Sample records for mapping interaction sites

  1. Interactive NCORP Map Details Community Research Sites | Division of Cancer Prevention

    Cancer.gov

    An interactive map of the NCI Community Oncology Research Program (NCORP) with detailed information on hundreds of community sites that take part in clinical trials is available on the NCORP website. NCORP Map NCORP Community Sites, Minority/Underserved Community Sites, and Research Bases |

  2. Mapping Interaction Sites on Human Chemokine Receptors by Deep Mutational Scanning.

    PubMed

    Heredia, Jeremiah D; Park, Jihye; Brubaker, Riley J; Szymanski, Steven K; Gill, Kevin S; Procko, Erik

    2018-06-01

    Chemokine receptors CXCR4 and CCR5 regulate WBC trafficking and are engaged by the HIV-1 envelope glycoprotein gp120 during infection. We combine a selection of human CXCR4 and CCR5 libraries comprising nearly all of ∼7000 single amino acid substitutions with deep sequencing to define sequence-activity landscapes for surface expression and ligand interactions. After consideration of sequence constraints for surface expression, known interaction sites with HIV-1-blocking Abs were appropriately identified as conserved residues following library sorting for Ab binding, validating the use of deep mutational scanning to map functional interaction sites in G protein-coupled receptors. Chemokine CXCL12 was found to interact with residues extending asymmetrically into the CXCR4 ligand-binding cavity, similar to the binding surface of CXCR4 recognized by an antagonistic viral chemokine previously observed crystallographically. CXCR4 mutations distal from the chemokine binding site were identified that enhance chemokine recognition. This included disruptive mutations in the G protein-coupling site that diminished calcium mobilization, as well as conservative mutations to a membrane-exposed site (CXCR4 residues H79 2.45 and W161 4.50 ) that increased ligand binding without loss of signaling. Compared with CXCR4-CXCL12 interactions, CCR5 residues conserved for gp120 (HIV-1 BaL strain) interactions map to a more expansive surface, mimicking how the cognate chemokine CCL5 makes contacts across the entire CCR5 binding cavity. Acidic substitutions in the CCR5 N terminus and extracellular loops enhanced gp120 binding. This study demonstrates how comprehensive mutational scanning can define functional interaction sites on receptors, and novel mutations that enhance receptor activities can be found simultaneously. Copyright © 2018 by The American Association of Immunologists, Inc.

  3. Carbene footprinting accurately maps binding sites in protein-ligand and protein-protein interactions

    NASA Astrophysics Data System (ADS)

    Manzi, Lucio; Barrow, Andrew S.; Scott, Daniel; Layfield, Robert; Wright, Timothy G.; Moses, John E.; Oldham, Neil J.

    2016-11-01

    Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex example, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.

  4. Usability Evaluation of Public Web Mapping Sites

    NASA Astrophysics Data System (ADS)

    Wang, C.

    2014-04-01

    Web mapping sites are interactive maps that are accessed via Webpages. With the rapid development of Internet and Geographic Information System (GIS) field, public web mapping sites are not foreign to people. Nowadays, people use these web mapping sites for various reasons, in that increasing maps and related map services of web mapping sites are freely available for end users. Thus, increased users of web mapping sites led to more usability studies. Usability Engineering (UE), for instance, is an approach for analyzing and improving the usability of websites through examining and evaluating an interface. In this research, UE method was employed to explore usability problems of four public web mapping sites, analyze the problems quantitatively and provide guidelines for future design based on the test results. Firstly, the development progress for usability studies were described, and simultaneously several usability evaluation methods such as Usability Engineering (UE), User-Centered Design (UCD) and Human-Computer Interaction (HCI) were generally introduced. Then the method and procedure of experiments for the usability test were presented in detail. In this usability evaluation experiment, four public web mapping sites (Google Maps, Bing maps, Mapquest, Yahoo Maps) were chosen as the testing websites. And 42 people, who having different GIS skills (test users or experts), gender (male or female), age and nationality, participated in this test to complete the several test tasks in different teams. The test comprised three parts: a pretest background information questionnaire, several test tasks for quantitative statistics and progress analysis, and a posttest questionnaire. The pretest and posttest questionnaires focused on gaining the verbal explanation of their actions qualitatively. And the design for test tasks targeted at gathering quantitative data for the errors and problems of the websites. Then, the results mainly from the test part were analyzed. The

  5. Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation*♦

    PubMed Central

    Yamano, Koji; Queliconi, Bruno B.; Koyano, Fumika; Saeki, Yasushi; Hirokawa, Takatsugu; Tanaka, Keiji; Matsuda, Noriyuki

    2015-01-01

    Damaged mitochondria are eliminated through autophagy machinery. A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser65 by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. PMID:26260794

  6. DIMA 3.0: Domain Interaction Map.

    PubMed

    Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

    2011-01-01

    Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

  7. Facilitating participatory multilevel decision-making by using interactive mental maps.

    PubMed

    Pfeiffer, Constanze; Glaser, Stephanie; Vencatesan, Jayshree; Schliermann-Kraus, Elke; Drescher, Axel; Glaser, Rüdiger

    2008-11-01

    Participation of citizens in political, economic or social decisions is increasingly recognized as a precondition to foster sustainable development processes. Since spatial information is often important during planning and decision making, participatory mapping gains in popularity. However, little attention has been paid to the fact that information must be presented in a useful way to reach city planners and policy makers. Above all, the importance of visualisation tools to support collaboration, analytical reasoning, problem solving and decision-making in analysing and planning processes has been underestimated. In this paper, we describe how an interactive mental map tool has been developed in a highly interdisciplinary disaster management project in Chennai, India. We moved from a hand drawn mental maps approach to an interactive mental map tool. This was achieved by merging socio-economic and geospatial data on infrastructure, local perceptions, coping and adaptation strategies with remote sensing data and modern technology of map making. This newly developed interactive mapping tool allowed for insights into different locally-constructed realities and facilitated the communication of results to the wider public and respective policy makers. It proved to be useful in visualising information and promoting participatory decision-making processes. We argue that the tool bears potential also for health research projects. The interactive mental map can be used to spatially and temporally assess key health themes such as availability of, and accessibility to, existing health care services, breeding sites of disease vectors, collection and storage of water, waste disposal, location of public toilets or defecation sites.

  8. Mapping NEHRP VS30 site classes

    USGS Publications Warehouse

    Holzer, T.L.; Padovani, A.C.; Bennett, M.J.; Noce, T.E.; Tinsley, J. C.

    2005-01-01

    Site-amplification potential in a 140-km2 area on the eastern shore of San Francisco Bay, California, was mapped with data from 210 seismic cone penetration test (SCPT) soundings. NEHRP VS30 values were computed on a 50-m grid by both taking into account the thickness and using mean values of locally measured shear-wave velocities of shallow geologic units. The resulting map of NEHRP VS30 site classes differs from other published maps that (1) do not include unit thickness and (2) are based on regional compilations of velocity. Although much of the area in the new map is now classified as NEHRP Site Class D, the velocities of the geologic deposits within this area are either near the upper or lower VS30 boundary of Class D. If maps of NEHRP site classes are to be based on geologic maps, velocity distributions of geologic units may need to be considered in the definition of VS30 boundaries of NEHRP site classes. ?? 2005, Earthquake Engineering Research Institute.

  9. Protein-Protein Interaction Site Predictions with Three-Dimensional Probability Distributions of Interacting Atoms on Protein Surfaces

    PubMed Central

    Chen, Ching-Tai; Peng, Hung-Pin; Jian, Jhih-Wei; Tsai, Keng-Chang; Chang, Jeng-Yih; Yang, Ei-Wen; Chen, Jun-Bo; Ho, Shinn-Ying; Hsu, Wen-Lian; Yang, An-Suei

    2012-01-01

    Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI) sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins) and were tested on an independent dataset (consisting of 142 proteins). The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted correctly with

  10. Data visualization in interactive maps and time series

    NASA Astrophysics Data System (ADS)

    Maigne, Vanessa; Evano, Pascal; Brockmann, Patrick; Peylin, Philippe; Ciais, Philippe

    2014-05-01

    State-of-the-art data visualization has nothing to do with plots and maps we used few years ago. Many opensource tools are now available to provide access to scientific data and implement accessible, interactive, and flexible web applications. Here we will present a web site opened November 2013 to create custom global and regional maps and time series from research models and datasets. For maps, we explore and get access to data sources from a THREDDS Data Server (TDS) with the OGC WMS protocol (using the ncWMS implementation) then create interactive maps with the OpenLayers javascript library and extra information layers from a GeoServer. Maps become dynamic, zoomable, synchroneaously connected to each other, and exportable to Google Earth. For time series, we extract data from a TDS with the Netcdf Subset Service (NCSS) then display interactive graphs with a custom library based on the Data Driven Documents javascript library (D3.js). This time series application provides dynamic functionalities such as interpolation, interactive zoom on different axes, display of point values, and export to different formats. These tools were implemented for the Global Carbon Atlas (http://www.globalcarbonatlas.org): a web portal to explore, visualize, and interpret global and regional carbon fluxes from various model simulations arising from both human activities and natural processes, a work led by the Global Carbon Project.

  11. Interactive Geophysical Mapping on the Web

    NASA Astrophysics Data System (ADS)

    Meertens, C.; Hamburger, M.; Estey, L.; Weingroff, M.; Deardorff, R.; Holt, W.

    2002-12-01

    We have developed a set of interactive, web-based map utilities that make geophysical results accessible to a large number and variety of users. These tools provide access to pre-determined map regions via a simple Html/JavaScript interface or to user-selectable areas using a Java interface to a Generic Mapping Tools (GMT) engine. Users can access a variety of maps, satellite images, and geophysical data at a range of spatial scales for the earth and other planets of the solar system. Developed initially by UNAVCO for study of global-scale geodynamic processes, users can choose from a variety of base maps (satellite mosaics, global topography, geoid, sea-floor age, strain rate and seismic hazard maps, and others) and can then add a number of geographic and geophysical overlays for example coastlines, political boundaries, rivers and lakes, NEIC earthquake and volcano locations, stress axes, and observed and model plate motion and deformation velocity vectors representing a compilation of 2933 geodetic measurements from around the world. The software design is flexible allowing for construction of special editions for different target audiences. Custom maps been implemented for UNAVCO as the "Jules Verne Voyager" and "Voyager Junior", for the International Lithosphere Project's "Global Strain Rate Map", and for EarthScope Education and Outreach as "EarthScope Voyager Jr.". For the later, a number of EarthScope-specific features have been added, including locations of proposed USArray (seismic), Plate Boundary Observatory (geodetic), and San Andreas Fault Observatory at Depth sites plus detailed maps and geographically referenced examples of EarthScope-related scientific investigations. In addition, we are developing a website that incorporates background materials and curricular activities that encourage users to explore Earth processes. A cluster of map processing computers and nearly a terabyte of disk storage has been assembled to power the generation of

  12. Mapping structural landmarks, ligand binding sites and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions and variation in phenotypes in inherited diseases affecting basement membranes

    PubMed Central

    Des Parkin, J.; San Antonio, James D.; Pedchenko, Vadim; Hudson, Billy; Jensen, Shane T.; Savige, Judy

    2016-01-01

    Collagen IV is the major protein found in basement membranes. It comprises 3 heterotrimers (α1α1α2, α3α4α5, and α5α5α6) that form distinct networks, and are responsible for membrane strength and integrity. We constructed linear maps of the collagen IV heterotrimers (‘interactomes’) that indicated major structural landmarks, known and predicted ligand-binding sites, and missense mutations, in order to identify functional and disease-associated domains, potential interactions between ligands, and genotype-phenotype relationships. The maps documented more than 30 known ligand-binding sites as well as motifs for integrins, heparin, von Willebrand factor (VWF), decorin and bone morphogenetic protein (BMP). They predicted functional domains for angiogenesis and haemostasis, and disease domains for autoimmunity, tumor growth and inhibition, infection and glycation. Cooperative ligand interactions were indicated by binding site proximity, for example, between integrins, matrix metalloproteinases and heparin. The maps indicated that mutations affecting major ligand-binding sites, for example for Von Hippel Lindau (VHL) protein in the α1 chain or integrins in the α5 chain, resulted in distinctive phenotypes (Hereditary Angiopathy, Nephropathy, Aneurysms and muscle Cramps (HANAC) syndrome, and early onset Alport syndrome respectively). These maps further our understanding of basement membrane biology and disease, and suggest novel membrane interactions, functions, and therapeutic targets. PMID:21280145

  13. Direct optical mapping of transcription factor binding sites on field-stretched λ-DNA in nanofluidic devices

    PubMed Central

    Sriram, K. K.; Yeh, Jia-Wei; Lin, Yii-Lih; Chang, Yi-Ren; Chou, Chia-Fu

    2014-01-01

    Mapping transcription factor (TF) binding sites along a DNA backbone is crucial in understanding the regulatory circuits that control cellular processes. Here, we deployed a method adopting bioconjugation, nanofluidic confinement and fluorescence single molecule imaging for direct mapping of TF (RNA polymerase) binding sites on field-stretched single DNA molecules. Using this method, we have mapped out five of the TF binding sites of E. coli RNA polymerase to bacteriophage λ-DNA, where two promoter sites and three pseudo-promoter sites are identified with the corresponding binding frequency of 45% and 30%, respectively. Our method is quick, robust and capable of resolving protein-binding locations with high accuracy (∼ 300 bp), making our system a complementary platform to the methods currently practiced. It is advantageous in parallel analysis and less prone to false positive results over other single molecule mapping techniques such as optical tweezers, atomic force microscopy and molecular combing, and could potentially be extended to general mapping of protein–DNA interaction sites. PMID:24753422

  14. Molecular Interaction Map of the Mammalian Cell Cycle Control and DNA Repair Systems

    PubMed Central

    Kohn, Kurt W.

    1999-01-01

    Eventually to understand the integrated function of the cell cycle regulatory network, we must organize the known interactions in the form of a diagram, map, and/or database. A diagram convention was designed capable of unambiguous representation of networks containing multiprotein complexes, protein modifications, and enzymes that are substrates of other enzymes. To facilitate linkage to a database, each molecular species is symbolically represented only once in each diagram. Molecular species can be located on the map by means of indexed grid coordinates. Each interaction is referenced to an annotation list where pertinent information and references can be found. Parts of the network are grouped into functional subsystems. The map shows how multiprotein complexes could assemble and function at gene promoter sites and at sites of DNA damage. It also portrays the richness of connections between the p53-Mdm2 subsystem and other parts of the network. PMID:10436023

  15. statement of significance, location map, site plan, landscape plan, site ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    statement of significance, location map, site plan, landscape plan, site sections, evolution of cemetery landscape. - San Francisco National Cemetery, 1 Lincoln Boulevard, San Francisco, San Francisco County, CA

  16. Interactive Mapping on Virtual Terrain Models Using RIMS (Real-time, Interactive Mapping System)

    NASA Astrophysics Data System (ADS)

    Bernardin, T.; Cowgill, E.; Gold, R. D.; Hamann, B.; Kreylos, O.; Schmitt, A.

    2006-12-01

    Recent and ongoing space missions are yielding new multispectral data for the surfaces of Earth and other planets at unprecedented rates and spatial resolution. With their high spatial resolution and widespread coverage, these data have opened new frontiers in observational Earth and planetary science. But they have also precipitated an acute need for new analytical techniques. To address this problem, we have developed RIMS, a Real-time, Interactive Mapping System that allows scientists to visualize, interact with, and map directly on, three-dimensional (3D) displays of georeferenced texture data, such as multispectral satellite imagery, that is draped over a surface representation derived from digital elevation data. The system uses a quadtree-based multiresolution method to render in real time high-resolution (3 to 10 m/pixel) data over large (800 km by 800 km) spatial areas. It allows users to map inside this interactive environment by generating georeferenced and attributed vector-based elements that are draped over the topography. We explain the technique using 15 m ASTER stereo-data from Iraq, P.R. China, and other remote locations because our particular motivation is to develop a technique that permits the detailed (10 m to 1000 m) neotectonic mapping over large (100 km to 1000 km long) active fault systems that is needed to better understand active continental deformation on Earth. RIMS also includes a virtual geologic compass that allows users to fit a plane to geologic surfaces and thereby measure their orientations. It also includes tools that allow 3D surface reconstruction of deformed and partially eroded surfaces such as folded bedding planes. These georeferenced map and measurement data can be exported to, or imported from, a standard GIS (geographic information systems) file format. Our interactive, 3D visualization and analysis system is designed for those who study planetary surfaces, including neotectonic geologists, geomorphologists, marine

  17. DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites.

    PubMed

    Gowthaman, Ragul; Miller, Sven A; Rogers, Steven; Khowsathit, Jittasak; Lan, Lan; Bai, Nan; Johnson, David K; Liu, Chunjing; Xu, Liang; Anbanandam, Asokan; Aubé, Jeffrey; Roy, Anuradha; Karanicolas, John

    2016-05-12

    Protein-protein interactions represent an exciting and challenging target class for therapeutic intervention using small molecules. Protein interaction sites are often devoid of the deep surface pockets presented by "traditional" drug targets, and crystal structures reveal that inhibitors typically engage these sites using very shallow binding modes. As a consequence, modern virtual screening tools developed to identify inhibitors of traditional drug targets do not perform as well when they are instead deployed at protein interaction sites. To address the need for novel inhibitors of important protein interactions, here we introduce an alternate docking strategy specifically designed for this regime. Our method, termed DARC (Docking Approach using Ray-Casting), matches the topography of a surface pocket "observed" from within the protein to the topography "observed" when viewing a potential ligand from the same vantage point. We applied DARC to carry out a virtual screen against the protein interaction site of human antiapoptotic protein Mcl-1 and found that four of the top-scoring 21 compounds showed clear inhibition in a biochemical assay. The Ki values for these compounds ranged from 1.2 to 21 μM, and each had ligand efficiency comparable to promising small-molecule inhibitors of other protein-protein interactions. These hit compounds do not resemble the natural (protein) binding partner of Mcl-1, nor do they resemble any known inhibitors of Mcl-1. Our results thus demonstrate the utility of DARC for identifying novel inhibitors of protein-protein interactions.

  18. Interactive Web Interface to the Global Strain Rate Map Project

    NASA Astrophysics Data System (ADS)

    Meertens, C. M.; Estey, L.; Kreemer, C.; Holt, W.

    2004-05-01

    An interactive web interface allows users to explore the results of a global strain rate and velocity model and to compare them to other geophysical observations. The most recent model, an updated version of Kreemer et al., 2003, has 25 independent rigid plate-like regions separated by deformable boundaries covered by about 25,000 grid areas. A least-squares fit was made to 4900 geodetic velocities from 79 different geodetic studies. In addition, Quaternary fault slip rate data are used to infer geologic strain rate estimates (currently only for central Asia). Information about the style and direction of expected strain rate is inferred from the principal axes of the seismic strain rate field. The current model, as well as source data, references and an interactive map tool, are located at the International Lithosphere Program (ILP) "A Global Strain Rate Map (ILP II-8)" project website: http://www-world-strain-map.org. The purpose of the ILP GSRM project is to provide new information from this, and other investigations, that will contribute to a better understanding of continental dynamics and to the quantification of seismic hazards. A unique aspect of the GSRM interactive Java map tool is that the user can zoom in and make custom views of the model grid and results for any area of the globe selecting strain rate and style contour plots and principal axes, observed and model velocity fields in specified frames of reference, and geologic fault data. The results can be displayed with other data sets such Harvard CMT earthquake focal mechanisms, stress directions from the ILP World Stress Map Project, and topography. With the GSRM Java map tool, the user views custom maps generated by a Generic Mapping Tool (GMT) server. These interactive capabilities greatly extend what is possible to present in a published paper. A JavaScript version, using pre-constructed maps, as well as a related information site have also been created for broader education and outreach access

  19. Mapping of the immunophilin-immunosuppressant site of interaction on calcineurin.

    PubMed

    Husi, H; Luyten, M A; Zurini, M G

    1994-05-13

    The interaction of the immunosuppressive complexes cyclosporin A-cyclophilin A and FK506 binding protein-FK506 with the Ca(2+)- and calmodulin-dependent protein phosphatase calcineurin has been investigated by means of photoaffinity labeling and chemical cross-linking. Photolabeling of purified bovine brain calcineurin with the affinity label [O-[4-[4-(1-diazo-2,2,2-trifluoroethyl)benzoyl]aminobutanoyl]-D- serine8]cyclosporin in the presence of cyclophilin A results, in addition to the labeling of cyclophilin itself, in the transfer of some of the chemical probe to both the catalytic subunit A and the regulatory subunit B of calcineurin. Chemical cross-linking studies with disuccinimidyl suberate in the presence of either cyclophilin A, B, or C in complex with cyclosporin A or FK506 binding protein-FK506 result on the other hand in the apparently exclusive and strictly immunosuppressant-dependent formation of covalent immunophilin-calcineurin B subunit products. Cross-linking of immunophilins to calcineurin B subunit requires the presence of subunit A. In the present study, using a set of recombinant maltose-binding protein fusion products representing different stretches of the catalytic subunit A, we were able to map the minimal calcineurin A sequence necessary for immunophilin-ligand-calcineurin B interaction to occur.

  20. Modeling forest site productivity using mapped geospatial attributes within a South Carolina Landscape, USA

    DOE PAGES

    Parresol, B. R.; Scott, D. A.; Zarnoch, S. J.; ...

    2017-12-15

    Spatially explicit mapping of forest productivity is important to assess many forest management alternatives. We assessed the relationship between mapped variables and site index of forests ranging from southern pine plantations to natural hardwoods on a 74,000-ha landscape in South Carolina, USA. Mapped features used in the analysis were soil association, land use condition in 1951, depth to groundwater, slope and aspect. Basal area, species composition, age and height were the tree variables measured. Linear modelling identified that plot basal area, depth to groundwater, soils association and the interactions between depth to groundwater and forest group, and between land usemore » in 1951 and forest group were related to site index (SI) (R 2 =0.37), but this model had regression attenuation. We then used structural equation modeling to incorporate error-in-measurement corrections for basal area and groundwater to remove bias in the model. We validated this model using 89 independent observations and found the 95% confidence intervals for the slope and intercept of an observed vs. predicted site index error-corrected regression included zero and one, respectively, indicating a good fit. With error in measurement incorporated, only basal area, soil association, and the interaction between forest groups and land use were important predictors (R2 =0.57). Thus, we were able to develop an unbiased model of SI that could be applied to create a spatially explicit map based primarily on soils as modified by past (land use and forest type) and recent forest management (basal area).« less

  1. Modeling forest site productivity using mapped geospatial attributes within a South Carolina Landscape, USA

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

    Parresol, B. R.; Scott, D. A.; Zarnoch, S. J.

