Relationships between structural complexity, coral traits, and reef fish assemblages

NASA Astrophysics Data System (ADS)

Darling, Emily S.; Graham, Nicholas A. J.; Januchowski-Hartley, Fraser A.; Nash, Kirsty L.; Pratchett, Morgan S.; Wilson, Shaun K.

2017-06-01

With the ongoing loss of coral cover and the associated flattening of reef architecture, understanding the links between coral habitat and reef fishes is of critical importance. Here, we investigate whether considering coral traits and functional diversity provides new insights into the relationship between structural complexity and reef fish communities, and whether coral traits and community composition can predict structural complexity. Across 157 sites in Seychelles, Maldives, the Chagos Archipelago, and Australia's Great Barrier Reef, we find that structural complexity and reef zone are the strongest and most consistent predictors of reef fish abundance, biomass, species richness, and trophic structure. However, coral traits, diversity, and life histories provided additional predictive power for models of reef fish assemblages, and were key drivers of structural complexity. Our findings highlight that reef complexity relies on living corals—with different traits and life histories—continuing to build carbonate skeletons, and that these nuanced relationships between coral assemblages and habitat complexity can affect the structure of reef fish assemblages. Seascape-level estimates of structural complexity are rapid and cost effective with important implications for the structure and function of fish assemblages, and should be incorporated into monitoring programs.

Free draining base materials properties : final report.

DOT National Transportation Integrated Search

1992-03-01

The importance of providing a positive drainage system and removing free water from pavement structures has long been recognized. Inadequate drainage of the pavement structures has been identified as one of the primary causes of pavement distress. In...

Network of TAMCNS: Identifying Influence Regions Within the GCSS-MC Database

DTIC Science & Technology

2017-06-01

relationships between objects and provides tools to quantitatively determine objects whose influence impacts other objects or the system as a whole. This... methodology identifies the most important TAMCN and provides a list of TAMCNs in order of importance. We also analyze the community and core structure of...relationships between objects and provides tools to quantitatively determine objects whose influence impacts other objects or the system as a whole. This

CCProf: exploring conformational change profile of proteins

PubMed Central

Chang, Che-Wei; Chou, Chai-Wei; Chang, Darby Tien-Hao

2016-01-01

In many biological processes, proteins have important interactions with various molecules such as proteins, ions or ligands. Many proteins undergo conformational changes upon these interactions, where regions with large conformational changes are critical to the interactions. This work presents the CCProf platform, which provides conformational changes of entire proteins, named conformational change profile (CCP) in the context. CCProf aims to be a platform where users can study potential causes of novel conformational changes. It provides 10 biological features, including conformational change, potential binding target site, secondary structure, conservation, disorder propensity, hydropathy propensity, sequence domain, structural domain, phosphorylation site and catalytic site. All these information are integrated into a well-aligned view, so that researchers can capture important relevance between different biological features visually. The CCProf contains 986 187 protein structure pairs for 3123 proteins. In addition, CCProf provides a 3D view in which users can see the protein structures before and after conformational changes as well as binding targets that induce conformational changes. All information (e.g. CCP, binding targets and protein structures) shown in CCProf, including intermediate data are available for download to expedite further analyses. Database URL: http://zoro.ee.ncku.edu.tw/ccprof/ PMID:27016699

Exploring the Subtleties of Inverse Probability Weighting and Marginal Structural Models.

PubMed

Breskin, Alexander; Cole, Stephen R; Westreich, Daniel

2018-05-01

Since being introduced to epidemiology in 2000, marginal structural models have become a commonly used method for causal inference in a wide range of epidemiologic settings. In this brief report, we aim to explore three subtleties of marginal structural models. First, we distinguish marginal structural models from the inverse probability weighting estimator, and we emphasize that marginal structural models are not only for longitudinal exposures. Second, we explore the meaning of the word "marginal" in "marginal structural model." Finally, we show that the specification of a marginal structural model can have important implications for the interpretation of its parameters. Each of these concepts have important implications for the use and understanding of marginal structural models, and thus providing detailed explanations of them may lead to better practices for the field of epidemiology.

Clinical perspective: creating an effective practice peer review process-a primer.

PubMed

Gandhi, Manisha; Louis, Frances S; Wilson, Shae H; Clark, Steven L

2017-03-01

Peer review serves as an important adjunct to other hospital quality and safety programs. Despite its importance, the available literature contains virtually no guidance regarding the structure and function of effective peer review committees. This Clinical Perspective provides a summary of the purposes, structure, and functioning of effective peer review committees. We also discuss important legal considerations that are a necessary component of such processes. This discussion includes useful templates for case selection and review. Proper committee structure, membership, work flow, and leadership as well as close cooperation with the hospital medical executive committee and legal representatives are essential to any effective peer review process. A thoughtful, fair, systematic, and organized approach to creating a peer review process will lead to confidence in the committee by providers, hospital leadership, and patients. If properly constructed, such committees may also assist in monitoring and enforcing compliance with departmental protocols, thus reducing harm and promoting high-quality practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Multilevel Multi-Informant Structure of the Authoritative School Climate Survey

ERIC Educational Resources Information Center

Konold, Timothy; Cornell, Dewey; Huang, Francis; Meyer, Patrick; Lacey, Anna; Nekvasil, Erin; Heilbrun, Anna; Shukla, Kathan

2014-01-01

The Authoritative School Climate Survey was designed to provide schools with a brief assessment of 2 key characteristics of school climate--disciplinary structure and student support--that are hypothesized to influence 2 important school climate outcomes--student engagement and prevalence of teasing and bullying in school. The factor structure of…

Popular or Unpopular? Therapists' Use of Structured Interviews and Their Estimation of Patient Acceptance

ERIC Educational Resources Information Center

Bruchmuller, Katrin; Margraf, Jurgen; Suppiger, Andrea; Schneider, Silvia

2011-01-01

An accurate diagnosis is an important precondition for effective psychotherapeutic treatment. The use of structured interviews provides the gold standard for reliable diagnosis. Suppiger et al. (2009) showed that structured interviews have a high acceptance among patients. On a scale from 0 ("not at all satisfied") to 100 ("totally…

Differential stemflow yield from European beech saplings: the role and respective importance of individual canopy structure metrics

NASA Astrophysics Data System (ADS)

Levia, Delphis; Michalzik, Beate

2013-04-01

Stemflow yield from individual trees varies as a function of both meteorological conditions and canopy structure. The importance and differential effects of various metrics of canopy structure in relation to stemflow yield is inadequately understood and the subject of debate among forest hydrologists. It is possible to evaluate the role and respective importance of individual canopy structure metrics by holding meteorological conditions constant. Twelve isolated experimental European beech (Fagus sylvatica L.) saplings in Jena, Germany were exposed to identical meteorological conditions to examine the effects of canopy structure on stemflow production during the 2012 growing season. The canopy structure metrics being evaluated include: trunk diameter, trunk lean, tree height, projected crown area, branch inclination angle, branch count, and biomass (foliar and woody). Principal components analysis and multiple regression are utilized to determine the relative importance of different canopy structure metrics on stemflow yield. Experimental results will provide insight as to which metrics of canopy structure most strongly govern stemflow production. Ultimately, with a more thorough understanding of the unique contributions of various canopy structural metrics to stemflow yield, a useful conceptual guide of stemflow generation can be formulated on the basis of canopy structure for management purposes. Sponsor note: This research was funded by the Alexander von Humboldt Foundation.

Factors for improved fish passage waterway construction.

DOT National Transportation Integrated Search

2011-06-01

Streambeds are important fish passageways in Oregon; they provide for the necessary habitats and spawning cycles of a healthy fish population. Oregon state law requires that hydraulic structures located in water properly provide fish passage. Increas...

Lake shoreline and littoral physical habitat structure in a national lakes assessment

EPA Science Inventory

Riparian and littoral habitat components are important to lake biological assemblages, providing refuge from predation, living and egg-laying substrates, and food. Shoreline structure also affects nutrient cycling, littoral production, and sedimentation rates. Measures of ripar...

Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

MedlinePlus

... they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of this protein's most important jobs is to provide structure, flexibility, and stability to these cell structures. Titin ...

MCTBI: a web server for predicting metal ion effects in RNA structures.

PubMed

Sun, Li-Zhen; Zhang, Jing-Xiang; Chen, Shi-Jie

2017-08-01

Metal ions play critical roles in RNA structure and function. However, web servers and software packages for predicting ion effects in RNA structures are notably scarce. Furthermore, the existing web servers and software packages mainly neglect ion correlation and fluctuation effects, which are potentially important for RNAs. We here report a new web server, the MCTBI server (http://rna.physics.missouri.edu/MCTBI), for the prediction of ion effects for RNA structures. This server is based on the recently developed MCTBI, a model that can account for ion correlation and fluctuation effects for nucleic acid structures and can provide improved predictions for the effects of metal ions, especially for multivalent ions such as Mg 2+ effects, as shown by extensive theory-experiment test results. The MCTBI web server predicts metal ion binding fractions, the most probable bound ion distribution, the electrostatic free energy of the system, and the free energy components. The results provide mechanistic insights into the role of metal ions in RNA structure formation and folding stability, which is important for understanding RNA functions and the rational design of RNA structures. © 2017 Sun et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Designing drugs on the internet? Free web tools and services supporting medicinal chemistry.

PubMed

Ertl, Peter; Jelfs, Stephen

2007-01-01

The drug discovery process is supported by a multitude of freely available tools on the Internet. This paper summarizes some of the databases and tools that are of particular interest to medicinal chemistry. These include numerous data collections that provide access to valuable chemical data resources, allowing complex queries of compound structures, associated physicochemical properties and biological activities to be performed and, in many cases, providing links to commercial chemical suppliers. Further applications are available for searching protein-ligand complexes and identifying important binding interactions that occur. This is particularly useful for understanding the molecular recognition of ligands in the lead optimization process. The Internet also provides access to databases detailing metabolic pathways and transformations which can provide insight into disease mechanism, identify new targets entities or the potential off-target effects of a drug candidate. Furthermore, sophisticated online cheminformatics tools are available for processing chemical structures, predicting properties, and generating 2D or 3D structure representations--often required prior to more advanced analyses. The Internet provides a wealth of valuable resources that, if fully exploited, can greatly benefit the drug discovery community. In this paper, we provide an overview of some of the more important of these and, in particular, the freely accessible resources that are currently available.

Characterizing ceramics and the interfacial adhesion to resin: I - The relationship of microstructure, composition, properties and fractography.

PubMed

Della Bona, Alvaro

2005-03-01

The appeal of ceramics as structural dental materials is based on their light weight, high hardness values, chemical inertness, and anticipated unique tribological characteristics. A major goal of current ceramic research and development is to produce tough, strong ceramics that can provide reliable performance in dental applications. Quantifying microstructural parameters is important to develop structure/property relationships. Quantitative microstructural analysis provides an association among the constitution, physical properties, and structural characteristics of materials. Structural reliability of dental ceramics is a major factor in the clinical success of ceramic restorations. Complex stress distributions are present in most practical conditions and strength data alone cannot be directly extrapolated to predict structural performance.

G Protein-Coupled Receptor Rhodopsin: A Prospectus

PubMed Central

Filipek, Sławomir; Stenkamp, Ronald E.; Teller, David C.; Palczewski, Krzysztof

2006-01-01

Rhodopsin is a retinal photoreceptor protein of bipartite structure consisting of the transmembrane protein opsin and a light-sensitive chromophore 11-cis-retinal, linked to opsin via a protonated Schiff base. Studies on rhodopsin have unveiled many structural and functional features that are common to a large and pharmacologically important group of proteins from the G protein-coupled receptor (GPCR) superfamily, of which rhodopsin is the best-studied member. In this work, we focus on structural features of rhodopsin as revealed by many biochemical and structural investigations. In particular, the high-resolution structure of bovine rhodopsin provides a template for understanding how GPCRs work. We describe the sensitivity and complexity of rhodopsin that lead to its important role in vision. PMID:12471166

Structuring Homeland Security

DTIC Science & Technology

2002-04-09

20 AIRPORT SECURITY .............................................................................................. 20...using an existing command and control structure. Since September 11, 2001 airport security has been of heightened importance to the American public...In order to use Reserves to provide airport security the airports themselves should be made federal property. This would allow greater flexibility for

Theme-Oriented Group Therapy.

ERIC Educational Resources Information Center

Richards, R. Lynn; And Others

1990-01-01

Describes the three major influences on theme-oriented groups: theme-centered interactional, structured, and behavioral groups. Provides a comparison of the composition and structure of theme groups during the current decade. Summarizes the general principles thought to be important in the construction and development of theme-oriented groups.…

An alternative potentiometric method for determining chloride content in concrete samples from reinforced-concrete bridges.

DOT National Transportation Integrated Search

2002-01-01

Analysis of chloride contents in ground concrete samples collected from reinforced concrete bridges and other structures exposed to deicing salts or seawater has become an important part of the inspection for such structures. Such an analysis provide...

Parametric imaging of collagen structural changes in human osteoarthritic cartilage using optical polarization tractography

NASA Astrophysics Data System (ADS)

Ravanfar, Mohammadreza; Pfeiffer, Ferris M.; Bozynski, Chantelle C.; Wang, Yuanbo; Yao, Gang

2017-12-01

Collagen degeneration is an important pathological feature of osteoarthritis. The purpose of this study is to investigate whether the polarization-sensitive optical coherence tomography (PSOCT)-based optical polarization tractography (OPT) can be useful in imaging collagen structural changes in human osteoarthritic cartilage samples. OPT eliminated the banding artifacts in conventional PSOCT by calculating the depth-resolved local birefringence and fiber orientation. A close comparison between OPT and PSOCT showed that OPT provided improved visualization and characterization of the zonal structure in human cartilage. Experimental results obtained in this study also underlined the importance of knowing the collagen fiber orientation in conventional polarized light microscopy assessment. In addition, parametric OPT imaging was achieved by quantifying the surface roughness, birefringence, and fiber dispersion in the superficial zone of the cartilage. These quantitative parametric images provided complementary information on the structural changes in cartilage, which can be useful for a comprehensive evaluation of collagen damage in osteoarthritic cartilage.

Probabilistic Structural Analysis Methods (PSAM) for select space propulsion system structural components

NASA Technical Reports Server (NTRS)

Cruse, T. A.

1987-01-01

The objective is the development of several modular structural analysis packages capable of predicting the probabilistic response distribution for key structural variables such as maximum stress, natural frequencies, transient response, etc. The structural analysis packages are to include stochastic modeling of loads, material properties, geometry (tolerances), and boundary conditions. The solution is to be in terms of the cumulative probability of exceedance distribution (CDF) and confidence bounds. Two methods of probability modeling are to be included as well as three types of structural models - probabilistic finite-element method (PFEM); probabilistic approximate analysis methods (PAAM); and probabilistic boundary element methods (PBEM). The purpose in doing probabilistic structural analysis is to provide the designer with a more realistic ability to assess the importance of uncertainty in the response of a high performance structure. Probabilistic Structural Analysis Method (PSAM) tools will estimate structural safety and reliability, while providing the engineer with information on the confidence that should be given to the predicted behavior. Perhaps most critically, the PSAM results will directly provide information on the sensitivity of the design response to those variables which are seen to be uncertain.

Probabilistic Structural Analysis Methods for select space propulsion system structural components (PSAM)

NASA Technical Reports Server (NTRS)

Cruse, T. A.; Burnside, O. H.; Wu, Y.-T.; Polch, E. Z.; Dias, J. B.

1988-01-01

The objective is the development of several modular structural analysis packages capable of predicting the probabilistic response distribution for key structural variables such as maximum stress, natural frequencies, transient response, etc. The structural analysis packages are to include stochastic modeling of loads, material properties, geometry (tolerances), and boundary conditions. The solution is to be in terms of the cumulative probability of exceedance distribution (CDF) and confidence bounds. Two methods of probability modeling are to be included as well as three types of structural models - probabilistic finite-element method (PFEM); probabilistic approximate analysis methods (PAAM); and probabilistic boundary element methods (PBEM). The purpose in doing probabilistic structural analysis is to provide the designer with a more realistic ability to assess the importance of uncertainty in the response of a high performance structure. Probabilistic Structural Analysis Method (PSAM) tools will estimate structural safety and reliability, while providing the engineer with information on the confidence that should be given to the predicted behavior. Perhaps most critically, the PSAM results will directly provide information on the sensitivity of the design response to those variables which are seen to be uncertain.

The what, where, how and why of gene ontology—a primer for bioinformaticians

PubMed Central

du Plessis, Louis; Škunca, Nives

2011-01-01

With high-throughput technologies providing vast amounts of data, it has become more important to provide systematic, quality annotations. The Gene Ontology (GO) project is the largest resource for cataloguing gene function. Nonetheless, its use is not yet ubiquitous and is still fraught with pitfalls. In this review, we provide a short primer to the GO for bioinformaticians. We summarize important aspects of the structure of the ontology, describe sources and types of functional annotations, survey measures of GO annotation similarity, review typical uses of GO and discuss other important considerations pertaining to the use of GO in bioinformatics applications. PMID:21330331

[Design of Complex Cavity Structure in Air Route System of Automated Peritoneal Dialysis Machine].

PubMed

Quan, Xiaoliang

2017-07-30

This paper introduced problems about Automated Peritoneal Dialysis machine(APD) that the lack of technical issues such as the structural design of the complex cavities. To study the flow characteristics of this special structure, the application of ANSYS CFX software is used with k-ε turbulence model as the theoretical basis of fluid mechanics. The numerical simulation of flow field simulation result in the internal model can be gotten after the complex structure model is imported into ANSYS CFX module. Then, it will present the distribution of complex cavities inside the flow field and the flow characteristics parameter, which will provide an important reference design for APD design.

Quantum chemical studies of estrogenic compounds

USDA-ARS?s Scientific Manuscript database

Quantum chemical methods are potent tools to provide information on the chemical structure and electronic properties of organic molecules. Modern computational chemistry methods have provided a great deal of insight into the binding of estrogenic compounds to estrogenic receptors (ER), an important ...

The spectroscopic chemical and photophysical properties of Martian soils and their analogs

NASA Technical Reports Server (NTRS)

Coyne, Lelia M.

1987-01-01

The program of research outlined should advance significantly the understanding of the spectral signal of montmorillonites in general and the variations produced in it by structural and surface ferric and ferrous iron and interlayer water as a function of several environmental conditions that are different between Earth and Mars. In addition, an extensive data base was collected providing spectral characterization of several features (iron, both surface and structural, OH-groups, both structural and from adsorbed water and O(-) centers) that are known, or thought to be, influential in directing the surface activity of these important materials. With this data base with which to assess the results of the Viking labeled release simulation studies, it should be possible to gain important insights into the mechanisms of surface reactivity for this important chemical reaction. The results to be gained from these studies will provide a significant body of ground base truth from which to assess: the presence of smectite clays on Mars; the mineralogical form in which the Martian iron is bound; establish upper limits on the present surface water content of Martian soils; perhaps provide insights on the Martian surface radiation history; and to make strong predictions about the nature of surface chemistry on Mars, if iron-bearing clays are a significant component of the surface mineralogical assemblage.

Peroxisome protein import: a complex journey.

PubMed

Baker, Alison; Lanyon-Hogg, Thomas; Warriner, Stuart L

2016-06-15

The import of proteins into peroxisomes possesses many unusual features such as the ability to import folded proteins, and a surprising diversity of targeting signals with differing affinities that can be recognized by the same receptor. As understanding of the structure and function of many components of the protein import machinery has grown, an increasingly complex network of factors affecting each step of the import pathway has emerged. Structural studies have revealed the presence of additional interactions between cargo proteins and the PEX5 receptor that affect import potential, with a subtle network of cargo-induced conformational changes in PEX5 being involved in the import process. Biochemical studies have also indicated an interdependence of receptor-cargo import with release of unloaded receptor from the peroxisome. Here, we provide an update on recent literature concerning mechanisms of protein import into peroxisomes. © 2016 The Author(s).

Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach

NASA Astrophysics Data System (ADS)

Neves, Marco A. C.; Simões, Sérgio; Sá e Melo, M. Luisa

2010-12-01

CXCR4 is a G-protein coupled receptor for CXCL12 that plays an important role in human immunodeficiency virus infection, cancer growth and metastasization, immune cell trafficking and WHIM syndrome. In the absence of an X-ray crystal structure, theoretical modeling of the CXCR4 receptor remains an important tool for structure-function analysis and to guide the discovery of new antagonists with potential clinical use. In this study, the combination of experimental data and molecular modeling approaches allowed the development of optimized ligand-receptor models useful for elucidation of the molecular determinants of small molecule binding and functional antagonism. The ligand-guided homology modeling approach used in this study explicitly re-shaped the CXCR4 binding pocket in order to improve discrimination between known CXCR4 antagonists and random decoys. Refinement based on multiple test-sets with small compounds from single chemotypes provided the best early enrichment performance. These results provide an important tool for structure-based drug design and virtual ligand screening of new CXCR4 antagonists.

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

PubMed Central

2017-01-01

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

Bioinspired photonic structures by the reflector layer of firefly lantern for highly efficient chemiluminescence

PubMed Central

Chen, Linfeng; Shi, Xiaodi; Li, Mingzhu; Hu, Junping; Sun, Shufeng; Su, Bin; Wen, Yongqiang; Han, Dong; Jiang, Lei; Song, Yanlin

2015-01-01

Fireflies have drawn considerable attention for thousands of years due to their highly efficient bioluminescence, which is important for fundamental research and photonic applications. However, there are few reports on the reflector layer (RL) of firefly lantern, which contributes to the bright luminescence. Here we presented the detailed microstructure of the RL consisting of random hollow granules, which had high reflectance in the range from 450 nm to 800 nm. Inspired by the firefly lantern, artificial films with high reflectance in the visible region were fabricated using hollow silica microparticles mimicking the structure of the RL. Additionally, the bioinspired structures provided an efficient RL for the chemiluminescence system and could substantially enhance the initial chemiluminescence intensity. The work not only provides new insight into the bright bioluminescence of fireflies, but also is importance for the design of photonic materials for theranostics, detection, and imaging. PMID:26264643

Challenges and opportunities for tissue-engineering polarized epithelium.

PubMed

Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

2014-02-01

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

Single-Molecule FRET Spectroscopy and the Polymer Physics of Unfolded and Intrinsically Disordered Proteins.

PubMed

Schuler, Benjamin; Soranno, Andrea; Hofmann, Hagen; Nettels, Daniel

2016-07-05

The properties of unfolded proteins have long been of interest because of their importance to the protein folding process. Recently, the surprising prevalence of unstructured regions or entirely disordered proteins under physiological conditions has led to the realization that such intrinsically disordered proteins can be functional even in the absence of a folded structure. However, owing to their broad conformational distributions, many of the properties of unstructured proteins are difficult to describe with the established concepts of structural biology. We have thus seen a reemergence of polymer physics as a versatile framework for understanding their structure and dynamics. An important driving force for these developments has been single-molecule spectroscopy, as it allows structural heterogeneity, intramolecular distance distributions, and dynamics to be quantified over a wide range of timescales and solution conditions. Polymer concepts provide an important basis for relating the physical properties of unstructured proteins to folding and function.

[Criteria of quality of structure in rehabilitation units with inpatient treatment].

PubMed

Klein, K; Farin, E; Jäckel, W H; Blatt, O; Schliehe, F

2004-04-01

The structure of a rehabilitation unit is an important feature of the quality of care. Adequate and qualitatively good structures provide the basis for appropriate therapy offers and treatment and eventually, a better health for rehabilitants. The quality of structures is generally recorded without any evaluation of the aspects in particular. The definition of standards is the basis for such an evaluation. The project presented is aimed at the definition of relevant structural standards for rehab units with inpatient treatment for musculoskeletal, cardiac, neurological, gastroenterological, oncological, pneumological and dermatological diseases. Here, the distinction between basal criteria which have to be fulfilled by every rehab unit with inpatient treatment and criteria important for a well-aimed assignment of patients with specific needs ("assignment criteria") should be made. Apart from the documentation of structural attributes, the structural quality of a rehab unit can be described individually as well as in comparison with other units. Relevant structural criteria were defined in expert meetings by means of a modified Delphi-technique with five inquiries. Overall, 199 "basal criteria" and "assignment criteria" were defined. All criteria can be assigned to the two domains general structural characteristics (general characteristics and equipment of rooms; medical/technical equipment; therapy, education, care; staff) and process-related structures (conceptual frames; internal quality management; internal communication and personnel development). The structural standards are applicable to units for musculoskeletal, cardiac, neurological, oncological, gastroenterological, dermatological and pneumological rehabilitation financed by the two main providers of rehabilitation, the statutory pension insurance scheme and the statutory health insurance scheme for all other five indications. The definition of structural standards agreed by experts in a formal consensus process, provides comprehensive and concrete requirements for German rehab units with inpatient medical rehabilitation. If the two main providers of rehabilitation both use the standards this can be regarded as a hallmark on the path to a unitary programme for quality management. The results enable units to analyse their weak points not just on an individual basis but allow also for a comparison between units, along with contributing to optimizing the structural quality of rehab units.

Long-Term Memory and Learning

ERIC Educational Resources Information Center

Crossland, John

2011-01-01

The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

A primer on polymer nomenclature: Structure-based, sourced-based and trade names

USDA-ARS?s Scientific Manuscript database

Polymer nomenclature is important because it is part of the language of polymer science and is needed for polymer identification, reference, and documentation. A primer on polymer nomenclature is provided herein for people new to the field or for instructional use. Both structure-based and source-...

Energetic and flexibility properties captured by long molecular dynamics simulations of a membrane-embedded pMHCII-TCR complex.

PubMed

Bello, Martiniano; Correa-Basurto, José

2016-04-01

Although crystallographic data have provided important molecular insight into the interactions in the pMHC-TCR complex, the inherent features of this structural approach cause it to only provide a static picture of the interactions. While unbiased molecular dynamics simulations (UMDSs) have provided important information about the dynamic structural behavior of the pMHC-TCR complex, most of them have modeled the pMHC-TCR complex as soluble, when in physiological conditions, this complex is membrane bound; therefore, following this latter UMDS protocol might hamper important dynamic results. In this contribution, we performed three independent 300 ns-long UMDSs of the pMHCII-TCR complex anchored in two opposing membranes to explore the structural and energetic properties of the recognition of pMHCII by the TCR. The conformational ensemble generated through UMDSs was subjected to clustering and Cartesian principal component analyses (cPCA) to explore the dynamical behavior of the pMHCII-TCR association. Furthermore, based on the conformational population sampled through UMDSs, the effective binding free energy, per-residue free energy decomposition, and alanine scanning mutations were explored for the native pMHCII-TCR complex, as well as for 12 mutations (p1-p12MHCII-TCR) introduced in the native peptide. Clustering analyses and cPCA provide insight into the rocking motion of the TCR onto pMHCII, together with the presence of new electrostatic interactions not observed through crystallographic methods. Energetic results provide evidence of the main contributors to the pMHC-TCR complex formation as well as the key residues involved in this molecular recognition process.

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

PubMed Central

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

2010-01-01

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

Mixture models for protein structure ensembles.

PubMed

Hirsch, Michael; Habeck, Michael

2008-10-01

Protein structure ensembles provide important insight into the dynamics and function of a protein and contain information that is not captured with a single static structure. However, it is not clear a priori to what extent the variability within an ensemble is caused by internal structural changes. Additional variability results from overall translations and rotations of the molecule. And most experimental data do not provide information to relate the structures to a common reference frame. To report meaningful values of intrinsic dynamics, structural precision, conformational entropy, etc., it is therefore important to disentangle local from global conformational heterogeneity. We consider the task of disentangling local from global heterogeneity as an inference problem. We use probabilistic methods to infer from the protein ensemble missing information on reference frames and stable conformational sub-states. To this end, we model a protein ensemble as a mixture of Gaussian probability distributions of either entire conformations or structural segments. We learn these models from a protein ensemble using the expectation-maximization algorithm. Our first model can be used to find multiple conformers in a structure ensemble. The second model partitions the protein chain into locally stable structural segments or core elements and less structured regions typically found in loops. Both models are simple to implement and contain only a single free parameter: the number of conformers or structural segments. Our models can be used to analyse experimental ensembles, molecular dynamics trajectories and conformational change in proteins. The Python source code for protein ensemble analysis is available from the authors upon request.

Wildlife response to stand structure of deciduous woodlands

Treesearch

Robert A. Hodorff; Carolyn Hull Sieg; Raymond L. Linder

1988-01-01

Deciduous woodlands provide important habitat for wildlife but comprise Fraxinus pennsylvanica) woodlands in northwestern South Dakota. Closed-canopy stands were multilayered communities with dense...

Structural Magnetic Resonance Imaging Markers of Alzheimer's Disease and Its Retranslation to Rodent Models.

PubMed

Kincses, Zsigmond Tamas; Király, András; Veréb, Dániel; Vécsei, László

2015-01-01

The importance of imaging biomarkers has been acknowledged in the diagnosis and in the follow-up of Alzheimer's disease (AD), one of the major causes of dementia. Next to the molecular biomarkers and PET imaging investigations, structural MRI approaches provide important information about the disease progression and about the pathomechanism. Furthermore,a growing body of literature retranslates these imaging biomarkers to various rodent models of the disease. The goal of this review is to provide an overview of the macro- and microstructural imaging biomarkers of AD, concentrating on atrophy measures and diffusion MRI alterations. A survey is also given of the imaging approaches used in rodent models of dementias that can promote drug development.

Modeling the Structure of Composite Supernova Remnants

NASA Astrophysics Data System (ADS)

Slane, Patrick

2015-09-01

The dynamical structure of a composite SNR, along with its broadband emission, provides crucial constraints on the ejecta mass and explosion energy, the properties of the pulsar that powers the associated wind nebula, and the ultimate fate of the particles that it injects. Of particular importance is the effect of asymmetries introduced through spatial variations in the ambient medium density and by rapid motion of the pulsar. Here we propose hydrodynamical and semi-analytical modeling of G21.5-0.9 and G292.0+1.8, SNRs for which deep Chandra observations have provided key input parameters for these models. We will derive ambient conditions and pulsar properties that lead to the observed morphology, broadband emission, and shock conditions in these important composite systems.

Quality Assurance in Breast Health Care and Requirement for Accreditation in Specialized Units

PubMed Central

Güler, Sertaç Ata; Güllüoğlu, Bahadır M.

2014-01-01

Breast health is a subject of increasing importance. The statistical increase in the frequency of breast cancer and the consequent increase in death rate increase the importance of quality of services to be provided for breast health. For these reasons, the minimum standards and optimum quality metrics of breast care provided to the community are determined. The quality parameters for breast care service include the results, the structure and the operation of services. Within this group, the results of breast health services are determined according to clinical results, patient satisfaction and financial condition. The structure of quality services should include interdisciplinary meetings, written standards for specific procedures and the existence of standardized reporting systems. Establishing breast centers that adopt integrated multidisciplinary working principles and their cost-effective maintenance are important in terms of operation of breast health services. The importance of using a “reviewing/auditing” procedure that checks if all of these functions existing in the health system are carried out at the desired level and an “accreditation” system indicating that the working breast units/centers provide minimum quality adequacy in all aspects, is undeniable. Currently, the accreditation system for breast centers is being used in the European Union and the United States for the last 5–10 years. This system is thought to provide standardization in breast care services, and is accepted as one of the important factors that resulted in reduction in mortality associated with breast cancer. PMID:28331658

Quality Assurance in Breast Health Care and Requirement for Accreditation in Specialized Units.

PubMed

Güler, Sertaç Ata; Güllüoğlu, Bahadır M

2014-07-01

Breast health is a subject of increasing importance. The statistical increase in the frequency of breast cancer and the consequent increase in death rate increase the importance of quality of services to be provided for breast health. For these reasons, the minimum standards and optimum quality metrics of breast care provided to the community are determined. The quality parameters for breast care service include the results, the structure and the operation of services. Within this group, the results of breast health services are determined according to clinical results, patient satisfaction and financial condition. The structure of quality services should include interdisciplinary meetings, written standards for specific procedures and the existence of standardized reporting systems. Establishing breast centers that adopt integrated multidisciplinary working principles and their cost-effective maintenance are important in terms of operation of breast health services. The importance of using a "reviewing/auditing" procedure that checks if all of these functions existing in the health system are carried out at the desired level and an "accreditation" system indicating that the working breast units/centers provide minimum quality adequacy in all aspects, is undeniable. Currently, the accreditation system for breast centers is being used in the European Union and the United States for the last 5-10 years. This system is thought to provide standardization in breast care services, and is accepted as one of the important factors that resulted in reduction in mortality associated with breast cancer.

Generation of a Three-Dimensional Kidney Structure from Pluripotent Stem Cells.

PubMed

Yoshimura, Yasuhiro; Taguchi, Atsuhiro; Nishinakamura, Ryuichi

2017-01-01

The kidney is a vital organ that has an important role in the maintenance of homeostasis by fluid volume regulation and waste product excretion. This role cannot be performed without the three-dimensional (3D) structure of the kidney. Therefore, it is important to generate the 3D structure of the kidney when inducing functional kidney tissue or the whole organ from pluripotent stem cells. In this chapter, we describe the detailed methods to induce kidney progenitor cells from pluripotent stem cells, which are based on embryological development. We also provide a method to generate 3D kidney tissue with vascularized glomeruli upon transplantation.

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

PubMed

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

2011-06-02

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

Combined X-ray and NMR Analysis of the Stability of the Cyclotide Cystine Knot Fold That Underpins Its Insecticidal Activity and Potential Use as a Drug Scaffold*S⃞

PubMed Central

Wang, Conan K.; Hu, Shu-Hong; Martin, Jennifer L.; Sjögren, Tove; Hajdu, Janos; Bohlin, Lars; Claeson, Per; Göransson, Ulf; Rosengren, K. Johan; Tang, Jun; Tan, Ning-Hua; Craik, David J.

2009-01-01

Cyclotides are a family of plant defense proteins that are highly resistant to adverse chemical, thermal, and enzymatic treatment. Here, we present the first crystal structure of a cyclotide, varv F, from the European field pansy, Viola arvensis, determined at a resolution of 1.8 Å. The solution state NMR structure was also determined and, combined with measurements of biophysical parameters for several cyclotides, provided an insight into the structural features that account for the remarkable stability of the cyclotide family. The x-ray data confirm the cystine knot topology and the circular backbone, and delineate a conserved network of hydrogen bonds that contribute to the stability of the cyclotide fold. The structural role of a highly conserved Glu residue that has been shown to regulate cyclotide function was also determined, verifying its involvement in a stabilizing hydrogen bond network. We also demonstrate that varv F binds to dodecylphosphocholine micelles, defining the binding orientation and showing that its structure remains unchanged upon binding, further demonstrating that the cyclotide fold is rigid. This study provides a biological insight into the mechanism by which cyclotides maintain their native activity in the unfavorable environment of predator insect guts. It also provides a structural basis for explaining how a cluster of residues important for bioactivity may be involved in self-association interactions in membranes. As well as being important for their bioactivity, the structural rigidity of cyclotides makes them very suitable as a stable template for peptide-based drug design. PMID:19211551

Investigating the effect of an arterial hypertension drug on the structural properties of plasma protein.

PubMed

Hassan, Natalia; Maldonado-Valderrama, Julia; Gunning, A Patrick; Morris, V J; Ruso, Juan M

2011-10-15

Propanolol is a betablocker drug used in the treatment of arterial hypertension related diseases. In order to achieve an optimal performance of this drug it is important to consider the possible interactions of propanolol with plasma proteins. In this work, we have used several experimental techniques to characterise the effect of addition of the betablocker propanolol on the properties of bovine plasma fibrinogen (FB). Differential scanning calorimeter (DSC), circular dichroism (CD), dynamic light scattering (DLS), surface tension techniques and atomic force microscopy (AFM) measurements have been combined to carry out a detailed physicochemical and surface characterization of the mixed system. As a result, DSC measurements show that propranolol can play two opposite roles, either acting as a structure stabilizer at low molar concentrations or as a structure destabilizer at higher concentrations, in different domains of fibrinogen. CD measurements have revealed that the effect of propanolol on the secondary structure of fibrinogen depends on the temperature and the drug concentration and the DLS analysis showed evidence for protein aggregation. Interestingly, surface tension measurements provided further evidence of the conformational change induced by propanolol on the secondary structure of FB by importantly increasing the surface tension of the system. Finally, AFM imaging of the fibrinogen system provided direct visualization of the protein structure in the presence of propanolol. Combination of these techniques has produced complementary information on the behavior of the mixed system, providing new insights into the structural properties of proteins with potential medical interest. Copyright © 2011 Elsevier B.V. All rights reserved.

Visualization of molecular structures using HoloLens-based augmented reality

PubMed Central

Hoffman, MA; Provance, JB

2017-01-01

Biological molecules and biologically active small molecules are complex three dimensional structures. Current flat screen monitors are limited in their ability to convey the full three dimensional characteristics of these molecules. Augmented reality devices, including the Microsoft HoloLens, offer an immersive platform to change how we interact with molecular visualizations. We describe a process to incorporate the three dimensional structures of small molecules and complex proteins into the Microsoft HoloLens using aspirin and the human leukocyte antigen (HLA) as examples. Small molecular structures can be introduced into the HoloStudio application, which provides native support for rotating, resizing and performing other interactions with these molecules. Larger molecules can be imported through the Unity gaming development platform and then Microsoft Visual Developer. The processes described here can be modified to import a wide variety of molecular structures into augmented reality systems and improve our comprehension of complex structural features. PMID:28815109

Complementary aspects of diffusion imaging and fMRI; I: structure and function.

PubMed

Mulkern, Robert V; Davis, Peter E; Haker, Steven J; Estepar, Raul San Jose; Panych, Lawrence P; Maier, Stephan E; Rivkin, Michael J

2006-05-01

Studying the intersection of brain structure and function is an important aspect of modern neuroscience. The development of magnetic resonance imaging (MRI) over the last 25 years has provided new and powerful tools for the study of brain structure and function. Two tools in particular, diffusion imaging and functional MRI (fMRI), are playing increasingly important roles in elucidating the complementary aspects of brain structure and function. In this work, we review basic technical features of diffusion imaging and fMRI for studying the integrity of white matter structural components and for determining the location and extent of cortical activation in gray matter, respectively. We then review a growing body of literature in which the complementary aspects of diffusion imaging and fMRI, applied as separate examinations but analyzed in tandem, have been exploited to enhance our knowledge of brain structure and function.

Protein Crystallography in Vaccine Research and Development.

PubMed

Malito, Enrico; Carfi, Andrea; Bottomley, Matthew J

2015-06-09

The use of protein X-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. However, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. Here, we review the important contributions that protein crystallography has made so far to vaccine research and development. We discuss several examples of the crystallographic characterization of vaccine antigen structures, alone or in complexes with ligands or receptors. We cover the critical role of high-resolution epitope mapping by reviewing structures of complexes between antigens and their cognate neutralizing, or protective, antibody fragments. Most importantly, we provide recent examples where structural insights obtained via protein crystallography have been used to design novel optimized vaccine antigens. This review aims to illustrate the value of protein crystallography in the emerging discipline of structural vaccinology and its impact on the rational design of vaccines.

Protein Crystallography in Vaccine Research and Development

PubMed Central

Malito, Enrico; Carfi, Andrea; Bottomley, Matthew J.

2015-01-01

The use of protein X-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. However, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. Here, we review the important contributions that protein crystallography has made so far to vaccine research and development. We discuss several examples of the crystallographic characterization of vaccine antigen structures, alone or in complexes with ligands or receptors. We cover the critical role of high-resolution epitope mapping by reviewing structures of complexes between antigens and their cognate neutralizing, or protective, antibody fragments. Most importantly, we provide recent examples where structural insights obtained via protein crystallography have been used to design novel optimized vaccine antigens. This review aims to illustrate the value of protein crystallography in the emerging discipline of structural vaccinology and its impact on the rational design of vaccines. PMID:26068237

Institutional change to support regime transformation: Lessons from Australia's water sector

NASA Astrophysics Data System (ADS)

Werbeloff, Lara; Brown, Rebekah; Cocklin, Chris

2017-07-01

Institutional change is fundamental to regime transformation, and a necessary part of moving toward integrated water management. However, insight into the role of institutional change processes in such transitions is currently limited. A more nuanced understanding of institutional frameworks is necessary, both to advance understanding of institutional change in the context of transitions toward improved water management and to inform strategies for guiding such processes. To this end, we examine two contemporary cases of transformative change in Australia's urban water sector, exploring the evolution of institutional change in each city. This paper offers insights into regime transformation, providing guidance on types of institutional structures and the ways structure-change initiatives can be sequenced to support a transition. The results reveal the importance of regulation in embedding regime change and suggest that engagement with structural frameworks should begin early in transition processes to ensure the timely introduction of supporting regulation. Our findings also highlight the inextricable link between culture-based and structure-based change initiatives, and the importance of using a diverse range of institutional change mechanisms in a mutually reinforcing way to provide a strong foundation for change. These findings provide a foundation for further scholarly examination of institutional change mechanisms, while also serving to inform the strategic activities of transition-oriented organizations and actors.

The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylation

PubMed Central

Mueller-Dieckmann, Christoph; Kernstock, Stefan; Lisurek, Michael; von Kries, Jens Peter; Haag, Friedrich; Weiss, Manfred S.; Koch-Nolte, Friedrich

2006-01-01

Posttranslational modifications are used by cells from all kingdoms of life to control enzymatic activity and to regulate protein function. For many cellular processes, including DNA repair, spindle function, and apoptosis, reversible mono- and polyADP-ribosylation constitutes a very important regulatory mechanism. Moreover, many pathogenic bacteria secrete toxins which ADP-ribosylate human proteins, causing diseases such as whooping cough, cholera, and diphtheria. Whereas the 3D structures of numerous ADP-ribosylating toxins and related mammalian enzymes have been elucidated, virtually nothing is known about the structure of protein de-ADP-ribosylating enzymes. Here, we report the 3Dstructure of human ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3 constitutes the archetype of an all-α-helical protein fold and provides insights into the reversibility of protein ADP-ribosylation. Two magnesium ions flanked by highly conserved amino acids pinpoint the active-site crevice. Recombinant hARH3 binds free ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylates poly- but not monoADP-ribosylated proteins. Docking experiments indicate a possible binding mode for ADP-ribose polymers and suggest a reaction mechanism. Our results underscore the importance of endogenous ADP-ribosylation cycles and provide a basis for structure-based design of ADP-ribosylhydrolase inhibitors. PMID:17015823

Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies.

PubMed

Rudolph, Michael J; Vance, David J; Cheung, Jonah; Franklin, Matthew C; Burshteyn, Fiana; Cassidy, Michael S; Gary, Ebony N; Herrera, Cristina; Shoemaker, Charles B; Mantis, Nicholas J

2014-08-26

Ricin is a select agent toxin and a member of the RNA N-glycosidase family of medically important plant and bacterial ribosome-inactivating proteins. In this study, we determined X-ray crystal structures of the enzymatic subunit of ricin (RTA) in complex with the antigen binding domains (VHH) of five unique single-chain monoclonal antibodies that differ in their respective toxin-neutralizing activities. None of the VHHs made direct contact with residues involved in RTA's RNA N-glycosidase activity or induced notable allosteric changes in the toxin's subunit. Rather, the five VHHs had overlapping structural epitopes on the surface of the toxin and differed in the degree to which they made contact with prominent structural elements in two folding domains of the RTA. In general, RTA interactions were influenced most by the VHH CDR3 (CDR, complementarity-determining region) elements, with the most potent neutralizing antibody having the shortest and most conformationally constrained CDR3. These structures provide unique insights into the mechanisms underlying toxin neutralization and provide critically important information required for the rational design of ricin toxin subunit vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multilevel multi-informant structure of the authoritative school climate survey.

PubMed

Konold, Timothy; Cornell, Dewey; Huang, Francis; Meyer, Patrick; Lacey, Anna; Nekvasil, Erin; Heilbrun, Anna; Shukla, Kathan

2014-09-01

The Authoritative School Climate Survey was designed to provide schools with a brief assessment of 2 key characteristics of school climate--disciplinary structure and student support--that are hypothesized to influence 2 important school climate outcomes--student engagement and prevalence of teasing and bullying in school. The factor structure of these 4 constructs was examined with exploratory and confirmatory factor analyses in a statewide sample of 39,364 students (Grades 7 and 8) attending 423 schools. Notably, the analyses used a multilevel structural approach to model the nesting of students in schools for purposes of evaluating factor structure, demonstrating convergent and concurrent validity and gauging the structural invariance of concurrent validity coefficients across gender. These findings provide schools with a core group of school climate measures guided by authoritative discipline theory. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Internal Capabilities, External Network Position, and Knowledge Creation

ERIC Educational Resources Information Center

Liao, Yin-Chi

2010-01-01

Despite the general consensus on the importance of interfirm networks, there is an ongoing debate centering on which type of network structure is most beneficial to firm performance. While spanning structural holes--a network position with disconnected partners--is argued to be advantageous in terms of providing access to diverse knowledge,…

The Flow of International Students from a Macro Perspective: A Network Analysis

ERIC Educational Resources Information Center

Barnett, George A.; Lee, Moosung; Jiang, Ke; Park, Han Woo

2016-01-01

This paper provides a network analysis of the international flow of students among 210 countries and the factors determining the structure of this flow. Among these factors, bilateral hyperlink connections between countries and the number of telephone minutes (communication variables) are the most important predictors of the flow's structure,…

The Willingness to Change to Formalized Child Care Arrangements: Parental Considerations of Cost and Quality.

ERIC Educational Resources Information Center

Camasso, Michael J.; Roche, Susan E.

1991-01-01

Data from 1988 sample of 1,058 state employees provided evidence that family structure, price, and quality were important determinants of parent's willingness to change from informal to formal child care arrangements. Measured 43 facets of program structure, curriculum, and child development goals. (Author/NB)

Situational and Structural Variation in Youth Perceptions of Maternal Guilt Induction

ERIC Educational Resources Information Center

Rote, Wendy M.; Smetana, Judith G.

2017-01-01

Parental induction of empathy-related guilt plays an important role in children's moral development. However, guilt induction can also be psychologically controlling and detrimental for youth adjustment. This study provided a more nuanced view of parental guilt induction by examining how the nature of a child's misdeed and the structure and…

Mobility balance in the light-emitting layer governs the polaron accumulation and operational stability of organic light-emitting diodes

NASA Astrophysics Data System (ADS)

Kim, Jae-Min; Lee, Chang-Heon; Kim, Jang-Joo

2017-11-01

Organic light-emitting diode (OLED) displays are lighter and more flexible, have a wider color gamut, and consume less power than conventional displays. Stable materials and the structural design of the device are important for OLED longevity. Control of charge transport and accumulation in the device is particularly important because the interaction of excitons and polarons results in material degradation. This research investigated the charge dynamics of OLEDs experimentally and by drift-diffusion modeling. Parallel capacitance-voltage measurements of devices provided knowledge of charge behavior at different driving voltages. A comparison of exciplex-forming co-host and single host structures established that the mobility balance in the emitting layers determined the amount of accumulated polarons in those layers. Consequently, an exciplex-forming co-host provides a superior structure in terms of device lifetime and efficiency because of its well-balanced mobility. Minimizing polaron accumulation is key to achieving long OLED device lifetimes. This is a crucial aspect of device physics that must be considered in the device design structure.

Hydrolytic catalysis and structural stabilization in a designed metalloprotein

PubMed Central

Zastrow, Melissa L.; Peacock, Anna F. A.; Stuckey, Jeanne A.; Pecoraro, Vincent L.

2011-01-01

Metal ions are an important part of many natural proteins, providing structural, catalytic and electron transfer functions. Reproducing these functions in a designed protein is the ultimate challenge to our understanding of them. Here, we present an artificial metallohydrolase, which has been shown by X-ray crystallography to contain two different metal ions – a Zn(II) ion which is important for catalytic activity and a Hg(II) ion which provides structural stability. This metallohydrolase displays catalytic activity that compares well with several characteristic reactions of natural enzymes. It catalyses p-nitrophenyl acetate hydrolysis (pNPA) to within ~100-fold of the efficiency of human carbonic anhydrase (CA)II and is at least 550-fold better than comparable synthetic complexes. Similarly, CO2 hydration occurs with an efficiency within ~500-fold of CAII. While histidine residues in the absence of Zn(II) exhibit pNPA hydrolysis, miniscule apopeptide activity is observed for CO2 hydration. The kinetic and structural analysis of this first de novo designed hydrolytic metalloenzyme uncovers necessary design features for future metalloenzymes containing one or more metals. PMID:22270627

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

National Plant Diagnostic Network, Taxonomic training videos: Aphids under the microscope - overview

USDA-ARS?s Scientific Manuscript database

Training is a critical part of aphid (Hemiptera: Aphididae) identification. This training video provides provides an overview of general aphid morphology by using a compound microscope. The narrator discusses and highlights structures on the aphid that are important to make a species identification....

RNA Characterization by Solid-State NMR Spectroscopy.

PubMed

Yang, Yufei; Wang, Shenlin

2018-06-21

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

DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis, rice, and budding yeast.

PubMed

Liu, Yun-Hua; Zhang, Meiping; Wu, Chengcang; Huang, James J; Zhang, Hong-Bin

2014-01-01

Knowledge of how a genome is structured and organized from its constituent elements is crucial to understanding its biology and evolution. Here, we report the genome structuring and organization pattern as revealed by systems analysis of the sequences of three model species, Arabidopsis, rice and yeast, at the whole-genome and chromosome levels. We found that all fundamental function elements (FFE) constituting the genomes, including genes (GEN), DNA transposable elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR), and (or) low complexity repeats (LCR), are structured in a nonrandom and correlative manner, thus leading to a hypothesis that the DNA of the species is structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE differ in their importance in the formation and evolution of the DNA jigsaw puzzle structure between species. DTE and RTE play more important roles than GEN, LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than LCR, SSR, and DTE in rice. The genes having multiple recognized functions play more important roles than those having single functions. These results provide useful knowledge necessary for better understanding genome biology and evolution of the species and for effective molecular breeding of rice.

Modeling the Dependency Structure of Integrated Intensity Processes

PubMed Central

Ma, Yong-Ki

2015-01-01

This paper studies an important issue of dependence structure. To model this structure, the intensities within the Cox processes are driven by dependent shot noise processes, where jumps occur simultaneously and their sizes are correlated. The joint survival probability of the integrated intensities is explicitly obtained from the copula with exponential marginal distributions. Subsequently, this result can provide a very useful guide for credit risk management. PMID:26270638

Correlation Between Chain Architecture and Hydration Water Structure in Polysaccharides.

PubMed

Grossutti, Michael; Dutcher, John R

2016-03-14

The physical properties of confined water can differ dramatically from those of bulk water. Hydration water associated with polysaccharides provides a particularly interesting example of confined water, because differences in polysaccharide structure provide different spatially confined environments for water sorption. We have used attenuated total reflection infrared (ATR-IR) spectroscopy to investigate the structure of hydration water in films of three different polysaccharides under controlled relative humidity (RH) conditions. We compare the results obtained for films of highly branched, dendrimer-like phytoglycogen nanoparticles to those obtained for two unbranched polysaccharides, hyaluronic acid (HA), and chitosan. We find similarities between the water structuring in the two linear polysaccharides and significant differences for phytoglycogen. In particular, the results suggest that the high degree of branching in phytoglycogen leads to a much more well-ordered water structure (low density, high connectivity network water), indicating the strong influence of chain architecture on the structuring of water. These measurements provide unique insight into the relationship between the structure and hydration of polysaccharides, which is important for understanding and exploiting these sustainable nanomaterials in a wide range of applications.

SA-Mot: a web server for the identification of motifs of interest extracted from protein loops

PubMed Central

Regad, Leslie; Saladin, Adrien; Maupetit, Julien; Geneix, Colette; Camproux, Anne-Claude

2011-01-01

The detection of functional motifs is an important step for the determination of protein functions. We present here a new web server SA-Mot (Structural Alphabet Motif) for the extraction and location of structural motifs of interest from protein loops. Contrary to other methods, SA-Mot does not focus only on functional motifs, but it extracts recurrent and conserved structural motifs involved in structural redundancy of loops. SA-Mot uses the structural word notion to extract all structural motifs from uni-dimensional sequences corresponding to loop structures. Then, SA-Mot provides a description of these structural motifs using statistics computed in the loop data set and in SCOP superfamily, sequence and structural parameters. SA-Mot results correspond to an interactive table listing all structural motifs extracted from a target structure and their associated descriptors. Using this information, the users can easily locate loop regions that are important for the protein folding and function. The SA-Mot web server is available at http://sa-mot.mti.univ-paris-diderot.fr. PMID:21665924

SA-Mot: a web server for the identification of motifs of interest extracted from protein loops.

PubMed

Regad, Leslie; Saladin, Adrien; Maupetit, Julien; Geneix, Colette; Camproux, Anne-Claude

2011-07-01

The detection of functional motifs is an important step for the determination of protein functions. We present here a new web server SA-Mot (Structural Alphabet Motif) for the extraction and location of structural motifs of interest from protein loops. Contrary to other methods, SA-Mot does not focus only on functional motifs, but it extracts recurrent and conserved structural motifs involved in structural redundancy of loops. SA-Mot uses the structural word notion to extract all structural motifs from uni-dimensional sequences corresponding to loop structures. Then, SA-Mot provides a description of these structural motifs using statistics computed in the loop data set and in SCOP superfamily, sequence and structural parameters. SA-Mot results correspond to an interactive table listing all structural motifs extracted from a target structure and their associated descriptors. Using this information, the users can easily locate loop regions that are important for the protein folding and function. The SA-Mot web server is available at http://sa-mot.mti.univ-paris-diderot.fr.

