3B could be the most efficient AFPs in order to avoid the formation of ice crystals, even when gu3A has a higher affinity for ice. By determining the interaction of AFPs at the ice/water interface, it will be possible to understand the process of adaptation of psychrophilic bacteria to Antarctic ice.

Multi-scale quantum point contact model for filamentary conduction in resistive random access memories devices

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

Lian, Xiaojuan, E-mail: xjlian2005@gmail.com; Cartoixà, Xavier; Miranda, Enrique

2014-06-28

We depart from first-principle simulations of electron transport along paths of oxygen vacancies in HfO{sub 2} to reformulate the Quantum Point Contact (QPC) model in terms of a bundle of such vacancy paths. By doing this, the number of model parameters is reduced and a much clearer link between the microscopic structure of the conductive filament (CF) and its electrical properties can be provided. The new multi-scale QPC model is applied to two different HfO{sub 2}-based devices operated in the unipolar and bipolar resistive switching (RS) modes. Extraction of the QPC model parameters from a statistically significant number of CFsmore » allows revealing significant structural differences in the CF of these two types of devices and RS modes.« less

Structural analysis according to reduced data: VIII. Refinement of the extended model of aspherical atoms

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

Dudka, A. P.

A program for the refinement of the model of aspherical atoms within the Stewart-Hansen-Coppens formalism has been developed. Deformation scattering up to the 8th expansion order in multipoles has been taken into account for the first time. The program was tested for 11 crystals. The effect of the result of interpolation of radial scattering curves on the model parameters is considered. The importance of introduction of multipoles of high (5th-8th) orders into the model for a number of crystals is shown. The use of the extended multipole model for a silicon crystal revealed some new specific features of the electronicmore » structure: consideration of multipoles up to the 7th order makes it possible to explain the intensity of the forbidden 222 reflection.« less

The impact of natural transformation on adaptation in spatially structured bacterial populations.

PubMed

Moradigaravand, Danesh; Engelstädter, Jan

2014-06-20

Recent studies have demonstrated that natural transformation and the formation of highly structured populations in bacteria are interconnected. In spite of growing evidence about this connection, little is known about the dynamics of natural transformation in spatially structured bacterial populations. In this work, we model the interdependency between the dynamics of the bacterial gene pool and those of environmental DNA in space to dissect the effect of transformation on adaptation. Our model reveals that even with only a single locus under consideration, transformation with a free DNA fragment pool results in complex adaptation dynamics that do not emerge in previous models focusing only on the gene shuffling effect of transformation at multiple loci. We demonstrate how spatial restriction on population growth and DNA diffusion in the environment affect the impact of transformation on adaptation. We found that in structured bacterial populations intermediate DNA diffusion rates predominantly cause transformation to impede adaptation by spreading deleterious alleles in the population. Overall, our model highlights distinctive evolutionary consequences of bacterial transformation in spatially restricted compared to planktonic bacterial populations.

Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization

PubMed Central

Huang, Ruili; Xia, Menghang; Sakamuru, Srilatha; Zhao, Jinghua; Shahane, Sampada A.; Attene-Ramos, Matias; Zhao, Tongan; Austin, Christopher P.; Simeonov, Anton

2016-01-01

Target-specific, mechanism-oriented in vitro assays post a promising alternative to traditional animal toxicology studies. Here we report the first comprehensive analysis of the Tox21 effort, a large-scale in vitro toxicity screening of chemicals. We test ∼10,000 chemicals in triplicates at 15 concentrations against a panel of nuclear receptor and stress response pathway assays, producing more than 50 million data points. Compound clustering by structure similarity and activity profile similarity across the assays reveals structure–activity relationships that are useful for the generation of mechanistic hypotheses. We apply structural information and activity data to build predictive models for 72 in vivo toxicity end points using a cluster-based approach. Models based on in vitro assay data perform better in predicting human toxicity end points than animal toxicity, while a combination of structural and activity data results in better models than using structure or activity data alone. Our results suggest that in vitro activity profiles can be applied as signatures of compound mechanism of toxicity and used in prioritization for more in-depth toxicological testing. PMID:26811972

Multi-scale, multi-method geophysical investigations of the Valles Caldera

NASA Astrophysics Data System (ADS)

Barker, J. E.; Daneshvar, S.; Langhans, A.; Okorie, C.; Parapuzha, A.; Perez, N.; Turner, A.; Smith, E.; Carchedi, C. J. W.; Creighton, A.; Folsom, M.; Bedrosian, P.; Pellerin, L.; Feucht, D. W.; Kelly, S.; Ferguson, J. F.; McPhee, D.

2017-12-01

In 2016, the Summer of Applied Geophysical Experience (SAGE) program, in cooperation with the National Park Service, began a multi-year investigation into the structure and evolution of the Valles Caldera in northern New Mexico. The Valles Caldera is a 20-km wide topographic depression in the Jemez Mountains volcanic complex that formed during two massive ignimbrite eruptions at 1.65 and 1.26 Ma. Post-collapse volcanic activity in the caldera includes the rise of Redondo peak, a 1 km high resurgent dome, periodic eruptions of the Valles rhyolite along an inferred ring fracture zone, and the presence of a geothermal reservoir beneath the western caldera with temperatures in excess of 300°C at a mere 2 km depth. Broad sediment-filled valleys associated with lava-dammed Pleistocene lakes occupy much of the northern and southeastern caldera. SAGE activities to date have included collection of new gravity data (>120 stations) throughout the caldera, a transient electromagnetic (TEM) survey of Valle Grande, reprocessing of industrial magnetotelluric (MT) data collected in the 1980s, and new MT data collection both within and outside of the caldera. Gravity modeling provides constraints on the pre-Caldera structure, estimates of the thickness of Caldera fill, and reveals regional structural trends reflected in the geometry of post-Caldera collapse. At a more local scale, TEM-derived resistivity models image rhyolite flows radiating outward from nearby vents into the lacustrine sediments filling Valle Grande. Resistivity models along a 6-km long profile also provide hints of structural dismemberment along the inferred Valles and Toledo ring fracture zones. Preliminary MT modeling at the caldera scale reveals conductive caldera fill, the resistive crystalline basement, and an enigmatic mid-crustal conductor likely related to magmatic activity that post-dates caldera formation.

Comparative and Evolutionary Analysis of Grass Pollen Allergens Using Brachypodium distachyon as a Model System.

PubMed

Sharma, Akanksha; Sharma, Niharika; Bhalla, Prem; Singh, Mohan

2017-01-01

Comparative genomics have facilitated the mining of biological information from a genome sequence, through the detection of similarities and differences with genomes of closely or more distantly related species. By using such comparative approaches, knowledge can be transferred from the model to non-model organisms and insights can be gained in the structural and evolutionary patterns of specific genes. In the absence of sequenced genomes for allergenic grasses, this study was aimed at understanding the structure, organisation and expression profiles of grass pollen allergens using the genomic data from Brachypodium distachyon as it is phylogenetically related to the allergenic grasses. Combining genomic data with the anther RNA-Seq dataset revealed 24 pollen allergen genes belonging to eight allergen groups mapping on the five chromosomes in B. distachyon. High levels of anther-specific expression profiles were observed for the 24 identified putative allergen-encoding genes in Brachypodium. The genomic evidence suggests that gene encoding the group 5 allergen, the most potent trigger of hay fever and allergic asthma originated as a pollen specific orphan gene in a common grass ancestor of Brachypodium and Triticiae clades. Gene structure analysis showed that the putative allergen-encoding genes in Brachypodium either lack or contain reduced number of introns. Promoter analysis of the identified Brachypodium genes revealed the presence of specific cis-regulatory sequences likely responsible for high anther/pollen-specific expression. With the identification of putative allergen-encoding genes in Brachypodium, this study has also described some important plant gene families (e.g. expansin superfamily, EF-Hand family, profilins etc) for the first time in the model plant Brachypodium. Altogether, the present study provides new insights into structural characterization and evolution of pollen allergens and will further serve as a base for their functional characterization in related grass species.

Understanding Nomophobia: Structural Equation Modeling and Semantic Network Analysis of Smartphone Separation Anxiety.

PubMed

Han, Seunghee; Kim, Ki Joon; Kim, Jang Hyun

2017-07-01

This study explicates nomophobia by developing a research model that identifies several determinants of smartphone separation anxiety and by conducting semantic network analyses on smartphone users' verbal descriptions of the meaning of their smartphones. Structural equation modeling of the proposed model indicates that personal memories evoked by smartphones encourage users to extend their identity onto their devices. When users perceive smartphones as their extended selves, they are more likely to get attached to the devices, which, in turn, leads to nomophobia by heightening the phone proximity-seeking tendency. This finding is also supplemented by the results of the semantic network analyses revealing that the words related to memory, self, and proximity-seeking are indeed more frequently used in the high, compared with low, nomophobia group.

Insight into mitochondrial structure and function from electron tomography.

PubMed

Frey, T G; Renken, C W; Perkins, G A

2002-09-10

In recent years, electron tomography has provided detailed three-dimensional models of mitochondria that have redefined our concept of mitochondrial structure. The models reveal an inner membrane consisting of two components, the inner boundary membrane (IBM) closely apposed to the outer membrane and the cristae membrane that projects into the matrix compartment. These two components are connected by tubular structures of relatively uniform size called crista junctions. The distribution of crista junction sizes and shapes is predicted by a thermodynamic model based upon the energy of membrane bending, but proteins likely also play a role in determining the conformation of the inner membrane. Results of structural studies of mitochondria during apoptosis demonstrate that cytochrome c is released without detectable disruption of the outer membrane or extensive swelling of the mitochondrial matrix, suggesting the formation of an outer membrane pore large enough to allow passage of holo-cytochrome c. The possible compartmentation of inner membrane function between the IBM and the cristae membrane is also discussed.

Geometrical structure of Neural Networks: Geodesics, Jeffrey's Prior and Hyper-ribbons

NASA Astrophysics Data System (ADS)

Hayden, Lorien; Alemi, Alex; Sethna, James

2014-03-01

Neural networks are learning algorithms which are employed in a host of Machine Learning problems including speech recognition, object classification and data mining. In practice, neural networks learn a low dimensional representation of high dimensional data and define a model manifold which is an embedding of this low dimensional structure in the higher dimensional space. In this work, we explore the geometrical structure of a neural network model manifold. A Stacked Denoising Autoencoder and a Deep Belief Network are trained on handwritten digits from the MNIST database. Construction of geodesics along the surface and of slices taken from the high dimensional manifolds reveal a hierarchy of widths corresponding to a hyper-ribbon structure. This property indicates that neural networks fall into the class of sloppy models, in which certain parameter combinations dominate the behavior. Employing this information could prove valuable in designing both neural network architectures and training algorithms. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No . DGE-1144153.

A new rational-based optimal design strategy of ship structure based on multi-level analysis and super-element modeling method

NASA Astrophysics Data System (ADS)

Sun, Li; Wang, Deyu

2011-09-01

A new multi-level analysis method of introducing the super-element modeling method, derived from the multi-level analysis method first proposed by O. F. Hughes, has been proposed in this paper to solve the problem of high time cost in adopting a rational-based optimal design method for ship structural design. Furthermore, the method was verified by its effective application in optimization of the mid-ship section of a container ship. A full 3-D FEM model of a ship, suffering static and quasi-static loads, was used as the analyzing object for evaluating the structural performance of the mid-ship module, including static strength and buckling performance. Research results reveal that this new method could substantially reduce the computational cost of the rational-based optimization problem without decreasing its accuracy, which increases the feasibility and economic efficiency of using a rational-based optimal design method in ship structural design.

High-angular-resolution stellar imaging with occultations from the Cassini spacecraft - III. Mira

NASA Astrophysics Data System (ADS)

Stewart, Paul N.; Tuthill, Peter G.; Nicholson, Philip D.; Hedman, Matthew M.

2016-04-01

We present an analysis of spectral and spatial data of Mira obtained by the Cassini spacecraft, which not only observed the star's spectra over a broad range of near-infrared wavelengths, but was also able to obtain high-resolution spatial information by watching the star pass behind Saturn's rings. The observed spectral range of 1-5 microns reveals the stellar atmosphere in the crucial water-bands which are unavailable to terrestrial observers, and the simultaneous spatial sampling allows the origin of spectral features to be located in the stellar environment. Models are fitted to the data, revealing the spectral and spatial structure of molecular layers surrounding the star. High-resolution imagery is recovered revealing the layered and asymmetric nature of the stellar atmosphere. The observational data set is also used to confront the state-of-the-art cool opacity-sampling dynamic extended atmosphere models of Mira variables through a detailed spectral and spatial comparison, revealing in general a good agreement with some specific departures corresponding to particular spectral features.

Agent-based model with multi-level herding for complex financial systems

NASA Astrophysics Data System (ADS)

Chen, Jun-Jie; Tan, Lei; Zheng, Bo

2015-02-01

In complex financial systems, the sector structure and volatility clustering are respectively important features of the spatial and temporal correlations. However, the microscopic generation mechanism of the sector structure is not yet understood. Especially, how to produce these two features in one model remains challenging. We introduce a novel interaction mechanism, i.e., the multi-level herding, in constructing an agent-based model to investigate the sector structure combined with volatility clustering. According to the previous market performance, agents trade in groups, and their herding behavior comprises the herding at stock, sector and market levels. Further, we propose methods to determine the key model parameters from historical market data, rather than from statistical fitting of the results. From the simulation, we obtain the sector structure and volatility clustering, as well as the eigenvalue distribution of the cross-correlation matrix, for the New York and Hong Kong stock exchanges. These properties are in agreement with the empirical ones. Our results quantitatively reveal that the multi-level herding is the microscopic generation mechanism of the sector structure, and provide new insight into the spatio-temporal interactions in financial systems at the microscopic level.

Agent-based model with multi-level herding for complex financial systems

PubMed Central

Chen, Jun-Jie; Tan, Lei; Zheng, Bo

2015-01-01

In complex financial systems, the sector structure and volatility clustering are respectively important features of the spatial and temporal correlations. However, the microscopic generation mechanism of the sector structure is not yet understood. Especially, how to produce these two features in one model remains challenging. We introduce a novel interaction mechanism, i.e., the multi-level herding, in constructing an agent-based model to investigate the sector structure combined with volatility clustering. According to the previous market performance, agents trade in groups, and their herding behavior comprises the herding at stock, sector and market levels. Further, we propose methods to determine the key model parameters from historical market data, rather than from statistical fitting of the results. From the simulation, we obtain the sector structure and volatility clustering, as well as the eigenvalue distribution of the cross-correlation matrix, for the New York and Hong Kong stock exchanges. These properties are in agreement with the empirical ones. Our results quantitatively reveal that the multi-level herding is the microscopic generation mechanism of the sector structure, and provide new insight into the spatio-temporal interactions in financial systems at the microscopic level. PMID:25669427

The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function.

PubMed

Banach, Mateusz; Konieczny, Leszek; Roterman, Irena

2014-10-21

In this paper we show that the fuzzy oil drop model represents a general framework for describing the generation of hydrophobic cores in proteins and thus provides insight into the influence of the water environment upon protein structure and stability. The model has been successfully applied in the study of a wide range of proteins, however this paper focuses specifically on domains representing immunoglobulin-like folds. Here we provide evidence that immunoglobulin-like domains, despite being structurally similar, differ with respect to their participation in the generation of hydrophobic core. It is shown that β-structural fragments in β-barrels participate in hydrophobic core formation in a highly differentiated manner. Quantitatively measured participation in core formation helps explain the variable stability of proteins and is shown to be related to their biological properties. This also includes the known tendency of immunoglobulin domains to form amyloids, as shown using transthyretin to reveal the clear relation between amyloidogenic properties and structural characteristics based on the fuzzy oil drop model. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Segments.

ERIC Educational Resources Information Center

Zemsky, Robert; Shaman, Susan; Shapiro, Daniel B.

2001-01-01

Presents a market taxonomy for higher education, including what it reveals about the structure of the market, the model's technical attributes, and its capacity to explain pricing behavior. Details the identification of the principle seams separating one market segment from another and how student aspirations help to organize the market, making…

13C AND 15N IN MICROARTHROPODS REVEAL LITTLE RESPONSE OF DOUGLAS-FIR ECOSYSTEMS TO CLIMATE CHANGE

EPA Science Inventory

Understanding ecosystem carbon (C) and nitrogen (N) cycling under global change requires experiments maintaining natural interactions among soil structure, soil communities, nutrient availability, and plant growth. In model Douglas-fir ecosystems maintained for five growing seaso...

Exploration of the folding dynamics of human telomeric G-quadruplex with a hybrid atomistic structure-based model

NASA Astrophysics Data System (ADS)

Bian, Yunqiang; Ren, Weitong; Song, Feng; Yu, Jiafeng; Wang, Jihua

2018-05-01

Structure-based models or Gō-like models, which are built from one or multiple particular experimental structures, have been successfully applied to the folding of proteins and RNAs. Recently, a variant termed the hybrid atomistic model advances the description of backbone and side chain interactions of traditional structure-based models, by borrowing the description of local interactions from classical force fields. In this study, we assessed the validity of this model in the folding problem of human telomeric DNA G-quadruplex, where local dihedral terms play important roles. A two-state model was developed and a set of molecular dynamics simulations was conducted to study the folding dynamics of sequence Htel24, which was experimentally validated to adopt two different (3 + 1) hybrid G-quadruplex topologies in K+ solution. Consistent with the experimental observations, the hybrid-1 conformation was found to be more stable and the hybrid-2 conformation was kinetically more favored. The simulations revealed that the hybrid-2 conformation folded in a higher cooperative manner, which may be the reason why it was kinetically more accessible. Moreover, by building a Markov state model, a two-quartet G-quadruplex state and a misfolded state were identified as competing states to complicate the folding process of Htel24. Besides, the simulations also showed that the transition between hybrid-1 and hybrid-2 conformations may proceed an ensemble of hairpin structures. The hybrid atomistic structure-based model reproduced the kinetic partitioning folding dynamics of Htel24 between two different folds, and thus can be used to study the complex folding processes of other G-quadruplex structures.

Stress barriers controlling lateral migration of magma revealed by seismic tomography.

PubMed

Martí, J; Villaseñor, A; Geyer, A; López, C; Tryggvason, A

2017-01-13

Understanding how monogenetic volcanic systems work requires full comprehension of the local and regional stresses that govern magma migration inside them and why/how they seem to change from one eruption to another. During the 2011-2012 El Hierro eruption (Canary Islands) the characteristics of unrest, including a continuous change in the location of seismicity, made the location of the future vent unpredictable, so short term hazard assessment was highly imprecise. A 3D P-wave velocity model is obtained using arrival times of the earthquakes occurred during that pre-eruptive unrest and several latter post-eruptive seismic crises not related to further eruptions. This model reveals the rheological and structural complexity of the interior of El Hierro volcanic island. It shows a number of stress barriers corresponding to regional tectonic structures and blocked pathways from previous eruptions, which controlled ascent and lateral migration of magma and, together with the existence of N-S regional compression, reduced its options to find a suitable path to reach the surface and erupt.

Stress barriers controlling lateral migration of magma revealed by seismic tomography

NASA Astrophysics Data System (ADS)

Martí, J.; Villaseñor, A.; Geyer, A.; López, C.; Tryggvason, A.

2017-01-01

Understanding how monogenetic volcanic systems work requires full comprehension of the local and regional stresses that govern magma migration inside them and why/how they seem to change from one eruption to another. During the 2011-2012 El Hierro eruption (Canary Islands) the characteristics of unrest, including a continuous change in the location of seismicity, made the location of the future vent unpredictable, so short term hazard assessment was highly imprecise. A 3D P-wave velocity model is obtained using arrival times of the earthquakes occurred during that pre-eruptive unrest and several latter post-eruptive seismic crises not related to further eruptions. This model reveals the rheological and structural complexity of the interior of El Hierro volcanic island. It shows a number of stress barriers corresponding to regional tectonic structures and blocked pathways from previous eruptions, which controlled ascent and lateral migration of magma and, together with the existence of N-S regional compression, reduced its options to find a suitable path to reach the surface and erupt.

Bem Sex Role Inventory Validation in the International Mobility in Aging Study.

PubMed

Ahmed, Tamer; Vafaei, Afshin; Belanger, Emmanuelle; Phillips, Susan P; Zunzunegui, Maria-Victoria

2016-09-01

This study investigated the measurement structure of the Bem Sex Role Inventory (BSRI) with different factor analysis methods. Most previous studies on validity applied exploratory factor analysis (EFA) to examine the BSRI. We aimed to assess the psychometric properties and construct validity of the 12-item short-form BSRI in a sample administered to 1,995 older adults from wave 1 of the International Mobility in Aging Study (IMIAS). We used Cronbach's alpha to assess internal consistency reliability and confirmatory factor analysis (CFA) to assess psychometric properties. EFA revealed a three-factor model, further confirmed by CFA and compared with the original two-factor structure model. Results revealed that a two-factor solution (instrumentality-expressiveness) has satisfactory construct validity and superior fit to data compared to the three-factor solution. The two-factor solution confirms expected gender differences in older adults. The 12-item BSRI provides a brief, psychometrically sound, and reliable instrument in international samples of older adults.

Intraplate deformation on north-dipping basement structures in the Northern Gawler Craton, Australia: reactivation of original terrane boundaries or later intra-cratonic thrusts?

NASA Astrophysics Data System (ADS)

Baines, G.; Giles, D.; Betts, P. G.; Backé, G.

2007-12-01

Multiple intraplate orogenic events have deformed Neoproterozoic to Carboniferous sedimentary sequences that cover the Archean to Mesoproterozoic basement of the northern Gawler Craton, Australia. These intraplate orogenies reactivated north-dipping basement penetrating faults that are imaged on seismic reflection profiles. These north-dipping structures pre-date Neoproterozoic deposition but their relationships to significant linear magnetic and gravity anomalies that delineate unexposed Archean to Early Mesoproterozoic basement terranes are unclear. The north-dipping structures are either terrane boundaries that formed during continental amalgamation or later faults, which formed during a mid- to late-Mesoproterozoic transpressional orogeny and cross-cut the original lithological terrane boundaries. We model magnetic and gravity data to determine the 3D structure of the unexposed basement of the northern Gawler Craton. These models are constrained by drill hole and surface observations, seismic reflection profiles and petrophysical data, such that geologically reasonable models that can satisfy the data are limited. The basement structures revealed by this modelling approach constrain the origin and significance of the north-dipping structures that were active during the later intraplate Petermann, Delamerian and Alice Springs Orogenies. These results have bearing on which structures are likely to be active during present-day intraplate deformation in other areas, including, for example, current seismic activity along similar basement structures in the Adelaide "Geosyncline".

Syn- and anti-conformations of 5'-deoxy- and 5'-O-methyl-uridine 2',3'-cyclic monophosphate.

PubMed

Grabarkiewicz, Tomasz; Hoffmann, Marcin

2006-01-01

Two uridine 2',3'-cyclic monophosphate (cUMP) derivatives, 5'-deoxy (DcUMP) and 5'-O-methyl (McUMP), were studied by means of quantum chemical methods. Aqueous solvent effects were estimated based on the isodensity-surface polarized-continuum model (IPCM). Gas phase calculations revealed only slight energy differences between the syn- and anti-conformers of both compounds: the relative energies of the syn-structure are -0.9 and 0.2 kcal mol(-1) for DcUMP and McUMP, respectively. According to the results from the IPCM calculations, however, both syn-conformers become about 14 kcal mol(-1) more stable in aqueous solution than their corresponding anti-structures. Additionally, the effects of a countercation and protonation on DcUMP were studied, revealing that the syn-structure is also favored over the anti-one for these systems.

On the Origin of Banded Structure in Dusty Protoplanetary Disks: HL Tau and TW Hya

NASA Astrophysics Data System (ADS)

Boley, A. C.

2017-11-01

Recent observations of HL Tau revealed remarkably detailed structure within the system’s circumstellar disk. A range of hypotheses have been proposed to explain the morphology, including, e.g., planet-disk interactions, condensation fronts, and secular gravitational instabilities. While embedded planets seem to be able to explain some of the major structure in the disk through interactions with gas and dust, the substructures, such as low-contrast rings and bands, are not so easily reproduced. Here, we show that dynamical interactions between three planets (only two of which are modeled) and an initial population of large planetesimals can potentially explain both the major and minor banded features within the system. In this context, the small grains, which are coupled to the gas and reveal the disk morphology, are produced by the collisional evolution of the newly formed planetesimals, which are ubiquitous in the system and are decoupled from the gas.

Synthesis and controlled release properties of 2,4-dichlorophenoxy acetate-zinc layered hydroxide nanohybrid

NASA Astrophysics Data System (ADS)

Bashi, Abbas M.; Hussein, Mohd Zobir; Zainal, Zulkarnain; Tichit, Didier

2013-07-01

Direct reaction of ZnO with 2,4-dichlorophenoxyacetic acid (24D) solutions of different concentrations allows obtaining new organic-inorganic nanohybrid materials formed by intercalation of 24D into interlayers of zinc layered hydroxide (ZLH). XRD patterns show a progressive evolution of the structure as 24D concentration increases. The nanohybrid obtained at higher 24D concentration (24D-ZLH(0.4)) reveals a well ordered layered structure with two different basal spacings at 25.2 Å and 24 Å. The FTIR spectrum showing the vibrations bands of the functional groups of 24D and of the ZLH confirms the intercalation. SEM images are in agreement with the structural evolution observed by XRD and reveal the ribbon morphology of the nanohybrids. The release studies of 24D showed a rapid release of 94% for the first 100 min governed by the pseudo-second order kinetic model.