    Spatially explicit mapping of forest productivity is important to assess many forest management alternatives. We assessed the relationship between mapped variables and site index of forests ranging from southern pine plantations to natural hardwoods on a 74,000-ha landscape in South Carolina, USA. Mapped features used in the analysis were soil association, land use condition in 1951, depth to groundwater, slope and aspect. Basal area, species composition, age and height were the tree variables measured. Linear modelling identified that plot basal area, depth to groundwater, soils association and the interactions between depth to groundwater and forest group, and between land usemore » in 1951 and forest group were related to site index (SI) (R 2 =0.37), but this model had regression attenuation. We then used structural equation modeling to incorporate error-in-measurement corrections for basal area and groundwater to remove bias in the model. We validated this model using 89 independent observations and found the 95% confidence intervals for the slope and intercept of an observed vs. predicted site index error-corrected regression included zero and one, respectively, indicating a good fit. With error in measurement incorporated, only basal area, soil association, and the interaction between forest groups and land use were important predictors (R2 =0.57). Thus, we were able to develop an unbiased model of SI that could be applied to create a spatially explicit map based primarily on soils as modified by past (land use and forest type) and recent forest management (basal area).« less

  2. Small Molecule Interactome Mapping by Photoaffinity Labeling Reveals Binding Site Hotspots for the NSAIDs.

    PubMed

    Gao, Jinxu; Mfuh, Adelphe; Amako, Yuka; Woo, Christina M

    2018-03-28

    Many therapeutics elicit cell-type specific polypharmacology that is executed by a network of molecular recognition events between a small molecule and the whole proteome. However, measurement of the structures that underpin the molecular associations between the proteome and even common therapeutics, such as the nonsteroidal anti-inflammatory drugs (NSAIDs), is limited by the inability to map the small molecule interactome. To address this gap, we developed a platform termed small molecule interactome mapping by photoaffinity labeling (SIM-PAL) and applied it to the in cellulo direct characterization of specific NSAID binding sites. SIM-PAL uses (1) photochemical conjugation of NSAID derivatives in the whole proteome and (2) enrichment and isotope-recoding of the conjugated peptides for (3) targeted mass spectrometry-based assignment. Using SIM-PAL, we identified the NSAID interactome consisting of over 1000 significantly enriched proteins and directly characterized nearly 200 conjugated peptides representing direct binding sites of the photo-NSAIDs with proteins from Jurkat and K562 cells. The enriched proteins were often identified as parts of complexes, including known targets of NSAID activity (e.g., NF-κB) and novel interactions (e.g., AP-2, proteasome). The conjugated peptides revealed direct NSAID binding sites from the cell surface to the nucleus and a specific binding site hotspot for the three photo-NSAIDs on histones H2A and H2B. NSAID binding stabilized COX-2 and histone H2A by cellular thermal shift assay. Since small molecule stabilization of protein complexes is a gain of function regulatory mechanism, it is conceivable that NSAIDs affect biological processes through these broader proteomic interactions. SIM-PAL enabled characterization of NSAID binding site hotspots and is amenable to map global binding sites for virtually any molecule of interest.

  3. Unmanned Aerial Vehicle (UAV) Data Acquisition for Archaeological Site Identification and Mapping

    NASA Astrophysics Data System (ADS)

    Handayani, W.; Ayuningtyas, E. A.; Candra R, F. S.; Arif S, B.; Argadyanto, B.

    2017-12-01

    Archaeological sites as part of human history and located around community are important to be preserved for connecting historical information from generation to generation. Mapping of archaeological sites can be done as one of preservation efforts. Yogyakarta has several archaeological sites such as Pleret Palace, the former royal palace of Mataram Islam in the 16th Century. Data limitations and the difficulty of reconstructing the site sketches into a map become obstacles in archaeological sites mapping. Unmanned Aerial Vehicle (UAV) can be an alternative of high-resolution spatial data acquisition for detail mapping, including archaeological sites mapping. This study aims to see how far the UAV acquisition results can be used for Archaeological Site mapping in Pleret Palace. Data acquisition using UAV generated to mosaic orthophoto, Digital Surface Model (DSM), and Digital Terrain Model (DTM). Archaeological sites identified using DTM and matched with site sketch made by Cultural Agency. From these data, it can be recognized some relics form, such as palace fortress, moats and canals, and also dikes of Segarayasa. This research is expected to be a reference in archaeological site mapping using detailed spatial data, especially UAV. Furthermore, it can be obtained archaeological site map close to real condition; as well as archaeological sites preservation in Indonesia.

  4. CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.

    PubMed

    Zhang, Zijun; Xing, Yi

    2017-09-19

    Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation. CLAM recovered a large number of novel RNA regulatory sites inaccessible by uniquely mapped reads. The functional significance of these sites was demonstrated by consensus motif patterns and association with alternative splicing (splicing factors), transcript abundance (AGO2) and mRNA half-life (m6A). CLAM provides a useful tool to discover novel protein-RNA interactions and RNA modification sites from CLIP-seq and RIP-seq data, and reveals the significant contribution of repetitive elements to the RNA regulatory landscape of the human transcriptome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false FM transmitter site map submissions. 73.4108 Section 73.4108 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4108 FM transmitter site map...

  6. Computational Prediction and Experimental Verification of New MAP Kinase Docking Sites and Substrates Including Gli Transcription Factors

    PubMed Central

    Whisenant, Thomas C.; Ho, David T.; Benz, Ryan W.; Rogers, Jeffrey S.; Kaake, Robyn M.; Gordon, Elizabeth A.; Huang, Lan; Baldi, Pierre; Bardwell, Lee

    2010-01-01

    In order to fully understand protein kinase networks, new methods are needed to identify regulators and substrates of kinases, especially for weakly expressed proteins. Here we have developed a hybrid computational search algorithm that combines machine learning and expert knowledge to identify kinase docking sites, and used this algorithm to search the human genome for novel MAP kinase substrates and regulators focused on the JNK family of MAP kinases. Predictions were tested by peptide array followed by rigorous biochemical verification with in vitro binding and kinase assays on wild-type and mutant proteins. Using this procedure, we found new ‘D-site’ class docking sites in previously known JNK substrates (hnRNP-K, PPM1J/PP2Czeta), as well as new JNK-interacting proteins (MLL4, NEIL1). Finally, we identified new D-site-dependent MAPK substrates, including the hedgehog-regulated transcription factors Gli1 and Gli3, suggesting that a direct connection between MAP kinase and hedgehog signaling may occur at the level of these key regulators. These results demonstrate that a genome-wide search for MAP kinase docking sites can be used to find new docking sites and substrates. PMID:20865152

  7. Surface-material maps of Viking landing sites on Mars

    NASA Technical Reports Server (NTRS)

    Moore, H. J.; Keller, J. M.

    1991-01-01

    Researchers mapped the surface materials at the Viking landing sites on Mars to gain a better understanding of the materials and rock populations at the sites and to provide information for future exploration. The maps extent to about 9 m in front of each lander and are about 15 m wide - an area comparable to the area of a pixel in high resolution Viking Orbiter images. The maps are divided into the near and far fields. Data for the near fields are from 1/10 scale maps, umpublished maps, and lander images. Data for the far fields are from 1/20 scale contour maps, contoured lander camera mosaics, and lander images. Rocks are located on these maps using stereometric measurements and the contour maps. Frequency size distribution of rocks and the responses of soil-like materials to erosion by engine exhausts during landings are discussed.

  8. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false FM transmitter site map submissions. 73.4108... RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4108 FM transmitter site map submissions. See Memorandum Opinion and Order and Public Notice, adopted October 24, 1986. 1 FCC Rcd 381 (1986...

  9. Interactive computer methods for generating mineral-resource maps

    USGS Publications Warehouse

    Calkins, James Alfred; Crosby, A.S.; Huffman, T.E.; Clark, A.L.; Mason, G.T.; Bascle, R.J.

    1980-01-01

    Inasmuch as maps are a basic tool of geologists, the U.S. Geological Survey's CRIB (Computerized Resources Information Bank) was constructed so that the data it contains can be used to generate mineral-resource maps. However, by the standard methods used-batch processing and off-line plotting-the production of a finished map commonly takes 2-3 weeks. To produce computer-generated maps more rapidly, cheaply, and easily, and also to provide an effective demonstration tool, we have devised two related methods for plotting maps as alternatives to conventional batch methods. These methods are: 1. Quick-Plot, an interactive program whose output appears on a CRT (cathode-ray-tube) device, and 2. The Interactive CAM (Cartographic Automatic Mapping system), which combines batch and interactive runs. The output of the Interactive CAM system is final compilation (not camera-ready) paper copy. Both methods are designed to use data from the CRIB file in conjunction with a map-plotting program. Quick-Plot retrieves a user-selected subset of data from the CRIB file, immediately produces an image of the desired area on a CRT device, and plots data points according to a limited set of user-selected symbols. This method is useful for immediate evaluation of the map and for demonstrating how trial maps can be made quickly. The Interactive CAM system links the output of an interactive CRIB retrieval to a modified version of the CAM program, which runs in the batch mode and stores plotting instructions on a disk, rather than on a tape. The disk can be accessed by a CRT, and, thus, the user can view and evaluate the map output on a CRT immediately after a batch run, without waiting 1-3 days for an off-line plot. The user can, therefore, do most of the layout and design work in a relatively short time by use of the CRT, before generating a plot tape and having the map plotted on an off-line plotter.

  10. Prediction of protein-protein interaction sites using electrostatic desolvation profiles.

    PubMed

    Fiorucci, Sébastien; Zacharias, Martin

    2010-05-19

    Protein-protein complex formation involves removal of water from the interface region. Surface regions with a small free energy penalty for water removal or desolvation may correspond to preferred interaction sites. A method to calculate the electrostatic free energy of placing a neutral low-dielectric probe at various protein surface positions has been designed and applied to characterize putative interaction sites. Based on solutions of the finite-difference Poisson equation, this method also includes long-range electrostatic contributions and the protein solvent boundary shape in contrast to accessible-surface-area-based solvation energies. Calculations on a large set of proteins indicate that in many cases (>90%), the known binding site overlaps with one of the six regions of lowest electrostatic desolvation penalty (overlap with the lowest desolvation region for 48% of proteins). Since the onset of electrostatic desolvation occurs even before direct protein-protein contact formation, it may help guide proteins toward the binding region in the final stage of complex formation. It is interesting that the probe desolvation properties associated with residue types were found to depend to some degree on whether the residue was outside of or part of a binding site. The probe desolvation penalty was on average smaller if the residue was part of a binding site compared to other surface locations. Applications to several antigen-antibody complexes demonstrated that the approach might be useful not only to predict protein interaction sites in general but to map potential antigenic epitopes on protein surfaces. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Prediction of Protein-Protein Interaction Sites Using Electrostatic Desolvation Profiles

    PubMed Central

    Fiorucci, Sébastien; Zacharias, Martin

    2010-01-01

    Abstract Protein-protein complex formation involves removal of water from the interface region. Surface regions with a small free energy penalty for water removal or desolvation may correspond to preferred interaction sites. A method to calculate the electrostatic free energy of placing a neutral low-dielectric probe at various protein surface positions has been designed and applied to characterize putative interaction sites. Based on solutions of the finite-difference Poisson equation, this method also includes long-range electrostatic contributions and the protein solvent boundary shape in contrast to accessible-surface-area-based solvation energies. Calculations on a large set of proteins indicate that in many cases (>90%), the known binding site overlaps with one of the six regions of lowest electrostatic desolvation penalty (overlap with the lowest desolvation region for 48% of proteins). Since the onset of electrostatic desolvation occurs even before direct protein-protein contact formation, it may help guide proteins toward the binding region in the final stage of complex formation. It is interesting that the probe desolvation properties associated with residue types were found to depend to some degree on whether the residue was outside of or part of a binding site. The probe desolvation penalty was on average smaller if the residue was part of a binding site compared to other surface locations. Applications to several antigen-antibody complexes demonstrated that the approach might be useful not only to predict protein interaction sites in general but to map potential antigenic epitopes on protein surfaces. PMID:20441756

  12. NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data

    PubMed Central

    Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

    2010-01-01

    A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware. PMID:21344013

  13. NeuroMap: A Spline-Based Interactive Open-Source Software for Spatiotemporal Mapping of 2D and 3D MEA Data.

    PubMed

    Abdoun, Oussama; Joucla, Sébastien; Mazzocco, Claire; Yvert, Blaise

    2011-01-01

    A major characteristic of neural networks is the complexity of their organization at various spatial scales, from microscopic local circuits to macroscopic brain-scale areas. Understanding how neural information is processed thus entails the ability to study them at multiple scales simultaneously. This is made possible using microelectrodes array (MEA) technology. Indeed, high-density MEAs provide large-scale coverage (several square millimeters) of whole neural structures combined with microscopic resolution (about 50 μm) of unit activity. Yet, current options for spatiotemporal representation of MEA-collected data remain limited. Here we present NeuroMap, a new interactive Matlab-based software for spatiotemporal mapping of MEA data. NeuroMap uses thin plate spline interpolation, which provides several assets with respect to conventional mapping methods used currently. First, any MEA design can be considered, including 2D or 3D, regular or irregular, arrangements of electrodes. Second, spline interpolation allows the estimation of activity across the tissue with local extrema not necessarily at recording sites. Finally, this interpolation approach provides a straightforward analytical estimation of the spatial Laplacian for better current sources localization. In this software, coregistration of 2D MEA data on the anatomy of the neural tissue is made possible by fine matching of anatomical data with electrode positions using rigid-deformation-based correction of anatomical pictures. Overall, NeuroMap provides substantial material for detailed spatiotemporal analysis of MEA data. The package is distributed under GNU General Public License and available at http://sites.google.com/site/neuromapsoftware.

  14. Quantitative genetic-interaction mapping in mammalian cells

    PubMed Central

    Roguev, Assen; Talbot, Dale; Negri, Gian Luca; Shales, Michael; Cagney, Gerard; Bandyopadhyay, Sourav; Panning, Barbara; Krogan, Nevan J

    2013-01-01

    Mapping genetic interactions (GIs) by simultaneously perturbing pairs of genes is a powerful tool for understanding complex biological phenomena. Here we describe an experimental platform for generating quantitative GI maps in mammalian cells using a combinatorial RNA interference strategy. We performed ~11,000 pairwise knockdowns in mouse fibroblasts, focusing on 130 factors involved in chromatin regulation to create a GI map. Comparison of the GI and protein-protein interaction (PPI) data revealed that pairs of genes exhibiting positive GIs and/or similar genetic profiles were predictive of the corresponding proteins being physically associated. The mammalian GI map identified pathways and complexes but also resolved functionally distinct submodules within larger protein complexes. By integrating GI and PPI data, we created a functional map of chromatin complexes in mouse fibroblasts, revealing that the PAF complex is a central player in the mammalian chromatin landscape. PMID:23407553

  15. QuickMap: a public tool for large-scale gene therapy vector insertion site mapping and analysis.

    PubMed

    Appelt, J-U; Giordano, F A; Ecker, M; Roeder, I; Grund, N; Hotz-Wagenblatt, A; Opelz, G; Zeller, W J; Allgayer, H; Fruehauf, S; Laufs, S

    2009-07-01

    Several events of insertional mutagenesis in pre-clinical and clinical gene therapy studies have created intense interest in assessing the genomic insertion profiles of gene therapy vectors. For the construction of such profiles, vector-flanking sequences detected by inverse PCR, linear amplification-mediated-PCR or ligation-mediated-PCR need to be mapped to the host cell's genome and compared to a reference set. Although remarkable progress has been achieved in mapping gene therapy vector insertion sites, public reference sets are lacking, as are the possibilities to quickly detect non-random patterns in experimental data. We developed a tool termed QuickMap, which uniformly maps and analyzes human and murine vector-flanking sequences within seconds (available at www.gtsg.org). Besides information about hits in chromosomes and fragile sites, QuickMap automatically determines insertion frequencies in +/- 250 kb adjacency to genes, cancer genes, pseudogenes, transcription factor and (post-transcriptional) miRNA binding sites, CpG islands and repetitive elements (short interspersed nuclear elements (SINE), long interspersed nuclear elements (LINE), Type II elements and LTR elements). Additionally, all experimental frequencies are compared with the data obtained from a reference set, containing 1 000 000 random integrations ('random set'). Thus, for the first time a tool allowing high-throughput profiling of gene therapy vector insertion sites is available. It provides a basis for large-scale insertion site analyses, which is now urgently needed to discover novel gene therapy vectors with 'safe' insertion profiles.

  16. Global Mapping of the Yeast Genetic Interaction Network

    NASA Astrophysics Data System (ADS)

    Tong, Amy Hin Yan; Lesage, Guillaume; Bader, Gary D.; Ding, Huiming; Xu, Hong; Xin, Xiaofeng; Young, James; Berriz, Gabriel F.; Brost, Renee L.; Chang, Michael; Chen, YiQun; Cheng, Xin; Chua, Gordon; Friesen, Helena; Goldberg, Debra S.; Haynes, Jennifer; Humphries, Christine; He, Grace; Hussein, Shamiza; Ke, Lizhu; Krogan, Nevan; Li, Zhijian; Levinson, Joshua N.; Lu, Hong; Ménard, Patrice; Munyana, Christella; Parsons, Ainslie B.; Ryan, Owen; Tonikian, Raffi; Roberts, Tania; Sdicu, Anne-Marie; Shapiro, Jesse; Sheikh, Bilal; Suter, Bernhard; Wong, Sharyl L.; Zhang, Lan V.; Zhu, Hongwei; Burd, Christopher G.; Munro, Sean; Sander, Chris; Rine, Jasper; Greenblatt, Jack; Peter, Matthias; Bretscher, Anthony; Bell, Graham; Roth, Frederick P.; Brown, Grant W.; Andrews, Brenda; Bussey, Howard; Boone, Charles

    2004-02-01

    A genetic interaction network containing ~1000 genes and ~4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ~4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

  17. Mapping of the Rsd Contact Site on the Sigma 70 Subunit of Escherichia coli RNA Polymerase

    PubMed Central

    Jishage, Miki; Dasgupta, Dipak; Ishihama, Akira

    2001-01-01

    Rsd (regulator of sigma D) is an anti-sigma factor for the Escherichia coli RNA polymerase ς70 subunit. The contact site of Rsd on ς70 was analyzed after mapping of the contact-dependent cleavage sites by Rsd-tethered iron-p-bromoacetamidobenzyl EDTA and by analysis of the complex formation between Ala-substituted ς70 and Rsd. Results indicate that the Rsd contact site is located downstream of the promoter −35 recognition helix-turn-helix motif within region 4, overlapping with the regions involved in interaction with both core enzyme and ς70 contact transcription factors. PMID:11292818

  18. Mapping of the Rsd contact site on the sigma 70 subunit of Escherichia coli RNA polymerase.

    PubMed

    Jishage, M; Dasgupta, D; Ishihama, A

    2001-05-01

    Rsd (regulator of sigma D) is an anti-sigma factor for the Escherichia coli RNA polymerase sigma(70) subunit. The contact site of Rsd on sigma(70) was analyzed after mapping of the contact-dependent cleavage sites by Rsd-tethered iron-p-bromoacetamidobenzyl EDTA and by analysis of the complex formation between Ala-substituted sigma(70) and Rsd. Results indicate that the Rsd contact site is located downstream of the promoter -35 recognition helix-turn-helix motif within region 4, overlapping with the regions involved in interaction with both core enzyme and sigma(70) contact transcription factors.

  19. A global interaction network maps a wiring diagram of cellular function

    PubMed Central

    Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

    2017-01-01

    We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

  20. The Westfield River Watershed Interactive Atlas: mapping recreation data on the web

    Treesearch

    Robert S. Bristow; Steven Riberdy

    2002-01-01

    Imagine searching the web to create a map to your house. You could use one of the many Internet mapping sites like MapBlast™ or MapQuest™ to create such a map. But maybe you wish to get a map of trails for the Grand Canyon. The National Park Service web site could serve that need. Or you may wish to get a map to show you the way from the Orlando...

  1. A rice kinase-protein interaction map.

    PubMed

    Ding, Xiaodong; Richter, Todd; Chen, Mei; Fujii, Hiroaki; Seo, Young Su; Xie, Mingtang; Zheng, Xianwu; Kanrar, Siddhartha; Stevenson, Rebecca A; Dardick, Christopher; Li, Ying; Jiang, Hao; Zhang, Yan; Yu, Fahong; Bartley, Laura E; Chern, Mawsheng; Bart, Rebecca; Chen, Xiuhua; Zhu, Lihuang; Farmerie, William G; Gribskov, Michael; Zhu, Jian-Kang; Fromm, Michael E; Ronald, Pamela C; Song, Wen-Yuan

    2009-03-01

    Plants uniquely contain large numbers of protein kinases, and for the vast majority of the 1,429 kinases predicted in the rice (Oryza sativa) genome, little is known of their functions. Genetic approaches often fail to produce observable phenotypes; thus, new strategies are needed to delineate kinase function. We previously developed a cost-effective high-throughput yeast two-hybrid system. Using this system, we have generated a protein interaction map of 116 representative rice kinases and 254 of their interacting proteins. Overall, the resulting interaction map supports a large number of known or predicted kinase-protein interactions from both plants and animals and reveals many new functional insights. Notably, we found a potential widespread role for E3 ubiquitin ligases in pathogen defense signaling mediated by receptor-like kinases, particularly by the kinases that may have evolved from recently expanded kinase subfamilies in rice. We anticipate that the data provided here will serve as a foundation for targeted functional studies in rice and other plants. The application of yeast two-hybrid and TAPtag analyses for large-scale plant protein interaction studies is also discussed.

  2. Multiscale site-response mapping: A case study of Parkfield, California

    USGS Publications Warehouse

    Thompson, E.M.; Baise, L.G.; Kayen, R.E.; Morgan, E.C.; Kaklamanos, J.

    2011-01-01

    The scale of previously proposed methods for mapping site-response ranges from global coverage down to individual urban regions. Typically, spatial coverage and accuracy are inversely related.We use the densely spaced strong-motion stations in Parkfield, California, to estimate the accuracy of different site-response mapping methods and demonstrate a method for integrating multiple site-response estimates from the site to the global scale. This method is simply a weighted mean of a suite of different estimates, where the weights are the inverse of the variance of the individual estimates. Thus, the dominant site-response model varies in space as a function of the accuracy of the different models. For mapping applications, site-response models should be judged in terms of both spatial coverage and the degree of correlation with observed amplifications. Performance varies with period, but in general the Parkfield data show that: (1) where a velocity profile is available, the square-rootof- impedance (SRI) method outperforms the measured VS30 (30 m divided by the S-wave travel time to 30 m depth) and (2) where velocity profiles are unavailable, the topographic slope method outperforms surficial geology for short periods, but geology outperforms slope at longer periods. We develop new equations to estimate site response from topographic slope, derived from the Next Generation Attenuation (NGA) database.