Comparative analyses of structural features and scaffold diversity for purchasable compound libraries.

PubMed

Shang, Jun; Sun, Huiyong; Liu, Hui; Chen, Fu; Tian, Sheng; Pan, Peichen; Li, Dan; Kong, Dexin; Hou, Tingjun

2017-04-21

Large purchasable screening libraries of small molecules afforded by commercial vendors are indispensable sources for virtual screening (VS). Selecting an optimal screening library for a specific VS campaign is quite important to improve the success rates and avoid wasting resources in later experimental phases. Analysis of the structural features and molecular diversity for different screening libraries can provide valuable information to the decision making process when selecting screening libraries for VS. In this study, the structural features and scaffold diversity of eleven purchasable screening libraries and Traditional Chinese Medicine Compound Database (TCMCD) were analyzed and compared. Their scaffold diversity represented by the Murcko frameworks and Level 1 scaffolds was characterized by the scaffold counts and cumulative scaffold frequency plots, and visualized by Tree Maps and SAR Maps. The analysis demonstrates that, based on the standardized subsets with similar molecular weight distributions, Chembridge, ChemicalBlock, Mucle, TCMCD and VitasM are more structurally diverse than the others. Compared with all purchasable screening libraries, TCMCD has the highest structural complexity indeed but more conservative molecular scaffolds. Moreover, we found that some representative scaffolds were important components of drug candidates against different drug targets, such as kinases and guanosine-binding protein coupled receptors, and therefore the molecules containing pharmacologically important scaffolds found in screening libraries might be potential inhibitors against the relevant targets. This study may provide valuable perspective on which purchasable compound libraries are better for you to screen. Graphical abstract Selecting diverse compound libraries with scaffold analyses.

Teaching resources. Protein phosphatases.

PubMed

Salton, Stephen R

2005-03-01

This Teaching Resource provides lecture notes and slides for a class covering the structure and function of protein phosphatases and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with a discussion of the importance of phosphatases in physiology, recognized by the award of a Nobel Prize in 1992, and then proceeds to describe the two types of protein phosphatases: serine/threonine and tyrosine phosphatases. The information covered includes the structure, regulation, and substrate specificity of protein phosphatases, with an emphasis on their importance in disease and clinical settings.

C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation.

PubMed

Li, Chuang; Peng, Qiongfang; Wan, Xiao; Sun, Haili; Tang, Jun

2017-10-15

Promyelocytic leukemia protein (PML) nuclear bodies (NBs), which are sub-nuclear protein structures, are involved in a variety of important cellular functions. PML-NBs are assembled by PML isoforms, and contact between small ubiquitin-like modifiers (SUMOs) with the SUMO interaction motif (SIM) are critically involved in this process. PML isoforms contain a common N-terminal region and a variable C-terminus. However, the contribution of the C-terminal regions to PML-NB formation remains poorly defined. Here, using high-resolution microscopy, we show that mutation of the SIM distinctively influences the structure of NBs formed by each individual PML isoform, with that of PML-III and PML-V minimally changed, and PML-I and PML-IV dramatically impaired. We further identify several C-terminal elements that are important in regulating NB structure and provide strong evidence to suggest that the 8b element in PML-IV possesses a strong ability to interact with SUMO-1 and SUMO-2, and critically participates in NB formation. Our findings highlight the importance of PML C-termini in NB assembly and function, and provide molecular insight into the PML-NB assembly of each distinctive isoform. © 2017. Published by The Company of Biologists Ltd.

Complex networks with scale-free nature and hierarchical modularity

NASA Astrophysics Data System (ADS)

Shekatkar, Snehal M.; Ambika, G.

2015-09-01

Generative mechanisms which lead to empirically observed structure of networked systems from diverse fields like biology, technology and social sciences form a very important part of study of complex networks. The structure of many networked systems like biological cell, human society and World Wide Web markedly deviate from that of completely random networks indicating the presence of underlying processes. Often the main process involved in their evolution is the addition of links between existing nodes having a common neighbor. In this context we introduce an important property of the nodes, which we call mediating capacity, that is generic to many networks. This capacity decreases rapidly with increase in degree, making hubs weak mediators of the process. We show that this property of nodes provides an explanation for the simultaneous occurrence of the observed scale-free structure and hierarchical modularity in many networked systems. This also explains the high clustering and small-path length seen in real networks as well as non-zero degree-correlations. Our study also provides insight into the local process which ultimately leads to emergence of preferential attachment and hence is also important in understanding robustness and control of real networks as well as processes happening on real networks.

Mission-oriented requirements for updating MIL-H-8501. Volume 2: STI background and rationale. [military rotorcraft

NASA Technical Reports Server (NTRS)

Clement, W. F.; Hoh, R. H.; Mitchell, D. G.; Ferguson, S. W., III

1985-01-01

A supplement to the structure of a new flying and ground handling qualities specification for military rotorcraft structure is presented in order to explain the background and rationale for the specification structure, the proposed forms of criteria, and the status of the existing data base. Critical gaps in the data base for the new structure are defined, and recommendations are provided for the research required to address the most important of these gaps.

Lewin's Impact on Education: Instilling Cooperation and Conflict Management Skills in School Children.

ERIC Educational Resources Information Center

Maruyama, Geoffrey

1992-01-01

A Lewinian orientation to educational problems fits current innovative thinking in education (e.g., models for making education multicultural), and provides the bases of important applied work on cooperative learning techniques and constructive ways of structuring conflict within educational settings. Lewinian field theory provides a broad…

Tropical Rainforest Education. ERIC Digest.

ERIC Educational Resources Information Center

Rillero, Peter

This digest provides four guideposts for tropical rainforest education: (1) structure; (2) location and climate; (3) importance; and (4) conservation of resources. Research is cited and background information provided about the layers of life and the adaptations of life within the tropical rain forest. Aspects of life within and near rain forests…

Eros in Stereo

NASA Image and Video Library

2000-05-07

Stereo imaging, an important tool on NASA NEAR Shoemaker for geologic analysis of Eros, provides three-dimensional information on the asteroid landforms and structures. 3D glasses are necessary to view this image.

NASTRAN analysis of the 1/8-scale space shuttle dynamic model

NASA Technical Reports Server (NTRS)

Bernstein, M.; Mason, P. W.; Zalesak, J.; Gregory, D. J.; Levy, A.

1973-01-01

The space shuttle configuration has more complex structural dynamic characteristics than previous launch vehicles primarily because of the high model density at low frequencies and the high degree of coupling between the lateral and longitudinal motions. An accurate analytical representation of these characteristics is a primary means for treating structural dynamics problems during the design phase of the shuttle program. The 1/8-scale model program was developed to explore the adequacy of available analytical modeling technology and to provide the means for investigating problems which are more readily treated experimentally. The basic objectives of the 1/8-scale model program are: (1) to provide early verification of analytical modeling procedures on a shuttle-like structure, (2) to demonstrate important vehicle dynamic characteristics of a typical shuttle design, (3) to disclose any previously unanticipated structural dynamic characteristics, and (4) to provide for development and demonstration of cost effective prototype testing procedures.

Computer codes developed and under development at Lewis

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

1992-01-01

The objective of this summary is to provide a brief description of: (1) codes developed or under development at LeRC; and (2) the development status of IPACS with some typical early results. The computer codes that have been developed and/or are under development at LeRC are listed in the accompanying charts. This list includes: (1) the code acronym; (2) select physics descriptors; (3) current enhancements; and (4) present (9/91) code status with respect to its availability and documentation. The computer codes list is grouped by related functions such as: (1) composite mechanics; (2) composite structures; (3) integrated and 3-D analysis; (4) structural tailoring; and (5) probabilistic structural analysis. These codes provide a broad computational simulation infrastructure (technology base-readiness) for assessing the structural integrity/durability/reliability of propulsion systems. These codes serve two other very important functions: they provide an effective means of technology transfer; and they constitute a depository of corporate memory.

Examining Quality in Two Preschool Settings: Publicly Funded Early Childhood Education and Inclusive Early Childhood Education Classrooms

ERIC Educational Resources Information Center

Pelatti, Christina Yeager; Dynia, Jaclyn M.; Logan, Jessica A.; Justice, Laura M.; Kaderavek, Joan

2016-01-01

Background: Although classroom quality is an important consideration, few recent research studies have examined the process and structural quality in publicly funded early childhood education (ECE) and inclusive ECE classrooms. This study provides an important contribution to the literature by comparing two conceptualizations of quality in…

Increasing access to sexual health care for rural and regional young people: Similarities and differences in the views of young people and service providers.

PubMed

Johnston, Karen; Harvey, Caroline; Matich, Paula; Page, Priscilla; Jukka, Clare; Hollins, Jane; Larkins, Sarah

2015-10-01

This study aims to describe the views of sexual health service providers on access issues for young people and consider them together with the views of young people themselves. A cross-sectional mixed-methods study design involving semi-structured interviews with health service providers and an electronic survey with young people. Four towns in rural and regional Queensland, Australia. A total of 32 service providers: 9 sexual health nurses, 8 general practitioners, 6 school-based youth health nurses, 5 sexual health educators, 2 Australian Aboriginal health workers and 2 youth workers. There were 391 young people who participated in the Young People's Survey. Themes generated from interviews with service providers and quantitative data from young people addressing access to sexual and reproductive health (SRH) services for rural and regional young people. Service providers frequently identified structural barriers, confidentiality and lack of awareness of SRH services as barriers for young people seeking SRH care. Young people also reported that structural factors such as transport, cost and service operating hours were important; however, they placed greater value on personal attributes of service providers, particularly welcoming and non-judgemental attitudes. Health service policy and training focused on attitudinal qualities of individual service providers may improve access to SRH services for young people. Selective staff recruitment and professional development are important to increase sensitivity to youth issues. Promotion of non-judgemental and confidential care may also improve access for youth. © 2015 National Rural Health Alliance Inc.

Vinyl Sulfones as Antiparasitic Agents and a Structural Basis for Drug Design*

PubMed Central

Kerr, Iain D.; Lee, Ji H.; Farady, Christopher J.; Marion, Rachael; Rickert, Mathias; Sajid, Mohammed; Pandey, Kailash C.; Caffrey, Conor R.; Legac, Jennifer; Hansell, Elizabeth; McKerrow, James H.; Craik, Charles S.; Rosenthal, Philip J.; Brinen, Linda S.

2009-01-01

Cysteine proteases of the papain superfamily are implicated in a number of cellular processes and are important virulence factors in the pathogenesis of parasitic disease. These enzymes have therefore emerged as promising targets for antiparasitic drugs. We report the crystal structures of three major parasite cysteine proteases, cruzain, falcipain-3, and the first reported structure of rhodesain, in complex with a class of potent, small molecule, cysteine protease inhibitors, the vinyl sulfones. These data, in conjunction with comparative inhibition kinetics, provide insight into the molecular mechanisms that drive cysteine protease inhibition by vinyl sulfones, the binding specificity of these important proteases and the potential of vinyl sulfones as antiparasitic drugs. PMID:19620707

Hyaluronic acid: its role in voice.

PubMed

Ward, P Daniel; Thibeault, Susan L; Gray, Steven D

2002-09-01

The extracellular matrix (ECM), once regarded simply as a structural scaffold, is now recognized as an important modulator of cellular behavior and function. One component that plays a prominent role in this process is hyaluronic acid (HA)--a molecule found in many different tissues. Research into the roles of HA indicates that it plays a key role in tissue viscosity, shock absorption, and space filling. Specifically, research into the role of HA in laryngology indicates that it has profound effects on the structure and viscosity of vocal folds. This article provides an introduction to the structure and biological functions of HA and its importance in voice. In addition, an overview of the pharmaceutical applications of HA is discussed.

CASTp 3.0: computed atlas of surface topography of proteins.

PubMed

Tian, Wei; Chen, Chang; Lei, Xue; Zhao, Jieling; Liang, Jie

2018-06-01

Geometric and topological properties of protein structures, including surface pockets, interior cavities and cross channels, are of fundamental importance for proteins to carry out their functions. Computed Atlas of Surface Topography of proteins (CASTp) is a web server that provides online services for locating, delineating and measuring these geometric and topological properties of protein structures. It has been widely used since its inception in 2003. In this article, we present the latest version of the web server, CASTp 3.0. CASTp 3.0 continues to provide reliable and comprehensive identifications and quantifications of protein topography. In addition, it now provides: (i) imprints of the negative volumes of pockets, cavities and channels, (ii) topographic features of biological assemblies in the Protein Data Bank, (iii) improved visualization of protein structures and pockets, and (iv) more intuitive structural and annotated information, including information of secondary structure, functional sites, variant sites and other annotations of protein residues. The CASTp 3.0 web server is freely accessible at http://sts.bioe.uic.edu/castp/.

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques.

PubMed

Bigler, Erin D

2015-09-01

Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury.

Correlation Between Chain Architecture and Hydration Water Structure in Polysaccharides

NASA Astrophysics Data System (ADS)

Grossutti, Michael; Dutcher, John

The physical properties of confined water can differ dramatically from those of bulk water. Hydration water associated with polysaccharides provides a particularly important example of confined water, with differences in polysaccharide structure providing different spatially confined environments for water adsorption. We have used attenuated total reflection infrared (ATR-IR) spectroscopy to investigate the structure of hydration water in films of three different polysaccharides under controlled relative humidity (RH) conditions. We compare the results obtained for films of highly branched, monodisperse phytoglycogen nanoparticles to those obtained for two unbranched polysaccharides, hyaluronic acid (HA) and chitosan. We find similarities between water structuring in the two linear polysaccharides, and significant differences for phytoglycogen. In particular, the phytoglycogen nanoparticles exhibited high network water connectivity, and a large increase in the fraction of multimer water clusters with increasing RH, whereas the water structure for HA and chitosan was found to be insensitive to changes in RH. These measurements provide unique insight into the relationship between the chain architecture and hydration of polysaccharides.

Influence of DNA sequence on the structure of minicircles under torsional stress

PubMed Central

Wang, Qian; Irobalieva, Rossitza N.; Chiu, Wah; Schmid, Michael F.; Fogg, Jonathan M.; Zechiedrich, Lynn

2017-01-01

Abstract The sequence dependence of the conformational distribution of DNA under various levels of torsional stress is an important unsolved problem. Combining theory and coarse-grained simulations shows that the DNA sequence and a structural correlation due to topology constraints of a circle are the main factors that dictate the 3D structure of a 336 bp DNA minicircle under torsional stress. We found that DNA minicircle topoisomers can have multiple bend locations under high torsional stress and that the positions of these sharp bends are determined by the sequence, and by a positive mechanical correlation along the sequence. We showed that simulations and theory are able to provide sequence-specific information about individual DNA minicircles observed by cryo-electron tomography (cryo-ET). We provided a sequence-specific cryo-ET tomogram fitting of DNA minicircles, registering the sequence within the geometric features. Our results indicate that the conformational distribution of minicircles under torsional stress can be designed, which has important implications for using minicircle DNA for gene therapy. PMID:28609782

Precambrian Basement Structure Map of the Continental United States - An Interpretation of Geologic and Aeromagnetic Data

USGS Publications Warehouse

Sims, Paul K.; Saltus, Richard W.; Anderson, Eric D.

2008-01-01

The Precambrian basement rocks of the continental United States are largely covered by younger sedimentary and volcanic rocks, and the availability of updated aeromagnetic data (NAMAG, 2002) provides a means to infer major regional basement structures and tie together the scattered, but locally abundant, geologic information. Precambrian basement structures in the continental United States have strongly influenced later Proterozoic and Phanerozoic tectonism within the continent, and there is a growing awareness of the utility of these structures in deciphering major younger tectonic and related episodes. Interest in the role of basement structures in the evolution of continents has been recently stimulated, particularly by publications of the Geological Society of London (Holdsworth and others, 1998; Holdsworth and others, 2001). These publications, as well as others, stress the importance of reactivation of basement structures in guiding the subsequent evolution of continents. Knowledge of basement structures is an important key to understanding the geology of continental interiors.

Structure-based drug design: aiming for a perfect fit

PubMed Central

van Montfort, Rob L.M.; Workman, Paul

2017-01-01

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

Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces.

PubMed

Michaelides, Angelos; Martinez, Todd J; Alavi, Ali; Kresse, Georg; Manby, Frederick R

2015-09-14

This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science.

Learning Organisations: A Literature Review and Critique

DTIC Science & Technology

2014-01-01

autocratic, laissez - faire and democratic work-group principles attributed to Lewin, provided evidence that people would learn and self-manage in an...each with their own particular emphasis on learning, leadership behaviours and organisational structure. A Learning Organisation’s salient...the organisational and structural factors that affect learning. These include the importance specific leadership actions or practices, the utility of

Hierarchical population structure in greater sage-grouse provides insight into management boundary delineation

Treesearch

Todd B. Cross; David E. Naugle; John C. Carlson; Michael K. Schwartz

2016-01-01

Understanding population structure is important for guiding ongoing conservation and restoration efforts. The greater sage-grouse (Centrocercus urophasianus) is a species of concern distributed across 1.2 million km2 of western North America. We genotyped 1499 greater sagegrouse from 297 leks across Montana, North Dakota and South Dakota using a 15 locus...

Micronesian mangrove forest structure and tree responses to a severe typhoon

Treesearch

J. Boone Kauffman; Thomas G. Cole

2010-01-01

Tropical cyclones are common disturbances that have strong effects on mangrove composition and structure. Because there are numerous ecosystem services provided by mangroves, it is important to understand their adaptations and responses to these climatic events. In April 2004, Typhoon Sudal, a category 3-4 cyclone, passed over the state of Yap, Federated States of...

Dynaflow User’s Guide

DTIC Science & Technology

1988-11-01

264 ANALYSIS RESTART. ............. ..... ....... 269 1.0 TITLE CARD. .............. ............. 271 2.0 CONTROL CARDS...stress soil model will provide a tool for such analysis of waterfront structures. To understand the significance of liquefaction, it is important to note...Implementing this effective stress soil model into a finite element computer program would allow analysis of soil and structure together. TECHNICAL BACKGROUND

Multifunctional Composite Structures

DTIC Science & Technology

2010-03-01

78  Design of vibrating / oscillating wings for MAV ................................................. 79  6...62  Oscillating structural mechanism ................................................................... 80  Fig. 63  Mode shapes of vibration ...allowing  it  to  perform  important  tasks  including  actuation,  sensing,  energy  storage  and  energy  harvesting   in  addition  to  providing

Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.

PubMed

Howard, Rebecca J; Trudell, James R; Harris, R Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

PubMed Central

Trudell, James R.; Harris, R. Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

What Matters in Scientific Explanations: Effects of Elaboration and Content

PubMed Central

Rottman, Benjamin M.; Keil, Frank C.

2011-01-01

Given the breadth and depth of available information, determining which components of an explanation are most important is a crucial process for simplifying learning. Three experiments tested whether people believe that components of an explanation with more elaboration are more important. In Experiment 1, participants read separate and unstructured components that comprised explanations of real-world scientific phenomena, rated the components on their importance for understanding the explanations, and drew graphs depicting which components elaborated on which other components. Participants gave higher importance scores for components that they judged to be elaborated upon by other components. Experiment 2 demonstrated that experimentally increasing the amount of elaboration of a component increased the perceived importance of the elaborated component. Furthermore, Experiment 3 demonstrated that elaboration increases the importance of the elaborated information by providing insight into understanding the elaborated information; information that was too technical to provide insight into the elaborated component did not increase the importance of the elaborated component. While learning an explanation, people piece together the structure of elaboration relationships between components and use the insight provided by elaboration to identify important components. PMID:21924709

Multicomplex-based pharmacophore-guided 3D-QSAR studies of N-substituted 2'-(aminoaryl)benzothiazoles as Aurora-A inhibitors.

PubMed

He, Gu; Qiu, Minghua; Li, Rui; Ouyang, Liang; Wu, Fengbo; Song, Xiangrong; Cheng, Li; Xiang, Mingli; Yu, Luoting

2012-06-01

Aurora-A has been known as one of the most important targets for cancer therapy, and some Aurora-A inhibitors have entered clinical trails. In this study, combination of the ligand-based and structure-based methods is used to clarify the essential quantitative structure-activity relationship of known Aurora-A inhibitors, and multicomplex-based pharmacophore-guided method has been suggested to generate a comprehensive pharmacophore of Aurora-A kinase based on a collection of crystal structures of Aurora-A-inhibitor complex. This model has been successfully used to identify the bioactive conformation and align 37 structurally diverse N-substituted 2'-(aminoaryl)benzothiazoles derivatives. The quantitative structure-activity relationship analyses have been performed on these Aurora-A inhibitors based on multicomplex-based pharmacophore-guided alignment. These results may provide important information for further design and virtual screening of novel Aurora-A inhibitors. © 2012 John Wiley & Sons A/S.

Modes of therapeutic action.

PubMed

Jones, E E

1997-12-01

The dialectic in psychoanalysis between theories about the mutative effects of interpretation and psychological knowledge and those concerning the effects of interpersonal interaction constitutes an important tension for approaches to psychoanalytic technique. This essay briefly summarises the thinking around these alternative conceptualisations of therapeutic action, and introduces a new empirically derived model, that of 'repetitive interaction structure', which attempts to bridge therapeutic action by insight and by relationship. Interaction structure is a way of formulating those aspects of the analytic process that have come to be termed intersubjectivity, transference-countertransference enactments and role responsiveness. The concept operationalises important aspects of interpersonal interaction, and can help specify the two-person patterns that emerge in an analysis. Patient and analyst interact in repetitive ways; these patterns of interaction, which are slow to change, probably reflect the psychological structure of both patient and analyst, whether psychic structure is conceptualised in terms of object-representations or compromise formations and impulse-defence configurations. Therapeutic action is located in the experience, recognition and understanding by patient and analyst of these repetitive interactions. Interaction structures stress the importance of the intrapsychic as a basis for what becomes manifest in the interactive field. Clinical illustrations from a psychoanalysis are provided, and research on repetitive interaction structures is described.

Paragenesis and Geochronology of the Nopal I Uranium Deposit, Mexico

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

M. Fayek; M. Ren

2007-02-14

Uranium deposits can, by analogy, provide important information on the long-term performance of radioactive waste forms and radioactive waste repositories. Their complex mineralogy and variable elemental and isotopic compositions can provide important information, provided that analyses are obtained on the scale of several micrometers. Here, we present a structural model of the Nopal I deposit as well as petrography at the nanoscale coupled with preliminary U-Th-Pb ages and O isotopic compositions of uranium-rich minerals obtained by Secondary Ion Mass Spectrometry (SIMS). This multi-technique approach promises to provide ''natural system'' data on the corrosion rate of uraninite, the natural analogue ofmore » spent nuclear fuel.« less

Structure-Based Characterization of Multiprotein Complexes

PubMed Central

Wiederstein, Markus; Gruber, Markus; Frank, Karl; Melo, Francisco; Sippl, Manfred J.

2014-01-01

Summary Multiprotein complexes govern virtually all cellular processes. Their 3D structures provide important clues to their biological roles, especially through structural correlations among protein molecules and complexes. The detection of such correlations generally requires comprehensive searches in databases of known protein structures by means of appropriate structure-matching techniques. Here, we present a high-speed structure search engine capable of instantly matching large protein oligomers against the complete and up-to-date database of biologically functional assemblies of protein molecules. We use this tool to reveal unseen structural correlations on the level of protein quaternary structure and demonstrate its general usefulness for efficiently exploring complex structural relationships among known protein assemblies. PMID:24954616

Access to finance from different finance provider types: Farmer knowledge of the requirements.

PubMed

Wulandari, Eliana; Meuwissen, Miranda P M; Karmana, Maman H; Oude Lansink, Alfons G J M

2017-01-01

Analysing farmer knowledge of the requirements of finance providers can provide valuable insights to policy makers about ways to improve farmers' access to finance. This study compares farmer knowledge of the requirements to obtain finance with the actual requirements set by different finance provider types, and investigates the relation between demographic and socioeconomic factors and farmer knowledge of finance requirements. We use a structured questionnaire to collect data from a sample of finance providers and farmers in Java Island, Indonesia. We find that the most important requirements to acquire finance vary among different finance provider types. We also find that farmers generally have little knowledge of the requirements, which are important to each type of finance provider. Awareness campaigns are needed to increase farmer knowledge of the diversity of requirements among the finance provider types.

Access to finance from different finance provider types: Farmer knowledge of the requirements

PubMed Central

Meuwissen, Miranda P. M.; Karmana, Maman H.; Oude Lansink, Alfons G. J. M.

2017-01-01

Analysing farmer knowledge of the requirements of finance providers can provide valuable insights to policy makers about ways to improve farmers’ access to finance. This study compares farmer knowledge of the requirements to obtain finance with the actual requirements set by different finance provider types, and investigates the relation between demographic and socioeconomic factors and farmer knowledge of finance requirements. We use a structured questionnaire to collect data from a sample of finance providers and farmers in Java Island, Indonesia. We find that the most important requirements to acquire finance vary among different finance provider types. We also find that farmers generally have little knowledge of the requirements, which are important to each type of finance provider. Awareness campaigns are needed to increase farmer knowledge of the diversity of requirements among the finance provider types. PMID:28877174

Schaffer Collateral Inputs to CA1 Excitatory and Inhibitory Neurons Follow Different Connectivity Rules.

PubMed

Kwon, Osung; Feng, Linqing; Druckmann, Shaul; Kim, Jinhyun

2018-05-30

Neural circuits, governed by a complex interplay between excitatory and inhibitory neurons, are the substrate for information processing, and the organization of synaptic connectivity in neural network is an important determinant of circuit function. Here, we analyzed the fine structure of connectivity in hippocampal CA1 excitatory and inhibitory neurons innervated by Schaffer collaterals (SCs) using mGRASP in male mice. Our previous study revealed spatially structured synaptic connectivity between CA3 and CA1 pyramidal cells (PCs). Surprisingly, parvalbumin-positive interneurons (PVs) showed a significantly more random pattern spatial structure. Notably, application of Peters' rule for synapse prediction by random overlap between axons and dendrites enhanced structured connectivity in PCs, but, by contrast, made the connectivity pattern in PVs more random. In addition, PCs in a deep sublayer of striatum pyramidale appeared more highly structured than PCs in superficial layers, and little or no sublayer specificity was found in PVs. Our results show that CA1 excitatory PCs and inhibitory PVs innervated by the same SC inputs follow different connectivity rules. The different organizations of fine scale structured connectivity in hippocampal excitatory and inhibitory neurons provide important insights into the development and functions of neural networks. SIGNIFICANCE STATEMENT Understanding how neural circuits generate behavior is one of the central goals of neuroscience. An important component of this endeavor is the mapping of fine-scale connection patterns that underlie, and help us infer, signal processing in the brain. Here, using our recently developed synapse detection technology (mGRASP and neuTube), we provide detailed profiles of synaptic connectivity in excitatory (CA1 pyramidal) and inhibitory (CA1 parvalbumin-positive) neurons innervated by the same presynaptic inputs (CA3 Schaffer collaterals). Our results reveal that these two types of CA1 neurons follow different connectivity patterns. Our new evidence for differently structured connectivity at a fine scale in hippocampal excitatory and inhibitory neurons provides a better understanding of hippocampal networks and will guide theoretical and experimental studies. Copyright © 2018 the authors 0270-6474/18/385140-13$15.00/0.

The crystallization and structural analysis of cellulases (and other glycoside hydrolases): strategies and tactics.

PubMed

Roberts, Shirley M; Davies, Gideon J

2012-01-01

The three-dimensional (3-D) structures of cellulases, and other glycoside hydrolases, are a central feature of research in carbohydrate chemistry and biochemistry. 3-D structure is used to inform protein engineering campaigns, both academic and industrial, which are typically used to improve the stability or activity of an enzyme. Examples of classical protein engineering goals include higher thermal stability, reduced metal-ion dependency, detergent and protease resistance, decreased product inhibition, and altered specificity. 3-D structure may also be used to interpret the behavior of enzyme variants that are derived from screening or random mutagenesis approaches, with a view to establishing an iterative design process. In other areas, 3-D structure is used as one of the many tools to probe enzymatic catalysis, typically dovetailing with physical organic chemistry approaches to provide complete reaction mechanisms for enzymes by visualizing catalytic site interactions at different stages of the reaction. Such mechanistic insight is not only fundamentally important, impacting on inhibitor and drug design approaches with ramifications way beyond cellulose hydrolysis, but also provides the framework for the design of enzyme variants to use as biocatalysts for the synthesis of bespoke oligosaccharides. Here we review some of the strategies and tactics that may be applied to the X-ray structure solution of cellulases (and other carbohydrate-active enzymes). The general approach is first to decide why you are doing the work, then to establish correct domain boundaries for truncated constructs (typically the catalytic domain only), and finally to pursue crystallization of pure, homogeneous, and monodisperse protein with appropriate ligand and additive combinations. Cellulase-specific strategies are important for the delineation of domain boundaries, while glycoside hydrolases generally also present challenges and opportunities for the selection and optimization of ligands to both aid crystallization, and also provide structural and mechanistic insight. As the many roles for plant cell wall degrading enzymes increase, so does the need for rapid high-quality structure determination to provide a sound structural foundation for understanding mechanism and specificity, and for future protein engineering strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Poland's Education and Training: Boosting and Adapting Human Capital. OECD Economics Department Working Papers, No. 495

ERIC Educational Resources Information Center

O'Brien, Paul; Paczynski, Wojciech

2006-01-01

An effective system of education and training is important for both social and economic reasons. Its role in the Polish economy is to provide the current and future labour force with skills to facilitate both continuing productivity growth and reallocation of resources as structural adjustment proceeds. Important reforms to decentralise primary…

Knowledge representation issues for explaining plans

NASA Technical Reports Server (NTRS)

Prince, Mary Ellen; Johannes, James D.

1988-01-01

Explanations are recognized as an important facet of intelligent behavior. Unfortunately, expert systems are currently limited in their ability to provide useful, intelligent justifications of their results. We are currently investigating the issues involved in providing explanation facilities for expert planning systems. This investigation addresses three issues: knowledge content, knowledge representation, and explanation structure.

Lessons on RNA Silencing Mechanisms in Plants from Eukaryotic Argonaute Structures[W

PubMed Central

Poulsen, Christian; Vaucheret, Hervé; Brodersen, Peter

2013-01-01

RNA silencing refers to a collection of gene regulatory mechanisms that use small RNAs for sequence specific repression. These mechanisms rely on ARGONAUTE (AGO) proteins that directly bind small RNAs and thereby constitute the central component of the RNA-induced silencing complex (RISC). AGO protein function has been probed extensively by mutational analyses, particularly in plants where large allelic series of several AGO proteins have been isolated. Structures of entire human and yeast AGO proteins have only very recently been obtained, and they allow more precise analyses of functional consequences of mutations obtained by forward genetics. To a large extent, these analyses support current models of regions of particular functional importance of AGO proteins. Interestingly, they also identify previously unrecognized parts of AGO proteins with profound structural and functional importance and provide the first hints at structural elements that have important functions specific to individual AGO family members. A particularly important outcome of the analysis concerns the evidence for existence of Gly-Trp (GW) repeat interactors of AGO proteins acting in the plant microRNA pathway. The parallel analysis of AGO structures and plant AGO mutations also suggests that such interactions with GW proteins may be a determinant of whether an endonucleolytically competent RISC is formed. PMID:23303917

Lessons on RNA silencing mechanisms in plants from eukaryotic argonaute structures.

PubMed

Poulsen, Christian; Vaucheret, Hervé; Brodersen, Peter

2013-01-01

RNA silencing refers to a collection of gene regulatory mechanisms that use small RNAs for sequence specific repression. These mechanisms rely on ARGONAUTE (AGO) proteins that directly bind small RNAs and thereby constitute the central component of the RNA-induced silencing complex (RISC). AGO protein function has been probed extensively by mutational analyses, particularly in plants where large allelic series of several AGO proteins have been isolated. Structures of entire human and yeast AGO proteins have only very recently been obtained, and they allow more precise analyses of functional consequences of mutations obtained by forward genetics. To a large extent, these analyses support current models of regions of particular functional importance of AGO proteins. Interestingly, they also identify previously unrecognized parts of AGO proteins with profound structural and functional importance and provide the first hints at structural elements that have important functions specific to individual AGO family members. A particularly important outcome of the analysis concerns the evidence for existence of Gly-Trp (GW) repeat interactors of AGO proteins acting in the plant microRNA pathway. The parallel analysis of AGO structures and plant AGO mutations also suggests that such interactions with GW proteins may be a determinant of whether an endonucleolytically competent RISC is formed.

Determining the structure-mechanics relationships of dense microtubule networks with confocal microscopy and magnetic tweezers-based microrheology.

PubMed

Yang, Yali; Valentine, Megan T

2013-01-01

The microtubule (MT) cytoskeleton is essential in maintaining the shape, strength, and organization of cells. Its spatiotemporal organization is fundamental for numerous dynamic biological processes, and mechanical stress within the MT cytoskeleton provides an important signaling mechanism in mitosis and neural development. This raises important questions about the relationships between structure and mechanics in complex MT structures. In vitro, reconstituted cytoskeletal networks provide a minimal model of cell mechanics while also providing a testing ground for the fundamental polymer physics of stiff polymer gels. Here, we describe our development and implementation of a broad tool kit to study structure-mechanics relationships in reconstituted MT networks, including protocols for the assembly of entangled and cross-linked MT networks, fluorescence imaging, microstructure characterization, construction and calibration of magnetic tweezers devices, and mechanical data collection and analysis. In particular, we present the design and assembly of three neodymium iron boron (NdFeB)-based magnetic tweezers devices optimized for use with MT networks: (1) high-force magnetic tweezers devices that enable the application of nano-Newton forces and possible meso- to macroscale materials characterization; (2) ring-shaped NdFeB-based magnetic tweezers devices that enable oscillatory microrheology measurements; and (3) portable magnetic tweezers devices that enable direct visualization of microscale deformation in soft materials under applied force. Copyright © 2013 Elsevier Inc. All rights reserved.

Near-Seafloor Magnetic Exploration of Submarine Hydrothermal Systems in the Kermadec Arc

NASA Astrophysics Data System (ADS)

Caratori Tontini, F.; de Ronde, C. E. J.; Tivey, M.; Kinsey, J. C.

2014-12-01

Magnetic data can provide important information about hydrothermal systems because hydrothermal alteration can drastically reduce the magnetization of the host volcanic rocks. Near-seafloor data (≤70 m altitude) are required to map hydrothermal systems in detail; Autonomous Underwater Vehicles (AUVs) are the ideal platform to provide this level of resolution. Here, we show the results of high-resolution magnetic surveys by the ABE and Sentry AUVs for selected submarine volcanoes of the Kermadec arc. 3-D magnetization models derived from the inversion of magnetic data, when combined with high resolution seafloor bathymetry derived from multibeam surveys, provide important constraints on the subseafloor geometry of hydrothermal upflow zones and the structural control on the development of seafloor hydrothermal vent sites as well as being a tool for the discovery of previously unknown hydrothermal sites. Significant differences exist between the magnetic expressions of hydrothermal sites at caldera volcanoes ("donut" pattern) and cones ("Swiss cheese" pattern), respectively. Subseafloor 3-D magnetization models also highlight structural differences between focused and diffuse vent sites.

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

Datta, Kaustuv; Neder, Reinhard B.; Chen, Jun

Revelation of unequivocal structural information at the atomic level for complex systems is uniquely important for deeper and generic understanding of the structure property connections and a key challenge in materials science. Here in this paper we report an experimental study of the local structure by applying total elastic scattering and Raman scattering analyses to an important non-relaxor ferroelectric solid solution exhibiting the so-called composition-induced morphotropic phase boundary (MPB), where concomitant enhancement of physical properties have been detected. The powerful combination of static and dynamic structural probes enabled us to derive direct correspondence between the atomic-level structural correlations and reportedmore » properties. The atomic pair distribution functions obtained from the neutron total scattering experiments were analysed through big-box atom-modelling implementing reverse Monte Carlo method, from which distributions of magnitudes and directions of off-centred cationic displacements were extracted. We found that an enhanced randomness of the displacement-directions for all ferroelectrically active cations combined with a strong dynamical coupling between the A- and B-site cations of the perovskite structure, can explain the abrupt amplification of piezoelectric response of the system near MPB. Finally, altogether this provides a more fundamental basis in inferring structure-property connections in similar systems including important implications in designing novel and bespoke materials.« less

Hilbert space structure in quantum gravity: an algebraic perspective

DOE PAGES

Giddings, Steven B.

2015-12-16

If quantum gravity respects the principles of quantum mechanics, suitably generalized, it may be that a more viable approach to the theory is through identifying the relevant quantum structures rather than by quantizing classical spacetime. Here, this viewpoint is supported by difficulties of such quantization, and by the apparent lack of a fundamental role for locality. In finite or discrete quantum systems, important structure is provided by tensor factorizations of the Hilbert space. However, even in local quantum field theory properties of the generic type III von Neumann algebras and of long range gauge fields indicate that factorization of themore » Hilbert space is problematic. Instead it is better to focus on the structure of the algebra of observables, and in particular on its subalgebras corresponding to regions. This paper suggests that study of analogous algebraic structure in gravity gives an important perspective on the nature of the quantum theory. Significant departures from the subalgebra structure of local quantum field theory are found, working in the correspondence limit of long-distances/low-energies. Particularly, there are obstacles to identifying commuting algebras of localized operators. In addition to suggesting important properties of the algebraic structure, this and related observations pose challenges to proposals of a fundamental role for entanglement.« less

Hilbert space structure in quantum gravity: an algebraic perspective

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

Giddings, Steven B.

If quantum gravity respects the principles of quantum mechanics, suitably generalized, it may be that a more viable approach to the theory is through identifying the relevant quantum structures rather than by quantizing classical spacetime. Here, this viewpoint is supported by difficulties of such quantization, and by the apparent lack of a fundamental role for locality. In finite or discrete quantum systems, important structure is provided by tensor factorizations of the Hilbert space. However, even in local quantum field theory properties of the generic type III von Neumann algebras and of long range gauge fields indicate that factorization of themore » Hilbert space is problematic. Instead it is better to focus on the structure of the algebra of observables, and in particular on its subalgebras corresponding to regions. This paper suggests that study of analogous algebraic structure in gravity gives an important perspective on the nature of the quantum theory. Significant departures from the subalgebra structure of local quantum field theory are found, working in the correspondence limit of long-distances/low-energies. Particularly, there are obstacles to identifying commuting algebras of localized operators. In addition to suggesting important properties of the algebraic structure, this and related observations pose challenges to proposals of a fundamental role for entanglement.« less

Monte Carlo study of the honeycomb structure of anthraquinone molecules on Cu(111)

NASA Astrophysics Data System (ADS)

Kim, Kwangmoo; Einstein, T. L.

2011-06-01

Using Monte Carlo calculations of the two-dimensional (2D) triangular lattice gas model, we demonstrate a mechanism for the spontaneous formation of honeycomb structure of anthraquinone (AQ) molecules on a Cu(111) plane. In our model long-range attractions play an important role, in addition to the long-range repulsions and short-range attractions proposed by Pawin, Wong, Kwon, and Bartels [ScienceSCIEAS0036-807510.1126/science.1129309 313, 961 (2006)]. We provide a global account of the possible combinations of long-range attractive coupling constants which lead to a honeycomb superstructure. We also provide the critical temperature of disruption of the honeycomb structure and compare the critical local coverage rate of AQ’s where the honeycomb structure starts to form with the experimental observations.

Why is a computational framework for motivational and metacognitive control needed?

NASA Astrophysics Data System (ADS)

Sun, Ron

2018-01-01

This paper discusses, in the context of computational modelling and simulation of cognition, the relevance of deeper structures in the control of behaviour. Such deeper structures include motivational control of behaviour, which provides underlying causes for actions, and also metacognitive control, which provides higher-order processes for monitoring and regulation. It is argued that such deeper structures are important and thus cannot be ignored in computational cognitive architectures. A general framework based on the Clarion cognitive architecture is outlined that emphasises the interaction amongst action selection, motivation, and metacognition. The upshot is that it is necessary to incorporate all essential processes; short of that, the understanding of cognition can only be incomplete.

The Big Picture

ERIC Educational Resources Information Center

Coleman, William F.

2004-01-01

The importance of chemistry in daily life of the students is discussed. The approach provides a connection between the details of molecular structure, bonding and reactivity with many aspects of the impact of chemistry on the society.

Structure/function relationships in serotonin transporter: new insights from the structure of a bacterial transporter.

PubMed

Rudnick, G

2006-01-01

Serotonin transporter (SERT) serves the important function of taking up serotonin (5-HT) released during serotonergic neurotransmission. It is the target for important therapeutic drugs and psychostimulants. SERT catalyzes the influx of 5-HT together with Na+ and Cl- in a 1:1:1 stoichiometry. In the same catalytic cycle, there is coupled efflux of one K+ ion. SERT is one member of a large family of amino acid and amine transporters that is believed to utilize similar mechanisms of transport. A bacterial member of this family was recently crystallized, revealing the structural basis of these transporters. In light of the new structure, previous results with SERT have been re-interpreted, providing new insight into the substrate binding site, the permeation pathway, and the conformational changes that occur during the transport cycle.

Structural basis of nonribosomal peptide macrocyclization in fungi.

PubMed

Zhang, Jinru; Liu, Nicholas; Cacho, Ralph A; Gong, Zhou; Liu, Zhu; Qin, Wenming; Tang, Chun; Tang, Yi; Zhou, Jiahai

2016-12-01

Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (C T ) domain and the holo thiolation (T)-C T complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

First-Year Biology Students' Understandings of Meiosis: An Investigation Using a Structural Theoretical Framework

ERIC Educational Resources Information Center

Quinn, Frances; Pegg, John; Panizzon, Debra

2009-01-01

Meiosis is a biological concept that is both complex and important for students to learn. This study aims to explore first-year biology students' explanations of the process of meiosis, using an explicit theoretical framework provided by the Structure of the Observed Learning Outcome (SOLO) model. The research was based on responses of 334…

Build your own soil: exploring microfluidics to create microbial habitat structures

PubMed Central

Aleklett, Kristin; Kiers, E Toby; Ohlsson, Pelle; Shimizu, Thomas S; Caldas, Victor EA; Hammer, Edith C

2018-01-01

Soil is likely the most complex ecosystem on earth. Despite the global importance and extraordinary diversity of soils, they have been notoriously challenging to study. We show how pioneering microfluidic techniques provide new ways of studying soil microbial ecology by allowing simulation and manipulation of chemical conditions and physical structures at the microscale in soil model habitats. PMID:29135971

A Four- and Five-Factor Structural Model for Wechsler Tests: Does It Really Matter Clinically?

ERIC Educational Resources Information Center

Schwartz, David M.

2013-01-01

The purpose of this commentary is to focus on the clinical utility of the four- and five-factor structural models for the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). It provides a discussion of important considerations when evaluating the clinical utility of the…

Bonding and Structure. Independent Learning Project for Advanced Chemistry (ILPAC). Unit S4.

ERIC Educational Resources Information Center

Inner London Education Authority (England).

This unit on chemical bonding is one of 10 first year units produced by the Independent Learning Project for Advanced Chemistry (ILPAC). The unit, which consists of two levels, provides an introduction to the main types of chemical bonding and important aspects of structure. The main emphasis is placed on such topics as ionic and covalent bonding,…

Micronesian mangrove forest structure and tree responses to a severe typhoon

Treesearch

J. Boone Kauffman; Thomas G. Cole

2010-01-01

Tropical cyclones are common disturbances that have strong effects on mangrove composition and structure. Because there are numerous ecosystem services provided by mangroves, it is important to understand their adaptations and responses to these climatic events. In April 2004, Typhoon Sudal, a category 3–4 cyclone, passed over the state of Yap, Federated States of...

Object-oriented classification of forest structure from light detection and ranging data for stand mapping

Treesearch

Alicia A. Sullivan; Robert J. McGaughey; Hans-Erik Andersen; Peter Schiess

2009-01-01

Stand delineation is an important step in the process of establishing a forest inventory and provides the spatial framework for many forest management decisions. Many methods for extracting forest structure characteristics for stand delineation and other purposes have been researched in the past, primarily focusing on high-resolution imagery and satellite data. High-...

Organizational Learning from Cross-Cultural Experiences: An Ethnomethodological Case Study Examining the Relative Importance of Social Structure and Cultural Values during Dynamic Interaction

ERIC Educational Resources Information Center

Waldecker, Gary T.

2011-01-01

This study explored how social structure and cultural values dynamically interact in collective learning between two religious organizations cooperating in a joint project. It further explored the enablers of and impediments to collective learning in this context. The study employed the theoretical framework provided by the Organizational Learning…

Analyzing canopy structure in Pacific Northwest old-growth forests with a stand-scale crown model

Treesearch

Robert Van Pelt; Malcolm P. North

1996-01-01

I n forests, the canopy is the locale of critical ecosystem processes such as photosynthesis and evapotranspiration. and it provides essential habitat for a highly diverse array of animals, plants, and other organisms. Despite its importance, the structure of the canopy as a whole has had little quantitative study because limited access makes quantification difficult...

Interfacial Shear Strength of Multilayer Graphene Oxide Films.

PubMed

Daly, Matthew; Cao, Changhong; Sun, Hao; Sun, Yu; Filleter, Tobin; Singh, Chandra Veer

2016-02-23

Graphene oxide (GO) is considered as one of the most promising layered materials with tunable physical properties and applicability in many important engineering applications. In this work, the interfacial behavior of multilayer GO films was directly investigated via GO-to-GO friction force microscopy, and the interfacial shear strength (ISS) was measured to be 5.3 ± 3.2 MPa. Based on high resolution atomic force microscopy images and the available chemical data, targeted molecular dynamics simulations were performed to evaluate the influence of functional structure, topological defects, and interlayer registry on the shear response of the GO films. Theoretical values for shear strength ranging from 17 to 132 MPa were predicted for the different structures studied, providing upper bounds for the ISS. Computational results also revealed the atomic origins of the stochastic nature of friction measurements. Specifically, the wide scatter in experimental measurements was attributed to variations in functional structure and topological defects within the sliding volume. The findings of this study provide important insight for understanding the significant differences in strength between monolayer and bulk graphene oxide materials and can be useful for engineering topological structures with tunable mechanical properties.

An Automatic Method for Geometric Segmentation of Masonry Arch Bridges for Structural Engineering Purposes

NASA Astrophysics Data System (ADS)

Riveiro, B.; DeJong, M.; Conde, B.

2016-06-01

Despite the tremendous advantages of the laser scanning technology for the geometric characterization of built constructions, there are important limitations preventing more widespread implementation in the structural engineering domain. Even though the technology provides extensive and accurate information to perform structural assessment and health monitoring, many people are resistant to the technology due to the processing times involved. Thus, new methods that can automatically process LiDAR data and subsequently provide an automatic and organized interpretation are required. This paper presents a new method for fully automated point cloud segmentation of masonry arch bridges. The method efficiently creates segmented, spatially related and organized point clouds, which each contain the relevant geometric data for a particular component (pier, arch, spandrel wall, etc.) of the structure. The segmentation procedure comprises a heuristic approach for the separation of different vertical walls, and later image processing tools adapted to voxel structures allows the efficient segmentation of the main structural elements of the bridge. The proposed methodology provides the essential processed data required for structural assessment of masonry arch bridges based on geometric anomalies. The method is validated using a representative sample of masonry arch bridges in Spain.

Probing Xist RNA Structure in Cells Using Targeted Structure-Seq

PubMed Central

Rutenberg-Schoenberg, Michael; Simon, Matthew D.

2015-01-01

The long non-coding RNA (lncRNA) Xist is a master regulator of X-chromosome inactivation in mammalian cells. Models for how Xist and other lncRNAs function depend on thermodynamically stable secondary and higher-order structures that RNAs can form in the context of a cell. Probing accessible RNA bases can provide data to build models of RNA conformation that provide insight into RNA function, molecular evolution, and modularity. To study the structure of Xist in cells, we built upon recent advances in RNA secondary structure mapping and modeling to develop Targeted Structure-Seq, which combines chemical probing of RNA structure in cells with target-specific massively parallel sequencing. By enriching for signals from the RNA of interest, Targeted Structure-Seq achieves high coverage of the target RNA with relatively few sequencing reads, thus providing a targeted and scalable approach to analyze RNA conformation in cells. We use this approach to probe the full-length Xist lncRNA to develop new models for functional elements within Xist, including the repeat A element in the 5’-end of Xist. This analysis also identified new structural elements in Xist that are evolutionarily conserved, including a new element proximal to the C repeats that is important for Xist function. PMID:26646615

Linking models and data on vegetation structure

NASA Astrophysics Data System (ADS)

Hurtt, G. C.; Fisk, J.; Thomas, R. Q.; Dubayah, R.; Moorcroft, P. R.; Shugart, H. H.

2010-06-01

For more than a century, scientists have recognized the importance of vegetation structure in understanding forest dynamics. Now future satellite missions such as Deformation, Ecosystem Structure, and Dynamics of Ice (DESDynI) hold the potential to provide unprecedented global data on vegetation structure needed to reduce uncertainties in terrestrial carbon dynamics. Here, we briefly review the uses of data on vegetation structure in ecosystem models, develop and analyze theoretical models to quantify model-data requirements, and describe recent progress using a mechanistic modeling approach utilizing a formal scaling method and data on vegetation structure to improve model predictions. Generally, both limited sampling and coarse resolution averaging lead to model initialization error, which in turn is propagated in subsequent model prediction uncertainty and error. In cases with representative sampling, sufficient resolution, and linear dynamics, errors in initialization tend to compensate at larger spatial scales. However, with inadequate sampling, overly coarse resolution data or models, and nonlinear dynamics, errors in initialization lead to prediction error. A robust model-data framework will require both models and data on vegetation structure sufficient to resolve important environmental gradients and tree-level heterogeneity in forest structure globally.

Structural comparison of nickel electrodes and precursor phases

NASA Technical Reports Server (NTRS)

Cornilsen, Bahne C.; Shan, Xiaoyin; Loyselle, Patricia

1989-01-01

Researchers summarize previous Raman spectroscopic results and discuss important structural differences in the various phases of active mass and active mass precursors. Raman spectra provide unique signatures for these phases, and allow one to distinguish each phase, even when the compound is amorphous to x rays (i.e., does not scatter x rays because of a lack of order and/or small particle size). The structural changes incurred during formation, charge and discharge, cobalt addition, and aging are discussed. The oxidation states and dopant contents are explained in terms of the nonstoichiometric structures.

Characterizing Exterior and Interior Tropical Forest Structure Variability with Full-Waveform Airborne LIDAR Data in Lopé, Gabon

NASA Astrophysics Data System (ADS)

Marselis, S.; Tang, H.; Blair, J. B.; Hofton, M. A.; Armston, J.; Dubayah, R.

2017-12-01

Terrestrial ecotones, transition zones between ecological systems, have been identified as important regions to monitor the effects of environmental and human pressures on ecosystems. To observe such changes, the variability in vegetation horizontal and vertical structure must be characterized. The objective of this study is to quantify changes in vegetation structure in a tropical forest-savanna mosaic using airborne waveform lidar data. The study area is located in the northern part of the Lopé National Park in Gabon and is comprised of the vegetation types: savanna, colonizing forest, monodominant Okoumé forest, young Marantaceae forest and mixed Marantaceae forest. The lidar data were collected by the Land Vegetation and Ice Sensor (LVIS) in early March 2016, during the AfriSAR campaign. Metrics derived from the LVIS waveforms were then used to classify the five main vegetation types and characterize observed structural variability within types and across ecotones. Several supervised and unsupervised classification alogrithms, in combination with statistical analysis, were applied. The investigated methods are promising in their use to directly describe the structural variability within and between different vegetation types, map these vegetation types and the extent and location of their transition zones, and to characterize, among other attributes, the sharpness and width of such ecotones. These results provide important information in ecosystem studies as these methods can be used to study changes in vegetation structure, species-specific habitat, or the effects of deforestation and other human and natural pressures on the exterior and interior forest structure. These methods thus provide ample opportunity to assess the vegetation structure in degraded and second growth tropical forests to explore effects of e.g. grazing, logging or fragmentation. From this study we can conclude that lidar waveform remote sensing is highly useful in distinguishing vegetation types and their transition zones which will be increasingly important when assessing the impact of natural and human pressures on the world's tropical forests.

Experimental correlation of melt structures, nucleation rates, and thermal histories of silicate melts

NASA Technical Reports Server (NTRS)

Boynton, W. V.; DRAKE; HILDEBRAND; JONES; LEWIS; TREIMAN; WARK

1987-01-01

The theory and measurement of the structure of liquids is an important aspect of modern metallurgy and igneous petrology. Liquid structure exerts strong controls on both the types of crystals that may precipitate from melts and on the chemical composition of those crystals. An interesting aspect of melt structure studies is the problem of melt memories; that is, a melt can retain a memory of previous thermal history. This memory can influence both nucleation behavior and crystal composition. This melt memory may be characterized quantitatively with techniques such as Raman, infrared and NMR spectroscopy to provide information on short-range structure. Melt structure studies at high temperature will take advantage of the microgravity conditions of the Space Station to perform containerless experiments. Melt structure determinations at high temperature (experiments that are greatly facilitated by containerless technology) will provide invaluable information for materials science, glass technology, and geochemistry. In conjunction with studies of nucleation behavior and nucleation rates, information relevant to nucleation in magma chambers in terrestrial planets will be acquired.

Structural Characteristics and Function of a New Kind of Thermostable Trehalose Synthase from Thermobaculum terrenum.