Structure resonances due to space charge in periodic focusing channels

NASA Astrophysics Data System (ADS)

Li, Chao; Jameson, R. A.

2018-02-01

The Vlasov-Poisson model is one of the most effective methods to study the space charge dominated beam evolution self-consistently in a periodic focusing channel. Since the approach to get the solution with this model is not trivial, previous studies are limited in degenerated conditions, either in smoothed channel (constant focusing) [I. Hofmann, Phys. Rev. E 57, 4713 (1998)] or in alternating gradient focusing channel with equal initial beam emittance condition in the degrees of freedom [I. Hofmann et al., Part. Accel. 13, 145 (1983); Chao Li et al., THOBA02, IPAC2016]. To establish a basis, we intentionally limit this article to the study of the pure transverse periodic focusing lattice with arbitrary initial beam condition, and the same lattice structure in both degrees of freedom, but with possibility of different focusing strengths. This will show the extension of the existing work. The full Hamiltonian is invoked for a pure transverse focusing lattice in various initial beam conditions, revealing different mode structure and additional modes beyond those of the degenerated cases. Application of the extended method to realistic lattices (including longitudinal accelerating elements) and further details will then reveal many new insights, and will be presented in later work.

Waveform Modeling Reveals Important Features of the Subduction Zone Seismic Structure Beneath the Tyrrhenian Sea, Italy

NASA Astrophysics Data System (ADS)

Di Luccio, F.; Persaud, P.; Pino, N. A.; Clayton, R. W.; Helmberger, D. V.; Li, D.

2016-12-01

Seismic images of the slab in southern Italy indicate a complex geodynamic system, although these images are strongly affected by limitations due to instrumental coverage, in terms of depth resolution and lateral extent. To help improve our knowledge of the structure of the Calabrian subduction zone, we analyze waveforms of regional events that occurred between 2001 and 2015 beneath the Tyrrhenian sea in the western Mediterranean. The selected events are deeper than 200 km and they were recorded at the Italian seismic network managed by Istituto Nazionale di Geofisica e Vulcanologia in Italy. We have also included recordings at ocean bottom seismometers and hydrophones, which were installed for a few months in 2000-2001, 2004-2005 and 2007-2008. Accurate selection of the source-to receiver raypaths can reveal significant differences at receivers, which are perpendicular to the trench with respect to other stations. P-wave complexity, converted phases and frequency content are some of the features we have observed for selected events. To investigate the slab structure, we model the waveforms using the 2D staggered grid Finite Difference method on graphics processing units developed by Li et al. (Geophys. J. Int., 2014).

Interactive comparison and remediation of collections of macromolecular structures.

PubMed

Moriarty, Nigel W; Liebschner, Dorothee; Klei, Herbert E; Echols, Nathaniel; Afonine, Pavel V; Headd, Jeffrey J; Poon, Billy K; Adams, Paul D

2018-01-01

Often similar structures need to be compared to reveal local differences throughout the entire model or between related copies within the model. Therefore, a program to compare multiple structures and enable correction any differences not supported by the density map was written within the Phenix framework (Adams et al., Acta Cryst 2010; D66:213-221). This program, called Structure Comparison, can also be used for structures with multiple copies of the same protein chain in the asymmetric unit, that is, as a result of non-crystallographic symmetry (NCS). Structure Comparison was designed to interface with Coot(Emsley et al., Acta Cryst 2010; D66:486-501) and PyMOL(DeLano, PyMOL 0.99; 2002) to facilitate comparison of large numbers of related structures. Structure Comparison analyzes collections of protein structures using several metrics, such as the rotamer conformation of equivalent residues, displays the results in tabular form and allows superimposed protein chains and density maps to be quickly inspected and edited (via the tools in Coot) for consistency, completeness and correctness. © 2017 The Protein Society.

The performance of fine-grained and coarse-grained elastic network models and its dependence on various factors.

PubMed

Na, Hyuntae; Song, Guang

2015-07-01

In a recent work we developed a method for deriving accurate simplified models that capture the essentials of conventional all-atom NMA and identified two best simplified models: ssNMA and eANM, both of which have a significantly higher correlation with NMA in mean square fluctuation calculations than existing elastic network models such as ANM and ANMr2, a variant of ANM that uses the inverse of the squared separation distances as spring constants. Here, we examine closely how the performance of these elastic network models depends on various factors, namely, the presence of hydrogen atoms in the model, the quality of input structures, and the effect of crystal packing. The study reveals the strengths and limitations of these models. Our results indicate that ssNMA and eANM are the best fine-grained elastic network models but their performance is sensitive to the quality of input structures. When the quality of input structures is poor, ANMr2 is a good alternative for computing mean-square fluctuations while ANM model is a good alternative for obtaining normal modes. © 2015 Wiley Periodicals, Inc.

Fiber Optic Thermographic Detection of Flaws in Composites

NASA Technical Reports Server (NTRS)

Wu, Meng-Chou; Winfree, William P.

2009-01-01

Optical fibers with multiple Bragg gratings bonded to surfaces of structures were used for thermographic detection of subsurface defects in structures. The investigated structures included a 10-ply composite specimen with subsurface delaminations of various sizes and depths. Both during and following the application of a thermal heat flux to the surface, the individual Bragg grating sensors measured the temporal and spatial temperature variations. The obtained data were analyzed with thermal modeling to reveal particular characteristics of the interested areas. These results were found to be consistent with the simulation results.

Structural defects in GaN revealed by Transmission Electron Microscopy

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

Liliental-Weber, Zuzanna

This paper reviews the various types of structural defects observed by Transmission Electron Microscopy in GaN heteroepitaxial layers grown on foreign substrates and homoepitaxial layers grown on bulk GaN substrates. The structural perfection of these layers is compared to the platelet self-standing crystals grown by High Nitrogen Pressure Solution. Defects in undoped and Mg doped GaN are discussed. Lastly, some models explaining the formation of inversion domains in heavily Mg doped layers that are possible defects responsible for the difficulties of p-doping in GaN are also reviewed.

Structural defects in GaN revealed by Transmission Electron Microscopy

DOE PAGES

Liliental-Weber, Zuzanna

2014-09-08

This paper reviews the various types of structural defects observed by Transmission Electron Microscopy in GaN heteroepitaxial layers grown on foreign substrates and homoepitaxial layers grown on bulk GaN substrates. The structural perfection of these layers is compared to the platelet self-standing crystals grown by High Nitrogen Pressure Solution. Defects in undoped and Mg doped GaN are discussed. Lastly, some models explaining the formation of inversion domains in heavily Mg doped layers that are possible defects responsible for the difficulties of p-doping in GaN are also reviewed.

Could the stellar magnetic field explain the structures in the AU Mic debris disk?

NASA Astrophysics Data System (ADS)

Sezestre, Élie; Augereau, Jean-Charles

2016-05-01

Recent SPHERE and reprocessed HST images of the edge-on AU Mic debris disk have revealed arch-like structures moving away from the star on unbound trajectories. No model in the literature can readily explain these features. Here, we explore the effect of the large-scale, stellar magnetic field on the dust dynamics. We show that our study may place constraints on the dust production location.

Structure and self-assembly of the calcium binding matrix protein of human metapneumovirus.

PubMed

Leyrat, Cedric; Renner, Max; Harlos, Karl; Huiskonen, Juha T; Grimes, Jonathan M

2014-01-07

The matrix protein (M) of paramyxoviruses plays a key role in determining virion morphology by directing viral assembly and budding. Here, we report the crystal structure of the human metapneumovirus M at 2.8 Å resolution in its native dimeric state. The structure reveals the presence of a high-affinity Ca²⁺ binding site. Molecular dynamics simulations (MDS) predict a secondary lower-affinity site that correlates well with data from fluorescence-based thermal shift assays. By combining small-angle X-ray scattering with MDS and ensemble analysis, we captured the structure and dynamics of M in solution. Our analysis reveals a large positively charged patch on the protein surface that is involved in membrane interaction. Structural analysis of DOPC-induced polymerization of M into helical filaments using electron microscopy leads to a model of M self-assembly. The conservation of the Ca²⁺ binding sites suggests a role for calcium in the replication and morphogenesis of pneumoviruses. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data reveals a conserved fold of the m02-m06 viral immune modulator family.

PubMed

Sgourakis, Nikolaos G; Natarajan, Kannan; Ying, Jinfa; Vogeli, Beat; Boyd, Lisa F; Margulies, David H; Bax, Ad

2014-09-02

Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a β fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module. Copyright © 2014 Elsevier Ltd. All rights reserved.

Wrench tectonics in Abu Dhabi, United Arab Emirates

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

Ibrahim, M.; Mohamed, A.S.

1995-08-01

Recent studies of the geodynamics and tectonic history of the Arabian plate throughout geologic time have revealed that Wrench forces played an important role in the structural generation and deformation of Petroleum basins and reservoirs of the United Arab Emirates. The tectonic analysis of Abu Dhabi revealed that basin facies evolution were controlled by wrench tectonics, examples are the Pre-Cambrian salt basin, the Permo-Triassic and Jurassic basins. In addition, several sedimentary patterns were strongly influenced by wrench tectonics, the Lower Cretaceous Shuaiba platform margin and associated reservoirs is a good example. Wrench faults, difficult to identify by conventional methods, weremore » examined from a regional perspective and through careful observation and assessment of many factors. Subsurface structural mapping and geoseismic cross-sections supported by outcrop studies and geomorphological features revealed a network of strike slip faults in Abu Dhabi. Structural modelling of these wench forces including the use of strain ellipses was applied both on regional and local scales. This effort has helped in reinterpreting some structural settings, some oil fields were interpreted as En Echelon buckle folds associated with NE/SW dextral wrench faults. Several flower structures were interpreted along NW/SE sinistral wrench faults which have significant hydrocarbon potential. Synthetic and Antithetic strike slip faults and associated fracture systems have played a significant role in field development and reservoir management studies. Four field examples were discussed.« less

Geoinformation modeling system for analysis of atmosphere pollution impact on vegetable biosystems using space images

NASA Astrophysics Data System (ADS)

Polichtchouk, Yuri; Ryukhko, Viatcheslav; Tokareva, Olga; Alexeeva, Mary

2002-02-01

Geoinformation modeling system structure for assessment of the environmental impact of atmospheric pollution on forest- swamp ecosystems of West Siberia is considered. Complex approach to the assessment of man-caused impact based on the combination of sanitary-hygienic and landscape-geochemical approaches is reported. Methodical problems of analysis of atmosphere pollution impact on vegetable biosystems using geoinformation systems and remote sensing data are developed. Landscape structure of oil production territories in southern part of West Siberia are determined on base of processing of space images from spaceborn Resource-O. Particularities of atmosphere pollution zones modeling caused by gas burning in torches in territories of oil fields are considered. For instance, a pollution zones were revealed modeling of contaminants dispersal in atmosphere by standard model. Polluted landscapes areas are calculated depending on oil production volume. It is shown calculated data is well approximated by polynomial models.

Generation Mechanism of Nonlinear Rayleigh Surface Waves for Randomly Distributed Surface Micro-Cracks.

PubMed

Ding, Xiangyan; Li, Feilong; Zhao, Youxuan; Xu, Yongmei; Hu, Ning; Cao, Peng; Deng, Mingxi

2018-04-23

This paper investigates the propagation of Rayleigh surface waves in structures with randomly distributed surface micro-cracks using numerical simulations. The results revealed a significant ultrasonic nonlinear effect caused by the surface micro-cracks, which is mainly represented by a second harmonic with even more distinct third/quadruple harmonics. Based on statistical analysis from the numerous results of random micro-crack models, it is clearly found that the acoustic nonlinear parameter increases linearly with micro-crack density, the proportion of surface cracks, the size of micro-crack zone, and the excitation frequency. This study theoretically reveals that nonlinear Rayleigh surface waves are feasible for use in quantitatively identifying the physical characteristics of surface micro-cracks in structures.

Silicon-carbon bond inversions driven by 60-keV electrons in graphene.

PubMed

Susi, Toma; Kotakoski, Jani; Kepaptsoglou, Demie; Mangler, Clemens; Lovejoy, Tracy C; Krivanek, Ondrej L; Zan, Recep; Bangert, Ursel; Ayala, Paola; Meyer, Jannik C; Ramasse, Quentin

2014-09-12

We demonstrate that 60-keV electron irradiation drives the diffusion of threefold-coordinated Si dopants in graphene by one lattice site at a time. First principles simulations reveal that each step is caused by an electron impact on a C atom next to the dopant. Although the atomic motion happens below our experimental time resolution, stochastic analysis of 38 such lattice jumps reveals a probability for their occurrence in a good agreement with the simulations. Conversions from three- to fourfold coordinated dopant structures and the subsequent reverse process are significantly less likely than the direct bond inversion. Our results thus provide a model of nondestructive and atomically precise structural modification and detection for two-dimensional materials.

Generation Mechanism of Nonlinear Rayleigh Surface Waves for Randomly Distributed Surface Micro-Cracks

PubMed Central

Ding, Xiangyan; Li, Feilong; Xu, Yongmei; Cao, Peng; Deng, Mingxi

2018-01-01

This paper investigates the propagation of Rayleigh surface waves in structures with randomly distributed surface micro-cracks using numerical simulations. The results revealed a significant ultrasonic nonlinear effect caused by the surface micro-cracks, which is mainly represented by a second harmonic with even more distinct third/quadruple harmonics. Based on statistical analysis from the numerous results of random micro-crack models, it is clearly found that the acoustic nonlinear parameter increases linearly with micro-crack density, the proportion of surface cracks, the size of micro-crack zone, and the excitation frequency. This study theoretically reveals that nonlinear Rayleigh surface waves are feasible for use in quantitatively identifying the physical characteristics of surface micro-cracks in structures. PMID:29690580

Complex pectin metabolism by gut bacteria reveals novel catalytic functions

PubMed Central

Baslé, Arnaud; Gray, Joseph; Venditto, Immacolata; Briggs, Jonathon; Zhang, Xiaoyang; Labourel, Aurore; Terrapon, Nicolas; Buffetto, Fanny; Nepogodiev, Sergey; Xiao, Yao; Field, Robert A.; Zhu, Yanping; O’Neil, Malcolm A.; Urbanowicz, Breeana R.; York, William S.; Davies, Gideon J.; Abbott, D. Wade; Ralet, Marie-Christine; Martens, Eric C.; Henrissat, Bernard; Gilbert, Harry J.

2017-01-01

Carbohydrate polymers drive microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron utilizes the most structurally complex glycan known; the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but one of its 21 distinct glycosidic linkages. We show that rhamnogalacturonan-II side-chain and backbone deconstruction are coordinated, to overcome steric constraints, and that degradation reveals previously undiscovered enzyme families and novel catalytic activities. The degradome informs revision of the current structural model of RG-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycans in the human diet. PMID:28329766

Prediction of blood-brain partitioning: a model based on molecular electronegativity distance vector descriptors.

PubMed

Zhang, Yong-Hong; Xia, Zhi-Ning; Qin, Li-Tang; Liu, Shu-Shen

2010-09-01

The objective of this paper is to build a reliable model based on the molecular electronegativity distance vector (MEDV) descriptors for predicting the blood-brain barrier (BBB) permeability and to reveal the effects of the molecular structural segments on the BBB permeability. Using 70 structurally diverse compounds, the partial least squares regression (PLSR) models between the BBB permeability and the MEDV descriptors were developed and validated by the variable selection and modeling based on prediction (VSMP) technique. The estimation ability, stability, and predictive power of a model are evaluated by the estimated correlation coefficient (r), leave-one-out (LOO) cross-validation correlation coefficient (q), and predictive correlation coefficient (R(p)). It has been found that PLSR model has good quality, r=0.9202, q=0.7956, and R(p)=0.6649 for M1 model based on the training set of 57 samples. To search the most important structural factors affecting the BBB permeability of compounds, we performed the values of the variable importance in projection (VIP) analysis for MEDV descriptors. It was found that some structural fragments in compounds, such as -CH(3), -CH(2)-, =CH-, =C, triple bond C-, -CH<, =C<, =N-, -NH-, =O, and -OH, are the most important factors affecting the BBB permeability. (c) 2010. Published by Elsevier Inc.

Charge structure in volcanic plumes: a comparison of plume properties predicted by an integral plume model to observations of volcanic lightning during the 2010 eruption of Eyjafjallajökull, Iceland.

PubMed

Woodhouse, Mark J; Behnke, Sonja A

Observations of volcanic lightning made using a lightning mapping array during the 2010 eruption of Eyjafjallajökull allow the trajectory and growth of the volcanic plume to be determined. The lightning observations are compared with predictions of an integral model of volcanic plumes that includes descriptions of the interaction with wind and the effects of moisture. We show that the trajectory predicted by the integral model closely matches the observational data and the model well describes the growth of the plume downwind of the vent. Analysis of the lightning signals reveals information on the dominant charge structure within the volcanic plume. During the Eyjafjallajökull eruption both monopole and dipole charge structures were observed in the plume. By using the integral plume model, we propose the varying charge structure is connected to the availability of condensed water and low temperatures at high altitudes in the plume, suggesting ice formation may have contributed to the generation of a dipole charge structure via thunderstorm-style ice-based charging mechanisms, though overall this charging mechanism is believed to have had only a weak influence on the production of lightning.

Simulation of the as-cast structure of Al-4.0wt.%Cu ingots with a 5-phase mixed columnar-equiaxed solidification model

NASA Astrophysics Data System (ADS)

Wu, M.; Ahmadein, M.; Kharicha, A.; Ludwig, A.; Li, J. H.; Schumacher, P.

2012-07-01

Empirical knowledge about the formation of the as-cast structure, mostly obtained before 1980s, has revealed two critical issues: one is the origin of the equiaxed crystals; one is the competing growth of the columnar and equiaxed structures, and the columnar-to-equiaxed transition (CET). Unfortunately, the application of empirical knowledge to predict and control the as-cast structure was very limited, as the flow and crystal transport were not considered. Therefore, a 5-phase mixed columnar-equiaxed solidification model was recently proposed by the current authors based on modeling the multiphase transport phenomena. The motivation of the recent work is to determine and evaluate the necessary modeling parameters, and to validate the mixed columnar-equiaxed solidification model by comparison with laboratory castings. In this regard an experimental method was recommended for in-situ determination of the nucleation parameters. Additionally, some classical experiments of the Al-Cu ingots were conducted and the as-cast structural information including distinct columnar and equiaxed zones, macrosegregation, and grain size distribution were analysed. The final simulation results exhibited good agreement with experiments in the case of high pouring temperature, whereas disagreement in the case of low pouring temperature. The reasons for the disagreement are discussed.

Structural model of the eastern Achara-Trialeti fold and thrust belt using seismic reflection profiles

NASA Astrophysics Data System (ADS)

Alania, Victor; Chabukiani, Alexander; Enukidze, Onise; Razmadze, Alexander; Sosson, Marc; Tsereteli, Nino; Varazanashvili, Otar

2017-04-01

Our study focused on the structural geometry at the eastern Achara-Trialeti fold and thrust belt (ATFTB) located at the retro-wedge of the Lesser Caucasus orogen (Alania et al., 2016a). Our interpretation has integrated seismic reflection profiles, several oil-wells, and the surface geology data to reveal structural characteristics of the eastern ATFTB. Fault-related folding theories were used to seismic interpretation (Shaw et al., 2004). Seismic reflection data reveal the presence of basement structural wedge, south-vergent backthrust, north-vergent forethrust and some structural wedges (or duplex). The rocks are involved in the deformation range from Paleozoic basement rocks to Tertiary strata. Building of thick-skinned structures of eastern Achara-Trialeti was formed by basement wedges propagated from south to north along detachment horizons within the cover generating thin-skinned structures. The kinematic evolution of the south-vergent backthrust zone with respect to the northward propagating structural wedge (or duplexes). The main style of deformation within the backthrust belt is a series of fault-propagation folds. Frontal part of eastern ATFTB are represent by triangle zone (Alania et al., 2016b; Sosson et al., 2016). A detailed study was done for Tbilisi area: seismic refection profiles, serial balanced cross-sections, and earthquakes reveal the presence of an active blind thrust fault beneath Tbilisi. 2 & 3-D structural models show that 2002 Mw 4.5 Tbilisi earthquake related to a north-vergent blind thrust. Empirical relations between blind fault rupture area and magnitude suggest that these fault segments could generate earthquakes of Mw 6.5. The growth fault-propagation fold has been observed near Tbilisi in the frontal part of eastern ATFTB. Seismic reflection profile through Ormoiani syncline shows that south-vergent growth fault-propagation fold related to out-of-the-syncline thrust. The outcrop of fault-propagation fold shown the geometry of the hangingwall structure with the syn-folding growth stratal sequence. Pre-growth Oligocene strata are overlain by Late (?) Quaternary alluvial fan gravels, sands and clays. Growth unconformity of back-limb showing flat clays unconformably on top of Oligocene sandstone and shale beds. The growth strata geometry of growth fold is related to the progressive limb-rotation model (Hardy & Poblet, 1994). References Alania, V., et al., 2016a. Structure of the eastern Achara-Trialeti fold and thrust belt using seismic reflection profiles: implication for tectonic model of the Lesser Caucasus orogen. 35TH International Geological Congress (IGC), 27 August - 4 September, 2016, Cape Town, South Africa. Alania, V., et al., 2016b. Growth structures, piggyback basins and growth strata of Georgian part of Kura foreland fold and thrust belt: implication for Late Alpine kinematic evolution. Geological Society, London, Special Publications no. 428, doi:10.1144/SP428.5. Hardy, S., and J. Poblet, 1994. Geometric and numerical model of progressive limb rotation in detachment folds: Geology, v. 22, p. 371-374. Shaw, J., Connors, C. & J. Suppe, 2005. Seismic interpretation of contractional fault-related folds. AAPG Studies in Geology 53, 156 pp. Sosson, M., et al., 2016. The Eastern Black Sea-Caucasus region during Cretaceous: new evidence to constrain its tectonic evolution. Compte-Rendus Geosciences, v. 348, Issue 1, p. 23-32.

Crystal structure of the human astrovirus capsid spike.

PubMed

Dong, Jinhui; Dong, Liping; Méndez, Ernesto; Tao, Yizhi

2011-08-02

Astroviruses are single-stranded, plus-sense RNA viruses that infect both mammals and birds, causing gastroenteritis and other extraintestinal diseases. Clinical studies have established astroviruses as the second leading cause of viral diarrhea in young children. Here we report the crystal structure of the human astrovirus dimeric surface spike determined to 1.8-Å resolution. The overall structure of each spike/projection domain has a unique three-layered β-sandwiches fold, with a core, six-stranded β-barrel structure that is also found in the hepatitis E virus capsid protrusions, suggesting a closer phylogenetic relationship between these two viruses than previously acknowledged. Based on a hepatitis E virus capsid model, we performed homology modeling and produced a complete, T = 3 astrovirus capsid model with features remarkably similar to those observed in a cryoelectron microscopy reconstruction image of a human astrovirus. Mapping conserved residues onto the astrovirus projection domain revealed a putative receptor binding site with amino acid compositions characteristic for polysaccharide recognition. Our results will have an important impact on future characterization of astrovirus structure and function, and will likely have practical applications in the development of vaccines and antivirals.

Microphysical variability of Amazonian deep convective cores observed by CloudSat and simulated by a multi-scale modeling framework

NASA Astrophysics Data System (ADS)

Brant Dodson, J.; Taylor, Patrick C.; Branson, Mark

2018-05-01

Recently launched cloud observing satellites provide information about the vertical structure of deep convection and its microphysical characteristics. In this study, CloudSat reflectivity data is stratified by cloud type, and the contoured frequency by altitude diagrams reveal a double-arc structure in deep convective cores (DCCs) above 8 km. This suggests two distinct hydrometeor modes (snow versus hail/graupel) controlling variability in reflectivity profiles. The day-night contrast in the double arcs is about four times larger than the wet-dry season contrast. Using QuickBeam, the vertical reflectivity structure of DCCs is analyzed in two versions of the Superparameterized Community Atmospheric Model (SP-CAM) with single-moment (no graupel) and double-moment (with graupel) microphysics. Double-moment microphysics shows better agreement with observed reflectivity profiles; however, neither model variant captures the double-arc structure. Ultimately, the results show that simulating realistic DCC vertical structure and its variability requires accurate representation of ice microphysics, in particular the hail/graupel modes, though this alone is insufficient.

Hydrophobic potential of mean force as a solvation function for protein structure prediction.

PubMed

Lin, Matthew S; Fawzi, Nicolas Lux; Head-Gordon, Teresa

2007-06-01

We have developed a solvation function that combines a Generalized Born model for polarization of protein charge by the high dielectric solvent, with a hydrophobic potential of mean force (HPMF) as a model for hydrophobic interaction, to aid in the discrimination of native structures from other misfolded states in protein structure prediction. We find that our energy function outperforms other reported scoring functions in terms of correct native ranking for 91% of proteins and low Z scores for a variety of decoy sets, including the challenging Rosetta decoys. This work shows that the stabilizing effect of hydrophobic exposure to aqueous solvent that defines the HPMF hydration physics is an apparent improvement over solvent-accessible surface area models that penalize hydrophobic exposure. Decoys generated by thermal sampling around the native-state basin reveal a potentially important role for side-chain entropy in the future development of even more accurate free energy surfaces.