  3. Interactive map of refugee movement in Europe

    NASA Astrophysics Data System (ADS)

    Calka, Beata; Cahan, Bruce

    2016-12-01

    Considering the recent mass movement of people fleeing war and oppression, an analysis of changes in migration, in particular an analysis of the final destination refugees choose, seems to be of utmost importance. Many international organisations like UNHCR (the United Nations High Commissioner for Refugees) or EuroStat gather and provide information on the number of refugees and the routes they follow. What is also needed to study the state of affairs closely is a visual form presenting the rapidly changing situation. An analysis of the problem together with up-to-date statistical data presented in the visual form of a map is essential. This article describes methods of preparing such interactive maps displaying movement of refugees in European Union countries. Those maps would show changes taking place throughout recent years but also the dynamics of the development of the refugee crisis in Europe. The ArcGIS software was applied to make the map accessible on the Internet. Additionally, online sources and newspaper articles were used to present the movement of migrants. The interactive map makes it possible to watch spatial data with an opportunity to navigate within the map window. Because of that it is a clear and convenient tool to visualise such processes as refugee migration in Europe.

  4. A Global Survey and Interactive Map Suite of Deep Underground Facilities; Examples of Geotechnical and Engineering Capabilities, Achievements, Challenges: (Mines, Shafts, Tunnels, Boreholes, Sites and Underground Facilities for Nuclear Waste and Physics R&D)

    NASA Astrophysics Data System (ADS)

    Tynan, M. C.; Russell, G. P.; Perry, F.; Kelley, R.; Champenois, S. T.

    2017-12-01

    This global survey presents a synthesis of some notable geotechnical and engineering information reflected in four interactive layer maps for selected: 1) deep mines and shafts; 2) existing, considered or planned radioactive waste management deep underground studies, sites, or disposal facilities; 3) deep large diameter boreholes, and 4) physics underground laboratories and facilities from around the world. These data are intended to facilitate user access to basic information and references regarding deep underground "facilities", history, activities, and plans. In general, the interactive maps and database [http://gis.inl.gov/globalsites/] provide each facility's approximate site location, geology, and engineered features (e.g.: access, geometry, depth, diameter, year of operations, groundwater, lithology, host unit name and age, basin; operator, management organization, geographic data, nearby cultural features, other). Although the survey is not all encompassing, it is a comprehensive review of many of the significant existing and historical underground facilities discussed in the literature addressing radioactive waste management and deep mined geologic disposal safety systems. The global survey is intended to support and to inform: 1) interested parties and decision makers; 2) radioactive waste disposal and siting option evaluations, and 3) safety case development as a communication tool applicable to any mined geologic disposal facility as a demonstration of historical and current engineering and geotechnical capabilities available for use in deep underground facility siting, planning, construction, operations and monitoring.

  5. Mapping and analysis of phosphorylation sites: a quick guide for cell biologists

    PubMed Central

    Dephoure, Noah; Gould, Kathleen L.; Gygi, Steven P.; Kellogg, Douglas R.

    2013-01-01

    A mechanistic understanding of signaling networks requires identification and analysis of phosphorylation sites. Mass spectrometry offers a rapid and highly sensitive approach to mapping phosphorylation sites. However, mass spectrometry has significant limitations that must be considered when planning to carry out phosphorylation-site mapping. Here we provide an overview of key information that should be taken into consideration before beginning phosphorylation-site analysis, as well as a step-by-step guide for carrying out successful experiments. PMID:23447708

  6. Interactive Maps for Community in Online Learning

    ERIC Educational Resources Information Center

    Cavanaugh, Terence W.; Cavanaugh, Cathy

    2008-01-01

    The online courses studied here used the visual medium of the interactive geographic map as a form of dialogue to reduce students' sense of transactional distance during the course, build their skills with Web 2.0 media, and increase their motivation. Using the dynamic map and the related online spreadsheet, the course participants created digital…

  7. A Mobile, Map-Based Tasking Interface for Human-Robot Interaction

    DTIC Science & Technology

    2010-12-01

    A MOBILE, MAP-BASED TASKING INTERFACE FOR HUMAN-ROBOT INTERACTION By Eli R. Hooten Thesis Submitted to the Faculty of the Graduate School of...SUBTITLE A Mobile, Map-Based Tasking Interface for Human-Robot Interaction 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...3 II.1 Interactive Modalities and Multi-Touch . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 II.2

  8. Evaluation of Mapping Methodologies at a Legacy Test Site

    NASA Astrophysics Data System (ADS)

    Sussman, A. J.; Schultz-Fellenz, E. S.; Roback, R. C.; Kelley, R. E.; Drellack, S.; Reed, D.; Miller, E.; Cooper, D. I.; Sandoval, M.; Wang, R.

    2013-12-01

    On June 12th, 1985, a nuclear test with an announced yield between 20-150kt was detonated in rhyolitic lava in a vertical emplacement borehole at a depth of 608m below the surface. This test did not collapse to the surface and form a crater, but rather resulted in a subsurface collapse with more subtle surface expressions of deformation, providing an opportunity to evaluate the site using a number of surface mapping methodologies. The site was investigated over a two-year time span by several mapping teams. In order to determine the most time efficient and accurate approach for mapping post-shot surface features at a legacy test site, a number of different techniques were employed. The site was initially divided into four quarters, with teams applying various methodologies, techniques, and instrumentations to each quarter. Early methods included transect lines and site gridding with a Brunton pocket transit, flagging tape, measuring tape, and stakes; surveying using a hand-held personal GPS to locate observed features with an accuracy of × 5-10m; and extensive photo-documentation. More recent methods have incorporated the use of near survey grade GPS devices to allow careful location and mapping of surface features. Initially, gridding was employed along with the high resolution GPS surveys, but this was found to be time consuming and of little observational value. Raw visual observation (VOB) data included GPS coordinates for artifacts or features of interest, field notes, and photographs. A categorization system was used to organize the myriad of items, in order to aid in database searches and for visual presentation of findings. The collected data set was imported into a geographic information system (GIS) as points, lines, or polygons and overlain onto a digital color orthophoto map of the test site. Once these data were mapped, spectral data were collected using a high resolution field spectrometer. In addition to geo-locating the field observations with 10cm

  9. Mapping DNA damage-dependent genetic interactions in yeast via party mating and barcode fusion genetics.

    PubMed

    Díaz-Mejía, J Javier; Celaj, Albi; Mellor, Joseph C; Coté, Atina; Balint, Attila; Ho, Brandon; Bansal, Pritpal; Shaeri, Fatemeh; Gebbia, Marinella; Weile, Jochen; Verby, Marta; Karkhanina, Anna; Zhang, YiFan; Wong, Cassandra; Rich, Justin; Prendergast, D'Arcy; Gupta, Gaurav; Öztürk, Sedide; Durocher, Daniel; Brown, Grant W; Roth, Frederick P

    2018-05-28

    Condition-dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State-of-the-art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double-mutant strains, does not scale readily to multi-condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG-GI), by which double-mutant strains generated via en masse "party" mating can also be monitored en masse for growth to detect genetic interactions. By using site-specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG-GI enables multiplexed quantitative tracking of double mutants via next-generation sequencing. We applied BFG-GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4NQO), bleomycin, zeocin, and three other DNA-damaging environments. BFG-GI recapitulated known genetic interactions and yielded new condition-dependent genetic interactions. We validated and further explored a subnetwork of condition-dependent genetic interactions involving MAG1 , SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  10. Using Temporal Modulation Sensitivity to Select Stimulation Sites for Processor MAPs in Cochlear Implant Listeners

    PubMed Central

    Garadat, Soha N.; Zwolan, Teresa A.; Pfingst, Bryan E.

    2013-01-01

    Previous studies in our laboratory showed that temporal acuity as assessed by modulation detection thresholds (MDTs) varied across activation sites and that this site-to-site variability was subject specific. Using two 10-channel MAPs, the previous experiments showed that processor MAPs that had better across-site mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs tested in the same subject. The current study extends our earlier work on developing more optimal fitting strategies to test the feasibility of using a site-selection approach in the clinical domain. This study examined the hypothesis that revising the clinical speech processor MAP for cochlear implant (CI) recipients by turning off selected sites that have poorer temporal acuity and reallocating frequencies to the remaining electrodes would lead to improved speech recognition. Twelve CI recipients participated in the experiments. We found that site selection procedure based on MDTs in the presence of a masker resulted in improved performance on consonant recognition and recognition of sentences in noise. In contrast, vowel recognition was poorer with the experimental MAP than with the clinical MAP, possibly due to reduced spectral resolution when sites were removed from the experimental MAP. Overall, these results suggest a promising path for improving recipient outcomes using personalized processor-fitting strategies based on a psychophysical measure of temporal acuity. PMID:23881208

  11. Global Land Survey Impervious Mapping Project Web Site

    NASA Technical Reports Server (NTRS)

    DeColstoun, Eric Brown; Phillips, Jacqueline

    2014-01-01

    The Global Land Survey Impervious Mapping Project (GLS-IMP) aims to produce the first global maps of impervious cover at the 30m spatial resolution of Landsat. The project uses Global Land Survey (GLS) Landsat data as its base but incorporates training data generated from very high resolution commercial satellite data and using a Hierarchical segmentation program called Hseg. The web site contains general project information, a high level description of the science, examples of input and output data, as well as links to other relevant projects.

  12. Vegetation inventory, mapping, and classification report, Fort Bowie National Historic Site

    USGS Publications Warehouse

    Studd, Sarah; Fallon, Elizabeth; Crumbacher, Laura; Drake, Sam; Villarreal, Miguel

    2013-01-01

    A vegetation mapping and characterization effort was conducted at Fort Bowie National Historic Site in 2008-10 by the Sonoran Desert Network office in collaboration with researchers from the Office of Arid lands studies, Remote Sensing Center at the University of Arizona. This vegetation mapping effort was completed under the National Park Service Vegetation Inventory program which aims to complete baseline mapping inventories at over 270 national park units. The vegetation map data was collected to provide park managers with a digital map product that met national standards of spatial and thematic accuracy, while also placing the vegetation into a regional and even national context. Work comprised of three major field phases 1) concurrent field-based classification data collection and mapping (map unit delineation), 2) development of vegetation community types at the National Vegetation Classification alliance or association level and 3) map accuracy assessment. Phase 1 was completed in late 2008 and early 2009. Community type descriptions were drafted to meet the then-current hierarchy (version 1) of the National Vegetation Classification System (NVCS) and these were applied to each of the mapped areas. This classification was developed from both plot level data and censused polygon data (map units) as this project was conducted as a concurrent mapping and classification effort. The third stage of accuracy assessment completed in the fall of 2010 consisted of a complete census of each map unit and was conducted almost entirely by park staff. Following accuracy assessment the map was amended where needed and final products were developed including this report, a digital map and full vegetation descriptions. Fort Bowie National Historic Site covers only 1000 acres yet has a relatively complex landscape, topography and geology. A total of 16 distinct communities were described and mapped at Fort Bowie NHS. These ranged from lush riparian woodlands lining the

  13. Identification of continuous interaction sites in PLA(2)-based protein complexes by peptide arrays.

    PubMed

    Fortes-Dias, Consuelo Latorre; Santos, Roberta Márcia Marques dos; Magro, Angelo José; Fontes, Marcos Roberto de Mattos; Chávez-Olórtegui, Carlos; Granier, Claude

    2009-01-01

    Crotoxin (CA.CB) is a beta-neurotoxin from Crotalus durissus terrificus snake venom that is responsible for main envenomation effects upon biting by this snake. It is a heterodimer of an acidic protein (CA) devoid of any biological activity per se and a basic, enzymatically active, PLA(2) counterpart (CB). Both lethal and enzymatic activities of crotoxin have been shown to be inhibited by CNF, a protein from the blood of C. d. terrificus snakes. CNF replaces CA in the CA.CB complex, forming a stable, non-toxic complex CNF.CB. The molecular sites involved in the tight interfacial protein-protein interactions in these PLA(2)-based complexes have not been clearly determined. To help address this question, we used the peptide arrays approach to map possible interfacial interaction sites in CA.CB and CNF.CB. Amino acid stretches putatively involved in these interactions were firstly identified in the primary structure of CB. Further analysis of the interfacial availability of these stretches in the presumed biologically active structure of CB, suggested two interaction main sites, located at the amino-terminus and beta-wing regions. Peptide segments at the carboxyl-terminus of CB were also suggested to play a secondary role in the binding of both CA and CNF.

  14. Optimal mapping of site-specific multivariate soil properties.

    PubMed

    Burrough, P A; Swindell, J

    1997-01-01

    This paper demonstrates how geostatistics and fuzzy k-means classification can be used together to improve our practical understanding of crop yield-site response. Two aspects of soil are important for precision farming: (a) sensible classes for a given crop, and (b) their spatial variation. Local site classifications are more sensitive than general taxonomies and can be provided by the method of fuzzy k-means to transform a multivariate data set with i attributes measured at n sites into k overlapping classes; each site has a membership value mk for each class in the range 0-1. Soil variation is of interest when conditions vary over patches manageable by agricultural machinery. The spatial variation of each of the k classes can be analysed by computing the variograms of mk over the n sites. Memberships for each of the k classes can be mapped by ordinary kriging. Areas of class dominance and the transition zones between them can be identified by an inter-class confusion index; reducing the zones to boundaries gives crisp maps of dominant soil groups that can be used to guide precision farming equipment. Automation of the procedure is straightforward given sufficient data. Time variations in soil properties can be automatically incorporated in the computation of membership values. The procedures are illustrated with multi-year crop yield data collected from a 5 ha demonstration field at the Royal Agricultural College in Cirencester, UK.

  15. Preliminary analysis of Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) for mineralogic mapping at sites in Nevada and Colorado

    NASA Technical Reports Server (NTRS)

    Kruse, Fred A.; Taranik, Dan L.; Kierein-Young, Kathryn S.

    1988-01-01

    Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data for sites in Nevada and Colorado were evaluated to determine their utility for mineralogical mapping in support of geologic investigations. Equal energy normalization is commonly used with imaging spectrometer data to reduce albedo effects. Spectra, profiles, and stacked, color-coded spectra were extracted from the AVIRIS data using an interactive analysis program (QLook) and these derivative data were compared to Airborne Imaging Spectrometer (AIS) results, field and laboratory spectra, and geologic maps. A feature extraction algorithm was used to extract and characterize absorption features from AVIRIS and laboratory spectra, allowing direct comparison of the position and shape of absorption features. Both muscovite and carbonate spectra were identified in the Nevada AVIRIS data by comparison with laboratory and AIS spectra, and an image was made that showed the distribution of these minerals for the entire site. Additional, distinctive spectra were located for an unknown mineral. For the two Colorado sites, the signal-to-noise problem was significantly worse and attempts to extract meaningful spectra were unsuccessful. Problems with the Colorado AVIRIS data were accentuated by the IAR reflectance technique because of moderate vegetation cover. Improved signal-to-noise and alternative calibration procedures will be required to produce satisfactory reflectance spectra from these data. Although the AVIRIS data were useful for mapping strong mineral absorption features and producing mineral maps at the Nevada site, it is clear that significant improvements to the instrument performance are required before AVIRIS will be an operational instrument.

  16. Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis

    PubMed Central

    Moore, Michael; Zhang, Chaolin; Gantman, Emily Conn; Mele, Aldo; Darnell, Jennifer C.; Darnell, Robert B.

    2014-01-01

    Summary Identifying sites where RNA binding proteins (RNABPs) interact with target RNAs opens the door to understanding the vast complexity of RNA regulation. UV-crosslinking and immunoprecipitation (CLIP) is a transformative technology in which RNAs purified from in vivo cross-linked RNA-protein complexes are sequenced to reveal footprints of RNABP:RNA contacts. CLIP combined with high throughput sequencing (HITS-CLIP) is a generalizable strategy to produce transcriptome-wide RNA binding maps with higher accuracy and resolution than standard RNA immunoprecipitation (RIP) profiling or purely computational approaches. Applying CLIP to Argonaute proteins has expanded the utility of this approach to mapping binding sites for microRNAs and other small regulatory RNAs. Finally, recent advances in data analysis take advantage of crosslinked-induced mutation sites (CIMS) to refine RNA-binding maps to single-nucleotide resolution. Once IP conditions are established, HITS-CLIP takes approximately eight days to prepare RNA for sequencing. Established pipelines for data analysis, including for CIMS, take 3-4 days. PMID:24407355

  17. Site plan, map, and statement of significance Promontory Route ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Site plan, map, and statement of significance - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

  18. JET2 Viewer: a database of predicted multiple, possibly overlapping, protein-protein interaction sites for PDB structures.

    PubMed

    Ripoche, Hugues; Laine, Elodie; Ceres, Nicoletta; Carbone, Alessandra

    2017-01-04

    The database JET2 Viewer, openly accessible at http://www.jet2viewer.upmc.fr/, reports putative protein binding sites for all three-dimensional (3D) structures available in the Protein Data Bank (PDB). This knowledge base was generated by applying the computational method JET 2 at large-scale on more than 20 000 chains. JET 2 strategy yields very precise predictions of interacting surfaces and unravels their evolutionary process and complexity. JET2 Viewer provides an online intelligent display, including interactive 3D visualization of the binding sites mapped onto PDB structures and suitable files recording JET 2 analyses. Predictions were evaluated on more than 15 000 experimentally characterized protein interfaces. This is, to our knowledge, the largest evaluation of a protein binding site prediction method. The overall performance of JET 2 on all interfaces are: Sen = 52.52, PPV = 51.24, Spe = 80.05, Acc = 75.89. The data can be used to foster new strategies for protein-protein interactions modulation and interaction surface redesign. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Site Map | USDA Plant Hardiness Zone Map

    Science.gov Websites

    Acknowledgments & Citation Copyright Map & Data Downloads Map Downloads Geography (GIS) Downloads Multi ; Citation Copyright Map & Data Downloads Map Downloads Geography (GIS) Downloads Multi-ZIP Code Finder

  20. Mapping General Anesthetic Sites in Heteromeric γ-Aminobutyric Acid Type A Receptors Reveals a Potential For Targeting Receptor Subtypes.

    PubMed

    Forman, Stuart A; Miller, Keith W

    2016-11-01

    IV general anesthetics, including propofol, etomidate, alphaxalone, and barbiturates, produce important actions by enhancing γ-aminobutyric acid type A (GABAA) receptor activation. In this article, we review scientific studies that have located and mapped IV anesthetic sites using photoaffinity labeling and substituted cysteine modification protection. These anesthetics bind in transmembrane pockets between subunits of typical synaptic GABAA receptors, and drugs that display stereoselectivity also show remarkably selective interactions with distinct interfacial sites. These results suggest strategies for developing new drugs that selectively modulate distinct GABAA receptor subtypes.

  1. Topographic mapping of the Apollo 16 landing site

    NASA Technical Reports Server (NTRS)

    Hill, R. O.; Bender, M. J.

    1972-01-01

    The techniques are described for obtaining high resolution photographs from the Apollo 14 lunar orbiter for topographic mapping of the Descartes landing site for use in planning Apollo 16. The Apollo 16 spacecraft landed approximately 250 m from the selected target point, and few topographic surprises were encountered.

  2. The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

    PubMed

    Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

    2015-07-14

    A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

  3. Protein-Binding RNA Aptamers Affect Molecular Interactions Distantly from Their Binding Sites

    PubMed Central

    Dupont, Daniel M.; Thuesen, Cathrine K.; Bøtkjær, Kenneth A.; Behrens, Manja A.; Dam, Karen; Sørensen, Hans P.; Pedersen, Jan S.; Ploug, Michael; Jensen, Jan K.; Andreasen, Peter A.

    2015-01-01

    Nucleic acid aptamer selection is a powerful strategy for the development of regulatory agents for molecular intervention. Accordingly, aptamers have proven their diligence in the intervention with serine protease activities, which play important roles in physiology and pathophysiology. Nonetheless, there are only a few studies on the molecular basis underlying aptamer-protease interactions and the associated mechanisms of inhibition. In the present study, we use site-directed mutagenesis to delineate the binding sites of two 2´-fluoropyrimidine RNA aptamers (upanap-12 and upanap-126) with therapeutic potential, both binding to the serine protease urokinase-type plasminogen activator (uPA). We determine the subsequent impact of aptamer binding on the well-established molecular interactions (plasmin, PAI-1, uPAR, and LRP-1A) controlling uPA activities. One of the aptamers (upanap-126) binds to the area around the C-terminal α-helix in pro-uPA, while the other aptamer (upanap-12) binds to both the β-hairpin of the growth factor domain and the kringle domain of uPA. Based on the mapping studies, combined with data from small-angle X-ray scattering analysis, we construct a model for the upanap-12:pro-uPA complex. The results suggest and highlight that the size and shape of an aptamer as well as the domain organization of a multi-domain protein such as uPA, may provide the basis for extensive sterical interference with protein ligand interactions considered distant from the aptamer binding site. PMID:25793507

  4. Clustering of color map pixels: an interactive approach

    NASA Astrophysics Data System (ADS)

    Moon, Yiu Sang; Luk, Franklin T.; Yuen, K. N.; Yeung, Hoi Wo

    2003-12-01

    The demand for digital maps continues to arise as mobile electronic devices become more popular nowadays. Instead of creating the entire map from void, we may convert a scanned paper map into a digital one. Color clustering is the very first step of the conversion process. Currently, most of the existing clustering algorithms are fully automatic. They are fast and efficient but may not work well in map conversion because of the numerous ambiguous issues associated with printed maps. Here we introduce two interactive approaches for color clustering on the map: color clustering with pre-calculated index colors (PCIC) and color clustering with pre-calculated color ranges (PCCR). We also introduce a memory model that could enhance and integrate different image processing techniques for fine-tuning the clustering results. Problems and examples of the algorithms are discussed in the paper.

  5. A simulation of Earthquake Loss Estimation in Southeastern Korea using HAZUS and the local site classification Map

    NASA Astrophysics Data System (ADS)

    Kang, S.; Kim, K.

    2013-12-01

    Regionally varying seismic hazards can be estimated using an earthquake loss estimation system (e.g. HAZUS-MH). The estimations for actual earthquakes help federal and local authorities develop rapid, effective recovery measures. Estimates for scenario earthquakes help in designing a comprehensive earthquake hazard mitigation plan. Local site characteristics influence the ground motion. Although direct measurements are desirable to construct a site-amplification map, such data are expensive and time consuming to collect. Thus we derived a site classification map of the southern Korean Peninsula using geologic and geomorphologic data, which are readily available for the entire southern Korean Peninsula. Class B sites (mainly rock) are predominant in the area, although localized areas of softer soils are found along major rivers and seashores. The site classification map is compared with independent site classification studies to confirm our site classification map effectively represents the local behavior of site amplification during an earthquake. We then estimated the losses due to a magnitude 6.7 scenario earthquake in Gyeongju, southeastern Korea, with and without the site classification map. Significant differences in loss estimates were observed. The loss without the site classification map decreased without variation with increasing epicentral distance, while the loss with the site classification map varied from region to region, due to both the epicentral distance and local site effects. The major cause of the large loss expected in Gyeongju is the short epicentral distance. Pohang Nam-Gu is located farther from the earthquake source region. Nonetheless, the loss estimates in the remote city are as large as those in Gyeongju and are attributed to the site effect of soft soil found widely in the area.