PubMed

Wang, Junqing; Ren, Xudong; Wang, Ruiming; Su, Jing; Wang, Feng

2017-09-06

Trehalose has important applications in the food industry and pharmaceutical manufacturing. The thermostable enzyme trehalose synthase from Thermobaculum terrenum (TtTS) catalyzes the reversible interconversion of maltose and trehalose. Here, we investigated the structural characteristics of TtTS in complex with the inhibitor TriS. TtTS exhibits the typical three domain glycoside hydrolase family 13 structure. The catalytic cleft consists of Asp202-Glu244-Asp310 and various conserved substrate-binding residues. However, among trehalose synthases, TtTS demonstrates obvious thermal stability. TtTS has more polar (charged) amino acids distributed on its protein structure surface and more aromatic amino acids buried within than other mesophilic trehalose synthases. Furthermore, TtTS structural analysis revealed four potential metal ion-binding sites rather than the two in a homologous structure. These factors may render TtTS relatively more thermostable among mesophilic trehalose synthases. The detailed thermophilic enzyme structure provided herein may provide guidance for further protein engineering in the design of stabilized enzymes.

Substrate-bound Crystal Structures Reveal Features Unique to Mycobacterium tuberculosis N-Acetyl-glucosamine 1-Phosphate Uridyltransferase and a Catalytic Mechanism for Acetyl Transfer

PubMed Central

Jagtap, Pravin Kumar Ankush; Soni, Vijay; Vithani, Neha; Jhingan, Gagan Deep; Bais, Vaibhav Singh; Nandicoori, Vinay Kumar; Prakash, Balaji

2012-01-01

N-Acetyl-glucosamine-1-phosphate uridyltransferase (GlmU), a bifunctional enzyme involved in bacterial cell wall synthesis is exclusive to prokaryotes. GlmU, now recognized as a promising target to develop new antibacterial drugs, catalyzes two key reactions: acetyl transfer and uridyl transfer at two independent domains. Hitherto, we identified GlmU from Mycobacterium tuberculosis (GlmUMtb) to be unique in possessing a 30-residue extension at the C terminus. Here, we present the crystal structures of GlmUMtb in complex with substrates/products bound at the acetyltransferase active site. Analysis of these and mutational data, allow us to infer a catalytic mechanism operative in GlmUMtb. In this SN2 reaction, His-374 and Asn-397 act as catalytic residues by enhancing the nucleophilicity of the attacking amino group of glucosamine 1-phosphate. Ser-416 and Trp-460 provide important interactions for substrate binding. A short helix at the C-terminal extension uniquely found in mycobacterial GlmU provides the highly conserved Trp-460 for substrate binding. Importantly, the structures reveal an uncommon mode of acetyl-CoA binding in GlmUMtb; we term this the U conformation, which is distinct from the L conformation seen in the available non-mycobacterial GlmU structures. Residues, likely determining U/L conformation, were identified, and their importance was evaluated. In addition, we identified that the primary site for PknB-mediated phosphorylation is Thr-418, near the acetyltransferase active site. Down-regulation of acetyltransferase activity upon Thr-418 phosphorylation is rationalized by the structures presented here. Overall, this work provides an insight into substrate recognition, catalytic mechanism for acetyl transfer, and features unique to GlmUMtb, which may be exploited for the development of inhibitors specific to GlmU. PMID:22969087

Deterioration of concrete structures in coastal environment due to carbonation.

PubMed

Balaji, K V G D; Gopalaraju, S S S V; Trilochan, Jena

2010-07-01

Failure of existing concrete structures takes place due to lack of durability, and not due to less structural strength. One of the important aspects of durability is carbonation depth. The rate of carbonation in concrete is influenced by both its physical properties and exposure conditions. Rebar corrodes when carbonation reaches to a depth of concrete cover provided. In the present work, various concrete structures with different life periods and exposed to different weather conditions have been considered to study the carbonation effect. It is observed that the effect of carbonation is more in the structures located near to the sea coast and on windward face of the structure.

Combination of interferometry and thermography data for cultural heritage structural diagnostic research

NASA Astrophysics Data System (ADS)

Tornari, Vivi; Andrianakis, Michalis; Hatzigiannakis, Kostas; Kosma, Kiki; Detalle, Vincent; Giovanacci, David

2017-07-01

The demand for non destructive and non invasive structural diagnostic techniques able to perform on field remote structural evaluation of historical structures and works of art it faces an increased demand. The techniques must have some basic important characteristics The non destructivity, accuracy, repeatability, non physical contact, portability, resolution, broad range of applicability depending on the type of artwork and the question at hand, are all among the important requirements underlying the requirement for on-field structural diagnostics. In this respect there are two known techniques that have been developed at full to provide a suited structural diagnostic application in artwork conservation. The systems presented here but discussed in detail elsewhere are stimulated infrared thermography (SIRT) and digital holographic speckle pattern interferometry (DHSPI) the prior can be found n market at commercial devise level while the latter is at laboratory prototype level. The two systems are being exploited for their complimentary advantages and in this paper are used in combined testing on art related targets according to the above criteria to confirm the enhanced diagnostic information that their complimentary use provides. Results confirm the effectiveness of each technique alone and the combination of data of both techniques in the conservation field. Each system is first briefly described and examples are given with the aim to present the suitability and appropriateness for use in structural documentation analysis and reports. The experimental work is in laboratory work-in-progress focusing on the hybriding of data synthesis.

Molecular recognition of PTS-1 cargo proteins by Pex5p: implications for protein mistargeting in primary hyperoxaluria.

PubMed

Mesa-Torres, Noel; Tomic, Nenad; Albert, Armando; Salido, Eduardo; Pey, Angel L

2015-02-13

Peroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1), where alanine:glyoxylate aminotransferase (AGT) undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3-4 orders of magnitude) reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.

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

PubMed

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

2015-02-01

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

Crystal structure of Streptococcus pneumoniae pneumolysin provides key insights into early steps of pore formation

PubMed Central

Lawrence, Sara L.; Feil, Susanne C.; Morton, Craig J.; Farrand, Allison J.; Mulhern, Terrence D.; Gorman, Michael A.; Wade, Kristin R.; Tweten, Rodney K.; Parker, Michael W.

2015-01-01

Pore-forming proteins are weapons often used by bacterial pathogens to breach the membrane barrier of target cells. Despite their critical role in infection important structural aspects of the mechanism of how these proteins assemble into pores remain unknown. Streptococcus pneumoniae is the world’s leading cause of pneumonia, meningitis, bacteremia and otitis media. Pneumolysin (PLY) is a major virulence factor of S. pneumoniae and a target for both small molecule drug development and vaccines. PLY is a member of the cholesterol-dependent cytolysins (CDCs), a family of pore-forming toxins that form gigantic pores in cell membranes. Here we present the structure of PLY determined by X-ray crystallography and, in solution, by small-angle X-ray scattering. The crystal structure reveals PLY assembles as a linear oligomer that provides key structural insights into the poorly understood early monomer-monomer interactions of CDCs at the membrane surface. PMID:26403197

Structural Health Management for Future Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Prosser, W. H.; Allison, S. G.; Woodard, S. E.; Wincheski, R. A.; Cooper, E. G.; Price, D. C.; Hedley, M.; Prokopenko, M.; Scott, D. A.; Tessler, A.

2004-01-01

Structural Health Management (SHM) will be of critical importance to provide the safety, reliability and affordability necessary for the future long duration space missions described in America's Vision for Space Exploration. Long duration missions to the Moon, Mars and beyond cannot be accomplished with the current paradigm of periodic, ground based structural integrity inspections. As evidenced by the Columbia tragedy, this approach is also inadequate for the current Shuttle fleet, thus leading to its initial implementation of on-board SHM sensing for impact detection as part of the return to flight effort. However, future space systems, to include both vehicles as well as structures such as habitation modules, will require an integrated array of onboard in-situ sensing systems. In addition, advanced data systems architectures will be necessary to communicate, store and process massive amounts of SHM data from large numbers of diverse sensors. Further, improved structural analysis and design algorithms will be necessary to incorporate SHM sensing into the design and construction of aerospace structures, as well as to fully utilize these sensing systems to provide both diagnosis and prognosis of structural integrity. Ultimately, structural integrity information will feed into an Integrated Vehicle Health Management (IVHM) system that will provide real-time knowledge of structural, propulsion, thermal protection and other critical systems for optimal vehicle management and mission control. This paper will provide an overview of NASA research and development in the area of SHM as well as to highlight areas of technology improvement necessary to meet these future mission requirements.

GENETICS AND POPULATION-LEVEL RISK ASSESSMENT

EPA Science Inventory

Genetic variation defines population structure and provides the mechanism for populations to adapt to novel stressors. Despite its fundamental importance in understanding populations, genetic information has been included rarely in models of population dynamics (endangered speci...

Geologic framework and petroleum systems of Cook Inlet basin, south-central Alaska

USGS Publications Warehouse

LePain, D.L.; Stanley, Richard G.; Helmold, K.P.; Shellenbaum, D.P.; Stone, D.M.; Hite, D.M.

2013-01-01

This report provides a comprehensive overview of the stratigraphy, structure, tectonics, and petroleum systems of the Cook Inlet basin, an important oil- and gas-producing region in south-central Alaska.

Crystal Structures of Human SIRT[subscript 3] Displaying Substrate-induced Conformational Changes

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

Jin, Lei; Wei, Wentao; Jiang, Yaobin

2009-11-04

SIRT3 is a major mitochondrial NAD{sup +}-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets of crystal structures of human SIRT3, an apo-structure with no substrate, a structure with a peptide containing acetyl lysine of its natural substrate acetyl-CoA synthetase 2, a reaction intermediate structure trapped by a thioacetyl peptide, and a structure with the dethioacetylated peptide bound. These structures provide insights into themore » conformational changes induced by the two substrates required for the reaction, the acetylated substrate peptide and NAD+. In addition, the binding study by isothermal titration calorimetry suggests that the acetylated peptide is the first substrate to bind to SIRT3, before NAD{sup +}. These structures and biophysical studies provide key insight into the structural and functional relationship of the SIRT3 deacetylation activity.« less

Structure-based characterization of multiprotein complexes.

PubMed

Wiederstein, Markus; Gruber, Markus; Frank, Karl; Melo, Francisco; Sippl, Manfred J

2014-07-08

Multiprotein complexes govern virtually all cellular processes. Their 3D structures provide important clues to their biological roles, especially through structural correlations among protein molecules and complexes. The detection of such correlations generally requires comprehensive searches in databases of known protein structures by means of appropriate structure-matching techniques. Here, we present a high-speed structure search engine capable of instantly matching large protein oligomers against the complete and up-to-date database of biologically functional assemblies of protein molecules. We use this tool to reveal unseen structural correlations on the level of protein quaternary structure and demonstrate its general usefulness for efficiently exploring complex structural relationships among known protein assemblies. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

Jabbari, Hosna; Wark, Ian; Montemagno, Carlo

2018-01-01

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

Explaining Estimated Economies of Scale and Scope in Higher Education: A Meta-Regression Analysis

ERIC Educational Resources Information Center

Zhang, Liang-Cheng; Worthington, Andrew C.

2018-01-01

Numerous studies have investigated economies of scale and scope in higher education as a means of providing public and private providers of college and university teaching, research and other services and their stakeholders with knowledge of the cost structures that underpin provision in this economically and socially important sector. However,…

Reconstructing vegetation past: Pre-Euro-American vegetation for the midwest driftless area, USA

Treesearch

Monika E. Shea; Lisa A. Schulte; Brian J. Palik

2014-01-01

Historical reference conditions provide important context for creating ecological restoration and management plans. The U.S. 19th Century Public Land Survey (PLS) records provide extensive ecological information for constructing such reference conditions. We used PLS records to reconstruct pre-Euro-American tree species cover class and vegetation structure types for...

An effective introduction to structural crystallography using 1D Gaussian atoms

NASA Astrophysics Data System (ADS)

Smith, Emily; Evans, Gwyndaf; Foadi, James

2017-11-01

The most important quantitative aspects of computational structural crystallography can be introduced in a satisfactory way using 1D truncated and periodic Gaussian functions to represent the atoms in a crystal lattice. This paper describes in detail and demonstrates 1D structural crystallography starting with the definition of such truncated Gaussians. The availability of the computer programme CRONE makes possible the repetition of the examples provided in the paper as well as the creation of new ones.

Acoustic Modeling of Lightweight Structures: A Literature Review

NASA Astrophysics Data System (ADS)

Yang, Shasha; Shen, Cheng

2017-10-01

This paper gives an overview of acoustic modeling for three kinds of typical lightweight structures including double-leaf plate system, stiffened single (or double) plate and porous material. Classical models are citied to provide frame work of theoretical modeling for acoustic property of lightweight structures; important research advances derived by our research group and other authors are introduced to describe the current state of art for acoustic research. Finally, remaining problems and future research directions are concluded and prospected briefly

Modal loss mechanism of micro-structured VCSELs studied using full vector FDTD method.

PubMed

Jo, Du-Ho; Vu, Ngoc Hai; Kim, Jin-Tae; Hwang, In-Kag

2011-09-12

Modal properties of vertical cavity surface-emitting lasers (VCSELs) with holey structures are studied using a finite difference time domain (FDTD) method. We investigate loss behavior with respect to the variation of structural parameters, and explain the loss mechanism of VCSELs. We also propose an effective method to estimate the modal loss based on mode profiles obtained using FDTD simulation. Our results could provide an important guideline for optimization of the microstructures of high-power single-mode VCSELs.

Multiple-wavelength neutron holography with pulsed neutrons

PubMed Central

Hayashi, Kouichi; Ohoyama, Kenji; Happo, Naohisa; Matsushita, Tomohiro; Hosokawa, Shinya; Harada, Masahide; Inamura, Yasuhiro; Nitani, Hiroaki; Shishido, Toetsu; Yubuta, Kunio

2017-01-01

Local structures around impurities in solids provide important information for understanding the mechanisms of material functions, because most of them are controlled by dopants. For this purpose, the x-ray absorption fine structure method, which provides radial distribution functions around specific elements, is most widely used. However, a similar method using neutron techniques has not yet been developed. If one can establish a method of local structural analysis with neutrons, then a new frontier of materials science can be explored owing to the specific nature of neutron scattering—that is, its high sensitivity to light elements and magnetic moments. Multiple-wavelength neutron holography using the time-of-flight technique with pulsed neutrons has great potential to realize this. We demonstrated multiple-wavelength neutron holography using a Eu-doped CaF2 single crystal and obtained a clear three-dimensional atomic image around trivalent Eu substituted for divalent Ca, revealing an interesting feature of the local structure that allows it to maintain charge neutrality. The new holography technique is expected to provide new information on local structures using the neutron technique. PMID:28835917

Multiple-wavelength neutron holography with pulsed neutrons.

PubMed

Hayashi, Kouichi; Ohoyama, Kenji; Happo, Naohisa; Matsushita, Tomohiro; Hosokawa, Shinya; Harada, Masahide; Inamura, Yasuhiro; Nitani, Hiroaki; Shishido, Toetsu; Yubuta, Kunio

2017-08-01

Local structures around impurities in solids provide important information for understanding the mechanisms of material functions, because most of them are controlled by dopants. For this purpose, the x-ray absorption fine structure method, which provides radial distribution functions around specific elements, is most widely used. However, a similar method using neutron techniques has not yet been developed. If one can establish a method of local structural analysis with neutrons, then a new frontier of materials science can be explored owing to the specific nature of neutron scattering-that is, its high sensitivity to light elements and magnetic moments. Multiple-wavelength neutron holography using the time-of-flight technique with pulsed neutrons has great potential to realize this. We demonstrated multiple-wavelength neutron holography using a Eu-doped CaF 2 single crystal and obtained a clear three-dimensional atomic image around trivalent Eu substituted for divalent Ca, revealing an interesting feature of the local structure that allows it to maintain charge neutrality. The new holography technique is expected to provide new information on local structures using the neutron technique.

Understanding the structure and structural degradation mechanisms in high-voltage lithium-ion battery cathode oxides. A review of materials diagnostics

DOE PAGES

Mohanty, Debasish; Li, Jianlin; Nagpure, Shrikant C; ...

2015-12-21

Materials diagnostic techniques are the principal tools used in the development of low-cost, high-performance electrodes for next-generation lithium-based energy storage technologies. Also, this review highlights the importance of materials diagnostic techniques in unraveling the structure and the structural degradation mechanisms in high-voltage, high-capacity oxides that have the potential to be implemented in high-energy-density lithium-ion batteries for transportation that can use renewable energy and is less-polluting than today. The rise in CO 2 concentration in the earth’s atmosphere due to the use of petroleum products in vehicles and the dramatic increase in the cost of gasoline demand the replacement of currentmore » internal combustion engines in our vehicles with environmentally friendly, carbon free systems. Therefore, vehicles powered fully/partially by electricity are being introduced into today’s transportation fleet. As power requirements in all-electric vehicles become more demanding, lithium-ion battery (LiB) technology is now the potential candidate to provide higher energy density. Moreover, discovery of layered high-voltage lithium-manganese–rich (HV-LMR) oxides has provided a new direction toward developing high-energy-density LiBs because of their ability to deliver high capacity (~250 mA h/g) and to be operated at high operating voltage (~4.7 V). Unfortunately, practical use of HV-LMR electrodes is not viable because of structural changes in the host oxide during operation that can lead to fundamental and practical issues. This article provides the current understanding on the structure and structural degradation pathways in HV-LMR oxides, and manifests the importance of different materials diagnostic tools to unraveling the key mechanism(s). Furthermore, the fundamental insights reported, might become the tools to manipulate the chemical and/or structural aspects of HV-LMR oxides for low cost, high-energy-density LiB applications.« less

The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery.

PubMed

Papaleo, Elena; Saladino, Giorgio; Lambrughi, Matteo; Lindorff-Larsen, Kresten; Gervasio, Francesco Luigi; Nussinov, Ruth

2016-06-08

Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.

HDAPD: a web tool for searching the disease-associated protein structures

PubMed Central

2010-01-01

Background The protein structures of the disease-associated proteins are important for proceeding with the structure-based drug design to against a particular disease. Up until now, proteins structures are usually searched through a PDB id or some sequence information. However, in the HDAPD database presented here the protein structure of a disease-associated protein can be directly searched through the associated disease name keyed in. Description The search in HDAPD can be easily initiated by keying some key words of a disease, protein name, protein type, or PDB id. The protein sequence can be presented in FASTA format and directly copied for a BLAST search. HDAPD is also interfaced with Jmol so that users can observe and operate a protein structure with Jmol. The gene ontological data such as cellular components, molecular functions, and biological processes are provided once a hyperlink to Gene Ontology (GO) is clicked. Further, HDAPD provides a link to the KEGG map such that where the protein is placed and its relationship with other proteins in a metabolic pathway can be found from the map. The latest literatures namely titles, journals, authors, and abstracts searched from PubMed for the protein are also presented as a length controllable list. Conclusions Since the HDAPD data content can be routinely updated through a PHP-MySQL web page built, the new database presented is useful for searching the structures for some disease-associated proteins that may play important roles in the disease developing process for performing the structure-based drug design to against the diseases. PMID:20158919

Sequence-structure mapping errors in the PDB: OB-fold domains

PubMed Central

Venclovas, Česlovas; Ginalski, Krzysztof; Kang, Chulhee

2004-01-01

The Protein Data Bank (PDB) is the single most important repository of structural data for proteins and other biologically relevant molecules. Therefore, it is critically important to keep the PDB data, as much as possible, error-free. In this study, we have analyzed PDB crystal structures possessing oligonucleotide/oligosaccharide binding (OB)-fold, one of the highly populated folds, for the presence of sequence-structure mapping errors. Using energy-based structure quality assessment coupled with sequence analyses, we have found that there are at least five OB-structures in the PDB that have regions where sequences have been incorrectly mapped onto the structure. We have demonstrated that the combination of these computation techniques is effective not only in detecting sequence-structure mapping errors, but also in providing guidance to correct them. Namely, we have used results of computational analysis to direct a revision of X-ray data for one of the PDB entries containing a fairly inconspicuous sequence-structure mapping error. The revised structure has been deposited with the PDB. We suggest use of computational energy assessment and sequence analysis techniques to facilitate structure determination when homologs having known structure are available to use as a reference. Such computational analysis may be useful in either guiding the sequence-structure assignment process or verifying the sequence mapping within poorly defined regions. PMID:15133161

Fragment-based prediction of skin sensitization using recursive partitioning

NASA Astrophysics Data System (ADS)

Lu, Jing; Zheng, Mingyue; Wang, Yong; Shen, Qiancheng; Luo, Xiaomin; Jiang, Hualiang; Chen, Kaixian

2011-09-01

Skin sensitization is an important toxic endpoint in the risk assessment of chemicals. In this paper, structure-activity relationships analysis was performed on the skin sensitization potential of 357 compounds with local lymph node assay data. Structural fragments were extracted by GASTON (GrAph/Sequence/Tree extractiON) from the training set. Eight fragments with accuracy significantly higher than 0.73 ( p < 0.1) were retained to make up an indicator descriptor fragment. The fragment descriptor and eight other physicochemical descriptors closely related to the endpoint were calculated to construct the recursive partitioning tree (RP tree) for classification. The balanced accuracy of the training set, test set I, and test set II in the leave-one-out model were 0.846, 0.800, and 0.809, respectively. The results highlight that fragment-based RP tree is a preferable method for identifying skin sensitizers. Moreover, the selected fragments provide useful structural information for exploring sensitization mechanisms, and RP tree creates a graphic tree to identify the most important properties associated with skin sensitization. They can provide some guidance for designing of drugs with lower sensitization level.

Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time.

PubMed

Guo, Dong; IJzerman, Adriaan P

2018-01-01

G protein-coupled receptors (GPCRs) are integral membrane proteins and represent the largest class of drug targets. During the past decades progress in structural biology has enabled the crystallographic elucidation of the architecture of these important macromolecules. It also provided atomic-level visualization of ligand-receptor interactions, dramatically boosting the impact of structure-based approaches in drug discovery. However, knowledge obtained through crystallography is limited to static structural information. Less information is available showing how a ligand associates with or dissociates from a given receptor, whose importance is in fact increasingly recognized by the drug research community. Owing to recent advances in computer power and algorithms, molecular dynamics stimulations have become feasible that help in analyzing the kinetics of the ligand binding process. Here, we review what is currently known about the dynamics of GPCRs in the context of ligand association and dissociation, as determined through both crystallography and computer simulations. We particularly focus on the molecular basis of ligand dissociation from GPCRs and provide case studies that predict ligand dissociation pathways and residence time.

Biological structure and dynamics of fish assemblages in tributaries of eastern Lake Ontario

USGS Publications Warehouse

McKenna, James E.; Munawar, M.

2003-01-01

Interest in effective management of Great Lakes natural resources and restoration of native populations has stimulated interest in the conditions and ecological role of tributaries in the Great Lakes ecosystem. Rivers of Lake Ontario's eastern basin provide an excellent opportunity to examine important tributaries and their relationship to Lake Ontario. This paper reports on the results of an investigation of fish assemblage structure in lower reaches of the Salmon and Oswego Rivers and at their interfaces with Lake Ontario. These two systems represent conditions near the end points on a continuum from highly disturbed to pristine. They are also of great interest to resource managers for their important fisheries and other economic values. The objective was to identify distinct fish assemblages within these systems and relate their characteristics to biotic and abiotic conditions in an attempt to determine factors responsible for structuring and maintaining those species assemblages. This information is intended to provide baseline information for monitoring the status of these rivers and coastal systems and to aid in the development of models of ecological health.

Langley's CSI evolutionary model: Phase 2

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Reaves, Mercedes C.; Elliott, Kenny B.; Belvin, W. Keith; Teter, John E.

1995-01-01

Phase 2 testbed is part of a sequence of laboratory models, developed at NASA Langley Research Center, to enhance our understanding on how to model, control, and design structures for space applications. A key problem with structures that must perform in space is the appearance of unwanted vibrations during operations. Instruments, design independently by different scientists, must share the same vehicle causing them to interact with each other. Once in space, these problems are difficult to correct and therefore, prediction via analysis design, and experiments is very important. Phase 2 laboratory model and its predecessors are designed to fill a gap between theory and practice and to aid in understanding important aspects in modeling, sensor and actuator technology, ground testing techniques, and control design issues. This document provides detailed information on the truss structure and its main components, control computer architecture, and structural models generated along with corresponding experimental results.

Delinquency Among Members of Hong Kong Youth Street Gangs: The Role of the Organizational Structures of Gangs and Triad Affiliations.

PubMed

Chui, Wing Hong; Khiatani, Paul Vinod

2018-07-01

This study explores the importance of organizational structures and formal affiliations with the Hong Kong triads to delinquency among youth street gang members in Hong Kong. More specifically, this study examines the relative importance of the number of organizational structures and triad affiliation to patterns of delinquency in a sample of active members of youth street gangs ( N = 201). With the aid of outreach social workers, a convenience sampling method was used to recruit a gender-balanced sample of at-risk youths. Logistic regression analysis of the survey data that was gathered indicated that formal affiliation to Hong Kong triads and the presence of organizational structures significantly increased the odds of delinquency (independently of each other). Suggestions for future research on gang membership and delinquency, with particular reference to the Asian context, are provided.

A computational prediction of structure and function of novel homologue of Arabidopsis thaliana Vps51/Vps67 subunit in Corchorus olitorius.

PubMed

Zaman, Aubhishek; Fancy, Nurun Nahar

2012-12-01

Vps mediated vesicular transport is important for transferring macromolecules trapped inside a vesicle. Although highly abundant, Vps shows tremendous sequence variation among diverse array of species. However, this difference in sequence, which seems to also translate into substantial functional variation, is hardly characterized in Corchorus spp. Here, our computational study investigates structural and functional features of one of the Vps subunit namely Vps51/Vps67 in C. olitorius. Broad scale structural characterization revealed novel information about the overall Vps structure and binding sites. Moreover, functional analyses indicate interaction partners which were unexplored to date. Since membrane trafficking is essentially associated with nutrient uptake and chemical de-toxification, characterization of the Vps subunit can well provide us with better insight into important agronomic traits such as stress response, immune response and phytoremediation capacity.

Optimization of hierarchical structure and nanoscale-enabled plasmonic refraction for window electrodes in photovoltaics.

PubMed

Han, Bing; Peng, Qiang; Li, Ruopeng; Rong, Qikun; Ding, Yang; Akinoglu, Eser Metin; Wu, Xueyuan; Wang, Xin; Lu, Xubing; Wang, Qianming; Zhou, Guofu; Liu, Jun-Ming; Ren, Zhifeng; Giersig, Michael; Herczynski, Andrzej; Kempa, Krzysztof; Gao, Jinwei

2016-09-26

An ideal network window electrode for photovoltaic applications should provide an optimal surface coverage, a uniform current density into and/or from a substrate, and a minimum of the overall resistance for a given shading ratio. Here we show that metallic networks with quasi-fractal structure provides a near-perfect practical realization of such an ideal electrode. We find that a leaf venation network, which possesses key characteristics of the optimal structure, indeed outperforms other networks. We further show that elements of hierarchal topology, rather than details of the branching geometry, are of primary importance in optimizing the networks, and demonstrate this experimentally on five model artificial hierarchical networks of varied levels of complexity. In addition to these structural effects, networks containing nanowires are shown to acquire transparency exceeding the geometric constraint due to the plasmonic refraction.

Ecological intereactions of reef building corals

EPA Science Inventory

Coral reefs are very important marine ecosystems because they support tremendous biodiversity and reefs are critical economic resources many coastal nations. Tropical reef structures are largely built by stony corals. This presentation provides background on basic coral biology t...

Advances in the Biology and Chemistry of Sialic Acids

PubMed Central

Chen, Xi; Varki, Ajit

2010-01-01

Sialic acids are a subset of nonulosonic acids, which are nine-carbon alpha-keto aldonic acids. Natural existing sialic acid-containing structures are presented in different sialic acid forms, various sialyl linkages, and on diverse underlying glycans. They play important roles in biological, pathological, and immunological processes. Sialobiology has been a challenging and yet attractive research area. Recent advances in chemical and chemoenzymatic synthesis as well as large-scale E. coli cell-based production have provided a large library of sialoside standards and derivatives in amounts sufficient for structure-activity relationship studies. Sialoglycan microarrays provide an efficient platform for quick identification of preferred ligands for sialic acid-binding proteins. Future research on sialic acid will continue to be at the interface of chemistry and biology. Research efforts will not only lead to a better understanding of the biological and pathological importance of sialic acids and their diversity, but could also lead to the development of therapeutics. PMID:20020717

Geological Mapping of the North Polar Region of Venus (V-1 Snegurochka Planitia): Significant Problems and Comparisons to the Earth's Archean

NASA Technical Reports Server (NTRS)

Head, James W.; Hurwitz, D. M.; Ivanov, M. A.; Basilevsky, A. T.; Kumar, P. Senthil

2008-01-01

The geological features, structures, thermal conditions, interpreted processes, and outstanding questions related to both the Earth's Archean and Venus share many similarities and we are using a problem-oriented approach to Venus mapping, guided by perspectives from the Archean record of the Earth, to gain new insight into both. The Earth's preserved and well-documented Archean record provides important insight into high heat-flux tectonic and magmatic environments and structures and Venus reveals the current configuration and recent geological record of analogous high-temperature environments unmodified by subsequent several billion years of segmentation and overprinting, as on Earth. We have problems on which progress might be made through comparison. Here we present the major goals of the geological mapping of the V-1 Snegurochka Planitia Quadrangle, and themes that could provide important insights into both planets:

System for definition of the central-chest vasculature

NASA Astrophysics Data System (ADS)

Taeprasartsit, Pinyo; Higgins, William E.

2009-02-01

Accurate definition of the central-chest vasculature from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. For instance, the aorta and pulmonary artery help in automatic definition of the Mountain lymph-node stations for lung-cancer staging. This work presents a system for defining major vascular structures in the central chest. The system provides automatic methods for extracting the aorta and pulmonary artery and semi-automatic methods for extracting the other major central chest arteries/veins, such as the superior vena cava and azygos vein. Automatic aorta and pulmonary artery extraction are performed by model fitting and selection. The system also extracts certain vascular structure information to validate outputs. A semi-automatic method extracts vasculature by finding the medial axes between provided important sites. Results of the system are applied to lymph-node station definition and guidance of bronchoscopic biopsy.

Multidisciplinary Simulation of Graphite-Composite and Cermet Fuel Elements for NTP Point of Departure Designs

NASA Technical Reports Server (NTRS)

Stewart, Mark E.; Schnitzler, Bruce G.

2015-01-01

This paper compares the expected performance of two Nuclear Thermal Propulsion fuel types. High fidelity, fluid/thermal/structural + neutronic simulations help predict the performance of graphite-composite and cermet fuel types from point of departure engine designs from the Nuclear Thermal Propulsion project. Materials and nuclear reactivity issues are reviewed for each fuel type. Thermal/structural simulations predict thermal stresses in the fuel and thermal expansion mis-match stresses in the coatings. Fluid/thermal/structural/neutronic simulations provide predictions for full fuel elements. Although NTP engines will utilize many existing chemical engine components and technologies, nuclear fuel elements are a less developed engine component and introduce design uncertainty. Consequently, these fuel element simulations provide important insights into NTP engine performance.

Biomimicry in textiles: past, present and potential. An overview

PubMed Central

Eadie, Leslie; Ghosh, Tushar K.

2011-01-01

The natural world around us provides excellent examples of functional systems built with a handful of materials. Throughout the millennia, nature has evolved to adapt and develop highly sophisticated methods to solve problems. There are numerous examples of functional surfaces, fibrous structures, structural colours, self-healing, thermal insulation, etc., which offer important lessons for the textile products of the future. This paper provides a general overview of the potential of bioinspired textile structures by highlighting a few specific examples of pertinent, inherently sustainable biological systems. Biomimetic research is a rapidly growing field and its true potential in the development of new and sustainable textiles can only be realized through interdisciplinary research rooted in a holistic understanding of nature. PMID:21325320

Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease*

PubMed Central

Packer, Nicolle H.; Schulz, Benjamin L.

2016-01-01

The glycoproteome remains severely understudied because of significant analytical challenges associated with glycoproteomics, the system-wide analysis of intact glycopeptides. This review introduces important structural aspects of protein N-glycosylation and summarizes the latest technological developments and applications in LC-MS/MS-based qualitative and quantitative N-glycoproteomics. These maturing technologies provide unique structural insights into the N-glycoproteome and its synthesis and regulation by complementing existing methods in glycoscience. Modern glycoproteomics is now sufficiently mature to initiate efforts to capture the molecular complexity displayed by the N-glycoproteome, opening exciting opportunities to increase our understanding of the functional roles of protein N-glycosylation in human health and disease. PMID:26929216

Biomimicry in textiles: past, present and potential. An overview.

PubMed

Eadie, Leslie; Ghosh, Tushar K

2011-06-06

The natural world around us provides excellent examples of functional systems built with a handful of materials. Throughout the millennia, nature has evolved to adapt and develop highly sophisticated methods to solve problems. There are numerous examples of functional surfaces, fibrous structures, structural colours, self-healing, thermal insulation, etc., which offer important lessons for the textile products of the future. This paper provides a general overview of the potential of bioinspired textile structures by highlighting a few specific examples of pertinent, inherently sustainable biological systems. Biomimetic research is a rapidly growing field and its true potential in the development of new and sustainable textiles can only be realized through interdisciplinary research rooted in a holistic understanding of nature. © 2011 The Royal Society

Protein docking by the interface structure similarity: how much structure is needed?

PubMed

Sinha, Rohita; Kundrotas, Petras J; Vakser, Ilya A

2012-01-01

The increasing availability of co-crystallized protein-protein complexes provides an opportunity to use template-based modeling for protein-protein docking. Structure alignment techniques are useful in detection of remote target-template similarities. The size of the structure involved in the alignment is important for the success in modeling. This paper describes a systematic large-scale study to find the optimal definition/size of the interfaces for the structure alignment-based docking applications. The results showed that structural areas corresponding to the cutoff values <12 Å across the interface inadequately represent structural details of the interfaces. With the increase of the cutoff beyond 12 Å, the success rate for the benchmark set of 99 protein complexes, did not increase significantly for higher accuracy models, and decreased for lower-accuracy models. The 12 Å cutoff was optimal in our interface alignment-based docking, and a likely best choice for the large-scale (e.g., on the scale of the entire genome) applications to protein interaction networks. The results provide guidelines for the docking approaches, including high-throughput applications to modeled structures.

Exploring Human Diseases and Biological Mechanisms by Protein Structure Prediction and Modeling.

PubMed

Wang, Juexin; Luttrell, Joseph; Zhang, Ning; Khan, Saad; Shi, NianQing; Wang, Michael X; Kang, Jing-Qiong; Wang, Zheng; Xu, Dong

2016-01-01

Protein structure prediction and modeling provide a tool for understanding protein functions by computationally constructing protein structures from amino acid sequences and analyzing them. With help from protein prediction tools and web servers, users can obtain the three-dimensional protein structure models and gain knowledge of functions from the proteins. In this chapter, we will provide several examples of such studies. As an example, structure modeling methods were used to investigate the relation between mutation-caused misfolding of protein and human diseases including epilepsy and leukemia. Protein structure prediction and modeling were also applied in nucleotide-gated channels and their interaction interfaces to investigate their roles in brain and heart cells. In molecular mechanism studies of plants, rice salinity tolerance mechanism was studied via structure modeling on crucial proteins identified by systems biology analysis; trait-associated protein-protein interactions were modeled, which sheds some light on the roles of mutations in soybean oil/protein content. In the age of precision medicine, we believe protein structure prediction and modeling will play more and more important roles in investigating biomedical mechanism of diseases and drug design.

The influence of care provider access to structural empowerment on individualized care in long-term-care facilities.

PubMed

Caspar, Sienna; O'Rourke, Norm

2008-07-01

Implementing management initiatives that enable formal caregivers to provide quality, individualized care to older adults in long-term-care (LTC) facilities is increasingly important given that the number of LTC residents is projected to triple by 2031. The objective of this study was to explore the relationship between care provider access to structural empowerment and the provision of individualized care in LTC. We computed structural equation models separately for registered nurses and licensed practical nurses (n = 242) and care aides (n = 326) to examine the relationship between access to empowerment structures (i.e., informal power, formal power, information, support, resources, opportunity) and the provision of individualized care. We subsequently undertook invariance analyses to determine if the association between empowerment structures and reported provision of individualized care differed between caregiver groups. Access to structural empowerment had a statistically significant, positive association with provision of individualized care for both groups. For registered nurses/licensed practical nurses and care aides, empowerment explained 50% and 45% of observed variance in individualized care, respectively. These notable percentages did not differ significantly between caregiver groups. Of the empowerment structures, support, especially in the form of access to educational opportunities and recognition for a job well done, seems to be particularly significant to care providers. Findings from this study suggest that provision of individualized care in LTC may be enhanced when formal caregivers have appreciable access to empowerment structures.

Results from a first production of enhanced Silicon Sensor Test Structures produced by ITE Warsaw

NASA Astrophysics Data System (ADS)

Bergauer, T.; Dragicevic, M.; Frey, M.; Grabiec, P.; Grodner, M.; Hänsel, S.; Hartmann, F.; Hoffmann, K.-H.; Hrubec, J.; Krammer, M.; Kucharski, K.; Macchiolo, A.; Marczewski, J.

2009-01-01

Monitoring the manufacturing process of silicon sensors is essential to ensure stable quality of the produced detectors. During the CMS silicon sensor production we were utilising small Test Structures (TS) incorporated on the cut-away of the wafers to measure certain process-relevant parameters. Experience from the CMS production and quality assurance led to enhancements of these TS. Another important application of TS is the commissioning of new vendors. The measurements provide us with a good understanding of the capabilities of a vendor's process. A first batch of the new TS was produced at the Institute of Electron Technology in Warsaw Poland. We will first review the improvements to the original CMS test structures and then discuss a selection of important measurements performed on this first batch.

Trends in Asset Structure between Not-for-Profit and Investor Owned Hospitals

PubMed Central

Song, Paula H.; Reiter, Kristin L.

2010-01-01

The delivery of health care is a capital intensive industry and thus hospital investment strategy continues to be an important area of interest for both health policy and research. Much attention has been given to hospitals’ capital investment policies with relatively little attention to investments in financial assets, which serve an important role in NFP hospitals. This study describes and analyzes trends in aggregate asset structure between NFP and IO hospitals during the post-capital based PPS implementation period, providing the first documentation of long-term trends in hospital investment. We find hospitals’ aggregate asset structure differs significantly based on ownership, size, and profitability. For both NFP and IO hospitals, financial securities have remained consistent over time, while fixed asset representation has declined in IO hospitals. PMID:20519429

Engineered control of enzyme structural dynamics and function.

PubMed

Boehr, David D; D'Amico, Rebecca N; O'Rourke, Kathleen F

2018-04-01

Enzymes undergo a range of internal motions from local, active site fluctuations to large-scale, global conformational changes. These motions are often important for enzyme function, including in ligand binding and dissociation and even preparing the active site for chemical catalysis. Protein engineering efforts have been directed towards manipulating enzyme structural dynamics and conformational changes, including targeting specific amino acid interactions and creation of chimeric enzymes with new regulatory functions. Post-translational covalent modification can provide an additional level of enzyme control. These studies have not only provided insights into the functional role of protein motions, but they offer opportunities to create stimulus-responsive enzymes. These enzymes can be engineered to respond to a number of external stimuli, including light, pH, and the presence of novel allosteric modulators. Altogether, the ability to engineer and control enzyme structural dynamics can provide new tools for biotechnology and medicine. © 2018 The Protein Society.

Perceptions of homelessness in older homeless veterans, VA homeless program staff liaisons, and housing intervention providers.

PubMed

Molinari, Victor A; Brown, Lisa M; Frahm, Kathryn A; Schinka, John A; Casey, Roger

2013-05-01

To understand the needs and challenges encountered by older homeless veterans. We conducted six focus groups of older veterans, two focus groups, and one semi-structured interview of VA staff liaisons, and two focus groups and one semi-structured interview of housing intervention providers. Major themes for older veterans: 1) negative homelessness experience; 2) benefits of the structured transitional housing program; 3) importance of peer outreach; and 4) need for age-tailored job placement programs. Major themes for VA staff liaison/housing intervention providers: 1) belief that the transitional housing program has made a positive change; 2) need for individualized criteria to address the unique needs of veterans; 3) distinct differences between older and younger homeless veterans; 4) outreach services; 5) permanent housing issues; and 6) coordination of services. Compared with younger veterans, older veterans have less social support, greater employment and health challenges, and, perhaps greater motivation to change.

Determinants of RNA binding and translational repression by the Bicaudal-C regulatory protein.

PubMed

Zhang, Yan; Park, Sookhee; Blaser, Susanne; Sheets, Michael D

2014-03-14

Bicaudal-C (Bic-C) RNA binding proteins function as important translational repressors in multiple biological contexts within metazoans. However, their RNA binding sites are unknown. We recently demonstrated that Bic-C functions in spatially regulated translational repression of the xCR1 mRNA during Xenopus development. This repression contributes to normal development by confining the xCR1 protein, a regulator of key signaling pathways, to specific cells of the embryo. In this report, we combined biochemical approaches with in vivo mRNA reporter assays to define the minimal Bic-C target site within the xCR1 mRNA. This 32-nucleotide Bic-C target site is predicted to fold into a stem-loop secondary structure. Mutational analyses provided evidence that this stem-loop structure is important for Bic-C binding. The Bic-C target site was sufficient for Bic-C mediated repression in vivo. Thus, we describe the first RNA binding site for a Bic-C protein. This identification provides an important step toward understanding the mechanisms by which evolutionarily conserved Bic-C proteins control cellular function in metazoans.

Development and Application of a Structural Health Monitoring System Based on Wireless Smart Aggregates

PubMed Central

Ma, Haoyan; Li, Peng; Song, Gangbing; Wu, Jianxin

2017-01-01

Structural health monitoring (SHM) systems can improve the safety and reliability of structures, reduce maintenance costs, and extend service life. Research on concrete SHMs using piezoelectric-based smart aggregates have reached great achievements. However, the newly developed techniques have not been widely applied in practical engineering, largely due to the wiring problems associated with large-scale structural health monitoring. The cumbersome wiring requires much material and labor work, and more importantly, the associated maintenance work is also very heavy. Targeting a practical large scale concrete crack detection (CCD) application, a smart aggregates-based wireless sensor network system is proposed for the CCD application. The developed CCD system uses Zigbee 802.15.4 protocols, and is able to perform dynamic stress monitoring, structural impact capturing, and internal crack detection. The system has been experimentally validated, and the experimental results demonstrated the effectiveness of the proposed system. This work provides important support for practical CCD applications using wireless smart aggregates. PMID:28714927

Development and Application of a Structural Health Monitoring System Based on Wireless Smart Aggregates.

PubMed

Yan, Shi; Ma, Haoyan; Li, Peng; Song, Gangbing; Wu, Jianxin

2017-07-17

Structural health monitoring (SHM) systems can improve the safety and reliability of structures, reduce maintenance costs, and extend service life. Research on concrete SHMs using piezoelectric-based smart aggregates have reached great achievements. However, the newly developed techniques have not been widely applied in practical engineering, largely due to the wiring problems associated with large-scale structural health monitoring. The cumbersome wiring requires much material and labor work, and more importantly, the associated maintenance work is also very heavy. Targeting a practical large scale concrete crack detection (CCD) application, a smart aggregates-based wireless sensor network system is proposed for the CCD application. The developed CCD system uses Zigbee 802.15.4 protocols, and is able to perform dynamic stress monitoring, structural impact capturing, and internal crack detection. The system has been experimentally validated, and the experimental results demonstrated the effectiveness of the proposed system. This work provides important support for practical CCD applications using wireless smart aggregates.

The metabolism of structured triacylglycerols.

PubMed

Mu, Huiling; Porsgaard, Trine

2005-11-01

The triacylglycerol (TAG) structure in addition to the overall fatty acid profile is of importance when considering the nutritional effect of a dietary fat. This review aims at summarizing our current knowledge of the digestion, absorption, uptake, and transport of structured TAGs, with particular emphasis on the following aspects: gastric emptying, specificity of pancreatic lipase, lymphatic transport and clearance of chylomicrons, effects of lipid structure on tissue lipid compositions and the fecal loss of fats. So an overview will be provided for how the structure and fatty acid composition of TAGs affect their absorption and the distribution of the fatty acids in the body following digestion and absorption.

Diffusion-advection within dynamic biological gaps driven by structural motion

NASA Astrophysics Data System (ADS)

Asaro, Robert J.; Zhu, Qiang; Lin, Kuanpo

2018-04-01

To study the significance of advection in the transport of solutes, or particles, within thin biological gaps (channels), we examine theoretically the process driven by stochastic fluid flow caused by random thermal structural motion, and we compare it with transport via diffusion. The model geometry chosen resembles the synaptic cleft; this choice is motivated by the cleft's readily modeled structure, which allows for well-defined mechanical and physical features that control the advection process. Our analysis defines a Péclet-like number, AD, that quantifies the ratio of time scales of advection versus diffusion. Another parameter, AM, is also defined by the analysis that quantifies the full potential extent of advection in the absence of diffusion. These parameters provide a clear and compact description of the interplay among the well-defined structural, geometric, and physical properties vis-a ̀-vis the advection versus diffusion process. For example, it is found that AD˜1 /R2 , where R is the cleft diameter and hence diffusion distance. This curious, and perhaps unexpected, result follows from the dependence of structural motion that drives fluid flow on R . AM, on the other hand, is directly related (essentially proportional to) the energetic input into structural motion, and thereby to fluid flow, as well as to the mechanical stiffness of the cleftlike structure. Our model analysis thus provides unambiguous insight into the prospect of competition of advection versus diffusion within biological gaplike structures. The importance of the random, versus a regular, nature of structural motion and of the resulting transient nature of advection under random motion is made clear in our analysis. Further, by quantifying the effects of geometric and physical properties on the competition between advection and diffusion, our results clearly demonstrate the important role that metabolic energy (ATP) plays in this competitive process.

Selected Topics in Light Front Field Theory and Applications to the High Energy Phenomena

NASA Astrophysics Data System (ADS)

Kundu, Rajen

1999-10-01

In this thesis, we have presented some of the aspects of light-front (LF) field theory through their successful application in the Deep Inelastic Scattering (DIS). We have developed a LFQCD Hamiltonian description of the DIS structure functions starting from Bjorken-Johnson-Low limit of virtual forward Compton scattering amplitude and using LF current commutators. We worked in the LF gauge A^+=0 and used the old-fashioned LFQCD perturbation theory in our calculations. The importance of our work are summarized below. Our approach shares the intution of parton model and addresses directly the structure functions, which are experimental objects, instead of its moments as in OPE method. Moreover, it can potentially incorporate the non-perturbative contents of the structure functions as we have demonstrated by introducing a new factorization scheme. In the context of nucleonic helicity structure, the well known gauge fixed LF helicity operator is shown to provide consistent physical information and helps us defining new relevant structure functions. The anomalous dimensions relevant for the Q^2-evolution of such structure functions are calculated. Our study is important in establishing the equivalance of LF field theory and the usual equal-time one through perturbative calculations of the dressed parton structure functions reproducing the well known results. Also the importance of Gallilean boost symmetry in understanding the correctness of any higher order calculation using (x^+)-ordered LFQCD perturbation theory are emphasized.

Structural Color Tuning: Mixing Melanin-Like Particles with Different Diameters to Create Neutral Colors.

PubMed

Kawamura, Ayaka; Kohri, Michinari; Yoshioka, Shinya; Taniguchi, Tatsuo; Kishikawa, Keiki

2017-04-18

We present the ability to tune structural colors by mixing colloidal particles. To produce high-visibility structural colors, melanin-like core-shell particles composed of a polystyrene (PSt) core and a polydopamine (PDA) shell, were used as components. The results indicated that neutral structural colors could be successfully obtained by simply mixing two differently sized melanin-like PSt@PDA core-shell particles. In addition, the arrangements of the particles, which were important factors when forming structural colors, were investigated by mathematical processing using a 2D Fourier transform technique and Voronoi diagrams. These findings provide new insights for the development of structural color-based ink applications.

Near-terminator and earthshine photography. [special lunar photography obtained during Apollo 17 flight

NASA Technical Reports Server (NTRS)

Head, J. W.; Lloyd, D.

1973-01-01

Photographic results obtained during the Apollo 17 flight for the near terminator and earthshine conditions are discussed. Lunar surface photographs taken in the vicinity of the sunshine terminator provide important information that is not obtained on photographs taken at higher sun evaluation angles. Earthshine photography also provides data on low relief, crater morphology, and small scale structures. Examples of photographs of the lunar surface taken under both conditions are provided.

XVII International Conference on Hadron Spectroscopy and Structure

NASA Astrophysics Data System (ADS)

2017-09-01

The Hadron 2017 Conference is the seventeenth of a series of biennial conferences started in 1985 at Maryland, USA. Its official name, XVII International Conference on Hadron Spectroscopy and Structure, includes for the first time the term structure to emphasize the importance that this issue has acquired in recent editions of the series. The aim of the conference is to provide an overview of the present status and progress in hadron structure and dynamics, as well as a preview of the forthcoming investigations. It will cover lectures on both experimental and theoretical aspects, including in particular the presentation of new results.

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.

Crystal structure of enolase from Drosophila melanogaster.

PubMed

Sun, Congcong; Xu, Baokui; Liu, Xueyan; Zhang, Zhen; Su, Zhongliang

2017-04-01

Enolase is an important enzyme in glycolysis and various biological processes. Its dysfunction is closely associated with diseases. Here, the enolase from Drosophila melanogaster (DmENO) was purified and crystallized. A crystal of DmENO diffracted to 2.0 Å resolution and belonged to space group R32. The structure was solved by molecular replacement. Like most enolases, DmENO forms a homodimer with conserved residues in the dimer interface. DmENO possesses an open conformation in this structure and contains conserved elements for catalytic activity. This work provides a structural basis for further functional and evolutionary studies of enolase.

Identification of kin structure among Guam rail founders: a comparison of pedigrees and DNA profiles

USGS Publications Warehouse

Haig, Susan M.; Ballou, J.D.; Casna, N.J.

1994-01-01

Kin structure among founders can have a significant effect on subsequent population structure. Here we use the correlation between DNA profile similarity and relatedness calculated from pedigrees to test hypotheses regarding kin structure among founders to the captive Guam rail (Rallus owstoni) population. Five different pedigrees were generated under the following hypotheses: (i) founders are unrelated; (ii) founders are unrelated except for same-nest chicks; (iii) founders from the same major site are siblings; (iv) founders from the same local site are siblings; and (v) founders are related as defined by a UPGMA cluster analysis of DNA similarity data. Relatedness values from pedigrees 1, 2 and 5 had the highest correlation with DNA similarity but the correlation between relatedness and similarity were not significantly different among pedigrees. Pedigree 5 resulted in the highest correlation overall when using only relatedness values that changed as a result of different founder hypotheses. Thus, founders were assigned relatedness based on pedigree 5 because it had the highest correlations with DNA similarity, was the most conservative approach, and incorporated all field data. The analyses indicated that estimating relatedness using DNA profiles remains problematic, therefore we compared mean kinship, a measure of genetic importance, with mean DNA profile similarity to determine if genetic importance among individuals could be determined via use of DNA profiles alone. The significant correlation suggests this method may provide more information about population structure than was previously thought. Thus, DNA profiles can provide a reasonable explanation for founder relatedness and mean DNA profile similarity may be helpful in determining relative genetic importance of individuals when detailed pedigrees are absent.

Ion Spectral Structures Observed by the Van Allen Probes and Cluster

NASA Astrophysics Data System (ADS)

Ferradas, C.; Zhang, J.; Luo, H.; Kistler, L. M.; Spence, H. E.; Larsen, B.; Skoug, R. M.; Funsten, H. O.; Reeves, G. D.

2014-12-01

During the last decades several missions have recorded the presence of dynamic spectral features of energetic ions in the inner magnetosphere. Previous studies have revealed single "nose-like" structures occurring alone and simultaneous nose-like structures (up to three). In this study we also include signatures of new types of ion structure, namely "trunk-like" and "tusk-like" structures. All the ion structures are named after the characteristic shapes of energy bands or gaps in the energy-time spectrograms of in situ measured ion fluxes. They constitute the observational signatures of ion acceleration, transport, and loss in the global magnetosphere. Multi-spacecraft analysis of these structures is important to understand their spatial distribution and temporal evolution. Mass spectrometers onboard Cluster (in a polar orbit) and the Van Allen Probes (in an equatorial orbit) measure energetic hydrogen, helium, and oxygen ions near the inner edge of the plasma sheet, where these ion structures are observed. We present a statistical study of the ion structures, using >1-year measurements from the two missions during the Van Allen Probes era. The results provide important details about the spatial distribution (dependence on geocentric distance and magnetic local time), spectral features of the structures (e.g., characteristic energy and differences among species), and geomagnetic and solar wind conditions under which these structures occur.

Genetic structure of the threatened Phaedranassa schizantha (Amaryllidaceae)

USDA-ARS?s Scientific Manuscript database

Population genetic analysis can provide important information for the conservation of endangered species. Phaedranassa schizantha Baker (Amaryllidaceae) is an endangered species endemic to Ecuador. Taxonomically P. schizantha was described as two varieties: P. schizantha var. schizantha and P. schiz...

The Wood and Bark of Hardwoods Growing on Southern Pine Sites - A Pictorial Atlas

Treesearch

Charles W. McMillin; Floyd G. Manwiller

1980-01-01

Provides a pictorial description of the structure and appearance of 23 pine-site hardwoods, an overview of hardwood anatomy, and data on the resource and certain important physical properties of stemwood and bark.

Healthcare preferences of lesbian, gay, bisexual, transgender and questioning youth.