Object view in spatial system dynamics: a grassland farming example

PubMed Central

Neuwirth, Christian; Hofer, Barbara; Schaumberger, Andreas

2016-01-01

Abstract Spatial system dynamics (SSD) models are typically implemented by linking stock variables to raster grids while the use of object representations of human artefacts such as buildings or ownership has been limited. This limitation is addressed by this article, which demonstrates the use of object representations in SSD. The objects are parcels of land that are attributed to grassland farms. The model simulates structural change in agriculture, i.e., change in the size of farms. The aim of the model is to reveal relations between structural change, farmland fragmentation and variable farmland quality. Results show that fragmented farms tend to become consolidated by structural change, whereas consolidated initial conditions result in a significant increase of fragmentation. Consolidation is reinforced by a dynamic land market and high transportation costs. The example demonstrates the capabilities of the object-based approach for integrating object geometries (parcel shapes) and relations between objects (distances between parcels) dynamically in SSD. PMID:28190972

A kinetic model for the characteristic surface morphologies of thin films by directional vapor deposition

NASA Astrophysics Data System (ADS)

Li, Kun-Dar; Huang, Po-Yu

2017-12-01

In order to simulate a process of directional vapor deposition, in this study, a numerical approach was applied to model the growth and evolution of surface morphologies for the crystallographic structures of thin films. The critical factors affecting the surface morphologies in a deposition process, such as the crystallographic symmetry, anisotropic interfacial energy, shadowing effect, and deposition rate, were all enclosed in the theoretical model. By altering the parameters of crystallographic symmetry in the structures, the faceted nano-columns with rectangular and hexagonal shapes were established in the simulation results. Furthermore, for revealing the influences of the anisotropic strength and the deposition rate theoretically on the crystallographic structure formations, various parameters adjusted in the numerical calculations were also investigated. Not only the morphologies but also the surface roughnesses for different processing conditions were distinctly demonstrated with the quantitative analysis of the simulations.

Structural Basis for Assembly of the MnIV/FeIII Cofactor in the Class Ic Ribonucleotide Reductase from Chlamydia trachomatis‡

PubMed Central

Dassama, Laura M.K.; Krebs, Carsten; Bollinger, J. Martin; Rosenzweig, Amy C.; Boal, Amie K.

2013-01-01

The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct) employs a MnIV/FeIII cofactor in each monomer of its β2 subunit to initiate nucleotide reduction. The cofactor forms by reaction of MnII/FeII-β2 with O2. Previously, in vitro cofactor assembly from apo β2 and divalent metal ions produced a mixture of two forms, with Mn in site 1 (MnIV/FeIII) or site 2 (FeIII/MnIV), of which the more active MnIV/FeIII product predominates. Here we have addressed the basis for metal site-selectivity by solving X-ray crystal structures of apo, MnII, and MnII/FeII complexes of Ct β2. A structure obtained anaerobically with equimolar MnII, FeII, and apo protein reveals exclusive incorporation of MnII in site 1 and FeII in site 2, in contrast to the more modest site-selectivity achieved previously. Site-specificity is controlled thermodynamically by the apo protein structure, as only minor adjustments of ligands occur upon metal binding. Additional structures imply that, by itself, MnII binds in either site. Together the structures are consistent with a model for in vitro cofactor assembly in which FeII specificity for site 2 drives assembly of the appropriately configured heterobimetallic center, provided that FeII is substoichiometric. This model suggests that use of an MnIV/FeIII cofactor in vivo could be an adaptation to FeII limitation. A 1.8 Å resolution model of the MnII/FeII-β2 complex reveals additional structural determinants for activation of the cofactor, including a proposed site for side-on (η2) addition of O2 to FeII and a short (3.2 Å) MnII-FeII interionic distance, promoting formation of the MnIV/FeIV activation intermediate. PMID:23924396

A study of the native cell wall structures of the marine alga Ventricaria ventricosa (Siphonocladales, Chlorophyceae) using atomic force microscopy.

PubMed

Eslick, Enid M; Beilby, Mary J; Moon, Anthony R

2014-04-01

A substantial proportion of the architecture of the plant cell wall remains unknown with a few cell wall models being proposed. Moreover, even less is known about the green algal cell wall. Techniques that allow direct visualization of the cell wall in as near to its native state are of importance in unravelling the spatial arrangement of cell wall structures and hence in the development of cell wall models. Atomic force microscopy (AFM) was used to image the native cell wall of living cells of Ventricaria ventricosa (V. ventricosa) at high resolution under physiological conditions. The cell wall polymers were identified mainly qualitatively via their structural appearance. The cellulose microfibrils (CMFs) were easily recognizable and the imaging results indicate that the V. ventricosa cell wall has a cross-fibrillar structure throughout. We found the native wall to be abundant in matrix polysaccharides existing in different curing states. The soft phase matrix polysaccharides susceptible by the AFM scanning tip existed as a glutinous fibrillar meshwork, possibly incorporating both the pectic- and hemicellulosic-type substances. The hard phase matrix producing clearer images, revealed coiled fibrillar structures associated with CMFs, sometimes being resolved as globular structures by the AFM tip. The coiling fibrillar structures were also seen in the images of isolated cell wall fragments. The mucilaginous component of the wall was discernible from the gelatinous cell wall matrix as it formed microstructural domains over the surface. AFM has been successful in imaging the native cell wall and revealing novel findings such as the 'coiling fibrillar structures' and cell wall components which have previously not been seen, that is, the gelatinous matrix phase.

THE ENERGY-DEPENDENT POSITION OF THE IBEX RIBBON DUE TO THE SOLAR WIND STRUCTURE

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

Swaczyna, Paweł; Bzowski, Maciej; Sokół, Justyna M., E-mail: pswaczyna@cbk.waw.pl

2016-08-10

Observations of energetic neutral atoms (ENAs) allow for remote studies of the condition of plasma in the heliosphere and the neighboring local interstellar medium. The first results from the Interstellar Boundary Explorer ( IBEX ) revealed an arc-like enhancement of the ENA intensity in the sky, known as the ribbon. The ribbon was not expected from the heliospheric models prior to the launch of IBEX . One proposed explanation for the ribbon is the mechanism of secondary ENA emission. The ribbon reveals energy-dependent structure in the relative intensity along its circumference and in its position. That is, the geometric centermore » of the ribbon varies systematically by about 10° in the energy range 0.7–4.3 keV. Here, we show by analytical modeling that this effect is a consequence of the helio-latitudinal structure of the solar wind reflected in the secondary ENAs. Along with a recently measured distance to the ribbon’s source just beyond the heliopause, our findings support the connection of the ribbon with the local interstellar magnetic field by the mechanism of secondary ENA emission. However, the magnitude of the center shift in the highest IBEX energy channel is much larger in the observations than expected from the modeling. This may be due to another, not currently recognized, process of ENA generation.« less

Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

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

Rockel, Beate; Schmaler, Tilo; Huang, Xiaohua

2014-07-25

Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with themore » 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts are very similar, Flag-CSN pulldowns are a proper alternative to CSN preparation from erythrocytes.« less

Accurate 3d Scanning of Damaged Ancient Greek Inscriptions for Revealing Weathered Letters

NASA Astrophysics Data System (ADS)

Papadaki, A. I.; Agrafiotis, P.; Georgopoulos, A.; Prignitz, S.

2015-02-01

In this paper two non-invasive non-destructive alternative techniques to the traditional and invasive technique of squeezes are presented alongside with specialized developed processing methods, aiming to help the epigraphists to reveal and analyse weathered letters in ancient Greek inscriptions carved in masonry or marble. The resulting 3D model would serve as a detailed basis for the epigraphists to try to decipher the inscription. The data were collected by using a Structured Light scanner. The creation of the final accurate three dimensional model is a complicated procedure requiring large computation cost and human effort. It includes the collection of geometric data in limited space and time, the creation of the surface, the noise filtering and the merging of individual surfaces. The use of structured light scanners is time consuming and requires costly hardware and software. Therefore an alternative methodology for collecting 3D data of the inscriptions was also implemented for reasons of comparison. Hence, image sequences from varying distances were collected using a calibrated DSLR camera aiming to reconstruct the 3D scene through SfM techniques in order to evaluate the efficiency and the level of precision and detail of the obtained reconstructed inscriptions. Problems in the acquisition processes as well as difficulties in the alignment step and mesh optimization are also encountered. A meta-processing framework is proposed and analysed. Finally, the results of processing and analysis and the different 3D models are critically inspected and then evaluated by a specialist in terms of accuracy, quality and detail of the model and the capability of revealing damaged and "hidden" letters.

Beyond a bigger brain: Multivariable structural brain imaging and intelligence

PubMed Central

Ritchie, Stuart J.; Booth, Tom; Valdés Hernández, Maria del C.; Corley, Janie; Maniega, Susana Muñoz; Gow, Alan J.; Royle, Natalie A.; Pattie, Alison; Karama, Sherif; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

2015-01-01

People with larger brains tend to score higher on tests of general intelligence (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comprehensive cognitive test battery. Using structural equation modelling, we related six common magnetic resonance imaging-derived brain variables that represent normal and abnormal features—brain volume, cortical thickness, white matter structure, white matter hyperintensity load, iron deposits, and microbleeds—to g and to fluid intelligence. As expected, brain volume accounted for the largest portion of variance (~ 12%, depending on modelling choices). Adding the additional variables, especially cortical thickness (+~ 5%) and white matter hyperintensity load (+~ 2%), increased the predictive value of the model. Depending on modelling choices, all neuroimaging variables together accounted for 18–21% of the variance in intelligence. These results reveal which structural brain imaging measures relate to g over and above the largest contributor, total brain volume. They raise questions regarding which other neuroimaging measures might account for even more of the variance in intelligence. PMID:26240470

Recovering hidden diagonal structures via non-negative matrix factorization with multiple constraints.

PubMed

Yang, Xi; Han, Guoqiang; Cai, Hongmin; Song, Yan

2017-03-31

Revealing data with intrinsically diagonal block structures is particularly useful for analyzing groups of highly correlated variables. Earlier researches based on non-negative matrix factorization (NMF) have been shown to be effective in representing such data by decomposing the observed data into two factors, where one factor is considered to be the feature and the other the expansion loading from a linear algebra perspective. If the data are sampled from multiple independent subspaces, the loading factor would possess a diagonal structure under an ideal matrix decomposition. However, the standard NMF method and its variants have not been reported to exploit this type of data via direct estimation. To address this issue, a non-negative matrix factorization with multiple constraints model is proposed in this paper. The constraints include an sparsity norm on the feature matrix and a total variational norm on each column of the loading matrix. The proposed model is shown to be capable of efficiently recovering diagonal block structures hidden in observed samples. An efficient numerical algorithm using the alternating direction method of multipliers model is proposed for optimizing the new model. Compared with several benchmark models, the proposed method performs robustly and effectively for simulated and real biological data.

Subjective well-being associated with size of social network and social support of elderly.

PubMed

Wang, Xingmin

2016-06-01

The current study examined the impact of size of social network on subjective well-being of elderly, mainly focused on confirmation of the mediator role of perceived social support. The results revealed that both size of social network and perceived social support were significantly correlated with subjective well-being. Structural equation modeling indicated that perceived social support partially mediated size of social network to subjective well-being. The final model also revealed significant both paths from size of social network to subjective well-being through perceived social support. The findings extended prior researches and provided valuable evidence on how to promote mental health of the elderly. © The Author(s) 2014.

Structural and Functional Insights into WRKY3 and WRKY4 Transcription Factors to Unravel the WRKY–DNA (W-Box) Complex Interaction in Tomato (Solanum lycopersicum L.). A Computational Approach

PubMed Central

Aamir, Mohd; Singh, Vinay K.; Meena, Mukesh; Upadhyay, Ram S.; Gupta, Vijai K.; Singh, Surendra

2017-01-01

The WRKY transcription factors (TFs), play crucial role in plant defense response against various abiotic and biotic stresses. The role of WRKY3 and WRKY4 genes in plant defense response against necrotrophic pathogens is well-reported. However, their functional annotation in tomato is largely unknown. In the present work, we have characterized the structural and functional attributes of the two identified tomato WRKY transcription factors, WRKY3 (SlWRKY3), and WRKY4 (SlWRKY4) using computational approaches. Arabidopsis WRKY3 (AtWRKY3: NP_178433) and WRKY4 (AtWRKY4: NP_172849) protein sequences were retrieved from TAIR database and protein BLAST was done for finding their sequential homologs in tomato. Sequence alignment, phylogenetic classification, and motif composition analysis revealed the remarkable sequential variation between, these two WRKYs. The tomato WRKY3 and WRKY4 clusters with Solanum pennellii showing the monophyletic origin and evolution from their wild homolog. The functional domain region responsible for sequence specific DNA-binding occupied in both proteins were modeled [using AtWRKY4 (PDB ID:1WJ2) and AtWRKY1 (PDBID:2AYD) as template protein structures] through homology modeling using Discovery Studio 3.0. The generated models were further evaluated for their accuracy and reliability based on qualitative and quantitative parameters. The modeled proteins were found to satisfy all the crucial energy parameters and showed acceptable Ramachandran statistics when compared to the experimentally resolved NMR solution structures and/or X-Ray diffracted crystal structures (templates). The superimposition of the functional WRKY domains from SlWRKY3 and SlWRKY4 revealed remarkable structural similarity. The sequence specific DNA binding for two WRKYs was explored through DNA-protein interaction using Hex Docking server. The interaction studies found that SlWRKY4 binds with the W-box DNA through WRKYGQK with Tyr408, Arg409, and Lys419 with the initial flanking sequences also get involved in binding. In contrast, the SlWRKY3 made interaction with RKYGQK along with the residues from zinc finger motifs. Protein-protein interactions studies were done using STRING version 10.0 to explore all the possible protein partners involved in associative functional interaction networks. The Gene ontology enrichment analysis revealed the functional dimension and characterized the identified WRKYs based on their functional annotation. PMID:28611792

Protein Secondary Structures (alpha-helix and beta-sheet) at a Cellular Levle and Protein Fractions in Relation to Rumen Degradation Behaviours of Protein: A New Approach

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

Yu,P.

2007-01-01

Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the {alpha}-helix and {beta}-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of {beta}-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present studymore » were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution ({approx}10 {mu}m). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of {alpha}-helixes and {beta}-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P <0.05) the percentage of {alpha}-helixes (from 47.1% to 36.1%: S-FTIR absorption intensity), increased the percentage of {beta}-sheets (from 37.2% to 49.8%: S-FTIR absorption intensity) and reduced the {alpha}-helix to {beta}-sheet ratio (from 0.3 to 0.7) in the golden flaxseeds, which indicated a negative effect of the roasting on protein values, utilisation and bioavailability. These results were proved by the Cornell Net Carbohydrate Protein System in situ animal trial, which also revealed that roasting increased the amount of protein bound to lignin, and well as of the Maillard reaction protein (both of which are poorly used by ruminants), and increased the level of indigestible and undegradable protein in ruminants. The present results demonstrate the potential of highly spatially resolved synchrotron-based infrared microspectroscopy to locate 'pure' protein in feed tissues, and reveal protein secondary structures and digestive behaviour, making a significant step forward in and an important contribution to protein nutritional research. Further study is needed to determine the sensitivities of protein secondary structures to various heat-processing conditions, and to quantify the relationship between protein secondary structures and the nutrient availability and digestive behaviour of various protein sources. Information from the present study arising from the synchrotron-based IR probing of the protein secondary structures of protein sources at the cellular level will be valuable as a guide to maintaining protein quality and predicting digestive behaviours.« less

Jammed Limit of Bijel Structure Formation

DOE PAGES

Welch, P. M.; Lee, M. N.; Parra-Vasquez, A. N. G.; ...

2017-11-02

Over the past decade, methods to control microstructure in heterogeneous mixtures by arresting spinodal decomposition via the addition of colloidal particles have led to an entirely new class of bicontinuous materials known as bijels. We present a new model for the development of these materials that yields to both numerical and analytical evaluation. This model reveals that a single dimensionless parameter that captures both chemical and environmental variables dictates the dynamics and ultimate structure formed in bijels. We also demonstrate that this parameter must fall within a fixed range in order for jamming to occur during spinodal decomposition, as wellmore » as show that known experimental trends for the characteristic domain sizes and time scales for formation are recovered by this model.« less

Diagnostic analysis of observed and numerically simulated cloud and precipitation structures during pre-ERICA

NASA Technical Reports Server (NTRS)

Perkey, Donald J.; Doty, Kevin G.; Robertson, Franklin R.

1989-01-01

A preliminary 140-km simulation of a rapid cyclogenesis, using the Limited Area Mesoscale Prediction System (LAMPS) is discussed. A three-dimensional version of LAMPS used in the simulation is described, along with a trajectory model utilizing the three-hourly output history files from the LAMPS model. Preliminary integrations of the LAMPS code as well as passive microwave digital data from SSM/I aboard the DMSP satellite are used for exploring the evolving baroclinic structure and moisture field of the cyclone event. A trajectory analysis of the model histories reveals a significant role for preconditioning of the low-level upstream air, which is then drawn into the ascending warm conveyor belt ahead of the storm.

The system-resonance approach in modeling genetic structures.

PubMed

Petoukhov, Sergey V

2016-01-01

The founder of the theory of resonance in structural chemistry Linus Pauling established the importance of resonance patterns in organization of living systems. Any living organism is a great chorus of coordinated oscillatory processes. From the formal point of view, biological organism is an oscillatory system with a great number of degrees of freedom. Such systems are studied in the theory of oscillations using matrix mathematics of their resonance characteristics. This study is devoted to a new approach for modeling genetically inherited structures and processes in living organisms using mathematical tools of the theory of resonances. This approach reveals hidden relationships in a number of genetic phenomena and gives rise to a new class of bio-mathematical models, which contribute to a convergence of biology with physics and informatics. In addition some relationships of molecular-genetic ensembles with mathematics of noise-immunity coding of information in modern communications technology are shown. Perspectives of applications of the phenomena of vibrational mechanics for modeling in biology are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Computational modelling of mesoscale dislocation patterning and plastic deformation of single crystals

NASA Astrophysics Data System (ADS)

Xia, Shengxu; El-Azab, Anter

2015-07-01

We present a continuum dislocation dynamics model that predicts the formation of dislocation cell structure in single crystals at low strains. The model features a set of kinetic equations of the curl type that govern the space and time evolution of the dislocation density in the crystal. These kinetic equations are coupled to stress equilibrium and deformation kinematics using the eigenstrain approach. A custom finite element method has been developed to solve the coupled system of equations of dislocation kinetics and crystal mechanics. The results show that, in general, dislocations self-organize in patterns under their mutual interactions. However, the famous dislocation cell structure has been found to form only when cross slip is implemented in the model. Cross slip is also found to lower the yield point, increase the hardening rate, and sustain an increase in the dislocation density over the hardening regime. Analysis of the cell structure evolution reveals that the average cell size decreases with the applied stress, which is consistent with the similitude principle.

ALAMEDA, a Structural–Functional Model for Faba Bean Crops: Morphological Parameterization and Verification

PubMed Central

RUIZ-RAMOS, MARGARITA; MÍNGUEZ, M. INÉS

2006-01-01

• Background Plant structural (i.e. architectural) models explicitly describe plant morphology by providing detailed descriptions of the display of leaf and stem surfaces within heterogeneous canopies and thus provide the opportunity for modelling the functioning of plant organs in their microenvironments. The outcome is a class of structural–functional crop models that combines advantages of current structural and process approaches to crop modelling. ALAMEDA is such a model. • Methods The formalism of Lindenmayer systems (L-systems) was chosen for the development of a structural model of the faba bean canopy, providing both numerical and dynamic graphical outputs. It was parameterized according to the results obtained through detailed morphological and phenological descriptions that capture the detailed geometry and topology of the crop. The analysis distinguishes between relationships of general application for all sowing dates and stem ranks and others valid only for all stems of a single crop cycle. • Results and Conclusions The results reveal that in faba bean, structural parameterization valid for the entire plant may be drawn from a single stem. ALAMEDA was formed by linking the structural model to the growth model ‘Simulation d'Allongement des Feuilles’ (SAF) with the ability to simulate approx. 3500 crop organs and components of a group of nine plants. Model performance was verified for organ length, plant height and leaf area. The L-system formalism was able to capture the complex architecture of canopy leaf area of this indeterminate crop and, with the growth relationships, generate a 3D dynamic crop simulation. Future development and improvement of the model are discussed. PMID:16390842

Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1

PubMed Central

Ryu, Stephen I.; Shenoy, Krishna V.; Cunningham, John P.; Churchland, Mark M.

2016-01-01

Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure—a basic example is the frequency spectrum—and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were ‘simplest’ (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models. PMID:27814353

Mothers' Expectancies and Young Adolescents' Perceived Physical Competence: A Yearlong Study.

ERIC Educational Resources Information Center

Bois, Julien E.; Sarrazin, Philippe G.; Brustad, Robert J.; Trouilloud, David O.; Cury, Francois

2002-01-01

Investigated the role of mothers' expectancies in shaping their child's perceived physical competence. Structural equation modeling revealed that mothers' perceptions of their child's physical competence predicted their child's own perceived physical competence 1 year later, independent of the child's previously demonstrated physical ability and…

Using decision trees to understand structure in missing data

PubMed Central

Tierney, Nicholas J; Harden, Fiona A; Harden, Maurice J; Mengersen, Kerrie L

2015-01-01

Objectives Demonstrate the application of decision trees—classification and regression trees (CARTs), and their cousins, boosted regression trees (BRTs)—to understand structure in missing data. Setting Data taken from employees at 3 different industrial sites in Australia. Participants 7915 observations were included. Materials and methods The approach was evaluated using an occupational health data set comprising results of questionnaires, medical tests and environmental monitoring. Statistical methods included standard statistical tests and the ‘rpart’ and ‘gbm’ packages for CART and BRT analyses, respectively, from the statistical software ‘R’. A simulation study was conducted to explore the capability of decision tree models in describing data with missingness artificially introduced. Results CART and BRT models were effective in highlighting a missingness structure in the data, related to the type of data (medical or environmental), the site in which it was collected, the number of visits, and the presence of extreme values. The simulation study revealed that CART models were able to identify variables and values responsible for inducing missingness. There was greater variation in variable importance for unstructured as compared to structured missingness. Discussion Both CART and BRT models were effective in describing structural missingness in data. CART models may be preferred over BRT models for exploratory analysis of missing data, and selecting variables important for predicting missingness. BRT models can show how values of other variables influence missingness, which may prove useful for researchers. Conclusions Researchers are encouraged to use CART and BRT models to explore and understand missing data. PMID:26124509

All-Atom Multiscale Molecular Dynamics Theory and Simulation of Self-Assembly, Energy Transfer and Structural Transition in Nanosystems

NASA Astrophysics Data System (ADS)

Espinosa Duran, John Michael

The study of nanosystems and their emergent properties requires the development of multiscale computational models, theories and methods that preserve atomic and femtosecond resolution, to reveal details that cannot be resolved experimentally today. Considering this, three long time scale phenomena were studied using molecular dynamics and multiscale methods: self-assembly of organic molecules on graphite, energy transfer in nanosystems, and structural transition in vault nanoparticles. Molecular dynamics simulations of the self-assembly of alkoxybenzonitriles with different tail lengths on graphite were performed to learn about intermolecular interactions and phases exhibited by self-organized materials. This is important for the design of ordered self-assembled organic photovoltaic materials with greater efficiency than the disordered blends. Simulations revealed surface dynamical behaviors that cannot be resolved experimentally today due to the lack of spatiotemporal resolution. Atom-resolved structures predicted by simulations agreed with scanning tunneling microscopy images and unit cell measurements. Then, a multiscale theory based on the energy density as a field variable is developed to study energy transfer in nanoscale systems. For applications like photothermal microscopy or cancer phototherapy is required to understand how the energy is transferred to/from nanosystems. This multiscale theory could be applied in this context and here is tested for cubic nanoparticles immersed in water for energy being transferred to/from the nanoparticle. The theory predicts the energy transfer dynamics and reveals phenomena that cannot be described by current phenomenological theories. Finally, temperature-triggered structural transitions were revealed for vault nanoparticles using molecular dynamics and multiscale simulations. Vault is a football-shaped supramolecular assembly very distinct from the commonly observed icosahedral viruses. It has very promising applications in drug delivery and has been extensively studied experimentally. Sub-microsecond multiscale simulations at 310 K on the vault revealed the opening and closing of fractures near the shoulder while preserving the overall structure. This fracture mechanism could explain the uptake and release of small drugs while maintaining the overall structure. Higher temperature simulations show the generation of large fractures near the waist, which enables interaction of the external medium with the inner vault residues. Simulation results agreed with microscopy and spectroscopy measurements, and revealed new structures and mechanisms.

A Rasch analysis of the Brief Pain Inventory Interference subscale reveals three dimensions and an age bias.