  6. Golgi: Interactive Online Brain Mapping

    PubMed Central

    Brown, Ramsay A.; Swanson, Larry W.

    2015-01-01

    Golgi (http://www.usegolgi.com) is a prototype interactive brain map of the rat brain that helps researchers intuitively interact with neuroanatomy, connectomics, and cellular and chemical architecture. The flood of “-omic” data urges new ways to help researchers connect discrete findings to the larger context of the nervous system. Here we explore Golgi’s underlying reasoning and techniques and how our design decisions balance the constraints of building both a scientifically useful and usable tool. We demonstrate how Golgi can enhance connectomic literature searches with a case study investigating a thalamocortical circuit involving the Nucleus Accumbens and we explore Golgi’s potential and future directions for growth in systems neuroscience and connectomics. PMID:26635596

  7. Updating the Geologic Maps of the Apollo 15, 16, and 17 Landing Sites

    NASA Astrophysics Data System (ADS)

    Garry, W. B.; Mest, S. C.; Yingst, R. A.; Ostrach, L. R.; Petro, N. E.; Cohen, B. A.

    2018-06-01

    Our team is funded through NASA's Planetary Data Archiving, Restoration, and Tools (PDART) program to produce two new USGS Special Investigation Maps (SIM) for the Apollo 15, 16, and 17 missions: a regional map (1:200K) and a landing-site map (1:24K).

  8. A hyper-temporal remote sensing protocol for high-resolution mapping of ecological sites

    PubMed Central

    Karl, Jason W.

    2017-01-01

    Ecological site classification has emerged as a highly effective land management framework, but its utility at a regional scale has been limited due to the spatial ambiguity of ecological site locations in the U.S. or the absence of ecological site maps in other regions of the world. In response to these shortcomings, this study evaluated the use of hyper-temporal remote sensing (i.e., hundreds of images) for high spatial resolution mapping of ecological sites. We posit that hyper-temporal remote sensing can provide novel insights into the spatial variability of ecological sites by quantifying the temporal response of land surface spectral properties. This temporal response provides a spectral ‘fingerprint’ of the soil-vegetation-climate relationship which is central to the concept of ecological sites. Consequently, the main objective of this study was to predict the spatial distribution of ecological sites in a semi-arid rangeland using a 28-year time series of normalized difference vegetation index from Landsat TM 5 data and modeled using support vector machine classification. Results from this study show that support vector machine classification using hyper-temporal remote sensing imagery was effective in modeling ecological site classes, with a 62% correct classification. These results were compared to Gridded Soil Survey Geographic database and expert delineated maps of ecological sites which had a 51 and 89% correct classification, respectively. An analysis of the effects of ecological state on ecological site misclassifications revealed that sites in degraded states (e.g., shrub-dominated/shrubland and bare/annuals) had a higher rate of misclassification due to their close spectral similarity with other ecological sites. This study identified three important factors that need to be addressed to improve future model predictions: 1) sampling designs need to fully represent the range of both within class (i.e., states) and between class (i.e., ecological

  9. A hyper-temporal remote sensing protocol for high-resolution mapping of ecological sites.

    PubMed

    Maynard, Jonathan J; Karl, Jason W

    2017-01-01

    Ecological site classification has emerged as a highly effective land management framework, but its utility at a regional scale has been limited due to the spatial ambiguity of ecological site locations in the U.S. or the absence of ecological site maps in other regions of the world. In response to these shortcomings, this study evaluated the use of hyper-temporal remote sensing (i.e., hundreds of images) for high spatial resolution mapping of ecological sites. We posit that hyper-temporal remote sensing can provide novel insights into the spatial variability of ecological sites by quantifying the temporal response of land surface spectral properties. This temporal response provides a spectral 'fingerprint' of the soil-vegetation-climate relationship which is central to the concept of ecological sites. Consequently, the main objective of this study was to predict the spatial distribution of ecological sites in a semi-arid rangeland using a 28-year time series of normalized difference vegetation index from Landsat TM 5 data and modeled using support vector machine classification. Results from this study show that support vector machine classification using hyper-temporal remote sensing imagery was effective in modeling ecological site classes, with a 62% correct classification. These results were compared to Gridded Soil Survey Geographic database and expert delineated maps of ecological sites which had a 51 and 89% correct classification, respectively. An analysis of the effects of ecological state on ecological site misclassifications revealed that sites in degraded states (e.g., shrub-dominated/shrubland and bare/annuals) had a higher rate of misclassification due to their close spectral similarity with other ecological sites. This study identified three important factors that need to be addressed to improve future model predictions: 1) sampling designs need to fully represent the range of both within class (i.e., states) and between class (i.e., ecological sites

  10. Quantitative maps of genetic interactions in yeast - comparative evaluation and integrative analysis.

    PubMed

    Lindén, Rolf O; Eronen, Ville-Pekka; Aittokallio, Tero

    2011-03-24

    High-throughput genetic screening approaches have enabled systematic means to study how interactions among gene mutations contribute to quantitative fitness phenotypes, with the aim of providing insights into the functional wiring diagrams of genetic interaction networks on a global scale. However, it is poorly known how well these quantitative interaction measurements agree across the screening approaches, which hinders their integrated use toward improving the coverage and quality of the genetic interaction maps in yeast and other organisms. Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies. We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.

  11. Electrostatic interaction map reveals a new binding position for tropomyosin on F-actin.

    PubMed

    Rynkiewicz, Michael J; Schott, Veronika; Orzechowski, Marek; Lehman, William; Fischer, Stefan

    2015-12-01

    Azimuthal movement of tropomyosin around the F-actin thin filament is responsible for muscle activation and relaxation. Recently a model of αα-tropomyosin, derived from molecular-mechanics and electron microscopy of different contractile states, showed that tropomyosin is rather stiff and pre-bent to present one specific face to F-actin during azimuthal transitions. However, a new model based on cryo-EM of troponin- and myosin-free filaments proposes that the interacting-face of tropomyosin can differ significantly from that in the original model. Because resolution was insufficient to assign tropomyosin side-chains, the interacting-face could not be unambiguously determined. Here, we use structural analysis and energy landscapes to further examine the proposed models. The observed bend in seven crystal structures of tropomyosin is much closer in direction and extent to the original model than to the new model. Additionally, we computed the interaction map for repositioning tropomyosin over the F-actin surface, but now extended over a much larger surface than previously (using the original interacting-face). This map shows two energy minima-one corresponding to the "blocked-state" as in the original model, and the other related by a simple 24 Å translation of tropomyosin parallel to the F-actin axis. The tropomyosin-actin complex defined by the second minimum fits perfectly into the recent cryo-EM density, without requiring any change in the interacting-face. Together, these data suggest that movement of tropomyosin between regulatory states does not require interacting-face rotation. Further, they imply that thin filament assembly may involve an interplay between initially seeded tropomyosin molecules growing from distinct binding-site regions on actin.

  12. 13. "CIVIL, SITE PLAN AND VICINITY MAP, AREA LOCATIONS." Test ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. "CIVIL, SITE PLAN AND VICINITY MAP, AREA LOCATIONS." Test Area 1-125. Specifications No. ENG (NASA)-04-35363-1; Drawing No. 60-09-34; sheet 11. Ref. No. C-l. D.O. SERIES 1597/1. Approved for siting on 24 April 1962. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Leuhman Ridge near Highways 58 & 395, Boron, Kern County, CA

  13. Interactive map communication: pilot study of the visual perceptions and preferences of public health practitioners.

    PubMed

    Koenig, A; Samarasundera, E; Cheng, T

    2011-08-01

    To conduct a pilot study into the comprehension and visualisation preferences of geographic information by public health practitioners (PHPs), particularly in the context of interactive, Internet-based atlases. Structured human-computer interaction interviews. Seven academia-based PHPs were interviewed as information service users based on a structured questionnaire to assess their understanding of geographic representations of morbidity data, and identify their visualisation preferences in a geographic information systems environment. Awareness of area-based deprivation indices and the Index of Multiple Deprivation 2007 health and disability domain was near-universal. However, novice users of disease maps had difficulties in interpreting data classifications, in understanding supplementary information in the form of box plots and histograms, and in making use of links between interactive tabular and cartographic information. Choices for colour plans when viewing maps showed little agreement between users, although pre-viewing comments showed preferences for red-blue diverging schema. PHPs new to geographic information would benefit from enhanced interpretive support documentation to meet their needs when using Internet-based, interactive public health atlases, which are rarely provided at such sites. Technical, software-related support alone is insufficient. Increased interaction between PHPs and mapmakers would be beneficial to maximise the potential of the current growth in interactive, electronic atlases, and improve geographic information support for public health decision-making and informing the wider public. Copyright © 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  14. O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.

    PubMed

    Fan, Qiong; Moen, Anders; Anonsen, Jan Haug; Bindesbøll, Christian; Sæther, Thomas; Carlson, Cathrine Rein; Grønning-Wang, Line M

    2018-05-05

    The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses. We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity. Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver. In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20 LWKPGAQDASSQAQGGSSCILRE 42 . However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro. Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion. Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain. We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain. Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Considerations for applying digital soil mapping to ecological sites

    USDA-ARS?s Scientific Manuscript database

    Recent advancements in the spatial prediction of soil properties are not currently being fully utilized for ecological studies. Linking digital soil mapping (DSM) with ecological sites (ES) has the potential to better land management decisions by improving spatial resolution and precision as well as...

  16. Biochemical investigations and mapping of the calcium-binding sites of heparinase I from Flavobacterium heparinum.

    PubMed

    Shriver, Z; Liu, D; Hu, Y; Sasisekharan, R

    1999-02-12

    The heparinases from Flavobacterium heparinum are lyases that specifically cleave heparin-like glycosaminoglycans. Previously, amino acids located in the active site of heparinase I have been identified and mapped. In an effort to further understand the mechanism by which heparinase I cleaves its polymer substrate, we sought to understand the role of calcium, as a necessary cofactor, in the enzymatic activity of heparinase I. Specifically, we undertook a series of biochemical and biophysical experiments to answer the question of whether heparinase I binds to calcium and, if so, which regions of the protein are involved in calcium binding. Using the fluorescent calcium analog terbium, we found that heparinase I tightly bound divalent and trivalent cations. Furthermore, we established that this interaction was specific for ions that closely approximate the ionic radius of calcium. Through the use of the modification reagents N-ethyl-5-phenylisoxazolium-3'-sulfonate (Woodward's reagent K) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, we showed that the interaction between heparinase I and calcium was essential for proper functioning of the enzyme. Preincubation with either calcium alone or calcium in the presence of heparin was able to protect the enzyme from inactivation by these modifying reagents. In addition, through mapping studies of Woodward's reagent K-modified heparinase I, we identified two putative calcium-binding sites, CB-1 (Glu207-Ala219) and CB-2 (Thr373-Arg384), in heparinase I that not only are specifically modified by Woodward's reagent K, leading to loss of enzymatic activity, but also conform to the calcium-coordinating consensus motif.

  17. Satellite Power System (SPS) mapping of exclusion areas for rectenna sites

    NASA Technical Reports Server (NTRS)

    Blackburn, J. B., Jr.; Bavinger, B. A.

    1978-01-01

    The areas of the United States that were not available as potential sites for receiving antennas that are an integral part of the Satellite Power System concept are presented. Thirty-six variables with the potential to exclude the rectenna were mapped and coded in a computer. Some of these variables exclude a rectenna from locating within the area of its spatial influence, and other variables potentially exclude the rectenna. These maps of variables were assembled from existing data and were mapped on a grid system.

  18. Effective stochastic generator with site-dependent interactions

    NASA Astrophysics Data System (ADS)

    Khamehchi, Masoumeh; Jafarpour, Farhad H.

    2017-11-01

    It is known that the stochastic generators of effective processes associated with the unconditioned dynamics of rare events might consist of non-local interactions; however, it can be shown that there are special cases for which these generators can include local interactions. In this paper, we investigate this possibility by considering systems of classical particles moving on a one-dimensional lattice with open boundaries. The particles might have hard-core interactions similar to the particles in an exclusion process, or there can be many arbitrary particles at a single site in a zero-range process. Assuming that the interactions in the original process are local and site-independent, we will show that under certain constraints on the microscopic reaction rules, the stochastic generator of an unconditioned process can be local but site-dependent. As two examples, the asymmetric zero-temperature Glauber model and the A-model with diffusion are presented and studied under the above-mentioned constraints.

  19. Digital geologic map database of the Nevada Test Site area, Nevada

    USGS Publications Warehouse

    Wahl, R.R.; Sawyer, D.A.; Minor, S.A.; Carr, M.D.; Cole, J.C.; Swadley, W.C.; Laczniak, R.J.; Warren, R.G.; Green, K.S.; Engle, C.M.

    1997-01-01

    Forty years of geologic investigations at the Nevada Test Site (NTS) have been digitized. These data include all geologic information that: (1) has been collected, and (2) can be represented on a map within the map borders at the map scale is included in the map digital coverages. The following coverages are included with this dataset: Coverage Type Description geolpoly Polygon Geologic outcrops geolflts line Fault traces geolatts Point Bedding attitudes, etc. geolcald line Caldera boundaries geollins line Interpreted lineaments geolmeta line Metamorphic gradients The above coverages are attributed with numeric values and interpreted information. The entity files documented below show the data associated with each coverage.

  20. Acoustic mapping of the regional seafloor geology in and around Hawaiian ocean dredged-material disposal sites

    USGS Publications Warehouse

    Torresan, Michael E.; Gardner, James V.

    2000-01-01

    During January and February 1998 the U.S. Geological Survey Coastal and Marine Geology Team (USGS) conducted regional high-resolution multibeam mapping surveys of the area surrounding EPA-designated ocean disposal sites located offshore of the Hawaiian Islands of Oahu, Kauai, Maui, and Hawaii. The sites are all located within 5 nautical miles of shore on insular shelves or slopes. Regional maps were required of areas much larger than the disposal sites themselves to assess both the regional seafloor geology and the immediate vicinity of the disposal sites. The purpose of the disposal site surveys was to delimit the extent of disposal material by producing detailed bathymetric and backscatter maps of the seafloor with a ± 1 m spatial accuracy and <1% depth error. The advantage of using multibeam over conventional towed, single-beam sidescan sonar is that the multibeam data are accurately georeferenced for precise location of all imaged features. The multibeam produces a coregistered acoustic-backscatter map that is often required to locate individual disposal deposits. These data were collected by the USGS as part of its regional seafloor mapping and in support of ocean disposal site monitoring studies conducted in cooperation with the US Environmental Protection Agency (EPA) and the US Army Corps of Engineers (COE).

  1. Constraining the interaction between dark sectors with future HI intensity mapping observations

    NASA Astrophysics Data System (ADS)

    Xu, Xiaodong; Ma, Yin-Zhe; Weltman, Amanda

    2018-04-01

    We study a model of interacting dark matter and dark energy, in which the two components are coupled. We calculate the predictions for the 21-cm intensity mapping power spectra, and forecast the detectability with future single-dish intensity mapping surveys (BINGO, FAST and SKA-I). Since dark energy is turned on at z ˜1 , which falls into the sensitivity range of these radio surveys, the HI intensity mapping technique is an efficient tool to constrain the interaction. By comparing with current constraints on dark sector interactions, we find that future radio surveys will produce tight and reliable constraints on the coupling parameters.

  2. Interaction between LSD and dopamine D2/3 binding sites in pig brain.

    PubMed

    Minuzzi, Luciano; Nomikos, George G; Wade, Mark R; Jensen, Svend B; Olsen, Aage K; Cumming, Paul

    2005-06-15

    The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD. (c) 2005 Wiley-Liss, Inc.

  3. A Bayesian-Based Novel Methodology to Generate Reliable Site Response Mapping Sensitive to Data Uncertainties

    NASA Astrophysics Data System (ADS)

    Chakraborty, A.; Goto, H.

    2017-12-01

    The 2011 off the Pacific coast of Tohoku earthquake caused severe damage in many areas further inside the mainland because of site-amplification. Furukawa district in Miyagi Prefecture, Japan recorded significant spatial differences in ground motion even at sub-kilometer scales. The site responses in the damage zone far exceeded the levels in the hazard maps. A reason why the mismatch occurred is that mapping follow only the mean value at the measurement locations with no regard to the data uncertainties and thus are not always reliable. Our research objective is to develop a methodology to incorporate data uncertainties in mapping and propose a reliable map. The methodology is based on a hierarchical Bayesian modeling of normally-distributed site responses in space where the mean (μ), site-specific variance (σ2) and between-sites variance(s2) parameters are treated as unknowns with a prior distribution. The observation data is artificially created site responses with varying means and variances for 150 seismic events across 50 locations in one-dimensional space. Spatially auto-correlated random effects were added to the mean (μ) using a conditionally autoregressive (CAR) prior. The inferences on the unknown parameters are done using Markov Chain Monte Carlo methods from the posterior distribution. The goal is to find reliable estimates of μ sensitive to uncertainties. During initial trials, we observed that the tau (=1/s2) parameter of CAR prior controls the μ estimation. Using a constraint, s = 1/(k×σ), five spatial models with varying k-values were created. We define reliability to be measured by the model likelihood and propose the maximum likelihood model to be highly reliable. The model with maximum likelihood was selected using a 5-fold cross-validation technique. The results show that the maximum likelihood model (μ*) follows the site-specific mean at low uncertainties and converges to the model-mean at higher uncertainties (Fig.1). This result is

  4. Model-Mapped RPA for Determining the Effective Coulomb Interaction

    NASA Astrophysics Data System (ADS)

    Sakakibara, Hirofumi; Jang, Seung Woo; Kino, Hiori; Han, Myung Joon; Kuroki, Kazuhiko; Kotani, Takao

    2017-04-01

    We present a new method to obtain a model Hamiltonian from first-principles calculations. The effective interaction contained in the model is determined on the basis of random phase approximation (RPA). In contrast to previous methods such as projected RPA and constrained RPA (cRPA), the new method named "model-mapped RPA" takes into account the long-range part of the polarization effect to determine the effective interaction in the model. After discussing the problems of cRPA, we present the formulation of the model-mapped RPA, together with a numerical test for the single-band Hubbard model of HgBa2CuO4.

  5. SELMAP - SELEX affinity landscape MAPping of transcription factor binding sites using integrated microfluidics

    PubMed Central

    Chen, Dana; Orenstein, Yaron; Golodnitsky, Rada; Pellach, Michal; Avrahami, Dorit; Wachtel, Chaim; Ovadia-Shochat, Avital; Shir-Shapira, Hila; Kedmi, Adi; Juven-Gershon, Tamar; Shamir, Ron; Gerber, Doron

    2016-01-01

    Transcription factors (TFs) alter gene expression in response to changes in the environment through sequence-specific interactions with the DNA. These interactions are best portrayed as a landscape of TF binding affinities. Current methods to study sequence-specific binding preferences suffer from limited dynamic range, sequence bias, lack of specificity and limited throughput. We have developed a microfluidic-based device for SELEX Affinity Landscape MAPping (SELMAP) of TF binding, which allows high-throughput measurement of 16 proteins in parallel. We used it to measure the relative affinities of Pho4, AtERF2 and Btd full-length proteins to millions of different DNA binding sites, and detected both high and low-affinity interactions in equilibrium conditions, generating a comprehensive landscape of the relative TF affinities to all possible DNA 6-mers, and even DNA10-mers with increased sequencing depth. Low quantities of both the TFs and DNA oligomers were sufficient for obtaining high-quality results, significantly reducing experimental costs. SELMAP allows in-depth screening of hundreds of TFs, and provides a means for better understanding of the regulatory processes that govern gene expression. PMID:27628341

  6. Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps

    PubMed Central

    Huang, Hailiang; Jedynak, Bruno M; Bader, Joel S

    2007-01-01

    Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either a high false-discovery rate (interaction sets have low overlap because each set is contaminated by a large number of stochastic false-positive interactions) or a high false-negative rate (interaction sets have low overlap because each misses many true interactions). We extend capture–recapture theory to provide the first unified model for false-positive and false-negative rates for two-hybrid screens. Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported interactions are likely false positives. Membrane proteins have higher false-discovery rates on average, and signal transduction proteins have lower rates. The overall false-negative rate ranges from 75% for worm to 90% for fly, which arises from a roughly 50% false-negative rate due to statistical undersampling and a 55% to 85% false-negative rate due to proteins that appear to be systematically lost from the assays. Finally, statistical model selection conclusively rejects the Erdös-Rényi network model in favor of the power law model for yeast and the truncated power law for worm and fly degree distributions. Much as genome sequencing coverage estimates were essential for planning the human genome sequencing project, the coverage estimates developed here will be valuable for guiding future proteomic screens. All software and datasets are available in Datasets S1 and S2, Figures S1–S5, and Tables S1−S6, and are also available from our Web site, http://www.baderzone.org. PMID:18039026

  7. A Web-Based Interactive Mapping System of State Wide School Performance: Integrating Google Maps API Technology into Educational Achievement Data

    ERIC Educational Resources Information Center

    Wang, Kening; Mulvenon, Sean W.; Stegman, Charles; Anderson, Travis

    2008-01-01

    Google Maps API (Application Programming Interface), released in late June 2005 by Google, is an amazing technology that allows users to embed Google Maps in their own Web pages with JavaScript. Google Maps API has accelerated the development of new Google Maps based applications. This article reports a Web-based interactive mapping system…

  8. Seismic Hazard Maps for Seattle, Washington, Incorporating 3D Sedimentary Basin Effects, Nonlinear Site Response, and Rupture Directivity

    USGS Publications Warehouse

    Frankel, Arthur D.; Stephenson, William J.; Carver, David L.; Williams, Robert A.; Odum, Jack K.; Rhea, Susan

    2007-01-01

    This report presents probabilistic seismic hazard maps for Seattle, Washington, based on over 500 3D simulations of ground motions from scenario earthquakes. These maps include 3D sedimentary basin effects and rupture directivity. Nonlinear site response for soft-soil sites of fill and alluvium was also applied in the maps. The report describes the methodology for incorporating source and site dependent amplification factors into a probabilistic seismic hazard calculation. 3D simulations were conducted for the various earthquake sources that can affect Seattle: Seattle fault zone, Cascadia subduction zone, South Whidbey Island fault, and background shallow and deep earthquakes. The maps presented in this document used essentially the same set of faults and distributed-earthquake sources as in the 2002 national seismic hazard maps. The 3D velocity model utilized in the simulations was validated by modeling the amplitudes and waveforms of observed seismograms from five earthquakes in the region, including the 2001 M6.8 Nisqually earthquake. The probabilistic seismic hazard maps presented here depict 1 Hz response spectral accelerations with 10%, 5%, and 2% probabilities of exceedance in 50 years. The maps are based on determinations of seismic hazard for 7236 sites with a spacing of 280 m. The maps show that the most hazardous locations for this frequency band (around 1 Hz) are soft-soil sites (fill and alluvium) within the Seattle basin and along the inferred trace of the frontal fault of the Seattle fault zone. The next highest hazard is typically found for soft-soil sites in the Duwamish Valley south of the Seattle basin. In general, stiff-soil sites in the Seattle basin exhibit higher hazard than stiff-soil sites outside the basin. Sites with shallow bedrock outside the Seattle basin have the lowest estimated hazard for this frequency band.