PubMed

Hoffman, Neal D; Freeman, Katherine; Swann, Stephanie

2009-09-01

Lesbian, gay, bisexual, transgender and questioning (LGBTQ) youth appear to be at higher risk for certain adverse health outcomes, and to have several personal, cultural and structural barriers to accessing healthcare. Little is known, however, about the experiences of LGBTQ youth with healthcare providers and healthcare services. Our goal was to recruit a sample of LGBTQ youth and to determine their preferences regarding healthcare providers, healthcare settings and the health issues that they consider important to discuss with a healthcare provider. We conducted a cross-sectional Internet-based survey. Respondents ages 13-21 years and living in the U.S. or Canada were asked to review three lists of items pertaining to qualities of healthcare providers, qualities of offices or health centers, and concerns or problems to discuss with a healthcare provider, and then to assign for each item a relative importance. Items in each of the three lists were then ranked, and differences among ranks were assessed. Inter-group differences by age, gender, and race/ethnicity were also assessed. 733 youth met eligibility criteria. Youth indicated as most important competence overall and specifically in issues unique to taking care of youth and LGBTQ persons, as well as being respected and treated by providers the same as other youth. Notably, youth ranked as least important the provider's gender and sexual orientation. Youth ranked accessibility issues higher than specific services provided. As health concerns to discuss with a provider, youth ranked preventive healthcare, nutrition, safe sex, and family as important as common morbidities. Youth placed as much importance on provider qualities and interpersonal skills as provider knowledge and experience, and placed little importance on a provider's gender and sexual orientation. Youth indicated the importance of providers addressing not only health risks, but also wellness and health promotion, and to do so within the context of home and family. Subgroup analyses underscore the need for greater sensitivity to both cultural and developmental differences among LGBTQ youth. These results provide a foundation for further research about healthcare services and delivery systems for youth, training initiatives for healthcare providers, and the role of utilizing the Internet for health research purposes to access and recruit hard-to-reach youth.

Designing food structures for nutrition and health benefits.

PubMed

Norton, Jennifer E; Wallis, Gareth A; Spyropoulos, Fotis; Lillford, Peter J; Norton, Ian T

2014-01-01

In addition to providing specific sensory properties (e.g., flavor or textures), there is a need to produce foods that also provide functionality within the gastrointestinal (GI) tract, over and above simple nutrition. As such, there is a need to understand the physical and chemical processes occurring in the mouth, stomach, small intestine, and large intestine, in addition to the food structure-physiology interactions. In vivo techniques and in vitro models have allowed us to study and simulate these processes, which aids us in the design of food microstructures that can provide functionality within the human body. Furthermore, it is important to be aware of the health or nutritional needs of different groups of consumers when designing food structures, to provide targeted functionality. Examples of three groups of consumers (elderly, obese, and athletes) are given to demonstrate their differing nutritional requirements and the formulation engineering approaches that can be utilized to improve the health of these individuals. Eating is a pleasurable process, but foods of the future will be required to provide much more in terms of functionality for health and nutrition.

Antenatal education for childbirth-epidural analgesia.

PubMed

Cutajar, Lisa; Cyna, Allan M

2018-05-07

The language structures used by antenatal educators have not been previously researched in the context of antenatal childbirth classes. Epidural analgesia for labour is a common, and a frequently asked about, component of antenatal education for parents in hospitals providing maternity care. We aimed to identify the way information is described and presented by childbirth educators to assess content and determine which language structures such as metaphor, suggestion, information and storytelling are utilized. This observational study of antenatal education was conducted at a single tertiary referral center for maternity care in Western Sydney, Australia. All three childbirth educators agreed to be video recorded whilst providing information to parents during antenatal classes. Audio data was subsequently transcribed and then analysed by two researchers, independently categorising the various language structures and types of information provided. For the purposes of the current study, data concerning a single topic was used for the analysis-'epidural analgesia for labour'. Language structures used were highly variable between educators, as was the content and time taken for the information being provided. Our findings represent a first attempt to identify baseline information used in the clinical setting of antenatal education in order to categories communication structures used. This study has identified areas for further improvements and consistency in the way educators provide information to parents and has important implications for future midwifery practice, education and research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

PubMed Central

Baskerville, Edward B.; Dobson, Andy P.; Bedford, Trevor; Allesina, Stefano; Anderson, T. Michael; Pascual, Mercedes

2011-01-01

Food webs, networks of feeding relationships in an ecosystem, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. A standard approach in food-web analysis, and network analysis in general, has been to identify compartments, or modules, defined by many links within compartments and few links between them. This approach can identify large habitat boundaries in the network but may fail to identify other important structures. Empirical analyses of food webs have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure using a flexible definition that can describe both functional trophic roles and standard compartments. We apply this method to a newly compiled plant-mammal food web from the Serengeti ecosystem that includes high taxonomic resolution at the plant level, allowing a simultaneous examination of the signature of both habitat and trophic roles in network structure. We find that groups at the plant level reflect habitat structure, coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial pattern, in contrast to the standard compartments typically identified. The network topology supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence. Furthermore, our Bayesian approach provides a powerful, flexible framework for the study of network structure, and we believe it will prove instrumental in a variety of biological contexts. PMID:22219719

The Implementation of a Structured Nursing Leadership Development Program for Succession Planning in a Health System.

PubMed

Ramseur, Priscilla; Fuchs, Mary Ann; Edwards, Pamela; Humphreys, Janice

2018-01-01

Preparing future nursing leaders to be successful is important because many current leaders will retire in large numbers in the future. A structured nursing leadership development program utilizing the Essentials of Nurse Manager Orientation online program provided future nursing leaders with content aligned with nursing leadership competencies. Paired with assigned mentors and monthly leadership sessions, the participants increased their perception of leadership competence.

Wildlife habitats in managed rangelands—the Great Basin of southeastern Oregon: the relationship of terrestrial vertebrates to plant communities and structural conditions (Part 1).

Treesearch

Chris Maser; Jack Ward Thomas; Ralph G. Anderson

1984-01-01

The relationships of terrestrial vertebrates to plant communities, structural conditions, and special habitats in the Great Basin of southeastern Oregon are described. The importance of habitat components to wildlife and the predictability of management activities on wildlife are examined in terms of managed rangelands. The paper does not provide guidelines but rather...

Structural model of dodecameric heat-shock protein Hsp21: Flexible N-terminal arms interact with client proteins while C-terminal tails maintain the dodecamer and chaperone activity.

PubMed

Rutsdottir, Gudrun; Härmark, Johan; Weide, Yoran; Hebert, Hans; Rasmussen, Morten I; Wernersson, Sven; Respondek, Michal; Akke, Mikael; Højrup, Peter; Koeck, Philip J B; Söderberg, Christopher A G; Emanuelsson, Cecilia

2017-05-12

Small heat-shock proteins (sHsps) prevent aggregation of thermosensitive client proteins in a first line of defense against cellular stress. The mechanisms by which they perform this function have been hard to define due to limited structural information; currently, there is only one high-resolution structure of a plant sHsp published, that of the cytosolic Hsp16.9. We took interest in Hsp21, a chloroplast-localized sHsp crucial for plant stress resistance, which has even longer N-terminal arms than Hsp16.9, with a functionally important and conserved methionine-rich motif. To provide a framework for investigating structure-function relationships of Hsp21 and understanding these sequence variations, we developed a structural model of Hsp21 based on homology modeling, cryo-EM, cross-linking mass spectrometry, NMR, and small-angle X-ray scattering. Our data suggest a dodecameric arrangement of two trimer-of-dimer discs stabilized by the C-terminal tails, possibly through tail-to-tail interactions between the discs, mediated through extended I X V X I motifs. Our model further suggests that six N-terminal arms are located on the outside of the dodecamer, accessible for interaction with client proteins, and distinct from previous undefined or inwardly facing arms. To test the importance of the I X V X I motif, we created the point mutant V181A, which, as expected, disrupts the Hsp21 dodecamer and decreases chaperone activity. Finally, our data emphasize that sHsp chaperone efficiency depends on oligomerization and that client interactions can occur both with and without oligomer dissociation. These results provide a generalizable workflow to explore sHsps, expand our understanding of sHsp structural motifs, and provide a testable Hsp21 structure model to inform future investigations. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Are X-rays the key to integrated computational materials engineering?

DOE PAGES

Ice, Gene E.

2015-11-01

The ultimate dream of materials science is to predict materials behavior from composition and processing history. Owing to the growing power of computers, this long-time dream has recently found expression through worldwide excitement in a number of computation-based thrusts: integrated computational materials engineering, materials by design, computational materials design, three-dimensional materials physics and mesoscale physics. However, real materials have important crystallographic structures at multiple length scales, which evolve during processing and in service. Moreover, real materials properties can depend on the extreme tails in their structural and chemical distributions. This makes it critical to map structural distributions with sufficient resolutionmore » to resolve small structures and with sufficient statistics to capture the tails of distributions. For two-dimensional materials, there are high-resolution nondestructive probes of surface and near-surface structures with atomic or near-atomic resolution that can provide detailed structural, chemical and functional distributions over important length scales. Furthermore, there are no nondestructive three-dimensional probes with atomic resolution over the multiple length scales needed to understand most materials.« less

Protein modeling and molecular dynamics simulation of SlWRKY4 protein cloned from drought tolerant tomato (Solanum habrochaites) line EC520061.

PubMed

Karkute, Suhas G; Easwaran, Murugesh; Gujjar, Ranjit Singh; Piramanayagam, Shanmughavel; Singh, Major

2015-10-01

WRKY genes are members of one of the largest families of plant transcription factors and play an important role in response to biotic and abiotic stresses, and overall growth and development. Understanding the interaction of WRKY proteins with other proteins/ligands in plant cells is of utmost importance to develop plants having tolerance to biotic and abiotic stresses. The SlWRKY4 gene was cloned from a drought tolerant wild species of tomato (Solanum habrochaites) and the secondary structure and 3D modeling of this protein were predicted using Schrödinger Suite-Prime. Predicted structures were also subjected to plot against Ramachandran's conformation, and the modeled structure was minimized using Macromodel. Finally, the minimized structure was simulated in the water environment to check the protein stability. The behavior of the modeled structure was well-simulated and analyzed through RMSD and RMSF of the protein. The present work provides the modeled 3D structure of SlWRKY4 that will help in understanding the mechanism of gene regulation by further in silico interaction studies.

Atomic-level structural correlations across the morphotropic phase boundary of a ferroelectric solid solution: xBiMg 1/2Ti 1/2O 3-(1$-$x)PbTiO 3

DOE PAGES

Datta, Kaustuv; Neder, Reinhard B.; Chen, Jun; ...

2017-03-28

Revelation of unequivocal structural information at the atomic level for complex systems is uniquely important for deeper and generic understanding of the structure property connections and a key challenge in materials science. Here in this paper we report an experimental study of the local structure by applying total elastic scattering and Raman scattering analyses to an important non-relaxor ferroelectric solid solution exhibiting the so-called composition-induced morphotropic phase boundary (MPB), where concomitant enhancement of physical properties have been detected. The powerful combination of static and dynamic structural probes enabled us to derive direct correspondence between the atomic-level structural correlations and reportedmore » properties. The atomic pair distribution functions obtained from the neutron total scattering experiments were analysed through big-box atom-modelling implementing reverse Monte Carlo method, from which distributions of magnitudes and directions of off-centred cationic displacements were extracted. We found that an enhanced randomness of the displacement-directions for all ferroelectrically active cations combined with a strong dynamical coupling between the A- and B-site cations of the perovskite structure, can explain the abrupt amplification of piezoelectric response of the system near MPB. Finally, altogether this provides a more fundamental basis in inferring structure-property connections in similar systems including important implications in designing novel and bespoke materials.« less

Cognitive Flexibility through Metastable Neural Dynamics Is Disrupted by Damage to the Structural Connectome.

PubMed

Hellyer, Peter J; Scott, Gregory; Shanahan, Murray; Sharp, David J; Leech, Robert

2015-06-17

Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome. Copyright © 2015 the authors 0270-6474/15/359050-14$15.00/0.

Reconstitution of Homomeric GluA2flop Receptors in Supported Lipid Membranes

PubMed Central

Baranovic, Jelena; Ramanujan, Chandra S.; Kasai, Nahoko; Midgett, Charles R.; Madden, Dean R.; Torimitsu, Keiichi; Ryan, John F.

2013-01-01

AMPA receptors (AMPARs) are glutamate-gated ion channels ubiquitous in the vertebrate central nervous system, where they mediate fast excitatory neurotransmission and act as molecular determinants of memory formation and learning. Together with detailed analyses of individual AMPAR domains, structural studies of full-length AMPARs by electron microscopy and x-ray crystallography have provided important insights into channel assembly and function. However, the correlation between the structure and functional states of the channel remains ambiguous particularly because these functional states can be assessed only with the receptor bound within an intact lipid bilayer. To provide a basis for investigating AMPAR structure in a membrane environment, we developed an optimized reconstitution protocol using a receptor whose structure has previously been characterized by electron microscopy. Single-channel recordings of reconstituted homomeric GluA2flop receptors recapitulate key electrophysiological parameters of the channels expressed in native cellular membranes. Atomic force microscopy studies of the reconstituted samples provide high-resolution images of membrane-embedded full-length AMPARs at densities comparable to those in postsynaptic membranes. The data demonstrate the effect of protein density on conformational flexibility and dimensions of the receptors and provide the first structural characterization of functional membrane-embedded AMPARs, thus laying the foundation for correlated structure-function analyses of the predominant mediators of excitatory synaptic signals in the brain. PMID:23382380

Eliciting consumer preferences for health plans.

PubMed

Booske, B C; Sainfort, F; Hundt, A S

1999-10-01

To examine (1) what people say is important to them in choosing a health plan; (2) the effect, if any, that giving health plan information has on what people say is important to them; and (3) the effect of preference elicitation methods on what people say is important. A random sample of 201 Wisconsin state employees who participated in a health plan choice experiment during the 1995 open enrollment period. We designed a computer system to guide subjects through the review of information about health plan options. The system began by eliciting the stated preferences of the subjects before they viewed the information, at time 0. Subjects were given an opportunity to revise their preference structures first after viewing summary information about four health plans (time 1) and then after viewing more extensive, detailed information about the same options (time 2). At time 2, these individuals were also asked to rate the relative importance of a predefined list of health plan features presented to them. Data were collected on the number of attributes listed at each point in time and the importance weightings assigned to each attribute. In addition, each item on the attribute list was content analyzed. The provision of information changes the preference structures of individuals. Costs (price) and coverage dominated the attributes cited both before and after looking at health plan information. When presented with information on costs, quality, and how plans work, many of these relatively well educated consumers revised their preference structures; yet coverage and costs remained the primary cited attributes. Although efforts to provide health plan information should continue, decisions on the information to provide and on making it available are not enough. Individuals need help in understanding, processing, and using the information to construct their preferences and make better decisions.

Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal

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

Nakada, Ryohei; Hirano, Hidemi; Structural Biology Research Center, Graduate School of Science, Nagoya University

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in every EBV-positive tumor and is essential for the maintenance, replication, and transcription of the EBV genome in the nucleus of host cells. EBNA1 is a serine phosphoprotein, and it has been shown that phosphorylation of S385 in the nuclear localization signal (NLS) of EBNA1 increases the binding affinity to the nuclear import adaptor importin-α1 as well as importin-α5, and stimulates nuclear import of EBNA1. To gain insights into how phosphorylation of the EBNA1 NLS regulates nuclear import, we have determined the crystal structures of two peptide complexes of importin-α1: onemore » with S385-phosphorylated EBNA1 NLS peptide, determined at 2.0 Å resolution, and one with non-phosphorylated EBNA1 NLS peptide, determined at 2.2 Å resolution. The structures show that EBNA1 NLS binds to the major and minor NLS-binding sites of importin-α1, and indicate that the binding affinity of the EBNA1 NLS to the minor NLS-binding site could be enhanced by phosphorylation of S385 through electrostatic interaction between the phosphate group of phospho-S385 and K392 of importin-α1 (corresponding to R395 of importin-α5) on armadillo repeat 8. - Highlights: • Nuclear import of EBNA1 can be regulated by phosphorylation of NLS. • Crystal structures of importin-α1 bound to the NLS peptides of EBNA1 are solved. • Structures provide insights into how phosphorylation can regulate nuclear import.« less

The Cryoelectron Microscopy Structure of the Type 1 Chaperone-Usher Pilus Rod.

PubMed

Hospenthal, Manuela K; Zyla, Dawid; Costa, Tiago R D; Redzej, Adam; Giese, Christoph; Lillington, James; Glockshuber, Rudi; Waksman, Gabriel

2017-12-05

Adhesive chaperone-usher pili are long, supramolecular protein fibers displayed on the surface of many bacterial pathogens. The type 1 and P pili of uropathogenic Escherichia coli (UPEC) play important roles during urinary tract colonization, mediating attachment to the bladder and kidney, respectively. The biomechanical properties of the helical pilus rods allow them to reversibly uncoil in response to flow-induced forces, allowing UPEC to retain a foothold in the unique and hostile environment of the urinary tract. Here we provide the 4.2-Å resolution cryo-EM structure of the type 1 pilus rod, which together with the previous P pilus rod structure rationalizes the remarkable "spring-like" properties of chaperone-usher pili. The cryo-EM structure of the type 1 pilus rod differs in its helical parameters from the structure determined previously by a hybrid approach. We provide evidence that these structural differences originate from different quaternary structures of pili assembled in vivo and in vitro. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Method for providing an arbitrary three-dimensional microstructure in silicon using an anisotropic deep etch

DOEpatents

Morales, Alfredo M.; Gonzales, Marcela

2004-06-15

The present invention describes a method for fabricating an embossing tool or an x-ray mask tool, providing microstructures that smoothly vary in height from point-to-point in etched substrates, i.e., structure which can vary in all three dimensions. The process uses a lithographic technique to transfer an image pattern in the surface of a silicon wafer by exposing and developing the resist and then etching the silicon substrate. Importantly, the photoresist is variably exposed so that when developed some of the resist layer remains. The remaining undeveloped resist acts as an etchant barrier to the reactive plasma used to etch the silicon substrate and therefore provides the ability etch structures of variable depths.

Deletion of a gene cluster encoding pectin degrading enzymes in Caldicellulosiruptor bescii reveals an important role for pectin in plant biomass recalcitrance

DOE PAGES

Chung, Daehwan; Pattathil, Sivakumar; Biswal, Ajaya K.; ...

2014-10-10

A major obstacle, and perhaps the most important economic barrier to the effective use of plant biomass for the production of fuels, chemicals, and bioproducts, is our current lack of knowledge of how to efficiently and effectively deconstruct wall polymers for their subsequent use as feedstocks. Plants represent the most desired source of renewable energy and hydrocarbons because they fix CO 2, making their use carbon neutral. Their biomass structure, however, is a barrier to deconstruction, and this is often referred to as recalcitrance. Members of the bacterial genus Caldicellulosiruptor have the ability to grow on unpretreated plant biomass andmore » thus provide an assay for plant deconstruction and biomass recalcitrance. Using recently developed genetic tools for manipulation of these bacteria, a deletion of a gene cluster encoding enzymes for pectin degradation was constructed, and the resulting mutant was reduced in its ability to grow on both dicot and grass biomass, but not on soluble sugars. The plant biomass from three phylogenetically diverse plants, Arabidopsis (a herbaceous dicot), switchgrass (a monocot grass), and poplar (a woody dicot), was used in these analyses. These biomass types have cell walls that are significantly different from each other in both structure and composition. While pectin is a relatively minor component of the grass and woody dicot substrates, the reduced growth of the mutant on all three biomass types provides direct evidence that pectin plays an important role in biomass recalcitrance. Glycome profiling of the plant material remaining after growth of the mutant on Arabidopsis biomass compared to the wild-type revealed differences in the rhamnogalacturonan I, homogalacturonan, arabinogalactan, and xylan profiles. In contrast, only minor differences were observed in the glycome profiles of the switchgrass and poplar biomass. In conclusion, the combination of microbial digestion and plant biomass analysis provides a new and important platform to identify plant wall structures whose presence reduces the ability of microbes to deconstruct plant walls and to identify enzymes that specifically deconstruct those structures.« less

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

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

Zemla, A; Lang, D; Kostova, T

2010-11-29

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

Fuzzy Edge Connectivity of Graphical Fuzzy State Space Model in Multi-connected System

NASA Astrophysics Data System (ADS)

Harish, Noor Ainy; Ismail, Razidah; Ahmad, Tahir

2010-11-01

Structured networks of interacting components illustrate complex structure in a direct or intuitive way. Graph theory provides a mathematical modeling for studying interconnection among elements in natural and man-made systems. On the other hand, directed graph is useful to define and interpret the interconnection structure underlying the dynamics of the interacting subsystem. Fuzzy theory provides important tools in dealing various aspects of complexity, imprecision and fuzziness of the network structure of a multi-connected system. Initial development for systems of Fuzzy State Space Model (FSSM) and a fuzzy algorithm approach were introduced with the purpose of solving the inverse problems in multivariable system. In this paper, fuzzy algorithm is adapted in order to determine the fuzzy edge connectivity between subsystems, in particular interconnected system of Graphical Representation of FSSM. This new approach will simplify the schematic diagram of interconnection of subsystems in a multi-connected system.

Optimization of hierarchical structure and nanoscale-enabled plasmonic refraction for window electrodes in photovoltaics

PubMed Central

Han, Bing; Peng, Qiang; Li, Ruopeng; Rong, Qikun; Ding, Yang; Akinoglu, Eser Metin; Wu, Xueyuan; Wang, Xin; Lu, Xubing; Wang, Qianming; Zhou, Guofu; Liu, Jun-Ming; Ren, Zhifeng; Giersig, Michael; Herczynski, Andrzej; Kempa, Krzysztof; Gao, Jinwei

2016-01-01

An ideal network window electrode for photovoltaic applications should provide an optimal surface coverage, a uniform current density into and/or from a substrate, and a minimum of the overall resistance for a given shading ratio. Here we show that metallic networks with quasi-fractal structure provides a near-perfect practical realization of such an ideal electrode. We find that a leaf venation network, which possesses key characteristics of the optimal structure, indeed outperforms other networks. We further show that elements of hierarchal topology, rather than details of the branching geometry, are of primary importance in optimizing the networks, and demonstrate this experimentally on five model artificial hierarchical networks of varied levels of complexity. In addition to these structural effects, networks containing nanowires are shown to acquire transparency exceeding the geometric constraint due to the plasmonic refraction. PMID:27667099

An Overview of Biological Macromolecule Crystallization

PubMed Central

Krauss, Irene Russo; Merlino, Antonello; Vergara, Alessandro; Sica, Filomena

2013-01-01

The elucidation of the three dimensional structure of biological macromolecules has provided an important contribution to our current understanding of many basic mechanisms involved in life processes. This enormous impact largely results from the ability of X-ray crystallography to provide accurate structural details at atomic resolution that are a prerequisite for a deeper insight on the way in which bio-macromolecules interact with each other to build up supramolecular nano-machines capable of performing specialized biological functions. With the advent of high-energy synchrotron sources and the development of sophisticated software to solve X-ray and neutron crystal structures of large molecules, the crystallization step has become even more the bottleneck of a successful structure determination. This review introduces the general aspects of protein crystallization, summarizes conventional and innovative crystallization methods and focuses on the new strategies utilized to improve the success rate of experiments and increase crystal diffraction quality. PMID:23727935

Population inertia and its sensitivity to changes in vital rates and population structure

USGS Publications Warehouse

Koons, David N.; Holmes, Randall R.; Grand, James B.

2007-01-01

Because the (st)age structure of a population may rarely be stable, studies of transient population dynamics and population momentum are becoming ever more popular. Yet, studies of "population momentum" are restricted in the sense that they describe the inertia of population size resulting from a demographic transition to the stationary population growth rate. Although rarely mentioned, inertia in population size is a general phenomenon and can be produced by any demographic transition or perturbation. Because population size is of central importance in demography, conservation, and management, formulas relating the sensitivity of population inertia to changes in underlying vital rates and population structure could provide much-needed insight into the dynamics of populations with unstable (st)age structure. Here, we derive such formulas, which are readily computable, and provide examples of their potential use in studies of life history and applied arenas of population study. ?? 2007 by the Ecological Society of America.

Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.

PubMed

Howard, Rebecca J; Carnevale, Vincenzo; Delemotte, Lucie; Hellmich, Ute A; Rothberg, Brad S

2018-04-01

Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process-for example with neuroactive drugs-demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data management and conceptual alignment. Here, we seek to provide contemporary context, concrete examples, and a look to the future for bridging disciplinary gaps in biological ion transport. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

The Dual Role of Vegetation as a Constraint on Mass and Energy Flux into the Critical Zone and as an Emergent Property of Geophysical Critical Zone Structure

NASA Astrophysics Data System (ADS)

Brooks, P. D.; Swetnam, T. L.; Barnard, H. R.; Singha, K.; Harpold, A.; Litvak, M. E.

2017-12-01

Spatial patterns in vegetation long have been used to scale both landsurface-atmosphere exchanges of water and carbon as well as to infer subsurface structure. These pursuits typical proceed in isolation and rarely do inferences gained from one community propagate to related efforts in another. Perhaps more importantly, vegetation often is treated as an emergent property of landscape-climate interactions rather than an active modifier of both critical zone structure and energy fluxes. We posit that vegetation structure and activity are under utilized as a tool towards understanding landscape evolution and present examples that begin to disentangle the role of vegetation as both an emergent property and an active control on critical zone structure and function. As climate change, population growth, and land use changes threaten water resources worldwide, the need for the new insights vegetation can provide becomes not just a basic science priority, but a pressing applied science question with clear societal importance. This presentation will provide an overview of recent efforts to address the dual role of vegetation in both modifying and reflecting critical zone structure in the western North American forests. For example, interactions between topography and stand scale vegetation structure influence both solar radiation and turbulence altering landscape scale partitioning of evaporation vs transpiration with major impacts of surface water supply. Similarly, interactions between topographic shading, lateral redistribution of plant available water, and subsurface storage create a mosaic of drought resistance and resilience across complex terrain. These complex interactions between geophysical and vegetation components of critical zone structure result in predictable patterns in catchment scale hydrologic partitioning within individual watersheds while simultaneously suggesting testable hypotheses for why catchments under similar climate regimes respond so differently to drought stress.

Street tree structural differences and associated stormwater benefits in metropolitan Cincinnati, Ohio, USA

EPA Science Inventory

Green infrastructure approaches leverage vegetation and soil to improve environmental quality. Municipal street trees are crucial components of urban green infrastructure because they provide stormwater interception benefits and other ecosystem services. Thus, it is important to ...

Key Ecological Interactions of Reef Building Corals - 11-16-2011

EPA Science Inventory

Coral reefs are very important marine ecosystems because they support tremendous biodiversity and reefs are critical economic resources many coastal nations. Tropical reef structures are largely built by stony corals. This presentation provides background on basic coral biology t...

Chemistry from Issues.

ERIC Educational Resources Information Center

Harding, Jan; Donaldson, Jim

1986-01-01

Describes the "Chemistry from Issues" project at Chelsea College. Provides the background information, rationale, and overall structure of a proposed course about the importance of chemistry to common culture. Outlines one module about the British steel industry that has been taught at King's College. (TW)

Comparative Study on Cushion Performance Between 3D Printed Kelvin Structure and 3D Printed Lattice Structure

NASA Astrophysics Data System (ADS)

Priyadarshini, Lakshmi

Frequently transported packaging goods are more prone to damage due to impact, jolting or vibration in transit. Fragile goods, for example, glass, ceramics, porcelain are susceptible to mechanical stresses. Hence ancillary materials like cushions play an important role when utilized within package. In this work, an analytical model of a 3D cellular structure is established based on Kelvin model and lattice structure. The research will provide a comparative study between the 3D printed Kelvin unit structure and 3D printed lattice structure. The comparative investigation is based on parameters defining cushion performance such as cushion creep, indentation, and cushion curve analysis. The applications of 3D printing is in rapid prototyping where the study will provide information of which model delivers better form of energy absorption. 3D printed foam will be shown as a cost-effective approach as prototype. The research also investigates about the selection of material for 3D printing process. As cushion development demands flexible material, three-dimensional printing with material having elastomeric properties is required. Further, the concept of cushion design is based on Kelvin model structure and lattice structure. The analytical solution provides the cushion curve analysis with respect to the results observed when load is applied over the cushion. The results are reported on basis of attenuation and amplification curves.

Biomimetic photonic materials with tunable structural colors.

PubMed

Xu, Jun; Guo, Zhiguang

2013-09-15

Nature is a huge gallery of art involving nearly perfect structures and forms over the millions of years developing. Inspiration from natural structures exhibiting structural colors is first discussed. We give some examples of natural one-, two-, and three-dimensional photonic structures. This review article presents a brief summary of recent progress on bio-inspired photonic materials with variable structural colors, including the different facile and efficient routes to construct the nano-architectures, and the development of the artificial variable structural color photonic materials. Besides the superior optical properties, the excellent functions such as robust mechanical strength, good wettability are also mentioned, as well as the technical importance in various applications. This review will provide significant insight into the fabrication, design and application of the structural color materials. Copyright © 2013 Elsevier Inc. All rights reserved.

Reproduction numbers for epidemic models with households and other social structures. I. Definition and calculation of R0

PubMed Central

Pellis, Lorenzo; Ball, Frank; Trapman, Pieter

2012-01-01

The basic reproduction number R0 is one of the most important quantities in epidemiology. However, for epidemic models with explicit social structure involving small mixing units such as households, its definition is not straightforward and a wealth of other threshold parameters has appeared in the literature. In this paper, we use branching processes to define R0, we apply this definition to models with households or other more complex social structures and we provide methods for calculating it. PMID:22085761

Fast computational methods for predicting protein structure from primary amino acid sequence

DOEpatents

Agarwal, Pratul Kumar [Knoxville, TN

2011-07-19

The present invention provides a method utilizing primary amino acid sequence of a protein, energy minimization, molecular dynamics and protein vibrational modes to predict three-dimensional structure of a protein. The present invention also determines possible intermediates in the protein folding pathway. The present invention has important applications to the design of novel drugs as well as protein engineering. The present invention predicts the three-dimensional structure of a protein independent of size of the protein, overcoming a significant limitation in the prior art.

Surgical Considerations of Intractable Mesial Temporal Lobe Epilepsy

PubMed Central

Boling, Warren W.

2018-01-01

Surgery of temporal lobe epilepsy is the best opportunity for seizure freedom in medically intractable patients. The surgical approach has evolved to recognize the paramount importance of the mesial temporal structures in the majority of patients with temporal lobe epilepsy who have a seizure origin in the mesial temporal structures. For those individuals with medically intractable mesial temporal lobe epilepsy, a selective amygdalohippocampectomy surgery can be done that provides an excellent opportunity for seizure freedom and limits the resection to temporal lobe structures primarily involved in seizure genesis. PMID:29461485

Measuring client satisfaction and the quality of family planning services: A comparative analysis of public and private health facilities in Tanzania, Kenya and Ghana

PubMed Central

2011-01-01

Background Public and private family planning providers face different incentive structures, which may affect overall quality and ultimately the acceptability of family planning for their intended clients. This analysis seeks to quantify differences in the quality of family planning (FP) services at public and private providers in three representative sub-Saharan African countries (Tanzania, Kenya and Ghana), to assess how these quality differentials impact upon FP clients' satisfaction, and to suggest how quality improvements can improve contraceptive continuation rates. Methods Indices of technical, structural and process measures of quality are constructed from Service Provision Assessments (SPAs) conducted in Tanzania (2006), Kenya (2004) and Ghana (2002) using direct observation of facility attributes and client-provider interactions. Marginal effects from multivariate regressions controlling for client characteristics and the multi-stage cluster sample design assess the relative importance of different measures of structural and process quality at public and private facilities on client satisfaction. Results Private health facilities appear to be of higher (interpersonal) process quality than public facilities but not necessarily higher technical quality in the three countries, though these differentials are considerably larger at lower level facilities (clinics, health centers, dispensaries) than at hospitals. Family planning client satisfaction, however, appears considerably higher at private facilities - both hospitals and clinics - most likely attributable to both process and structural factors such as shorter waiting times and fewer stockouts of methods and supplies. Conclusions Because the public sector represents the major source of family planning services in developing countries, governments and Ministries of Health should continue to implement and to encourage incentives, perhaps performance-based, to improve quality at public sector health facilities, as well as to strengthen regulatory and monitoring structures to ensure quality at both public and private facilities. In the meantime, private providers appear to be fulfilling an important gap in the provision of FP services in these countries. PMID:21864335

Measuring client satisfaction and the quality of family planning services: a comparative analysis of public and private health facilities in Tanzania, Kenya and Ghana.

PubMed

Hutchinson, Paul L; Do, Mai; Agha, Sohail

2011-08-24

Public and private family planning providers face different incentive structures, which may affect overall quality and ultimately the acceptability of family planning for their intended clients. This analysis seeks to quantify differences in the quality of family planning (FP) services at public and private providers in three representative sub-Saharan African countries (Tanzania, Kenya and Ghana), to assess how these quality differentials impact upon FP clients' satisfaction, and to suggest how quality improvements can improve contraceptive continuation rates. Indices of technical, structural and process measures of quality are constructed from Service Provision Assessments (SPAs) conducted in Tanzania (2006), Kenya (2004) and Ghana (2002) using direct observation of facility attributes and client-provider interactions. Marginal effects from multivariate regressions controlling for client characteristics and the multi-stage cluster sample design assess the relative importance of different measures of structural and process quality at public and private facilities on client satisfaction. Private health facilities appear to be of higher (interpersonal) process quality than public facilities but not necessarily higher technical quality in the three countries, though these differentials are considerably larger at lower level facilities (clinics, health centers, dispensaries) than at hospitals. Family planning client satisfaction, however, appears considerably higher at private facilities - both hospitals and clinics - most likely attributable to both process and structural factors such as shorter waiting times and fewer stockouts of methods and supplies. Because the public sector represents the major source of family planning services in developing countries, governments and Ministries of Health should continue to implement and to encourage incentives, perhaps performance-based, to improve quality at public sector health facilities, as well as to strengthen regulatory and monitoring structures to ensure quality at both public and private facilities. In the meantime, private providers appear to be fulfilling an important gap in the provision of FP services in these countries.

High Performance Fortran for Aerospace Applications

NASA Technical Reports Server (NTRS)

Mehrotra, Piyush; Zima, Hans; Bushnell, Dennis M. (Technical Monitor)

2000-01-01

This paper focuses on the use of High Performance Fortran (HPF) for important classes of algorithms employed in aerospace applications. HPF is a set of Fortran extensions designed to provide users with a high-level interface for programming data parallel scientific applications, while delegating to the compiler/runtime system the task of generating explicitly parallel message-passing programs. We begin by providing a short overview of the HPF language. This is followed by a detailed discussion of the efficient use of HPF for applications involving multiple structured grids such as multiblock and adaptive mesh refinement (AMR) codes as well as unstructured grid codes. We focus on the data structures and computational structures used in these codes and on the high-level strategies that can be expressed in HPF to optimally exploit the parallelism in these algorithms.

Advanced probabilistic methods for quantifying the effects of various uncertainties in structural response

NASA Technical Reports Server (NTRS)

Nagpal, Vinod K.

1988-01-01

The effects of actual variations, also called uncertainties, in geometry and material properties on the structural response of a space shuttle main engine turbopump blade are evaluated. A normal distribution was assumed to represent the uncertainties statistically. Uncertainties were assumed to be totally random, partially correlated, and fully correlated. The magnitude of these uncertainties were represented in terms of mean and variance. Blade responses, recorded in terms of displacements, natural frequencies, and maximum stress, was evaluated and plotted in the form of probabilistic distributions under combined uncertainties. These distributions provide an estimate of the range of magnitudes of the response and probability of occurrence of a given response. Most importantly, these distributions provide the information needed to estimate quantitatively the risk in a structural design.

The importance of shortleaf pine for wildlife and diversity in mixed oak-pine forests and in pine-grassland woodlands

Treesearch

Ronald E. Masters

2007-01-01

Shortleaf pine, by virtue of its wide distribution and occurrence in many forest types in eastern North America, is an important species that provides high habitat value for many wildlife species. Shortleaf pine functions as a structural habitat element in both mixed oak-pine forests and in pine-grassland woodlands. It also adds diversity throughout all stages of plant...

Wildlife habitats in managed rangelands—the Great Basin of southeastern Oregon: plant communities and their importance to wildlife.

Treesearch

J. Edward Dealy; Donavin A. Leckenby; Diane M. Concannon

1981-01-01

Plant communities in the Great Basin of southeastern Oregon are described, and a field key is provided. The value of a plant community’s vertical and horizontal structure and the seasonal availability of its forage are examined in relation to wildlife habitat in managed rangelands. Further, the importance of individual and combined plant communities to wildlife in...

Prey-driven control of predator assemblages: zooplankton abundance drives aquatic beetle colonization.

PubMed

Pintar, Matthew R; Resetarits, William J

2017-08-01

Trophic interactions are critical determinants of community structure and ecosystem function. In freshwater habitats, top predators are traditionally viewed as drivers of ecosystem structure, shaping populations of consumers and primary producers. The temporary nature of small water bodies makes them dependent on colonization by many organisms, particularly insects that form highly diverse predator assemblages. We conducted mesocosm experiments with naturally colonizing populations of aquatic beetles to assess how prey (zooplankton) abundances influenced colonization and assemblages of natural populations of aquatic beetles. We experimentally demonstrate that zooplankton populations can be proximate regulators of predator populations and assemblages via prey-density-dependent predator recruitment. Our results provide support for the importance of prey populations in structuring predator populations and the role of habitat selection in structuring communities. We indicate that traditional views of predators as drivers of ecosystem structure in many systems may not provide a comprehensive picture, particularly in the context of highly disturbed or ephemeral habitats. © 2017 by the Ecological Society of America.

Crystal structure of a Schistosoma mansoni septin reveals the phenomenon of strand slippage in septins dependent on the nature of the bound nucleotide.

PubMed

Zeraik, Ana E; Pereira, Humberto M; Santos, Yuri V; Brandão-Neto, José; Spoerner, Michael; Santos, Maiara S; Colnago, Luiz A; Garratt, Richard C; Araújo, Ana P U; DeMarco, Ricardo

2014-03-14

Septins are filament-forming GTP-binding proteins involved in important cellular events, such as cytokinesis, barrier formation, and membrane remodeling. Here, we present two crystal structures of the GTPase domain of a Schistosoma mansoni septin (SmSEPT10), one bound to GDP and the other to GTP. The structures have been solved at an unprecedented resolution for septins (1.93 and 2.1 Å, respectively), which has allowed for unambiguous structural assignment of regions previously poorly defined. Consequently, we provide a reliable model for functional interpretation and a solid foundation for future structural studies. Upon comparing the two complexes, we observe for the first time the phenomenon of a strand slippage in septins. Such slippage generates a front-back communication mechanism between the G and NC interfaces. These data provide a novel mechanistic framework for the influence of nucleotide binding to the GTPase domain, opening new possibilities for the study of the dynamics of septin filaments.

Resolution of ab initio shapes determined from small-angle scattering.

PubMed

Tuukkanen, Anne T; Kleywegt, Gerard J; Svergun, Dmitri I

2016-11-01

Spatial resolution is an important characteristic of structural models, and the authors of structures determined by X-ray crystallography or electron cryo-microscopy always provide the resolution upon publication and deposition. Small-angle scattering of X-rays or neutrons (SAS) has recently become a mainstream structural method providing the overall three-dimensional structures of proteins, nucleic acids and complexes in solution. However, no quantitative resolution measure is available for SAS-derived models, which significantly hampers their validation and further use. Here, a method is derived for resolution assessment for ab initio shape reconstruction from scattering data. The inherent variability of the ab initio shapes is utilized and it is demonstrated how their average Fourier shell correlation function is related to the model resolution. The method is validated against simulated data for proteins with known high-resolution structures and its efficiency is demonstrated in applications to experimental data. It is proposed that henceforth the resolution be reported in publications and depositions of ab initio SAS models.

Resolution of ab initio shapes determined from small-angle scattering

PubMed Central

Tuukkanen, Anne T.; Kleywegt, Gerard J.; Svergun, Dmitri I.

2016-01-01

Spatial resolution is an important characteristic of structural models, and the authors of structures determined by X-ray crystallography or electron cryo-microscopy always provide the resolution upon publication and deposition. Small-angle scattering of X-rays or neutrons (SAS) has recently become a mainstream structural method providing the overall three-dimensional structures of proteins, nucleic acids and complexes in solution. However, no quantitative resolution measure is available for SAS-derived models, which significantly hampers their validation and further use. Here, a method is derived for resolution assessment for ab initio shape reconstruction from scattering data. The inherent variability of the ab initio shapes is utilized and it is demonstrated how their average Fourier shell correlation function is related to the model resolution. The method is validated against simulated data for proteins with known high-resolution structures and its efficiency is demonstrated in applications to experimental data. It is proposed that henceforth the resolution be reported in publications and depositions of ab initio SAS models. PMID:27840683

Trends in asset structure between not-for-profit and investor-owned hospitals.

PubMed

Song, Paula H; Reiter, Kristin L

2010-12-01

The delivery of health care is a capital-intensive industry, and thus, hospital investment strategy continues to be an important area of interest for both health policy and research. Much attention has been given to hospitals' capital investment policies with relatively little attention to investments in financial assets, which serve an important role in not-for-profit (NFP) hospitals. This study describes and analyzes trends in aggregate asset structure between NFP and investor-owned (IO) hospitals during the post-capital-based prospective payment system implementation period, providing the first documentation of long-term trends in hospital investment. The authors find hospitals' aggregate asset structure differs significantly based on ownership, size, and profitability. For both NFP and IO hospitals, financial securities have remained consistent over time, while fixed asset representation has declined in IO hospitals.

A Versatile Strategy for the Semisynthetic Production of Ser65 Phosphorylated Ubiquitin and Its Biochemical and Structural Characterisation

PubMed Central

Han, Cong; Pao, Kuan-Chuan; Kazlauskaite, Agne; Muqit, Miratul M K; Virdee, Satpal

2015-01-01

Ubiquitin phosphorylation is emerging as an important regulatory layer in the ubiquitin system. This is exemplified by the phosphorylation of ubiquitin on Ser65 by the Parkinson's disease-associated kinase PINK1, which mediates the activation of the E3 ligase Parkin. Additional phosphorylation sites on ubiquitin might also have important cellular roles. Here we report a versatile strategy for preparing phosphorylated ubiquitin. We biochemically and structurally characterise semisynthetic phospho-Ser65-ubiquitin. Unexpectedly, we observed disulfide bond formation between ubiquitin molecules, and hence a novel crystal form. The method outlined provides a direct approach to study the combinatorial effects of phosphorylation on ubiquitin function. Our analysis also suggests that disulfide engineering of ubiquitin could be a useful strategy for obtaining alternative crystal forms of ubiquitin species thereby facilitating structural validation. PMID:26010437

Using simulation to interpret experimental data in terms of protein conformational ensembles.

PubMed

Allison, Jane R

2017-04-01

In their biological environment, proteins are dynamic molecules, necessitating an ensemble structural description. Molecular dynamics simulations and solution-state experiments provide complimentary information in the form of atomically detailed coordinates and averaged or distributions of structural properties or related quantities. Recently, increases in the temporal and spatial scale of conformational sampling and comparison of the more diverse conformational ensembles thus generated have revealed the importance of sampling rare events. Excitingly, new methods based on maximum entropy and Bayesian inference are promising to provide a statistically sound mechanism for combining experimental data with molecular dynamics simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calculation of the nucleon structure function from the nucleon wave function

NASA Technical Reports Server (NTRS)

Hussar, Paul E.

1993-01-01

Harmonic oscillator wave functions have played an historically important role in our understanding of the structure of the nucleon, most notably by providing insight into the mass spectra of the low-lying states. High energy scattering experiments are known to give us a picture of the nucleon wave function at high-momentum transfer and in a frame in which the nucleon is traveling fast. A simple model that crosses the twin bridges of momentum scale and Lorentz frame that separate the pictures of the nucleon wave function provided by the deep inelastic scattering data and by the oscillator model is presented.

Development of the Noise-Resistant and Sound Focusing Accessory of Ultrasonic Leak Detector for Spacecraft on Orbit

NASA Astrophysics Data System (ADS)

Sun, W.; Yan, R. X.; Sun, L. C.; Shao, R. P.

2017-12-01

Ultrasonic signal produced by the gas leak is so week that it is difficult to detect, and easily interfered. So developing the noise-resistant and sound focusing accessory for the ultrasonic leak detector is very important for improving ultrasonic leak detector sensitivity and noise-resistant capability. Based on the theory analysis of the leak ultrasonic signal reverberation and anacampsis, the 5A06 aluminium alloy and nylon were selected as the material of noise-resistant and sound focusing accessory by calculation and compare. Then the circular cone trumpet structure was design as the accessory main structure, and the nylon expansion port, nylon shrinking port and aluminium alloy expansion port structures were manufactured. The different structure characters were shown by the contrasting experiment. The results indicate that the nylon expansion circular cone trumpet structure has better sound focusing performance and it can improve the testing sound pressure amplitude 10 bigger than the detector without the accessory. And the aluminium alloy expansion circular cone trumpet structure has better noise-resistant ability than others. These conclusions are very important for the spacecraft leak detection and it can provide some references for the design of the noise-resistant and sound focusing structure.

Study of structural reliability of existing concrete structures

NASA Astrophysics Data System (ADS)

Druķis, P.; Gaile, L.; Valtere, K.; Pakrastiņš, L.; Goremikins, V.

2017-10-01

Structural reliability of buildings has become an important issue after the collapse of a shopping center in Riga 21.11.2013, caused the death of 54 people. The reliability of a building is the practice of designing, constructing, operating, maintaining and removing buildings in ways that ensure maintained health, ward suffered injuries or death due to use of the building. Evaluation and improvement of existing buildings is becoming more and more important. For a large part of existing buildings, the design life has been reached or will be reached in the near future. The structures of these buildings need to be reassessed in order to find out whether the safety requirements are met. The safety requirements provided by the Eurocodes are a starting point for the assessment of safety. However, it would be uneconomical to require all existing buildings and structures to comply fully with these new codes and corresponding safety levels, therefore the assessment of existing buildings differs with each design situation. This case study describes the simple and practical procedure of determination of minimal reliability index β of existing concrete structures designed by different codes than Eurocodes and allows to reassess the actual reliability level of different structural elements of existing buildings under design load.

Canopy structural complexity influences forest canopy reflectance: linking terrestrial lidar with Landsat observations

NASA Astrophysics Data System (ADS)

Hardiman, B. S.; Atkins, J.; Dahlin, K.; Fahey, R. T.; Gough, C. M.

2016-12-01

Canopy physical structure - leaf quantity and arrangement - strongly affects light interception and distribution. As such, canopy physical structure is a key driver of forest carbon (C) dynamics. Terrestrial lidar systems (TLS) provide spatially explicit, quantitative characterizations of canopy physical structure at scales commensurate with plot-scale C cycling processes. As an example, previous TLS-based studies established that light use efficiency is positively correlated with canopy physical structure, influencing the trajectory of net primary production throughout forest development. Linking TLS measurements of canopy structure to multispectral satellite observations of forest canopies may enable scaling of ecosystem C cycling processes from leaves to continents. We will report on our study relating a suite of canopy structural metrics to well-established remotely sensed measurements (NDVI, EVI, albedo, tasseled cap indices, etc.) which are indicative of important forest characteristics (leaf area, canopy nitrogen, light interception, etc.). We used Landsat data, which provides observations at 30m resolution, a scale comparable to that of TLS. TLS data were acquired during 2009-2016 from forest sites throughout Eastern North America, comprised primarily of NEON and Ameriflux sites. Canopy physical structure data were compared with contemporaneous growing-season Landsat data. Metrics of canopy physical structure are expected to covary with forest composition and dominant PFT, likely influencing interaction strength between TLS and Landsat canopy metrics. More structurally complex canopies (those with more heterogeneous distributions of leaf area) are expected to have lower albedo, suggesting greater canopy light absorption (higher fAPAR) than simpler canopies. We expect that vegetation indices (NDVI, EVI) will increase with TLS metrics of spatial heterogeneity, and not simply quantity, of leaves, supporting our hypothesis that canopy light absorption is dependent on both leaf quantity and arrangement. Relating satellite observations of canopy properties to TLS metrics of canopy physical structure represents an important advance for modelling canopy energy balance and forest C cycling processes at large spatial scales.

Immediate use of prosody and context in predicting a syntactic structure.

PubMed

Nakamura, Chie; Arai, Manabu; Mazuka, Reiko

2012-11-01

Numerous studies have reported an effect of prosodic information on parsing but whether prosody can impact even the initial parsing decision is still not evident. In a visual world eye-tracking experiment, we investigated the influence of contrastive intonation and visual context on processing temporarily ambiguous relative clause sentences in Japanese. Our results showed that listeners used the prosodic cue to make a structural prediction before hearing disambiguating information. Importantly, the effect was limited to cases where the visual scene provided an appropriate context for the prosodic cue, thus eliminating the explanation that listeners have simply associated marked prosodic information with a less frequent structure. Furthermore, the influence of the prosodic information was also evident following disambiguating information, in a way that reflected the initial analysis. The current study demonstrates that prosody, when provided with an appropriate context, influences the initial syntactic analysis and also the subsequent cost at disambiguating information. The results also provide first evidence for pre-head structural prediction driven by prosodic and contextual information with a head-final construction. Copyright © 2012 Elsevier B.V. All rights reserved.

Structural constraints on the three-dimensional geometry of simple viruses: case studies of a new predictive tool

PubMed Central

Keef, Thomas; Wardman, Jessica P.; Ranson, Neil A.; Stockley, Peter G.; Twarock, Reidun

2013-01-01

Understanding the fundamental principles of virus architecture is one of the most important challenges in biology and medicine. Crick and Watson were the first to propose that viruses exhibit symmetry in the organization of their protein containers for reasons of genetic economy. Based on this, Caspar and Klug introduced quasi-equivalence theory to predict the relative locations of the coat proteins within these containers and classified virus structure in terms of T-numbers. Here it is shown that quasi-equivalence is part of a wider set of structural constraints on virus structure. These constraints can be formulated using an extension of the underlying symmetry group and this is demonstrated with a number of case studies. This new concept in virus biology provides for the first time predictive information on the structural constraints on coat protein and genome topography, and reveals a previously unrecognized structural interdependence of the shapes and sizes of different viral components. It opens up the possibility of distinguishing the structures of different viruses with the same T-number, suggesting a refined viral structure classification scheme. It can moreover be used as a basis for models of virus function, e.g. to characterize the start and end configurations of a structural transition important for infection. PMID:23403965

Structural constraints on the three-dimensional geometry of simple viruses: case studies of a new predictive tool.

PubMed

Keef, Thomas; Wardman, Jessica P; Ranson, Neil A; Stockley, Peter G; Twarock, Reidun

2013-03-01

Understanding the fundamental principles of virus architecture is one of the most important challenges in biology and medicine. Crick and Watson were the first to propose that viruses exhibit symmetry in the organization of their protein containers for reasons of genetic economy. Based on this, Caspar and Klug introduced quasi-equivalence theory to predict the relative locations of the coat proteins within these containers and classified virus structure in terms of T-numbers. Here it is shown that quasi-equivalence is part of a wider set of structural constraints on virus structure. These constraints can be formulated using an extension of the underlying symmetry group and this is demonstrated with a number of case studies. This new concept in virus biology provides for the first time predictive information on the structural constraints on coat protein and genome topography, and reveals a previously unrecognized structural interdependence of the shapes and sizes of different viral components. It opens up the possibility of distinguishing the structures of different viruses with the same T-number, suggesting a refined viral structure classification scheme. It can moreover be used as a basis for models of virus function, e.g. to characterize the start and end configurations of a structural transition important for infection.

SemMat: Federated Semantic Services Platform for Open materials Science and Engineering

DTIC Science & Technology

2017-01-01

identified the following two important tasks to remedy the data heterogeneity challenge to promote data integration: (1) creating the semantic...sourced from the structural and bio -materials domains. For structural materials data, we reviewed and used MIL-HDBK-5J [11] and MIL-HDBK-17. Furthermore...documents about composite materials provided by our domain expert. Based on the suggestions given by domain experts in bio -materials, the following

Use of New Commercial, Off-the-Shelf, High-Definition Structure Scanning Fathometer/Depth Finder For Coastal Current Survey Operations

NASA Astrophysics Data System (ADS)

Roggenstein, E. B.; Gray, G.

2013-12-01

The National Oceanic and Atmospheric Administration (NOAA) National Ocean Service (NOS) Center for Operational Oceanographic Products and Services (COOPS) manages three national observing system programs. These are the National Water level Observation Network (NWLON) (210 stations), the 23 NOAA/Physical Oceanographic Real-Time Systems (PORTS), and National Currents Observing Program (NCOP) (approximately 70 deployments/year). In support of its mission COOPS operates and maintains a number of small boats. During vessel operations, side-scan sonar data are at times needed to provide information about bottom structure for future work in the area. For example, potential hazards, obstructions, or bottom morphology features that have not been identified on localized charts for a given area could be used to inform decisions on planned installations. Side-scan sonar capability is also important when attempting to reacquire bottom mounts that fail to surface at the conclusion of a current meter survey. Structure mapping and side-scan capabilities have been added to recent consumer-level, commercial, off-the-shelf fathometers, generally intended for recreational, commercial fishing, and diving applications. We are proposing to investigate these systems' viability for meeting survey requirements. We assess their ability to provide a flexible alternative to research/commercial oceanographic level side-scan system at a significant cost savings. Such systems could provide important information to support scientific missions that require qualitative seafloor imagery.