PubMed

Walton, David M; Beattie, Tyler; Putos, Joseph; MacDermid, Joy C

2016-06-01

The Brief Pain Inventory is composed of two quantifiable scales: pain severity and pain interference. The reported factor structure of the interference subscale is not consistent in the extant literature, with no clear choice between a single- or two-factor structure. Here, we report on the results of Rasch-based analysis of the interference subscale using a large population-based ambulatory patient database (the Quebec Pain Registry). Observational cohort. A total of 1,000 responses were randomly drawn from a total database of 5,654 for this analysis. Both the original 7-item and an expanded 10-item version (Tyler 2002) of the interference subscale were evaluated. Rasch analysis revealed significant misfit of both versions of the scale, with the original 7-item version outperforming the expanded 10-item version. Analysis of dimensionality revealed that both versions showed improved model fit when considered two subscales (affective and physical interference) with the item on sleep interference removed or considered separately. Additionally, significant uniform differential item functioning was identified for 6 of the 7 original items when the sample was stratified by age above or below 55 years. The interference subscale achieved adequate model fit when considered as two separate subscales with age as a mediator of response, while interpreting the sleep interference item separately. A transformation matrix revealed that in all cases, ordinal-level change at the extreme ends of the scale appears to be more meaningful than does a similar change at the midpoints. The Interference subscale of the BPI should be interpreted as two separate subscales (Affective Interference, Physical Interference) with the sleep item removed or interpreted separately for optimal fit to the Rasch model. Implications for research and clinical use are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis

PubMed Central

Kuang, Siyun; Zheng, Jun; Yang, Hui; Li, Suhua; Duan, Shuyan; Shen, Yanfang; Ji, Chaoneng; Gan, Jianhua; Xu, Xue-Wei; Li, Jixi

2017-01-01

Recent findings have revealed that the protein gasdermin D (GSDMD) plays key roles in cell pyroptosis. GSDMD binds lipids and forms pore structures to induce pyroptosis upon microbial infection and associated danger signals. However, detailed structural information for GSDMD remains unknown. Here, we report the crystal structure of the C-terminal domain of human GSDMD (GSDMD-C) at 2.64-Å resolution. The first loop on GSDMD-C inserts into the N-terminal domain (GSDMD-N), which helps stabilize the conformation of the full-length GSDMD. Substitution of this region by a short linker sequence increased levels of cell death. Mutants F283A and F283R can increase protein heterogeneity in vitro and are capable of undergoing cell pyroptosis in 293T cells. The small-angle X-ray–scattering envelope of human GSDMD is consistent with the modeled GSDMD structure and mouse GSDMA3 structure, which suggests that GSDMD adopts an autoinhibited conformation in solution. The positive potential surface of GSDMD-N covered by GSDMD-C is exposed after being released from the autoinhibition state and can form high-order oligomers via a charge–charge interaction. Furthermore, by mapping different regions of GSDMD, we determined that one short segment is sufficient to kill bacteria in vitro and can efficiently inhibit cell growth in Escherichia coli and Mycobacterium Smegmatis. These findings reveal that GSDMD-C acts as an auto-inhibition executor and GSDMD-N could form pore structures via a charge–charge interaction upon cleavage by caspases during cell pyroptosis. PMID:28928145

Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis.

PubMed

Kuang, Siyun; Zheng, Jun; Yang, Hui; Li, Suhua; Duan, Shuyan; Shen, Yanfang; Ji, Chaoneng; Gan, Jianhua; Xu, Xue-Wei; Li, Jixi

2017-10-03

Recent findings have revealed that the protein gasdermin D (GSDMD) plays key roles in cell pyroptosis. GSDMD binds lipids and forms pore structures to induce pyroptosis upon microbial infection and associated danger signals. However, detailed structural information for GSDMD remains unknown. Here, we report the crystal structure of the C-terminal domain of human GSDMD (GSDMD-C) at 2.64-Å resolution. The first loop on GSDMD-C inserts into the N-terminal domain (GSDMD-N), which helps stabilize the conformation of the full-length GSDMD. Substitution of this region by a short linker sequence increased levels of cell death. Mutants F283A and F283R can increase protein heterogeneity in vitro and are capable of undergoing cell pyroptosis in 293T cells. The small-angle X-ray-scattering envelope of human GSDMD is consistent with the modeled GSDMD structure and mouse GSDMA3 structure, which suggests that GSDMD adopts an autoinhibited conformation in solution. The positive potential surface of GSDMD-N covered by GSDMD-C is exposed after being released from the autoinhibition state and can form high-order oligomers via a charge-charge interaction. Furthermore, by mapping different regions of GSDMD, we determined that one short segment is sufficient to kill bacteria in vitro and can efficiently inhibit cell growth in Escherichia coli and Mycobacterium Smegmatis These findings reveal that GSDMD-C acts as an auto-inhibition executor and GSDMD-N could form pore structures via a charge-charge interaction upon cleavage by caspases during cell pyroptosis.

Gratitude mediates the effect of emotional intelligence on subjective well-being: A structural equation modeling analysis.

PubMed

Geng, Yuan

2016-11-01

This study investigated the relationship among emotional intelligence, gratitude, and subjective well-being in a sample of university students. A total of 365 undergraduates completed the emotional intelligence scale, the gratitude questionnaire, and the subjective well-being measures. The results of the structural equation model showed that emotional intelligence is positively associated with gratitude and subjective well-being, that gratitude is positively associated with subjective well-being, and that gratitude partially mediates the positive relationship between emotional intelligence and subjective well-being. Bootstrap test results also revealed that emotional intelligence has a significant indirect effect on subjective well-being through gratitude.

Why do workaholics experience depression? A study with Chinese University teachers.

PubMed

Nie, Yingzhi; Sun, Haitao

2016-10-01

This study focuses on the relationships of workaholism to job burnout and depression of university teachers. The direct and indirect (via job burnout) effects of workaholism on depression were investigated in 412 Chinese university teachers. Structural equation modeling and bootstrap method were used. Results revealed that workaholism, job burnout, and depression significantly correlated with each other. Structural equation modeling and bootstrap test indicated the partial mediation role of job burnout on the relationship between workaholism and depression. The findings shed some light on how workaholism influenced depression and provided valuable evidence for prevention of depression in work. © The Author(s) 2015.

Identification of possible non-stationary effects in a new type of vortex furnace

NASA Astrophysics Data System (ADS)

Shadrin, Evgeniy Yu.; Anufriev, Igor S.; Papulov, Anatoly P.

2017-10-01

The article presents the results of an experimental study of pressure and velocity pulsations in the model of improved vortex furnace with distributed air supply and vertically oriented nozzles of the secondary blast. Investigation of aerodynamic characteristics of a swirling flow with different regime parameters was conducted in an isothermal laboratory model (in 1:25 scale) of vortex furnace using laser Doppler measuring system and pressure pulsations analyzer. The obtained results have revealed a number of features of the flow structure, and the spectral analysis of pressure and velocity pulsations allows to speak about the absence of large-scale unsteady vortical structures in the studied design.

Imprints of the Molecular Electronic Structure in the Photoelectron Spectra of Strong-Field Ionized Asymmetric Triatomic Model Molecules

NASA Astrophysics Data System (ADS)

Paul, Matthias; Yue, Lun; Gräfe, Stefanie

2018-06-01

We examine the circular dichroism in the angular distribution of photoelectrons of triatomic model systems ionized by strong-field ionization. Following our recent work on this effect [Paul, Yue, and Gräfe, J. Mod. Opt. 64, 1104 (2017), 10.1080/09500340.2017.1299883], we demonstrate how the symmetry and electronic structure of the system is imprinted into the photoelectron momentum distribution. We use classical trajectories to reveal the origin of the threefolded pattern in the photoelectron momentum distribution, and show how an asymmetric nuclear configuration of the triatomic system effects the photoelectron spectra.

Maintaining the confidentiality of plot locations by exploiting the low sensitivity of forest structure models to different spectral extraction kernels

Treesearch

Sean P. Healey; Elizabeth Lapoint; Gretchen G. Moisen; Scott L. Powell

2011-01-01

The United States Forest Service Forest Inventory and Analysis (FIA) unit maintains a large national network of inventory plots.While the consistency and extent of this network make FIA data attractive for ecological modelling, the FIA is charged by statute not to publicly reveal inventory plot locations. However, use of FIA plot data by the remote sensing community...

Secondary Students' Writing Achievement Goals: Assessing the Mediating Effects of Mastery and Performance Goals on Writing Self-Efficacy, Affect, and Writing Achievement

PubMed Central

Yilmaz Soylu, Meryem; Zeleny, Mary G.; Zhao, Ruomeng; Bruning, Roger H.; Dempsey, Michael S.; Kauffman, Douglas F.

2017-01-01

The two studies reported here explored the factor structure of the newly constructed Writing Achievement Goal Scale (WAGS), and examined relationships among secondary students' writing achievement goals, writing self-efficacy, affect for writing, and writing achievement. In the first study, 697 middle school students completed the WAGS. A confirmatory factor analysis revealed a good fit for this data with a three-factor model that corresponds with mastery, performance approach, and performance avoidance goals. The results of Study 1 were an indication for the researchers to move forward with Study 2, which included 563 high school students. The secondary students completed the WAGS, as well as the Self-efficacy for Writing Scale, and the Liking Writing Scale. Students also self-reported grades for writing and for language arts courses. Approximately 6 weeks later, students completed a statewide writing assessment. We tested a theoretical model representing relationships among Study 2 variables using structural equation modeling including students' responses to the study scales and students' scores on the statewide assessment. Results from Study 2 revealed a good fit between a model depicting proposed relationships among the constructs and the data. Findings are discussed relative to achievement goal theory and writing. PMID:28878707

Theory for Deducing Volcanic Activity From Size Distributions in Plinian Pyroclastic Fall Deposits

NASA Astrophysics Data System (ADS)

Iriyama, Yu; Toramaru, Atsushi; Yamamoto, Tetsuo

2018-03-01

Stratigraphic variation in the grain size distribution (GSD) of plinian pyroclastic fall deposits reflects volcanic activity. To extract information on volcanic activity from the analyses of deposits, we propose a one-dimensional theory that provides a formula connecting the sediment GSD to the source GSD. As the simplest case, we develop a constant-source model (CS model), in which the source GSD and the source height are constant during the duration of release of particles. We assume power laws of particle radii for the terminal fall velocity and the source GSD. The CS model can describe an overall (i.e., entire vertically variable) feature of the GSD structure of the sediment. It is shown that the GSD structure is characterized by three parameters, that is, the duration of supply of particles to the source scaled by the fall time of the largest particle, ts/tM, and the power indices of the terminal fall velocity p and of the source GSD q. We apply the CS model to samples of the Worzel D ash layer and compare the sediment GSD structure calculated by using the CS model to the observed structure. The results show that the CS model reproduces the overall structure of the observed GSD. We estimate the duration of the eruption and the q value of the source GSD. Furthermore, a careful comparison of the observed and calculated GSDs reveals new interpretation of the original sediment GSD structure of the Worzel D ash layer.

Biocatalysis with thermostable enzymes: structure and properties of a thermophilic 'ene'-reductase related to old yellow enzyme.

PubMed

Adalbjörnsson, Björn V; Toogood, Helen S; Fryszkowska, Anna; Pudney, Christopher R; Jowitt, Thomas A; Leys, David; Scrutton, Nigel S

2010-01-25

We report the crystal structure of a thermophilic "ene" reductase (TOYE) isolated from Thermoanaerobacter pseudethanolicus E39. The crystal structure reveals a tetrameric enzyme and an active site that is relatively large compared to most other structurally determined and related Old Yellow Enzymes. The enzyme adopts higher order oligomeric states (octamers and dodecamers) in solution, as revealed by sedimentation velocity and multiangle laser light scattering. Bead modelling indicates that the solution structure is consistent with the basic tetrameric structure observed in crystallographic studies and electron microscopy. TOYE is stable at high temperatures (T(m)>70 degrees C) and shows increased resistance to denaturation in water-miscible organic solvents compared to the mesophilic Old Yellow Enzyme family member, pentaerythritol tetranitrate reductase. TOYE has typical ene-reductase properties of the Old Yellow Enzyme family. There is currently major interest in using Old Yellow Enzyme family members in the preparative biocatalysis of a number of activated alkenes. The increased stability of TOYE in organic solvents is advantageous for biotransformations in which water-miscible organic solvents and biphasic reaction conditions are required to both deliver novel substrates and minimize product racemisation.

Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

DOE PAGES

Melero, Cristina; Ollikainen, Noah; Harwood, Ian; ...

2014-10-13

Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test thismore » strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.« less

Recent Asteroid Disruptions in the WISE Dataset - Constraining Asteroid Surface Properties Using Solar System Dust Bands

NASA Astrophysics Data System (ADS)

Kehoe, A. E.; Shaw, C.; Kehoe, T. J. J.

2017-12-01

Zodiacal dust bands are a fine-structure feature of the mid-IR emission profile of the zodiacal cloud. The dust bands have been studied for many years dating back to the InfraRed Astronomical Satellite (IRAS) data of the 1980's. The recent discovery and modeling (Espy et al., 2009; 2010; Espy Kehoe et al., 2015) of a very young, still-forming dust band structure has shown that, in the early stages following an asteroid disruption, much information on the dust parameters of the original disruption is retained in the band. Partial dust bands allow a never-before-seen observational look at the size distribution and cross-sectional area of dust produced in an asteroidal disruption, before it has been lost or significantly altered by orbital and collisional decay. The study of these partial band structures reveals information on the way asteroids disrupt and allow us to reconstruct the surface properties of the parent asteroid, including the depth of the surface regolith and the size distribution of particles composing the regolith. Using the greatly increased sensitivity of the Wide-field Infrared Survey Explorer (WISE), we can now detect much fainter (and thus younger) dust bands. The WISE data also reveals much better longitudinal resolution of the bands, allowing a better constraint on the source and age of the disruption. We will present our newest results from the WISE dataset, including detection of faint partial dust bands, improved models of more prominent bands, and our constraints on the asteroid surface properties from modeling these structures.

Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

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

Melero, Cristina; Ollikainen, Noah; Harwood, Ian

Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test thismore » strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.« less

The neural correlates of obsessive-compulsive disorder: a multimodal perspective.

PubMed

Moreira, P S; Marques, P; Soriano-Mas, C; Magalhães, R; Sousa, N; Soares, J M; Morgado, P

2017-08-29

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder.

Genetic diversity and population structure among six cattle breeds in South Africa using a whole genome SNP panel

PubMed Central

Makina, Sithembile O.; Muchadeyi, Farai C.; van Marle-Köster, Este; MacNeil, Michael D.; Maiwashe, Azwihangwisi

2014-01-01

Information about genetic diversity and population structure among cattle breeds is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of cattle breeds. This study investigated genetic diversity and the population structure among six cattle breeds in South African (SA) including Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), Bonsmara (n = 44), Angus (n = 31), and Holstein (n = 29). Genetic diversity within cattle breeds was analyzed using three measures of genetic diversity namely allelic richness (AR), expected heterozygosity (He) and inbreeding coefficient (f). Genetic distances between breed pairs were evaluated using Nei's genetic distance. Population structure was assessed using model-based clustering (ADMIXTURE). Results of this study revealed that the allelic richness ranged from 1.88 (Afrikaner) to 1.73 (Nguni). Afrikaner cattle had the lowest level of genetic diversity (He = 0.24) and the Drakensberger cattle (He = 0.30) had the highest level of genetic variation among indigenous and locally-developed cattle breeds. The level of inbreeding was lower across the studied cattle breeds. As expected the average genetic distance was the greatest between indigenous cattle breeds and Bos taurus cattle breeds but the lowest among indigenous and locally-developed breeds. Model-based clustering revealed some level of admixture among indigenous and locally-developed breeds and supported the clustering of the breeds according to their history of origin. The results of this study provided useful insight regarding genetic structure of SA cattle breeds. PMID:25295053

First-Principles Predictions of Near-Edge X-ray Absorption Fine Structure Spectra of Semiconducting Polymers

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

Su, Gregory M.; Patel, Shrayesh N.; Pemmaraju, C. D.

The electronic structure and molecular orientation of semiconducting polymers in thin films determine their ability to transport charge. Methods based on near-edge X-ray absorption fine structure (NEXAFS) spectroscopy can be used to probe both the electronic structure and microstructure of semiconducting polymers in both crystalline and amorphous films. However, it can be challenging to interpret NEXAFS spectra on the basis of experimental data alone, and accurate, predictive calculations are needed to complement experiments. Here, we show that first-principles density functional theory (DFT) can be used to model NEXAFS spectra of semiconducting polymers and to identify the nature of transitions inmore » complicated NEXAFS spectra. Core-level X-ray absorption spectra of a set of semiconducting polymers were calculated using the excited electron and core-hole (XCH) approach based on constrained-occupancy DFT. A comparison of calculations on model oligomers and periodic structures with experimental data revealed the requirements for accurate prediction of NEXAFS spectra of both conjugated homopolymers and donor–acceptor polymers. The NEXAFS spectra predicted by the XCH approach were applied to study molecular orientation in donor–acceptor polymers using experimental spectra and revealed the complexity of using carbon edge spectra in systems with large monomeric units. The XCH approach has sufficient accuracy in predicting experimental NEXAFS spectra of polymers that it should be considered for design and analysis of measurements using soft X-ray techniques, such as resonant soft X-ray scattering and scanning transmission X-ray microscopy.« less

Crystal structure of extracellular domain of human lectin-like transcript 1 (LLT1), the ligand for natural killer receptor-P1A.

PubMed

Kita, Shunsuke; Matsubara, Haruki; Kasai, Yoshiyuki; Tamaoki, Takaharu; Okabe, Yuki; Fukuhara, Hideo; Kamishikiryo, Jun; Krayukhina, Elena; Uchiyama, Susumu; Ose, Toyoyuki; Kuroki, Kimiko; Maenaka, Katsumi

2015-06-01

Emerging evidence has revealed the pivotal roles of C-type lectin-like receptors (CTLRs) in the regulation of a wide range of immune responses. Human natural killer cell receptor-P1A (NKRP1A) is one of the CTLRs and recognizes another CTLR, lectin-like transcript 1 (LLT1) on target cells to control NK, NKT and Th17 cells. The structural basis for the NKRP1A-LLT1 interaction was limitedly understood. Here, we report the crystal structure of the ectodomain of LLT1. The plausible receptor-binding face of the C-type lectin-like domain is flat, and forms an extended β-sheet. The residues of this face are relatively conserved with another CTLR, keratinocyte-associated C-type lectin, which binds to the CTLR member, NKp65. A LLT1-NKRP1A complex model, prepared using the crystal structures of LLT1 and the keratinocyte-associated C-type lectin-NKp65 complex, reasonably satisfies the charge consistency and the conformational complementarity to explain a previous mutagenesis study. Furthermore, crystal packing and analytical ultracentrifugation revealed dimer formation, which supports a complex model. Our results provide structural insights for understanding the binding modes and signal transduction mechanisms, which are likely to be conserved in the CTLR family, and for further rational drug design towards regulating the LLT1 function. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic diversity and population structure among six cattle breeds in South Africa using a whole genome SNP panel.

PubMed

Makina, Sithembile O; Muchadeyi, Farai C; van Marle-Köster, Este; MacNeil, Michael D; Maiwashe, Azwihangwisi

2014-01-01

Information about genetic diversity and population structure among cattle breeds is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of cattle breeds. This study investigated genetic diversity and the population structure among six cattle breeds in South African (SA) including Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), Bonsmara (n = 44), Angus (n = 31), and Holstein (n = 29). Genetic diversity within cattle breeds was analyzed using three measures of genetic diversity namely allelic richness (AR), expected heterozygosity (He) and inbreeding coefficient (f). Genetic distances between breed pairs were evaluated using Nei's genetic distance. Population structure was assessed using model-based clustering (ADMIXTURE). Results of this study revealed that the allelic richness ranged from 1.88 (Afrikaner) to 1.73 (Nguni). Afrikaner cattle had the lowest level of genetic diversity (He = 0.24) and the Drakensberger cattle (He = 0.30) had the highest level of genetic variation among indigenous and locally-developed cattle breeds. The level of inbreeding was lower across the studied cattle breeds. As expected the average genetic distance was the greatest between indigenous cattle breeds and Bos taurus cattle breeds but the lowest among indigenous and locally-developed breeds. Model-based clustering revealed some level of admixture among indigenous and locally-developed breeds and supported the clustering of the breeds according to their history of origin. The results of this study provided useful insight regarding genetic structure of SA cattle breeds.

Effect of fullerenol surface chemistry on nanoparticle binding-induced protein misfolding

NASA Astrophysics Data System (ADS)

Radic, Slaven; Nedumpully-Govindan, Praveen; Chen, Ran; Salonen, Emppu; Brown, Jared M.; Ke, Pu Chun; Ding, Feng

2014-06-01

Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation -- a common strategy for solubilizing and functionalizing fullerene -- on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding.Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation -- a common strategy for solubilizing and functionalizing fullerene -- on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding. Electronic supplementary information (ESI) is available: Fluorescence spectra, ITC, CD spectra and other data as described in the text. See DOI: 10.1039/c4nr01544d

Interrelation of structure and operational states in cascading failure of overloading lines in power grids

NASA Astrophysics Data System (ADS)

Xue, Fei; Bompard, Ettore; Huang, Tao; Jiang, Lin; Lu, Shaofeng; Zhu, Huaiying

2017-09-01

As the modern power system is expected to develop to a more intelligent and efficient version, i.e. the smart grid, or to be the central backbone of energy internet for free energy interactions, security concerns related to cascading failures have been raised with consideration of catastrophic results. The researches of topological analysis based on complex networks have made great contributions in revealing structural vulnerabilities of power grids including cascading failure analysis. However, existing literature with inappropriate assumptions in modeling still cannot distinguish the effects between the structure and operational state to give meaningful guidance for system operation. This paper is to reveal the interrelation between network structure and operational states in cascading failure and give quantitative evaluation by integrating both perspectives. For structure analysis, cascading paths will be identified by extended betweenness and quantitatively described by cascading drop and cascading gradient. Furthermore, the operational state for cascading paths will be described by loading level. Then, the risk of cascading failure along a specific cascading path can be quantitatively evaluated considering these two factors. The maximum cascading gradient of all possible cascading paths can be used as an overall metric to evaluate the entire power grid for its features related to cascading failure. The proposed method is tested and verified on IEEE30-bus system and IEEE118-bus system, simulation evidences presented in this paper suggests that the proposed model can identify the structural causes for cascading failure and is promising to give meaningful guidance for the protection of system operation in the future.

P-polarized reflectance spectroscopy: A high sensitive real-time monitoring technique to study surface kinetics under steady state epitaxial deposition conditions

NASA Technical Reports Server (NTRS)

Dietz, Nikolaus; Bachmann, Klaus J.

1995-01-01

This paper describes the results of real-time optical monitoring of epitaxial growth processes by p-polarized reflectance spectroscopy (PRS) using a single wavelength application under pulsed chemical beam epitaxy (PCBE) condition. The high surface sensitivity of PRS allows the monitoring of submonolayer precursors coverage on the surface as shown for GaP homoepitaxy and GaP on Si heteroepitaxy as examples. In the case of heteroepitaxy, the growth rate and optical properties are revealed by PRS using interference oscillations as they occur during growth. Super-imposed on these interference oscillations, the PRS signal exhibits a fine structure caused by the periodic alteration of the surface chemistry by the pulsed supply of chemical precursors. This fine structure is modeled under conditions where the surface chemistry cycles between phosphorus supersaturated and phosphorus depleted surfaces. The mathematical model describes the fine structure using a surface layer that increases during the tertiarybutyl phosphine (TBP) supply and decreases during and after the triethylgallium (TEG) pulse, which increases the growing GaP film thickness. The imaginary part of the dielectric function of the surface layer is revealed from the turning points in the fine structure, where the optical response to the first precursor pulse in the cycle sequence changes sign. The amplitude of the fine structure is determined by the surface layer thickness and the complex dielectric functions for the surface layer with the underlying bulk film. Surface kinetic data can be obtained by analyzing the rise and decay transients of the fine structure.

Observing Consistency in Online Communication Patterns for User Re-Identification

PubMed Central

Venter, Hein S.

2016-01-01

Comprehension of the statistical and structural mechanisms governing human dynamics in online interaction plays a pivotal role in online user identification, online profile development, and recommender systems. However, building a characteristic model of human dynamics on the Internet involves a complete analysis of the variations in human activity patterns, which is a complex process. This complexity is inherent in human dynamics and has not been extensively studied to reveal the structural composition of human behavior. A typical method of anatomizing such a complex system is viewing all independent interconnectivity that constitutes the complexity. An examination of the various dimensions of human communication pattern in online interactions is presented in this paper. The study employed reliable server-side web data from 31 known users to explore characteristics of human-driven communications. Various machine-learning techniques were explored. The results revealed that each individual exhibited a relatively consistent, unique behavioral signature and that the logistic regression model and model tree can be used to accurately distinguish online users. These results are applicable to one-to-one online user identification processes, insider misuse investigation processes, and online profiling in various areas. PMID:27918593

Fractal structure enables temporal prediction in music.

PubMed

Rankin, Summer K; Fink, Philip W; Large, Edward W

2014-10-01

1/f serial correlations and statistical self-similarity (fractal structure) have been measured in various dimensions of musical compositions. Musical performances also display 1/f properties in expressive tempo fluctuations, and listeners predict tempo changes when synchronizing. Here the authors show that the 1/f structure is sufficient for listeners to predict the onset times of upcoming musical events. These results reveal what information listeners use to anticipate events in complex, non-isochronous acoustic rhythms, and this will entail innovative models of temporal synchronization. This finding could improve therapies for Parkinson's and related disorders and inform deeper understanding of how endogenous neural rhythms anticipate events in complex, temporally structured communication signals.

Numerical and analytical investigation towards performance enhancement of a newly developed rockfall protective cable-net structure

NASA Astrophysics Data System (ADS)

Dhakal, S.; Bhandary, N. P.; Yatabe, R.; Kinoshita, N.