  9. Web Mapping for Promoting Interaction and Collaboration in Community Land Planning

    NASA Astrophysics Data System (ADS)

    Veenendaal, B.; Dhliwayo, M.

    2013-10-01

    There is an inherent advantage of geographic information Systems (GIS) and mapping in facilitating dialogue between experts and non-experts during land use plan development. Combining visual mapping information and effective user interaction can result in considerable benefits for developing countries like Botswana. Although the adoption of information and communication technologies has lagged behind that for developed countries, initiatives by the Botswana government in providing suitable information infrastructures, including internet and web based communications, are enabling multiple users to interact and collaborate in community land planning. A web mapping application was developed for the Maun Development Plan (MDP) in the Okavango Delta region in Botswana. It was designed according to requirements of land planners and managers and implemented using ArcGIS Viewer for Flex. Land planners and managers from two organisations in Maun involved in the development of the MDP were asked to evaluate the web mapping tools. This paper describes the results of implementation and some preliminary results of the web mapping evaluation.

  10. Depth-to-Ice Map of an Arctic Site on Mars

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Color coding in this map of a far-northern site on Mars indicates the change in nighttime ground-surface temperature between summer and fall. This site, like most of high-latitude Mars, has water ice mixed with soil near the surface. The ice is probably in a rock-hard frozen layer beneath a few centimeters or inches of looser, dry soil. The amount of temperature change at the surface likely corresponds to how close to the surface the icy material lies.

    The dense, icy layer retains heat better than the looser soil above it, so where the icy layer is closer to the surface, the surface temperature changes more slowly than where the icy layer is buried deeper. On the map, areas of the surface that cooled more slowly between summer and autumn (interpreted as having the ice closer to the surface) are coded blue and green. Areas that cooled more quickly (interpreted as having more distance to the ice) are coded red and yellow.

    The depth to the top of the icy layer estimated from these observations, as little as 5 centimeters (2 inches), matches modeling of where it would be if Mars has an active cycle of water being exchanged by diffusion between atmospheric water vapor and subsurface water ice.

    This map and its interpretation are in a May 3, 2007, report in the journal Nature by Joshua Bandfield of Arizona State University, Tempe. The Thermal Emission Imaging System camera on NASA's Mars Odyssey orbiter collected the data presented in the map. The site is centered near 67.5 degrees north latitude, 132 degrees east longitude, in the Martian arctic plains called Vastitas Borealis. It was formerly a candidate landing site for NASA's Phoenix Mars Lander mission. This site is within the portion of the planet where, in 2002, the Gamma Ray Spectrometer suite of instruments on Mars Odyssey found evidence for water ice lying just below the surface. The information from the Gamma Ray Spectrometer is averaged over patches of ground hundreds of kilometers

  11. Autonomous multispecies reaction-diffusion systems with more-than-two-site interactions

    NASA Astrophysics Data System (ADS)

    Shariati, Ahmad; Aghamohammadi, Amir; Khorrami, Mohammad

    2001-12-01

    Autonomous multispecies systems with more-than-two-neighbor interactions are studied. Conditions necessary and sufficient for the closedness of the evolution equations of the n-point functions are obtained. The average numbers of the particles at each site for one species and three-site interactions, and its generalization to the more-than-three-site interactions, are explicitly obtained. Generalizations of the Glauber model in different directions, using generalized rates, generalized numbers of states at each site, and generalized numbers of interacting sites, are also investigated.

  12. Genome-wide maps of nuclear lamina interactions in single human cells.

    PubMed

    Kind, Jop; Pagie, Ludo; de Vries, Sandra S; Nahidiazar, Leila; Dey, Siddharth S; Bienko, Magda; Zhan, Ye; Lajoie, Bryan; de Graaf, Carolyn A; Amendola, Mario; Fudenberg, Geoffrey; Imakaev, Maxim; Mirny, Leonid A; Jalink, Kees; Dekker, Job; van Oudenaarden, Alexander; van Steensel, Bas

    2015-09-24

    Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Modeling forest site productivity using mapped geospatial attributes within a South Carolina landscape, USA

    Treesearch

    B.R. Parresol; D.A. Scott; S.J. Zarnoch; L.A. Edwards; J.I. Blake

    2017-01-01

    Spatially explicit mapping of forest productivity is important to assess many forest management alternatives. We assessed the relationship between mapped variables and site index of forests ranging from southern pine plantations to natural hardwoods on a 74,000-ha landscape in South Carolina, USA. Mapped features used in the analysis were soil association, land use...

  14. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps

    PubMed Central

    2013-01-01

    Background Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. Results NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. Conclusions NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps

  15. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps.

    PubMed

    Kuperstein, Inna; Cohen, David P A; Pook, Stuart; Viara, Eric; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

    2013-10-07

    Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.

  16. Integrating Radar Image Data with Google Maps

    NASA Technical Reports Server (NTRS)

    Chapman, Bruce D.; Gibas, Sarah

    2010-01-01

    A public Web site has been developed as a method for displaying the multitude of radar imagery collected by NASA s Airborne Synthetic Aperture Radar (AIRSAR) instrument during its 16-year mission. Utilizing NASA s internal AIRSAR site, the new Web site features more sophisticated visualization tools that enable the general public to have access to these images. The site was originally maintained at NASA on six computers: one that held the Oracle database, two that took care of the software for the interactive map, and three that were for the Web site itself. Several tasks were involved in moving this complicated setup to just one computer. First, the AIRSAR database was migrated from Oracle to MySQL. Then the back-end of the AIRSAR Web site was updated in order to access the MySQL database. To do this, a few of the scripts needed to be modified; specifically three Perl scripts that query that database. The database connections were then updated from Oracle to MySQL, numerous syntax errors were corrected, and a query was implemented that replaced one of the stored Oracle procedures. Lastly, the interactive map was designed, implemented, and tested so that users could easily browse and access the radar imagery through the Google Maps interface.

  17. Coastline Mapping and Cultural Review to Predict Sea Level Rise Impact on Hawaiian Archeological Sites

    NASA Astrophysics Data System (ADS)

    Clinton, J.

    2017-12-01

    Much of Hawaii's history is recorded in archeological sites. Researchers and cultural practitioners have been studying and reconstructing significant archeological sites for generations. Climate change, and more specifically, sea level rise may threaten these sites. Our research records current sea levels and then projects possible consequences to these cultural monuments due to sea level rise. In this mixed methods study, research scientists, cultural practitioners, and secondary students use plane-table mapping techniques to create maps of coastlines and historic sites. Students compare historical records to these maps, analyze current sea level rise trends, and calculate future sea levels. They also gather data through interviews with community experts and kupuna (elders). If climate change continues at projected rates, some historic sites will be in danger of negative impact due to sea level rise. Knowing projected sea levels at specific sites allows for preventative action and contributes to raised awareness of the impacts of climate change to the Hawaiian Islands. Students will share results with the community and governmental agencies in hopes of inspiring action to minimize climate change. It will take collaboration between scientists and cultural communities to inspire future action on climate change.

  18. Understanding Urban Watersheds through Digital Interactive Maps, San Francisco Bay Area, California

    NASA Astrophysics Data System (ADS)

    Sowers, J. M.; Ticci, M. G.; Mulvey, P.

    2014-12-01

    Dense urbanization has resulted in the "disappearance" of many local creeks in urbanized areas surrounding the San Francisco Bay. Long reaches of creeks now flow in underground pipes. Municipalities and water agencies trying to reduce non-point-source pollution are faced with a public that cannot see and therefore does not understand the interconnected nature of the drainage system or its ultimate discharge to the bay. Since 1993, we have collaborated with the Oakland Museum, the San Francisco Estuary Institute, public agencies, and municipalities to create creek and watershed maps to address the need for public understanding of watershed concepts. Fifteen paper maps are now published (www.museumca.org/creeks), which have become a standard reference for educators and anyone working on local creek-related issues. We now present digital interactive creek and watershed maps in Google Earth. Four maps are completed covering urbanized areas of Santa Clara and Alameda Counties. The maps provide a 3D visualization of the watersheds, with cartography draped over the landscape in transparent colors. Each mapped area includes both Present and Past (circa 1800s) layers which can be clicked on or off by the user. The Present layers include the modern drainage network, watershed boundaries, and reservoirs. The Past layers include the 1800s-era creek systems, tidal marshes, lagoons, and other habitats. All data are developed in ArcGIS software and converted to Google Earth format. To ensure the maps are interesting and engaging, clickable icons pop-up provide information on places to visit, restoration projects, history, plants, and animals. Maps of Santa Clara Valley are available at http://www.valleywater.org/WOW.aspx. Maps of western Alameda County will soon be available at http://acfloodcontrol.org/. Digital interactive maps provide several advantages over paper maps. They are seamless within each map area, and the user can zoom in or out, and tilt, and fly over to explore

  19. Prediction of Carbohydrate Binding Sites on Protein Surfaces with 3-Dimensional Probability Density Distributions of Interacting Atoms

    PubMed Central

    Tsai, Keng-Chang; Jian, Jhih-Wei; Yang, Ei-Wen; Hsu, Po-Chiang; Peng, Hung-Pin; Chen, Ching-Tai; Chen, Jun-Bo; Chang, Jeng-Yih; Hsu, Wen-Lian; Yang, An-Suei

    2012-01-01

    Non-covalent protein-carbohydrate interactions mediate molecular targeting in many biological processes. Prediction of non-covalent carbohydrate binding sites on protein surfaces not only provides insights into the functions of the query proteins; information on key carbohydrate-binding residues could suggest site-directed mutagenesis experiments, design therapeutics targeting carbohydrate-binding proteins, and provide guidance in engineering protein-carbohydrate interactions. In this work, we show that non-covalent carbohydrate binding sites on protein surfaces can be predicted with relatively high accuracy when the query protein structures are known. The prediction capabilities were based on a novel encoding scheme of the three-dimensional probability density maps describing the distributions of 36 non-covalent interacting atom types around protein surfaces. One machine learning model was trained for each of the 30 protein atom types. The machine learning algorithms predicted tentative carbohydrate binding sites on query proteins by recognizing the characteristic interacting atom distribution patterns specific for carbohydrate binding sites from known protein structures. The prediction results for all protein atom types were integrated into surface patches as tentative carbohydrate binding sites based on normalized prediction confidence level. The prediction capabilities of the predictors were benchmarked by a 10-fold cross validation on 497 non-redundant proteins with known carbohydrate binding sites. The predictors were further tested on an independent test set with 108 proteins. The residue-based Matthews correlation coefficient (MCC) for the independent test was 0.45, with prediction precision and sensitivity (or recall) of 0.45 and 0.49 respectively. In addition, 111 unbound carbohydrate-binding protein structures for which the structures were determined in the absence of the carbohydrate ligands were predicted with the trained predictors. The overall

  20. Interactive web-based mapping: bridging technology and data for health

    PubMed Central

    2011-01-01

    Background The Community Health Information System (CHIS) online mapping system was first launched in 1998. Its overarching goal was to provide researchers, residents and organizations access to health related data reflecting the overall health and well-being of their communities within the Greater Houston area. In September 2009, initial planning and development began for the next generation of CHIS. The overarching goal for the new version remained to make health data easily accessible for a wide variety of research audiences. However, in the new version we specifically sought to make the CHIS truly interactive and give the user more control over data selection and reporting. Results In July 2011, a beta version of the next-generation of the application was launched. This next-generation is also a web based interactive mapping tool comprised of two distinct portals: the Breast Health Portal and Project Safety Net. Both are accessed via a Google mapping interface. Geographic coverage for the portals is currently an 8 county region centered on Harris County, Texas. Data accessed by the application include Census 2000, Census 2010 (underway), cancer incidence from the Texas Cancer Registry (TX Dept. of State Health Services), death data from Texas Vital Statistics, clinic locations for free and low-cost health services, along with service lists, hours of operation, payment options and languages spoken, uninsured and poverty data. Conclusions The system features query on the fly technology, which means the data is not generated until the query is provided to the system. This allows users to interact in real-time with the databases and generate customized reports and maps. To the author's knowledge, the Breast Health Portal and Project Safety Net are the first local-scale interactive online mapping interfaces for public health data which allow users to control the data generated. For example, users may generate breast cancer incidence rates by Census tract, in real

  1. Interactive web-based mapping: bridging technology and data for health.

    PubMed

    Highfield, Linda; Arthasarnprasit, Jutas; Ottenweller, Cecelia A; Dasprez, Arnaud

    2011-12-23

    The Community Health Information System (CHIS) online mapping system was first launched in 1998. Its overarching goal was to provide researchers, residents and organizations access to health related data reflecting the overall health and well-being of their communities within the Greater Houston area. In September 2009, initial planning and development began for the next generation of CHIS. The overarching goal for the new version remained to make health data easily accessible for a wide variety of research audiences. However, in the new version we specifically sought to make the CHIS truly interactive and give the user more control over data selection and reporting. In July 2011, a beta version of the next-generation of the application was launched. This next-generation is also a web based interactive mapping tool comprised of two distinct portals: the Breast Health Portal and Project Safety Net. Both are accessed via a Google mapping interface. Geographic coverage for the portals is currently an 8 county region centered on Harris County, Texas. Data accessed by the application include Census 2000, Census 2010 (underway), cancer incidence from the Texas Cancer Registry (TX Dept. of State Health Services), death data from Texas Vital Statistics, clinic locations for free and low-cost health services, along with service lists, hours of operation, payment options and languages spoken, uninsured and poverty data. The system features query on the fly technology, which means the data is not generated until the query is provided to the system. This allows users to interact in real-time with the databases and generate customized reports and maps. To the author's knowledge, the Breast Health Portal and Project Safety Net are the first local-scale interactive online mapping interfaces for public health data which allow users to control the data generated. For example, users may generate breast cancer incidence rates by Census tract, in real time, for women aged 40

  2. Photocopy: Composite Map of Crossing Site by Daniel J. Mordell ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy: Composite Map of Crossing Site by Daniel J. Mordell from Canal Society of New York State. Bottoming Out: Useful and Interesting Notes Collected for Members of the Canal Society of New York State. Vol. 18-19. Syracuse, 1962. - Erie Canal (Enlarged), Schoharie Creek Aqueduct, Spanning Schoharie Creek, Fort Hunter, Montgomery County, NY

  3. A Global Survey of Deep Underground Facilities; Examples of Geotechnical and Engineering Capabilities, Achievements, Challenges (Mines, Shafts, Tunnels, Boreholes, Sites and Underground Facilities for Nuclear Waste and Physics R&D): A Guide to Interactive Global Map Layers, Table Database, References and Notes

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

    Tynan, Mark C.; Russell, Glenn P.; Perry, Frank V.

    These associated tables, references, notes, and report present a synthesis of some notable geotechnical and engineering information used to create four interactive layer maps for selected: 1) deep mines and shafts; 2) existing, considered or planned radioactive waste management deep underground studies or disposal facilities 3) deep large diameter boreholes, and 4) physics underground laboratories and facilities from around the world. These data are intended to facilitate user access to basic information and references regarding “deep underground” facilities, history, activities, and plans. In general, the interactive maps and database provide each facility’s approximate site location, geology, and engineered features (e.g.:more » access, geometry, depth, diameter, year of operations, groundwater, lithology, host unit name and age, basin; operator, management organization, geographic data, nearby cultural features, other). Although the survey is not comprehensive, it is representative of many of the significant existing and historical underground facilities discussed in the literature addressing radioactive waste management and deep mined geologic disposal safety systems. The global survey is intended to support and to inform: 1) interested parties and decision makers; 2) radioactive waste disposal and siting option evaluations, and 3) safety case development applicable to any mined geologic disposal facility as a demonstration of historical and current engineering and geotechnical capabilities available for use in deep underground facility siting, planning, construction, operations and monitoring.« less

  4. Value of epicardial potential maps in localizing pre-excitation sites for radiofrequency ablation. A simulation study

    NASA Astrophysics Data System (ADS)

    Hren, Rok

    1998-06-01

    Using computer simulations, we systematically investigated the limitations of an inverse solution that employs the potential distribution on the epicardial surface as an equivalent source model in localizing pre-excitation sites in Wolff-Parkinson-White syndrome. A model of the human ventricular myocardium that features an anatomically accurate geometry, an intramural rotating anisotropy and a computational implementation of the excitation process based on electrotonic interactions among cells, was used to simulate body surface potential maps (BSPMs) for 35 pre-excitation sites positioned along the atrioventricular ring. Two individualized torso models were used to account for variations in torso boundaries. Epicardial potential maps (EPMs) were computed using the L-curve inverse solution. The measure for accuracy of the localization was the distance between a position of the minimum in the inverse EPMs and the actual site of pre-excitation in the ventricular model. When the volume conductor properties and lead positions of the torso were precisely known and the measurement noise was added to the simulated BSPMs, the minimum in the inverse EPMs was at 12 ms after the onset on average within cm of the pre-excitation site. When the standard torso model was used to localize the sites of onset of the pre-excitation sequence initiated in individualized male and female torso models, the mean distance between the minimum and the pre-excitation site was cm for the male torso and cm for the female torso. The findings of our study indicate that a location of the minimum in EPMs computed using the inverse solution can offer non-invasive means for pre-interventional planning of the ablative treatment.

  5. Functional genomics platform for pooled screening and mammalian genetic interaction maps

    PubMed Central

    Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

    2014-01-01

    Systematic genetic interaction maps in microorganisms are powerful tools for identifying functional relationships between genes and defining the function of uncharacterized genes. We have recently implemented this strategy in mammalian cells as a two-stage approach. First, genes of interest are robustly identified in a pooled genome-wide screen using complex shRNA libraries. Second, phenotypes for all pairwise combinations of hit genes are measured in a double-shRNA screen and used to construct a genetic interaction map. Our protocol allows for rapid pooled screening under various conditions without a requirement for robotics, in contrast to arrayed approaches. Each stage of the protocol can be implemented in ~2 weeks, with additional time for analysis and generation of reagents. We discuss considerations for screen design, and present complete experimental procedures as well as a full computational analysis suite for identification of hits in pooled screens and generation of genetic interaction maps. While the protocols outlined here were developed for our original shRNA-based approach, they can be applied more generally, including to CRISPR-based approaches. PMID:24992097

  6. Topographic Map of Pathfinder Landing Site

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Topographic map of the landing site, to a distance of 60 meters from the lander in the LSC coordinate system. The lander is shown schematically in the center; 2.5 meter radius circle (black) centered on the camera was not mapped. Gentle relief [root mean square (rms) elevation variation 0.5 m; rms a directional slope 4O] and organization of topography into northwest and northeast-trending ridges about 20 meters apart are apparent. Roughly 30% of the illustrated area is hidden from the camera behind these ridges. Contours (0.2 m interval) and color coding of elevations were generated from a digital terrain model, which was interpolated by kriging from approximately 700 measured points. Angular and parallax point coordinates were measured manually on a large (5 m length) anaglyphic uncontrolled mosaic and used to calculate Cartesian (LSC) coordinates. Errors in azimuth on the order of 10 are therefore likely; elevation errors were minimized by referencing elevations to the local horizon. The uncertainty in range measurements increases quadratically with range. Given a measurement error of 1/2 pixel, the expected precision in range is 0.3 meter at 10 meter range, and 10 meters at 60 meter range. Repeated measurements were made, compared, and edited for consistency to improve the range precision. Systematic errors undoubtedly remain and will be corrected in future maps compiled digitally from geometrically controlled images. Cartographic processing by U.S. Geological Survey.

    NOTE: original caption as published in Science Magazine

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  7. Optimal design method to minimize users' thinking mapping load in human-machine interactions.

    PubMed

    Huang, Yanqun; Li, Xu; Zhang, Jie

    2015-01-01

    The discrepancy between human cognition and machine requirements/behaviors usually results in serious mental thinking mapping loads or even disasters in product operating. It is important to help people avoid human-machine interaction confusions and difficulties in today's mental work mastered society. Improving the usability of a product and minimizing user's thinking mapping and interpreting load in human-machine interactions. An optimal human-machine interface design method is introduced, which is based on the purpose of minimizing the mental load in thinking mapping process between users' intentions and affordance of product interface states. By analyzing the users' thinking mapping problem, an operating action model is constructed. According to human natural instincts and acquired knowledge, an expected ideal design with minimized thinking loads is uniquely determined at first. Then, creative alternatives, in terms of the way human obtains operational information, are provided as digital interface states datasets. In the last, using the cluster analysis method, an optimum solution is picked out from alternatives, by calculating the distances between two datasets. Considering multiple factors to minimize users' thinking mapping loads, a solution nearest to the ideal value is found in the human-car interaction design case. The clustering results show its effectiveness in finding an optimum solution to the mental load minimizing problems in human-machine interaction design.

  8. Learning to merge: a new tool for interactive mapping

    NASA Astrophysics Data System (ADS)

    Porter, Reid B.; Lundquist, Sheng; Ruggiero, Christy

    2013-05-01

    The task of turning raw imagery into semantically meaningful maps and overlays is a key area of remote sensing activity. Image analysts, in applications ranging from environmental monitoring to intelligence, use imagery to generate and update maps of terrain, vegetation, road networks, buildings and other relevant features. Often these tasks can be cast as a pixel labeling problem, and several interactive pixel labeling tools have been developed. These tools exploit training data, which is generated by analysts using simple and intuitive paint-program annotation tools, in order to tailor the labeling algorithm for the particular dataset and task. In other cases, the task is best cast as a pixel segmentation problem. Interactive pixel segmentation tools have also been developed, but these tools typically do not learn from training data like the pixel labeling tools do. In this paper we investigate tools for interactive pixel segmentation that also learn from user input. The input has the form of segment merging (or grouping). Merging examples are 1) easily obtained from analysts using vector annotation tools, and 2) more challenging to exploit than traditional labels. We outline the key issues in developing these interactive merging tools, and describe their application to remote sensing.

  9. Developing nurses' intercultural/intraprofessional communication skills using the EXCELLence in Cultural Experiential Learning and Leadership Social Interaction Maps.