Using a Java Dynamic Tree to manage the terminology in a suite of medical applications.

PubMed

Yang, K; Evens, M W; Trace, D A

2008-01-01

Now that the National Library of Medicine has made SNOMED-CT widely available, we are trying to manage the terminology of a whole suite of medical applications and map our terminology into that in SNOMED. This paper describes the design and implementation of the Java Dynamic Tree that provides structure to our medical terminology and explains how it functions as the core of our system. The tree was designed to reflect the stages in a patient interview, so it contains components for identifying the patient and the provider, a large set of chief complaints, review of systems, physical examination, several history modules, medications, laboratory tests, imaging, and special procedures. The tree is mirrored in a commercial DBMS, which also stores multi-encounter patient data, disorder patterns for our Bayesian diagnostic system, and the data and rules for other expert systems. The DBMS facilitates the import and export of large terminology files. Our Java Dynamic Tree allows the health care provider to view the entire terminology along with the structure that supports it, as well as the mechanism for the generation of progress notes and other documents, in terms of a single hierarchical structure. Changes in terminology can be propagated through the system under the control of the expert. The import/ export facility has been a major help by replacing our original terminology by the terminology in SNOMED-CT.

Effects of Sibling Structure and Interaction on Children's Categorization Style

ERIC Educational Resources Information Center

Cicirelli, Victor G.

1973-01-01

One hundred sixty sibling pairs from two child families were sampled for sibling interaction behaviors as they relate to measures of categorization style. The study provides additional evidence of the importance of a child's siblings to his cognitive development. (Editor/RK)

How to build a molecular shock absorber.

PubMed

McGough, A

1999-12-02

Newly determined structures of the alpha-helical repeats that make up the key 'rod' domains of spectrin and alpha-actinin - which serve as spacers between their actin-binding domains - have provided important insights into how these proteins function as molecular shock absorbers in cells.

X-ray crystallographic data for minerals

USGS Publications Warehouse

Robie, Richard A.; Bethke, Philip M.; Toulmin, M.S.; Edwards, Jerry L.

1963-01-01

X-ray crystallographic data are of particular importance to the mineralogist. Beyond the considerations of structural chemistry they provide. one of the most accurate methods for phase and/or compositional determination and for obtaining _the molar volumes and densities of minerals {Robie and Bethke, 1962).

Spatial and temporal influences on hydrologic connectivity: A mathematical formalization

EPA Science Inventory

Connectivity between landscape elements has been an important consideration in landscape ecology since at least the mid-1980s. In particular, the use of random landscapes to study the interaction between connectivity, landscape structure, and dispersal mechanisms has provided in...

What Next for Networks and Netwars

DTIC Science & Technology

2001-01-01

Jacques Derrida , Michel Foucault, 30Standard sources on neorealism include a range of writings by Kenneth Waltz and John Mearshimer in particular. The...address banking networks, and Jacques (1990), which provides a classic defense of the importance of hierarchy in corporate structures. What Next for

Characterizing rider safety in terms of asphalt pavement surface texture.

DOT National Transportation Integrated Search

2013-10-01

The overall goal of the pavement design is to meet the intended service life and more importantly to provide a safe riding surface for the traveling : public. Therefore, pavements can experience structural failure (i.e. rutting or cracking) or functi...

Structural insights into the inactivation of CRISPR-Cas systems by diverse anti-CRISPR proteins.

PubMed

Zhu, Yuwei; Zhang, Fan; Huang, Zhiwei

2018-03-19

A molecular arms race is progressively being unveiled between prokaryotes and viruses. Prokaryotes utilize CRISPR-mediated adaptive immune systems to kill the invading phages and mobile genetic elements, and in turn, the viruses evolve diverse anti-CRISPR proteins to fight back. The structures of several anti-CRISPR proteins have now been reported, and here we discuss their structural features, with a particular emphasis on topology, to discover their similarities and differences. We summarize the CRISPR-Cas inhibition mechanisms of these anti-CRISPR proteins in their structural context. Considering anti-CRISPRs in this way will provide important clues for studying their origin and evolution.

Improved structural integrity through advances in reliable residual stress measurement: the impact of ENGIN-X

NASA Astrophysics Data System (ADS)

Edwards, L.; Santisteban, J. R.

The determination of accurate reliable residual stresses is critical to many fields of structural integrity. Neutron stress measurement is a non-destructive technique that uniquely provides insights into stress fields deep within engineering components and structures. As such, it has become an increasingly important tool within engineering, leading to improved manufacturing processes to reduce stress and distortion as well as to the definition of more precise lifing procedures. This paper describes the likely impact of the next generation of dedicated engineering stress diffractometers currently being constructed and the utility of the technique using examples of residual stresses both beneficial and detrimental to structural integrity.

RSRE: RNA structural robustness evaluator

PubMed Central

Shu, Wenjie; Zheng, Zhiqiang; Wang, Shengqi

2007-01-01

Biological robustness, defined as the ability to maintain stable functioning in the face of various perturbations, is an important and fundamental topic in current biology, and has become a focus of numerous studies in recent years. Although structural robustness has been explored in several types of RNA molecules, the origins of robustness are still controversial. Computational analysis results are needed to make up for the lack of evidence of robustness in natural biological systems. The RNA structural robustness evaluator (RSRE) web server presented here provides a freely available online tool to quantitatively evaluate the structural robustness of RNA based on the widely accepted definition of neutrality. Several classical structure comparison methods are employed; five randomization methods are implemented to generate control sequences; sub-optimal predicted structures can be optionally utilized to mitigate the uncertainty of secondary structure prediction. With a user-friendly interface, the web application is easy to use. Intuitive illustrations are provided along with the original computational results to facilitate analysis. The RSRE will be helpful in the wide exploration of RNA structural robustness and will catalyze our understanding of RNA evolution. The RSRE web server is freely available at http://biosrv1.bmi.ac.cn/RSRE/ or http://biotech.bmi.ac.cn/RSRE/. PMID:17567615

Cell–scaffold interaction within engineered tissue

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

Chen, Haiping; Liu, Yuanyuan, E-mail: Yuanyuan_liu@shu.edu.cn; Jiang, Zhenglong

The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted largemore » amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.« less

A Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-terminal Domain.

PubMed

Li, Weiwei; Wu, Baixing; Soca, Wibowo Adian; An, Lei

2018-05-02

Classical swine fever virus (CSFV) is the ringleader of Classical swine fever (CSF). The non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a de novo mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding on the mechanism of CSFV RNA synthesis, here we solved the first crystal structure of CSFV-NS5B. Our studies show that the CSFV-NS5B RdRp contains characteristic fingers, palm domain and thumb domain as well as a unique N-terminal domain (NTD) that had never been observed. Mutagenesis studies on NS5B validated the importance of NTD in the catalytic activity of this novel RNA-dependent RNA polymerase. Moreover, our results shed light on the understanding of CSFV infection. IMPORTANCE Pigs are important domestic animal. However, a highly contagious viral disease named Classical swine fever (CSF) causes devastating economic losses. Classical swine fever virus (CSFV) is the primary culprit of CSF, which is a positive-sense single-stranded RNA virus belonging to the Pestivirus genus, Flaviviridae family. Genome replication of CSFV depends on RNA-dependent RNA polymerase known as NS5B. However, the structure of CSFV-NS5B has never been reported, and the mechanism of CSFV replication is poorly understood. Here, we solved the first crystal structure of CSFV-NS5B, analyzed the function of characteristic fingers, palm, and thumb domains. Additionally, our structure also revealed the presence of a novel N-terminal domain (NTD). Biochemical studies demonstrated that the NTD of CSFV-NS5B is very important for RNA-dependent RNA polymerase (RdRp) activity. Collectively, our studies provide a structural basis for future rational design of anti-CSFV drugs which is critically important as no effective anti-CSFV drugs have been developed. Copyright © 2018 American Society for Microbiology.

A taxonomy of health networks and systems: bringing order out of chaos.

PubMed Central

Bazzoli, G J; Shortell, S M; Dubbs, N; Chan, C; Kralovec, P

1999-01-01

OBJECTIVE: To use existing theory and data for empirical development of a taxonomy that identifies clusters of organizations sharing common strategic/structural features. DATA SOURCES: Data from the 1994 and 1995 American Hospital Association Annual Surveys, which provide extensive data on hospital involvement in hospital-led health networks and systems. STUDY DESIGN: Theories of organization behavior and industrial organization economics were used to identify three strategic/structural dimensions: differentiation, which refers to the number of different products/services along a healthcare continuum; integration, which refers to mechanisms used to achieve unity of effort across organizational components; and centralization, which relates to the extent to which activities take place at centralized versus dispersed locations. These dimensions were applied to three components of the health service/product continuum: hospital services, physician arrangements, and provider-based insurance activities. DATA EXTRACTION METHODS: We identified 295 health systems and 274 health networks across the United States in 1994, and 297 health systems and 306 health networks in 1995 using AHA data. Empirical measures aggregated individual hospital data to the health network and system level. PRINCIPAL FINDINGS: We identified a reliable, internally valid, and stable four-cluster solution for health networks and a five-cluster solution for health systems. We found that differentiation and centralization were particularly important in distinguishing unique clusters of organizations. High differentiation typically occurred with low centralization, which suggests that a broader scope of activity is more difficult to centrally coordinate. Integration was also important, but we found that health networks and systems typically engaged in both ownership-based and contractual-based integration or they were not integrated at all. CONCLUSIONS: Overall, we were able to classify approximately 70 percent of hospital-led health networks and 90 percent of hospital-led health systems into well-defined organizational clusters. Given the widespread perception that organizational change in healthcare has been chaotic, our research suggests that important and meaningful similarities exist across many evolving organizations. The resulting taxonomy provides a new lexicon for researchers, policymakers, and healthcare executives for characterizing key strategic and structural features of evolving organizations. The taxonomy also provides a framework for future inquiry about the relationships between organizational strategy, structure, and performance, and for assessing policy issues, such as Medicare Provider Sponsored Organizations, antitrust, and insurance regulation. Images Figure 2A Figure 2A Figure 2B Figure 2B PMID:10029504

Women's and care providers' perspectives of quality prenatal care: a qualitative descriptive study

PubMed Central

2012-01-01

Background Much attention has been given to the adequacy of prenatal care use in promoting healthy outcomes for women and their infants. Adequacy of use takes into account the timing of initiation of prenatal care and the number of visits. However, there is emerging evidence that the quality of prenatal care may be more important than adequacy of use. The purpose of our study was to explore women's and care providers' perspectives of quality prenatal care to inform the development of items for a new instrument, the Quality of Prenatal Care Questionnaire. We report on the derivation of themes resulting from this first step of questionnaire development. Methods A qualitative descriptive approach was used. Semi-structured interviews were conducted with 40 pregnant women and 40 prenatal care providers recruited from five urban centres across Canada. Data were analyzed using inductive open and then pattern coding. The final step of analysis used a deductive approach to assign the emergent themes to broader categories reflective of the study's conceptual framework. Results The three main categories informed by Donabedian's model of quality health care were structure of care, clinical care processes, and interpersonal care processes. Structure of care themes included access, physical setting, and staff and care provider characteristics. Themes under clinical care processes were health promotion and illness prevention, screening and assessment, information sharing, continuity of care, non-medicalization of pregnancy, and women-centredness. Interpersonal care processes themes were respectful attitude, emotional support, approachable interaction style, and taking time. A recurrent theme woven throughout the data reflected the importance of a meaningful relationship between a woman and her prenatal care provider that was characterized by trust. Conclusions While certain aspects of structure of care were identified as being key dimensions of quality prenatal care, clinical and interpersonal care processes emerged as being most essential to quality care. These processes are important as they have a role in mitigating adverse outcomes, promoting involvement of women in their own care, and keeping women engaged in care. The findings suggest key considerations for the planning, delivery, and evaluation of prenatal care. Most notably, care should be woman-centred and embrace shared decision making as an essential element. PMID:22502640

The Impact of Services on Economic Complexity: Service Sophistication as Route for Economic Growth.

PubMed

Stojkoski, Viktor; Utkovski, Zoran; Kocarev, Ljupco

2016-01-01

Economic complexity reflects the amount of knowledge that is embedded in the productive structure of an economy. By combining tools from network science and econometrics, a robust and stable relationship between a country's productive structure and its economic growth has been established. Here we report that not only goods but also services are important for predicting the rate at which countries will grow. By adopting a terminology which classifies manufactured goods and delivered services as products, we investigate the influence of services on the country's productive structure. In particular, we provide evidence that complexity indices for services are in general higher than those for goods, which is reflected in a general tendency to rank countries with developed service sector higher than countries with economy centred on manufacturing of goods. By focusing on country dynamics based on experimental data, we investigate the impact of services on the economic complexity of countries measured in the product space (consisting of both goods and services). Importantly, we show that diversification of service exports and its sophistication can provide an additional route for economic growth in both developing and developed countries.

The Impact of Services on Economic Complexity: Service Sophistication as Route for Economic Growth

PubMed Central

Utkovski, Zoran; Kocarev, Ljupco

2016-01-01

Economic complexity reflects the amount of knowledge that is embedded in the productive structure of an economy. By combining tools from network science and econometrics, a robust and stable relationship between a country’s productive structure and its economic growth has been established. Here we report that not only goods but also services are important for predicting the rate at which countries will grow. By adopting a terminology which classifies manufactured goods and delivered services as products, we investigate the influence of services on the country’s productive structure. In particular, we provide evidence that complexity indices for services are in general higher than those for goods, which is reflected in a general tendency to rank countries with developed service sector higher than countries with economy centred on manufacturing of goods. By focusing on country dynamics based on experimental data, we investigate the impact of services on the economic complexity of countries measured in the product space (consisting of both goods and services). Importantly, we show that diversification of service exports and its sophistication can provide an additional route for economic growth in both developing and developed countries. PMID:27560133

SerpentinaDB: a database of plant-derived molecules of Rauvolfia serpentina.

PubMed

Pathania, Shivalika; Ramakrishnan, Sai Mukund; Randhawa, Vinay; Bagler, Ganesh

2015-08-04

Plant-derived molecules (PDMs) are known to be a rich source of diverse scaffolds that could serve as a basis for rational drug design. Structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel PDMs and their analogs as therapeutic agents. Rauvolfia serpentina is an important medicinal plant, endemic to Himalayan mountain ranges of Indian subcontinent, reported to be of immense therapeutic value against various diseases. We present SerpentinaDB, a structured compilation of 147 R. serpentina PDMs, inclusive of their plant part source, chemical classification, IUPAC, SMILES, physicochemical properties, and 3D chemical structures with associated references. It also provides refined search option for identification of analogs of natural molecules against ZINC database at user-defined cut-off. SerpentinaDB is an exhaustive resource of R. serpentina molecules facilitating prospection for therapeutic molecules from a medicinally important source of natural products. It also provides refined search option to explore the neighborhood of chemical space against ZINC database to identify analogs of natural molecules obtained as leads. In a previous study, we have demonstrated the utility of this resource by identifying novel aldose reductase inhibitors towards intervention of complications of diabetes.

Effects of long-term nutrient additions on Arctic tundra, stream, and lake ecosystems: beyond NPP.

PubMed

Gough, Laura; Bettez, Neil D; Slavik, Karie A; Bowden, William B; Giblin, Anne E; Kling, George W; Laundre, James A; Shaver, Gaius R

2016-11-01

Primary producers form the base of food webs but also affect other ecosystem characteristics, such as habitat structure, light availability, and microclimate. Here, we examine changes caused by 5-30+ years of nutrient addition and resulting increases in net primary productivity (NPP) in tundra, streams, and lakes in northern Alaska. The Arctic provides an important opportunity to examine how ecosystems characterized by low diversity and low productivity respond to release from nutrient limitation. We review how responses of algae and plants affect light availability, perennial biotic structures available for consumers, oxygen levels, and temperature. Sometimes, responses were similar across all three ecosystems; e.g., increased NPP significantly reduced light to the substrate following fertilization. Perennial biotic structures increased in tundra and streams but not in lakes, and provided important new habitat niches for consumers as well as other producers. Oxygen and temperature responses also differed. Life history traits (e.g., longevity) of the primary producers along with the fate of detritus drove the responses and recovery. As global change persists and nutrients become more available in the Arctic and elsewhere, incorporating these factors as response variables will enable better prediction of ecosystem changes and feedbacks in this biome and others.

Experimental observation of the topological structure of exceptional points in an ultrathin hybridized metamaterial

NASA Astrophysics Data System (ADS)

Kang, Ming; Zhu, Weiren; Rukhlenko, Ivan D.

2017-12-01

The exceptional point (EP), which is one of the most important branch-type singularities exclusive to non-Hermitian systems, has been observed recently in various synthetic materials, giving rise to counterintuitive phenomena due to the nontrivial topology of the EP. Here, we present a direct experimental observation of the topological structure of the EPs via the angle-resolved transmission measurement of a hybridized metamaterial. Both eigenvalues and eigenvectors show branch-point singularities in the investigated biparametric space of frequency and incident angle. Importantly, the angle-resolved transmission coefficients provide all the information about the eigenvalues as well as the corresponding eigenvectors in the biparametric space, revealing the nontrivial topological structure of the EP, such as mode switching and the topological phase for a parameter loop encircling the EP. It is shown that the appearance of the EP in the scattering matrix is related directly to the perfect unidirectional transmission and the chirality of the EP corresponds to the maximum or minimum value of the asymmetric factor. Our investigation uncovers the capabilities of metamaterials for exploring the physics of EPs and their potential for having extreme optical properties, which provide potential applications in the spectral band ranging from microwaves to visible frequencies.

Comparative study on the welded structure fatigue strength assessment method

NASA Astrophysics Data System (ADS)

Hu, Tao

2018-04-01

Due to the welding structure is widely applied in various industries, especially the pressure container, motorcycle, automobile, aviation, ship industry, such as large crane steel structure, so for welded structure fatigue strength evaluation is particularly important. For welded structure fatigue strength evaluation method mainly has four kinds of, the more from the use of two kinds of welded structure fatigue strength evaluation method, namely the nominal stress method and the hot spot stress evaluation method, comparing from its principle, calculation method for the process analysis and research, compare the similarities and the advantages and disadvantages, the analysis of practical engineering problems to provide the reference for every profession and trade, as well as the future welded structure fatigue strength and life evaluation method put forward outlook.

Underexpanded Screeching Jets From Circular, Rectangular, and Elliptic Nozzles

NASA Technical Reports Server (NTRS)

Panda, J.; Raman, G.; Zaman, K. B. M. Q.

2004-01-01

The screech frequency and amplitude, the shock spacing, the hydrodynamic-acoustic standing wave spacing, and the convective velocity of large organized structures are measured in the nominal Mach number range of 1.1 less than or = Mj less that or = l0.9 for supersonic, underexpanded jets exhausting from a circular, a rectangular and an elliptic nozzle. This provides a carefully measured data set useful in comparing the importance of various physical parameters in the screech generation process. The hydrodynamic-acoustic standing wave is formed between the potential pressure field of large turbulent structures and the acoustic pressure field of the screech sound. It has been demonstrated earlier that in the currently available screech frequency prediction models replacement of the shock spacing by the standing wave spacing provides an exact expression. In view of this newly found evidence, a comparison is made between the average standing wavelength and the average shock spacing. It is found that there exists a small, yet important, difference, which is dependent on the azimuthal screech mode. For example, in the flapping modes of circular, rectangular, and elliptic jets, the standing wavelength is slightly longer than the shock spacing, while for the helical screech mode in a circular jet the opposite is true. This difference accounts for the departure of the existing models from predicting the exact screech frequency. Another important parameter, necessary in screech prediction, is the convective velocity of the large organized structures. It is demonstrated that the presence of the hydrodynamic-acoustic standing wave, even inside the jet shear layer, becomes a significant source of error in the convective velocity data obtained using the conventional methods. However, a new relationship, using the standing wavelength and screech frequency is shown to provide more accurate results.

Safe Corridor to Access Clivus for Endoscopic Trans-Sphenoidal Surgery: A Radiological and Anatomical Study

PubMed Central

Cheng, Ye; Zhang, Siwen; Chen, Yong; Zhao, Gang

2015-01-01

Purpose Penetration of the clivus is required for surgical access of the brain stem. The endoscopic transclivus approach is a difficult procedure with high risk of injury to important neurovascular structures. We undertook a novel anatomical and radiological investigation to understand the structure of the clivus and neurovascular structures relevant to the extended trans-nasal trans-sphenoid procedure and determine a safe corridor for the penetration of the clivus. Method We examined the clivus region in the computed tomographic angiography (CTA) images of 220 adults, magnetic resonance (MR) images of 50 adults, and dry skull specimens of 10 adults. Multiplanar reconstruction (MPR) of the CT images was performed, and the anatomical features of the clivus were studied in the coronal, sagittal, and axial planes. The data from the images were used to determine the anatomical parameters of the clivus and neurovascular structures, such as the internal carotid artery and inferior petrosal sinus. Results The examination of the CTA and MR images of the enrolled subjects revealed that the thickness of the clivus helped determine the depth of the penetration, while the distance from the sagittal midline to the important neurovascular structures determined the width of the penetration. Further, data from the CTA and MR images were consistent with those retrieved from the examination of the cadaveric specimens. Conclusion Our findings provided certain pointers that may be useful in guiding the surgery such that inadvertent injury to vital structures is avoided and also provided supportive information for the choice of the appropriate endoscopic equipment. PMID:26368821

Using Entropy Maximization to Understand the Determinants of Structural Dynamics beyond Native Contact Topology

PubMed Central

Lezon, Timothy R.; Bahar, Ivet

2010-01-01

Comparison of elastic network model predictions with experimental data has provided important insights on the dominant role of the network of inter-residue contacts in defining the global dynamics of proteins. Most of these studies have focused on interpreting the mean-square fluctuations of residues, or deriving the most collective, or softest, modes of motions that are known to be insensitive to structural and energetic details. However, with increasing structural data, we are in a position to perform a more critical assessment of the structure-dynamics relations in proteins, and gain a deeper understanding of the major determinants of not only the mean-square fluctuations and lowest frequency modes, but the covariance or the cross-correlations between residue fluctuations and the shapes of higher modes. A systematic study of a large set of NMR-determined proteins is analyzed using a novel method based on entropy maximization to demonstrate that the next level of refinement in the elastic network model description of proteins ought to take into consideration properties such as contact order (or sequential separation between contacting residues) and the secondary structure types of the interacting residues, whereas the types of amino acids do not play a critical role. Most importantly, an optimal description of observed cross-correlations requires the inclusion of destabilizing, as opposed to exclusively stabilizing, interactions, stipulating the functional significance of local frustration in imparting native-like dynamics. This study provides us with a deeper understanding of the structural basis of experimentally observed behavior, and opens the way to the development of more accurate models for exploring protein dynamics. PMID:20585542

Using entropy maximization to understand the determinants of structural dynamics beyond native contact topology.

PubMed

Lezon, Timothy R; Bahar, Ivet

2010-06-17

Comparison of elastic network model predictions with experimental data has provided important insights on the dominant role of the network of inter-residue contacts in defining the global dynamics of proteins. Most of these studies have focused on interpreting the mean-square fluctuations of residues, or deriving the most collective, or softest, modes of motions that are known to be insensitive to structural and energetic details. However, with increasing structural data, we are in a position to perform a more critical assessment of the structure-dynamics relations in proteins, and gain a deeper understanding of the major determinants of not only the mean-square fluctuations and lowest frequency modes, but the covariance or the cross-correlations between residue fluctuations and the shapes of higher modes. A systematic study of a large set of NMR-determined proteins is analyzed using a novel method based on entropy maximization to demonstrate that the next level of refinement in the elastic network model description of proteins ought to take into consideration properties such as contact order (or sequential separation between contacting residues) and the secondary structure types of the interacting residues, whereas the types of amino acids do not play a critical role. Most importantly, an optimal description of observed cross-correlations requires the inclusion of destabilizing, as opposed to exclusively stabilizing, interactions, stipulating the functional significance of local frustration in imparting native-like dynamics. This study provides us with a deeper understanding of the structural basis of experimentally observed behavior, and opens the way to the development of more accurate models for exploring protein dynamics.

Cityscape genetics: structural vs. functional connectivity of an urban lizard population.

PubMed

Beninde, Joscha; Feldmeier, Stephan; Werner, Maike; Peroverde, Daniel; Schulte, Ulrich; Hochkirch, Axel; Veith, Michael

2016-10-01

Functional connectivity is essential for the long-term persistence of populations. However, many studies assess connectivity with a focus on structural connectivity only. Cityscapes, namely urban landscapes, are particularly dynamic and include numerous potential anthropogenic barriers to animal movements, such as roads, traffic or buildings. To assess and compare structural connectivity of habitats and functional connectivity of gene flow of an urban lizard, we here combined species distribution models (SDMs) with an individual-based landscape genetic optimization procedure. The most important environmental factors of the SDMs are structural diversity and substrate type, with high and medium levels of structural diversity as well as open and rocky/gravel substrates contributing most to structural connectivity. By contrast, water cover was the best model of all environmental factors following landscape genetic optimization. The river is thus a major barrier to gene flow, while of the typical anthropogenic factors only buildings showed an effect. Nonetheless, using SDMs as a basis for landscape genetic optimization provided the highest ranked model for functional connectivity. Optimizing SDMs in this way can provide a sound basis for models of gene flow of the cityscape, and elsewhere, while presence-only and presence-absence modelling approaches showed differences in performance. Additionally, interpretation of results based on SDM factor importance can be misleading, dictating more thorough analyses following optimization of SDMs. Such approaches can be adopted for management strategies, for example aiming to connect native common wall lizard populations or disconnect them from non-native introduced populations, which are currently spreading in many cities in Central Europe. © 2016 John Wiley & Sons Ltd.

Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design.

PubMed

Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi

2006-03-31

Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of "domain-specific" second-generation ACE inhibitors.

Structural Basis for Iloprost as a Dual Peroxisome Proliferator-activated Receptor [alpha/delta] Agonist

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

Jin, Lihua; Lin, Shengchen; Rong, Hui

2012-03-15

Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPAR{alpha} ligand-binding domain and PPAR{delta} ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPAR{alpha}/{delta} by this prostacyclin analog. In addition to conserved contacts for all PPAR{alpha} ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural andmore » functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPAR{alpha}/{delta} interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.« less

Evaluation of variability in high-resolution protein structures by global distance scoring.

PubMed

Anzai, Risa; Asami, Yoshiki; Inoue, Waka; Ueno, Hina; Yamada, Koya; Okada, Tetsuji

2018-01-01

Systematic analysis of the statistical and dynamical properties of proteins is critical to understanding cellular events. Extraction of biologically relevant information from a set of high-resolution structures is important because it can provide mechanistic details behind the functional properties of protein families, enabling rational comparison between families. Most of the current structural comparisons are pairwise-based, which hampers the global analysis of increasing contents in the Protein Data Bank. Additionally, pairing of protein structures introduces uncertainty with respect to reproducibility because it frequently accompanies other settings for superimposition. This study introduces intramolecular distance scoring for the global analysis of proteins, for each of which at least several high-resolution structures are available. As a pilot study, we have tested 300 human proteins and showed that the method is comprehensively used to overview advances in each protein and protein family at the atomic level. This method, together with the interpretation of the model calculations, provide new criteria for understanding specific structural variation in a protein, enabling global comparison of the variability in proteins from different species.

Evolutionary dynamics of collective action in spatially structured populations.

PubMed

Peña, Jorge; Nöldeke, Georg; Lehmann, Laurent

2015-10-07

Many models proposed to study the evolution of collective action rely on a formalism that represents social interactions as n-player games between individuals adopting discrete actions such as cooperate and defect. Despite the importance of spatial structure in biological collective action, the analysis of n-player games games in spatially structured populations has so far proved elusive. We address this problem by considering mixed strategies and by integrating discrete-action n-player games into the direct fitness approach of social evolution theory. This allows to conveniently identify convergence stable strategies and to capture the effect of population structure by a single structure coefficient, namely, the pairwise (scaled) relatedness among interacting individuals. As an application, we use our mathematical framework to investigate collective action problems associated with the provision of three different kinds of collective goods, paradigmatic of a vast array of helping traits in nature: "public goods" (both providers and shirkers can use the good, e.g., alarm calls), "club goods" (only providers can use the good, e.g., participation in collective hunting), and "charity goods" (only shirkers can use the good, e.g., altruistic sacrifice). We show that relatedness promotes the evolution of collective action in different ways depending on the kind of collective good and its economies of scale. Our findings highlight the importance of explicitly accounting for relatedness, the kind of collective good, and the economies of scale in theoretical and empirical studies of the evolution of collective action. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tunable bandgaps in a deployable metamaterial

NASA Astrophysics Data System (ADS)

Nanda, Aditya; Karami, M. Amin

2018-03-01

In this manuscript, we envision deployable structures (such as solar arrays) and origami-inspired foldable structures as metamaterials capable of tunable wave manipulation. Specifically, we present a metamaterial whose bandgaps can be modulated by changing the fold angle of adjacent panels. The repeating unit cell of the structure consists of a beam (representing a panel) and a torsional spring (representing the folding mechanism). Two important cases are considered. Firstly, the fold angle (angle between adjacent beams), Ψ, is zero and only flexural waves propagate. In the second case, the fold angle is greater than zero (Ψ > 0). This causes longitudinal and transverse vibration to be coupled. FEM models are used to validate both these analyses. Increasing the fold angle was found to inflict profound changes to the wave transmission characteristics of the structure. In general, increasing the fold angles caused the bandwidth of bandgaps to increase significantly. For the lowest four bandgaps we found bandwidth increases of 252 %, 177 %, 230 % and 163 % respectively at Ψ = 90 deg (relative to the bandwidths at Ψ = 0). In addition, significant increase in bandwidth of the odd-numbered bandgaps occurs even at small fold angles- the bandwidth for the first and third bandgaps effectively double in size (increase by 100%) at Ψ = 20 deg relative to those at Ψ = 0. This has important ramifications in the context of tunable wave manipulation and adaptive filtering. In addition, by expanding out the characteristic equation of transfer matrix for the straight structure, we prove that the upper band edge of the nth bandgap will always equal the nth simply supported natural frequency of the constituent beam. Further, we found that the ratio (EI/kt) is an important parameter affecting the bandwidth of bandgaps. For low values of the ratio, effectively, no bandgap exists. For higher values of the ratio (EI/kt), we obtain a relatively large bandgap over which no waves propagate. This can have important ramifications for the design of foldable structures. As an alternative to impedance-based structural health monitoring, these insights can aid in health monitoring of deployable structures by tracking the bandwidth of bandgaps which can provide important clues about the mechanical parameters of the structure.

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.

Probing disorder in isometric pyrochlore and related complex oxides

NASA Astrophysics Data System (ADS)

Shamblin, Jacob; Feygenson, Mikhail; Neuefeind, Joerg; Tracy, Cameron L.; Zhang, Fuxiang; Finkeldei, Sarah; Bosbach, Dirk; Zhou, Haidong; Ewing, Rodney C.; Lang, Maik

2016-05-01

There has been an increased focus on understanding the energetics of structures with unconventional ordering (for example, correlated disorder that is heterogeneous across different length scales). In particular, compounds with the isometric pyrochlore structure, A2B2O7, can adopt a disordered, isometric fluorite-type structure, (A, B)4O7, under extreme conditions. Despite the importance of the disordering process there exists only a limited understanding of the role of local ordering on the energy landscape. We have used neutron total scattering to show that disordered fluorite (induced intrinsically by composition/stoichiometry or at far-from-equilibrium conditions produced by high-energy radiation) consists of a local orthorhombic structural unit that is repeated by a pseudo-translational symmetry, such that orthorhombic and isometric arrays coexist at different length scales. We also show that inversion in isometric spinel occurs by a similar process. This insight provides a new basis for understanding order-to-disorder transformations important for applications such as plutonium immobilization, fast ion conduction, and thermal barrier coatings.

Structure of the human TRiC/CCT Subunit 5 associated with hereditary sensory neuropathy.

PubMed

Pereira, Jose H; McAndrew, Ryan P; Sergeeva, Oksana A; Ralston, Corie Y; King, Jonathan A; Adams, Paul D

2017-06-16

The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many human diseases, such as amyloid diseases, cancer, and neuropathies, making TRiC a potential therapeutic target. A detailed structural understanding of its ATP-dependent folding mechanism and substrate recognition is therefore of great importance. Of particular health-related interest is the mutation Histidine 147 to Arginine (H147R) in human TRiC subunit 5 (CCT5), which has been associated with hereditary sensory neuropathy. In this paper, we describe the crystal structures of CCT5 and the CCT5-H147R mutant, which provide important structural information for this vital protein-folding machine in humans. This first X-ray crystallographic study of a single human CCT subunit in the context of a hexadecameric complex can be expanded in the future to the other 7 subunits that form the TRiC complex.

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

Structural and mechanistic insights into phospholipid transfer by Ups1-Mdm35 in mitochondria

NASA Astrophysics Data System (ADS)

Watanabe, Yasunori; Tamura, Yasushi; Kawano, Shin; Endo, Toshiya

2015-08-01

Eukaryotic cells are compartmentalized into membrane-bounded organelles whose functions rely on lipid trafficking to achieve membrane-specific compositions of lipids. Here we focused on the Ups1-Mdm35 system, which mediates phosphatidic acid (PA) transfer between the outer and inner mitochondrial membranes, and determined the X-ray structures of Mdm35 and Ups1-Mdm35 with and without PA. The Ups1-Mdm35 complex constitutes a single domain that has a deep pocket and flexible Ω-loop lid. Structure-based mutational analyses revealed that a basic residue at the pocket bottom and the Ω-loop lid are important for PA extraction from the membrane following Ups1 binding. Ups1 binding to the membrane is enhanced by the dissociation of Mdm35. We also show that basic residues around the pocket entrance are important for Ups1 binding to the membrane and PA extraction. These results provide a structural basis for understanding the mechanism of PA transfer between mitochondrial membranes.

Clinical significance of knowledge about the structure, function, and impairments of working memory

PubMed Central

Brodziak, Andrzej; Brewczyński, Adam; Bajor, Grzegorz

2013-01-01

A review of contemporary research on the working memory system (WMS) is important, both due to the need to focus the discussion on further necessary investigations on the structure and function of this key part of the human brain, as well as to share this knowledge with clinicians. In our introduction we try to clarify the actual terminology and provide an intuitively understandable model for 3 basic cognitive operations: perception, recognition, imagery, and manipulation of recalled mental images. We emphasize the importance of knowledge of the structure and function of the WMS for the possibility to demonstrate the links between genetic polymorphisms and the prevalence to some mental disorders. We also review current knowledge of working memory dysfunction in the most common diseases and specific clinical situations such as maturation and aging. Finally, we briefly discuss methods for assessment of WMS capacity. This article establishes a kind of compendium of knowledge for clinicians who are not familiar with the structure and operation of the WMS. PMID:23645218

Home health nursing care agenda based on health policy in Korea.

PubMed

Ryu, Hosihn; An, Jiyoung; Koabyashi, Mia

2005-06-01

Home health nursing care (HHNC) in Korea has taken on an important role under the mandate of the national health care system since 2000. This program was developed to verify the possibility of early discharge of hospitalized patients and cost containment through a research and development project that was conducted with the government from 1994 to 1999. The process of development of HHNC provided an opportunity to realize the advancement and changes in the system into a consumer-focused structure. This is an important turning point for the Korean health care system that suggests certain possibilities for building a foundation for further changes in the service delivery structure. The structure, which had been limited to a supplier-oriented model, is moving to a consumer-oriented structure. Accordingly, the major function and role of nursing policy makers in Korea is to develop an agenda and alternatives for policy-making in a systematic manner and to present implementation strategies clearly.

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

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

NASA Astrophysics Data System (ADS)

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

2011-05-01

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

Structural Elucidation of Enzymatically Synthesized Galacto-oligosaccharides Using Ion-Mobility Spectrometry-Tandem Mass Spectrometry.

PubMed

Carević, Milica; Bezbradica, Dejan; Banjanac, Katarina; Milivojević, Ana; Fanuel, Mathieu; Rogniaux, Hélène; Ropartz, David; Veličković, Dušan

2016-05-11

Galacto-oligosaccharides (GOS) represent a diverse group of well-characterized prebiotic ingredients derived from lactose in a reaction catalyzed with β-galactosidases. Enzymatic transgalactosylation results in a mixture of compounds of various degrees of polymerization and types of linkages. Because structure plays an important role in terms of prebiotic activity, it is of crucial importance to provide an insight into the mechanism of transgalactosylation reaction and occurrence of different types of β-linkages during GOS synthesis. Our study proved that a novel one-step method, based on ion-mobility spectrometry-tandem mass spectrometry (IMS-MS/MS), enables complete elucidation of GOS structure. It has been shown that β-galactosidase from Aspergillus oryzae has the highest affinity toward formation of β-(1→3) or β-(1→6) linkages. Additionally, it was observed that the occurrence of different linkages varies during the reaction course, indicating that tailoring favorable GOS structures with improved prebiotic activity can be achieved by adequate control of enzymatic synthesis.

Social organization of self-management support of persons with diabetes: a health systems comparison.

PubMed

Schiøtz, Michaela; Frølich, Anne; Krasnik, Allan; Taylor, Warren; Hsu, John

2012-09-01

Identify important organizational elements for providing self-management support (SMS). Semi-structured qualitative interviews conducted in two healthcare systems. Kaiser Permanente Northern California and the Danish Health Care System. 36 managers and healthcare professionals in the two healthcare systems. Elements important to providing self-management support to persons with diabetes. Healthcare professionals' provision of SMS was influenced by healthcare system organization and their perceptions of SMS, the capability and responsibility of healthcare systems, and their roles in the healthcare organization. Enabling factors for providing SMS included: strong leadership; aligned incentives; use of an integrated health information technology (HIT) system; multidisciplinary healthcare provider teams; ongoing training for healthcare professionals; outreach; and quality goals. Barriers to providing SMS included lack of collaboration between providers and skeptical attitudes towards prevention and outreach. Implementation of SMS can be improved by an understanding of the elements that enhance its provision: (1) initiatives seeking to improve collaboration and integration between providers; (2) implementation of an integrated HIT system; and (3) ongoing training of healthcare professionals.

Topological constraints are major determinants of tRNA tertiary structure and dynamics and provide basis for tertiary folding cooperativity

PubMed Central

Mustoe, Anthony M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

2014-01-01

Recent studies have shown that basic steric and connectivity constraints encoded at the secondary structure level are key determinants of 3D structure and dynamics in simple two-way RNA junctions. However, the role of these topological constraints in higher order RNA junctions remains poorly understood. Here, we use a specialized coarse-grained molecular dynamics model to directly probe the thermodynamic contributions of topological constraints in defining the 3D architecture and dynamics of transfer RNA (tRNA). Topological constraints alone restrict tRNA's allowed conformational space by over an order of magnitude and strongly discriminate against formation of non-native tertiary contacts, providing a sequence independent source of folding specificity. Topological constraints also give rise to long-range correlations between the relative orientation of tRNA's helices, which in turn provides a mechanism for encoding thermodynamic cooperativity between distinct tertiary interactions. These aspects of topological constraints make it such that only several tertiary interactions are needed to confine tRNA to its native global structure and specify functionally important 3D dynamics. We further show that topological constraints are conserved across tRNA's different naturally occurring secondary structures. Taken together, our results emphasize the central role of secondary-structure-encoded topological constraints in defining RNA 3D structure, dynamics and folding. PMID:25217593

Microscopic structural descriptor of liquid water

NASA Astrophysics Data System (ADS)

Shi, Rui; Tanaka, Hajime

2018-03-01

The microscopic structure of liquid water has been believed to be the key to the understanding of the unique properties of this extremely important substance. Many structural descriptors have been developed for revealing local structural order in water, but their properties are still not well understood. The essential difficulty comes from structural fluctuations due to thermal noise, which are intrinsic to the liquid state. The most popular and widely used descriptors are the local structure index (LSI) and d5. Recently, Russo and Tanaka [Nat. Commun. 3, 3556 (2014)] introduced a new descriptor ζ which measures the translational order between the first and second shells considering hydrogen bonding (H-bonding) in the first shell. In this work, we compare the performance of these three structural descriptors for a popular water model known as TIP5P water. We show that local structural ordering can be properly captured only by the structural descriptor ζ, but not by the other two descriptors particularly at a high temperature, where thermal noise effects are severe. The key difference of ζ from LSI and d5 is that only ζ considers H-bonding which is crucial to detect high translational and tetrahedral order of not only oxygen but also hydrogen atoms. The importance of H-bonding is very natural, considering the fact that the locally favored structures are stabilized by energy gain due to the formation of four hydrogen bonds between the central water molecule and its neighboring ones in the first shell. Our analysis of the water structure by using ζ strongly supports the two-state model of water: water is a dynamic mixture of locally favored (ordered) and normal-liquid (disordered) structures. This work demonstrates the importance of H-bonding in the characterization of water's structures and provides a useful structural descriptor for water-type tetrahedral liquids to study their structure and dynamics.

Advancing Precambrian palaeomagnetism with the PALEOMAGIA and PINT(QPI) databases

PubMed Central

Veikkolainen, Toni H.; Biggin, Andrew J.; Pesonen, Lauri J.; Evans, David A.; Jarboe, Nicholas A.

2017-01-01

State-of-the-art measurements of the direction and intensity of Earth’s ancient magnetic field have made important contributions to our understanding of the geology and palaeogeography of Precambrian Earth. The PALEOMAGIA and PINT(QPI) databases provide thorough public collections of important palaeomagnetic data of this kind. They comprise more than 4,100 observations in total and have been essential in supporting our international collaborative efforts to understand Earth's magnetic history on a timescale far longer than that of the present Phanerozoic Eon. Here, we provide an overview of the technical structure and applications of both databases, paying particular attention to recent improvements and discoveries. PMID:28534869

Advancing Precambrian palaeomagnetism with the PALEOMAGIA and PINT(QPI) databases.

PubMed

Veikkolainen, Toni H; Biggin, Andrew J; Pesonen, Lauri J; Evans, David A; Jarboe, Nicholas A

2017-05-23

State-of-the-art measurements of the direction and intensity of Earth's ancient magnetic field have made important contributions to our understanding of the geology and palaeogeography of Precambrian Earth. The PALEOMAGIA and PINT( QPI ) databases provide thorough public collections of important palaeomagnetic data of this kind. They comprise more than 4,100 observations in total and have been essential in supporting our international collaborative efforts to understand Earth's magnetic history on a timescale far longer than that of the present Phanerozoic Eon. Here, we provide an overview of the technical structure and applications of both databases, paying particular attention to recent improvements and discoveries.

Pseudomonas aeruginosa 4-Amino-4-Deoxychorismate Lyase: Spatial Conservation of an Active Site Tyrosine and Classification of Two Types of Enzyme

PubMed Central

O'Rourke, Patrick E. F.; Eadsforth, Thomas C.; Fyfe, Paul K.; Shepherd, Sharon M.; Hunter, William N.

2011-01-01

4-Amino-4-deoxychorismate lyase (PabC) catalyzes the formation of 4-aminobenzoate, and release of pyruvate, during folate biosynthesis. This is an essential activity for the growth of Gram-negative bacteria, including important pathogens such as Pseudomonas aeruginosa. A high-resolution (1.75 Å) crystal structure of PabC from P. aeruginosa has been determined, and sequence-structure comparisons with orthologous structures are reported. Residues around the pyridoxal 5′-phosphate cofactor are highly conserved adding support to aspects of a mechanism generic for enzymes carrying that cofactor. However, we suggest that PabC can be classified into two groups depending upon whether an active site and structurally conserved tyrosine is provided from the polypeptide that mainly forms an active site or from the partner subunit in the dimeric assembly. We considered that the conserved tyrosine might indicate a direct role in catalysis: that of providing a proton to reduce the olefin moiety of substrate as pyruvate is released. A threonine had previously been suggested to fulfill such a role prior to our observation of the structurally conserved tyrosine. We have been unable to elucidate an experimentally determined structure of PabC in complex with ligands to inform on mechanism and substrate specificity. Therefore we constructed a computational model of the catalytic intermediate docked into the enzyme active site. The model suggests that the conserved tyrosine helps to create a hydrophobic wall on one side of the active site that provides important interactions to bind the catalytic intermediate. However, this residue does not appear to participate in interactions with the C atom that undergoes an sp 2 to sp 3 conversion as pyruvate is produced. The model and our comparisons rather support the hypothesis that an active site threonine hydroxyl contributes a proton used in the reduction of the substrate methylene to pyruvate methyl in the final stage of the mechanism. PMID:21935381

The Physics and Chemistry of Materials

NASA Astrophysics Data System (ADS)

Gersten, Joel I.; Smith, Frederick W.

2001-06-01

A comprehensive introduction to the structure, properties, and applications of materials This title provides the first unified treatment for the broad subject of materials. Authors Gersten and Smith use a fundamental approach to define the structure and properties of a wide range of solids on the basis of the local chemical bonding and atomic order present in the material. Emphasizing the physical and chemical origins of material properties, the book focuses on the most technologically important materials being utilized and developed by scientists and engineers. Appropriate for use in advanced materials courses, The Physics and Chemistry of Materials provides the background information necessary to assimilate the current academic and patent literature on materials and their applications. Problem sets, illustrations, and helpful tables complete this well-rounded new treatment. Five sections cover these important topics: * Structure of materials, including crystal structure, bonding in solids, diffraction and the reciprocal lattice, and order and disorder in solids * Physical properties of materials, including electrical, thermal, optical, magnetic, and mechanical properties * Classes of materials, including semiconductors, superconductors, magnetic materials, and optical materials in addition to metals, ceramics, polymers, dielectrics, and ferroelectrics * A section on surfaces, thin films, interfaces, and multilayers discusses the effects of spatial discontinuities in the physical and chemical structure of materials * A section on synthesis and processing examines the effects of synthesis on the structure and properties of various materials This book is enhanced by a Web-based supplement that offers advanced material together with an entire electronic chapter on the characterization of materials. The Physics and Chemistry of Materials is a complete introduction to the structure and properties of materials for students and an excellent reference for scientists and engineers.

Automated Quantification of Arbitrary Arm-Segment Structure in Spiral Galaxies

NASA Astrophysics Data System (ADS)

Davis, Darren Robert

This thesis describes a system that, given approximately-centered images of spiral galaxies, produces quantitative descriptions of spiral galaxy structure without the need for per-image human input. This structure information consists of a list of spiral arm segments, each associated with a fitted logarithmic spiral arc and a pixel region. This list-of-arcs representation allows description of arbitrary spiral galaxy structure: the arms do not need to be symmetric, may have forks or bends, and, more generally, may be arranged in any manner with a consistent spiral-pattern center (non-merging galaxies have a sufficiently well-defined center). Such flexibility is important in order to accommodate the myriad structure variations observed in spiral galaxies. From the arcs produced from our method it is possible to calculate measures of spiral galaxy structure such as winding direction, winding tightness, arm counts, asymmetry, or other values of interest (including user-defined measures). In addition to providing information about the spiral arm "skeleton" of each galaxy, our method can enable analyses of brightness within individual spiral arms, since we provide the pixel regions associated with each spiral arm segment. For winding direction, arm tightness, and arm count, comparable information is available (to various extents) from previous efforts; to the extent that such information is available, we find strong correspondence with our output. We also characterize the changes to (and invariances in) our output as a function of modifications to important algorithm parameters. By enabling generation of extensive data about spiral galaxy structure from large-scale sky surveys, our method will enable new discoveries and tests regarding the nature of galaxies and the universe, and will facilitate subsequent work to automatically fit detailed brightness models of spiral galaxies.

The demographic consequences of growing older and bigger in oyster populations.

PubMed

Moore, Jacob L; Lipcius, Romuald N; Puckett, Brandon; Schreiber, Sebastian J

2016-10-01

Structured population models, particularly size- or age-structured, have a long history of informing conservation and natural resource management. While size is often easier to measure than age and is the focus of many management strategies, age-structure can have important effects on population dynamics that are not captured in size-only models. However, relatively few studies have included the simultaneous effects of both age- and size-structure. To better understand how population structure, particularly that of age and size, impacts restoration and management decisions, we developed and compared a size-structured integral projection model (IPM) and an age- and size-structured IPM, using a population of Crassostrea gigas oysters in the northeastern Pacific Ocean. We analyzed sensitivity of model results across values of local retention that give populations decreasing in size to populations increasing in size. We found that age- and size-structured models yielded the best fit to the demographic data and provided more reliable results about long-term demography. Elasticity analysis showed that population growth rate was most sensitive to changes in the survival of both large (>175 mm shell length) and small (<75 mm shell length) oysters, indicating that a maximum size limit, in addition to a minimum size limit, could be an effective strategy for maintaining a sustainable population. In contrast, the purely size-structured model did not detect the importance of large individuals. Finally, patterns in stable age and stable size distributions differed between populations decreasing in size due to limited local retention and populations increasing in size due to high local retention. These patterns can be used to determine population status and restoration success. The methodology described here provides general insight into the necessity of including both age- and size-structure into modeling frameworks when using population models to inform restoration and management decisions. © 2016 by the Ecological Society of America.

Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c)

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

Naffin-Olivos, Jacqueline L.; Daab, Andrew; White, Andre

The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 Å and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serinemore » protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity« less

Recent advances in biomimetic sensing technologies.

PubMed

Johnson, E A C; Bonser, R H C; Jeronimidis, G

2009-04-28

The importance of biological materials has long been recognized from the molecular level to higher levels of organization. Whereas, in traditional engineering, hardness and stiffness are considered desirable properties in a material, biology makes considerable and advantageous use of softer, more pliable resources. The development, structure and mechanics of these materials are well documented and will not be covered here. The purpose of this paper is, however, to demonstrate the importance of such materials and, in particular, the functional structures they form. Using only a few simple building blocks, nature is able to develop a plethora of diverse materials, each with a very different set of mechanical properties and from which a seemingly impossibly large number of assorted structures are formed. There is little doubt that this is made possible by the fact that the majority of biological 'materials' or 'structures' are based on fibres and that these fibres provide opportunities for functional hierarchies. We show how these structures have inspired a new generation of innovative technologies in the science and engineering community. Particular attention is given to the use of insects as models for biomimetically inspired innovations.

Analysis of frame structure of medium and small truck crane

NASA Astrophysics Data System (ADS)

Cao, Fuyi; Li, Jinlong; Cui, Mengkai

2018-03-01

Truck crane is an important part of hoisting machinery. Frame, as the support component of the quality of truck crane, determines the safety of crane jib load and the rationality of structural design. In this paper, the truck crane frame is a box structure, the three-dimensional model is established in CATIA software, and imported into Hyperworks software for finite element analysis. On the base of doing constraints and loads for the finite element model of the frame, the finite element static analysis is carried out. And the static stress test verifies whether the finite element model and the frame structure design are reasonable; then the free modal analysis of the frame and the analysis of the first 8 - order modal vibration deformation are carried out. The analysis results show that the maximum stress value of the frame is greater than the yield limit value of the material, and the low-order modal value is close to the excitation frequency value, which needs to be improved to provide theoretical reference for the structural design of the truck crane frame.

Shuttle structural dynamics characteristics: The analysis and verification

NASA Technical Reports Server (NTRS)

Modlin, C. T., Jr.; Zupp, G. A., Jr.

1985-01-01

The space shuttle introduced a new dimension in the complexity of the structural dynamics of a space vehicle. The four-body configuration exhibited structural frequencies as low as 2 hertz with a model density on the order of 10 modes per hertz. In the verification process, certain mode shapes and frequencies were identified by the users as more important than others and, as such, the test objectives were oriented toward experimentally extracting those modes and frequencies for analysis and test correlation purposes. To provide the necessary experimental data, a series of ground vibration tests (GVT's) was conducted using test articles ranging from the 1/4-scale structural replica of the space shuttle to the full-scale vehicle. The vibration test and analysis program revealed that the mode shapes and frequency correlations below 10 hertz were good. The quality of correlation of modes between 10 and 20 hertz ranged from good to fair and that of modes above 20 hertz ranged from poor to good. Since the most important modes, based on user preference, were below 10 hertz, it was judged that the shuttle structural dynamic models were adequate for flight certifications.

The impact of recent improvements in cryo-electron microscopy technology on the understanding of bacterial ribosome assembly

PubMed Central

Razi, Aida; Britton, Robert A.

2017-01-01

Abstract Cryo-electron microscopy (cryo-EM) had played a central role in the study of ribosome structure and the process of translation in bacteria since the development of this technique in the mid 1980s. Until recently cryo-EM structures were limited to ∼10 Å in the best cases. However, the recent advent of direct electron detectors has greatly improved the resolution of cryo-EM structures to the point where atomic resolution is now achievable. This improved resolution will allow cryo-EM to make groundbreaking contributions in essential aspects of ribosome biology, including the assembly process. In this review, we summarize important insights that cryo-EM, in combination with chemical and genetic approaches, has already brought to our current understanding of the ribosomal assembly process in bacteria using previous detector technology. More importantly, we discuss how the higher resolution structures now attainable with direct electron detectors can be leveraged to propose precise testable models regarding this process. These structures will provide an effective platform to develop new antibiotics that target this fundamental cellular process. PMID:28180306

bcl::Cluster : A method for clustering biological molecules coupled with visualization in the Pymol Molecular Graphics System.