2012-04-01

In a previous companion paper, we presented a three-tier modelling of a particular type of rockfall protective cable-net structure (barrier), developed newly in Japan. Therein, we developed a three-dimensional, Finite Element based, nonlinear numerical model having been calibrated/back-calculated and verified with the element- and structure-level physical tests. Moreover, using a very simple, lumped-mass, single-degree-of-freedom, equivalently linear analytical model, a global-displacement-predictive correlation was devised by modifying the basic equation - obtained by combining the principles of conservation of linear momentum and energy - based on the back-analysis of the tests on the numerical model. In this paper, we use the developed models to explore the performance enhancement potential of the structure in terms of (a) the control of global displacement - possibly the major performance criterion for the proposed structure owing to a narrow space available in the targeted site, and (b) the increase in energy dissipation by the existing U-bolt-type Friction-brake Devices - which are identified to have performed weakly when integrated into the structure. A set of parametric investigations have revealed correlations to achieve the first objective in terms of the structure's mass, particularly by manipulating the wire-net's characteristics, and has additionally disclosed the effects of the impacting-block's parameters. Towards achieving the second objective, another set of parametric investigations have led to a proposal of a few innovative improvements in the constitutive behaviour (model) of the studied brake device (dissipator), in addition to an important recommendation of careful handling of the device based on the identified potential flaw.

Is cancer a pure growth curve or does it follow a kinetics of dynamical structural transformation?

PubMed

González, Maraelys Morales; Joa, Javier Antonio González; Cabrales, Luis Enrique Bergues; Pupo, Ana Elisa Bergues; Schneider, Baruch; Kondakci, Suleyman; Ciria, Héctor Manuel Camué; Reyes, Juan Bory; Jarque, Manuel Verdecia; Mateus, Miguel Angel O'Farril; González, Tamara Rubio; Brooks, Soraida Candida Acosta; Cáceres, José Luis Hernández; González, Gustavo Victoriano Sierra

2017-03-07

Unperturbed tumor growth kinetics is one of the more studied cancer topics; however, it is poorly understood. Mathematical modeling is a useful tool to elucidate new mechanisms involved in tumor growth kinetics, which can be relevant to understand cancer genesis and select the most suitable treatment. The classical Kolmogorov-Johnson-Mehl-Avrami as well as the modified Kolmogorov-Johnson-Mehl-Avrami models to describe unperturbed fibrosarcoma Sa-37 tumor growth are used and compared with the Gompertz modified and Logistic models. Viable tumor cells (1×10 5 ) are inoculated to 28 BALB/c male mice. Modified Gompertz, Logistic, Kolmogorov-Johnson-Mehl-Avrami classical and modified Kolmogorov-Johnson-Mehl-Avrami models fit well to the experimental data and agree with one another. A jump in the time behaviors of the instantaneous slopes of classical and modified Kolmogorov-Johnson-Mehl-Avrami models and high values of these instantaneous slopes at very early stages of tumor growth kinetics are observed. The modified Kolmogorov-Johnson-Mehl-Avrami equation can be used to describe unperturbed fibrosarcoma Sa-37 tumor growth. It reveals that diffusion-controlled nucleation/growth and impingement mechanisms are involved in tumor growth kinetics. On the other hand, tumor development kinetics reveals dynamical structural transformations rather than a pure growth curve. Tumor fractal property prevails during entire TGK.

Noise produced by the large-scale transition region structure of turbulent jets

NASA Technical Reports Server (NTRS)

Hardin, J. C.

1974-01-01

The 'orderly' structure which has been observed recently by numerous researchers within the transition region of subsonic turbulent jets is analyzed to reveal its noise-producing potential. For the case of a circular jet, this structure is modeled as a train of toroidal vortex rings which are formed near the jet exit and propagate downstream. The noise produced by the model is evaluated from a reformulation of Lighthill's expression for the far-field acoustic density which emphasizes the importance of the vorticity within the turbulent flow field. It is shown that the noise production occurs mainly close to the jet exit and depends primarily upon temporal changes in the toroidal radii. These results suggest a new approach to noise suppression which has been substantiated experimentally.

Perturbations in DNA structure upon interaction with porphyrins revealed by chemical probes, DNA footprinting and molecular modelling.

PubMed

Ford, K G; Neidle, S

1995-06-01

The interactions of several porphyrins with a 74 base-pair DNA sequence have been examined by footprinting and chemical protection methods. Tetra-(4-N-methyl-(pyridyl)) porphyrin (TMPy), two of its metal complexes and tetra-(4-trimethylanilinium) porphyrin (TMAP) bind to closely similar AT-rich sequences. The three TMPy ligands produce modest changes in DNA structure and base accessibility on binding, in contrast to the large-scale conformational changes observed with TMAP. Molecular modelling studies have been performed on TMPy and TMAP bound in the AT-rich minor groove of an oligonucleotide. These have shown that significant structural change is needed to accommodate the bulky trimethyl substituent groups of TMAP, in contrast to the facile minor groove fit of TMPy.

Mesoscale Variability in SUCCESS Data

NASA Technical Reports Server (NTRS)

Eckermann, Stephen D.

1998-01-01

Analysis of meteorological, chemical, and microphysical data from the airborne SUCCESS mission is reported. Careful analysis of the complex DC-8 flight pattern of May 2, 1996 reveals 19 linear or nearly linear flight segments within six main geographical areas, which we have analyzed. Significant mountain wave activity is revealed in the data from the MMS and MTP instruments on the DC-8, which resembles previous observations of mountain wave structures near Boulder, CO. Strong mountain-wave-induced upwelling downwind of the Rockies is noted. Turbulence is also noted in regions of the mountain wave consistent with overturning near the tropopause. Zonal winds recorded on the ER-2 are shown to consistent with mountain wave breaking at or near critical levels in the stratosphere, consistent with the strong turbulence reported by the pilot during the ER-2 flight. Those observations have been supported with spectral analyses and modeling studies. "Postcasts" of mountain wave activity on May 2, 1996, using the Naval Research Laboratory Mountain Wave Forecast Model (NRL/MWFM) predicts both strong mountain wave activity near the tropopause (as measured by the DC-8) and strong mountain-wave-induced turbulence in the stratosphere (as encountered by the ER-2). Two-dimensional simulations of fluid flow over topography reveal similar isentropic structures to observations.

Structural models of the MscL gating mechanism

NASA Technical Reports Server (NTRS)

Sukharev, S.; Durell, S. R.; Guy, H. R.

2001-01-01

Three-dimensional structural models of the mechanosensitive channel of large conductance, MscL, from the bacteria Mycobacterium tuberculosis and Escherichia coli were developed for closed, intermediate, and open conformations. The modeling began with the crystal structure of M. tuberculosis MscL, a homopentamer with two transmembrane alpha-helices, M1 and M2, per subunit. The first 12 N-terminal residues, not resolved in the crystal structure, were modeled as an amphipathic alpha-helix, called S1. A bundle of five parallel S1 helices are postulated to form a cytoplasmic gate. As membrane tension induces expansion, the tilts of M1 and M2 are postulated to increase as they move away from the axis of the pore. Substantial expansion is postulated to occur before the increased stress in the S1 to M1 linkers pulls the S1 bundle apart. During the opening transition, the S1 helices and C-terminus amphipathic alpha-helices, S3, are postulated to dock parallel to the membrane surface on the perimeter of the complex. The proposed gating mechanism reveals critical spatial relationships between the expandable transmembrane barrel formed by M1 and M2, the gate formed by S1 helices, and "strings" that link S1s to M1s. These models are consistent with numerous experimental results and modeling criteria.

Structural Determination of a Transcribing RNA Polymerase II Complex

DTIC Science & Technology

2000-05-01

A be extended and evaluated by the solution of pol II cocrystal structures, with the use of the pol II model for molecular replacement. Co- crystals...with TFIIB and TFIIE (78) should reveal the trajectory of DNA in the initial pol - II-promoter complex. Cocrystals containing pol II in the act of...transcription (79) will show the locations of nucleic acids in an elongation complex. Cocrystals with TFIIS (80) may indicate the proposed exit pathway

Observation of Quasi-Two-Dimensional Nonlinear Interactions in a Drift-Wave Streamer

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

Yamada, T.; Nagashima, Y.; Itoh, S.-I.

2010-11-26

A streamer, which is a bunching of drift-wave fluctuations, and its mediator, which generates the streamer by coupling with other fluctuations, have been observed in a cylindrical magnetized plasma. Their radial structures were investigated in detail by using the biphase analysis. Their quasi-two-dimensional structures were revealed to be equivalent with a pair of fast and slow modes predicted by a nonlinear Schroedinger equation based on the Hasegawa-Mima model.

Learning strategies and general cognitive ability as predictors of gender- specific academic achievement

PubMed Central

Ruffing, Stephanie; Wach, F. -Sophie; Spinath, Frank M.; Brünken, Roland; Karbach, Julia

2015-01-01

Recent research has revealed that learning behavior is associated with academic achievement at the college level, but the impact of specific learning strategies on academic success as well as gender differences therein are still not clear. Therefore, the aim of this study was to investigate gender differences in the incremental contribution of learning strategies over general cognitive ability in the prediction of academic achievement. The relationship between these variables was examined by correlation analyses. A set of t-tests was used to test for gender differences in learning strategies, whereas structural equation modeling as well as multi-group analyses were applied to investigate the incremental contribution of learning strategies for male and female students’ academic performance. The sample consisted of 461 students (mean age = 21.2 years, SD = 3.2). Correlation analyses revealed that general cognitive ability as well as the learning strategies effort, attention, and learning environment were positively correlated with academic achievement. Gender differences were found in the reported application of many learning strategies. Importantly, the prediction of achievement in structural equation modeling revealed that only effort explained incremental variance (10%) over general cognitive ability. Results of multi-group analyses showed no gender differences in this prediction model. This finding provides further knowledge regarding gender differences in learning research and the specific role of learning strategies for academic achievement. The incremental assessment of learning strategy use as well as gender-differences in their predictive value contributes to the understanding and improvement of successful academic development. PMID:26347698

Learning strategies and general cognitive ability as predictors of gender- specific academic achievement.

PubMed

Ruffing, Stephanie; Wach, F-Sophie; Spinath, Frank M; Brünken, Roland; Karbach, Julia

2015-01-01

Recent research has revealed that learning behavior is associated with academic achievement at the college level, but the impact of specific learning strategies on academic success as well as gender differences therein are still not clear. Therefore, the aim of this study was to investigate gender differences in the incremental contribution of learning strategies over general cognitive ability in the prediction of academic achievement. The relationship between these variables was examined by correlation analyses. A set of t-tests was used to test for gender differences in learning strategies, whereas structural equation modeling as well as multi-group analyses were applied to investigate the incremental contribution of learning strategies for male and female students' academic performance. The sample consisted of 461 students (mean age = 21.2 years, SD = 3.2). Correlation analyses revealed that general cognitive ability as well as the learning strategies effort, attention, and learning environment were positively correlated with academic achievement. Gender differences were found in the reported application of many learning strategies. Importantly, the prediction of achievement in structural equation modeling revealed that only effort explained incremental variance (10%) over general cognitive ability. Results of multi-group analyses showed no gender differences in this prediction model. This finding provides further knowledge regarding gender differences in learning research and the specific role of learning strategies for academic achievement. The incremental assessment of learning strategy use as well as gender-differences in their predictive value contributes to the understanding and improvement of successful academic development.

Blasting response of the Eiffel Tower

NASA Astrophysics Data System (ADS)

Horlyck, Lachlan; Hayes, Kieran; Caetano, Ryan; Tahmasebinia, Faham; Ansourian, Peter; Alonso-Marroquin, Fernando

2016-08-01

A finite element model of the Eiffel Tower was constructed using Strand7 software. The model replicates the existing tower, with dimensions justified through the use of original design drawings. A static and dynamic analysis was conducted to determine the actions of the tower under permanent, imposed and wind loadings, as well as under blast pressure loads and earthquake loads due to an explosion. It was observed that the tower utilises the full axial capacity of individual members by acting as a `truss of trusses'. As such, permanent and imposed loads are efficiently transferred to the primary columns through compression, while wind loads induce tensile forces in the windward legs and compressive forces in the leeward. Under blast loading, the tower experienced both ground vibrations and blast pressures. Ground vibrations induced a negligibly small earthquake loading into the structure which was ignored in subsequent analyses. The blast pressure was significant, and a dynamic analysis of this revealed that further research is required into the damping qualities of the structure due to soil and mechanical properties. In the worst case scenario, the blast was assumed to completely destroy several members in the adjacent leg. Despite this weakened condition, it was observed that the tower would still be able to sustain static loads, at least for enough time for occupant evacuation. Further, an optimised design revealed the structure was structurally sound under a 46% reduction of the metal tower's mass.

Electronic bandstructure of semiconductor dilute bismide structures

NASA Astrophysics Data System (ADS)

Erucar, T.; Nutku, F.; Donmez, O.; Erol, A.

2017-02-01

In this work electronic band structure of dilute bismide GaAs/GaAs1-xBix quantum well structures with 1.8% and 3.75% bismuth compositions have been investigated both experimentally and theoretically. Photoluminescence (PL) measurements reveal that effective bandgap of the samples decreases approximately 65 meV per bismuth concentration. Temperature dependence of the effective bandgap is obtained to be higher for the sample with higher bismuth concentration. Moreover, both asymmetric characteristic at the low energy tail of the PL and full width at half maximum (FWHM) of PL peak increase with increasing bismuth composition as a result of increased Bi related defects located above valence band (VB). In order to explain composition dependence of the effective bandgap quantitatively, valence band anti-crossing (VBAC) model is used. Bismuth composition and temperature dependence of effective bandgap in a quantum well structure is modeled by solving Schrödinger equation and compared with experimental PL data.

Sparse dynamical Boltzmann machine for reconstructing complex networks with binary dynamics

NASA Astrophysics Data System (ADS)

Chen, Yu-Zhong; Lai, Ying-Cheng

2018-03-01

Revealing the structure and dynamics of complex networked systems from observed data is a problem of current interest. Is it possible to develop a completely data-driven framework to decipher the network structure and different types of dynamical processes on complex networks? We develop a model named sparse dynamical Boltzmann machine (SDBM) as a structural estimator for complex networks that host binary dynamical processes. The SDBM attains its topology according to that of the original system and is capable of simulating the original binary dynamical process. We develop a fully automated method based on compressive sensing and a clustering algorithm to construct the SDBM. We demonstrate, for a variety of representative dynamical processes on model and real world complex networks, that the equivalent SDBM can recover the network structure of the original system and simulates its dynamical behavior with high precision.

Hidden electronic rule in the “cluster-plus-glue-atom” model

PubMed Central

Du, Jinglian; Dong, Chuang; Melnik, Roderick; Kawazoe, Yoshiyuki; Wen, Bin

2016-01-01

Electrons and their interactions are intrinsic factors to affect the structure and properties of materials. Based on the “cluster-cluster-plus-glue-atom” model, an electron counting rule for complex metallic alloys (CMAs) has been revealed in this work (i. e. the CPGAMEC rule). Our results on the cluster structure and electron concentration of CMAs with apparent cluster features, indicate that the valence electrons’ number per unit cluster formula for these CMAs are specific constants of eight-multiples and twelve-multiples. It is thus termed as specific electrons cluster formula. This CPGAMEC rule has been demonstrated as a useful guidance to direct the design of CMAs with desired properties, while its practical applications and underlying mechanism have been illustrated on the basis of CMAs’ cluster structural features. Our investigation provides an aggregate picture with intriguing electronic rule and atomic structural features of CMAs. PMID:27642002

Earliest evidence for the structure of Homo sapiens populations in Africa

NASA Astrophysics Data System (ADS)

Scerri, Eleanor M. L.; Drake, Nick A.; Jennings, Richard; Groucutt, Huw S.

2014-10-01

Understanding the structure and variation of Homo sapiens populations in Africa is critical for interpreting multiproxy evidence of their subsequent dispersals into Eurasia. However, there is no consensus on early H. sapiens demographic structure, or its effects on intra-African dispersals. Here, we show how a patchwork of ecological corridors and bottlenecks triggered a successive budding of populations across the Sahara. Using a temporally and spatially explicit palaeoenvironmental model, we found that the Sahara was not uniformly ameliorated between ∼130 and 75 thousand years ago (ka), as has been stated. Model integration with multivariate analyses of corresponding stone tools then revealed several spatially defined technological clusters which correlated with distinct palaeobiomes. Similarities between technological clusters were such that they decreased with distance except where connected by palaeohydrological networks. These results indicate that populations at the Eurasian gateway were strongly structured, which has implications for refining the demographic parameters of dispersals out of Africa.

Sparse dynamical Boltzmann machine for reconstructing complex networks with binary dynamics.

PubMed

Chen, Yu-Zhong; Lai, Ying-Cheng

2018-03-01

Revealing the structure and dynamics of complex networked systems from observed data is a problem of current interest. Is it possible to develop a completely data-driven framework to decipher the network structure and different types of dynamical processes on complex networks? We develop a model named sparse dynamical Boltzmann machine (SDBM) as a structural estimator for complex networks that host binary dynamical processes. The SDBM attains its topology according to that of the original system and is capable of simulating the original binary dynamical process. We develop a fully automated method based on compressive sensing and a clustering algorithm to construct the SDBM. We demonstrate, for a variety of representative dynamical processes on model and real world complex networks, that the equivalent SDBM can recover the network structure of the original system and simulates its dynamical behavior with high precision.

Photosynthesis. Electronic structure of the oxygen-evolving complex in photosystem II prior to O-O bond formation.

PubMed

Cox, Nicholas; Retegan, Marius; Neese, Frank; Pantazis, Dimitrios A; Boussac, Alain; Lubitz, Wolfgang

2014-08-15

The photosynthetic protein complex photosystem II oxidizes water to molecular oxygen at an embedded tetramanganese-calcium cluster. Resolving the geometric and electronic structure of this cluster in its highest metastable catalytic state (designated S3) is a prerequisite for understanding the mechanism of O-O bond formation. Here, multifrequency, multidimensional magnetic resonance spectroscopy reveals that all four manganese ions of the catalyst are structurally and electronically similar immediately before the final oxygen evolution step; they all exhibit a 4+ formal oxidation state and octahedral local geometry. Only one structural model derived from quantum chemical modeling is consistent with all magnetic resonance data; its formation requires the binding of an additional water molecule. O-O bond formation would then proceed by the coupling of two proximal manganese-bound oxygens in the transition state of the cofactor. Copyright © 2014, American Association for the Advancement of Science.

Comparison of different bioheat transfer models for assessment of burns injuries

NASA Astrophysics Data System (ADS)

Łapka, Piotr; Furmański, Piotr; Wiśniewski, Tomasz S.

2016-12-01

Two bioheat transfer models i.e.: the classical Pennes model and a more realistic two-equation model which accounted for blood vessel structure in the skin as well as heat transfer in the tissue and arteria blood were coupled with heat and mass transfer model in the protective multilayer garment. The clothing model included conductive-radiative heat transfer with water vapor diffusion in pores and air gaps as well as sorption and desorption of water in fibers. Thermal radiation was modeled rigorously e.g.: both the tissue and fabrics were assumed non-gray, absorbing, emitting and anisotropically scattering. Additionally different refractive indices of fabrics, air and tissue and resulting optical phenomena at separating interfaces were accounted for. Both bioheat models were applied for predicting skin temperature distributions and possibility of burns for different exposition times and radiative heat fluxes incident on external surface of the protective garment. Performed analyses revealed that heat transfer in the skin subjected to high heat flux is independent of the blood vessel structure.

Relaxation-type nonlocal inertial-number rheology for dry granular flows

NASA Astrophysics Data System (ADS)

Lee, Keng-lin; Yang, Fu-ling

2017-12-01

We propose a constitutive model to describe the nonlocality, hysteresis, and several flow features of dry granular materials. Taking the well-known inertial number I as a measure of sheared-induced local fluidization, we derive a relaxation model for I according to the evolution of microstructure during avalanche and dissipation processes. The model yields a nonmonotonic flow law for a homogeneous flow, accounting for hysteretic solid-fluid transition and intermittency in quasistatic flows. For an inhomogeneous flow, the model predicts a generalized Bagnold shear stress revealing the interplay of two microscopic nonlocal mechanisms: collisions among correlated structures and the diffusion of fluidization within the structures. In describing a uniform flow down an incline, the model reproduces the hysteretic starting and stopping heights and the Pouliquen flow rule for mean velocity. Moreover, a dimensionless parameter reflecting the nonlocal effect on the flow is discovered, which controls the transition between Bagnold and creeping flow dynamics.

Marine geophysics. New global marine gravity model from CryoSat-2 and Jason-1 reveals buried tectonic structure.

PubMed

Sandwell, David T; Müller, R Dietmar; Smith, Walter H F; Garcia, Emmanuel; Francis, Richard

2014-10-03

Gravity models are powerful tools for mapping tectonic structures, especially in the deep ocean basins where the topography remains unmapped by ships or is buried by thick sediment. We combined new radar altimeter measurements from satellites CryoSat-2 and Jason-1 with existing data to construct a global marine gravity model that is two times more accurate than previous models. We found an extinct spreading ridge in the Gulf of Mexico, a major propagating rift in the South Atlantic Ocean, abyssal hill fabric on slow-spreading ridges, and thousands of previously uncharted seamounts. These discoveries allow us to understand regional tectonic processes and highlight the importance of satellite-derived gravity models as one of the primary tools for the investigation of remote ocean basins. Copyright © 2014, American Association for the Advancement of Science.

SVD-aided pseudo principal-component analysis: A new method to speed up and improve determination of the optimum kinetic model from time-resolved data

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

Oang, Key Young; Yang, Cheolhee; Muniyappan, Srinivasan

Determination of the optimum kinetic model is an essential prerequisite for characterizing dynamics and mechanism of a reaction. Here, we propose a simple method, termed as singular value decomposition-aided pseudo principal-component analysis (SAPPA), to facilitate determination of the optimum kinetic model from time-resolved data by bypassing any need to examine candidate kinetic models. We demonstrate the wide applicability of SAPPA by examining three different sets of experimental time-resolved data and show that SAPPA can efficiently determine the optimum kinetic model. In addition, the results of SAPPA for both time-resolved X-ray solution scattering (TRXSS) and transient absorption (TA) data of themore » same protein reveal that global structural changes of protein, which is probed by TRXSS, may occur more slowly than local structural changes around the chromophore, which is probed by TA spectroscopy.« less

Thylakoid membrane landscape in the sixties: a tribute to Andrew Benson.

PubMed

Anderson, Jan M

2007-05-01

Prior to the 1960s, the model for the molecular structure of cell membranes consisted of a lipid bilayer held in place by a thin film of electrostatically-associated protein stretched over the bilayer surface: (the Danielli-Davson-Robertson "unit membrane" model). Andrew Benson, an expert in the lipids of chloroplast thylakoid membranes, questioned the relevance of the unit membrane model for biological membranes, especially for thylakoid membranes, instead of emphasizing evidence in favour of hydrophobic interactions of membrane lipids within complementary hydrophobic regions of membrane-spanning proteins. With Elliot Weier, Benson postulated a remarkable subunit lipoprotein monolayer model for thylakoids. Following the advent of freeze fracture microscopy and the fluid lipid-protein mosaic model by Singer and Nicolson, the subunits, membrane-spanning integral proteins, span a dynamic lipid bilayer. Now that high resolution X-ray structures of photosystems I and II are being revealed, the seminal contribution of Andrew Benson can be appreciated.

Resolving Microzooplankton Functional Groups In A Size-Structured Planktonic Model

NASA Astrophysics Data System (ADS)

Taniguchi, D.; Dutkiewicz, S.; Follows, M. J.; Jahn, O.; Menden-Deuer, S.

2016-02-01

Microzooplankton are important marine grazers, often consuming a large fraction of primary productivity. They consist of a great diversity of organisms with different behaviors, characteristics, and rates. This functional diversity, and its consequences, are not currently reflected in large-scale ocean ecological simulations. How should these organisms be represented, and what are the implications for their biogeography? We develop a size-structured, trait-based model to characterize a diversity of microzooplankton functional groups. We compile and examine size-based laboratory data on the traits, revealing some patterns with size and functional group that we interpret with mechanistic theory. Fitting the model to the data provides parameterizations of key rates and properties, which we employ in a numerical ocean model. The diversity of grazing preference, rates, and trophic strategies enables the coexistence of different functional groups of micro-grazers under various environmental conditions, and the model produces testable predictions of the biogeography.

Predictors of Satisfaction in Geographically Close and Long-Distance Relationships

ERIC Educational Resources Information Center

Lee, Ji-yeon; Pistole, M. Carole

2012-01-01

In this study, the authors examined geographically close (GCRs) and long-distance (LDRs) romantic relationship satisfaction as explained by insecure attachment, self-disclosure, gossip, and idealization. After college student participants (N = 536) completed a Web survey, structural equation modeling (SEM) multigroup analysis revealed that the GCR…

Future Teachers' Legal Training in Belarus and Kazakhstan

ERIC Educational Resources Information Center

Matsiuk, Liudmyla

2017-01-01

The content of legal education of future primary school teachers which is adequate to the structural and functional model of teacher's professional readiness for increasing legal literacy of primary school pupils has been revealed and the main groups of competences, namely, normative and institutional, ideological and value-based, forecasting,…

Physical Models of Schooling, the 'Ought' Question and Educational Change.

ERIC Educational Resources Information Center

Bauer, Norman J.