    PubMed

    Henderson, Saras; Barker, Michelle

    2017-09-27

    To examine how the use of Social Interaction Maps, a tool in the EXCELLence in Cultural Experiential Learning and Leadership Program, can enhance the development of nurses' intercultural/intraprofessional communication skills. Nurses face communication challenges when interacting with others from similar background as well as those from a culturally and linguistically diverse background. We used the EXCELLence in Cultural Experiential Learning and Leadership Program's Social Interaction Maps tool to foster intercultural/intraprofessional communication skills in nurses. Social Interaction Maps describe verbal and nonverbal communication behaviours that model ways of communicating in a culturally appropriate manner. The maps include four stages of an interaction, namely Approach, Bridging, Communicating and Departing using the acronym ABCD. Qualitative approach was used with a purposeful sample of nurses enrolled in a postgraduate course. Fifteen participants were recruited. The Social Interaction Map tool was taught to participants in a workshop where they engaged in sociocultural communication activities using scenarios. Participants were asked to apply Social Interaction Maps in their workplaces. Six weeks later, participants completed a semistructured open-ended questionnaire and participated in a discussion forum on their experience of using Social Interaction Maps. Data were content-analysed. Four themes identified in the use of the Social Interaction Maps were (i) enhancing self-awareness of communication skills; (ii) promoting skills in being nonconfrontational during difficult interactions; (iii) highlighting the importance of A (Approach) and B (Bridging) in interaction with others; and (iv) awareness of how others interpret what is said C (Communicating) and discussing to resolve issues before closure D (Departing). Application of the EXCELLence in Cultural Experiential Learning and Leadership Social Interaction Mapping tool was shown to be useful in

  10. An Interactive Immersive Serious Game Application for Kunyu Quantu World Map

    NASA Astrophysics Data System (ADS)

    Peng, S.-T.; Hsu, S.-Y.; Hsieh, K.-C.

    2015-08-01

    In recent years, more and more digital technologies and innovative concepts are applied on museum education. One of the concepts applied is "Serious game." Serious game is not designed for entertainment purpose but allows users to learn real world's cultural and educational knowledge in the virtual world through game-experiencing. Technologies applied on serious game are identical to those applied on entertainment game. Nowadays, the interactive technology applications considering users' movement and gestures in physical spaces are developing rapidly, which are extensively used in entertainment games, such as Kinect-based games. The ability to explore space via Kinect-based games can be incorporated into the design of serious game. The ancient world map, Kunyu Quantu, from the collection of the National Palace Museum is therefore applied in serious game development. In general, the ancient world map does not only provide geological information, but also contains museum knowledge. This particular ancient world map is an excellent content applied in games as teaching material. In the 17th century, it was first used by a missionary as a medium to teach the Kangxi Emperor of the latest geologic and scientific spirits from the West. On this map, it also includes written biological knowledge and climate knowledge. Therefore, this research aims to present the design of the interactive and immersive serious game based installation that developed from the rich content of the Kunyu Quantu World Map, and to analyse visitor's experience in terms of real world's cultural knowledge learning and interactive responses.

  11. Oregon Magnetic and Gravity Maps and Data: A Web Site for Distribution of Data

    USGS Publications Warehouse

    Roberts, Carter W.; Kucks, Robert P.; Hill, Patricia L.

    2008-01-01

    This web site gives the results of a USGS project to acquire the best available, public-domain, aeromagnetic and gravity data in the United States and merge these data into uniform, composite grids for each State. The results for the State of Oregon are presented here on this site. Files of aeromagnetic and gravity grids and images are available for these States for downloading. In Oregon, 49 magnetic surveys have been knit together to form a single digital grid and map. Also, a complete Bouguer gravity anomaly grid and map was generated from 40,665 gravity station measurements in and adjacent to Oregon. In addition, a map shows the location of the aeromagnetic surveys, color-coded to the survey flight-line spacing. This project was supported by the Mineral Resource Program of the USGS.

  12. GIS-based interactive tool to map the advent of world conquerors

    NASA Astrophysics Data System (ADS)

    Lakkaraju, Mahesh

    The objective of this thesis is to show the scale and extent of some of the greatest empires the world has ever seen. This is a hybrid project between the GIS based interactive tool and the web-based JavaScript tool. This approach lets the students learn effectively about the emperors themselves while understanding how long and far their empires spread. In the GIS based tool, a map is displayed with various points on it, and when a user clicks on one point, the relevant information of what happened at that particular place is displayed. Apart from this information, users can also select the interactive animation button and can walk through a set of battles in chronological order. As mentioned, this uses Java as the main programming language, and MOJO (Map Objects Java Objects) provided by ESRI. MOJO is very effective as its GIS related features can be included in the application itself. This app. is a simple tool and has been developed for university or high school level students. D3.js is an interactive animation and visualization platform built on the Javascript framework. Though HTML5, CSS3, Javascript and SVG animations can be used to derive custom animations, this tool can help bring out results with less effort and more ease of use. Hence, it has become the most sought after visualization tool for multiple applications. D3.js has provided a map-based visualization feature so that we can easily display text-based data in a map-based interface. To draw the map and the points on it, D3.js uses data rendered in TOPO JSON format. The latitudes and longitudes can be provided, which are interpolated into the Map svg. One of the main advantages of doing it this way is that more information is retained when we use a visual medium.

  13. Mapping Site Remediation with Electrical Resistivity Tomography Explored via Coupled-Model Simulations

    NASA Astrophysics Data System (ADS)

    Power, C.; Gerhard, J. I.; Tsourlos, P.; Giannopoulos, A.

    2011-12-01

    Remediation programs for sites contaminated with dense non-aqueous phase liquids (DNAPLs) would benefit from an ability to non-intrusively map the evolving volume and extent of the DNAPL source zone. Electrical resistivity tomography (ERT) is a well-established geophysical tool, widely used outside the remediation industry, that has significant potential for mapping DNAPL source zones. However, that potential has not been realized due to challenges in data interpretation from contaminated sites - in either a qualitative or quantitative way. The objective of this study is to evaluate the potential of ERT to map realistic, evolving DNAPL source zones within complex subsurface environments during remedial efforts. For this purpose, a novel coupled model was developed that integrates a multiphase flow model (DNAPL3D-MT), which generates realistic DNAPL release scenarios, with 3DINV, an ERT model which calculates the corresponding resistivity response. This presentation will describe the developed model coupling methodology, which integrates published petrophysical relationships to generate an electrical resistivity field that accounts for both the spatial heterogeneity of subsurface soils and the evolving spatial distribution of fluids (including permeability, porosity, clay content and air/water/DNAPL saturation). It will also present an example in which the coupled model was employed to explore the ability of ERT to track the remediation of a DNAPL source zone. A field-scale, three-dimensional release of chlorinated solvent DNAPL into heterogeneous clayey sand was simulated, including the subsurface migration and subsequent removal of the DNAPL source zone via dissolution in groundwater. Periodic surveys of this site via ERT applied at the surface were then simulated and inversion programs were used to calculate the subsurface distribution of electrical properties. This presentation will summarize this approach and its potential as a research tool exploring the range

  14. Interactive Spacecraft Trajectory Design Strategies Featuring Poincare Map Topology

    NASA Astrophysics Data System (ADS)

    Schlei, Wayne R.

    Space exploration efforts are shifting towards inexpensive and more agile vehicles. Versatility regarding spacecraft trajectories refers to the agility to correct deviations from an intended path or even the ability to adapt the future path to a new destination--all with limited spaceflight resources (i.e., small DeltaV budgets). Trajectory design methods for such nimble vehicles incorporate equally versatile procedures that allow for rapid and interactive decision making while attempting to reduce Delta V budgets, leading to a versatile trajectory design platform. A versatile design paradigm requires the exploitation of Poincare map topology , or the interconnected web of dynamical structures, existing within the chaotic dynamics of multi-body gravitational models to outline low-Delta V transfer options residing nearby to a current path. This investigation details an autonomous procedure to extract the periodic orbits (topology nodes) and correlated asymptotic flow structures (or the invariant manifolds representing topology links). The autonomous process summarized in this investigation (termed PMATE) overcomes discontinuities on the Poincare section that arise in the applied multi-body model (the planar circular restricted three-body problem) and detects a wide variety of novel periodic orbits. New interactive capabilities deliver a visual analytics foundation for versatile spaceflight design, especially for initial guess generation and manipulation. Such interactive strategies include the selection of states and arcs from Poincare section visualizations and the capabilities to draw and drag trajectories to remove dependency on initial state input. Furthermore, immersive selection is expanded to cull invariant manifold structures, yielding low-DeltaV or even DeltaV-free transfers between periodic orbits. The application of interactive design strategies featuring a dense extraction of Poincare map topology is demonstrated for agile spaceflight with a simple

  15. The protein interaction map of bacteriophage lambda

    PubMed Central

    2011-01-01

    Background Bacteriophage lambda is a model phage for most other dsDNA phages and has been studied for over 60 years. Although it is probably the best-characterized phage there are still about 20 poorly understood open reading frames in its 48-kb genome. For a complete understanding we need to know all interactions among its proteins. We have manually curated the lambda literature and compiled a total of 33 interactions that have been found among lambda proteins. We set out to find out how many protein-protein interactions remain to be found in this phage. Results In order to map lambda's interactions, we have cloned 68 out of 73 lambda open reading frames (the "ORFeome") into Gateway vectors and systematically tested all proteins for interactions using exhaustive array-based yeast two-hybrid screens. These screens identified 97 interactions. We found 16 out of 30 previously published interactions (53%). We have also found at least 18 new plausible interactions among functionally related proteins. All previously found and new interactions are combined into structural and network models of phage lambda. Conclusions Phage lambda serves as a benchmark for future studies of protein interactions among phage, viruses in general, or large protein assemblies. We conclude that we could not find all the known interactions because they require chaperones, post-translational modifications, or multiple proteins for their interactions. The lambda protein network connects 12 proteins of unknown function with well characterized proteins, which should shed light on the functional associations of these uncharacterized proteins. PMID:21943085

  16. Web GIS in practice III: creating a simple interactive map of England's Strategic Health Authorities using Google Maps API, Google Earth KML, and MSN Virtual Earth Map Control

    PubMed Central

    Boulos, Maged N Kamel

    2005-01-01

    This eye-opener article aims at introducing the health GIS community to the emerging online consumer geoinformatics services from Google and Microsoft (MSN), and their potential utility in creating custom online interactive health maps. Using the programmable interfaces provided by Google and MSN, we created three interactive demonstrator maps of England's Strategic Health Authorities. These can be browsed online at – Google Maps API (Application Programming Interface) version, – Google Earth KML (Keyhole Markup Language) version, and – MSN Virtual Earth Map Control version. Google and MSN's worldwide distribution of "free" geospatial tools, imagery, and maps is to be commended as a significant step towards the ultimate "wikification" of maps and GIS. A discussion is provided of these emerging online mapping trends, their expected future implications and development directions, and associated individual privacy, national security and copyrights issues. Although ESRI have announced their planned response to Google (and MSN), it remains to be seen how their envisaged plans will materialize and compare to the offerings from Google and MSN, and also how Google and MSN mapping tools will further evolve in the near future. PMID:16176577

  17. High-resolution physical and functional mapping of the template adjacent DNA binding site in catalytically active telomerase.

    PubMed

    Romi, Erez; Baran, Nava; Gantman, Marina; Shmoish, Michael; Min, Bosun; Collins, Kathleen; Manor, Haim

    2007-05-22

    Telomerase is a cellular reverse transcriptase, which utilizes an integral RNA template to extend single-stranded telomeric DNA. We used site-specific photocrosslinking to map interactions between DNA primers and the catalytic protein subunit (tTERT) of Tetrahymena thermophila telomerase in functional enzyme complexes. Our assays reveal contact of the single-stranded DNA adjacent to the primer-template hybrid and tTERT residue W187 at the periphery of the N-terminal domain. This contact was detected in complexes with three different registers of template in the active site, suggesting that it is maintained throughout synthesis of a complete telomeric repeat. Substitution of nearby residue Q168, but not W187, alters the K(m) for primer elongation, implying that it plays a role in the DNA recognition. These findings are the first to directly demonstrate the physical location of TERT-DNA contacts in catalytically active telomerase and to identify amino acid determinants of DNA binding affinity. Our data also suggest a movement of the TERT active site relative to the template-adjacent single-stranded DNA binding site within a cycle of repeat synthesis.

  18. Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

    PubMed

    Marsh, Lorraine

    2015-01-01

    Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

  19. MIMO: an efficient tool for molecular interaction maps overlap

    PubMed Central

    2013-01-01

    Background Molecular pathways represent an ensemble of interactions occurring among molecules within the cell and between cells. The identification of similarities between molecular pathways across organisms and functions has a critical role in understanding complex biological processes. For the inference of such novel information, the comparison of molecular pathways requires to account for imperfect matches (flexibility) and to efficiently handle complex network topologies. To date, these characteristics are only partially available in tools designed to compare molecular interaction maps. Results Our approach MIMO (Molecular Interaction Maps Overlap) addresses the first problem by allowing the introduction of gaps and mismatches between query and template pathways and permits -when necessary- supervised queries incorporating a priori biological information. It then addresses the second issue by relying directly on the rich graph topology described in the Systems Biology Markup Language (SBML) standard, and uses multidigraphs to efficiently handle multiple queries on biological graph databases. The algorithm has been here successfully used to highlight the contact point between various human pathways in the Reactome database. Conclusions MIMO offers a flexible and efficient graph-matching tool for comparing complex biological pathways. PMID:23672344

  20. Mapping repulsive to attractive interaction in driven-dissipative quantum systems

    NASA Astrophysics Data System (ADS)

    Li, Andy C. Y.; Koch, Jens

    2017-11-01

    Repulsive and attractive interactions usually lead to very different physics. Striking exceptions exist in the dynamics of driven-dissipative quantum systems. For the example of a photonic Bose-Hubbard dimer, we establish a one-to-one mapping relating cases of onsite repulsion and attraction. We prove that the mapping is valid for an entire class of Markovian open quantum systems with a time-reversal-invariant Hamiltonian and physically meaningful inverse-sign Hamiltonian. To underline the broad applicability of the mapping, we illustrate the one-to-one correspondence between the nonequilibrium dynamics in a geometrically frustrated spin lattice and those in a non-frustrated partner lattice.

  1. Probing the communication of deoxythymidine triphosphate in HIV-1 reverse transcriptase by communication maps and interaction energy studies.

    PubMed

    Gnanasekaran, Ramachandran

    2017-11-08

    We calculate communication maps for HIV-1 Reverse Transcriptase (RT) to elucidate energy transfer pathways between deoxythymidine triphosphate (dTTP) and other parts of the protein. This approach locates energy transport channels from the dTTP to remote regions of the protein via residues and water molecules. We examine the water dynamics near the catalytic site of HIV-1 RT by molecular dynamics (MD) simulations. We find that, within the catalytic site, the relaxation of water molecules is similar to that of the hydration water molecules present in other proteins and the relaxation time scale is fast enough to transport energy and helps in communication between dTTP and other residues in the system. To quantify energy transfer, we also calculate the interaction energies of dTTP, 2Mg 2+ , doxy-guanosine nucleotide (DG22) with their surrounding residues by using the B3LYP-D3 method. The results, from classical vibrational energy diffusivity and QM interaction energy, are complementary to identify the important residues involved in the process of polymerization. The positive and negative interactions by dTTP with different types of residues in the catalytic region make the residues transfer energy through vibrational communication.

  2. A simple and efficient method for predicting protein-protein interaction sites.

    PubMed

    Higa, R H; Tozzi, C L

    2008-09-23

    Computational methods for predicting protein-protein interaction sites based on structural data are characterized by an accuracy between 70 and 80%. Some experimental studies indicate that only a fraction of the residues, forming clusters in the center of the interaction site, are energetically important for binding. In addition, the analysis of amino acid composition has shown that residues located in the center of the interaction site can be better discriminated from the residues in other parts of the protein surface. In the present study, we implement a simple method to predict interaction site residues exploiting this fact and show that it achieves a very competitive performance compared to other methods using the same dataset and criteria for performance evaluation (success rate of 82.1%).

  3. Similarity-transformed dyson mapping and SDG-interacting boson hamiltonian

    NASA Astrophysics Data System (ADS)

    Navrátil, P.; Dobeš, J.

    1991-10-01

    The sdg-interacting boson hamiltonian is constructed from the fermion shell-model input. The seniority boson mapping as given by the similarity-transformed Dyson boson mapping is used. The s, d, and g collective boson amplitudes are determined consistently from the mapped hamiltonian. Influence of the starting shell-model parameters is discussed. Calculations for the Sm isotopic chain and for the 148Sm, 150Nd, and 196Pt nuclei are presented. Calculated energy levels as well as E2 and E4 properties agree rather well with experimental ones. To obtain such agreement, the input shell-model parameters cannot be fixed at a constant set for several nuclei but have to be somewhat varied, especially in the deformed region. Possible reasons for this variation are discussed. Effects of the explicit g-boson consideration are shown.

  4. AlphaSpace: Fragment-Centric Topographical Mapping To Target Protein–Protein Interaction Interfaces

    PubMed Central

    2016-01-01

    Inhibition of protein–protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structural characterization of the surface using geometry-based pocket-detection methods. An attractive mapping strategy—that builds on the principles of fragment-based drug discovery (FBDD)—is to detect the fragment-centric modularity at the protein surface and then characterize the large PPI interface as a set of localized, fragment-targetable interaction regions. Here, we introduce AlphaSpace, a computational analysis tool designed for fragment-centric topographical mapping (FCTM) of PPI interfaces. Our approach uses the alpha sphere construct, a geometric feature of a protein’s Voronoi diagram, to map out concave interaction space at the protein surface. We introduce two new features—alpha-atom and alpha-space—and the concept of the alpha-atom/alpha-space pair to rank pockets for fragment-targetability and to facilitate the evaluation of pocket/fragment complementarity. The resulting high-resolution interfacial map of targetable pocket space can be used to guide the rational design and optimization of small molecule or biomimetic PPI inhibitors. PMID:26225450

  5. TumorMap: Exploring the Molecular Similarities of Cancer Samples in an Interactive Portal

    PubMed Central

    Newton, Yulia; Novak, Adam M.; Swatloski, Teresa; McColl, Duncan C.; Chopra, Sahil; Graim, Kiley; Weinstein, Alana S.; Baertsch, Robert; Salama, Sofie R.; Ellrott, Kyle; Chopra, Manu; Goldstein, Theodore C.; Haussler, David; Morozova, Olena; Stuart, Joshua M.

    2017-01-01

    Vast amounts of molecular data are being collected on tumor samples, which provide unique opportunities for discovering trends within and between cancer subtypes. Such cross-cancer analyses require computational methods that enable intuitive and interactive browsing of thousands of samples based on their molecular similarity. We created a portal called TumorMap to assist in exploration and statistical interrogation of high-dimensional complex “omics” data in an interactive and easily interpretable way. In the TumorMap, samples are arranged on a hexagonal grid based on their similarity to one another in the original genomic space and are rendered with Google’s Map technology. While the important feature of this public portal is the ability for the users to build maps from their own data, we pre-built genomic maps from several previously published projects. We demonstrate the utility of this portal by presenting results obtained from The Cancer Genome Atlas project data. PMID:29092953

  6. An interactive mapping tool for visualizing lacunarity of laser scanned point clouds

    NASA Astrophysics Data System (ADS)

    Kania, Adam; Székely, Balázs

    2016-04-01

    Lacunarity, a measure of the spatial distribution of the empty space in a certain model or real space over large spatial scales, is found to be a useful descriptive quantity in many fields using imagery, including, among others, geology, dentistry, neurology. Its application in ecology was suggested more than 20 years ago. The main problem of its application was the lack of appropriate high resolution data. Nowadays, full-waveform laser scanning, also known as FWF LiDAR, provides the tool for mapping the vegetation in unprecedented details and accuracy. Consequently, the lacunarity concept can be revitalized, in order to study the structure of the vegetation in this sense as well. Calculation of lacunarity, even if it is done in two dimensions (2D), is still has its problems: on one hand it is a number-crunching procedure, on the other hand, it produces 4D results: at each 3D point it returns a set of data that are function of scale. These data sets are difficult to visualize, to evaluate, and to compare. In order to solve this problem, an interactive mapping tool has been conceptualized that is designed to manipulate and visualize the data, lets the user set parameters for best visualization or comparison results. The system is able to load large amounts of data, visualize them as lacunarity curves, or map view as horizontal slices or in 3D point clouds coloured according to the user's choice. Lacunarity maps are presented as a series of (usually) horizontal profiles, e.g. rasters, which cells contain color-mapped values of selected lacunarity of the point cloud. As lacunarity is usually analysed in a series of successive windows sizes, the tool can show a series of rasters with sequentially animated lacunarity maps calculated for various window sizes. A very fast switching of colour schemes is possible to facilitate rapid visual feedback to better understand underlying data patterns exposed by lacunarity functions. In the comparison mode, two sites (or two areas

  7. Mapping Control and Affiliation in Teacher-Student Interaction with State Space Grids

    ERIC Educational Resources Information Center

    Mainhard, M. Tim; Pennings, Helena J. M.; Wubbels, Theo; Brekelmans, Mieke

    2012-01-01

    This paper explores how State Space Grids (SSG), a dynamic systems research method, can be used to map teacher-student interactions from moment-to-moment and thereby to incorporate temporal aspects of interaction. Interactions in two secondary school classrooms are described in terms of level of interpersonal control and affiliation, and of…

  8. An Interactive Map Viewer for the Urban Geology of Ottawa (Canada): an Example of Web Publishing

    NASA Astrophysics Data System (ADS)

    Giroux, D.; Bélanger, R.

    2003-04-01

    , subsurface database, stratigraphy, bedrock, surficial and hydrogeology maps, and a few others. At present, each layer of geospatial information in TSD's interactive map viewer is connected to simple independent flat files (i.e. shapefiles), but it is also possible to connect GEOSERV to other types of (relational) databases (e.g. Microsoft SQL Server, Oracle). Frequent updating of shapefiles could be a cumbersome task, when new records are added, since we have to completely rebuild the updated shapefiles. However, new attributes can be added to existing shapefiles easily. At present, the updating process can not be done on-the-fly; we must stop and restart the updated MapService if one of its shapefiles is changed. The public can access seventeen MapServices that provide interactive tools that users can use to query, zoom, pan, select, and so on, or print the map displayed on their monitor. The map viewer is light-weight as it uses HTML and Javascript, so end users do not have to download and install any plug-ins. A free CD and a companion web site were also developed to give access to complementary information, like high resolution raster maps and reports. Some of the datasets are available free of charge, on-line.

  9. Molecular Mapping of Restriction-Site Associated DNA Markers In Allotetraploid Upland Cotton.

    PubMed

    Wang, Yangkun; Ning, Zhiyuan; Hu, Yan; Chen, Jiedan; Zhao, Rui; Chen, Hong; Ai, Nijiang; Guo, Wangzhen; Zhang, Tianzhen

    2015-01-01

    Upland cotton (Gossypium hirsutum L., 2n = 52, AADD) is an allotetraploid, therefore the discovery of single nucleotide polymorphism (SNP) markers is difficult. The recent emergence of genome complexity reduction technologies based on the next-generation sequencing (NGS) platform has greatly expedited SNP discovery in crops with highly repetitive and complex genomes. Here we applied restriction-site associated DNA (RAD) sequencing technology for de novo SNP discovery in allotetraploid cotton. We identified 21,109 SNPs between the two parents and used these for genotyping of 161 recombinant inbred lines (RILs). Finally, a high dense linkage map comprising 4,153 loci over 3500-cM was developed based on the previous result. Using this map quantitative trait locus (QTLs) conferring fiber strength and Verticillium Wilt (VW) resistance were mapped to a more accurate region in comparison to the 1576-cM interval determined using the simple sequence repeat (SSR) genetic map. This suggests that the newly constructed map has more power and resolution than the previous SSR map. It will pave the way for the rapid identification of the marker-assisted selection in cotton breeding and cloning of QTL of interest traits.