PubMed

Alexander, Nathan; Woetzel, Nils; Meiler, Jens

2011-02-01

Clustering algorithms are used as data analysis tools in a wide variety of applications in Biology. Clustering has become especially important in protein structure prediction and virtual high throughput screening methods. In protein structure prediction, clustering is used to structure the conformational space of thousands of protein models. In virtual high throughput screening, databases with millions of drug-like molecules are organized by structural similarity, e.g. common scaffolds. The tree-like dendrogram structure obtained from hierarchical clustering can provide a qualitative overview of the results, which is important for focusing detailed analysis. However, in practice it is difficult to relate specific components of the dendrogram directly back to the objects of which it is comprised and to display all desired information within the two dimensions of the dendrogram. The current work presents a hierarchical agglomerative clustering method termed bcl::Cluster. bcl::Cluster utilizes the Pymol Molecular Graphics System to graphically depict dendrograms in three dimensions. This allows simultaneous display of relevant biological molecules as well as additional information about the clusters and the members comprising them.

Mimas: Tectonic structure and geologic history

NASA Technical Reports Server (NTRS)

Croft, Steven K.

1991-01-01

Mimas, the innermost of the major saturnian satellites, occupies an important place in comparative studies of icy satellites. It is the smallest icy satellite known to have a mostly spherical shape. Smaller icy objects like Hyperion and Puck are generally irregular in shape, while larger ones like Miranda and Enceladus are spherical. Thus Mimas is near the diameter where the combination of increasing surface gravity and internal heating begin to have a significant effect on global structure. The nature and extent of endogenic surface features provide important constraints on the interior structure and history of this transitional body. The major landforms on Mimas are impact craters. Mimas has one of the most heavily cratered surfaces in the solar system. The most prominent single feature on Mimas is Herschel, an unrelaxed complex crater 130 km in diameter. The only other recognized landforms on Mimas are tectonic grooves and lineaments. Groove locations were mapped by Schenk, but without analysis of groove structures or superposition relationships. Mimas' tectonic structures are remapped here in more detail than previously has been done, as part of a general study of tectonic features on icy satellites.

Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c).

PubMed

Naffin-Olivos, Jacqueline L; Daab, Andrew; White, Andre; Goldfarb, Nathan E; Milne, Amy C; Liu, Dali; Baikovitz, Jacqueline; Dunn, Ben M; Rengarajan, Jyothi; Petsko, Gregory A; Ringe, Dagmar

2017-05-02

The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 Å and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serine protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity.

On Finding and Using Identifiable Parameter Combinations in Nonlinear Dynamic Systems Biology Models and COMBOS: A Novel Web Implementation

PubMed Central

DiStefano, Joseph

2014-01-01

Parameter identifiability problems can plague biomodelers when they reach the quantification stage of development, even for relatively simple models. Structural identifiability (SI) is the primary question, usually understood as knowing which of P unknown biomodel parameters p 1,…, pi,…, pP are-and which are not-quantifiable in principle from particular input-output (I-O) biodata. It is not widely appreciated that the same database also can provide quantitative information about the structurally unidentifiable (not quantifiable) subset, in the form of explicit algebraic relationships among unidentifiable pi. Importantly, this is a first step toward finding what else is needed to quantify particular unidentifiable parameters of interest from new I–O experiments. We further develop, implement and exemplify novel algorithms that address and solve the SI problem for a practical class of ordinary differential equation (ODE) systems biology models, as a user-friendly and universally-accessible web application (app)–COMBOS. Users provide the structural ODE and output measurement models in one of two standard forms to a remote server via their web browser. COMBOS provides a list of uniquely and non-uniquely SI model parameters, and–importantly-the combinations of parameters not individually SI. If non-uniquely SI, it also provides the maximum number of different solutions, with important practical implications. The behind-the-scenes symbolic differential algebra algorithms are based on computing Gröbner bases of model attributes established after some algebraic transformations, using the computer-algebra system Maxima. COMBOS was developed for facile instructional and research use as well as modeling. We use it in the classroom to illustrate SI analysis; and have simplified complex models of tumor suppressor p53 and hormone regulation, based on explicit computation of parameter combinations. It’s illustrated and validated here for models of moderate complexity, with and without initial conditions. Built-in examples include unidentifiable 2 to 4-compartment and HIV dynamics models. PMID:25350289

Snohomish Estuary Wetlands Study. Volume I. Summary Report

DTIC Science & Technology

1979-05-01

Large marine facilities are structures used for _.. argy development (oil rigs and platforms), raw material pro-cessing, and marine terminals. Such...State) * Wetlands Land Use 20. A9rTlACT (Camthaism revaes ebb N rNeeaa-7 maid Identifr by block number) The study underlines the importance of wetlands...function of a habitat. This study was conducted using information on these and all other subjects. Additional data will provide important refinements

Surface relief model for photopolymers without cover plating.

PubMed

Gallego, S; Márquez, A; Ortuño, M; Francés, J; Marini, S; Beléndez, A; Pascual, I

2011-05-23

Relief surface changes provide interesting possibilities for storing diffractive optical elements on photopolymers and are an important source of information to characterize and understand the material behaviour. In this paper we present a 3-dimensional model based on direct measurements of parameters to predict the relief structures generated on the material. This model is successfully applied to different photopolymers with different values of monomer diffusion. The importance of monomer diffusion in depth is also discussed.

The Continental Margins of the Western North Atlantic.

ERIC Educational Resources Information Center

Schlee, John S.; And Others

1979-01-01

Presents an interpretation of geological and geophysical data, which provides a summary of the structural and sedimentary history of the United States Atlantic Margin. The importance of an understanding of the development of the outer continental shelf to future hydrocarbon exploration is detailed. (BT)

Building on Florida's strength in space : a plan for action

DOT National Transportation Integrated Search

1999-12-01

The report is structured as follows: : 1) Section II provides background information on the role of the space sector : in Florida. It is presented to help the reader understand: : 2) Why space is important to the current and future economy of Florida...

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

Michaelides, Angelos, E-mail: angelos.michaelides@ucl.ac.uk; Martinez, Todd J.; Alavi, Ali

This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science.

RIPARIAN FOREST INDICATORS OF POTENTIAL FUTURE STREAM CONDITION

EPA Science Inventory

Large wood in streams can play an extraordinarily important role in influencing the physical structure of streams and in providing habitat for aquatic organisms. Since wood is continually lost from streams, predicting the future input of wood to streams from riparian forests is c...

Exploring protein structure and dynamics through a project-oriented biochemistry laboratory module.

PubMed

Lipchock, James M; Ginther, Patrick S; Douglas, Bonnie B; Bird, Kelly E; Patrick Loria, J

2017-09-01

Here, we present a 10-week project-oriented laboratory module designed to provide a course-based undergraduate research experience in biochemistry that emphasizes the importance of biomolecular structure and dynamics in enzyme function. This module explores the impact of mutagenesis on an important active site loop for a biomedically-relevant human enzyme, protein tyrosine phosphatase 1B (PTP1B). Over the course of the semester students guide their own mutant of PTP1B from conception to characterization in a cost-effective manner and gain exposure to fundamental techniques in biochemistry, including site-directed DNA mutagenesis, bacterial recombinant protein expression, affinity column purification, protein quantitation, SDS-PAGE, and enzyme kinetics. This project-based approach allows an instructor to simulate a research setting and prepare students for productive research beyond the classroom. Potential modifications to expand or contract this module are also provided. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):403-410, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Spatial-temporal-covariance-based modeling, analysis, and simulation of aero-optics wavefront aberrations.

PubMed

Vogel, Curtis R; Tyler, Glenn A; Wittich, Donald J

2014-07-01

We introduce a framework for modeling, analysis, and simulation of aero-optics wavefront aberrations that is based on spatial-temporal covariance matrices extracted from wavefront sensor measurements. Within this framework, we present a quasi-homogeneous structure function to analyze nonhomogeneous, mildly anisotropic spatial random processes, and we use this structure function to show that phase aberrations arising in aero-optics are, for an important range of operating parameters, locally Kolmogorov. This strongly suggests that the d5/3 power law for adaptive optics (AO) deformable mirror fitting error, where d denotes actuator separation, holds for certain important aero-optics scenarios. This framework also allows us to compute bounds on AO servo lag error and predictive control error. In addition, it provides us with the means to accurately simulate AO systems for the mitigation of aero-effects, and it may provide insight into underlying physical processes associated with turbulent flow. The techniques introduced here are demonstrated using data obtained from the Airborne Aero-Optics Laboratory.

Biomolecular electrostatics and solvation: a computational perspective

PubMed Central

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G.; Schnieders, Michael J.; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A.

2012-01-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view towards describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g., solvent structure, polarization, ion binding, and nonpolar behavior) in order to provide a background to understand the different types of solvation models. PMID:23217364

Biomolecular electrostatics and solvation: a computational perspective.

PubMed

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

2012-11-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

Efficient 3D kinetic Monte Carlo method for modeling of molecular structure and dynamics.

PubMed

Panshenskov, Mikhail; Solov'yov, Ilia A; Solov'yov, Andrey V

2014-06-30

Self-assembly of molecular systems is an important and general problem that intertwines physics, chemistry, biology, and material sciences. Through understanding of the physical principles of self-organization, it often becomes feasible to control the process and to obtain complex structures with tailored properties, for example, bacteria colonies of cells or nanodevices with desired properties. Theoretical studies and simulations provide an important tool for unraveling the principles of self-organization and, therefore, have recently gained an increasing interest. The present article features an extension of a popular code MBN EXPLORER (MesoBioNano Explorer) aiming to provide a universal approach to study self-assembly phenomena in biology and nanoscience. In particular, this extension involves a highly parallelized module of MBN EXPLORER that allows simulating stochastic processes using the kinetic Monte Carlo approach in a three-dimensional space. We describe the computational side of the developed code, discuss its efficiency, and apply it for studying an exemplary system. Copyright © 2014 Wiley Periodicals, Inc.

Establishment of research-oriented hospital: an important way for translational medicine development in China.

PubMed

Li, Meina; Zhang, Lulu

2015-01-01

Globally, one of the major trends is the development of translational medicine. The traditional hospital structure could not meet the demands of translational medicine development any longer and to explore a novel hospital structure is imperative. Following the times, China proposed and implemented a development strategy for a first-class modern research-oriented hospital. To establish a research-oriented hospital has become an important strategy to guide the scientific development of high-quality medical institutions and to advance translational medicine development. To facilitate translational medicine by developing research-oriented hospital, the Chinese Research Hospital Association (CRHA) has been established, which provides service of medicine, talents cultivation, scientific research and clinical teaching and covers areas of theoretical research, academic exchange, translational medicine, talents training and practice guiding. On the whole, research-oriented hospital facilitated translational medicine by developing interdisciplinary platform, training core competencies in clinical and translational research, providing financial support of translational research, and hosting journals on translational medicine, etc.

Development of vehicle model test-bending of a simple structural surfaces model for automotive vehicle sedan

NASA Astrophysics Data System (ADS)

Nor, M. K. Mohd; Noordin, A.; Ruzali, M. F. S.; Hussen, M. H.; Mustapa@Othman, N.

2017-04-01

Simple Structural Surfaces (SSS) method is offered as a means of organizing the process for rationalizing the basic vehicle body structure load paths. The application of this simplified approach is highly beneficial in the development of modern passenger car structure design. In Malaysia, the SSS topic has been widely adopted and seems compulsory in various automotive programs related to automotive vehicle structures in many higher education institutions. However, there is no real physical model of SSS available to gain considerable insight and understanding into the function of each major subassembly in the whole vehicle structures. Based on this motivation, a real physical SSS of sedan model and the corresponding model vehicle tests of bending is proposed in this work. The proposed approach is relatively easy to understand as compared to Finite Element Method (FEM). The results prove that the proposed vehicle model test is useful to physically demonstrate the importance of providing continuous load path using the necessary structural components within the vehicle structures. It is clearly observed that the global bending stiffness reduce significantly when more panels are removed from the complete SSS model. The analysis shows the front parcel shelf is an important subassembly to sustain bending load.

Structure prediction of polyglutamine disease proteins: comparison of methods

PubMed Central

2014-01-01

Background The expansion of polyglutamine (poly-Q) repeats in several unrelated proteins is associated with at least ten neurodegenerative diseases. The length of the poly-Q regions plays an important role in the progression of the diseases. The number of glutamines (Q) is inversely related to the onset age of these polyglutamine diseases, and the expansion of poly-Q repeats has been associated with protein misfolding. However, very little is known about the structural changes induced by the expansion of the repeats. Computational methods can provide an alternative to determine the structure of these poly-Q proteins, but it is important to evaluate their performance before large scale prediction work is done. Results In this paper, two popular protein structure prediction programs, I-TASSER and Rosetta, have been used to predict the structure of the N-terminal fragment of a protein associated with Huntington's disease with 17 glutamines. Results show that both programs have the ability to find the native structures, but I-TASSER performs better for the overall task. Conclusions Both I-TASSER and Rosetta can be used for structure prediction of proteins with poly-Q repeats. Knowledge of poly-Q structure may significantly contribute to development of therapeutic strategies for poly-Q diseases. PMID:25080018

Metagenomic and Metatranscriptomic Analyses Reveal the Structure and Dynamics of a Dechlorinating Community Containing Dehalococcoides mccartyi and Corrinoid-Providing Microorganisms under Cobalamin-Limited Conditions

PubMed Central

Yu, Ke; Bælum, Jacob; Gao, Ying; Tremblay, Julien; Prestat, Emmanuel; Stenuit, Ben; Tringe, Susannah G.; Jansson, Janet; Zhang, Tong; Alvarez-Cohen, Lisa

2017-01-01

ABSTRACT The aim of this study is to obtain a systems-level understanding of the interactions between Dehalococcoides and corrinoid-supplying microorganisms by analyzing community structures and functional compositions, activities, and dynamics in trichloroethene (TCE)-dechlorinating enrichments. Metagenomes and metatranscriptomes of the dechlorinating enrichments with and without exogenous cobalamin were compared. Seven putative draft genomes were binned from the metagenomes. At an early stage (2 days), more transcripts of genes in the Veillonellaceae bin-genome were detected in the metatranscriptome of the enrichment without exogenous cobalamin than in the one with the addition of cobalamin. Among these genes, sporulation-related genes exhibited the highest differential expression when cobalamin was not added, suggesting a possible release route of corrinoids from corrinoid producers. Other differentially expressed genes include those involved in energy conservation and nutrient transport (including cobalt transport). The most highly expressed corrinoid de novo biosynthesis pathway was also assigned to the Veillonellaceae bin-genome. Targeted quantitative PCR (qPCR) analyses confirmed higher transcript abundances of those corrinoid biosynthesis genes in the enrichment without exogenous cobalamin than in the enrichment with cobalamin. Furthermore, the corrinoid salvaging and modification pathway of Dehalococcoides was upregulated in response to the cobalamin stress. This study provides important insights into the microbial interactions and roles played by members of dechlorinating communities under cobalamin-limited conditions. IMPORTANCE The key chloroethene-dechlorinating bacterium Dehalococcoides mccartyi is a cobalamin auxotroph, thus acquiring corrinoids from other community members. Therefore, it is important to investigate the microbe-microbe interactions between Dehalococcoides and the corrinoid-providing microorganisms in a community. This study provides systems-level information, i.e., taxonomic and functional compositions and dynamics of the supportive microorganisms in dechlorinating communities under different cobalamin conditions. The findings shed light on the important roles of Veillonellaceae species in the communities compared to other coexisting community members in producing and providing corrinoids for Dehalococcoides species under cobalamin-limited conditions. PMID:28188205

The specialty of family dentistry: a future for general dental practitioners?

PubMed

Li, R W; Chow, T W

2004-01-01

A new Specialty in dentistry, Family Dentistry, has been established to provide a structured, co-ordinated training for general dental practitioners who are the major oral health service providers. The training emphasizes the importance of continuing and comprehensive care, the interface between primary and secondary care, the relationship between the patient and his/her family and the community, and a holistic approach in treatment planning and delivery.

How to write a medical CV.

PubMed

Agha, Riaz; Whitehurst, Katharine; Jafree, Daniyal; Devabalan, Yadsan; Koshy, Kiron; Gundogan, Buket

2017-07-01

A medical curriculum vitae remains an important document that has 2 main roles: to distinguish candidates applying for various positions, whether that be jobs, posts, grants and it provides a means of keeping an up-to-date record of all your achievements and skills gained thus far. This article provides detailed guidance on how to structure an effective curriculum vitae to maximize your chances of success when applying for these positions.

How to write a medical CV

PubMed Central

Agha, Riaz; Whitehurst, Katharine; Jafree, Daniyal; Devabalan, Yadsan; Koshy, Kiron

2017-01-01

A medical curriculum vitae remains an important document that has 2 main roles: to distinguish candidates applying for various positions, whether that be jobs, posts, grants and it provides a means of keeping an up-to-date record of all your achievements and skills gained thus far. This article provides detailed guidance on how to structure an effective curriculum vitae to maximize your chances of success when applying for these positions. PMID:29177224

The methodology of multi-viewpoint clustering analysis

NASA Technical Reports Server (NTRS)

Mehrotra, Mala; Wild, Chris

1993-01-01

One of the greatest challenges facing the software engineering community is the ability to produce large and complex computer systems, such as ground support systems for unmanned scientific missions, that are reliable and cost effective. In order to build and maintain these systems, it is important that the knowledge in the system be suitably abstracted, structured, and otherwise clustered in a manner which facilitates its understanding, manipulation, testing, and utilization. Development of complex mission-critical systems will require the ability to abstract overall concepts in the system at various levels of detail and to consider the system from different points of view. Multi-ViewPoint - Clustering Analysis MVP-CA methodology has been developed to provide multiple views of large, complicated systems. MVP-CA provides an ability to discover significant structures by providing an automated mechanism to structure both hierarchically (from detail to abstract) and orthogonally (from different perspectives). We propose to integrate MVP/CA into an overall software engineering life cycle to support the development and evolution of complex mission critical systems.

A hierarchical structure for representing and learning fuzzy rules

NASA Technical Reports Server (NTRS)

Yager, Ronald R.

1993-01-01

Yager provides an example in which the flat representation of fuzzy if-then rules leads to unsatisfactory results. Consider a rule base consisting to two rules: if U is 12 the V is 29; if U is (10-15) the V is (25-30). If U = 12 we would get V is G where G = (25-30). The application of the defuzzification process leads to a selection of V = 27.5. Thus we see that the very specific instruction was not followed. The problem with the technique used is that the most specific information was swamped by the less specific information. In this paper we shall provide for a new structure for the representation of fuzzy if-then rules. The representational form introduced here is called a Hierarchical Prioritized Structure (HPS) representation. Most importantly in addition to overcoming the problem illustrated in the previous example this HPS representation has an inherent capability to emulate the learning of general rules and provides a reasonable accurate cognitive mapping of how human beings store information.

Multifunctional composites for energy storage

NASA Astrophysics Data System (ADS)

Shuvo, Mohammad Arif I.; Karim, Hasanul; Rajib, Md; Delfin, Diego; Lin, Yirong

2014-03-01

Electrochemical super-capacitors have become one of the most important topics in both academia and industry as novel energy storage devices because of their high power density, long life cycles, and high charge/discharge efficiency. Recently, there has been an increasing interest in the development of multifunctional structural energy storage devices such as structural super-capacitors for applications in aerospace, automobiles and portable electronics. These multifunctional structural super-capacitors provide lighter structures combining energy storage and load bearing functionalities. Due to their superior materials properties, carbon fiber composites have been widely used in structural applications for aerospace and automotive industries. Besides, carbon fiber has good electrical conductivity which will provide lower equivalent series resistance; therefore, it can be an excellent candidate for structural energy storage applications. Hence, this paper is focused on performing a pilot study for using nanowire/carbon fiber hybrids as building materials for structural energy storage materials; aiming at enhancing the charge/discharge rate and energy density. This hybrid material combines the high specific surface area of carbon fiber and pseudo-capacitive effect of metal oxide nanowires which were grown hydrothermally in an aligned fashion on carbon fibers. The aligned nanowire array could provide a higher specific surface area that leads to high electrode-electrolyte contact area and fast ion diffusion rates. Scanning Electron Microscopy (SEM) and XRay Diffraction (XRD) measurements were used for the initial characterization of this nanowire/carbon fiber hybrid material system. Electrochemical testing has been performed using a potentio-galvanostat. The results show that gold sputtered nanowire hybrid carbon fiber provides 65.9% better performance than bare carbon fiber cloth as super-capacitor.

Long-range energy transfer in self-assembled quantum dot-DNA cascades

NASA Astrophysics Data System (ADS)

Goodman, Samuel M.; Siu, Albert; Singh, Vivek; Nagpal, Prashant

2015-11-01

The size-dependent energy bandgaps of semiconductor nanocrystals or quantum dots (QDs) can be utilized in converting broadband incident radiation efficiently into electric current by cascade energy transfer (ET) between layers of different sized quantum dots, followed by charge dissociation and transport in the bottom layer. Self-assembling such cascade structures with angstrom-scale spatial precision is important for building realistic devices, and DNA-based QD self-assembly can provide an important alternative. Here we show long-range Dexter energy transfer in QD-DNA self-assembled single constructs and ensemble devices. Using photoluminescence, scanning tunneling spectroscopy, current-sensing AFM measurements in single QD-DNA cascade constructs, and temperature-dependent ensemble devices using TiO2 nanotubes, we show that Dexter energy transfer, likely mediated by the exciton-shelves formed in these QD-DNA self-assembled structures, can be used for efficient transport of energy across QD-DNA thin films.The size-dependent energy bandgaps of semiconductor nanocrystals or quantum dots (QDs) can be utilized in converting broadband incident radiation efficiently into electric current by cascade energy transfer (ET) between layers of different sized quantum dots, followed by charge dissociation and transport in the bottom layer. Self-assembling such cascade structures with angstrom-scale spatial precision is important for building realistic devices, and DNA-based QD self-assembly can provide an important alternative. Here we show long-range Dexter energy transfer in QD-DNA self-assembled single constructs and ensemble devices. Using photoluminescence, scanning tunneling spectroscopy, current-sensing AFM measurements in single QD-DNA cascade constructs, and temperature-dependent ensemble devices using TiO2 nanotubes, we show that Dexter energy transfer, likely mediated by the exciton-shelves formed in these QD-DNA self-assembled structures, can be used for efficient transport of energy across QD-DNA thin films. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04778a

Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

PubMed Central

Fu, Yao; Kao, Weiyuan John

2010-01-01

Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

Understanding Lithium Solvation and Diffusion through Topological Analysis of First-Principles Molecular Dynamics

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

Bhatia, Harsh; Gyulassy, Attila; Ong, Mitchell

2016-09-27

The performance of lithium-ion batteries is strongly influenced by the ionic conductivity of the electrolyte, which depends on the speed at which Li ions migrate across the cell and relates to their solvation structure. The choice of solvent can greatly impact, both, the solvation and diffusivity of Li ions. In this work, we present our application of the topological techniques to extract and predict such behavior in the data generated by the first-principles molecular dynamics simulation of Li ions in an important organic solvent -ethylene carbonate. More specifically, we use the scalar topology of the electron charge density field tomore » analyze the evolution of the solvation structures. This allows us to derive a parameter-free bond definition for lithium-oxygen bonds, to provide a quantitative measure for bond strength, and to understand the regions of influence of each atom in the simulation. This has provided new insights into how and under what conditions certain bonds may form and break. As a result, we can identify and, more importantly, predict, unstable configurations in solvation structures. This can be very useful in understanding when small changes to the atoms' movements can cause significantly different bond structures to evolve. Ultimately, this promises to allow scientists to explore lithium ion solvation and diffusion more systematically, with the aim of new insights and potentially accelerating the calculations themselves.« less

Study on the conformation changes of Lysozyme induced by Hypocrellin A: The mechanism investigation

NASA Astrophysics Data System (ADS)

Ma, Fei; Huang, He-Yong; Zhou, Lin; Yang, Chao; Zhou, Jia-Hong; Liu, Zheng-Ming

2012-11-01

The interactions between Lysozyme and Hypocrellin A are investigated in details using time-resolved fluorescence, fourier transform infrared spectroscopy (FTIR), circular dichroism spectroscopy (CD), three-dimensional fluorescence spectra, and thermal gravimetric analysis (TGA) techniques. The results of time-resolved fluorescence suggest that the quenching mechanism is static quenching. FTIR and CD spectroscopy provide evidences of the reducing of α-helix after interaction. Hypocrellin A could change the micro-environmental of Lysozyme according to hydrophobic interaction between the aromatic ring and the hydrophobic amino acid residues, and the altered polypeptide backbone structures induce the reduction of α-helical structures. Moreover, TGA study further demonstrates the structure changes of Lysozyme on the effect of Hypocrellin A. This study could provide some important information for the derivatives of HA in pharmacy, pharmacology and biochemistry.

Final report: ES11: The 23rd Annual Workshop on Electronic Structure Methods

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

Rappe, Andrew M.

2011-08-31

ES11: the 23rd Annual Workshop on Electronic Structure Methods was held from June 6-9, 2011 at the University of Pennsylvania. The local organizing committee (see Section II) led by PI Andrew M. Rappe supervised the organization of the conference, before, during, and after the meeting itself. The national organizing committee set the technical program of talks, and provided support and advice in various ways. The conference was well-attended (see Section III). An important feature of this conference was a series of panel discussions (see Section IV) to discuss the field of electronic structure and to set new directions. The technicalmore » program was of extraordinarily high quality (see Section V). The host institution, the University of Pennsylvania, provided a supportive environment for this meeting (see Section VI).« less

System among the corticosteroids: specificity and molecular dynamics

PubMed Central

Brookes, Jennifer C.; Galigniana, Mario D.; Harker, Anthony H.; Stoneham, A. Marshall; Vinson, Gavin P.

2012-01-01

Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand–receptor interactions. PMID:21613285

Local atomic and electronic structures in ferromagnetic topological insulator Cr-doped (BixSb1-x) 2Te3 studied by XAFS and ab initio calculations

NASA Astrophysics Data System (ADS)

Liu, Zhen; Wei, Xinyuan; Wang, Jiajia; Pan, Hong; Ji, Fuhao; Ye, Mao; Yang, Zhongqin; Qiao, Shan

2015-09-01

The local atomic and electronic structures around the dopants in Cr-doped (BixSb1 -x )2Te3 are studied by x-ray absorption fine structure (XAFS) measurements and first-principles calculations. Both Cr and Bi are confirmed substituting Sb sites (CrSb and BiSb). The six nearest Te atoms around Cr move towards Cr and shorten the Cr-Te bond lengths to 2.76 Å and 2.77 Å for x =0.1 and x =0.2 , respectively. Importantly, we reveal the hybridization between the Sb/Te p states and Cr d states by the presence of a pre-edge peak at Cr K -absorption edge, which is also supported by our ab initio calculations. These findings provide important clues to understand the mechanism of ferromagnetic order in this system with quantum anomalous Hall effect.

Structural Evolution of Supercritical CO2 across the Frenkel Line.

PubMed

Bolmatov, Dima; Zav'yalov, D; Gao, M; Zhernenkov, Mikhail

2014-08-21

Here, we study structural properties of the supercritical carbon dioxide and discover the existence of persistent medium-range order correlations, which make supercritical carbon dioxide nonuniform and heterogeneous on an intermediate length scale. We report on the CO2 heterogeneity shell structure where, in the first shell, both carbon and oxygen atoms experience gas-like-type interactions with short-range order correlations while within the second shell, oxygen atoms essentially exhibit a liquid-like type of interactions due to localization of transverse-like phonon packets. Importantly, we highlight a catalytic role of atoms inside of the nearest-neighbor heterogeneity shell in providing a mechanism for diffusion and proving the existence of an additional thermodynamic boundary in the supercritical carbon dioxide on an intermediate length scale. Finally, we discuss important implications for answering the intriguing question whether Venus may have had CO2 oceans and urge for an experimental detection of this persistent local-order heterogeneity.

Anticancer effect and structure-activity analysis of marine products isolated from metabolites of mangrove fungi in the South China Sea.

PubMed

Tao, Li-yang; Zhang, Jian-ye; Liang, Yong-ju; Chen, Li-ming; Zhen, Li-sheng; Wang, Fang; Mi, Yan-jun; She, Zhi-gang; To, Kenneth Kin Wah; Lin, Yong-cheng; Fu, Li-wu

2010-04-01

Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.

Chromatin Insulators and Topological Domains: Adding New Dimensions to 3D Genome Architecture

PubMed Central

Matharu, Navneet K.; Ahanger, Sajad H.

2015-01-01

The spatial organization of metazoan genomes has a direct influence on fundamental nuclear processes that include transcription, replication, and DNA repair. It is imperative to understand the mechanisms that shape the 3D organization of the eukaryotic genomes. Chromatin insulators have emerged as one of the central components of the genome organization tool-kit across species. Recent advancements in chromatin conformation capture technologies have provided important insights into the architectural role of insulators in genomic structuring. Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation. In this review, we will discuss the classical view and our renewed understanding of insulators as global genome organizers. We will also discuss the plasticity of chromatin structure and its re-organization during pluripotency and differentiation and in situations of cellular stress. PMID:26340639

Molecular Dynamics Methodologies for Probing Cannabinoid Ligand/Receptor Interaction

PubMed Central

Lynch, Diane L.; Hurst, Dow P.; Shore, Derek M.; Pitman, Mike C.; Reggio, Patricia H.

2018-01-01

The cannabinoid type 1 and 2 G-protein-coupled receptors are currently important pharmacological targets with significant drug discovery potential. These receptors have been shown to display functional selectivity or biased agonism, a property currently thought to have substantial therapeutic potential. Although recent advances in crystallization techniques have provided a wealth of structural information about this important class of membrane-embedded proteins, these structures lack dynamical information. In order to fully understand the interplay of structure and function for this important class of proteins, complementary techniques that address the dynamical aspects of their function are required such as NMR as well as a variety of other spectroscopies. Complimentary to these experimental approaches is molecular dynamics, which has been effectively used to help unravel, at the atomic level, the dynamics of ligand binding and activation of these membrane-bound receptors. Here, we discuss and present several representative examples of the application of molecular dynamics simulations to the understanding of the signatures of ligand-binding and -biased signaling at the cannabinoid type 1 and 2 receptors. PMID:28750815

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

Tucker, Eric; Boreman, Glenn, E-mail: gboreman@uncc.edu; D'Archangel, Jeffrey

Near- and far-field measurements of phase-ramped loop and patch structures are presented and compared to simulations. The far-field deflection measurements show that the phase-ramped structures can deflect a beam away from specular reflection, consistent with simulations. Scattering scanning near-field optical microscopy of the elements comprising the phase ramped structures reveals part of the underlying near-field phase contribution that dictates the far-field deflection, which correlates with the far-field phase behavior that was expected. These measurements provide insight into the resonances, coupling, and spatial phase variation among phase-ramped frequency selective surface (FSS) elements, which are important for the performance of FSS reflectarrays.

Biological water-oxidizing complex: a nano-sized manganese-calcium oxide in a protein environment.

PubMed

Najafpour, Mohammad Mahdi; Moghaddam, Atefeh Nemati; Yang, Young Nam; Aro, Eva-Mari; Carpentier, Robert; Eaton-Rye, Julian J; Lee, Choon-Hwan; Allakhverdiev, Suleyman I

2012-10-01

The resolution of Photosystem II (PS II) crystals has been improved using isolated PS II from the thermophilic cyanobacterium Thermosynechococcus vulcanus. The new 1.9 Å resolution data have provided detailed information on the structure of the water-oxidizing complex (Umena et al. Nature 473: 55-61, 2011). The atomic level structure of the manganese-calcium cluster is important for understanding the mechanism of water oxidation and to design an efficient catalyst for water oxidation in artificial photosynthetic systems. Here, we have briefly reviewed our knowledge of the structure and function of the cluster.

The ins and outs of lncRNA structure: How, why and what comes next?

PubMed

Blythe, Amanda J; Fox, Archa H; Bond, Charles S

2016-01-01

The field of structural biology has the unique advantage of being able to provide a comprehensive picture of biological mechanisms at the molecular and atomic level. Long noncoding RNAs (lncRNAs) represent the new frontier in the molecular biology of complex organisms yet remain the least characterised of all the classes of RNA. Thousands of new lncRNAs are being reported each year yet very little structural data exists for this rapidly expanding field. The length of lncRNAs ranges from 200 nt to over 100 kb in length and they generally exhibit low cellular abundance. Therefore, obtaining sufficient quantities of lncRNA to use for structural analysis is challenging. However, as technologies develop structures of lncRNAs are starting to emerge providing important information regarding their mechanism of action. Here we review the current methods used to determine the structure of lncRNA and lncRNA:protein complexes and describe the significant contribution structural biology has and will make to the field of lncRNA research. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

When elephants fall asleep: A literature review on elephant rest with case studies on elephant falling bouts, and practical solutions for zoo elephants.

PubMed

Schiffmann, Christian; Hoby, Stefan; Wenker, Christian; Hård, Therese; Scholz, Robert; Clauss, Marcus; Hatt, Jean-Michel

2018-05-01

Little attention has been paid to the resting and sleeping behavior of zoo elephants so far. An important concern is when elephants avoid lying down, due to degenerative joint and foot disease, social structure, or stressful environmental changes. Inability or unwillingness to lie down for resting is an important welfare issue, as it may impair sleep. We emphasize the importance of satisfying rest in elephants by reviewing the literature on resting behavior in elephants (Loxodonta africana and Elephas maximus) as well as the documentation of four cases from European zoos and our own direct observations in a zoo group of four female African elephants during 12 entire days. The common denominator in the case reports is the occurrence of a falling bout out of a standing position subsequently to a cessation of lying rest for different periods of time. Although well-known in horses as "episodic collapse" or "excessive drowsiness," this syndrome has not been described in elephants before. To enable its detection, we recommend nocturnal video monitoring for elephant-keeping institutions. The literature evaluation as well as own observational data suggest an inverse relationship between lying rest and standing rest. Preventative measures consist of enclosure modifications that facilitate lying rest (e.g., sand hills) or standing rest in a leaning position as a substitute. Anecdotal observations suggest that the provision of appropriate horizontal environmental structures may encourage safe, sleep-conducive standing rest. We provide drawings on how to install such structures. Effects of providing such structures should be evaluated in the future. © 2018 Wiley Periodicals, Inc.

Fast large-scale clustering of protein structures using Gauss integrals.

PubMed

Harder, Tim; Borg, Mikael; Boomsma, Wouter; Røgen, Peter; Hamelryck, Thomas

2012-02-15

Clustering protein structures is an important task in structural bioinformatics. De novo structure prediction, for example, often involves a clustering step for finding the best prediction. Other applications include assigning proteins to fold families and analyzing molecular dynamics trajectories. We present Pleiades, a novel approach to clustering protein structures with a rigorous mathematical underpinning. The method approximates clustering based on the root mean square deviation by first mapping structures to Gauss integral vectors--which were introduced by Røgen and co-workers--and subsequently performing K-means clustering. Compared to current methods, Pleiades dramatically improves on the time needed to perform clustering, and can cluster a significantly larger number of structures, while providing state-of-the-art results. The number of low energy structures generated in a typical folding study, which is in the order of 50,000 structures, can be clustered within seconds to minutes.

The oral case presentation: toward a performance-based rhetorical model for teaching and learning.

PubMed

Chan, Mei Yuit

2015-01-01

The oral case presentation is an important communicative activity in the teaching and assessment of students. Despite its importance, not much attention has been paid to providing support for teachers to teach this difficult task to medical students who are novices to this form of communication. As a formalized piece of talk that takes a regularized form and used for a specific communicative goal, the case presentation is regarded as a rhetorical activity and awareness of its rhetorical and linguistic characteristics should be given due consideration in teaching. This paper reviews practitioners' and the limited research literature that relates to expectations of medical educators about what makes a good case presentation, and explains the rhetorical aspect of the activity. It is found there is currently a lack of a comprehensive model of the case presentation that projects the rhetorical and linguistic skills needed to produce and deliver a good presentation. Attempts to describe the structure of the case presentation have used predominantly opinion-based methodologies. In this paper, I argue for a performance-based model that would not only allow a description of the rhetorical structure of the oral case presentation, but also enable a systematic examination of the tacit genre knowledge that differentiates the expert from the novice. Such a model will be a useful resource for medical educators to provide more structured feedback and teaching support to medical students in learning this important genre.

The oral case presentation: toward a performance-based rhetorical model for teaching and learning

PubMed Central

Chan, Mei Yuit

2015-01-01

The oral case presentation is an important communicative activity in the teaching and assessment of students. Despite its importance, not much attention has been paid to providing support for teachers to teach this difficult task to medical students who are novices to this form of communication. As a formalized piece of talk that takes a regularized form and used for a specific communicative goal, the case presentation is regarded as a rhetorical activity and awareness of its rhetorical and linguistic characteristics should be given due consideration in teaching. This paper reviews practitioners’ and the limited research literature that relates to expectations of medical educators about what makes a good case presentation, and explains the rhetorical aspect of the activity. It is found there is currently a lack of a comprehensive model of the case presentation that projects the rhetorical and linguistic skills needed to produce and deliver a good presentation. Attempts to describe the structure of the case presentation have used predominantly opinion-based methodologies. In this paper, I argue for a performance-based model that would not only allow a description of the rhetorical structure of the oral case presentation, but also enable a systematic examination of the tacit genre knowledge that differentiates the expert from the novice. Such a model will be a useful resource for medical educators to provide more structured feedback and teaching support to medical students in learning this important genre. PMID:26194482

Rapid Analysis of Mass Distribution of Radiation Shielding

NASA Technical Reports Server (NTRS)

Zapp, Edward

2007-01-01

Radiation Shielding Evaluation Toolset (RADSET) is a computer program that rapidly calculates the spatial distribution of mass of an arbitrary structure for use in ray-tracing analysis of the radiation-shielding properties of the structure. RADSET was written to be used in conjunction with unmodified commercial computer-aided design (CAD) software that provides access to data on the structure and generates selected three-dimensional-appearing views of the structure. RADSET obtains raw geometric, material, and mass data on the structure from the CAD software. From these data, RADSET calculates the distribution(s) of the masses of specific materials about any user-specified point(s). The results of these mass-distribution calculations are imported back into the CAD computing environment, wherein the radiation-shielding calculations are performed.

Metal carboxylates with open architectures.

PubMed

Rao, C N R; Natarajan, Srinivasan; Vaidhyanathan, R

2004-03-12

The field of inorganic open-framework materials is dominated by aluminosilicates and phosphates. The metal carboxylates have emerged as an important family in the last few years. This family includes not only mono- and dicarboxylates of transition, rare-earth, and main-group metals, but also a variety of hybrid structures. Some of the carboxylates possess novel adsorption and magnetic properties. Dicarboxylates and related species provide an effective means of designing novel hybrid structures with porous and other properties. In some of these structures, the dicarboxylate acts as a linker between two inorganic units. Hybrid nanocomposites are also of particular note, for example, cadmium oxalate host lattices that can accommodate extended alkali-metal halide structures. This Review discusses the synthesis, structure, and properties of various types of open-framework metal carboxylates.

Structure of an agonist-bound ionotropic glutamate receptor.

PubMed

Yelshanskaya, Maria V; Li, Minfen; Sobolevsky, Alexander I

2014-08-29

Ionotropic glutamate receptors (iGluRs) mediate most excitatory neurotransmission in the central nervous system and function by opening their ion channel in response to binding of agonist glutamate. Here, we report a structure of a homotetrameric rat GluA2 receptor in complex with partial agonist (S)-5-nitrowillardiine. Comparison of this structure with the closed-state structure in complex with competitive antagonist ZK 200775 suggests conformational changes that occur during iGluR gating. Guided by the structures, we engineered disulfide cross-links to probe domain interactions that are important for iGluR gating events. The combination of structural information, kinetic modeling, and biochemical and electrophysiological experiments provides insight into the mechanism of iGluR gating. Copyright © 2014, American Association for the Advancement of Science.

Diversity in ABC transporters: Type I, II and III importers

PubMed Central

Rice, Austin J.; Park, Aekyung

2014-01-01

ATP-binding cassette transporters are multi-subunit membrane pumps that transport substrates across membranes. While significant in the transport process, transporter architecture exhibits a range of diversity that we are only beginning to recognize. This divergence may provide insight into the mechanisms of substrate transport and homeostasis. Until recently, ABC importers have been classified into two types, but with the emergence of energy-coupling factor (ECF) transporters there are potentially three types of ABC importers. In this review, we summarize an expansive body of research on the three types of importers with an emphasis on the basics that underlie ABC importers, such as structure, subunit composition and mechanism. PMID:25155087

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network.

PubMed

Postnov, Dmitry D; Marsh, Donald J; Postnov, Dmitry E; Braunstein, Thomas H; Holstein-Rathlou, Niels-Henrik; Martens, Erik A; Sosnovtseva, Olga

2016-07-01

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (μCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons.

Semantic Feature Distinctiveness and Frequency

ERIC Educational Resources Information Center

Lamb, Katherine M.

2012-01-01

Lexical access is the process in which basic components of meaning in language, the lexical entries (words) are activated. This activation is based on the organization and representational structure of the lexical entries. Semantic features of words, which are the prominent semantic characteristics of a word concept, provide important information…

A population structure and genome-wide association analysis on the USDA soybean germplasm collection

USDA-ARS?s Scientific Manuscript database

Genotype-phenotype associations within the soybean (Glycine max) germplasm collection could provide valuable information on the frequency and distribution of alleles affecting economically important traits. Here we performed a genome-wide association study (GWAS) for seed protein and oil content in ...

Assess and Invest: Faculty Feedback on Library Tutorials

ERIC Educational Resources Information Center

Appelt, Kristina M.; Pendell, Kimberly

2010-01-01

Communication and collaboration with faculty are increasingly important in the development of both curriculum-integrated and stand-alone "just in time" library tutorials. In the final developmental stages of the Evidence-Based Practice online tutorials, faculty members were asked to provide input during structured faculty feedback…

Evaluation of biochars by temperature programmed oxidation/mass spectrometry

Treesearch

Michael Jackson; Thomas Eberhardt; Akwasi Boateng; Charles Mullen; Les Groom

2013-01-01

Biochars produced from thermochemical conversions of biomass were evaluated by temperature programmed oxidation (TPO). This technique, used to characterize carbon deposits on petroleum cracking catalysts, provides information on the oxidative stability of carbonaceous solids, where higher temperature reactivity indicates greater structural order, an important property...

Influence of land-use legacies following shrub reduction and seeding of big sagebrush sites

USDA-ARS?s Scientific Manuscript database

Big sagebrush (Artemisia tridentata Nutt.) plant communities provide important economic and ecosystem values, but often require management to reduce shrub density and rehabilitate understory vegetation. We studied vegetation structure and plant community responses to a two-way chain harrow treatment...

Argonne News Brief: Two Key Zika Proteins Unlocked at Advanced Photon Source

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

None

The Zika virus is a global health emergency. Now two new studies have revealed the molecular structure of important Zika virus proteins, providing scientists around the globe with new information about how the virus replicates—and potential avenues for antiviral drugs or vaccines.

HotRegion: a database of predicted hot spot clusters.

PubMed

Cukuroglu, Engin; Gursoy, Attila; Keskin, Ozlem

2012-01-01

Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided. HotRegion is accessible at http://prism.ccbb.ku.edu.tr/hotregion.

Goal importance within planned behaviour theory as 'the' predictor of study behaviour in college.

PubMed

Sideridis, G D; Kaissidis-Rodafinos, A

2001-12-01

The theory of planned behaviour has been rarely used for the explanation of student study behaviour and achievement. Although successful, the theory has been criticised for not including important cognitions, so goal importance was added in the present study. Goal importance refers to the weight-importance an individual assigns towards achieving a specific goal (Hollenbeck & Williams, 1987). The purpose of Study 1 was to explain the study behaviour habits of first year college students, using a) Ajzen and Madden's (1986) theory of planned behaviour, and b) planned behaviour with the addition of goal importance. The purpose of Study 2 was to replicate the findings of Study 1. The sample of Study 1 included 149 first year students of an American College located in northern Greece. Study 2 included 85 first year students of the same institution. The students in Study 1 were given a questionnaire four weeks prior to the end of the spring 1998 semester, and those in Study 2 in the autumn of 1998, including all elements of the theory of planned behaviour and goal importance. The data were modelled using Covariance Structural Modelling (CSM) and EQS 5.7b (Bentler, 1998). The planned behaviour model was not well supported in Study 1 providing a Comparative Fit Index (CFI) of.83. However, when goal importance was included in the equation, the resulting structural model produced a CFI of.94. The final structural model of Study 1 was re-tested with the sample of Study 2 and produced a CFI =.95. Findings suggest that goal importance is the causal agent in directing all elements necessary to achieve high levels of study behaviour. Future studies should examine the role of goal importance with other behaviours as well.

Probing the interaction of anticancer drug temsirolimus with human serum albumin: molecular docking and spectroscopic insight.

PubMed

Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees

2018-05-01

The binding interaction between temsirolimus, an important antirenal cancer drug, and HSA, an important carrier protein was scrutinized making use of UV and fluorescence spectroscopy. Hyper chromaticity observed in UV spectroscopy in the presence of temsirolimus as compared to free HSA suggests the formation of complex between HSA and temsirolimus. Fluorescence quenching experiments clearly showed quenching in the fluorescence of HSA in the presence of temsirolimus confirming the complex formation and also confirmed that static mode of interaction is operative for this binding process. Binding constant values obtained through UV and fluorescence spectroscopy reveal strong interaction; temsirolimus binds to HSA at 298 K with a binding constant of 2.9 × 10 4  M -1 implying the strength of interaction. The negative Gibbs free energy obtained through Isothermal titration calorimetry as well as quenching experiments suggests that binding process is spontaneous. Molecular docking further provides an insight of various residues that are involved in this binding process; showing the binding energy to be -12.9 kcal/mol. CD spectroscopy was retorted to analyze changes in secondary structure of HSA; increased intensity in presence of temsirolimus showing changes in secondary structure of HSA induced by temsirolimus. This study is of importance as it provides an insight into the binding mechanism of an important antirenal cancer drug with an important carrier protein. Once temsirolimus binds to HSA, it changes conformation of HSA which in turn can alter the functionality of this important carrier protein and this altered functionality of HSA can be highlighted in variety of diseases.

Gray scale x-ray mask

DOEpatents

Morales, Alfredo M [Livermore, CA; Gonzales, Marcela [Seattle, WA

2006-03-07

The present invention describes a method for fabricating an embossing tool or an x-ray mask tool, providing microstructures that smoothly vary in height from point-to-point in etched substrates, i.e., structure which can vary in all three dimensions. The process uses a lithographic technique to transfer an image pattern in the surface of a silicon wafer by exposing and developing the resist and then etching the silicon substrate. Importantly, the photoresist is variably exposed so that when developed some of the resist layer remains. The remaining undeveloped resist acts as an etchant barrier to the reactive plasma used to etch the silicon substrate and therefore provides the ability etch structures of variable depths.

Magnetic resonance imaging based functional imaging in paediatric oncology.

PubMed

Manias, Karen A; Gill, Simrandip K; MacPherson, Lesley; Foster, Katharine; Oates, Adam; Peet, Andrew C

2017-02-01

Imaging is central to management of solid tumours in children. Conventional magnetic resonance imaging (MRI) is the standard imaging modality for tumours of the central nervous system (CNS) and limbs and is increasingly used in the abdomen. It provides excellent structural detail, but imparts limited information about tumour type, aggressiveness, metastatic potential or early treatment response. MRI based functional imaging techniques, such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, probe tissue properties to provide clinically important information about metabolites, structure and blood flow. This review describes the role of and evidence behind these functional imaging techniques in paediatric oncology and implications for integrating them into routine clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metalloproteomics: Forward and Reverse Approaches in Metalloprotein Structural and Functional Characterization

PubMed Central

Shi, Wuxian; Chance, Mark R.

2010-01-01

About one-third of all proteins are associated with a metal. Metalloproteomics is defined as the structural and functional characterization of metalloproteins on a genome-wide scale. The methodologies utilized in metalloproteomics, including both forward (bottom-up) and reverse (top-down) technologies, to provide information on the identity, quantity and function of metalloproteins are discussed. Important techniques frequently employed in metalloproteomics include classical proteomics tools such as mass spectrometry and 2-D gels, immobilized-metal affinity chromatography, bioinformatics sequence analysis and homology modeling, X-ray absorption spectroscopy and other synchrotron radiation based tools. Combinative applications of these techniques provide a powerful approach to understand the function of metalloproteins. PMID:21130021

Free-falling Crystals: Biological Macromolecular Crystal Growth Studies in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Judge, Russell A.; Snell, E. H.; Pusey, M. L.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

Spacecraft orbiting the earth experience a reduced acceleration environment due to being in a state of continuous free-fall. This state colloquially termed microgravity, has produced improved X-ray diffraction quality crystals of biological macromolecules. Improvements in X-ray diffraction resolution (detail) or signal to noise, provide greater detail in the three-dimensional molecular structure providing information about the molecule, how it works, how to improve its function or how to impede it. Greater molecular detail obtained by crystallization in microgravity, has important implications for structural biology. In this article we examine the theories behind macromolecule crystal quality improvement in microgravity using results obtained from studies with the model protein, chicken egg white lysozyme.

Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators.

PubMed

Bohl, Casey E; Wu, Zengru; Chen, Jiyun; Mohler, Michael L; Yang, Jun; Hwang, Dong Jin; Mustafa, Suni; Miller, Duane D; Bell, Charles E; Dalton, James T

2008-10-15

Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with a substituted pendant arene referred to as the B-ring. We found that hydrophilic B-ring para-substituted analogs exhibit an additional region of hydrogen bonding not seen with steroidal compounds and that multiple halogen substitutions affect the B-ring conformation and aromatic interactions with Trp741. This information elucidates interactions important for high AR binding affinity and provides new insight for structure-based drug design.

The economics of end-stage renal disease care in Canada: incentives and impact on delivery of care.

PubMed

Manns, Braden J; Mendelssohn, David C; Taub, Kenneth J

2007-09-01

Examining international differences in health outcomes for end-stage renal disease (ESRD) patients requires an understanding of ESRD funding structures. In Canada, funding for all aspects of dialysis and transplant care, with the exception of drugs (for which supplementary insurance can be purchased), is provided for all citizens. Although ESRD programs across Canada's 10 provinces differ in funding structure, they share important economic characteristics, including being publicly funded and universal, and providing most facets of ESRD care for free. This paper explains how ESRD care fits into the Canadian health care system, describes the epidemiology of ESRD in Canada, and offers economic explanations for international discrepancies.

Genome sequence, comparative analysis and haplotype structure of the domestic dog.