This paper examines the methods used in designing school and classroom environments. The tools are labeled: (1) discipline-centered schooling; (2) empirical-naturalistic schooling; and (3) great works schooling. First, the outline endeavors to reveal the essential elements of the three tools that represent images, structures, or "maps" of…

The Mundrabilla Meteorite in Three-Dimensions

NASA Technical Reports Server (NTRS)

Gillies, D. C.; Carpenter, P. K.; Engel, H. P.

2003-01-01

Computed tomography (CT) using gamma radiation has revealed the interior structure of the anomalous iron meteorite, Mundrabilla. This meteorite is composed of 25 volume percent of iron sulfide with the remainder being iron-nickel. Both phases have been shown to be contiguous, and three dimensional models have been constructed using rapid prototyping techniques.

Three-dimensional model of the hydrostratigraphy and structure of the area in and around the U.S. Army-Camp Stanley Storage Activity Area, northern Bexar County, Texas

USGS Publications Warehouse

Pantea, Michael P.; Blome, Charles D.; Clark, Allan K.

2014-01-01

A three-dimensional model of the Camp Stanley Storage Activity area defines and illustrates the surface and subsurface hydrostratigraphic architecture of the military base and adjacent areas to the south and west using EarthVision software. The Camp Stanley model contains 11 hydrostratigraphic units in descending order: 1 model layer representing the Edwards aquifer; 1 model layer representing the upper Trinity aquifer; 6 model layers representing the informal hydrostratigraphic units that make up the upper part of the middle Trinity aquifer; and 3 model layers representing each, the Bexar, Cow Creek, and the top of the Hammett of the lower part of the middle Trinity aquifer. The Camp Stanley three-dimensional model includes 14 fault structures that generally trend northeast/southwest. The top of Hammett hydrostratigraphic unit was used to propagate and validate all fault structures and to confirm most of the drill-hole data. Differences between modeled and previously mapped surface geology reflect interpretation of fault relations at depth, fault relations to hydrostratigraphic contacts, and surface digital elevation model simplification to fit the scale of the model. In addition, changes based on recently obtained drill-hole data and field reconnaissance done during the construction of the model. The three-dimensional modeling process revealed previously undetected horst and graben structures in the northeastern and southern parts of the study area. This is atypical, as most faults in the area are en echelon that step down southeasterly to the Gulf Coast. The graben structures may increase the potential for controlling or altering local groundwater flow.

Closed-form solutions in stress-driven two-phase integral elasticity for bending of functionally graded nano-beams

NASA Astrophysics Data System (ADS)

Barretta, Raffaele; Fabbrocino, Francesco; Luciano, Raimondo; Sciarra, Francesco Marotti de

2018-03-01

Strain-driven and stress-driven integral elasticity models are formulated for the analysis of the structural behaviour of fuctionally graded nano-beams. An innovative stress-driven two-phases constitutive mixture defined by a convex combination of local and nonlocal phases is presented. The analysis reveals that the Eringen strain-driven fully nonlocal model cannot be used in Structural Mechanics since it is ill-posed and the local-nonlocal mixtures based on the Eringen integral model partially resolve the ill-posedeness of the model. In fact, a singular behaviour of continuous nano-structures appears if the local fraction tends to vanish so that the ill-posedness of the Eringen integral model is not eliminated. On the contrary, local-nonlocal mixtures based on the stress-driven theory are mathematically and mechanically appropriate for nanosystems. Exact solutions of inflected functionally graded nanobeams of technical interest are established by adopting the new local-nonlocal mixture stress-driven integral relation. Effectiveness of the new nonlocal approach is tested by comparing the contributed results with the ones corresponding to the mixture Eringen theory.

Molecular architecture of the yeast Mediator complex

PubMed Central

Robinson, Philip J; Trnka, Michael J; Pellarin, Riccardo; Greenberg, Charles H; Bushnell, David A; Davis, Ralph; Burlingame, Alma L; Sali, Andrej; Kornberg, Roger D

2015-01-01

The 21-subunit Mediator complex transduces regulatory information from enhancers to promoters, and performs an essential role in the initiation of transcription in all eukaryotes. Structural information on two-thirds of the complex has been limited to coarse subunit mapping onto 2-D images from electron micrographs. We have performed chemical cross-linking and mass spectrometry, and combined the results with information from X-ray crystallography, homology modeling, and cryo-electron microscopy by an integrative modeling approach to determine a 3-D model of the entire Mediator complex. The approach is validated by the use of X-ray crystal structures as internal controls and by consistency with previous results from electron microscopy and yeast two-hybrid screens. The model shows the locations and orientations of all Mediator subunits, as well as subunit interfaces and some secondary structural elements. Segments of 20–40 amino acid residues are placed with an average precision of 20 Å. The model reveals roles of individual subunits in the organization of the complex. DOI: http://dx.doi.org/10.7554/eLife.08719.001 PMID:26402457

Joint small-angle X-ray and neutron scattering data analysis of asymmetric lipid vesicles

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

Eicher, Barbara; Heberle, Frederick A.; Marquardt, Drew T.

2017-02-28

Low- and high-resolution models describing the internal transbilayer structure of asymmetric lipid vesicles have been developed. These models can be used for the joint analysis of small-angle neutron and X-ray scattering data. The models describe the underlying scattering length density/electron density profiles either in terms of slabs or through the so-called scattering density profile, previously applied to symmetric lipid vesicles. Both models yield structural details of asymmetric membranes, such as the individual area per lipid, and the hydrocarbon thickness of the inner and outer bilayer leaflets. The scattering density profile model, however, comes at a cost of increased computational effortmore » but results in greater structural resolution, showing a slightly lower packing of lipids in the outer bilayer leaflet of ~120 nm diameter palmitoyloleoyl phosphatidylcholine (POPC) vesicles, compared to the inner leaflet. Here, analysis of asymmetric dipalmitoyl phosphatidylcholine/POPC vesicles did not reveal evidence of transbilayer coupling between the inner and outer leaflets at 323 K, i.e.above the melting transition temperature of the two lipids.« less

Structure-based capacitance modeling and power loss analysis for the latest high-performance slant field-plate trench MOSFET

NASA Astrophysics Data System (ADS)

Kobayashi, Kenya; Sudo, Masaki; Omura, Ichiro

2018-04-01

Field-plate trench MOSFETs (FP-MOSFETs), with the features of ultralow on-resistance and very low gate–drain charge, are currently the mainstream of high-performance applications and their advancement is continuing as low-voltage silicon power devices. However, owing to their structure, their output capacitance (C oss), which leads to main power loss, remains to be a problem, especially in megahertz switching. In this study, we propose a structure-based capacitance model of FP-MOSFETs for calculating power loss easily under various conditions. Appropriate equations were modeled for C oss curves as three divided components. Output charge (Q oss) and stored energy (E oss) that were calculated using the model corresponded well to technology computer-aided design (TCAD) simulation, and we validated the accuracy of the model quantitatively. In the power loss analysis of FP-MOSFETs, turn-off loss was sufficiently suppressed, however, mainly Q oss loss increased depending on switching frequency. This analysis reveals that Q oss may become a significant issue in next-generation high-efficiency FP-MOSFETs.

Models of protein–ligand crystal structures: trust, but verify

PubMed Central

Deller, Marc C.

2015-01-01

X-ray crystallography provides the most accurate models of protein–ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein–ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein–ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein–ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein–ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein–ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein–ligand models for their computational and biological studies, and we provide an overview of how this can be achieved. PMID:25665575

Models of protein-ligand crystal structures: trust, but verify.

PubMed

Deller, Marc C; Rupp, Bernhard

2015-09-01

X-ray crystallography provides the most accurate models of protein-ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein-ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein-ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein-ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein-ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein-ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein-ligand models for their computational and biological studies, and we provide an overview of how this can be achieved.

Model of community emergence in weighted social networks

NASA Astrophysics Data System (ADS)

Kumpula, J. M.; Onnela, J.-P.; Saramäki, J.; Kertész, J.; Kaski, K.

2009-04-01

Over the years network theory has proven to be rapidly expanding methodology to investigate various complex systems and it has turned out to give quite unparalleled insight to their structure, function, and response through data analysis, modeling, and simulation. For social systems in particular the network approach has empirically revealed a modular structure due to interplay between the network topology and link weights between network nodes or individuals. This inspired us to develop a simple network model that could catch some salient features of mesoscopic community and macroscopic topology formation during network evolution. Our model is based on two fundamental mechanisms of network sociology for individuals to find new friends, namely cyclic closure and focal closure, which are mimicked by local search-link-reinforcement and random global attachment mechanisms, respectively. In addition we included to the model a node deletion mechanism by removing all its links simultaneously, which corresponds for an individual to depart from the network. Here we describe in detail the implementation of our model algorithm, which was found to be computationally efficient and produce many empirically observed features of large-scale social networks. Thus this model opens a new perspective for studying such collective social phenomena as spreading, structure formation, and evolutionary processes.

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).

PubMed

Salinas, Gustavo; Gao, Wei; Wang, Yang; Bonilla, Mariana; Yu, Long; Novikov, Andrey; Virginio, Veridiana G; Ferreira, Henrique B; Vieites, Marisol; Gladyshev, Vadim N; Gambino, Dinorah; Dai, Shaodong

2017-12-20

New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with Au I -MPO, a novel gold inhibitor, together with inhibition assays were performed. Au I -MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys 519 and Cys 573 in the Au I -TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys 519 and Cys 573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.

The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I)

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

Salinas, Gustavo; Gao, Wei; Wang, Yang

Aims: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with AuI-MPO, a novel gold inhibitor, together with inhibition assays were performed. Results: AuI-MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer–monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxinmore » (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys519 and Cys573 in the AuI-TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. Innovation: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. Conclusions: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys519 and Cys573 residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491–1504.« less

High-resolution synchrotron x-ray powder diffraction study of the incommensurate modulation in the martensite phase of Ni2MnGa: Evidence for nearly 7M modulation and phason broadening

NASA Astrophysics Data System (ADS)

Singh, Sanjay; Petricek, V.; Rajput, Parasmani; Hill, Adrian H.; Suard, E.; Barman, S. R.; Pandey, Dhananjai

2014-07-01

The modulated structure of the martensite phase of Ni2MnGa is revisited using high-resolution synchrotron x-ray powder diffraction measurements, which reveal higher-order satellite reflections up to the third order and phason broadening of the satellite peaks. The structure refinement, using the (3+1) dimensional superspace group approach, shows that the modulated structure of Ni2MnGa can be described by orthorhombic superspace group Immm(00γ)s00 with lattice parameters a=4.218 61(2)Å,b=5.546 96(3)Å, and c=4.187 63(2) Å, and an incommensurate modulation wave vector q =0.43160(3)c*=(3/7+δ)c*, where δ =0.00303(3) is the degree of incommensuration of the modulated structure. Additional satellite peak broadening, which could not be accounted for in terms of the anisotropic strain broadening based on a lattice parameter distribution, has been modeled in terms of phasons using fourth-rank covariant strain-tensor representation for incommensurate structures. The simulation of single-crystal diffraction patterns from the refined structural parameters unambiguously reveals a rational approximant structure with 7M modulation. The inhomogeneous displacement of different atomic sites on account of incommensurate modulation and the presence of phason broadening clearly rule out the adaptive phase model proposed recently by Kaufmann et al. [S. Kaufmann, U. K. Rößler, O. Heczko, M. Wuttig, J. Buschbeck, L. Schultz, and S. Fähler, Phys. Rev. Lett. 104, 145702 (2010), 10.1103/PhysRevLett.104.145702] and suggest that the modulation in Ni2MnGa originates from soft-mode phonons.

Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes.

PubMed

Xu, Zhiyu; Stogios, Peter J; Quaile, Andrew T; Forsberg, Kevin J; Patel, Sanket; Skarina, Tatiana; Houliston, Scott; Arrowsmith, Cheryl; Dantas, Gautam; Savchenko, Alexei

2017-09-08

Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 , 612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin, and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme and revealed a drug binding mechanism distinct from previously characterized AAC(6') enzymes. Together, our data highlights the presence of highly active antibiotic-modifying enzymes in the environmental microbiome and reveals unexpected diversity in substrate specificity. These observations of additional AAC enzymes must be considered in the search for novel aminoglycosides less prone to resistance.

Three-dimensional flows in a hyperelastic vessel under external pressure.

PubMed

Zhang, Sen; Luo, Xiaoyu; Cai, Zongxi

2018-05-09

We study the collapsible behaviour of a vessel conveying viscous flows subject to external pressure, a scenario that could occur in many physiological applications. The vessel is modelled as a three-dimensional cylindrical tube of nonlinear hyperelastic material. To solve the fully coupled fluid-structure interaction, we have developed a novel approach based on the Arbitrary Lagrangian-Eulerian (ALE) method and the frontal solver. The method of rotating spines is used to enable an automatic mesh adaptation. The numerical code is verified extensively with published results and those obtained using the commercial packages in simpler cases, e.g. ANSYS for the structure with the prescribed flow, and FLUENT for the fluid flow with prescribed structure deformation. We examine three different hyperelastic material models for the tube for the first time in this context and show that at the small strain, all three material models give similar results. However, for the large strain, results differ depending on the material model used. We further study the behaviour of the tube under a mode-3 buckling and reveal its complex flow patterns under various external pressures. To understand these flow patterns, we show how energy dissipation is associated with the boundary layers created at the narrowest collapsed section of the tube, and how the transverse flow forms a virtual sink to feed a strong axial jet. We found that the energy dissipation associated with the recirculation does not coincide with the flow separation zone itself, but overlaps with the streamlines that divide the three recirculation zones. Finally, we examine the bifurcation diagrams for both mode-3 and mode-2 collapses and reveal that multiple solutions exist for a range of the Reynolds number. Our work is a step towards modelling more realistic physiological flows in collapsible arteries and veins.

Computed and Experimental Flutter/LCO Onset for the Boeing Truss-Braced Wing Wind-Tunnel Model

NASA Technical Reports Server (NTRS)

Bartels, Robert E.; Scott, Robert C.; Funk, Christie J.; Allen, Timothy J.; Sexton, Bradley W.

2014-01-01

This paper presents high fidelity Navier-Stokes simulations of the Boeing Subsonic Ultra Green Aircraft Research truss-braced wing wind-tunnel model and compares the results to linear MSC. Nastran flutter analysis and preliminary data from a recent wind-tunnel test of that model at the NASA Langley Research Center Transonic Dynamics Tunnel. The simulated conditions under consideration are zero angle of attack, so that structural nonlinearity can be neglected. It is found that, for Mach number greater than 0.78, the linear flutter analysis predicts flutter onset dynamic pressure below the wind-tunnel test and that predicted by the Navier-Stokes analysis. Furthermore, the wind-tunnel test revealed that the majority of the high structural dynamics cases were wing limit cycle oscillation (LCO) rather than flutter. Most Navier-Stokes simulated cases were also LCO rather than hard flutter. There is dip in the wind-tunnel test flutter/LCO onset in the Mach 0.76-0.80 range. Conditions tested above that Mach number exhibited no aeroelastic instability at the dynamic pressures reached in the tunnel. The linear flutter analyses do not show a flutter/LCO dip. The Navier-Stokes simulations also do not reveal a dip; however, the flutter/LCO onset is at a significantly higher dynamic pressure at Mach 0.90 than at lower Mach numbers. The Navier-Stokes simulations indicate a mild LCO onset at Mach 0.82, then a more rapidly growing instability at Mach 0.86 and 0.90. Finally, the modeling issues and their solution related to the use of a beam and pod finite element model to generate the Navier-Stokes structure mode shapes are discussed.

Molecular modelling studies of kdr mutations in voltage gated sodium channel revealed significant conformational variations contributing to insecticide resistance.

PubMed

Yellapu, Nanda Kumar; Gopal, Jeyakodi; Kasinathan, Gunasekaran; Purushothaman, Jambulingam

2018-06-01

Voltage gated sodium channels (VGSC) of mosquito vectors are the primary targets of dichlorodiphenyltrichloroethane (DDT) and other synthetic pyrethroids used in public health programmes. The knockdown resistant (kdr) mutations in VGSC are associated with the insecticide resistance especially in Anophelines. The present study is aimed to emphasize and demarcate the impact of three kdr-mutations such as L1014S, L1014F and L1014H on insecticide resistance. The membrane model of sodium transport domain of VGSC (STD-VGSC) was constructed using de novo approach based on domain and trans-membrane predictions. The comparative molecular modelling studies of wild type and mutant models of STD-VGSC revealed that L1014F mutant was observed to be near native to the wild type model in all the respects, but, L1014S and L1014H mutations showed drastic variations in the energy levels, root mean square fluctuations (RMSF) that resulted in conformational variations. The predicted binding sites also showed variable cavity volumes and RMSF in L1014S and L1014H mutants. Further, DDT also found be bound in near native manner to wild type in L1014F mutant and with variable orientation and affinities in L1014S and L1014H mutants. The variations and fluctuations observed in mutant structures explained that each mutation has its specific impact on the conformation of VGSC and its binding with DDT. The study provides new insights into the structure-function-correlations of mutant STD-VGSC structures and demonstrates the role and effects of kdr mutations on insecticide resistance in mosquito vectors.

Structural architecture of oceanic plateau subduction offshore Eastern Java and the potential implications for geohazards

NASA Astrophysics Data System (ADS)

Shulgin, A.; Kopp, H.; Mueller, C.; Planert, L.; Lueschen, E.; Flueh, E. R.; Djajadihardja, Y.

2011-01-01

The region offshore Eastern Java represents one of the few places where the early stage of oceanic plateau subduction is occurring. We study the little investigated Roo Rise oceanic plateau on the Indian plate, subducting beneath Eurasia. The presence of the abnormal bathymetric features entering the trench has a strong effect on the evolution of the subduction system, and causes additional challenges on the assessment of geohazard risks. We present integrated results of a refraction/wide-angle reflection tomography, gravity modelling, and multichannel reflection seismic imaging using data acquired in 2006 south of Java near 113°E. The composite structural model reveals the previously unresolved deep geometry of the oceanic plateau and the subduction zone. The oceanic plateau crust is on average 15 km thick and covers an area of about 100 000 km2. Within our profile the Roo Rise crustal thickness ranges between 18 and 12 km. The upper oceanic crust shows high degree of fracturing, suggesting heavy faulting. The forearc crust has an average thickness of 14 km, with a sharp increase to 33 km towards Java, as revealed by gravity modelling. The complex geometry of the backstop suggests two possible models for the structural formation within this segment of the margin: either accumulation of the Roo Rise crustal fragments above the backstop or alternatively uplift of the backstop caused by basal accumulation of crustal fragments. The subducting plateau is affecting the stress field within the accretionary complex and the backstop edge, which favours the initiation of large, potentially tsunamogenic earthquakes such as the 1994 Mw= 7.8 tsunamogenic event.

Crystal structure at 2.8Å of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain reveals a charged surface suitable for HIP-protein interactor (HIPPI)

PubMed Central

Niu, Qian; Ybe, Joel A.

2008-01-01

Summary Huntington’s disease is a genetic neurological disorder that is triggered by the dissociation of the huntingtin protein (htt) from its obligate interaction partner Huntingtin-interacting protein 1 (HIP1). The release of htt permits HIP-protein interactor (HIPPI) to bind to its recognition site on HIP1 to form a HIPPI/HIP1 complex that recruits Procaspase-8 to begin the process of apoptosis. The interaction module between HIPPI and HIP1 was predicted to resemble a death-effector domain (DED). Our 2.8 Å crystal structure of the HIP1 371-481 sub-fragment that includes F432 and K474 important for HIPPI binding is not a DED, but is a partially opened coiled-coil. The HIP1 371-481 model reveals a basic surface we hypothesize is suitable for binding HIPPI. There is an opened region next to the putative HIPPI site that is highly negatively charged. The acidic residues in this region are highly conserved in HIP1 and a related protein, HIP1R from different organisms, but are not conserved in the yeast homolog of HIP1, sla2p. We have modeled ∼85% of the coiled-coil domain by joining our new HIP1 371-481 structure to the HIP1 482-586 model (PDB code: 2NO2). Finally, the middle of this coiled-coil domain may be intrinsically flexible and suggests a new interaction model where HIPPI binds to a “U” shaped HIP1 molecule. PMID:18155047

Spatial Structure of a Braided River: Metric Resolution Hydrodynamic Modeling Reveals What SWOT Might See

NASA Astrophysics Data System (ADS)

Schubert, J.; Sanders, B. F.; Andreadis, K.

2013-12-01

The Surface Water and Ocean Topography (SWOT) mission, currently under study by NASA (National Aeronautics and Space Administration) and CNES (Centre National d'Etudes Spatiales), is designed to provide global spatial measurements of surface water properties at resolutions better than 10 m and with centimetric accuracy. The data produced by SWOT will include irregularly spaced point clouds of the water surface height, with point spacings from roughly 2-50 m depending on a point's location within SWOT's swath. This could offer unprecedented insight into the spatial structure of rivers. Features that may be resolved include backwater profiles behind dams, drawdown profiles, uniform flow sections, critical flow sections, and even riffle-pool flow structures. In the event that SWOT scans a river during a major flood, it becomes possible to delineate the limits of the flood as well as the spatial structure of the water surface elevation, yielding insight into the dynamic interaction of channels and flood plains. The Platte River in Nebraska, USA, is a braided river with a width and slope of approximately 100 m and 100 cm/km, respectively. A 1 m resolution Digital Terrain Model (DTM) of the river basin, based on airborne lidar collected during low-flow conditions, was used to parameterize a two-dimensional, variable resolution, unstructured grid, hydrodynamic model that uses 3 m resolution triangles in low flow channels and 10 m resolution triangles in the floodplain. Use of a fine resolution mesh guarantees that local variability in topography is resolved, and after applying the hydrodynamic model, the effects of topographic variability are expressed as variability in the water surface height, depth-averaged velocity and flow depth. Flow is modeled over a reach length of 10 km for multi-day durations to capture both frequent (diurnal variations associated with regulated flow) and infrequent (extreme flooding) flow phenomena. Model outputs reveal a number of interesting features, including a high degree of variability in the water depth and velocity and lesser variability in the free-surface profile and river discharge. Hydraulic control sections are also revealed, and shown to depend on flow stage. Reach-averaging of model output is applied to study the macro-scale balance of forces in this system, and the scales at which such a force balance is appropriate. We find that the reach-average slope exhibits a declining reach-length dependence with increasing reach length, up to reach lengths of 1 km. Hence, 1 km appears to be the minimum appropriate length for reach-averaging, and at this scale, a diffusive-wave momentum balance is a reasonable approximation suitable for emerging models of discharge estimation that rely only on SWOT-observable river properties (width, height, slope, etc.).

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.

PubMed

Keedy, Daniel A; Hill, Zachary B; Biel, Justin T; Kang, Emily; Rettenmaier, T Justin; Brandao-Neto, Jose; Pearce, Nicholas M; von Delft, Frank; Wells, James A; Fraser, James S

2018-06-07

Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function. © 2018, Keedy et al.

Novel natural super-lattice materials with low thermal conductivity for thermoelectric applications: A first principles study

NASA Astrophysics Data System (ADS)

Sreeparvathy, P. C.; Kanchana, V.

2017-12-01

A systematic study which reveals the low thermal conductivity and high thermopower on a series of natural superlattice structures in the form BaXFCh (X: Cu, Ag, Ch: S, Se, Te), LaXSO (X: Cu, Ag) and SrCuTeF are presented. Low thermal conductivity is predicted by combining elastic constants and few well established models. The electronic properties reveal the highly two dimensional nature of band structure in the valence band, and this is confirmed through effective mass calculations. The huge difference in effective mass along different crystallographic directions in valence band introduces anisotropy in the transport properties for hole doping, and 'a' axis is found to be more favourable. In addition to these, the parameter A (S2σ/τT/κe /τ), which can decouple the relaxation time is also calculated, and it reveals the possibility of good thermoelectric properties in these compounds. Our results are comparable with prototype thermoelectric materials, and show better values than traditional TE materials.

Variable and complex food web structures revealed by exploring missing trophic links between birds and biofilm.

PubMed

Kuwae, Tomohiro; Miyoshi, Eiichi; Hosokawa, Shinya; Ichimi, Kazuhiko; Hosoya, Jun; Amano, Tatsuya; Moriya, Toshifumi; Kondoh, Michio; Ydenberg, Ronald C; Elner, Robert W

2012-04-01

Food webs are comprised of a network of trophic interactions and are essential to elucidating ecosystem processes and functions. However, the presence of unknown, but critical networks hampers understanding of complex and dynamic food webs in nature. Here, we empirically demonstrate a missing link, both critical and variable, by revealing that direct predator-prey relationships between shorebirds and biofilm are widespread and mediated by multiple ecological and evolutionary determinants. Food source mixing models and energy budget estimates indicate that the strength of the missing linkage is dependent on predator traits (body mass and foraging action rate) and the environment that determines food density. Morphological analyses, showing that smaller bodied species possess more developed feeding apparatus to consume biofilm, suggest that the linkage is also phylogenetically dependent and affords a compelling re-interpretation of niche differentiation. We contend that exploring missing links is a necessity for revealing true network structure and dynamics. © 2012 Blackwell Publishing Ltd/CNRS.

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9)

PubMed Central

Fu, Qinqin; Yuan, Y. Adam

2013-01-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA. PMID:23361462

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

PubMed

Fu, Qinqin; Yuan, Y Adam

2013-03-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

Penetrating adolescents' mental models of mp3 with ZMET.