  10. Parallel mapping of optical near-field interactions by molecular motor-driven quantum dots.

    PubMed

    Groß, Heiko; Heil, Hannah S; Ehrig, Jens; Schwarz, Friedrich W; Hecht, Bert; Diez, Stefan

    2018-04-30

    In the vicinity of metallic nanostructures, absorption and emission rates of optical emitters can be modulated by several orders of magnitude 1,2 . Control of such near-field light-matter interaction is essential for applications in biosensing 3 , light harvesting 4 and quantum communication 5,6 and requires precise mapping of optical near-field interactions, for which single-emitter probes are promising candidates 7-11 . However, currently available techniques are limited in terms of throughput, resolution and/or non-invasiveness. Here, we present an approach for the parallel mapping of optical near-field interactions with a resolution of <5 nm using surface-bound motor proteins to transport microtubules carrying single emitters (quantum dots). The deterministic motion of the quantum dots allows for the interpolation of their tracked positions, resulting in an increased spatial resolution and a suppression of localization artefacts. We apply this method to map the near-field distribution of nanoslits engraved into gold layers and find an excellent agreement with finite-difference time-domain simulations. Our technique can be readily applied to a variety of surfaces for scalable, nanometre-resolved and artefact-free near-field mapping using conventional wide-field microscopes.

  11. Jules Verne Voyager, Jr: An Interactive Map Tool for Teaching Plate Tectonics

    NASA Astrophysics Data System (ADS)

    Hamburger, M. W.; Meertens, C. M.

    2010-12-01

    We present an interactive, web-based map utility that can make new geological and geophysical results accessible to a large number and variety of users. The tool provides a user-friendly interface that allows users to access a variety of maps, satellite images, and geophysical data at a range of spatial scales. The map tool, dubbed 'Jules Verne Voyager, Jr.', allows users to interactively create maps of a variety of study areas around the world. The utility was developed in collaboration with the UNAVCO Consortium for study of global-scale tectonic processes. Users can choose from a variety of base maps (including "Face of the Earth" and "Earth at Night" satellite imagery mosaics, global topography, geoid, sea-floor age, strain rate and seismic hazard maps, and others), add a number of geographic and geophysical overlays (coastlines, political boundaries, rivers and lakes, earthquake and volcano locations, stress axes, etc.), and then superimpose both observed and model velocity vectors representing a compilation of 2933 GPS geodetic measurements from around the world. A remarkable characteristic of the geodetic compilation is that users can select from some 21 plates' frames of reference, allowing a visual representation of both 'absolute' plate motion (in a no-net rotation reference frame) and relative motion along all of the world's plate boundaries. The tool allows users to zoom among at least three map scales. The map tool can be viewed at http://jules.unavco.org/VoyagerJr/Earth. A more detailed version of the map utility, developed in conjunction with the EarthScope initiative, focuses on North America geodynamics, and provides more detailed geophysical and geographic information for the United States, Canada, and Mexico. The ‘EarthScope Voyager’ can be accessed at http://jules.unavco.org/VoyagerJr/EarthScope. Because the system uses pre-constructed gif images and overlays, the system can rapidly create and display maps to a large number of users

  12. Mapping of the binding sites involved in PSP94-CRISP-3 interaction by molecular dissection of the complex.

    PubMed

    Breed, Ananya A; Gomes, Amanda; Roy, Binita Sur; Mahale, Smita D; Pathak, Bhakti R

    2013-04-01

    Human Prostate Secretory Protein of 94 amino acids (PSP94) has been shown to bind human CRISP-3 (cysteine-rich secretory protein 3) with very high affinity. CRISP-3 belongs to the CRISP family of proteins having a PR-1 (pathogenesis related protein 1) domain at its N-terminal and ion channel regulatory (ICR) domain at its C-terminal connected by a hinge region. Functional significance of this complex is not yet known. In order to identify the residues and/or regions involved in PSP94-CRISP-3 interaction, site-directed mutagenesis was employed. Effect of the mutations on the interaction was studied by co-immunoprecipitation (Co-IP). For PSP94, amino acids Y(3), F(4), P(56) and the C-terminal β-strand were found to be crucial for interacting with CRISP-3. A disulfide bond between the two domains of PSP94 (C(37)A-C(73)A) was also important for this interaction. In case of CRISP-3, the N-terminal domain alone could not maintain a strong interaction with PSP94 but it required presence of the hinge region and not the C-terminal domain. Apart from CRISP-3, CRISP-2 was also found to interact with human PSP94. Based on our findings the most likely model of PSP94-CRISP-3 complex has been proposed. The terminal β-strands of PSP94 contact the first α-helix and the hinge region of CRISP-3. Involvement of the hinge region of CRISPs in interaction with PSP94 may affect the domain movement of CRISPs essential for the ion-channel regulatory activity resulting in inhibition of this activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. TumorMap: Exploring the Molecular Similarities of Cancer Samples in an Interactive Portal.

    PubMed

    Newton, Yulia; Novak, Adam M; Swatloski, Teresa; McColl, Duncan C; Chopra, Sahil; Graim, Kiley; Weinstein, Alana S; Baertsch, Robert; Salama, Sofie R; Ellrott, Kyle; Chopra, Manu; Goldstein, Theodore C; Haussler, David; Morozova, Olena; Stuart, Joshua M

    2017-11-01

    Vast amounts of molecular data are being collected on tumor samples, which provide unique opportunities for discovering trends within and between cancer subtypes. Such cross-cancer analyses require computational methods that enable intuitive and interactive browsing of thousands of samples based on their molecular similarity. We created a portal called TumorMap to assist in exploration and statistical interrogation of high-dimensional complex "omics" data in an interactive and easily interpretable way. In the TumorMap, samples are arranged on a hexagonal grid based on their similarity to one another in the original genomic space and are rendered with Google's Map technology. While the important feature of this public portal is the ability for the users to build maps from their own data, we pre-built genomic maps from several previously published projects. We demonstrate the utility of this portal by presenting results obtained from The Cancer Genome Atlas project data. Cancer Res; 77(21); e111-4. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Interactive Marine Spatial Planning: Siting Tidal Energy Arrays around the Mull of Kintyre

    PubMed Central

    Alexander, Karen A.; Janssen, Ron; Arciniegas, Gustavo; O'Higgins, Timothy G.; Eikelboom, Tessa; Wilding, Thomas A.

    2012-01-01

    The rapid development of the offshore renewable energy sector has led to an increased requirement for Marine Spatial Planning (MSP) and, increasingly, this is carried out in the context of the ‘ecosystem approach’ (EA) to management. We demonstrate a novel method to facilitate implementation of the EA. Using a real-time interactive mapping device (touch-table) and stakeholder workshops we gathered data and facilitated negotiation of spatial trade-offs at a potential site for tidal renewable energy off the Mull of Kintyre (Scotland). Conflicts between the interests of tidal energy developers and commercial and recreational users of the area were identified, and use preferences and concerns of stakeholders were highlighted. Social, cultural and spatial issues associated with conversion of common pool to private resource were also revealed. The method identified important gaps in existing spatial data and helped to fill these through interactive user inputs. The workshops developed a degree of consensus between conflicting users on the best areas for potential development suggesting that this approach should be adopted during MSP. PMID:22253865

  15. CellMap visualizes protein-protein interactions and subcellular localization

    PubMed Central

    Dallago, Christian; Goldberg, Tatyana; Andrade-Navarro, Miguel Angel; Alanis-Lobato, Gregorio; Rost, Burkhard

    2018-01-01

    Many tools visualize protein-protein interaction (PPI) networks. The tool introduced here, CellMap, adds one crucial novelty by visualizing PPI networks in the context of subcellular localization, i.e. the location in the cell or cellular component in which a PPI happens. Users can upload images of cells and define areas of interest against which PPIs for selected proteins are displayed (by default on a cartoon of a cell). Annotations of localization are provided by the user or through our in-house database. The visualizer and server are written in JavaScript, making CellMap easy to customize and to extend by researchers and developers. PMID:29497493

  16. Archaeological field survey automation: concurrent multisensor site mapping and automated analysis

    NASA Astrophysics Data System (ADS)

    Józefowicz, Mateusz; Sokolov, Oleksandr; Meszyński, Sebastian; Siemińska, Dominika; Kołosowski, Przemysław

    2016-04-01

    ABM SE develops mobile robots (rovers) used for analog research of Mars exploration missions. The rovers are all-terrain exploration platforms, carrying third-party payloads: scientific instrumentation. "Wisdom" ground penetrating radar for Exomars mission has been tested onboard, as well as electrical resistivity module and other devices. Robot has operated in various environments, such as Central European countryside, Dachstein ice caves or Sahara, Morocco (controlled remotely via satellite from Toruń, Poland. Currently ABM SE works on local and global positioning system for a Mars rover basing on image and IMU data. This is performed under a project from ESA. In the next Mars rover missions a Mars GIS model will be build, including an acquired GPR profile, DEM and regular image data, integrated into a concurrent 3D terrain model. It is proposed to use similar approach in surveys of archaeological sites, especially those, where solid architecture remains can be expected at shallow depths or being partially exposed. It is possible to deploy a rover that will concurrently map a selected site with GPR, 2D and 3D cameras to create a site model. The rover image processing algorithms are capable of automatic tracing of distinctive features (such as exposed structure remains on a desert ground, differences in color of the ground, etc.) and to mark regularities on a created map. It is also possible to correlate the 3D map with an aerial photo taken under any angle to achieve interpretation synergy. Currently the algorithms are an interpretation aid and their results must be confirmed by a human. The advantages of a rover over traditional approaches, such as a manual cart or a drone include: a) long hours of continuous work or work in unfavorable environment, such as high desert, frozen water pools or large areas, b) concurrent multisensory data acquisition, c) working from the ground level enables capturing of sites obstructed from the air (trees), d) it is possible to

  17. Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

    PubMed

    Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

    2016-05-12

    Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

  18. Design Considerations for Computer-Based Interactive Map Display Systems

    DTIC Science & Technology

    1979-02-01

    11 Five Dimensions for Map Display System Options . . . . . . . . . . . . . . . 12 Summary of...most advanced and exotic technologies- space , optical, computer, and graphic pro- duction; the focusing of vast organizational efforts; and the results...Information retrieval: "Where are all the radar sites in sector 12 ?," "What’s the name of this hill?," "Where’s the hill named B243?" Information storage

  19. Mapping jet-ISM interactions in X-ray binaries with ALMA: a GRS 1915+105 case study

    NASA Astrophysics Data System (ADS)

    Tetarenko, A. J.; Freeman, P.; Rosolowsky, E. W.; Miller-Jones, J. C. A.; Sivakoff, G. R.

    2018-03-01

    We present Atacama Large Millimetre/Sub-Millimetre Array (ALMA) observations of IRAS 19132+1035, a candidate jet-interstellar medium (ISM) interaction zone near the black hole X-ray binary (BHXB) GRS 1915+105. With these ALMA observations (combining data from the 12 m array and the Atacama Compact Array), we map the molecular line emission across the IRAS 19132+1035 region. We detect emission from the 12CO [J = 2 - 1], 13CO [ν = 0, J = 2 - 1], C18O [J = 2 - 1], H2CO [J = 30, 3 - 20, 2], H2CO [J = 32, 2 - 22, 1], H2CO [J = 32, 1 - 22, 0], SiO [ν = 0, J = 5 - 4], CH3OH [J = 42, 2 - 31, 2], and CS [ν = 0, J = 5 - 4] transitions. Given the morphological, spectral, and kinematic properties of this molecular emission, we present several lines of evidence that support the presence of a jet-ISM interaction at this site, including a jet-blown cavity in the molecular gas. This compelling new evidence identifies this site as a jet-ISM interaction zone, making GRS 1915+105, the third Galactic BHXB with at least one conclusive jet-ISM interaction zone. However, we find that this interaction occurs on much smaller scales than was postulated by previous work, where the BHXB jet does not appear to be dominantly powering the entire IRAS 19132+1035 region. Using estimates of the ISM conditions in the region, we utilize the detected cavity as a calorimeter to estimate the time-averaged power carried in the GRS 1915+105 jets of (8.4^{+7.7}_{-8.1})× 10^{32} erg s^{-1}. Overall, our analysis demonstrates that molecular lines are excellent diagnostic tools to identify and probe jet-ISM interaction zones near Galactic BHXBs.

  20. Improving a Synechocystis-based photoautotrophic chassis through systematic genome mapping and validation of neutral sites.

    PubMed

    Pinto, Filipe; Pacheco, Catarina C; Oliveira, Paulo; Montagud, Arnau; Landels, Andrew; Couto, Narciso; Wright, Phillip C; Urchueguía, Javier F; Tamagnini, Paula

    2015-12-01

    The use of microorganisms as cell factories frequently requires extensive molecular manipulation. Therefore, the identification of genomic neutral sites for the stable integration of ectopic DNA is required to ensure a successful outcome. Here we describe the genome mapping and validation of five neutral sites in the chromosome of Synechocystis sp. PCC 6803, foreseeing the use of this cyanobacterium as a photoautotrophic chassis. To evaluate the neutrality of these loci, insertion/deletion mutants were produced, and to assess their functionality, a synthetic green fluorescent reporter module was introduced. The constructed integrative vectors include a BioBrick-compatible multiple cloning site insulated by transcription terminators, constituting robust cloning interfaces for synthetic biology approaches. Moreover, Synechocystis mutants (chassis) ready to receive purpose-built synthetic modules/circuits are also available. This work presents a systematic approach to map and validate chromosomal neutral sites in cyanobacteria, and that can be extended to other organisms. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  1. Improving a Synechocystis-based photoautotrophic chassis through systematic genome mapping and validation of neutral sites

    PubMed Central

    Pinto, Filipe; Pacheco, Catarina C.; Oliveira, Paulo; Montagud, Arnau; Landels, Andrew; Couto, Narciso; Wright, Phillip C.; Urchueguía, Javier F.; Tamagnini, Paula

    2015-01-01

    The use of microorganisms as cell factories frequently requires extensive molecular manipulation. Therefore, the identification of genomic neutral sites for the stable integration of ectopic DNA is required to ensure a successful outcome. Here we describe the genome mapping and validation of five neutral sites in the chromosome of Synechocystis sp. PCC 6803, foreseeing the use of this cyanobacterium as a photoautotrophic chassis. To evaluate the neutrality of these loci, insertion/deletion mutants were produced, and to assess their functionality, a synthetic green fluorescent reporter module was introduced. The constructed integrative vectors include a BioBrick-compatible multiple cloning site insulated by transcription terminators, constituting robust cloning interfaces for synthetic biology approaches. Moreover, Synechocystis mutants (chassis) ready to receive purpose-built synthetic modules/circuits are also available. This work presents a systematic approach to map and validate chromosomal neutral sites in cyanobacteria, and that can be extended to other organisms. PMID:26490728

  2. Structure-function analysis of the extracellular domain of the pneumococcal cell division site positioning protein MapZ

    NASA Astrophysics Data System (ADS)

    Manuse, Sylvie; Jean, Nicolas L.; Guinot, Mégane; Lavergne, Jean-Pierre; Laguri, Cédric; Bougault, Catherine M.; Vannieuwenhze, Michael S.; Grangeasse, Christophe; Simorre, Jean-Pierre

    2016-06-01

    Accurate placement of the bacterial division site is a prerequisite for the generation of two viable and identical daughter cells. In Streptococcus pneumoniae, the positive regulatory mechanism involving the membrane protein MapZ positions precisely the conserved cell division protein FtsZ at the cell centre. Here we characterize the structure of the extracellular domain of MapZ and show that it displays a bi-modular structure composed of two subdomains separated by a flexible serine-rich linker. We further demonstrate in vivo that the N-terminal subdomain serves as a pedestal for the C-terminal subdomain, which determines the ability of MapZ to mark the division site. The C-terminal subdomain displays a patch of conserved amino acids and we show that this patch defines a structural motif crucial for MapZ function. Altogether, this structure-function analysis of MapZ provides the first molecular characterization of a positive regulatory process of bacterial cell division.

  3. Testing a small UAS for mapping artisanal diamond mining sites in Africa

    USGS Publications Warehouse

    Malpeli, Katherine C.; Chirico, Peter G.

    2015-01-01

    Remote sensing technology is advancing at an unprecedented rate. At the forefront of the new technological developments are unmanned aircraft systems (UAS). The advent of small, lightweight, low-cost, and user-friendly UAS is greatly expanding the potential applications of remote sensing technology and improving the set of tools available to researchers seeking to map and monitor terrain from above. In this article, we explore the applications of a small UAS for mapping informal diamond mining sites in Africa. We found that this technology provides aerial imagery of unparalleled resolution in a data-sparse, difficult to access, and remote terrain.

  4. DotMapper: an open source tool for creating interactive disease point maps.

    PubMed

    Smith, Catherine M; Hayward, Andrew C

    2016-04-12

    Molecular strain typing of tuberculosis isolates has led to increased understanding of the epidemiological characteristics of the disease and improvements in its control, diagnosis and treatment. However, molecular cluster investigations, which aim to detect previously unidentified cases, remain challenging. Interactive dot mapping is a simple approach which could aid investigations by highlighting cases likely to share epidemiological links. Current tools generally require technical expertise or lack interactivity. We designed a flexible application for producing disease dot maps using Shiny, a web application framework for the statistical software, R. The application displays locations of cases on an interactive map colour coded according to levels of categorical variables such as demographics and risk factors. Cases can be filtered by selecting combinations of these characteristics and by notification date. It can be used to rapidly identify geographic patterns amongst cases in molecular clusters of tuberculosis in space and time; generate hypotheses about disease transmission; identify outliers, and guide targeted control measures. DotMapper is a user-friendly application which enables rapid production of maps displaying locations of cases and their epidemiological characteristics without the need for specialist training in geographic information systems. Enhanced understanding of tuberculosis transmission using this application could facilitate improved detection of cases with epidemiological links and therefore lessen the public health impacts of the disease. It is a flexible system and also has broad international potential application to other investigations using geo-coded health information.

  5. Interactive Map | USDA Plant Hardiness Zone Map

    Science.gov Websites

    Choose Basemap: Terrain Road Map Satellite Image Turn on Basemap Roads and Labels Zone Color Transparency menu to switch between Terrain, Road Map, and Satellite Image. Turn on Basemap Roads and Labels Click option is available only for Terrain and Satellite Image basemap choices. Zone Color Transparency The

  6. A Protein Interaction Map of the Kalimantacin Biosynthesis Assembly Line

    PubMed Central

    Uytterhoeven, Birgit; Lathouwers, Thomas; Voet, Marleen; Michiels, Chris W.; Lavigne, Rob

    2016-01-01

    The antimicrobial secondary metabolite kalimantacin (also called batumin) is produced by a hybrid polyketide/non-ribosomal peptide system in Pseudomonas fluorescens BCCM_ID9359. In this study, the kalimantacin biosynthesis gene cluster is analyzed by yeast two-hybrid analysis, creating a protein–protein interaction map of the entire assembly line. In total, 28 potential interactions were identified, of which 13 could be confirmed further. These interactions include the dimerization of ketosynthase domains, a link between assembly line modules 9 and 10, and a specific interaction between the trans-acting enoyl reductase BatK and the carrier proteins of modules 8 and 10. These interactions reveal fundamental insight into the biosynthesis of secondary metabolites. This study is the first to reveal interactions in a complete biosynthetic pathway. Similar future studies could build a strong basis for engineering strategies in such clusters. PMID:27853452

  7. Predicting Ligand Binding Sites on Protein Surfaces by 3-Dimensional Probability Density Distributions of Interacting Atoms

    PubMed Central

    Jian, Jhih-Wei; Elumalai, Pavadai; Pitti, Thejkiran; Wu, Chih Yuan; Tsai, Keng-Chang; Chang, Jeng-Yih; Peng, Hung-Pin; Yang, An-Suei

    2016-01-01

    Predicting ligand binding sites (LBSs) on protein structures, which are obtained either from experimental or computational methods, is a useful first step in functional annotation or structure-based drug design for the protein structures. In this work, the structure-based machine learning algorithm ISMBLab-LIG was developed to predict LBSs on protein surfaces with input attributes derived from the three-dimensional probability density maps of interacting atoms, which were reconstructed on the query protein surfaces and were relatively insensitive to local conformational variations of the tentative ligand binding sites. The prediction accuracy of the ISMBLab-LIG predictors is comparable to that of the best LBS predictors benchmarked on several well-established testing datasets. More importantly, the ISMBLab-LIG algorithm has substantial tolerance to the prediction uncertainties of computationally derived protein structure models. As such, the method is particularly useful for predicting LBSs not only on experimental protein structures without known LBS templates in the database but also on computationally predicted model protein structures with structural uncertainties in the tentative ligand binding sites. PMID:27513851

  8. Signatures of Pleiotropy, Economy and Convergent Evolution in a Domain-Resolved Map of Human–Virus Protein–Protein Interaction Networks

    PubMed Central

    Garamszegi, Sara; Franzosa, Eric A.; Xia, Yu

    2013-01-01

    A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are

  9. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    PubMed

    Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

    2013-01-01

    A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are

  10. Depth-to-Ice Map of a Southern Mars Site Near Melea Planum

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Color coding in this map of a far-southern site on Mars indicates the change in nighttime ground-surface temperature between summer and fall. This site, like most of high-latitude Mars, has water ice mixed with soil near the surface. The ice is probably in a rock-hard frozen layer beneath a few centimeters or inches of looser, dry soil. The amount of temperature change at the surface likely corresponds to how close to the surface the icy material lies.

    The dense, icy layer retains heat better than the looser soil above it, so where the icy layer is closer to the surface, the surface temperature changes more slowly than where the icy layer is buried deeper. On the map, areas of the surface that cooled more slowly between summer and autumn (interpreted as having the ice closer to the surface) are coded blue and green. Areas that cooled more quickly (interpreted as having more distance to the ice) are coded red and yellow.

    The depth to the top of the icy layer estimated from these observations suggests that in some areas, but not others, water is being exchanged by diffusion between atmospheric water vapor and subsurface water ice. Differences in what type of material lies above the ice appear to affect the depth to the ice. The area in this image with the greatest seasonal change in surface temperature corresponds to an area of sand dunes.