PubMed

Lindblad-Toh, Kerstin; Wade, Claire M; Mikkelsen, Tarjei S; Karlsson, Elinor K; Jaffe, David B; Kamal, Michael; Clamp, Michele; Chang, Jean L; Kulbokas, Edward J; Zody, Michael C; Mauceli, Evan; Xie, Xiaohui; Breen, Matthew; Wayne, Robert K; Ostrander, Elaine A; Ponting, Chris P; Galibert, Francis; Smith, Douglas R; DeJong, Pieter J; Kirkness, Ewen; Alvarez, Pablo; Biagi, Tara; Brockman, William; Butler, Jonathan; Chin, Chee-Wye; Cook, April; Cuff, James; Daly, Mark J; DeCaprio, David; Gnerre, Sante; Grabherr, Manfred; Kellis, Manolis; Kleber, Michael; Bardeleben, Carolyne; Goodstadt, Leo; Heger, Andreas; Hitte, Christophe; Kim, Lisa; Koepfli, Klaus-Peter; Parker, Heidi G; Pollinger, John P; Searle, Stephen M J; Sutter, Nathan B; Thomas, Rachael; Webber, Caleb; Baldwin, Jennifer; Abebe, Adal; Abouelleil, Amr; Aftuck, Lynne; Ait-Zahra, Mostafa; Aldredge, Tyler; Allen, Nicole; An, Peter; Anderson, Scott; Antoine, Claudel; Arachchi, Harindra; Aslam, Ali; Ayotte, Laura; Bachantsang, Pasang; Barry, Andrew; Bayul, Tashi; Benamara, Mostafa; Berlin, Aaron; Bessette, Daniel; Blitshteyn, Berta; Bloom, Toby; Blye, Jason; Boguslavskiy, Leonid; Bonnet, Claude; Boukhgalter, Boris; Brown, Adam; Cahill, Patrick; Calixte, Nadia; Camarata, Jody; Cheshatsang, Yama; Chu, Jeffrey; Citroen, Mieke; Collymore, Alville; Cooke, Patrick; Dawoe, Tenzin; Daza, Riza; Decktor, Karin; DeGray, Stuart; Dhargay, Norbu; Dooley, Kimberly; Dooley, Kathleen; Dorje, Passang; Dorjee, Kunsang; Dorris, Lester; Duffey, Noah; Dupes, Alan; Egbiremolen, Osebhajajeme; Elong, Richard; Falk, Jill; Farina, Abderrahim; Faro, Susan; Ferguson, Diallo; Ferreira, Patricia; Fisher, Sheila; FitzGerald, Mike; Foley, Karen; Foley, Chelsea; Franke, Alicia; Friedrich, Dennis; Gage, Diane; Garber, Manuel; Gearin, Gary; Giannoukos, Georgia; Goode, Tina; Goyette, Audra; Graham, Joseph; Grandbois, Edward; Gyaltsen, Kunsang; Hafez, Nabil; Hagopian, Daniel; Hagos, Birhane; Hall, Jennifer; Healy, Claire; Hegarty, Ryan; Honan, Tracey; Horn, Andrea; Houde, Nathan; Hughes, Leanne; Hunnicutt, Leigh; Husby, M; Jester, Benjamin; Jones, Charlien; Kamat, Asha; Kanga, Ben; Kells, Cristyn; Khazanovich, Dmitry; Kieu, Alix Chinh; Kisner, Peter; Kumar, Mayank; Lance, Krista; Landers, Thomas; Lara, Marcia; Lee, William; Leger, Jean-Pierre; Lennon, Niall; Leuper, Lisa; LeVine, Sarah; Liu, Jinlei; Liu, Xiaohong; Lokyitsang, Yeshi; Lokyitsang, Tashi; Lui, Annie; Macdonald, Jan; Major, John; Marabella, Richard; Maru, Kebede; Matthews, Charles; McDonough, Susan; Mehta, Teena; Meldrim, James; Melnikov, Alexandre; Meneus, Louis; Mihalev, Atanas; Mihova, Tanya; Miller, Karen; Mittelman, Rachel; Mlenga, Valentine; Mulrain, Leonidas; Munson, Glen; Navidi, Adam; Naylor, Jerome; Nguyen, Tuyen; Nguyen, Nga; Nguyen, Cindy; Nguyen, Thu; Nicol, Robert; Norbu, Nyima; Norbu, Choe; Novod, Nathaniel; Nyima, Tenchoe; Olandt, Peter; O'Neill, Barry; O'Neill, Keith; Osman, Sahal; Oyono, Lucien; Patti, Christopher; Perrin, Danielle; Phunkhang, Pema; Pierre, Fritz; Priest, Margaret; Rachupka, Anthony; Raghuraman, Sujaa; Rameau, Rayale; Ray, Verneda; Raymond, Christina; Rege, Filip; Rise, Cecil; Rogers, Julie; Rogov, Peter; Sahalie, Julie; Settipalli, Sampath; Sharpe, Theodore; Shea, Terrance; Sheehan, Mechele; Sherpa, Ngawang; Shi, Jianying; Shih, Diana; Sloan, Jessie; Smith, Cherylyn; Sparrow, Todd; Stalker, John; Stange-Thomann, Nicole; Stavropoulos, Sharon; Stone, Catherine; Stone, Sabrina; Sykes, Sean; Tchuinga, Pierre; Tenzing, Pema; Tesfaye, Senait; Thoulutsang, Dawa; Thoulutsang, Yama; Topham, Kerri; Topping, Ira; Tsamla, Tsamla; Vassiliev, Helen; Venkataraman, Vijay; Vo, Andy; Wangchuk, Tsering; Wangdi, Tsering; Weiand, Michael; Wilkinson, Jane; Wilson, Adam; Yadav, Shailendra; Yang, Shuli; Yang, Xiaoping; Young, Geneva; Yu, Qing; Zainoun, Joanne; Zembek, Lisa; Zimmer, Andrew; Lander, Eric S

2005-12-08

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases

PubMed Central

Jain, Chetan Kumar; Majumder, Hemanta Kumar; Roychoudhury, Susanta

2017-01-01

DNA topoisomerases are important cellular enzymes found in almost all types of living cells (eukaryotic and prokaryotic). These enzymes are essential for various DNA metabolic processes e.g. replication, transcription, recombination, chromosomal decatenation etc. These enzymes are important molecular drug targets and inhibitors of these enzymes are widely used as effective anticancer and antibacterial drugs. However, topoisomerase inhibitors have some therapeutic limitations and they exert serious side effects during cancer chemotherapy. Thus, development of novel anticancer topoisomerase inhibitors is necessary for improving cancer chemotherapy. Nature serves as a repertoire of structurally and chemically diverse molecules and in the recent years many DNA topoisomerase inhibitors have been identified from natural sources. The present review discusses anticancer properties and therapeutic importance of eighteen recently identified natural topoisomerase inhibitors (from the year 2009 to 2015). Structural characteristics of these novel inhibitors provide backbones for designing and developing new anticancer drugs. PMID:28503091

How cryo‐electron microscopy and X‐ray crystallography complement each other

PubMed Central

Wang, Jia‐Wei

2016-01-01

Abstract With the ability to resolve structures of macromolecules at atomic resolution, X‐ray crystallography has been the most powerful tool in modern structural biology. At the same time, recent technical improvements have triggered a resolution revolution in the single particle cryo‐EM method. While the two methods are different in many respects, from sample preparation to structure determination, they both have the power to solve macromolecular structures at atomic resolution. It is important to understand the unique advantages and caveats of the two methods in solving structures and to appreciate the complementary nature of the two methods in structural biology. In this review we provide some examples, and discuss how X‐ray crystallography and cryo‐EM can be combined in deciphering structures of macromolecules for our full understanding of their biological mechanisms. PMID:27543495

How cryo-electron microscopy and X-ray crystallography complement each other.

PubMed

Wang, Hong-Wei; Wang, Jia-Wei

2017-01-01

With the ability to resolve structures of macromolecules at atomic resolution, X-ray crystallography has been the most powerful tool in modern structural biology. At the same time, recent technical improvements have triggered a resolution revolution in the single particle cryo-EM method. While the two methods are different in many respects, from sample preparation to structure determination, they both have the power to solve macromolecular structures at atomic resolution. It is important to understand the unique advantages and caveats of the two methods in solving structures and to appreciate the complementary nature of the two methods in structural biology. In this review we provide some examples, and discuss how X-ray crystallography and cryo-EM can be combined in deciphering structures of macromolecules for our full understanding of their biological mechanisms. © 2016 The Protein Society.

Capillary Assembly of Colloids: Interactions on Planar and Curved Interfaces

NASA Astrophysics Data System (ADS)

Liu, Iris B.; Sharifi-Mood, Nima; Stebe, Kathleen J.

2018-03-01

In directed assembly, small building blocks are assembled into an organized structure under the influence of guiding fields. Capillary interactions provide a versatile route for structure formation. Colloids adsorbed on fluid interfaces distort the interface, which creates an associated energy field. When neighboring distortions overlap, colloids interact to minimize interfacial area. Contact line pinning, particle shape, and surface chemistry play important roles in structure formation. Interface curvature acts like an external field; particles migrate and assemble in patterns dictated by curvature gradients. We review basic analysis and recent findings in this rapidly evolving literature. Understanding the roles of assembly is essential for tuning the mechanical, physical, and optical properties of the structure.

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis

PubMed Central

Du, Yushen; Wu, Nicholas C.; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting

2016-01-01

ABSTRACT Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. PMID:27803181

Concentration state dependence of the rheological and structural properties of reconstituted silk.

PubMed

Mo, Chunli; Holland, Chris; Porter, David; Shao, Zhengzhong; Vollrath, Fritz

2009-10-12

The ability to control the processing of artificial silk is key to the successful application of this important and high performance biopolymer. Understanding where our current reconstitution process can be improved will not only aid us in the creation of better materials, but will also provide insight into the natural material along the way. This study aims to understand what proportion of reconstituted silk contributes to its rheological properties and what conformational state the silk proteins are in. It shows, for the first time, that a change in rheological properties can be related to a change in silk structures present in solution and reveals a low concentration gel state for silk that may have important implications for future successful artificial processing of silk.

Zeolites with Continuously Tuneable Porosity**

PubMed Central

Wheatley, Paul S; Chlubná-Eliášová, Pavla; Greer, Heather; Zhou, Wuzong; Seymour, Valerie R; Dawson, Daniel M; Ashbrook, Sharon E; Pinar, Ana B; McCusker, Lynne B; Opanasenko, Maksym; Čejka, Jiří; Morris, Russell E

2014-01-01

Zeolites are important materials whose utility in industry depends on the nature of their porous structure. Control over microporosity is therefore a vitally important target. Unfortunately, traditional methods for controlling porosity, in particular the use of organic structure-directing agents, are relatively coarse and provide almost no opportunity to tune the porosity as required. Here we show how zeolites with a continuously tuneable surface area and micropore volume over a wide range can be prepared. This means that a particular surface area or micropore volume can be precisely tuned. The range of porosity we can target covers the whole range of useful zeolite porosity: from small pores consisting of 8-rings all the way to extra-large pores consisting of 14-rings. PMID:25284344

Single-particle mapping of nonequilibrium nanocrystal transformations

DOE PAGES

Ye, Xingchen; Jones, Matthew R.; Frechette, Layne B.; ...

2016-11-18

Chemists have developed mechanistic insight into numerous chemical reactions by thoroughly characterizing nonequilibrium species. Although methods to probe these processes are well established for molecules, analogous techniques for understanding intermediate structures in nanomaterials have been lacking. For this study, we monitor the shape evolution of individual anisotropic gold nanostructures as they are oxidatively etched in a graphene liquid cell with a controlled redox environment. Short-lived, nonequilibrium nanocrystals are observed, structurally analyzed, and rationalized through Monte Carlo simulations. Understanding these reaction trajectories provides important fundamental insight connecting high-energy nanocrystal morphologies to the development of kinetically stabilized surface features and demonstrates themore » importance of developing tools capable of probing short-lived nanoscale species at the single-particle level.« less

Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity

PubMed Central

Groves, Maria AT; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

2014-01-01

In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics. PMID:24256948

Quasi-static elastography comparison of hyaline cartilage structures

NASA Astrophysics Data System (ADS)

McCredie, A. J.; Stride, E.; Saffari, N.

2009-11-01

Joint cartilage, a load bearing structure in mammals, has only limited ability for regeneration after damage. For tissue engineers to design functional constructs, better understanding of the properties of healthy tissue is required. Joint cartilage is a specialised structure of hyaline cartilage; a poroviscoelastic solid containing fibril matrix reinforcements. Healthy joint cartilage is layered, which is thought to be important for correct tissue function. However, the behaviour of each layer during loading is poorly understood. Ultrasound elastography provides access to depth-dependent information in real-time for a sample during loading. A 15 MHz focussed transducer provided details from scatterers within a small fixed region in each sample. Quasi-static loading was applied to cartilage samples while ultrasonic signals before and during compressions were recorded. Ultrasonic signals were processed to provide time-shift profiles using a sum-squared difference method and cross-correlation. Two structures of hyaline cartilage have been tested ultrasonically and mechanically to determine method suitability for monitoring internal deformation differences under load and the effect of the layers on the global mechanical material behaviour. Results show differences in both the global mechanical properties and the ultrasonically tested strain distributions between the two structures tested. It was concluded that these differences are caused primarily by the fibril orientations.

Making partnerships work: issues of risk, trust and control for managers and service providers.

PubMed

Walker, Rae; Smith, Penny; Adam, Jenny

2009-03-01

Trust is widely recognised is a core feature of partnership relationships and one that facilitates joint work. It is an issue that must be addressed if partnerships are to enhance service system integration. In recent literature trust has been linked to concepts of risk and control. In this study of trust within a Primary Care Partnership (PCP) in Australia the experiences of risk and uncertainty, and control, of participants in different structural positions, were explored in detail. The data used in this paper was qualitative, derived from 63 interviews with managers and service providers participating in committees of the PCP. This paper reports on the differences in the experience of risk and uncertainty, trust and control, of managers and service providers working as boundary spanners through the committees of a PCP. For managers there were significant risks and uncertainties, and trust and control were important. For service providers there were few risks and uncertainties, and trust and control were of much less importance. Some policy implications of the differences in perspective are discussed, as are important areas for further research.

Significant structural reinterpretation of the giant October Field, Gulf of Suez, Egypt using SCAT, isogon based sections and 3D seismic

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

Sercombe, W.J.; Smith, G.W.; Morse, J.D.

1996-01-01

The October field, a sub-salt giant in the extensional Gulf of Suez (Egypt) has been structurally reinterpreted for new reserve opportunities. Quantitative SCAT analyses of the wellbore dip data have been integrated with 3D seismic by using dip isogons to construct local structural sections. SCAT dip analysis was critical to the reinterpretation because SCAT revealed important structural information that previously was unresolvable using conventional tadpole plots. In gross aspect, the October Field is a homocline that trends NW-SE, dips to the NE, and is closed on the SW (updip) by the major Clysmic Normal Fault. SCAT accurately calculated the overallmore » trend of the field, but also identified important structural anomalies near the Clysmic fault and in the northwest and southeast plunge ends. In the northwest plunge end, SCAT has identified new, south dipping blocks that are transitional to the structurally-higher North October field. The southeast plunge end has been reinterpreted with correct azimuthal trends and new fault-block prospects. These new SCAT results have successfully improved the 3D seismic interpretation by providing a foundation of accurate in-situ structural control in an area of poor-to-fair seismic quality below the Miocene salt package.« less

Significant structural reinterpretation of the giant October Field, Gulf of Suez, Egypt using SCAT, isogon based sections and 3D seismic

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

Sercombe, W.J.; Smith, G.W.; Morse, J.D.

1996-12-31

The October field, a sub-salt giant in the extensional Gulf of Suez (Egypt) has been structurally reinterpreted for new reserve opportunities. Quantitative SCAT analyses of the wellbore dip data have been integrated with 3D seismic by using dip isogons to construct local structural sections. SCAT dip analysis was critical to the reinterpretation because SCAT revealed important structural information that previously was unresolvable using conventional tadpole plots. In gross aspect, the October Field is a homocline that trends NW-SE, dips to the NE, and is closed on the SW (updip) by the major Clysmic Normal Fault. SCAT accurately calculated the overallmore » trend of the field, but also identified important structural anomalies near the Clysmic fault and in the northwest and southeast plunge ends. In the northwest plunge end, SCAT has identified new, south dipping blocks that are transitional to the structurally-higher North October field. The southeast plunge end has been reinterpreted with correct azimuthal trends and new fault-block prospects. These new SCAT results have successfully improved the 3D seismic interpretation by providing a foundation of accurate in-situ structural control in an area of poor-to-fair seismic quality below the Miocene salt package.« less

Structural characterisation of medically relevant protein assemblies by integrating mass spectrometry with computational modelling.

PubMed

Politis, Argyris; Schmidt, Carla

2018-03-20

Structural mass spectrometry with its various techniques is a powerful tool for the structural elucidation of medically relevant protein assemblies. It delivers information on the composition, stoichiometries, interactions and topologies of these assemblies. Most importantly it can deal with heterogeneous mixtures and assemblies which makes it universal among the conventional structural techniques. In this review we summarise recent advances and challenges in structural mass spectrometric techniques. We describe how the combination of the different mass spectrometry-based methods with computational strategies enable structural models at molecular levels of resolution. These models hold significant potential for helping us in characterizing the function of protein assemblies related to human health and disease. In this review we summarise the techniques of structural mass spectrometry often applied when studying protein-ligand complexes. We exemplify these techniques through recent examples from literature that helped in the understanding of medically relevant protein assemblies. We further provide a detailed introduction into various computational approaches that can be integrated with these mass spectrometric techniques. Last but not least we discuss case studies that integrated mass spectrometry and computational modelling approaches and yielded models of medically important protein assembly states such as fibrils and amyloids. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Investigations of fungal diversity in wooden structures and soils at historic sites on the Antarctic Peninsula.

PubMed

Arenz, Brett E; Blanchette, Robert A

2009-01-01

Investigations of microbial diversity in Antarctic are important to begin to understand ecosystem functioning and decomposition processes. This study documents fungi at 9 historic sites on the Antarctic Peninsula collected from wooden structures, other organic materials, and soils during a joint National Science Foundation and British Antarctic Survey expedition in 2007. Many of these sites had wooden structures built by the British during the World War II Operation Tabarin, but others visited included the American "East Base" on Stonington Island and the Swedish hut on Snow Hill Island. Fungi were cultured on several different media and pure cultures were obtained and identified by DNA sequencing of the internal transcribed spacer region. Cadophora species previously found to attack historic wooden structures on Ross Island, Antarctica, were found at all but 1 location sampled in the Peninsula region. Fungi causing decay in the historic wooden structures and artifacts and those causing mold problems inside the structures are of great concern, and conservation efforts are urgently needed to help preserve these important polar heritage structures. The results presented also expand our knowledge on the identity of fungi present throughout the Antarctic Peninsula region and provide insights into the organisms responsible for decomposition and nutrient recycling.

Rare variation facilitates inferences of fine-scale population structure in humans.

PubMed

O'Connor, Timothy D; Fu, Wenqing; Mychaleckyj, Josyf C; Logsdon, Benjamin; Auer, Paul; Carlson, Christopher S; Leal, Suzanne M; Smith, Joshua D; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A; Akey, Joshua M

2015-03-01

Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European-American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The structure of MgO-SiO2 glasses at elevated pressure.

PubMed

Wilding, Martin; Guthrie, Malcolm; Kohara, Shinji; Bull, Craig L; Akola, Jaakko; Tucker, Matt G

2012-06-06

The magnesium silicate system is an important geophysical analogue and neutron diffraction data from glasses formed in this system may also provide an initial framework for understanding the structure-dependent properties of related liquids that are important during planetary formation. Neutron diffraction data collected in situ for a single composition (38 mol% SiO(2)) magnesium silicate glass sample shows local changes in structure as pressure is increased from ambient conditions to 8.6 GPa at ambient temperature. A method for obtaining the fully corrected, total structure factor, S(Q), has been developed that allows accurate structural characterization as this weakly scattering glass sample is compressed. The measured S(Q) data indicate changes in chemical ordering with pressure and the real-space transforms show an increase in Mg-O coordination number and a distortion of the local environment around magnesium ions. We have used reverse Monte Carlo methods to compare the high pressure and ambient pressure structures and also compare the high pressure form with a more silica-poor glass (Mg(2)SiO(4)) that represents the approach to a more dense, void-free and topologically ordered structure. The Mg-O coordination number increases with pressure and we also find that the degree of continuous connectivity of Si-O bonds increases via a collapse of interstices.

Multicriteria Analysis of Assembling Buildings from Steel Frame Structures

NASA Astrophysics Data System (ADS)

Miniotaite, Ruta

2017-10-01

Steel frame structures are often used in the construction of public and industrial buildings. They are used for: all types of slope roofs; walls of newly-built public and industrial buildings; load bearing structures; roofs of renovated buildings. The process of assembling buildings from steel frame structures should be analysed as an integrated process influenced by such factors as construction materials and machinery used, the qualification level of construction workers, complexity of work, available finance. It is necessary to find a rational technological design solution for assembling buildings from steel frame structures by conducting a multiple criteria analysis. The analysis provides a possibility to evaluate the engineering considerations and find unequivocal solutions. The rational alternative of a complex process of assembling buildings from steel frame structures was found through multiple criteria analysis and multiple criteria evaluation. In multiple criteria evaluation of technological solutions for assembling buildings from steel frame structures by pairwise comparison method the criteria by significance are distributed as follows: durability is the most important criterion in the evaluation of alternatives; the price (EUR/unit of measurement) of a part of assembly process; construction workers’ qualification level (category); mechanization level of a part of assembling process (%), and complexity of assembling work (in points) are less important criteria.

Could the increased structural versatility imposed by non-halogen ligands bring something new for polynuclear superhalogens? A case study on binuclear [Mg2L5]- (L = -OH, -OOH and -OF) anions.

PubMed

Zhao, Ru-Fang; Yu, Le; Zhou, Fu-Qiang; Li, Jin-Feng; Yin, Bing

2017-10-11

A combined ab initio and DFT study is performed in this work to explore the superhalogen properties of polynuclear structures based on the ligands of -OH, -OOH and -OF. According to high-level CCSD(T) results, all the structures here are superhalogens whose properties are superior to the corresponding mononuclear ones. Although inferior to similar structures based on F ligands, some of the superhalogens here are capable of transcending the traditional ones based on Cl atoms. Therefore the superhalogen properties of the anions here are still promising and they have an important advantage of high safety, which is crucial for practical applications. An increased degree of structural versatility is imposed by these non-halogen ligands because of the various ways in which they connect the central atoms and their multiple orientations. It is important that this increased versatility will bring new factors, e.g., the larger spatial extent of the whole cluster and the existence of intra-molecular hydrogen bonds, which should favour high VDE values. These factors are not available in traditional halogen-based systems and they may play an important role in the future search for novel superhalogens. (HF + MP2)/2, ωB97XD as well as M06-2X are capable of providing accurate VDE values, close to the CCSD(T) results, and their absolute errors are even lower than that of the OVGF. Due to the good balance between the accuracy and efficiency, these methods could provide reliable predictions on large systems which cannot be treated with CCSD(T) or even with the OVGF. Balanced distribution of the extra electron, between the terminal and bridging ligands, is also shown to be favourable to realize a high VDE value.

Three-Dimensional Reconstruction of Thoracic Structures: Based on Chinese Visible Human

PubMed Central

Luo, Na; Tan, Liwen; Fang, Binji; Li, Ying; Xie, Bing; Liu, Kaijun; Chu, Chun; Li, Min

2013-01-01

We managed to establish three-dimensional digitized visible model of human thoracic structures and to provide morphological data for imaging diagnosis and thoracic and cardiovascular surgery. With Photoshop software, the contour line of lungs and mediastinal structures including heart, aorta and its ramus, azygos vein, superior vena cava, inferior vena cava, thymus, esophagus, diaphragm, phrenic nerve, vagus nerve, sympathetic trunk, thoracic vertebrae, sternum, thoracic duct, and so forth were segmented from the Chinese Visible Human (CVH)-1 data set. The contour data set of segmented thoracic structures was imported to Amira software and 3D thorax models were reconstructed via surface rendering and volume rendering. With Amira software, surface rendering reconstructed model of thoracic organs and its volume rendering reconstructed model were 3D reconstructed and can be displayed together clearly and accurately. It provides a learning tool of interpreting human thoracic anatomy and virtual thoracic and cardiovascular surgery for medical students and junior surgeons. PMID:24369489

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs.

PubMed

Li, Qianwen; Cai, Tiange; Huang, Yinghong; Xia, Xi; Cole, Susan P C; Cai, Yu

2017-05-27

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid-polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core-shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs', PNPs', and PLNs' structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system.

The crystal structure of human GlnRS provides basis for the development of neurological disorders

DOE PAGES

Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; ...

2016-02-10

Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

A Review of the Structure, Preparation, and Application of NLCs, PNPs, and PLNs

PubMed Central

Li, Qianwen; Cai, Tiange; Huang, Yinghong; Xia, Xi; Cole, Susan P. C.; Cai, Yu

2017-01-01

Nanostructured lipid carriers (NLCs) are modified solid lipid nanoparticles (SLNs) that retain the characteristics of the SLN, improve drug stability and loading capacity, and prevent drug leakage. Polymer nanoparticles (PNPs) are an important component of drug delivery. These nanoparticles can effectively direct drug delivery to specific targets and improve drug stability and controlled drug release. Lipid–polymer nanoparticles (PLNs), a new type of carrier that combines liposomes and polymers, have been employed in recent years. These nanoparticles possess the complementary advantages of PNPs and liposomes. A PLN is composed of a core–shell structure; the polymer core provides a stable structure, and the phospholipid shell offers good biocompatibility. As such, the two components increase the drug encapsulation efficiency rate, facilitate surface modification, and prevent leakage of water-soluble drugs. Hence, we have reviewed the current state of development for the NLCs’, PNPs’, and PLNs’ structures, preparation, and applications over the past five years, to provide the basis for further study on a controlled release drug delivery system. PMID:28554993

A New Protein Architecture for Processing Alkylation Damaged DNA: The Crystal Structure of DNA Glycosylase AlkD

PubMed Central

Rubinson, Emily H.; Metz, Audrey H.; O'Quin, Jami; Eichman, Brandt F.

2013-01-01

Summary DNA glycosylases safeguard the genome by locating and excising chemically modified bases from DNA. AlkD is a recently discovered bacterial DNA glycosylase that removes positively charged methylpurines from DNA, and was predicted to adopt a protein fold distinct from other DNA repair proteins. The crystal structure of Bacillus cereus AlkD presented here shows that the protein is composed exclusively of helical HEAT-like repeats, which form a solenoid perfectly shaped to accommodate a DNA duplex on the concave surface. Structural analysis of the variant HEAT repeats in AlkD provides a rationale for how this protein scaffolding motif has been modified to bind DNA. We report 7mG excision and DNA binding activities of AlkD mutants, along with a comparison of alkylpurine DNA glycosylase structures. Together, these data provide important insight into the requirements for alkylation repair within DNA and suggest that AlkD utilizes a novel strategy to manipulate DNA in its search for alkylpurine bases. PMID:18585735

Optical Coating Performance and Thermal Structure Design for Heat Reflectors of JWST Electronic Control Unit

NASA Technical Reports Server (NTRS)

Quijada, Manuel A.; Threat, Felix; Garrison, Matt; Perrygo, Chuck; Bousquet, Robert; Rashford, Robert

2008-01-01

The James Webb Space Telescope (JWST) consists of an infrared-optimized Optical Telescope Element (OTE) that is cooled down to 40 degrees Kelvin. A second adjacent component to the OTE is the Integrated Science Instrument Module, or ISIM. This module includes the electronic compartment, which provides the mounting surfaces and ambient thermally controlled environment for the instrument control electronics. Dissipating the 200 watts generated from the ISIM structure away from the OTE is of paramount importance so that the spacecraft's own heat does not interfere with the infrared light detected from distant cosmic sources. This technical challenge is overcome by a thermal subsystem unit that provides passive cooling to the ISIM control electronics. The proposed design of this thermal radiator consists of a lightweight structure made out of composite materials and low-emittance metal coatings. In this paper, we will present characterizations of the coating emittance, bidirectional reflectance, and mechanical structure design that will affect the performance of this passive cooling system.

The crystal structure of human GlnRS provides basis for the development of neurological disorders

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

Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen

Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

High-Resolution Crystal Structures of Streptococcus pneumoniae Nicotinamidase with Trapped Intermediates Provide Insights into the Catalytic Mechanism and Inhibition by Aldehydes

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

French, Jarrod B.; Cen, Yana; Sauve, Anthony A.

2010-11-11

Nicotinamidases are salvage enzymes that convert nicotinamide to nicotinic acid. These enzymes are essential for the recycling of nicotinamide into NAD{sup +} in most prokaryotes and most single-cell and multicellular eukaryotes, but not in mammals. The significance of these enzymes for nicotinamide salvage and for NAD{sup +} homeostasis has stimulated interest in nicotinamidases as possible antibiotic targets. Nicotinamidases are also regulators of intracellular nicotinamide concentrations, thereby regulating signaling of downstream NAD{sup +}-consuming enzymes, such as the NAD{sup +}-dependent deacetylases (sirtuins). Here, we report several high-resolution crystal structures of the nicotinamidase from Streptococcus pneumoniae (SpNic) in unliganded and ligand-bound forms. Themore » structure of the C136S mutant in complex with nicotinamide provides details about substrate binding, while a trapped nicotinoyl thioester in a complex with SpNic reveals the structure of the proposed thioester reaction intermediate. Examination of the active site of SpNic reveals several important features, including a metal ion that coordinates the substrate and the catalytically relevant water molecule and an oxyanion hole that both orients the substrate and offsets the negative charge that builds up during catalysis. Structures of this enzyme with bound nicotinaldehyde inhibitors elucidate the mechanism of inhibition and provide further details about the catalytic mechanism. In addition, we provide a biochemical analysis of the identity and role of the metal ion that orients the ligand in the active site and activates the water molecule responsible for hydrolysis of the substrate. These data provide structural evidence of several proposed reaction intermediates and allow for a more complete understanding of the catalytic mechanism of this enzyme.« less

Structural insights into ligand recognition and selectivity for class A, B, and C GPCRs

PubMed Central

Lee, Sang-Min; Booe, Jason M.; Pioszak, Augen A.

2015-01-01

The G protein-coupled receptor (GPCR) superfamily constitutes the largest collection of cell surface signaling proteins with approximately 800 members in the human genome. GPCRs regulate virtually all aspects of physiology and they are an important class of drug targets with ~30% of drugs on the market targeting a GPCR. Breakthroughs in GPCR structural biology in recent years have significantly expanded our understanding of GPCR structure and function and ushered in a new era of structure-based drug design for GPCRs. Crystal structures for nearly thirty distinct GPCRs are now available including receptors from each of the major classes, A, B, C, and F. These structures provide a foundation for understanding the molecular basis of GPCR pharmacology. Here, we review structural mechanisms of ligand recognition and selectivity of GPCRs with a focus on selected examples from classes A, B, and C, and we highlight major unresolved questions for future structural studies. PMID:25981303

Structural studies of G protein-coupled receptors.

PubMed

Lu, Mengjie; Wu, Beili

2016-11-01

G protein-coupled receptors (GPCRs) comprise the largest membrane protein family. These receptors sense a variety of signaling molecules, activate multiple intracellular signal pathways, and act as the targets of over 40% of marketed drugs. Recent progress on GPCR structural studies provides invaluable insights into the structure-function relationship of the GPCR superfamily, deepening our understanding about the molecular mechanisms of GPCR signal transduction. Here, we review recent breakthroughs on GPCR structure determination and the structural features of GPCRs, and take the structures of chemokine receptor CCR5 and purinergic receptors P2Y 1 R and P2Y 12 R as examples to discuss the importance of GPCR structures on functional studies and drug discovery. In addition, we discuss the prospect of GPCR structure-based drug discovery. © 2016 IUBMB Life, 68(11):894-903, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Ion spectral structures observed by the Van Allen Probes

NASA Astrophysics Data System (ADS)

Ferradas, C.; Zhang, J.; Spence, H. E.; Kistler, L. M.; Larsen, B.; Reeves, G. D.; Skoug, R. M.; Funsten, H. O.

2015-12-01

During the last decades several missions have recorded the presence of dynamic spectral features of energetic ions in the inner magnetosphere. Previous studies have reported single "nose-like" structures occurring alone and simultaneous nose-like structures (up to three). These ion structures are named after the characteristic shapes of energy bands or gaps in the energy-time spectrograms of in situ measured ion fluxes. They constitute the observational signatures of ion acceleration, transport, and loss in the global magnetosphere. The HOPE mass spectrometer onboard the Van Allen Probes measures energetic hydrogen, helium, and oxygen ions near the inner edge of the plasma sheet, where these ion structures are observed. We present a statistical study of nose-like structures, using 2-years measurements from the HOPE instrument. The results provide important details about the spatial distribution (dependence on geocentric distance), spectral features of the structures (differences among species), and geomagnetic conditions under which these structures occur.

From Sequence and Forces to Structure, Function and Evolution of Intrinsically Disordered Proteins

PubMed Central

Forman-Kay, Julie D.; Mittag, Tanja

2015-01-01

Intrinsically disordered proteins (IDPs), which lack persistent structure, are a challenge to structural biology due to the inapplicability of standard methods for characterization of folded proteins as well as their deviation from the dominant structure/function paradigm. Their widespread presence and involvement in biological function, however, has spurred the growing acceptance of the importance of IDPs and the development of new tools for studying their structure, dynamics and function. The interplay of folded and disordered domains or regions for function and the existence of a continuum of protein states with respect to conformational energetics, motional timescales and compactness is shaping a unified understanding of structure-dynamics-disorder/function relationships. On the 20th anniversary of this journal, Structure, we provide a historical perspective on the investigation of IDPs and summarize the sequence features and physical forces that underlie their unique structural, functional and evolutionary properties. PMID:24010708

From sequence and forces to structure, function, and evolution of intrinsically disordered proteins.

PubMed

Forman-Kay, Julie D; Mittag, Tanja

2013-09-03

Intrinsically disordered proteins (IDPs), which lack persistent structure, are a challenge to structural biology due to the inapplicability of standard methods for characterization of folded proteins as well as their deviation from the dominant structure/function paradigm. Their widespread presence and involvement in biological function, however, has spurred the growing acceptance of the importance of IDPs and the development of new tools for studying their structure, dynamics, and function. The interplay of folded and disordered domains or regions for function and the existence of a continuum of protein states with respect to conformational energetics, motional timescales, and compactness are shaping a unified understanding of structure-dynamics-disorder/function relationships. In the 20(th) anniversary of Structure, we provide a historical perspective on the investigation of IDPs and summarize the sequence features and physical forces that underlie their unique structural, functional, and evolutionary properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

SDSL-ESR-based protein structure characterization.

PubMed

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

2010-03-01

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

The Structural Changes of Tropical Cyclones Upon Interaction with Vertical Wind Shear

NASA Technical Reports Server (NTRS)

Ritchie, Elizabeth A.

2003-01-01

The Fourth Convection and Moisture Experiment (CAMEX-4) provided a unique opportunity to observe the distributions and document the roles of important atmospheric factors that impact the development of the core asymmetries and core structural changes of tropical cyclones embedded in vertical wind shear. The state-of-the-art instruments flown on the NASA DC-8 and ER-2, in addition to those on the NOAA aircraft, provided a unique set of observations that documented the core structure throughout the depth of the tropical cyclone. These data have been used to conduct a combined observational and modeling study using a state-of-the-art, high- resolution mesoscale model to examine the role of the environmental vertical wind shear in producing tropical cyclone core asymmetries, and the effects on the structure and intensity of tropical cyclones.The scientific objectives of this study were to obtain in situ measurements that would allow documentation of the physical mechanisms that influence the development of the asymmetric convection and its effect on the core structure of the tropical cyclone.

Plasmon-emitter interaction using integrated ring grating-nanoantenna structures.

PubMed

Rahbany, Nancy; Geng, Wei; Bachelot, Renaud; Couteau, Christophe

2017-05-05

Overcoming the diffraction limit to achieve high optical resolution is one of the main challenges in the fields of plasmonics, nanooptics and nanophotonics. In this work, we introduce novel plasmonic structures consisting of nanoantennas (nanoprisms, single bowtie nanoantennas and double bowtie nanoantennas) integrated in the center of ring diffraction gratings. Propagating surface plasmon polaritons (SPPs) are generated by the ring grating and coupled with localized surface plasmons (LSPs) at the nanoantennas exciting emitters placed in their gap. SPPs are widely used for optical waveguiding but provide low resolution due to their weak spatial confinement. In contrast, LSPs provide excellent sub-wavelength confinement but induce large losses. The phenomenon of SPP-LSP coupling witnessed in our structures allows for achieving more precise focusing at the nanoscale, causing an increase in the fluorescence emission of the emitters. Finite-difference time-domain simulations as well as experimental fabrication and optical characterization results are presented to study plasmon-emitter coupling between an ensemble of dye molecules and our integrated plasmonic structures. A comparison is given to highlight the importance of each structure on the photoluminescence and radiative decay enhancement of the molecules.

The structure of the Mycobacterium smegmatis trehalose synthase reveals an unusual active site configuration and acarbose-binding mode†

PubMed Central

Caner, Sami; Nguyen, Nham; Aguda, Adeleke; Zhang, Ran; Pan, Yuan T; Withers, Stephen G; Brayer, Gary D

2013-01-01

Trehalose synthase (TreS) catalyzes the reversible conversion of maltose into trehalose in mycobacteria as one of three biosynthetic pathways to this nonreducing disaccharide. Given the importance of trehalose to survival of mycobacteria, there has been considerable interest in understanding the enzymes involved in its production; indeed the structures of the key enzymes in the other two pathways have already been determined. Herein, we present the first structure of TreS from Mycobacterium smegmatis, thereby providing insights into the catalytic machinery involved in this intriguing intramolecular reaction. This structure, which is of interest both mechanistically and as a potential pharmaceutical target, reveals a narrow and enclosed active site pocket within which intramolecular substrate rearrangements can occur. We also present the structure of a complex of TreS with acarbose, revealing a hitherto unsuspected oligosaccharide-binding site within the C-terminal domain. This may well provide an anchor point for the association of TreS with glycogen, thereby enhancing its role in glycogen biosynthesis and degradation. PMID:23735230

Plasmon-emitter interaction using integrated ring grating-nanoantenna structures

NASA Astrophysics Data System (ADS)

Rahbany, Nancy; Geng, Wei; Bachelot, Renaud; Couteau, Christophe

2017-05-01

Overcoming the diffraction limit to achieve high optical resolution is one of the main challenges in the fields of plasmonics, nanooptics and nanophotonics. In this work, we introduce novel plasmonic structures consisting of nanoantennas (nanoprisms, single bowtie nanoantennas and double bowtie nanoantennas) integrated in the center of ring diffraction gratings. Propagating surface plasmon polaritons (SPPs) are generated by the ring grating and coupled with localized surface plasmons (LSPs) at the nanoantennas exciting emitters placed in their gap. SPPs are widely used for optical waveguiding but provide low resolution due to their weak spatial confinement. In contrast, LSPs provide excellent sub-wavelength confinement but induce large losses. The phenomenon of SPP-LSP coupling witnessed in our structures allows for achieving more precise focusing at the nanoscale, causing an increase in the fluorescence emission of the emitters. Finite-difference time-domain simulations as well as experimental fabrication and optical characterization results are presented to study plasmon-emitter coupling between an ensemble of dye molecules and our integrated plasmonic structures. A comparison is given to highlight the importance of each structure on the photoluminescence and radiative decay enhancement of the molecules.

Computer Vision-Based Structural Displacement Measurement Robust to Light-Induced Image Degradation for In-Service Bridges

PubMed Central

Lee, Junhwa; Lee, Kyoung-Chan; Cho, Soojin

2017-01-01

The displacement responses of a civil engineering structure can provide important information regarding structural behaviors that help in assessing safety and serviceability. A displacement measurement using conventional devices, such as the linear variable differential transformer (LVDT), is challenging owing to issues related to inconvenient sensor installation that often requires additional temporary structures. A promising alternative is offered by computer vision, which typically provides a low-cost and non-contact displacement measurement that converts the movement of an object, mostly an attached marker, in the captured images into structural displacement. However, there is limited research on addressing light-induced measurement error caused by the inevitable sunlight in field-testing conditions. This study presents a computer vision-based displacement measurement approach tailored to a field-testing environment with enhanced robustness to strong sunlight. An image-processing algorithm with an adaptive region-of-interest (ROI) is proposed to reliably determine a marker’s location even when the marker is indistinct due to unfavorable light. The performance of the proposed system is experimentally validated in both laboratory-scale and field experiments. PMID:29019950

Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41 Protein.

PubMed

Murphy, R Elliot; Samal, Alexandra B; Vlach, Jiri; Saad, Jamil S

2017-11-07

The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an unknown structure. It plays important roles in HIV-1 replication such as mediating envelope (Env) intracellular trafficking and incorporation into assembling virions, mechanisms of which are poorly understood. Here, we present the solution structure of gp41CT in a micellar environment and characterize its interaction with the membrane. We show that the N-terminal 45 residues are unstructured and not associated with the membrane. However, the C-terminal 105 residues form three membrane-bound amphipathic α helices with distinctive structural features such as variable degree of membrane penetration, hydrophobic and basic surfaces, clusters of aromatic residues, and a network of cation-π interactions. This work fills a major gap by providing the structure of the last segment of HIV-1 Env, which will provide insights into the mechanisms of Gag-mediated Env incorporation as well as the overall Env mobility and conformation on the virion surface. Copyright © 2017 Elsevier Ltd. All rights reserved.

Image analysis of the AXAF VETA-I x ray mirror

NASA Technical Reports Server (NTRS)

Freeman, Mark D.; Hughes, John P; Vanspeybroeck, L.; Weisskopf, M.; Bilbro, J.

1992-01-01

Initial core scan data of the VETA-I x-ray mirror proved disappointing, showing considerable unpredicted image structure and poor measured FWHM. 2-D core scans were performed, providing important insight into the nature of the distortion. Image deconvolutions using a ray traced model PSF was performed successfully to reinforce our conclusion regarding the origin of the astigmatism. A mechanical correction was made to the optical structure, and the mirror was tested successfully (FWHM 0.22 arcsec) as a result.

The Lens Capsule

PubMed Central

Danysh, Brian P.; Duncan, Melinda K.

2009-01-01

The lens capsule is a modified basement membrane that completely surrounds the ocular lens. It is known that this extracellular matrix is important for both the structure and biomechanics of the lens in addition to providing informational cues to maintain lens cell phenotype. This review covers the development and structure of the lens capsule, lens diseases associated with mutations in extracellular matrix genes and the role of the capsule in lens function including those proposed for visual accommodation, selective permeability to infectious agents, and cell signaling. PMID:18773892

A Visual Evaluation Study of Graph Sampling Techniques

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

Zhang, Fangyan; Zhang, Song; Wong, Pak C.

2017-01-29

We evaluate a dozen prevailing graph-sampling techniques with an ultimate goal to better visualize and understand big and complex graphs that exhibit different properties and structures. The evaluation uses eight benchmark datasets with four different graph types collected from Stanford Network Analysis Platform and NetworkX to give a comprehensive comparison of various types of graphs. The study provides a practical guideline for visualizing big graphs of different sizes and structures. The paper discusses results and important observations from the study.

Analysis and Visualization of Nerve Vessel Contacts for Neurovascular Decompression

NASA Astrophysics Data System (ADS)

Süßmuth, Jochen; Piazza, Alexander; Enders, Frank; Naraghi, Ramin; Greiner, Günther; Hastreiter, Peter

Neurovascular compression syndromes are caused by a pathological contact between cranial nerves and vascular structures at the surface of the brainstem. Aiming at improved pre-operative analysis of the target structures, we propose calculating distance fields to provide quantitative information of the important nerve-vessel contacts. Furthermore, we suggest reconstructing polygonal models for the nerves and vessels. Color-coding with the respective distance information is used for enhanced visualization. Overall, our new strategy contributes to a significantly improved clinical understanding.

Cone beam computed tomography in the diagnosis of dental disease.

PubMed

Tetradis, Sotirios; Anstey, Paul; Graff-Radford, Steven

2011-07-01

Conventional radiographs provide important information for dental disease diagnosis. However, they represent 2-D images of 3-D objects with significant structure superimposition and unpredictable magnification. Cone beam computed tomography, however, allows true 3-D visualization of the dentoalveolar structures, avoiding major limitations of conventional radiographs. Cone beam computed tomography images offer great advantages in disease detection for selected patients. The authors discuss cone beam computed tomography applications in dental disease diagnosis, reviewing the pertinent literature when available.

Mononuclear Cu/O2 Complexes

PubMed Central

Cramer, Christopher J.; Tolman, William B.

2008-01-01

Using interwoven experimental and theoretical methods, detailed studies of several structurally defined 1:1 Cu/O2 complexes have provided important fundamental chemical information useful for understanding the nature of intermediates involved in aerobic oxidations in synthetic and enzymatic copper-mediated catalysis. In particular, these studies have shed new light onto the factors that influence the mode of O2 coordination (end-on vs. side-on) and the electronic structure, which can vary between Cu(II)-superoxo and Cu(III)-peroxo extremes. PMID:17458929

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop

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

Adams, Paul  D.; Aertgeerts, Kathleen; Bauer, Cary

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank archive, ~75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery/design, and the goodness-of-fit of ligand models to electron density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide Protein Data Bank/Cambridge Crystallographicmore » Data Centre/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the Protein Data Bank? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated.« less

Hydrogeological controls on spatial patterns of groundwater discharge in peatlands

NASA Astrophysics Data System (ADS)

Hare, Danielle K.; Boutt, David F.; Clement, William P.; Hatch, Christine E.; Davenport, Glorianna; Hackman, Alex

2017-11-01

Peatland environments provide important ecosystem services including water and carbon storage, nutrient processing and retention, and wildlife habitat. However, these systems and the services they provide have been degraded through historical anthropogenic agricultural conversion and dewatering practices. Effective wetland restoration requires incorporating site hydrology and understanding groundwater discharge spatial patterns. Groundwater discharge maintains wetland ecosystems by providing relatively stable hydrologic conditions, nutrient inputs, and thermal buffering important for ecological structure and function; however, a comprehensive site-specific evaluation is rarely feasible for such resource-constrained projects. An improved process-based understanding of groundwater discharge in peatlands may help guide ecological restoration design without the need for invasive methodologies and detailed site-specific investigation. Here we examine a kettle-hole peatland in southeast Massachusetts historically modified for commercial cranberry farming. During the time of our investigation, a large process-based ecological restoration project was in the assessment and design phases. To gain insight into the drivers of site hydrology, we evaluated the spatial patterning of groundwater discharge and the subsurface structure of the peatland complex using heat-tracing methods and ground-penetrating radar. Our results illustrate that two groundwater discharge processes contribute to the peatland hydrologic system: diffuse lower-flux marginal matrix seepage and discrete higher-flux preferential-flow-path seepage. Both types of groundwater discharge develop through interactions with subsurface peatland basin structure, often where the basin slope is at a high angle to the regional groundwater gradient. These field observations indicate strong correlation between subsurface structures and surficial groundwater discharge. Understanding these general patterns may allow resource managers to more efficiently predict and locate groundwater seepage, confirm these using remote sensing technologies, and incorporate this information into restoration design for these critical ecosystems.

Application effectiveness of the microtremor survey method in the exploration of geothermal resources

NASA Astrophysics Data System (ADS)

Tian, Baoqing; Xu, Peifen; Ling, Suqun; Du, Jianguo; Xu, Xueqiu; Pang, Zhonghe

2017-10-01

Geophysical techniques are critical tools of geothermal resource surveys. In recent years, the microtremor survey method, which has two branch techniques (the microtremor sounding technique and the two-dimensional (2D) microtremor profiling technique), has become a common method for geothermal resource exploration. The results of microtremor surveys provide important deep information for probing structures of geothermal storing basins and researching the heat-controlling structures, as well as providing the basis for drilling positions of geothermal wells. In this paper, the southern Jiangsu geothermal resources area is taken as a study example. By comparing the results of microtremor surveys and drilling conclusions, and analyzing microtremor survey effectiveness, and geological and technical factors such as observation radius and sampling frequency, we study the applicability of the microtremor survey method and the optimal way of working with this method to achieve better detection results. A comparative study of survey results and geothermal drilling results shows that the microtremor sounding technique effectively distinguishes sub-layers and determines the depth of geothermal reservoirs in the area with excellent layer conditions. The error of depth is generally no more than 8% compared with the results of drilling. It detects deeper by adjusting the size of the probing radius. The 2D microtremor profiling technique probes exactly the buried structures which display as low velocity anomalies in the apparent velocity profile of the S-wave. The anomaly is the critical symbol of the 2D microtremor profiling technique to distinguish and explain the buried geothermal structures. 2D microtremor profiling results provide an important basis for locating exactly the geothermal well and reducing the risk of drilling dry wells.

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop

DOE PAGES

Adams, Paul  D.; Aertgeerts, Kathleen; Bauer, Cary; ...

2016-04-05

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank archive, ~75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery/design, and the goodness-of-fit of ligand models to electron density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide Protein Data Bank/Cambridge Crystallographicmore » Data Centre/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the Protein Data Bank? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated.« less

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop.

PubMed

Adams, Paul D; Aertgeerts, Kathleen; Bauer, Cary; Bell, Jeffrey A; Berman, Helen M; Bhat, Talapady N; Blaney, Jeff M; Bolton, Evan; Bricogne, Gerard; Brown, David; Burley, Stephen K; Case, David A; Clark, Kirk L; Darden, Tom; Emsley, Paul; Feher, Victoria A; Feng, Zukang; Groom, Colin R; Harris, Seth F; Hendle, Jorg; Holder, Thomas; Joachimiak, Andrzej; Kleywegt, Gerard J; Krojer, Tobias; Marcotrigiano, Joseph; Mark, Alan E; Markley, John L; Miller, Matthew; Minor, Wladek; Montelione, Gaetano T; Murshudov, Garib; Nakagawa, Atsushi; Nakamura, Haruki; Nicholls, Anthony; Nicklaus, Marc; Nolte, Robert T; Padyana, Anil K; Peishoff, Catherine E; Pieniazek, Susan; Read, Randy J; Shao, Chenghua; Sheriff, Steven; Smart, Oliver; Soisson, Stephen; Spurlino, John; Stouch, Terry; Svobodova, Radka; Tempel, Wolfram; Terwilliger, Thomas C; Tronrud, Dale; Velankar, Sameer; Ward, Suzanna C; Warren, Gregory L; Westbrook, John D; Williams, Pamela; Yang, Huanwang; Young, Jasmine

2016-04-05

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive, ∼75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and design, and the goodness-of-fit of ligand models to electron-density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide PDB/Cambridge Crystallographic Data Center/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the PDB? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Outcome of the first wwPDB/CCDC/D3R Ligand Validation Workshop

PubMed Central

Adams, Paul D.; Aertgeerts, Kathleen; Bauer, Cary; Bell, Jeffrey A.; Berman, Helen M.; Bhat, Talapady N.; Blaney, Jeff; Bolton, Evan; Bricogne, Gerard; Brown, David; Burley, Stephen K.; Case, David A.; Clark, Kirk L.; Darden, Tom; Emsley, Paul; Feher, Victoria A.; Feng, Zukang; Groom, Colin R.; Harris, Seth F.; Hendle, Jorg; Holder, Thomas; Joachimiak, Andrzej; Kleywegt, Gerard J.; Krojer, Tobias; Marcotrigiano, Joseph; Mark, Alan E.; Markley, John L.; Miller, Matthew; Minor, Wladek; Montelione, Gaetano T.; Murshudov, Garib; Nakagawa, Atsushi; Nakamura, Haruki; Nicholls, Anthony; Nicklaus, Marc; Nolte, Robert T.; Padyana, Anil K.; Peishoff, Catherine E.; Pieniazek, Susan; Read, Randy J.; Shao, Chenghua; Sheriff, Steven; Smart, Oliver; Soisson, Stephen; Spurlino, John; Stouch, Terry; Svobodova, Radka; Tempel, Wolfram; Terwilliger, Thomas C.; Tronrud, Dale; Velankar, Sameer; Ward, Suzanna; Warren, Gregory L.; Westbrook, John D.; Williams, Pamela; Yang, Huanwang; Young, Jasmine

2016-01-01

Summary Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank archive, ~75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery/design, and the goodness-of-fit of ligand models to electron density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide Protein Data Bank/Cambridge Crystallographic Data Centre/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30–31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the Protein Data Bank? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated. PMID:27050687

Distributed Hypothesis Testing in Distributed Sensor Networks

DTIC Science & Technology

1984-07-01

single structure(, object Is Itself an important task in many applica- tions. At least at he conceptual level, there is no dlffculty in treating targets...First, we need to provide a modeling framwork within which the models of the various nodes, constructed as discussed above, can be embedded. It is within

Implementing Service Excellence in Higher Education

ERIC Educational Resources Information Center

Khan, Hina; Matlay, Harry

2009-01-01

Purpose: The purpose of this paper is to provide a critical analysis of the importance of service excellence in higher education. Design/methodology/approach: The research upon which this paper is based employed a phenomenological approach. This method was selected for its focus on respondent perceptions and experiences. Both structured and…

Metaphor in Professional Counseling

ERIC Educational Resources Information Center

Wagener, Alwin E.

2017-01-01

Metaphors are linked to how individuals process information and emotions, and they are important to understand and utilize in counseling. A description of the structure of metaphors and metaphor theory is provided. The role of metaphors in emotional processing is explained, and the process of counseling is tied to the therapeutic usage of…

Corpus-Based Investigations of Language Use.

ERIC Educational Resources Information Center

Biber, Douglas; And Others

1996-01-01

Examines a representative text corpus to gain insights into language structure and use and to open new areas of linguistic inquiry. Various illustrations are presented that provide a glimpse into the value of corpus-based investigations for increasing one's understanding of language use and imparting insights important for designing effective…

Forestry effects on vertebrate species habitats in the riparian zone

Treesearch

Mariko Yamasaki

2000-01-01

Three factors influence a coarse-filter approach to the providing wildlife habitat in riparian areas in the northeastern United States. These are: 1) degree of riparian-upland forest connectivity; 2) water regime; and 3) key vegetation structures present in riparian areas that are important to terrestrial vertebrate species.

Science Library User Survey Report, University of California, Santa Cruz.

ERIC Educational Resources Information Center

Wei, Wei

A survey of 136 science faculty, graduate, and undergraduate students, and focus group interviews, provided perceptions and input to be used to rethink the science library's organizational structure and services. Users felt the following to be important library services: consulting the Melvyl databases; borrowing books; interlibrary loan services;…

A new chicken genome assembly provides insight into avian genome structure

USDA-ARS?s Scientific Manuscript database

The importance of the Gallus gallus (chicken) as a model organism and agricultural animal merits a continuation of sequence assembly improvement efforts. We present a new version of the chicken genome assembly (Gallus_gallus-5.0; GCA_000002315.3) built from combined long single molecule sequencing t...

Building Path Diagrams for Multilevel Models

ERIC Educational Resources Information Center

Curran, Patrick J.; Bauer, Daniel J.

2007-01-01

Multilevel models have come to play an increasingly important role in many areas of social science research. However, in contrast to other modeling strategies, there is currently no widely used approach for graphically diagramming multilevel models. Ideally, such diagrams would serve two functions: to provide a formal structure for deriving the…

Exploring Rating Quality in Rater-Mediated Assessments Using Mokken Scale Analysis

ERIC Educational Resources Information Center

Wind, Stefanie A.; Engelhard, George, Jr.

2016-01-01

Mokken scale analysis is a probabilistic nonparametric approach that offers statistical and graphical tools for evaluating the quality of social science measurement without placing potentially inappropriate restrictions on the structure of a data set. In particular, Mokken scaling provides a useful method for evaluating important measurement…

Potential climate change impacts on tidal wetland plant and algal assemblages in the Pacific Northwest

EPA Science Inventory

Tidal wetlands along the coast of the Pacific Northwest provide wildlife habitat and support important ecosystem functions such as primary productivity. The future structure and function of these ecosystems may be altered by sea-level rise (SLR) or other climate change effects. W...

Habitat selection is unaltered after severe insect infestation: Concerns for forest-dependent species

Treesearch

Claire A. Zugmeyer; John L. Koprowski

2009-01-01

Severe disturbance may alter or eliminate important habitat structure that helps preserve food caches of foodhoarding species. Recent recolonization of an insect-damaged forest by the endangered Mt. Graham red squirrel (Tamiasciurus hudsonicus grahamensis) provided an opportunity to examine habitat selection for midden (cache) sites following...