PubMed

Ling, I-Ling; Yang, Chun-Ming; Liu, Yi-Fen; Tsai, Yu-Hsuan

2009-01-01

This article demonstrates the application of the Zaltman metaphor-elicitation technique (ZMET) to help adolescent consumers delve into their unconscious thoughts and provide them with insights into the use of mp3. An analysis of interview transcripts and images revealed that the ZMET process provides a description of how the knowledge structures of adolescent consumers are subdivided and grouped around important themes that frame and motivate their involvement with a product. The findings reveal that there are 33 themes of consumer knowledge structure toward mp3. Furthermore, among these themes, there are four major concepts: size/form, convenience, relaxation, comfort, and appearance. The respondents' minds include not only rational components but emotional ingredients. Notably, the results also show that music can be an effective metaphor in the application of the ZMET method.

Crystal structure of a fully glycosylated HIV-1 gp120 core reveals a stabilizing role for the glycan at Asn262

DOE PAGES

Kong, Leopold; Wilson, Ian A.; Kwong, Peter D.

2014-12-26

The crystal structure of a fully glycosylated HIV-1 gp120 core in complex with CD4 receptor and Fab 17b at 4.5-Å resolution reveals 9 of the 15 N-linked glycans of core gp120 to be partially ordered. The glycan at position Asn262 had the most extensive and well-ordered electron density, and a GlcNAc 2Man 7 was modeled. Lastly, the GlcNAc stem of this glycan is largely buried in a cleft in gp120, suggesting a role in gp120 folding and stability. Its arms interact with the stems of neighboring glycans from the oligomannose patch, which is a major target for broadly neutralizing antibodies.

In Silico Characterization and Analysis of RTBP1 and NgTRF1 Protein Through MD Simulation and Molecular Docking: A Comparative Study.

PubMed

Mukherjee, Koel; Pandey, Dev Mani; Vidyarthi, Ambarish Saran

2015-09-01

Gaining access to sequence and structure information of telomere-binding proteins helps in understanding the essential biological processes involve in conserved sequence-specific interaction between DNA and the proteins. Rice telomere-binding protein (RTBP1) and Nicotiana glutinosa telomere repeat binding factor (NgTRF1) are helix-turn-helix motif type of proteins that plays role in telomeric DNA protection and length regulation. Both the proteins share same type of domain, but till now there is very less communication on the in silico studies of these complete proteins. Here we intend to do a comparative study between two proteins through modeling of the complete proteins, physiochemical characterization, MD simulation and DNA-protein docking. I-TASSER and CLC protein work bench was performed to find out the protein 3D structure as well as the different parameters to characterize the proteins. MD simulation was completed by GROMOS forcefield of GROMACS for 10 ns of time stretch. The simulated 3D structures were docked with template DNA (3D DNA modeled through 3D-DART) of TTTAGGG conserved sequence motif using HADDOCK Web server. By digging up all the facts about the proteins, it was revealed that around 120 amino acids in the tail part were showing a good sequence similarity between the proteins. Molecular modeling, sequence characterization and secondary structure prediction also indicate the similarity between the protein's structure and sequence. The result of MD simulation highlights on the RMSD, RMSF, Rg, PCA and energy plots which also conveys the similar type of motional behavior between them. The best complex formation for both the proteins in docking result also indicates for the first interaction site which is mainly the helix3 region of the DNA-binding domain. The overall computational analysis reveals that RTBP1 and NgTRF1 proteins display good amount of similarity in their physicochemical properties, structure, dynamics and binding mode.

Discovery of a diamond-based photonic crystal structure in beetle scales.

PubMed

Galusha, Jeremy W; Richey, Lauren R; Gardner, John S; Cha, Jennifer N; Bartl, Michael H

2008-05-01

We investigated the photonic crystal structure inside iridescent scales of the weevil Lamprocyphus augustus. By combining a high-resolution structure analysis technique based on sequential focused ion beam milling and scanning electron microscopy imaging with theoretical modeling and photonic band-structure calculations, we discovered a natural three-dimensional photonic structure with a diamond-based crystal lattice operating at visible wavelengths. Moreover, we found that within individual scales, the diamond-based structure is assembled in the form of differently oriented single-crystalline micrometer-sized pixels with only selected lattice planes facing the scales' top surface. A comparison of results obtained from optical microreflectance measurements with photonic band-structure calculations reveals that it is this sophisticated microassembly of the diamond-based crystal lattice that lends Lamprocyphus augustus its macroscopically near angle-independent green coloration.

The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s.

PubMed

Tavanti, Michele; Porter, Joanne L; Levy, Colin W; Gómez Castellanos, J Rubén; Flitsch, Sabine L; Turner, Nicholas J

2018-07-02

The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 Å resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of free modeling targets in CASP11 and ROLL.

PubMed

Kinch, Lisa N; Li, Wenlin; Monastyrskyy, Bohdan; Kryshtafovych, Andriy; Grishin, Nick V

2016-09-01

We present an assessment of 'template-free modeling' (FM) in CASP11and ROLL. Community-wide server performance suggested the use of automated scores similar to previous CASPs would provide a good system of evaluating performance, even in the absence of comprehensive manual assessment. The CASP11 FM category included several outstanding examples, including successful prediction by the Baker group of a 256-residue target (T0806-D1) that lacked sequence similarity to any existing template. The top server model prediction by Zhang's Quark, which was apparently selected and refined by several manual groups, encompassed the entire fold of target T0837-D1. Methods from the same two groups tended to dominate overall CASP11 FM and ROLL rankings. Comparison of top FM predictions with those from the previous CASP experiment revealed progress in the category, particularly reflected in high prediction accuracy for larger protein domains. FM prediction models for two cases were sufficient to provide functional insights that were otherwise not obtainable by traditional sequence analysis methods. Importantly, CASP11 abstracts revealed that alignment-based contact prediction methods brought about much of the CASP11 progress, producing both of the functionally relevant models as well as several of the other outstanding structure predictions. These methodological advances enabled de novo modeling of much larger domain structures than was previously possible and allowed prediction of functional sites. Proteins 2016; 84(Suppl 1):51-66. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Using Dispersed Modes During Model Correlation

NASA Technical Reports Server (NTRS)

Stewart, Eric C.; Hathcock, Megan L.

2017-01-01

The model correlation process for the modal characteristics of a launch vehicle is well established. After a test, parameters within the nominal model are adjusted to reflect structural dynamics revealed during testing. However, a full model correlation process for a complex structure can take months of man-hours and many computational resources. If the analyst only has weeks, or even days, of time in which to correlate the nominal model to the experimental results, then the traditional correlation process is not suitable. This paper describes using model dispersions to assist the model correlation process and decrease the overall cost of the process. The process creates thousands of model dispersions from the nominal model prior to the test and then compares each of them to the test data. Using mode shape and frequency error metrics, one dispersion is selected as the best match to the test data. This dispersion is further improved by using a commercial model correlation software. In the three examples shown in this paper, this dispersion based model correlation process performs well when compared to models correlated using traditional techniques and saves time in the post-test analysis.

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

PubMed

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

2016-09-26

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

Quaternary structure of human, Drosophila melanogaster and Caenorhabditis elegans MFE-2 in solution from synchrotron small-angle X-ray scattering.

PubMed

Mehtälä, Maija L; Haataja, Tatu J K; Blanchet, Clément E; Hiltunen, J Kalervo; Svergun, Dmitri I; Glumoff, Tuomo

2013-02-14

Multifunctional enzyme type 2 (MFE-2) forms part of the fatty acid β-oxidation pathway in peroxisomes. MFE-2s from various species reveal proteins with structurally homologous functional domains assembled in different compilations. Crystal structures of all domain types are known. SAXS data from human, fruit fly and Caenorhabditiselegans MFE-2s and their constituent domains were collected, and both ab initio and rigid body models constructed. Location of the putative substrate binding helper domain SCP-2L (sterol carrier protein 2-like), which is not part of MFE-2 protein in every species and not seen as part of any previous MFE-2 structures, was determined. The obtained models of human and C. elegans MFE-2 lend a direct structural support to the idea of the biological role of SCP-2L. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Reducing hydrologic model uncertainty in monthly streamflow predictions using multimodel combination

NASA Astrophysics Data System (ADS)

Li, Weihua; Sankarasubramanian, A.

2012-12-01

Model errors are inevitable in any prediction exercise. One approach that is currently gaining attention in reducing model errors is by combining multiple models to develop improved predictions. The rationale behind this approach primarily lies on the premise that optimal weights could be derived for each model so that the developed multimodel predictions will result in improved predictions. A new dynamic approach (MM-1) to combine multiple hydrological models by evaluating their performance/skill contingent on the predictor state is proposed. We combine two hydrological models, "abcd" model and variable infiltration capacity (VIC) model, to develop multimodel streamflow predictions. To quantify precisely under what conditions the multimodel combination results in improved predictions, we compare multimodel scheme MM-1 with optimal model combination scheme (MM-O) by employing them in predicting the streamflow generated from a known hydrologic model (abcd model orVICmodel) with heteroscedastic error variance as well as from a hydrologic model that exhibits different structure than that of the candidate models (i.e., "abcd" model or VIC model). Results from the study show that streamflow estimated from single models performed better than multimodels under almost no measurement error. However, under increased measurement errors and model structural misspecification, both multimodel schemes (MM-1 and MM-O) consistently performed better than the single model prediction. Overall, MM-1 performs better than MM-O in predicting the monthly flow values as well as in predicting extreme monthly flows. Comparison of the weights obtained from each candidate model reveals that as measurement errors increase, MM-1 assigns weights equally for all the models, whereas MM-O assigns higher weights for always the best-performing candidate model under the calibration period. Applying the multimodel algorithms for predicting streamflows over four different sites revealed that MM-1 performs better than all single models and optimal model combination scheme, MM-O, in predicting the monthly flows as well as the flows during wetter months.

Student perception and conceptual development as represented by student mental models of atomic structure

NASA Astrophysics Data System (ADS)

Park, Eun Jung

The nature of matter based upon atomic theory is a principal concept in science; hence, how to teach and how to learn about atoms is an important subject for science education. To this end, this study explored student perceptions of atomic structure and how students learn about this concept by analyzing student mental models of atomic structure. Changes in student mental models serve as a valuable resource for comprehending student conceptual development. Data was collected from students who were taking the introductory chemistry course. Responses to course examinations, pre- and post-questionnaires, and pre- and post-interviews were used to analyze student mental models of atomic structure. First, this study reveals that conceptual development can be achieved, either by elevating mental models toward higher levels of understanding or by developing a single mental model. This study reinforces the importance of higher-order thinking skills to enable students to relate concepts in order to construct a target model of atomic structure. Second, Bohr's orbital structure seems to have had a strong influence on student perceptions of atomic structure. With regard to this finding, this study suggests that it is instructionally important to teach the concept of "orbitals" related to "quantum theory." Third, there were relatively few students who had developed understanding at the level of the target model, which required student understanding of the basic ideas of quantum theory. This study suggests that the understanding of atomic structure based on the idea of quantum theory is both important and difficult. Fourth, this study included different student assessments comprised of course examinations, questionnaires, and interviews. Each assessment can be used to gather information to map out student mental models. Fifth, in the comparison of the pre- and post-interview responses, this study showed that high achieving students moved toward more improved models or to advanced levels of understanding. The analysis of mental models in this study has provided information describing student understanding of the nature and structure of an atom. In addition to an assessment of student cognition, information produced from this study can serve as an important resource for curriculum development, teacher education, and instruction.

Mining for recurrent long-range interactions in RNA structures reveals embedded hierarchies in network families.

PubMed

Reinharz, Vladimir; Soulé, Antoine; Westhof, Eric; Waldispühl, Jérôme; Denise, Alain

2018-05-04

The wealth of the combinatorics of nucleotide base pairs enables RNA molecules to assemble into sophisticated interaction networks, which are used to create complex 3D substructures. These interaction networks are essential to shape the 3D architecture of the molecule, and also to provide the key elements to carry molecular functions such as protein or ligand binding. They are made of organised sets of long-range tertiary interactions which connect distinct secondary structure elements in 3D structures. Here, we present a de novo data-driven approach to extract automatically from large data sets of full RNA 3D structures the recurrent interaction networks (RINs). Our methodology enables us for the first time to detect the interaction networks connecting distinct components of the RNA structure, highlighting their diversity and conservation through non-related functional RNAs. We use a graphical model to perform pairwise comparisons of all RNA structures available and to extract RINs and modules. Our analysis yields a complete catalog of RNA 3D structures available in the Protein Data Bank and reveals the intricate hierarchical organization of the RNA interaction networks and modules. We assembled our results in an online database (http://carnaval.lri.fr) which will be regularly updated. Within the site, a tool allows users with a novel RNA structure to detect automatically whether the novel structure contains previously observed RINs.

Boko Haram: A Systemic and Strategic Analysis

DTIC Science & Technology

2016-06-01

21 5 Example Structural System Model …..……………………………….…………21 6 Interconnections ...…………………………………………………….…………23 vii 7...result from exogenous, endogenous, or structural factors. Endogenous factors exist within the geographical bounds of the system state, but exogenous...of the system, the structural factors are a result of the anarchic nature of the international system. Changes in system states reveal long-term

Structural transition in lanthanum gallate and transformation of the fine structure of the EPR spectrum of a Gd3+ impurity center

NASA Astrophysics Data System (ADS)

Vazhenin, V. A.; Guseva, V. B.; Fokin, A. V.; Potapov, A. P.; Artyomov, M. Yu.

2011-04-01

Abrupt changes in resonance positions, hysteretic temperature behavior, and coexistence of phases, which indicate a first-order phase transition, have been revealed from measurements of temperature dependences of the EPR spectra of Gd3+ and Mn4+ centers in the vicinity of the structural transition of lanthanum gallate. The transformation of monoclinic Gd3+ centers into trigonal Gd3+ centers upon the phase transition has been used to estimate the adequacy of two approximations of the superposition model for parameters of the zero-field splitting of the ground state.

Structure of S-shaped growth in innovation diffusion

NASA Astrophysics Data System (ADS)

Shimogawa, Shinsuke; Shinno, Miyuki; Saito, Hiroshi

2012-05-01

A basic question on innovation diffusion is why the growth curve of the adopter population in a large society is often S shaped. From macroscopic, microscopic, and mesoscopic viewpoints, the growth of the adopter population is observed as the growth curve, individual adoptions, and differences among individual adoptions, respectively. The S shape can be explained if an empirical model of the growth curve can be deduced from models of microscopic and mesoscopic structures. However, even the structure of growth curve has not been revealed yet because long-term extrapolations by proposed models of S-shaped curves are unstable and it has been very difficult to predict the long-term growth and final adopter population. This paper studies the S-shaped growth from the viewpoint of social regularities. Simple methods to analyze power laws enable us to extract the structure of the growth curve directly from the growth data of recent basic telecommunication services. This empirical model of growth curve is singular at the inflection point and a logarithmic function of time after this point, which explains the unstable extrapolations obtained using previously proposed models and the difficulty in predicting the final adopter population. Because the empirical S curve can be expressed in terms of two power laws of the regularity found in social performances of individuals, we propose the hypothesis that the S shape represents the heterogeneity of the adopter population, and the heterogeneity parameter is distributed under the regularity in social performances of individuals. This hypothesis is so powerful as to yield models of microscopic and mesoscopic structures. In the microscopic model, each potential adopter adopts the innovation when the information accumulated by the learning about the innovation exceeds a threshold. The accumulation rate of information is heterogeneous among the adopter population, whereas the threshold is a constant, which is the opposite of previously proposed models. In the mesoscopic model, flows of innovation information incoming to individuals are organized as dimorphic and partially clustered. These microscopic and mesoscopic models yield the empirical model of the S curve and explain the S shape as representing the regularities of information flows generated through a social self-organization. To demonstrate the validity and importance of the hypothesis, the models of three level structures are applied to reveal the mechanism determining and differentiating diffusion speeds. The empirical model of S curves implies that the coefficient of variation of the flow rates determines the diffusion speed for later adopters. Based on this property, a model describing the inside of information flow clusters can be given, which provides a formula interconnecting the diffusion speed, cluster populations, and a network topological parameter of the flow clusters. For two recent basic telecommunication services in Japan, the formula represents the variety of speeds in different areas and enables us to explain speed gaps between urban and rural areas and between the two services. Furthermore, the formula provides a method to estimate the final adopter population.

The crustal structure in the transition zone between the western and eastern Barents Sea

NASA Astrophysics Data System (ADS)

Shulgin, Alexey; Mjelde, Rolf; Faleide, Jan Inge; Høy, Tore; Flueh, Ernst; Thybo, Hans

2018-07-01

We present a crustal-scale seismic profile in the Barents Sea based on new data. Wide-angle seismic data were recorded along a 600 km long profile at 38 ocean bottom seismometer and 52 onshore station locations. The modelling uses the joint refraction/reflection tomography approach where co-located multichannel seismic reflection data constrain the sedimentary structure. Further, forward gravity modelling is based on the seismic model. We also calculate net regional erosion based on the calculated shallow velocity structure. Our model reveals a complex crustal structure of the Baltic Shield to Barents shelf transition zone, as well as strong structural variability on the shelf itself. We document large volumes of pre-Carboniferous sedimentary strata in the transition zone which reach a total thickness of 10 km. A high-velocity crustal domain found below the Varanger Peninsula likely represents an independent crustal block. Large lower crustal bodies with very high velocity and density below the Varanger Peninsula and the Fedynsky High are interpreted as underplated material that may have fed mafic dykes in the Devonian. We speculate that these lower crustal bodies are linked to the Devonian rifting processes in the East European Craton, or belonging to the integral part of the Timanides, as observed onshore in the Pechora Basin.

Functional Analysis of Dopaminergic Systems in a DYT1 Knock-in Mouse Model of Dystonia

PubMed Central

Song, Chang-Hyun; Fan, Xueliang; Exeter, Cicely J.; Hess, Ellen J.; Jinnah, H. A.

2012-01-01

The dystonias are a group of disorders characterized by involuntary twisting movements and abnormal posturing. The most common of the inherited dystonias is DYT1 dystonia, which is due to deletion of a single GAG codon (ΔE) in the TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked with dysfunction of brain dopamine pathways, the integrity of these pathways was explored in a knock-in mouse model of DYT1 dystonia. In DYT1(ΔE) knock-in mice, neurochemical measures revealed only small changes in the content of dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain, but microdialysis studies revealed robust decreases in baseline and amphetamine-stimulated extracellular dopamine in the caudoputamen. Quantitative stereological methods revealed no evidence for striatal or midbrain atrophy, but substantia nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in gross motor activity and motor coordination without overt dystonia. Neuropharmacological challenges of dopamine systems revealed normal behavioral responses to amphetamine and a minor increase in sensitivity to haloperidol. These results demonstrate that this DYT1(ΔE) knock-in mouse model of dystonia harbors neurochemical and structural changes of the dopamine pathways, as well as motor abnormalities. PMID:22659308

PDBFlex: exploring flexibility in protein structures

PubMed Central

Hrabe, Thomas; Li, Zhanwen; Sedova, Mayya; Rotkiewicz, Piotr; Jaroszewski, Lukasz; Godzik, Adam

2016-01-01

The PDBFlex database, available freely and with no login requirements at http://pdbflex.org, provides information on flexibility of protein structures as revealed by the analysis of variations between depositions of different structural models of the same protein in the Protein Data Bank (PDB). PDBFlex collects information on all instances of such depositions, identifying them by a 95% sequence identity threshold, performs analysis of their structural differences and clusters them according to their structural similarities for easy analysis. The PDBFlex contains tools and viewers enabling in-depth examination of structural variability including: 2D-scaling visualization of RMSD distances between structures of the same protein, graphs of average local RMSD in the aligned structures of protein chains, graphical presentation of differences in secondary structure and observed structural disorder (unresolved residues), difference distance maps between all sets of coordinates and 3D views of individual structures and simulated transitions between different conformations, the latter displayed using JSMol visualization software. PMID:26615193

Structural dynamics of the lac repressor-DNA complex revealed by a multiscale simulation.

PubMed

Villa, Elizabeth; Balaeff, Alexander; Schulten, Klaus

2005-05-10

A multiscale simulation of a complex between the lac repressor protein (LacI) and a 107-bp-long DNA segment is reported. The complex between the repressor and two operator DNA segments is described by all-atom molecular dynamics; the size of the simulated system comprises either 226,000 or 314,000 atoms. The DNA loop connecting the operators is modeled as a continuous elastic ribbon, described mathematically by the nonlinear Kirchhoff differential equations with boundary conditions obtained from the coordinates of the terminal base pairs of each operator. The forces stemming from the looped DNA are included in the molecular dynamics simulations; the loop structure and the forces are continuously recomputed because the protein motions during the simulations shift the operators and the presumed termini of the loop. The simulations reveal the structural dynamics of the LacI-DNA complex in unprecedented detail. The multiple domains of LacI exhibit remarkable structural stability during the simulation, moving much like rigid bodies. LacI is shown to absorb the strain from the looped DNA mainly through its mobile DNA-binding head groups. Even with large fluctuating forces applied, the head groups tilt strongly and keep their grip on the operator DNA, while the remainder of the protein retains its V-shaped structure. A simulated opening of the cleft of LacI by 500-pN forces revealed the interactions responsible for locking LacI in the V-conformation.

Assessing the fit of the Dysphoric Arousal model across two nationally representative epidemiological surveys: The Australian NSMHWB and the United States NESARC.

PubMed

Armour, Cherie; Carragher, Natacha; Elhai, Jon D

2013-01-01

Since the initial inclusion of PTSD in the DSM nomenclature, PTSD symptomatology has been distributed across three symptom clusters. However, a wealth of empirical research has concluded that PTSD's latent structure is best represented by one of two four-factor models: Numbing or Dysphoria. Recently, a newly proposed five-factor Dysphoric Arousal model, which separates the DSM-IV's Arousal cluster into two factors of Anxious Arousal and Dysphoric Arousal, has gathered support across a variety of trauma samples. To date, the Dysphoric Arousal model has not been assessed using nationally representative epidemiological data. We employed confirmatory factor analysis to examine PTSD's latent structure in two independent population based surveys from American (NESARC) and Australia (NSWHWB). We specified and estimated the Numbing model, the Dysphoria model, and the Dysphoric Arousal model in both samples. Results revealed that the Dysphoric Arousal model provided superior fit to the data compared to the alternative models. In conclusion, these findings suggest that items D1-D3 (sleeping difficulties; irritability; concentration difficulties) represent a separate, fifth factor within PTSD's latent structure using nationally representative epidemiological data in addition to single trauma specific samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

Global QSAR modeling of logP values of phenethylamines acting as adrenergic alpha-1 receptor agonists.

PubMed

Yadav, Mukesh; Joshi, Shobha; Nayarisseri, Anuraj; Jain, Anuja; Hussain, Aabid; Dubey, Tushar

2013-06-01

Global QSAR models predict biological response of molecular structures which are generic in particular class. A global QSAR dataset admits structural features derived from larger chemical space, intricate to model but more applicable in medicinal chemistry. The present work is global in either sense of structural diversity in QSAR dataset or large number of descriptor input. Forty phenethylamine structure derivatives were selected from a large pool (904) of similar phenethylamines available in Pubchem database. LogP values of selected candidates were collected from physical properties database (PHYSPROP) determined in identical set of conditions. Attempts to model logP value have produced significant QSAR models. MLR aided linear one-variable and two-variable QSAR models with their respective R(2) (0.866, 0.937), R(2)A (0.862, 0.932), F-stat (181.936, 199.812) and Standard Error (0.365, 0.255) are statistically fit and found predictive after internal validation and external validation. The descriptors chosen after improvisation and optimization reveal mechanistic part of work in terms of Verhaar model of Fish base-line toxicity from MLOGP, i.e. (BLTF96) and 3D-MoRSE -signal 15 /unweighted molecular descriptor calculated by summing atom weights viewed by a different angular scattering function (Mor15u) are crucial in regulation of logP values of phenethylamines.

A radiosity-based model to compute the radiation transfer of soil surface

NASA Astrophysics Data System (ADS)

Zhao, Feng; Li, Yuguang

2011-11-01

A good understanding of interactions of electromagnetic radiation with soil surface is important for a further improvement of remote sensing methods. In this paper, a radiosity-based analytical model for soil Directional Reflectance Factor's (DRF) distributions was developed and evaluated. The model was specifically dedicated to the study of radiation transfer for the soil surface under tillage practices. The soil was abstracted as two dimensional U-shaped or V-shaped geometric structures with periodic macroscopic variations. The roughness of the simulated surfaces was expressed as a ratio of the height to the width for the U and V-shaped structures. The assumption was made that the shadowing of soil surface, simulated by U or V-shaped grooves, has a greater influence on the soil reflectance distribution than the scattering properties of basic soil particles of silt and clay. Another assumption was that the soil is a perfectly diffuse reflector at a microscopic level, which is a prerequisite for the application of the radiosity method. This radiosity-based analytical model was evaluated by a forward Monte Carlo ray-tracing model under the same structural scenes and identical spectral parameters. The statistics of these two models' BRF fitting results for several soil structures under the same conditions showed the good agreements. By using the model, the physical mechanism of the soil bidirectional reflectance pattern was revealed.

Homology models of main proteinase from coronavirus associated with SARS

NASA Astrophysics Data System (ADS)

Liu, Hsuan-Liang; Lin, Jin-Chung; Ho, Yih; Chen, Chin-Wen

2005-01-01

In this study, two homology models of the main proteinase (M pro) from the novel coronavirus associated with severe acute respiratory syndrome (SARS-CoV) were constructed. These models reveal three distinct functional domains, in which an intervening loop connecting domains II and III as well as a catalytic cleft containing the substrate binding subsites S1 and S2 between domains I and II are observed. S2 exhibits structural variations more significantly than S1 during the 200 ps molecular dynamics simulations because it is located at the open mouth of the catalytic cleft and the amino acid residues lining up this subsite are least conserved. In addition, the higher structural variation of S2 makes it flexible enough to accommodate a bulky hydrophobic residue from the substrate.

Optimal Network-based Intervention in the Presence of Undetectable Viruses.

PubMed

Youssef, Mina; Scoglio, Caterina

2014-08-01

This letter presents an optimal control framework to reduce the spread of viruses in networks. The network is modeled as an undirected graph of nodes and weighted links. We consider the spread of viruses in a network as a system, and the total number of infected nodes as the state of the system, while the control function is the weight reduction leading to slow/reduce spread of viruses. Our epidemic model overcomes three assumptions that were extensively used in the literature and produced inaccurate results. We apply the optimal control formulation to crucial network structures. Numerical results show the dynamical weight reduction and reveal the role of the network structure and the epidemic model in reducing the infection size in the presence of indiscernible infected nodes.

Optimal Network-based Intervention in the Presence of Undetectable Viruses

PubMed Central

Youssef, Mina; Scoglio, Caterina

2014-01-01

This letter presents an optimal control framework to reduce the spread of viruses in networks. The network is modeled as an undirected graph of nodes and weighted links. We consider the spread of viruses in a network as a system, and the total number of infected nodes as the state of the system, while the control function is the weight reduction leading to slow/reduce spread of viruses. Our epidemic model overcomes three assumptions that were extensively used in the literature and produced inaccurate results. We apply the optimal control formulation to crucial network structures. Numerical results show the dynamical weight reduction and reveal the role of the network structure and the epidemic model in reducing the infection size in the presence of indiscernible infected nodes. PMID:25422579

The NMR-Rosetta capsid model of M13 bacteriophage reveals a quadrupled hydrophobic packing epitope.

PubMed

Morag, Omry; Sgourakis, Nikolaos G; Baker, David; Goldbourt, Amir

2015-01-27

Filamentous phage are elongated semiflexible ssDNA viruses that infect bacteria. The M13 phage, belonging to the family inoviridae, has a length of ∼1 μm and a diameter of ∼7 nm. Here we present a structural model for the capsid of intact M13 bacteriophage using Rosetta model building guided by structure restraints obtained from magic-angle spinning solid-state NMR experimental data. The C5 subunit symmetry observed in fiber diffraction studies was enforced during model building. The structure consists of stacked pentamers with largely alpha helical subunits containing an N-terminal type II β-turn; there is a rise of 16.6-16.7 Å and a tilt of 36.1-36.6° between consecutive pentamers. The packing of the subunits is stabilized by a repeating hydrophobic stacking pocket; each subunit participates in four pockets by contributing different hydrophobic residues, which are spread along the subunit sequence. Our study provides, to our knowledge, the first magic-angle spinning NMR structure of an intact filamentous virus capsid and further demonstrates the strength of this technique as a method of choice to study noncrystalline, high-molecular-weight molecular assemblies.

The NMR–Rosetta capsid model of M13 bacteriophage reveals a quadrupled hydrophobic packing epitope

PubMed Central

Morag, Omry; Sgourakis, Nikolaos G.; Baker, David; Goldbourt, Amir

2015-01-01

Filamentous phage are elongated semiflexible ssDNA viruses that infect bacteria. The M13 phage, belonging to the family inoviridae, has a length of ∼1 μm and a diameter of ∼7 nm. Here we present a structural model for the capsid of intact M13 bacteriophage using Rosetta model building guided by structure restraints obtained from magic-angle spinning solid-state NMR experimental data. The C5 subunit symmetry observed in fiber diffraction studies was enforced during model building. The structure consists of stacked pentamers with largely alpha helical subunits containing an N-terminal type II β-turn; there is a rise of 16.6–16.7 Å and a tilt of 36.1–36.6° between consecutive pentamers. The packing of the subunits is stabilized by a repeating hydrophobic stacking pocket; each subunit participates in four pockets by contributing different hydrophobic residues, which are spread along the subunit sequence. Our study provides, to our knowledge, the first magic-angle spinning NMR structure of an intact filamentous virus capsid and further demonstrates the strength of this technique as a method of choice to study noncrystalline, high-molecular-weight molecular assemblies. PMID:25587134

Generation of the first structure-based pharmacophore model containing a selective "zinc binding group" feature to identify potential glyoxalase-1 inhibitors.

PubMed

Al-Balas, Qosay; Hassan, Mohammad; Al-Oudat, Buthina; Alzoubi, Hassan; Mhaidat, Nizar; Almaaytah, Ammar

2012-11-22

Within this study, a unique 3D structure-based pharmacophore model of the enzyme glyoxalase-1 (Glo-1) has been revealed. Glo-1 is considered a zinc metalloenzyme in which the inhibitor binding with zinc atom at the active site is crucial. To our knowledge, this is the first pharmacophore model that has a selective feature for a "zinc binding group" which has been customized within the structure-based pharmacophore model of Glo-1 to extract ligands that possess functional groups able to bind zinc atom solely from database screening. In addition, an extensive 2D similarity search using three diverse similarity techniques (Tanimoto, Dice, Cosine) has been performed over the commercially available "Zinc Clean Drug-Like Database" that contains around 10 million compounds to help find suitable inhibitors for this enzyme based on known inhibitors from the literature. The resultant hits were mapped over the structure based pharmacophore and the successful hits were further docked using three docking programs with different pose fitting and scoring techniques (GOLD, LibDock, CDOCKER). Nine candidates were suggested to be novel Glo-1 inhibitors containing the "zinc binding group" with the highest consensus scoring from docking.

Nonmigrating tidal modulation of the equatorial thermosphere and ionosphere anomaly

NASA Astrophysics Data System (ADS)

Lei, Jiuhou; Thayer, Jeffrey P.; Wang, Wenbin; Yue, Jia; Dou, Xiankang

2014-04-01

The modulation of nonmigrating tides on both the ionospheric equatorial ionization anomaly (EIA) and the equatorial thermosphere anomaly (ETA) is investigated on the basis of simulations from the Thermosphere Ionosphere Mesosphere Electrodynamics General Circulation Model (TIME-GCM). Our simulations demonstrate the distinct features of the EIA and ETA seen in observations after the inclusion of field-aligned ion drag in the model. Both the EIA and the ETA in the constant local time frame display an obvious zonal wave-4 structure associated with the modulation of nonmigrating tides. However, the modeled EIA and ETA show a primary zonal wave-1 structure when only the migrating tides are specified at the model lower boundary. Our simulations reveal that the zonal wave-4 structure of the ETA under both low and high solar activity conditions is mainly caused by the direct response of the upper thermosphere to the diurnal eastward wave number 3 and semidiurnal eastward wave number 2 nonmigrating tides from the lower atmosphere. There is a minor contribution from the ion-neutral coupling. The zonal wave-4 structure of the EIA is also caused by these nonmigrating tides but through the modulation of the neutral wind dynamo.

Endophilin-A1 BAR domain interaction with arachidonyl CoA.

PubMed

Petoukhov, Maxim V; Weissenhorn, Winfried; Svergun, Dmitri I

2014-01-01

Endophilin-A1 belongs to the family of BAR domain containing proteins that catalyze membrane remodeling processes via sensing, inducing and stabilizing membrane curvature. We show that the BAR domain of endophilin-A1 binds arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA into a defined structure. We studied low resolution structures of endophilin-A1-BAR and its complex with arachidonyl-CoA in solution using synchrotron small-angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be dimeric at lower concentrations but builds tetramers and higher order complexes with increasing concentrations. Extensive titration SAXS studies revealed that the BAR domain produces a homogenous complex with the lipid micelles. The structural model of the complexes revealed two arachidonyl-CoA micelles bound to the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the bound micelles significantly decreases compared to that of the free micelles, and this structural result may provide hints on the potential biological relevance of the endophilin-A1-BAR interaction with arachidonyl CoA.

Structure of granzyme C reveals an unusual mechanism of protease autoinhibition

PubMed Central

Kaiserman, Dion; Buckle, Ashley M.; Van Damme, Petra; Irving, James A.; Law, Ruby H. P.; Matthews, Antony Y.; Bashtannyk-Puhalovich, Tanya; Langendorf, Chris; Thompson, Philip; Vandekerckhove, Joël; Gevaert, Kris; Whisstock, James C.; Bird, Phillip I.

2009-01-01

Proteases act in important homeostatic pathways and are tightly regulated. Here, we report an unusual structural mechanism of regulation observed by the 2.5-Å X-ray crystal structure of the serine protease, granzyme C. Although the active-site triad residues adopt canonical conformations, the oxyanion hole is improperly formed, and access to the primary specificity (S1) pocket is blocked through a reversible rearrangement involving Phe-191. Specifically, a register shift in the 190-strand preceding the active-site serine leads to Phe-191 filling the S1 pocket. Mutation of a unique Glu–Glu motif at positions 192–193 unlocks the enzyme, which displays chymase activity, and proteomic analysis confirms that activity of the wild-type protease can be released through interactions with an appropriate substrate. The 2.5-Å structure of the unlocked enzyme reveals unprecedented flexibility in the 190-strand preceding the active-site serine that results in Phe-191 vacating the S1 pocket. Overall, these observations describe a broadly applicable mechanism of protease regulation that cannot be predicted by template-based modeling or bioinformatic approaches alone. PMID:19299505

Nano-structure of the laminin γ-1 short arm reveals an extended and curved multidomain assembly.

PubMed

Patel, Trushar R; Morris, Gordon A; Zwolanek, Daniela; Keene, Douglas R; Li, Jianhua; Harding, Stephen E; Koch, Manuel; Stetefeld, Jörg

2010-09-01

Laminins are multidomain glycoproteins that play important roles in development and maintenance of the extracellular matrix via their numerous interactions with other proteins. Several receptors for the laminin short arms revealed their importance in network formation and intercellular signaling. However, both the detailed structure of the laminin γ-1 short arm and its organization within the complexes is poorly understood due to the complexity of the molecule and the lack of a high-resolution structure. The presented data provide the first subatomic resolution structure for the laminin γ-1 short arm in solution. This was achieved using an integrated approach that combined a number of complementary biophysical techniques such as small angle X-ray scattering (SAXS), analytical ultracentrifugation, dynamic light scattering and electron microscopy. As a result of this study, we have obtained a significantly improved model for the laminin γ-1 short arm that represents a major step forward in molecular understanding of laminin-mediated complex formations. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Cryo-electron microscopy structure of human peroxiredoxin-3 filament reveals the assembly of a putative chaperone.

PubMed

Radjainia, Mazdak; Venugopal, Hariprasad; Desfosses, Ambroise; Phillips, Amy J; Yewdall, N Amy; Hampton, Mark B; Gerrard, Juliet A; Mitra, Alok K

2015-05-05

Peroxiredoxins (Prxs) are a ubiquitous class of thiol-dependent peroxidases that play an important role in the protection and response of cells to oxidative stress. The catalytic unit of typical 2-Cys Prxs are homodimers, which can self-associate to form complex assemblies that are hypothesized to have signaling and chaperone activity. Mitochondrial Prx3 forms dodecameric toroids, which can further stack to form filaments, the so-called high-molecular-weight (HMW) form that has putative holdase activity. We used single-particle analysis and helical processing of electron cryomicroscopy images of human Prx3 filaments induced by low pH to generate a ∼7-Å resolution 3D structure of the HMW form, the first such structure for a 2-Cys Prx. The pseudo-atomic model reveals interactions that promote the stacking of the toroids and shows that unlike previously reported data, the structure can accommodate a partially folded C terminus. The HMW filament lumen displays hydrophobic patches, which we hypothesize bestow holdase activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Job-related stress in psychiatric nurses in Japan caring for elderly patients with dementia.

PubMed

Yada, Hironori; Abe, Hiroshi; Lu, Xi; Wakizaki, Yuko; Omori, Hisamitsu; Matsuo, Hisae; Ishida, Yasushi; Katoh, Takahiko

2014-11-01

We investigated the specificity and structures of job-related stress in psychiatric dementia nurses (PDNs) caring for elderly patients with serious behavioral and psychological symptoms of dementia who required substantial assistance with activities of daily living, in order to obtain fundamental knowledge toward providing mental health care for these nurses. Subjects were 244 nurses [63 PDNs and 181 other psychiatric nurses (OPNs)] Analysis of covariance to examine the specificity of job-related stress in PDNs revealed physical workload and work environment to be more significant stressors, and irritability and anxiety to be more significant stress reactions in PDNs than in OPNs. An examination of PDNs' job-related stress structures established in a structural equation model with two stress reactions confirmed as specific outcomes for PDNs revealed a significant positive influence of work environment on irritability; utilization of techniques for anxiety and physical workload influenced both stress reactions. Our findings highlight the importance of reducing physical workload and environment and establishing a structure for nursing techniques in psychiatric dementia wards to improve the mental health of PDNs.

Membrane association of the PTEN tumor suppressor: Neutron scattering and MD simulations reveal the structure of protein-membranes complexes

PubMed Central

Nanda, Hirsh; Heinrich, Frank; Lösche, Mathias

2014-01-01

Neutron reflection (NR) from planar interfaces is an emerging technology that provides unique and otherwise inaccessible structural information on disordered molecular systems such as membrane proteins associated with fluid bilayers, thus addressing one of the remaining challenges of structural biology. Although intrinsically a low-resolution technique, using structural information from crystallography or NMR allows the construction of NR models that describe the architecture of protein-membrane complexes at high resolution. In addition, a combination of these methods with molecular dynamics (MD) simulations has the potential to reveal the dynamics of protein interactions with the bilayer in atomistic detail. We review recent advances in this area by discussing the application of these techniques to the complex formed by the PTEN phosphatase with the plasma membrane. These studies provide insights in the cellular regulation of PTEN, its interaction with PI(4,5)P2 in the inner plasma membrane and the pathway by which its substrate, PI(3,4,5)P3, accesses the PTEN catalytic site. PMID:25461777

Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV

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

Zheng, Yi; Han, Gye Won; Abagyan, Ruben

CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc. Molecular modeling indicated that HIV gp120 mimicked the chemokinemore » interaction with CCR5, providing an explanation for the ability of CCR5 to recognize diverse ligands and gp120 variants. Our findings reveal that structural plasticity facilitates receptor-chemokine specificity and enables exploitation by HIV, and provide insight into the design of small molecule and protein inhibitors for HIV and other CCR5-mediated diseases.« less

The complex and specific pMHC interactions with diverse HIV-1 TCR clonotypes reveal a structural basis for alterations in CTL function

NASA Astrophysics Data System (ADS)

Xia, Zhen; Chen, Huabiao; Kang, Seung-Gu; Huynh, Tien; Fang, Justin W.; Lamothe, Pedro A.; Walker, Bruce D.; Zhou, Ruhong

2014-02-01

Immune control of viral infections is modulated by diverse T cell receptor (TCR) clonotypes engaging peptide-MHC class I complexes on infected cells, but the relationship between TCR structure and antiviral function is unclear. Here we apply in silico molecular modeling with in vivo mutagenesis studies to investigate TCR-pMHC interactions from multiple CTL clonotypes specific for a well-defined HIV-1 epitope. Our molecular dynamics simulations of viral peptide-HLA-TCR complexes, based on two independent co-crystal structure templates, reveal that effective and ineffective clonotypes bind to the terminal portions of the peptide-MHC through similar salt bridges, but their hydrophobic side-chain packings can be very different, which accounts for the major part of the differences among these clonotypes. Non-specific hydrogen bonding to viral peptide also accommodates greater epitope variants. Furthermore, free energy perturbation calculations for point mutations on the viral peptide KK10 show excellent agreement with in vivo mutagenesis assays, with new predictions confirmed by additional experiments. These findings indicate a direct structural basis for heterogeneous CTL antiviral function.

Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant

NASA Astrophysics Data System (ADS)

Yuchi, Zhiguang; Yuen, Siobhan M. Wong King; Lau, Kelvin; Underhill, Ainsley Q.; Cornea, Razvan L.; Fessenden, James D.; van Petegem, Filip

2015-08-01

Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca2+-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

NASA Technical Reports Server (NTRS)

Hadley, Jill A.; Hall, Joseph C.; O'Brien, Ami; Ball, Richard

1992-01-01

The effect of simulated microgravity on the structure and function of the testis and epididymis cells was investigated in rats subjected to 7 days of tail suspension. Results of a histological examination revealed presence of disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. In addition, decreases in the content of testis protein and in testosterone levels in the testis, the interstitial fluid, and the epididymis were observed.

New features in Saturn's atmosphere revealed by high-resolution thermal infrared images

NASA Technical Reports Server (NTRS)

Gezari, D. Y.; Mumma, M. J.; Espenak, F.; Deming, D.; Bjoraker, G.; Woods, L.; Folz, W.

1989-01-01

Observations of the stratospheric IR emission structure on Saturn are presented. The high-spatial-resolution global images show a variety of new features, including a narrow equatorial belt of enhanced emission at 7.8 micron, a prominent symmetrical north polar hotspot at all three wavelengths, and a midlatitude structure which is asymmetrically brightened at the east limb. The results confirm the polar brightening and reversal in position predicted by recent models for seasonal thermal variations of Saturn's stratosphere.

Modelling of Surfaces. Part 2: Metallic Alloy Surfaces Using the BFS Method

NASA Technical Reports Server (NTRS)

Bozzolo, Guillermo; Ferrante, John; Kobistek, Robert J.

1994-01-01

Using BFS, a new semiempirical method for alloys, we study the surface structure of fcc ordered binary alloys. We concentrate on the calculation of surface energies and surface relaxations for the L1(sub 0) and L1(sub 2) ordered structures. Different terminations of the low-index faces are studied. Also, we present results for the interlayer relaxations for planes close to the surface, revealing different relaxations for atoms of different species producing a rippled surface layer.

Bringing diffuse X-ray scattering into focus

DOE PAGES

Wall, Michael E.; Wolff, Alexander M.; Fraser, James S.

2018-02-16

X-ray crystallography is experiencing a renaissance as a method for probing the protein conformational ensemble. The inherent limitations of Bragg analysis, however, which only reveals the mean structure, have given way to a surge in interest in diffuse scattering, which is caused by structure variations. Diffuse scattering is present in all macromolecular crystallography experiments. Recent studies are shedding light on the origins of diffuse scattering in protein crystallography, and provide clues for leveraging diffuse scattering to model protein motions with atomic detail.

Bringing diffuse X-ray scattering into focus

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

Wall, Michael E.; Wolff, Alexander M.; Fraser, James S.

X-ray crystallography is experiencing a renaissance as a method for probing the protein conformational ensemble. The inherent limitations of Bragg analysis, however, which only reveals the mean structure, have given way to a surge in interest in diffuse scattering, which is caused by structure variations. Diffuse scattering is present in all macromolecular crystallography experiments. Recent studies are shedding light on the origins of diffuse scattering in protein crystallography, and provide clues for leveraging diffuse scattering to model protein motions with atomic detail.

Structural characterization and viscoelastic constitutive modeling of skin.

PubMed

Sherman, Vincent R; Tang, Yizhe; Zhao, Shiteng; Yang, Wen; Meyers, Marc A

2017-04-15

A fascinating material, skin has a tensile response which exhibits an extended toe region of minimal stress up to nominal strains that, in some species, exceed 1, followed by significant stiffening until a roughly linear region. The large toe region has been attributed to its unique structure, consisting of a network of curved collagen fibers. Investigation of the structure of rabbit skin reveals that it consists of layers of wavy fibers, each one with a characteristic orientation. Additionally, the existence of two preferred layer orientations is suggested based on the results of small angle X-ray scattering. These observations are used to construct a viscoelastic model consisting of collagen in two orientations, which leads to an in-plane anisotropic response. The structure-based model presented incorporates the elastic straightening and stretching of fibrils, their rotation towards the tensile axis, and the viscous effects which occur in the matrix of the skin due to interfibrillar and interlamellar sliding. The model is shown to effectively capture key features which dictate the mechanical response of skin. Examination by transmission and scanning electron microscopy of rabbit dermis enabled the identification of the key elements in its structure. The organization of collagen fibrils into flat fibers was identified and incorporated into a constitutive model that reproduces the mechanical response of skin. This enhanced quantitative predictive capability can be used in the design of synthetic skin and skin-like structures. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Splitting of the neutral mechanical plane depends on the length of the multi-layer structure of flexible electronics.

PubMed

Li, Shuang; Su, Yewang; Li, Rui

2016-06-01

Multi-layer structures with soft (compliant) interlayers have been widely used in flexible electronics and photonics as an effective design for reducing interactions among the hard (stiff) layers and thus avoiding the premature failure of an entire device. The analytic model for bending of such a structure has not been well established due to its complex mechanical behaviour. Here, we present a rational analytic model, without any parameter fitting, to study the bending of a multi-layer structure on a cylinder, which is often regarded as an important approach to mechanical reliability testing of flexible electronics and photonics. For the first time, our model quantitatively reveals that, as the key for accurate strain control, the splitting of the neutral mechanical plane depends not only on the relative thickness of the middle layer, but also on the length-to-thickness ratio of the multi-layer structure. The model accurately captures the key quantities, including the axial strains in the top and bottom layers, the shear strain in the middle layer and the locations of the neutral mechanical planes of the top and bottom layers. The effects of the length of the multi-layer and the thickness of the middle layer are elaborated. This work is very useful for the design of multi-layer structure-based flexible electronics and photonics.

Splitting of the neutral mechanical plane depends on the length of the multi-layer structure of flexible electronics

PubMed Central

Li, Shuang; Li, Rui

2016-01-01

Multi-layer structures with soft (compliant) interlayers have been widely used in flexible electronics and photonics as an effective design for reducing interactions among the hard (stiff) layers and thus avoiding the premature failure of an entire device. The analytic model for bending of such a structure has not been well established due to its complex mechanical behaviour. Here, we present a rational analytic model, without any parameter fitting, to study the bending of a multi-layer structure on a cylinder, which is often regarded as an important approach to mechanical reliability testing of flexible electronics and photonics. For the first time, our model quantitatively reveals that, as the key for accurate strain control, the splitting of the neutral mechanical plane depends not only on the relative thickness of the middle layer, but also on the length-to-thickness ratio of the multi-layer structure. The model accurately captures the key quantities, including the axial strains in the top and bottom layers, the shear strain in the middle layer and the locations of the neutral mechanical planes of the top and bottom layers. The effects of the length of the multi-layer and the thickness of the middle layer are elaborated. This work is very useful for the design of multi-layer structure-based flexible electronics and photonics. PMID:27436977

Modeling of the axon membrane skeleton structure and implications for its mechanical properties

PubMed Central

Tzingounis, Anastasios V.

2017-01-01

Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM) to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young’s modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav), which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration. PMID:28241082

Modeling of the axon membrane skeleton structure and implications for its mechanical properties.

PubMed

Zhang, Yihao; Abiraman, Krithika; Li, He; Pierce, David M; Tzingounis, Anastasios V; Lykotrafitis, George

2017-02-01

Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM) to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy. Our proposed computational model accurately simulates the median value of the Young's modulus of the axon plasma membrane determined by atomic force microscopy. It also predicts that because the spectrin filaments are under entropic tension, the thermal random motion of the voltage-gated sodium channels (Nav), which are bound to ankyrin particles, a critical axonal protein, is reduced compared to the thermal motion when spectrin filaments are held at equilibrium. Lastly, our model predicts that because spectrin filaments are under tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disruption of the membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial under-tension configuration.

Molecular Phylogeny and Predicted 3D Structure of Plant beta-D-N-Acetylhexosaminidase

PubMed Central

Hossain, Md. Anowar

2014-01-01

beta-D-N-Acetylhexosaminidase, a family 20 glycosyl hydrolase, catalyzes the removal of β-1,4-linked N-acetylhexosamine residues from oligosaccharides and their conjugates. We constructed phylogenetic tree of β-hexosaminidases to analyze the evolutionary history and predicted functions of plant hexosaminidases. Phylogenetic analysis reveals the complex history of evolution of plant β-hexosaminidase that can be described by gene duplication events. The 3D structure of tomato β-hexosaminidase (β-Hex-Sl) was predicted by homology modeling using 1now as a template. Structural conformity studies of the best fit model showed that more than 98% of the residues lie inside the favoured and allowed regions where only 0.9% lie in the unfavourable region. Predicted 3D structure contains 531 amino acids residues with glycosyl hydrolase20b domain-I and glycosyl hydrolase20 superfamily domain-II including the (β/α)8 barrel in the central part. The α and β contents of the modeled structure were found to be 33.3% and 12.2%, respectively. Eleven amino acids were found to be involved in ligand-binding site; Asp(330) and Glu(331) could play important roles in enzyme-catalyzed reactions. The predicted model provides a structural framework that can act as a guide to develop a hypothesis for β-Hex-Sl mutagenesis experiments for exploring the functions of this class of enzymes in plant kingdom. PMID:25165734

Quantitative structure-activity relationship (QSAR) for insecticides: development of predictive in vivo insecticide activity models.

PubMed

Naik, P K; Singh, T; Singh, H

2009-07-01

Quantitative structure-activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r(2) values of 0.949 and 0.838 as well as [image omitted] values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD(50) values for the test set data with r(2) of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.