Multiple-Group Analysis Using the sem Package in the R System

ERIC Educational Resources Information Center

Evermann, Joerg

2010-01-01

Multiple-group analysis in covariance-based structural equation modeling (SEM) is an important technique to ensure the invariance of latent construct measurements and the validity of theoretical models across different subpopulations. However, not all SEM software packages provide multiple-group analysis capabilities. The sem package for the R…

Affect Regulation as a Mediator of Attachment and Deliberate Self-Harm

ERIC Educational Resources Information Center

Kimball, Joan S.; Diddams, Margaret

2007-01-01

The authors used structural equation modeling to test the mediational role of affect regulation on attachment and deliberate self-harm in 216 undergraduates. Results suggest that affect regulation mediates the relationship between attachment and deliberate self-harm, providing support for the theoretical importance of attachment and affect…

Keeping your forest soils healthy and productive.

Treesearch

Ole T. Helgerson; Richard E. Miller

2008-01-01

Soils are an integral structural part of your woodland and the larger forest ecosystem. Important forest soil functions include:Providing water, nutrients, and physical support for the growth of trees and other forest plantsAllowing an exchange of carbon dioxide, oxygen, and other gasses that affect root growth and...

Atlas and feature based 3D pathway visualization enhancement for skull base pre-operative fast planning from head CT

NASA Astrophysics Data System (ADS)

Aghdasi, Nava; Li, Yangming; Berens, Angelique; Moe, Kris S.; Bly, Randall A.; Hannaford, Blake

2015-03-01

Minimally invasive neuroendoscopic surgery provides an alternative to open craniotomy for many skull base lesions. These techniques provides a great benefit to the patient through shorter ICU stays, decreased post-operative pain and quicker return to baseline function. However, density of critical neurovascular structures at the skull base makes planning for these procedures highly complex. Furthermore, additional surgical portals are often used to improve visualization and instrument access, which adds to the complexity of pre-operative planning. Surgical approach planning is currently limited and typically involves review of 2D axial, coronal, and sagittal CT and MRI images. In addition, skull base surgeons manually change the visualization effect to review all possible approaches to the target lesion and achieve an optimal surgical plan. This cumbersome process relies heavily on surgeon experience and it does not allow for 3D visualization. In this paper, we describe a rapid pre-operative planning system for skull base surgery using the following two novel concepts: importance-based highlight and mobile portal. With this innovation, critical areas in the 3D CT model are highlighted based on segmentation results. Mobile portals allow surgeons to review multiple potential entry portals in real-time with improved visualization of critical structures located inside the pathway. To achieve this we used the following methods: (1) novel bone-only atlases were manually generated, (2) orbits and the center of the skull serve as features to quickly pre-align the patient's scan with the atlas, (3) deformable registration technique was used for fine alignment, (4) surgical importance was assigned to each voxel according to a surgical dictionary, and (5) pre-defined transfer function was applied to the processed data to highlight important structures. The proposed idea was fully implemented as independent planning software and additional data are used for verification and validation. The experimental results show: (1) the proposed methods provided greatly improved planning efficiency while optimal surgical plans were successfully achieved, (2) the proposed methods successfully highlighted important structures and facilitated planning, (3) the proposed methods require shorter processing time than classical segmentation algorithms, and (4) these methods can be used to improve surgical safety for surgical robots.

Design Through Manufacturing: The Solid Model-Finite Element Analysis Interface

NASA Technical Reports Server (NTRS)

Rubin, Carol

2002-01-01

State-of-the-art computer aided design (CAD) presently affords engineers the opportunity to create solid models of machine parts reflecting every detail of the finished product. Ideally, in the aerospace industry, these models should fulfill two very important functions: (1) provide numerical. control information for automated manufacturing of precision parts, and (2) enable analysts to easily evaluate the stress levels (using finite element analysis - FEA) for all structurally significant parts used in aircraft and space vehicles. Today's state-of-the-art CAD programs perform function (1) very well, providing an excellent model for precision manufacturing. But they do not provide a straightforward and simple means of automating the translation from CAD to FEA models, especially for aircraft-type structures. Presently, the process of preparing CAD models for FEA consumes a great deal of the analyst's time.

PARAMESH: A Parallel Adaptive Mesh Refinement Community Toolkit

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

Structural evolution of nrDNA ITS in Pinaceae and its phylogenetic implications.

PubMed

Kan, Xian-Zhao; Wang, Shan-Shan; Ding, Xin; Wang, Xiao-Quan

2007-08-01

Nuclear ribosomal DNA (nrDNA) has been considered as an important tool for inferring phylogenetic relationships at many taxonomic levels. In comparison with its fast concerted evolution in angiosperms, nrDNA is symbolized by slow concerted evolution and substantial ITS region length variation in gymnosperms, particularly in Pinaceae. Here we studied structure characteristics, including subrepeat composition, size, GC content and secondary structure, of nrDNA ITS regions of all Pinaceae genera. The results showed that the ITS regions of all taxa studied contained subrepeat units, ranging from 2 to 9 in number, and these units could be divided into two types, longer subrepeat (LSR) without the motif (5'-GGCCACCCTAGTC) and shorter subrepeat (SSR) with the motif. Phylogenetic analyses indicate that the homology of some SSRs still can be recognized, providing important informations for the evolutionary history of nrDNA ITS and phylogeny of Pinaceae. In particular, the adjacent tandem SSRs are not more closely related to one another than they are to remote SSRs in some genera, which may imply that multiple structure variations such as recombination have occurred in the ITS1 region of these groups. This study also found that GC content in the ITS1 region is relevant to its sequence length and subrepeat number, and could provide some phylogenetic information, especially supporting the close relationships among Picea, Pinus, and Cathaya. Moreover, several characteristics of the secondary structure of Pinaceae ITS1 were found as follows: (1) the structure is dominated by several extended hairpins; (2) the configuration complexity is positively correlated with subrepeat number; (3) paired subrepeats often partially overlap at the conserved motif (5'-GGCCACCCTAGTC), and form a long stem, while other subrepeats fold onto itself, leaving part of the conserved motif exposed in hairpin loops.

Structural determinants of ubiquitin-CXC chemokine receptor 4 interaction.

PubMed

Saini, Vikas; Marchese, Adriano; Tang, Wei-Jen; Majetschak, Matthias

2011-12-23

Ubiquitin, a post-translational protein modifier inside the cell, functions as a CXC chemokine receptor (CXCR) 4 agonist outside the cell. However, the structural determinants of the interaction between extracellular ubiquitin and CXCR4 remain unknown. Utilizing C-terminal truncated ubiquitin and ubiquitin mutants, in which surface residues that are known to interact with ubiquitin binding domains in interacting proteins are mutated (Phe-4, Leu-8, Ile-44, Asp-58, Val-70), we provide evidence that the ubiquitin-CXCR4 interaction follows a two-site binding mechanism in which the hydrophobic surfaces surrounding Phe-4 and Val-70 are important for receptor binding, whereas the flexible C terminus facilitates receptor activation. Based on these findings and the available crystal structures, we then modeled the ubiquitin-CXCR4 interface with the RosettaDock software followed by small manual adjustments, which were guided by charge complementarity and anticipation of a conformational switch of CXCR4 upon activation. This model suggests three residues of CXCR4 (Phe-29, Phe-189, Lys-271) as potential interaction sites. Binding studies with HEK293 cells overexpressing wild type and CXCR4 after site-directed mutagenesis confirm that these residues are important for ubiquitin binding but that they do not contribute to the binding of stromal cell-derived factor 1α. Our findings suggest that the structural determinants of the CXCR4 agonist activity of ubiquitin mimic the typical structure-function relationship of chemokines. Furthermore, we provide evidence for separate and specific ligand binding sites on CXCR4. As exogenous ubiquitin has been shown to possess therapeutic potential, our findings are expected to facilitate the structure-based design of new compounds with ubiquitin-mimetic actions on CXCR4.

Molecular Docking, Molecular Dynamics, and Structure-Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists.

PubMed

Noha, Stefan M; Schmidhammer, Helmut; Spetea, Mariana

2017-06-21

Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure-activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3-7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design.

Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding

NASA Astrophysics Data System (ADS)

Samanta, Sudipta; Mukherjee, Sanchita

2017-10-01

The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin.

PubMed

Kumar, Raj; Kukreja, Roshan V; Cai, Shuowei; Singh, Bal R

2014-06-01

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear. Since the endopeptidase domain (light chain; LC) of toxin apparently survives inside the neuronal cells for months, it is important to examine the structural features of this domain to understand its resistance to intracellular degradation. Published crystal structures (both botulinum neurotoxins and endopeptidase domain) have not provided adequate explanation for the intracellular longevity of the domain. Structural features obtained from spectroscopic analysis of LCA and LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation appears to be responsible for their optimal enzymatic activity at 37°C. LCE, on the other hand, was although optimally active at 37°C, but its active conformation differed from the PRIME conformation of LCA and LCB. This study establishes and confirms our earlier finding that an optimally active conformation of these proteins in the form of PRIME exists for the most poisonous poison, botulinum neurotoxin. There are substantial variations in the structural and functional characteristics of these active molten globule related structures among the three BoNT endopeptidases examined. These differential conformations of LCs are important in understanding the fundamental structural features of proteins, and their possible connection to intracellular longevity could provide significant clues for devising new countermeasures and effective therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

The unfoldomics decade: an update on intrinsically disordered proteins.

PubMed

Dunker, A Keith; Oldfield, Christopher J; Meng, Jingwei; Romero, Pedro; Yang, Jack Y; Chen, Jessica Walton; Vacic, Vladimir; Obradovic, Zoran; Uversky, Vladimir N

2008-09-16

Our first predictor of protein disorder was published just over a decade ago in the Proceedings of the IEEE International Conference on Neural Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997) Identifying disordered regions in proteins from amino acid sequence. Proceedings of the IEEE International Conference on Neural Networks, 1: 90-95). By now more than twenty other laboratory groups have joined the efforts to improve the prediction of protein disorder. While the various prediction methodologies used for protein intrinsic disorder resemble those methodologies used for secondary structure prediction, the two types of structures are entirely different. For example, the two structural classes have very different dynamic properties, with the irregular secondary structure class being much less mobile than the disorder class. The prediction of secondary structure has been useful. On the other hand, the prediction of intrinsic disorder has been revolutionary, leading to major modifications of the more than 100 year-old views relating protein structure and function. Experimentalists have been providing evidence over many decades that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. In addition, experimentalists are also showing that, for many proteins, their functions depend on the unstructured rather than structured state; such results are in marked contrast to the greater than hundred year old views such as the lock and key hypothesis. Despite extensive data on many important examples, including disease-associated proteins, the importance of disorder for protein function has been largely ignored. Indeed, to our knowledge, current biochemistry books don't present even one acknowledged example of a disorder-dependent function, even though some reports of disorder-dependent functions are more than 50 years old. The results from genome-wide predictions of intrinsic disorder and the results from other bioinformatics studies of intrinsic disorder are demanding attention for these proteins. Disorder prediction has been important for showing that the relatively few experimentally characterized examples are members of a very large collection of related disordered proteins that are wide-spread over all three domains of life. Many significant biological functions are now known to depend directly on, or are importantly associated with, the unfolded or partially folded state. Here our goal is to review the key discoveries and to weave these discoveries together to support novel approaches for understanding sequence-function relationships. Intrinsically disordered protein is common across the three domains of life, but especially common among the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are frequently, or very likely most often, located within regions of intrinsic disorder. Disorder-to-order transitions are coupled with the adoption of different structures with different partners. Also, the flexibility of intrinsic disorder helps different disordered regions to bind to a common binding site on a common partner. Such capacity for binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which such splicing events map to regions of disorder much more often than to regions of structure. Associating alternative splicing with disorder rather than structure alleviates theoretical and experimentally observed problems associated with the folding of different length, isomeric amino acid sequences. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several recent small molecules of interest as potential drugs have been shown to act by blocking protein-protein interactions based on intrinsic disorder of one of the partners. Study of these examples has led to a new approach for drug discovery, and bioinformatics analysis of the human proteome suggests that various disease-associated proteins are very rich in such disorder-based drug discovery targets.

Workshop on High-Field NMR and Biological Applications

NASA Astrophysics Data System (ADS)

Scientists at the Pacific Northwest Laboratory have been working toward the establishment of a new Molecular Science Research Center (MSRC). The primary scientific thrust of this new research center is in the areas of theoretical chemistry, chemical dynamics, surface and interfacial science, and studies on the structure and interactions of biological macromolecules. The MSRC will provide important new capabilities for studies on the structure of biological macromolecules. The MSRC program includes several types of advanced spectroscopic techniques for molecular structure analysis, and a theory and modeling laboratory for molecular mechanics/dynamics calculations and graphics. It is the goal to closely integrate experimental and theoretical studies on macromolecular structure, and to join these research efforts with those of the molecular biological programs to provide new insights into the structure/function relationships of biological macromolecules. One of the areas of structural biology on which initial efforts in the MSRC will be focused is the application of high field, 2-D NMR to the study of biological macromolecules. First, there is interest in obtaining 3-D structural information on large proteins and oligonucleotides. Second, one of the primary objectives is to closely link theoretical approaches to molecular structure analysis with the results obtained in experimental research using NMR and other spectroscopies.

Human physiology in space

NASA Technical Reports Server (NTRS)

Vernikos, J.

1996-01-01

The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

Geological and Structural Patterns on Titan Enhanced Through Cassini's SAR PCA and High-Resolution Radiometry

NASA Astrophysics Data System (ADS)

Paganelli, F.; Schubert, G.; Lopes, R. M. C.; Malaska, M.; Le Gall, A. A.; Kirk, R. L.

2016-12-01

The current SAR data coverage on Titan encompasses several areas in which multiple radar passes are present and overlapping, providing additional information to aid the interpretation of geological and structural features. We exploit the different combinations of look direction and variable incidence angle to examine Cassini Synthetic Aperture RADAR (SAR) data using the Principal Component Analysis (PCA) technique and high-resolution radiometry, as a tool to aid in the interpretation of geological and structural features. Look direction and variable incidence angle is of particular importance in the analysis of variance in the images, which aid in the perception and identification of geological and structural features, as extensively demonstrated in Earth and planetary examples. The PCA enhancement technique uses projected non-ortho-rectified SAR imagery in order to maintain the inherent differences in scattering and geometric properties due to the different look directions, while enhancing the geometry of surface features. The PC2 component provides a stereo view of the areas in which complex surface features and structural patterns can be enhanced and outlined. We focus on several areas of interest, in older and recently acquired flybys, in which evidence of geological and structural features can be enhanced and outlined in the PC1 and PC2 components. Results of this technique provide enhanced geometry and insights into the interpretation of the observed geological and structural features, thus allowing a better understanding towards the geology and tectonics on Titan.

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

DOE PAGES

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; ...

2015-10-12

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Structural, Functional, and Immunogenic Insights on Cu,Zn Superoxide Dismutase Pathogenic Virulence Factors from Neisseria meningitidis and Brucella abortus

PubMed Central

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.; Cabelli, Diane E.; Bruns, Cami K.; Belzer, Carol A.; Gorringe, Andrew R.; Langford, Paul R.; Tabatabai, Louisa B.; Kroll, J. Simon; Tainer, John A.

2015-01-01

ABSTRACT Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen and general pathogenicity factors and are therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomic details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and of SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly, and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes, and suggest general targets for antibacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors of or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, SODs aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling, and murine infection experiments. We identified virulence determinants common to the two homologs, assembly differences, and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and a basis for SOD-specific drug design and an extension of immunogen design to target two important pathogens that continue to pose global health threats. PMID:26459556

Structural, functional and immunogenic insights on Cu,Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

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

Pratt, Ashley J.; DiDonato, Michael; Shin, David S.

Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and health consequences. Superoxide dismutases are master regulators of reactive oxygen, general pathogenicity factors and therefore therapeutic targets. Cu,Zn superoxide dismutases (SODs) localized to the periplasm promote survival by detoxifying superoxide radicals generated by major host antimicrobial immune responses. We discovered that passive immunization with an antibody directed at N. meningitidis SOD (NmSOD) was protective in a mouse infection model. To define the relevant atomicmore » details and solution assembly states of this important virulence factor, we report high-resolution and X-ray scattering analyses of NmSOD and SOD from B. abortus (BaSOD). The NmSOD structures revealed an auxiliary tetrahedral Cu-binding site bridging the dimer interface; mutational analyses suggested that this metal site contributes to protein stability, with implications for bacterial defense mechanisms. Biochemical and structural analyses informed us about electrostatic substrate guidance, dimer assembly and an exposed C-terminal epitope in the NmSOD dimer. In contrast, the monomeric BaSOD structure provided insights for extending immunogenic peptide epitopes derived from the protein. These collective results reveal unique contributions of SOD to pathogenic virulence, refine predictive motifs for distinguishing SOD classes and suggest general targets for anti-bacterial immune responses. The identified functional contributions, motifs, and targets distinguishing bacterial and eukaryotic SOD assemblies presented here provide a foundation for efforts to develop SOD-specific inhibitors or vaccines against these harmful pathogens. IMPORTANCE By protecting microbes against reactive oxygen insults, Cu,Zn superoxide dismutases (SODs) aid survival of many bacteria within their hosts. Despite the ubiquity and conservation of these key enzymes, notable species-specific differences relevant to pathogenesis remain undefined. To probe mechanisms that govern the functioning of Neisseria meningitidis and Brucella abortus SODs, we used X-ray structures, enzymology, modeling and murine infection experiments. We identified virulence determinants common to both homologs, assembly differences and a unique metal reservoir within meningococcal SOD that stabilizes the enzyme and may provide a safeguard against copper toxicity. The insights reported here provide a rationale and basis for SOD-specific drugs and extension of immunogen design to target two important pathogens that continue to pose global health threats.« less

Stability Mechanisms of a Thermophilic Laccase Probed by Molecular Dynamics

PubMed Central

Christensen, Niels J.; Kepp, Kasper P.

2013-01-01

Laccases are highly stable, industrially important enzymes capable of oxidizing a large range of substrates. Causes for their stability are, as for other proteins, poorly understood. In this work, multiple-seed molecular dynamics (MD) was applied to a Trametes versicolor laccase in response to variable ionic strengths, temperatures, and glycosylation status. Near-physiological conditions provided excellent agreement with the crystal structure (average RMSD ∼0.92 Å) and residual agreement with experimental B-factors. The persistence of backbone hydrogen bonds was identified as a key descriptor of structural response to environment, whereas solvent-accessibility, radius of gyration, and fluctuations were only locally relevant. Backbone hydrogen bonds decreased systematically with temperature in all simulations (∼9 per 50 K), probing structural changes associated with enthalpy-entropy compensation. Approaching T opt (∼350 K) from 300 K, this change correlated with a beginning “unzipping” of critical β-sheets. 0 M ionic strength triggered partial denucleation of the C-terminal (known experimentally to be sensitive) at 400 K, suggesting a general salt stabilization effect. In contrast, F− (but not Cl−) specifically impaired secondary structure by formation of strong hydrogen bonds with backbone NH, providing a mechanism for experimentally observed small anion destabilization, potentially remedied by site-directed mutagenesis at critical intrusion sites. N-glycosylation was found to support structural integrity by increasing persistent backbone hydrogen bonds by ∼4 across simulations, mainly via prevention of F− intrusion. Hydrogen-bond loss in distinct loop regions and ends of critical β-sheets suggest potential strategies for laboratory optimization of these industrially important enzymes. PMID:23658618

Cancer-Related Analysis of Variants Toolkit (CRAVAT) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

CRAVAT is an easy to use web-based tool for analysis of cancer variants (missense, nonsense, in-frame indel, frameshift indel, splice site). CRAVAT provides scores and a variety of annotations that assist in identification of important variants. Results are provided in an interactive, highly graphical webpage and include annotated 3D structure visualization. CRAVAT is also available for local or cloud-based installation as a Docker container. MuPIT provides 3D visualization of mutation clusters and functional annotation and is now integrated with CRAVAT.

Computational tools for multi-linked flexible structures

NASA Technical Reports Server (NTRS)

Lee, Gordon K. F.; Brubaker, Thomas A.; Shults, James R.

1990-01-01

A software module which designs and tests controllers and filters in Kalman Estimator form, based on a polynomial state-space model is discussed. The user-friendly program employs an interactive graphics approach to simplify the design process. A variety of input methods are provided to test the effectiveness of the estimator. Utilities are provided which address important issues in filter design such as graphical analysis, statistical analysis, and calculation time. The program also provides the user with the ability to save filter parameters, inputs, and outputs for future use.

Structural and calorimetric studies demonstrate that the hepatocyte nuclear factor 1β (HNF1β) transcription factor is imported into the nucleus via a monopartite NLS sequence.

PubMed

Wiedmann, Mareike M; Aibara, Shintaro; Spring, David R; Stewart, Murray; Brenton, James D

2016-09-01

The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in ovarian clear cell carcinoma (CCC) and is a potential therapeutic target. To explore potential approaches that block HNF1β transcription we have identified and characterised extensively the nuclear localisation signal (NLS) for HNF1β and its interactions with the nuclear protein import receptor, Importin-α. Pull-down assays demonstrated that the DNA binding domain of HNF1β interacted with a spectrum of Importin-α isoforms and deletion constructs tagged with eGFP confirmed that the HNF1β (229)KKMRRNR(235) sequence was essential for nuclear localisation. We further characterised the interaction between the NLS and Importin-α using complementary biophysical techniques and have determined the 2.4Å resolution crystal structure of the HNF1β NLS peptide bound to Importin-α. The functional, biochemical, and structural characterisation of the nuclear localisation signal present on HNF1β and its interaction with the nuclear import protein Importin-α provide the basis for the development of compounds targeting transcription factor HNF1β via its nuclear import pathway. Copyright © 2016. Published by Elsevier Inc.

Polymer-induced compression of biological hydrogels

NASA Astrophysics Data System (ADS)

Datta, Sujit; Preska Steinberg, Asher; Ismagilov, Rustem

Hydrogels - such as mucus, blood clots, and the extracellular matrix - provide critical functions in biological systems. However, little is known about how their structure is influenced by many of the polymeric materials they come into contact with regularly. Here, we focus on one critically important biological hydrogel: colonic mucus. While several biological processes are thought to potentially regulate the mucus hydrogel structure, the polymeric composition of the gut environment has been ignored. We use Flory-Huggins solution theory to characterize polymer-mucus interactions. We find that gut polymers, including those small enough to penetrate the mucus hydrogel, can in fact alter mucus structure, changing its equilibrium degree of swelling and forcing it to compress. The extent of compression increases with increasing polymer concentration and size. We use experiments on mice to verify these predictions with common dietary and therapeutic gut polymers. Our results provide a foundation for investigating similar, previously overlooked, polymer-induced effects in other biological hydrogels.

Conformation guides molecular efficacy in docking screens of activated β-2 adrenergic G protein coupled receptor.

PubMed

Weiss, Dahlia R; Ahn, SeungKirl; Sassano, Maria F; Kleist, Andrew; Zhu, Xiao; Strachan, Ryan; Roth, Bryan L; Lefkowitz, Robert J; Shoichet, Brian K

2013-05-17

A prospective, large library virtual screen against an activated β2-adrenergic receptor (β2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists. In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling. This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable. However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated β2AR structure returned few hits of only marginal potency.

Temperature-independent fiber-Bragg-grating-based atmospheric pressure sensor

NASA Astrophysics Data System (ADS)

Zhang, Zhiguo; Shen, Chunyan; Li, Luming

2018-03-01

Atmospheric pressure is an important way to achieve a high degree of measurement for modern aircrafts, moreover, it is also an indispensable parameter in the meteorological telemetry system. With the development of society, people are increasingly concerned about the weather. Accurate and convenient atmospheric pressure parameters can provide strong support for meteorological analysis. However, electronic atmospheric pressure sensors currently in application suffer from several shortcomings. After an analysis and discussion, we propose an innovative structural design, in which a vacuum membrane box and a temperature-independent strain sensor based on an equal strength cantilever beam structure and fiber Bragg grating (FBG) sensors are used. We provide experimental verification of that the atmospheric pressure sensor device has the characteristics of a simple structure, lack of an external power supply, automatic temperature compensation, and high sensitivity. The sensor system has good sensitivity, which can be up to 100 nm/MPa, and repeatability. In addition, the device exhibits desired hysteresis.

Lateral Structure Formation in Polyelectrolyte Brushes Induced by Multivalent Ions

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

Brettmann, Blair; Pincus, Philip; Tirrell, Matthew

2017-01-13

We provide a theoretical model for the collapse of polyelectrolyte brushes in the presence of multivalent ions, focusing on the formation of lateral inhomogeneties in the collapsed state. Polyelectrolyte brushes are important in a variety of applications, including stabilizing colloidal particles and lubricating surfaces. Many uses rely on the extension of the densely grafted polymer chains from the surface in the extended brush morphology. In the presence Extended Brush of multivalent ions, brushes are significantly shorter than in monovalent ionic solutions, which greatly affects their properties. We base our theoretical analysis on an analogous collapse of polyelectrolyte brushes in amore » poor solvent, providing an energy balance representation for pinned micelles and cylindrical bundles. The equilibrium brush heights predicted for these structures are of a similar magnitude to those measured experimentally. The formation of lateral structures can open new avenues for stimuli-responsive applications that rely on nanoscale pattern formation on surfaces.« less

Water oxidation chemistry of photosystem II.

PubMed

Brudvig, Gary W

2008-03-27

Photosystem II (PSII) uses light energy to split water into protons, electrons and O2. In this reaction, nature has solved the difficult chemical problem of efficient four-electron oxidation of water to yield O2 without significant amounts of reactive intermediate species such as superoxide, hydrogen peroxide and hydroxyl radicals. In order to use nature's solution for the design of artificial catalysts that split water, it is important to understand the mechanism of the reaction. The recently published X-ray crystal structures of cyanobacterial PSII complexes provide information on the structure of the Mn and Ca ions, the redox-active tyrosine called YZ and the surrounding amino acids that comprise the O2-evolving complex (OEC). The emerging structure of the OEC provides constraints on the different hypothesized mechanisms for O2 evolution. The water oxidation mechanism of PSII is discussed in the light of biophysical and computational studies, inorganic chemistry and X-ray crystallographic information.

Interplay of weak interactions in the atom-by-atom condensation of xenon within quantum boxes

PubMed Central

Nowakowska, Sylwia; Wäckerlin, Aneliia; Kawai, Shigeki; Ivas, Toni; Nowakowski, Jan; Fatayer, Shadi; Wäckerlin, Christian; Nijs, Thomas; Meyer, Ernst; Björk, Jonas; Stöhr, Meike; Gade, Lutz H.; Jung, Thomas A.

2015-01-01

Condensation processes are of key importance in nature and play a fundamental role in chemistry and physics. Owing to size effects at the nanoscale, it is conceptually desired to experimentally probe the dependence of condensate structure on the number of constituents one by one. Here we present an approach to study a condensation process atom-by-atom with the scanning tunnelling microscope, which provides a direct real-space access with atomic precision to the aggregates formed in atomically defined ‘quantum boxes’. Our analysis reveals the subtle interplay of competing directional and nondirectional interactions in the emergence of structure and provides unprecedented input for the structural comparison with quantum mechanical models. This approach focuses on—but is not limited to—the model case of xenon condensation and goes significantly beyond the well-established statistical size analysis of clusters in atomic or molecular beams by mass spectrometry. PMID:25608225

Secbase: database module to retrieve secondary structure elements with ligand binding motifs.

PubMed

Koch, Oliver; Cole, Jason; Block, Peter; Klebe, Gerhard

2009-10-01

Secbase is presented as a novel extension module of Relibase. It integrates the information about secondary structure elements into the retrieval facilities of Relibase. The data are accessible via the extended Relibase user interface, and integrated retrieval queries can be addressed using an extended version of Reliscript. The primary information about alpha-helices and beta-sheets is used as provided by the PDB. Furthermore, a uniform classification of all turn families, based on recent clustering methods, and a new helix assignment that is based on this turn classification has been included. Algorithms to analyze the geometric features of helices and beta-strands were also implemented. To demonstrate the performance of the Secbase implementation, some application examples are given. They provide new insights into the involvement of secondary structure elements in ligand binding. A survey of water molecules detected next to the N-terminus of helices is analyzed to show their involvement in ligand binding. Additionally, the parallel oriented NH groups at the alpha-helix N-termini provide special binding motifs to bind particular ligand functional groups with two adjacent oxygen atoms, e.g., as found in negatively charged carboxylate or phosphate groups, respectively. The present study also shows that the specific structure of the first turn of alpha-helices provides a suitable explanation for stabilizing charged structures. The magnitude of the overall helix macrodipole seems to have no or only a minor influence on binding. Furthermore, an overview of the involvement of secondary structure elements with the recognition of some important endogenous ligands such as cofactors shows some distinct preference for particular binding motifs and amino acids.

Research resource: Update and extension of a glycoprotein hormone receptors web application.

PubMed

Kreuchwig, Annika; Kleinau, Gunnar; Kreuchwig, Franziska; Worth, Catherine L; Krause, Gerd

2011-04-01

The SSFA-GPHR (Sequence-Structure-Function-Analysis of Glycoprotein Hormone Receptors) database provides a comprehensive set of mutation data for the glycoprotein hormone receptors (covering the lutropin, the FSH, and the TSH receptors). Moreover, it provides a platform for comparison and investigation of these homologous receptors and helps in understanding protein malfunctions associated with several diseases. Besides extending the data set (> 1100 mutations), the database has been completely redesigned and several novel features and analysis tools have been added to the web site. These tools allow the focused extraction of semiquantitative mutant data from the GPHR subtypes and different experimental approaches. Functional and structural data of the GPHRs are now linked interactively at the web interface, and new tools for data visualization (on three-dimensional protein structures) are provided. The interpretation of functional findings is supported by receptor morphings simulating intramolecular changes during the activation process, which thus help to trace the potential function of each amino acid and provide clues to the local structural environment, including potentially relocated spatial counterpart residues. Furthermore, double and triple mutations are newly included to allow the analysis of their functional effects related to their spatial interrelationship in structures or homology models. A new important feature is the search option and data visualization by interactive and user-defined snake-plots. These new tools allow fast and easy searches for specific functional data and thereby give deeper insights in the mechanisms of hormone binding, signal transduction, and signaling regulation. The web application "Sequence-Structure-Function-Analysis of GPHRs" is accessible on the internet at http://www.ssfa-gphr.de/.

A Study to Understand the Potential Vulnerabilities to the Foundations of Historic Structures in Coastal Areas

NASA Astrophysics Data System (ADS)

Hall, C. L.; Curran, B.; Jefferson, M.; Routhier, M.; Mulukutla, G. K.

2011-12-01

Sea level rise, one of the most important manifestations of climate change is expected to result in increased coastal erosion and storm surge flooding. This work reports on a project undertaken to assess the vulnerability of foundations of historic structures in coastal areas to the potential consequences from climate change resulting from increased storm surge flooding. Foundations of historic buildings are especially vulnerable to the seepage and ground water intrusion. Many historic structures themselves are used to house valuable historic collections making it all the important to preserve and protect these structures. Data collected from a field subsurface geophysical survey, geospatial field survey, and a simulation to understand the hydrological conditions of the site useful to build an understanding of threats to foundations of historic structures located on the coast. The study site chosen for this project is the Strawbery Banke Living History Museum, in Portsmouth, NH. Located very close to the banks of the Piscataqua River at its meeting point with the Atlantic Ocean, it consists of many buildings of historical importance dating as far back as 1690. Upstream of the river is the tidal estuary system, the Great Bay which itself is formed by a confluence of seven major rivers, making it a highly dynamic, tide-dominated body of fresh and saltwater. Strawbery Banke is representative of historic structures, located on the Northeastern coast of the US, that will likely be impacted by climate change. The primary threat to the sub-structures for the site is Puddle Dock; a tidal inlet , that lies at the heart of the facility, that once provided direct river access to Strawbery Banke (and since filled around 1900). Results from the long term deployment of in -situ water level loggers in test wells, temperature and relative humidity sensors, and a ground penetration radar survey of the Puddle Dock, along with the detailed fine-scale elevation survey of the site provide a window into the seasonality of ground water levels and the dynamic equilibrium of fresh and saltwater. Initial analysis of the data indicates that at present Puddle Dock, acts as a conduit for tidal flows, albeit in a restrained manner. This can be attributed to the very unscientific way that it was filled perhaps with garbage, and other waste. It is anticipated the principles applied for this work can be replicated for assessing the vulnerability of other at-risk historical structures in the Northeastern US. Support for purchase of hardware came from National Geographic Society's Waitt Grant program, and the Undergraduate scholarships support was provided by a grant from University of New Hampshire's Joan and James Leitzel Center for Mathematics, Science and Engineering Education.

Ferroelectric Domain Structure and Local Piezoelectric Properties of Lead-Free (Ka0.5Na0.5)NbO3 and BiFeO3-Based Piezoelectric Ceramics

PubMed Central

Alikin, Denis; Turygin, Anton; Kholkin, Andrei; Shur, Vladimir

2017-01-01

Recent advances in the development of novel methods for the local characterization of ferroelectric domains open up new opportunities not only to image, but also to control and to create desired domain configurations (domain engineering). The morphotropic and polymorphic phase boundaries that are frequently used to increase the electromechanical and dielectric performance of ferroelectric ceramics have a tremendous effect on the domain structure, which can serve as a signature of complex polarization states and link local and macroscopic piezoelectric and dielectric responses. This is especially important for the study of lead-free ferroelectric ceramics, which is currently replacing traditional lead-containing materials, and great efforts are devoted to increasing their performance to match that of lead zirconate titanate (PZT). In this work, we provide a short overview of the recent progress in the imaging of domain structure in two major families of ceramic lead-free systems based on BiFeO3 (BFO) and (Ka0.5Na0.5)NbO3 (KNN). This can be used as a guideline for the understanding of domain processes in lead-free piezoelectric ceramics and provide further insight into the mechanisms of structure–property relationship in these technologically important material families. PMID:28772408

Analysis of the Free-Energy Surface of Proteins from Reversible Folding Simulations

PubMed Central

Allen, Lucy R.; Krivov, Sergei V.; Paci, Emanuele

2009-01-01

Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical λ-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins. PMID:19593364

Analysis of the free-energy surface of proteins from reversible folding simulations.

PubMed

Allen, Lucy R; Krivov, Sergei V; Paci, Emanuele

2009-07-01

Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical lambda-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins.

Reconstruction of vessel structures from serial whole slide sections of murine liver samples

NASA Astrophysics Data System (ADS)

Schwier, Michael; Hahn, Horst K.; Dahmen, Uta; Dirsch, Olaf

2013-03-01

Image-based analysis of the vascular structures of murine liver samples is an important tool for scientists to understand liver physiology and morphology. Typical assessment methods are MicroCT, which allows for acquiring images of the whole organ while lacking resolution for fine details, and confocal laser scanning microscopy, which allows detailed insights into fine structures while lacking the broader context. Imaging of histological serial whole slide sections is a recent technology able to fill this gap, since it provides a fine resolution up to the cellular level, but on a whole organ scale. However, whole slide imaging is a modality providing only 2D images. Therefore the challenge is to use stacks of serial sections from which to reconstruct the 3D vessel structures. In this paper we present a semi-automatic procedure to achieve this goal. We employ an automatic method that detects vessel structures based on continuity and shape characteristics. Furthermore it supports the user to perform manual corrections where required. With our methods we were able to successfully extract and reconstruct vessel structures from a stack of 100 and a stack of 397 serial sections of a mouse liver lobe, thus proving the potential of our approach.

Integrated material state awareness system with self-learning symbiotic diagnostic algorithms and models

NASA Astrophysics Data System (ADS)

Banerjee, Sourav; Liu, Lie; Liu, S. T.; Yuan, Fuh-Gwo; Beard, Shawn

2011-04-01

Materials State Awareness (MSA) goes beyond traditional NDE and SHM in its challenge to characterize the current state of material damage before the onset of macro-damage such as cracks. A highly reliable, minimally invasive system for MSA of Aerospace Structures, Naval structures as well as next generation space systems is critically needed. Development of such a system will require a reliable SHM system that can detect the onset of damage well before the flaw grows to a critical size. Therefore, it is important to develop an integrated SHM system that not only detects macroscale damages in the structures but also provides an early indication of flaw precursors and microdamages. The early warning for flaw precursors and their evolution provided by an SHM system can then be used to define remedial strategies before the structural damage leads to failure, and significantly improve the safety and reliability of the structures. Thus, in this article a preliminary concept of developing the Hybrid Distributed Sensor Network Integrated with Self-learning Symbiotic Diagnostic Algorithms and Models to accurately and reliably detect the precursors to damages that occur to the structure are discussed. Experiments conducted in a laboratory environment shows potential of the proposed technique.

Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale.

PubMed

Liu, Siyang; Huang, Shujia; Rao, Junhua; Ye, Weijian; Krogh, Anders; Wang, Jun

2015-01-01

Comprehensive recognition of genomic variation in one individual is important for understanding disease and developing personalized medication and treatment. Many tools based on DNA re-sequencing exist for identification of single nucleotide polymorphisms, small insertions and deletions (indels) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction of population-scale pan-genomes. Our study also highlights the usefulness of the de novo assembly strategy for definition of genome structure.

Effects of the enlargement of poly-glutamine segments on the structure and folding of ataxin-2 and ataxin-3 proteins

PubMed Central

Wen, Jingran; Scoles, Daniel R.; Facelli, Julio C.

2017-01-01

Spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) are two common autosomal-dominant inherited ataxia syndromes, both of which are related to the unstable expansion of tri-nucleotide CAG repeats in the coding region of the related ATXN2 and ATXN3 genes, respectively. The poly-glutamine (poly-Q) tract encoded by the CAG repeats has long been recognized as an important factor in disease pathogenesis and progress. In this study, using the I-TASSER method for 3D structure prediction, we investigated the effect of poly-Q tract enlargement on the structure and folding of ataxin-2 and ataxin-3 proteins. Our results show good agreement with the known experimental structures of the Josephin and UIM domains providing credence to the simulation results presented here, which show that the enlargement of the poly-Q region not only affects the local structure of these regions but also affects the structures of functional domains as well as the whole protein. The changes observed in the predicted models of the UIM domains in ataxin-3 when the poly-Q track is enlarged provide new insights on possible pathogenic mechanisms. PMID:26861241

Atomic scale chemical tomography of human bone

NASA Astrophysics Data System (ADS)

Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

2017-01-01

Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale - the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

The CONNECT project: Combining macro- and micro-structure.

PubMed

Assaf, Yaniv; Alexander, Daniel C; Jones, Derek K; Bizzi, Albero; Behrens, Tim E J; Clark, Chris A; Cohen, Yoram; Dyrby, Tim B; Huppi, Petra S; Knoesche, Thomas R; Lebihan, Denis; Parker, Geoff J M; Poupon, Cyril; Anaby, Debbie; Anwander, Alfred; Bar, Leah; Barazany, Daniel; Blumenfeld-Katzir, Tamar; De-Santis, Silvia; Duclap, Delphine; Figini, Matteo; Fischi, Elda; Guevara, Pamela; Hubbard, Penny; Hofstetter, Shir; Jbabdi, Saad; Kunz, Nicolas; Lazeyras, Francois; Lebois, Alice; Liptrot, Matthew G; Lundell, Henrik; Mangin, Jean-François; Dominguez, David Moreno; Morozov, Darya; Schreiber, Jan; Seunarine, Kiran; Nava, Simone; Poupon, Cyril; Riffert, Till; Sasson, Efrat; Schmitt, Benoit; Shemesh, Noam; Sotiropoulos, Stam N; Tavor, Ido; Zhang, Hui Gary; Zhou, Feng-Lei

2013-10-15

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison of Canadian and Swiss Surgical Training Curricula: Moving on Toward Competency-Based Surgical Education.

PubMed

Hoffmann, Henry; Oertli, Daniel; Mechera, Robert; Dell-Kuster, Salome; Rosenthal, Rachel; Reznick, Richard; MacDonald, Hugh

Quality of surgical training in the era of resident duty-hour restrictions (RDHR) is part of an ongoing debate. Most training elements are provided during surgical service. As exposure to surgical procedures is important but time-consuming, RDHR may affect quality of surgical training. Providing structured training elements may help to compensate for this shortcoming. This binational anonymous questionnaire-based study evaluates frequency, time, and structure of surgical training programs at 2 typical academic teaching hospitals with different RDHR. Departments of Surgery of University of Basel (Basel, Switzerland) and the Queen's University (Kingston, Ontario, Canada). Surgical consultants and residents of the Queen's University Hospital (Kingston, Ontario, Canada) and the University Hospital Basel (Basel, Switzerland) were eligible for this study. Questionnaire response rate was 37% (105/284). Queen's residents work 80 hours per week, receiving 7 hours of formal training (8.8% of workweek). Basel residents work 60 hours per week, including 1 hour of formal training (1.7% of working time). Queen's faculty and residents rated their program as "structured" or "rather structured" in contrast to Basel faculty and residents who rated their programs as "neutral" in structure or "unstructured." Respondents identified specific structured training elements more frequently at Queen's than in Basel. Two-thirds of residents responded that they seek out additional surgical experiences through voluntary extra work. Basel participants articulated a stronger need for improvement of current surgical training. Although Basel residents and consultants in both institutions fear negative influence of RDHR on the training program, this was not the case in Queen's residents. Providing more structured surgical training elements may be advantageous in providing optimal-quality surgical education in an era of work-hour restrictions. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

The influence of zeolites fly ash bead/TiO2 composite material surface morphologies on their adsorption and photocatalytic performance

NASA Astrophysics Data System (ADS)

Yang, Lu; Wang, Fazhou; Hakki, Amer; Macphee, Donald E.; Liu, Peng; Hu, Shuguang

2017-01-01

A low cost zeolite fly ash bead/TiO2 (ZFABT) composite materials with various surface structure features were prepared for describing those structures importance on TiO2 coating, adsorbability and photocatalytic performances. The results indicated that fly ash bead (FAB) surface was significantly altered by the precipitation/growth of secondary zeolite phases after alkali activation, which generates abundant open pores and stacked petal-liked spherical beads (∼2 μm, Sodalite zeolites). More importantly, this porosity increases as activation time was increased from 2 h to 12 h, through the precipitation of sodalite and then Na-P1 (lamellar crystals) and Na-X (octahedral crystals) zeolite structures. Compared to those of unsupported TiO2 or inactivated support/TiO2 samples, all of ZFABT samples exhibited a higher adsorption capacity and photocatalytic efficiency for RhB removal. However, adsorption is not only one factor to influence TiO2 surface reaction, the intraparticle diffusion rate of rhodamine B (RhB) molecules, and light penetration are also important parameters. Alkali activated 4 h ZFABT sample exhibited the highest photocatalytic activity, indicating its pore structure provided a better balance for those parameters to achieve a synergistic adsorption/photocatalytic process. The kinetics model suggested its high intraparticle diffusion rate allowed for more RhB molecules to easily reach the reaction surface, which is more important for high efficiency photocatalysis.

Structuration and sensemaking: frameworks for understanding the management of health information systems in the ICU.

PubMed

Ghosh, Tip

2007-01-01

This paper will describe two alternate conceptual frameworks (i.e. Structuration and Sensemaking) that will help to describe and provide insight into how best to implement health information systems in ICUs throughout the globe. Structuration and sensemaking are two competing ways to view the social world within hospitals. To examine the impact of information technology in health care organizations, it is important to explore the dynamic interplay between clinical decisionmaking, outcomes of HIT implementation, and individual characteristics of the organizational setting. The adaptation of information technology within health care organizations is by its very nature quite complex. The recursive pattern of social interactions that shape the implementation of technologies within that setting is key. Structuration theory provides an understanding of human work as social interaction within that organizational culture, mediated by artifacts such as tools, language, rules and procedures, and open to change. The ICU provides multiple opportunities for sensemaking. It involves caring for multiple patients simultaneously; is subject to high levels of uncertainty and is provided under significant time constraints. It is highly interdependent work, necessitating shared sensemaking as well as individual sensemaking. Sensemaking is made partially visible in this context as clinicians communicate to each other what they think is the cause of the patient's symptoms and how to treat them in the form of discussions about patient care, consultation requests, ancillary testing, and the electronic medical record. The collaborative nature of work in the ICU lends itself to the application of sensemaking and structuration theories.

Forest biomass, canopy structure, and species composition relationships with multipolarization L-band synthetic aperture radar data

NASA Technical Reports Server (NTRS)

Sader, Steven A.

1987-01-01

The effect of forest biomass, canopy structure, and species composition on L-band synthetic aperature radar data at 44 southern Mississippi bottomland hardwood and pine-hardwood forest sites was investigated. Cross-polarization mean digital values for pine forests were significantly correlated with green weight biomass and stand structure. Multiple linear regression with five forest structure variables provided a better integrated measure of canopy roughness and produced highly significant correlation coefficients for hardwood forests using HV/VV ratio only. Differences in biomass levels and canopy structure, including branching patterns and vertical canopy stratification, were important sources of volume scatter affecting multipolarization radar data. Standardized correction techniques and calibration of aircraft data, in addition to development of canopy models, are recommended for future investigations of forest biomass and structure using synthetic aperture radar.

New methodologies for multi-scale time-variant reliability analysis of complex lifeline networks

NASA Astrophysics Data System (ADS)

Kurtz, Nolan Scot

The cost of maintaining existing civil infrastructure is enormous. Since the livelihood of the public depends on such infrastructure, its state must be managed appropriately using quantitative approaches. Practitioners must consider not only which components are most fragile to hazard, e.g. seismicity, storm surge, hurricane winds, etc., but also how they participate on a network level using network analysis. Focusing on particularly damaged components does not necessarily increase network functionality, which is most important to the people that depend on such infrastructure. Several network analyses, e.g. S-RDA, LP-bounds, and crude-MCS, and performance metrics, e.g. disconnection bounds and component importance, are available for such purposes. Since these networks are existing, the time state is also important. If networks are close to chloride sources, deterioration may be a major issue. Information from field inspections may also have large impacts on quantitative models. To address such issues, hazard risk analysis methodologies for deteriorating networks subjected to seismicity, i.e. earthquakes, have been created from analytics. A bridge component model has been constructed for these methodologies. The bridge fragilities, which were constructed from data, required a deeper level of analysis as these were relevant for specific structures. Furthermore, chloride-induced deterioration network effects were investigated. Depending on how mathematical models incorporate new information, many approaches are available, such as Bayesian model updating. To make such procedures more flexible, an adaptive importance sampling scheme was created for structural reliability problems. Additionally, such a method handles many kinds of system and component problems with singular or multiple important regions of the limit state function. These and previously developed analysis methodologies were found to be strongly sensitive to the network size. Special network topologies may be more or less computationally difficult, while the resolution of the network also has large affects. To take advantage of some types of topologies, network hierarchical structures with super-link representation have been used in the literature to increase the computational efficiency by analyzing smaller, densely connected networks; however, such structures were based on user input and subjective at times. To address this, algorithms must be automated and reliable. These hierarchical structures may indicate the structure of the network itself. This risk analysis methodology has been expanded to larger networks using such automated hierarchical structures. Component importance is the most important objective from such network analysis; however, this may only provide the information of which bridges to inspect/repair earliest and little else. High correlations influence such component importance measures in a negative manner. Additionally, a regional approach is not appropriately modelled. To investigate a more regional view, group importance measures based on hierarchical structures have been created. Such structures may also be used to create regional inspection/repair approaches. Using these analytical, quantitative risk approaches, the next generation of decision makers may make both component and regional-based optimal decisions using information from both network function and further effects of infrastructure deterioration.

Design of Accelerator Online Simulator Server Using Structured Data

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

Shen, Guobao; /Brookhaven; Chu, Chungming

2012-07-06

Model based control plays an important role for a modern accelerator during beam commissioning, beam study, and even daily operation. With a realistic model, beam behaviour can be predicted and therefore effectively controlled. The approach used by most current high level application environments is to use a built-in simulation engine and feed a realistic model into that simulation engine. Instead of this traditional monolithic structure, a new approach using a client-server architecture is under development. An on-line simulator server is accessed via network accessible structured data. With this approach, a user can easily access multiple simulation codes. This paper describesmore » the design, implementation, and current status of PVData, which defines the structured data, and PVAccess, which provides network access to the structured data.« less

Crystal structure of isoflavone reductase from alfalfa (Medicago sativa L.).

PubMed

Wang, Xiaoqiang; He, Xianzhi; Lin, Jianqiao; Shao, Hui; Chang, Zhenzhan; Dixon, Richard A

2006-05-19

Isoflavonoids play important roles in plant defense and exhibit a range of mammalian health-promoting activities. Isoflavone reductase (IFR) specifically recognizes isoflavones and catalyzes a stereospecific NADPH-dependent reduction to (3R)-isoflavanone. The crystal structure of Medicago sativa IFR with deletion of residues 39-47 has been determined at 1.6A resolution. Structural analysis, molecular modeling and docking, and comparison with the structures of other NADPH-dependent enzymes, defined the putative binding sites for co-factor and substrate and potential key residues for enzyme activity and substrate specificity. Further mutagenesis has confirmed the role of Lys144 as a catalytic residue. This study provides a structural basis for understanding the enzymatic mechanism and substrate specificity of IFRs as well as the functions of IFR-like proteins.

An integrated approach using orthogonal analytical techniques to characterize heparan sulfate structure.

PubMed

Beccati, Daniela; Lech, Miroslaw; Ozug, Jennifer; Gunay, Nur Sibel; Wang, Jing; Sun, Elaine Y; Pradines, Joël R; Farutin, Victor; Shriver, Zachary; Kaundinya, Ganesh V; Capila, Ishan

2017-02-01

Heparan sulfate (HS), a glycosaminoglycan present on the surface of cells, has been postulated to have important roles in driving both normal and pathological physiologies. The chemical structure and sulfation pattern (domain structure) of HS is believed to determine its biological function, to vary across tissue types, and to be modified in the context of disease. Characterization of HS requires isolation and purification of cell surface HS as a complex mixture. This process may introduce additional chemical modification of the native residues. In this study, we describe an approach towards thorough characterization of bovine kidney heparan sulfate (BKHS) that utilizes a variety of orthogonal analytical techniques (e.g. NMR, IP-RPHPLC, LC-MS). These techniques are applied to characterize this mixture at various levels including composition, fragment level, and overall chain properties. The combination of these techniques in many instances provides orthogonal views into the fine structure of HS, and in other instances provides overlapping / confirmatory information from different perspectives. Specifically, this approach enables quantitative determination of natural and modified saccharide residues in the HS chains, and identifies unusual structures. Analysis of partially digested HS chains allows for a better understanding of the domain structures within this mixture, and yields specific insights into the non-reducing end and reducing end structures of the chains. This approach outlines a useful framework that can be applied to elucidate HS structure and thereby provides means to advance understanding of its biological role and potential involvement in disease progression. In addition, the techniques described here can be applied to characterization of heparin from different sources.

Health care providers' perceived barriers to and need for the implementation of a national integrated health care standard on childhood obesity in the Netherlands - a mixed methods approach.

PubMed

Schalkwijk, Annemarie A H; Nijpels, Giel; Bot, Sandra D M; Elders, Petra J M

2016-03-08

In 2010, a national integrated health care standard for (childhood) obesity was published and disseminated in the Netherlands. The aim of this study is to gain insight into the needs of health care providers and the barriers they face in terms of implementing this integrated health care standard. A mixed-methods approach was applied using focus groups, semi-structured, face-to-face interviews and an e-mail-based internet survey. The study's participants included: general practitioners (GPs) (focus groups); health care providers in different professions (face-to-face interviews) and health care providers, including GPs; youth health care workers; pediatricians; dieticians; psychologists and physiotherapists (survey). First, the transcripts from the focus groups were analyzed thematically. The themes identified in this process were then used to analyze the interviews. The results of the analysis of the qualitative data were used to construct the statements used in the e-mail-based internet survey. Responses to items were measured on a 5-point Likert scale and were categorized into three outcomes: 'agree' or 'important' (response categories 1 and 2), 'disagree' or 'not important'. Twenty-seven of the GPs that were invited (51 %) participated in four focus groups. Seven of the nine health care professionals that were invited (78 %) participated in the interviews and 222 questionnaires (17 %) were returned and included in the analysis. The following key barriers were identified with regard to the implementation of the integrated health care standard: reluctance to raise the subject; perceived lack of motivation and knowledge on the part of the parents; previous negative experiences with lifestyle programs; financial constraints and the lack of a structured multidisciplinary approach. The main needs identified were: increased knowledge and awareness on the part of both health care providers and parents/children; a social map of effective intervention; structural funding; task rearrangements; a central care coordinator and structural information feedback from the health care providers involved. The integrated health care standard stipulate that the care of overweight or obese children be provided using an integrated approach. The barriers and needs identified in this study can be used to define strategies to improve the implementation of the integrated health care standard pertaining to overweight and obese children in the Netherlands.

Commercialization of NESSUS: Status

NASA Technical Reports Server (NTRS)

Thacker, Ben H.; Millwater, Harry R.

1991-01-01

A plan was initiated in 1988 to commercialize the Numerical Evaluation of Stochastic Structures Under Stress (NESSUS) probabilistic structural analysis software. The goal of the on-going commercialization effort is to begin the transfer of Probabilistic Structural Analysis Method (PSAM) developed technology into industry and to develop additional funding resources in the general area of structural reliability. The commercialization effort is summarized. The SwRI NESSUS Software System is a general purpose probabilistic finite element computer program using state of the art methods for predicting stochastic structural response due to random loads, material properties, part geometry, and boundary conditions. NESSUS can be used to assess structural reliability, to compute probability of failure, to rank the input random variables by importance, and to provide a more cost effective design than traditional methods. The goal is to develop a general probabilistic structural analysis methodology to assist in the certification of critical components in the next generation Space Shuttle Main Engine.