    This map and its interpretation are in a May 3, 2007, report in the journal Nature by Joshua Bandfield of Arizona State University, Tempe. The Thermal Emission Imaging System camera on NASA's Mars Odyssey orbiter collected the data presented in the map. The site is centered near 67 degrees south latitude, 36.5 degrees east longitude, near a plain named Melea Planum. This site is within the portion of the planet where, in 2002, the Gamma Ray Spectrometer suite of instruments on Mars Odyssey found evidence for water ice lying just below the surface. The information from the Gamma Ray Spectrometer is

  11. Geologic map of the MTM 25047 and 20047 quadrangles, central Chryse Planitia/Viking 1 Lander site, Mars

    USGS Publications Warehouse

    Crumpler, L.S.; Craddock, R.A.; Aubele, J.C.

    2001-01-01

    This map uses Viking Orbiter image data and Viking 1 Lander image data to evaluate the geologic history of a part of Chryse Planitia, Mars. The map area lies at the termini of the Maja and Kasei Valles outwash channels and includes the site of the Viking 1 Lander. The photomosaic base for these quadrangles was assembled from 98 Viking Orbiter frames comprising 1204 pixels per line and 1056 lines and ranging in resolution from 20 to 200 m/pixel. These orbital image data were supplemented with images of the surface as seen from the Viking 1 Lander, one of only three sites on the martian surface where planetary geologic mapping is assisted by ground truth.

  12. Mapping the Interaction Site for a β-Scorpion Toxin in the Pore Module of Domain III of Voltage-gated Na+ Channels*

    PubMed Central

    Zhang, Joel Z.; Yarov-Yarovoy, Vladimir; Scheuer, Todd; Karbat, Izhar; Cohen, Lior; Gordon, Dalia; Gurevitz, Michael; Catterall, William A.

    2012-01-01

    Activation of voltage-gated sodium (Nav) channels initiates and propagates action potentials in electrically excitable cells. β-Scorpion toxins, including toxin IV from Centruroides suffusus suffusus (CssIV), enhance activation of NaV channels. CssIV stabilizes the voltage sensor in domain II in its activated state via a voltage-sensor trapping mechanism. Amino acid residues required for the action of CssIV have been identified in the S1-S2 and S3-S4 extracellular loops of domain II. The extracellular loops of domain III are also involved in toxin action, but individual amino acid residues have not been identified. We used site-directed mutagenesis and voltage clamp recording to investigate amino acid residues of domain III that are involved in CssIV action. In the IIISS2-S6 loop, five substitutions at four positions altered voltage-sensor trapping by CssIVE15A. Three substitutions (E1438A, D1445A, and D1445Y) markedly decreased voltage-sensor trapping, whereas the other two substitutions (N1436G and L1439A) increased voltage-sensor trapping. These bidirectional effects suggest that residues in IIISS2-S6 make both positive and negative interactions with CssIV. N1436G enhanced voltage-sensor trapping via increased binding affinity to the resting state, whereas L1439A increased voltage-sensor trapping efficacy. Based on these results, a three-dimensional model of the toxin-channel interaction was developed using the Rosetta modeling method. These data provide additional molecular insight into the voltage-sensor trapping mechanism of toxin action and define a three-point interaction site for β-scorpion toxins on NaV channels. Binding of α- and β-scorpion toxins to two distinct, pseudo-symmetrically organized receptor sites on NaV channels acts synergistically to modify channel gating and paralyze prey. PMID:22761417

  13. Perceived usefulness, perceived ease of use, and perceived enjoyment as drivers for the user acceptance of interactive mobile maps

    NASA Astrophysics Data System (ADS)

    Hussain, Azham; Mkpojiogu, Emmanuel O. C.; Yusof, Muhammad Mat

    2016-08-01

    This study examines the user perception of usefulness, ease of use and enjoyment as drivers for the users' complex interaction with map on mobile devices. TAM model was used to evaluate users' intention to use and their acceptance of interactive mobile map using the above three beliefs as antecedents. Quantitative research (survey) methodology was employed and the analysis and findings showed that all the three explanatory variables used in this study, explain the variability in the user acceptance of interactive mobile map technology. Perceived usefulness, perceived ease of use, and perceived enjoyment each have significant positive influence on user acceptance of interactive mobile maps. This study further validates the TAM model.

  14. Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

    PubMed

    Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

    2017-01-01

    Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

  15. Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

    PubMed Central

    Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

    2017-01-01

    Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

  16. A genome-wide map of hyper-edited RNA reveals numerous new sites.

    PubMed

    Porath, Hagit T; Carmi, Shai; Levanon, Erez Y

    2014-08-27

    Adenosine-to-inosine editing is one of the most frequent post-transcriptional modifications, manifested as A-to-G mismatches when comparing RNA sequences with their source DNA. Recently, a number of RNA-seq data sets have been screened for the presence of A-to-G editing, and hundreds of thousands of editing sites identified. Here we show that existing screens missed the majority of sites by ignoring reads with excessive ('hyper') editing that do not easily align to the genome. We show that careful alignment and examination of the unmapped reads in RNA-seq studies reveal numerous new sites, usually many more than originally discovered, and in precisely those regions that are most heavily edited. Specifically, we discover 327,096 new editing sites in the heavily studied Illumina Human BodyMap data and more than double the number of detected sites in several published screens. We also identify thousands of new sites in mouse, rat, opossum and fly. Our results establish that hyper-editing events account for the majority of editing sites.

  17. Efficient implementation of three-dimensional reference interaction site model self-consistent-field method: Application to solvatochromic shift calculations

    NASA Astrophysics Data System (ADS)

    Minezawa, Noriyuki; Kato, Shigeki

    2007-02-01

    The authors present an implementation of the three-dimensional reference interaction site model self-consistent-field (3D-RISM-SCF) method. First, they introduce a robust and efficient algorithm for solving the 3D-RISM equation. The algorithm is a hybrid of the Newton-Raphson and Picard methods. The Jacobian matrix is analytically expressed in a computationally useful form. Second, they discuss the solute-solvent electrostatic interaction. For the solute to solvent route, the electrostatic potential (ESP) map on a 3D grid is constructed directly from the electron density. The charge fitting procedure is not required to determine the ESP. For the solvent to solute route, the ESP acting on the solute molecule is derived from the solvent charge distribution obtained by solving the 3D-RISM equation. Matrix elements of the solute-solvent interaction are evaluated by the direct numerical integration. A remarkable reduction in the computational time is observed in both routes. Finally, the authors implement the first derivatives of the free energy with respect to the solute nuclear coordinates. They apply the present method to "solute" water and formaldehyde in aqueous solvent using the simple point charge model, and the results are compared with those from other methods: the six-dimensional molecular Ornstein-Zernike SCF, the one-dimensional site-site RISM-SCF, and the polarizable continuum model. The authors also calculate the solvatochromic shifts of acetone, benzonitrile, and nitrobenzene using the present method and compare them with the experimental and other theoretical results.

  18. Efficient implementation of three-dimensional reference interaction site model self-consistent-field method: application to solvatochromic shift calculations.

    PubMed

    Minezawa, Noriyuki; Kato, Shigeki

    2007-02-07

    The authors present an implementation of the three-dimensional reference interaction site model self-consistent-field (3D-RISM-SCF) method. First, they introduce a robust and efficient algorithm for solving the 3D-RISM equation. The algorithm is a hybrid of the Newton-Raphson and Picard methods. The Jacobian matrix is analytically expressed in a computationally useful form. Second, they discuss the solute-solvent electrostatic interaction. For the solute to solvent route, the electrostatic potential (ESP) map on a 3D grid is constructed directly from the electron density. The charge fitting procedure is not required to determine the ESP. For the solvent to solute route, the ESP acting on the solute molecule is derived from the solvent charge distribution obtained by solving the 3D-RISM equation. Matrix elements of the solute-solvent interaction are evaluated by the direct numerical integration. A remarkable reduction in the computational time is observed in both routes. Finally, the authors implement the first derivatives of the free energy with respect to the solute nuclear coordinates. They apply the present method to "solute" water and formaldehyde in aqueous solvent using the simple point charge model, and the results are compared with those from other methods: the six-dimensional molecular Ornstein-Zernike SCF, the one-dimensional site-site RISM-SCF, and the polarizable continuum model. The authors also calculate the solvatochromic shifts of acetone, benzonitrile, and nitrobenzene using the present method and compare them with the experimental and other theoretical results.

  19. Interactions of the GM2 activator protein with phosphatidylcholine bilayers: a site-directed spin-labeling power saturation study.

    PubMed

    Mathias, Jordan D; Ran, Yong; Carter, Jeffery D; Fanucci, Gail E

    2009-09-02

    The GM2 activator protein (GM2AP) is an accessory protein that is an essential component in the catabolism of the ganglioside GM2. A function of GM2AP is to bind and extract GM2 from intralysosomal vesicles, forming a soluble protein-lipid complex, which interacts with the hydrolase Hexosaminidase A, the enzyme that cleaves the terminal sugar group of GM2. Here, we used site-directed spin labeling with power saturation electron paramagnetic resonance to determine the surface-bound orientation of GM2AP upon phosphatidylcholine vesicles. Because GM2AP extracts lipid ligands from the vesicle and is undergoing exchange on and off the vesicle surface, we utilized a nickel-chelating lipid to localize the paramagnetic metal collider to the lipid bilayer-aqueous interface. Spin-labeled sites that collide with the lipid-bound metal relaxing agent provide a means for mapping sites of the protein that interact with the lipid bilayer interface. Results show that GM2AP binds to lipid bilayers such that the residues lining the lipid-binding cavity lie on the vesicle surface. This orientation creates a favorable microenvironment that can allow for the lipid tails to flip out of the bilayer directly into the hydrophobic pocket of GM2AP.

  20. Mapping of epitopes and structural analysis of antigenic sites in the nucleoprotein of rabies virus.

    PubMed

    Goto, H; Minamoto, N; Ito, H; Ito, N; Sugiyama, M; Kinjo, T; Kawai, A

    2000-01-01

    Linear epitopes on the rabies virus nucleoprotein (N) recognized by six MAbs raised against antigenic sites I (MAbs 6-4, 12-2 and 13-27) and IV (MAbs 6-9, 7-12 and 8-1) were investigated. Based on our previous studies on sites I and IV, 24 consecutively overlapping octapeptides and N- and C-terminal-deleted mutant N proteins were prepared. Results showed that all three site I epitopes studied and two site IV epitopes (for MAbs 8-1 and 6-9) mapped to aa 358-367, and that the other site IV epitope of MAb 7-12 mapped to aa 375-383. Tests using chimeric and truncated proteins showed that MAb 8-1 also requires the N-terminal sequence of the N protein to recognize its binding region more efficiently. Immunofluorescence studies demonstrated that all three site I-specific MAbs and one site IV-specific MAb (7-12) stained the N antigen that was diffusely distributed in the whole cytoplasm; the other two site IV-specific MAbs (6-9 and 8-1) detected only the N antigen in the cytoplasmic inclusion bodies (CIB). An antigenic site II-specific MAb (6-17) also detected CIB-associated N antigen alone. Furthermore, the level of diffuse N antigens decreased after treatment of infected cells with cycloheximide. These results suggest that epitopes at site I are expressed on the immature form of the N protein, but epitope structures of site IV MAbs 6-9 and 8-1 are created and/or exposed only after maturation of the N protein.

  1. Mapping intermolecular interactions and active site conformations: from human MMP-1 crystal structure to molecular dynamics free energy calculations.

    PubMed

    Nash, Anthony; Birch, Helen L; de Leeuw, Nora H

    2017-02-01

    The zinc-dependent Matrix Metalloproteinases (MMPs) found within the extracellular matrix (ECM) of vertebrates are linked to pathological processes such as arthritis, skin ulceration and cancer. Although a general backbone proteolytic mechanism is understood, crystallographic data continue to suggest an active site that is too narrow to encompass the respective substrate. We present a fully parameterised Molecular Dynamics (MD) study of the structural properties of an MMP-1-collagen crystallographic structure (Protein Data Bank - 4AUO), followed by an exploration of the free energy surface of a collagen polypeptide chain entering the active site, using a combined meta-dynamics and umbrella sampling (MDUS) approach. We conclude that the interactions between MMP-1 and the collagen substrate are in good agreement with a number of experimental studies. As such, our unrestrained MD simulations and our MDUS results, which indicate an energetic barrier for a local uncoiling and insertion event, can inform future investigations of the collagen-peptide non-bonded association steps with the active site prior to proteolytic mechanisms. The elucidation of such free energy barriers provides a better understanding of the role of the enzyme in the ECM and is important in the design of future MMP inhibitors.

  2. KIDFamMap: a database of kinase-inhibitor-disease family maps for kinase inhibitor selectivity and binding mechanisms

    PubMed Central

    Chiu, Yi-Yuan; Lin, Chih-Ta; Huang, Jhang-Wei; Hsu, Kai-Cheng; Tseng, Jen-Hu; You, Syuan-Ren; Yang, Jinn-Moon

    2013-01-01

    Kinases play central roles in signaling pathways and are promising therapeutic targets for many diseases. Designing selective kinase inhibitors is an emergent and challenging task, because kinases share an evolutionary conserved ATP-binding site. KIDFamMap (http://gemdock.life.nctu.edu.tw/KIDFamMap/) is the first database to explore kinase-inhibitor families (KIFs) and kinase-inhibitor-disease (KID) relationships for kinase inhibitor selectivity and mechanisms. This database includes 1208 KIFs, 962 KIDs, 55 603 kinase-inhibitor interactions (KIIs), 35 788 kinase inhibitors, 399 human protein kinases, 339 diseases and 638 disease allelic variants. Here, a KIF can be defined as follows: (i) the kinases in the KIF with significant sequence similarity, (ii) the inhibitors in the KIF with significant topology similarity and (iii) the KIIs in the KIF with significant interaction similarity. The KIIs within a KIF are often conserved on some consensus KIDFamMap anchors, which represent conserved interactions between the kinase subsites and consensus moieties of their inhibitors. Our experimental results reveal that the members of a KIF often possess similar inhibition profiles. The KIDFamMap anchors can reflect kinase conformations types, kinase functions and kinase inhibitor selectivity. We believe that KIDFamMap provides biological insights into kinase inhibitor selectivity and binding mechanisms. PMID:23193279

  3. Integrating physical and genetic maps: from genomes to interaction networks

    PubMed Central

    Beyer, Andreas; Bandyopadhyay, Sourav; Ideker, Trey

    2009-01-01

    Physical and genetic mapping data have become as important to network biology as they once were to the Human Genome Project. Integrating physical and genetic networks currently faces several challenges: increasing the coverage of each type of network; establishing methods to assemble individual interaction measurements into contiguous pathway models; and annotating these pathways with detailed functional information. A particular challenge involves reconciling the wide variety of interaction types that are currently available. For this purpose, recent studies have sought to classify genetic and physical interactions along several complementary dimensions, such as ordered versus unordered, alleviating versus aggravating, and first versus second degree. PMID:17703239

  4. Antiferromagnetic interaction between A'-site Mn spins in A-site-ordered perovskite YMn3Al4O12.

    PubMed

    Tohyama, Takenori; Saito, Takashi; Mizumaki, Masaichiro; Agui, Akane; Shimakawa, Yuichi

    2010-03-01

    The A-site-ordered perovskite YMn(3)Al(4)O(12) was prepared by high-pressure synthesis. Structural analysis with synchrotron powder X-ray diffraction data and the Mn L-edges X-ray absorption spectrum revealed that the compound has a chemical composition Y(3+)Mn(3+)(3)Al(3+)(4)O(2-)(12) with magnetic Mn(3+) at the A' site and non-magnetic Al(3+) at the B site. An antiferromagnetic interaction between the A'-site Mn(3+) spins is induced by the nearest neighboring Mn-Mn direct exchange interaction and causes an antiferromagnetic transition at 34.3 K.

  5. Mapping protein-RNA interactions by RCAP, RNA-cross-linking and peptide fingerprinting.

    PubMed

    Vaughan, Robert C; Kao, C Cheng

    2015-01-01

    RNA nanotechnology often feature protein RNA complexes. The interaction between proteins and large RNAs are difficult to study using traditional structure-based methods like NMR or X-ray crystallography. RCAP, an approach that uses reversible-cross-linking affinity purification method coupled with mass spectrometry, has been developed to map regions within proteins that contact RNA. This chapter details how RCAP is applied to map protein-RNA contacts within virions.

  6. Characterization of Protein-Carbohydrate Interactions by NMR Spectroscopy.

    PubMed

    Grondin, Julie M; Langelaan, David N; Smith, Steven P

    2017-01-01

    Solution-state nuclear magnetic resonance (NMR) spectroscopy can be used to monitor protein-carbohydrate interactions. Two-dimensional 1 H- 15 N heteronuclear single quantum coherence (HSQC)-based techniques described in this chapter can be used quickly and effectively to screen a set of possible carbohydrate binding partners, to quantify the dissociation constant (K d ) of any identified interactions, and to map the carbohydrate binding site on the structure of the protein. Here, we describe the titration of a family 32 carbohydrate binding module from Clostridium perfringens (CpCBM32) with the monosaccharide N-acetylgalactosamine (GalNAc), in which we calculate the apparent dissociation of the interaction, and map the GalNAc binding site onto the structure of CpCBM32.

  7. Student Interaction with Campus Help-Givers: Mapping the Network's Efficacy.

    ERIC Educational Resources Information Center

    Huebner, Lois A.; And Others

    Procedures to map the broad outline of student interaction with various help-giving persons and campus agencies were investigated. A sample of 633 undergraduate students completed an 8-part problem-solving questionnaire that identified current problems, problems that previously existed, the 5 most important problems, improvement rates for the most…

  8. GenProBiS: web server for mapping of sequence variants to protein binding sites.

    PubMed

    Konc, Janez; Skrlj, Blaz; Erzen, Nika; Kunej, Tanja; Janezic, Dusanka

    2017-07-03

    Discovery of potentially deleterious sequence variants is important and has wide implications for research and generation of new hypotheses in human and veterinary medicine, and drug discovery. The GenProBiS web server maps sequence variants to protein structures from the Protein Data Bank (PDB), and further to protein-protein, protein-nucleic acid, protein-compound, and protein-metal ion binding sites. The concept of a protein-compound binding site is understood in the broadest sense, which includes glycosylation and other post-translational modification sites. Binding sites were defined by local structural comparisons of whole protein structures using the Protein Binding Sites (ProBiS) algorithm and transposition of ligands from the similar binding sites found to the query protein using the ProBiS-ligands approach with new improvements introduced in GenProBiS. Binding site surfaces were generated as three-dimensional grids encompassing the space occupied by predicted ligands. The server allows intuitive visual exploration of comprehensively mapped variants, such as human somatic mis-sense mutations related to cancer and non-synonymous single nucleotide polymorphisms from 21 species, within the predicted binding sites regions for about 80 000 PDB protein structures using fast WebGL graphics. The GenProBiS web server is open and free to all users at http://genprobis.insilab.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Invariants, Attractors and Bifurcation in Two Dimensional Maps with Polynomial Interaction

    NASA Astrophysics Data System (ADS)

    Hacinliyan, Avadis Simon; Aybar, Orhan Ozgur; Aybar, Ilknur Kusbeyzi

    This work will present an extended discrete-time analysis on maps and their generalizations including iteration in order to better understand the resulting enrichment of the bifurcation properties. The standard concepts of stability analysis and bifurcation theory for maps will be used. Both iterated maps and flows are used as models for chaotic behavior. It is well known that when flows are converted to maps by discretization, the equilibrium points remain the same but a richer bifurcation scheme is observed. For example, the logistic map has a very simple behavior as a differential equation but as a map fold and period doubling bifurcations are observed. A way to gain information about the global structure of the state space of a dynamical system is investigating invariant manifolds of saddle equilibrium points. Studying the intersections of the stable and unstable manifolds are essential for understanding the structure of a dynamical system. It has been known that the Lotka-Volterra map and systems that can be reduced to it or its generalizations in special cases involving local and polynomial interactions admit invariant manifolds. Bifurcation analysis of this map and its higher iterates can be done to understand the global structure of the system and the artifacts of the discretization by comparing with the corresponding results from the differential equation on which they are based.

  10. The Documentation of Historic Maps of World Heritage Site City Suzhou

    NASA Astrophysics Data System (ADS)

    Guangwei, Z.

    2013-07-01

    Documentation and analysis of historic maps enhance understanding of temporal and spatial interactions between events and the evolution of physical canals upon which they occurred. And the challenge of this work lies on carefully sifting of information through the maps drawn with relative accuracy by traditional cartographical principles before the emergence of scientific survey. This research project focuses on sorting out the evolution of historic city Suzhou in a spatio-temporal view. The investigation was conducted through an in-depth analysis of historic maps. Re-projection of the geographical elements of the city to one single georeference, that is to say a standard map BASE, help acquiring an actual sense of the scale and facilitate the recognition of the city's evolution in clear details. It is an important contribution of this thesis in coordination of variously distorted geographical information contained in nineteen periods span from 1229 to 2013 into a single research resource. Through the work both quantitative and qualitative, a clear vision of the evolution and characteristics of the urban structure of ancient Suzhou is achieved. Meanwhile, in the process of projecting the historical geometrical information onto the topographic map, historical bibliographic and cartographic records is key to the data coordination and readjustment, this inspire as well on the cautious utilization of historical materials from ancient time in the recording, documentation work.

  11. KinMap: a web-based tool for interactive navigation through human kinome data.

    PubMed

    Eid, Sameh; Turk, Samo; Volkamer, Andrea; Rippmann, Friedrich; Fulle, Simone

    2017-01-05

    Annotations of the phylogenetic tree of the human kinome is an intuitive way to visualize compound profiling data, structural features of kinases or functional relationships within this important class of proteins. The increasing volume and complexity of kinase-related data underlines the need for a tool that enables complex queries pertaining to kinase disease involvement and potential therapeutic uses of kinase inhibitors. Here, we present KinMap, a user-friendly online tool that facilitates the interactive navigation through kinase knowledge by linking biochemical, structural, and disease association data to the human kinome tree. To this end, preprocessed data from freely-available sources, such as ChEMBL, the Protein Data Bank, and the Center for Therapeutic Target Validation platform are integrated into KinMap and can easily be complemented by proprietary data. The value of KinMap will be exemplarily demonstrated for uncovering new therapeutic indications of known kinase inhibitors and for prioritizing kinases for drug development efforts. KinMap represents a new generation of kinome tree viewers which facilitates interactive exploration of the human kinome. KinMap enables generation of high-quality annotated images of the human kinome tree as well as exchange of kinome-related data in scientific communications. Furthermore, KinMap supports multiple input and output formats and recognizes alternative kinase names and links them to a unified naming scheme, which makes it a useful tool across different disciplines and applications. A web-service of KinMap is freely available at http://www.kinhub.org/kinmap/ .

  12. High-resolution melt analysis to identify and map sequence-tagged site anchor points onto linkage maps: a white lupin (Lupinus albus) map as an exemplar.

    PubMed

    Croxford, Adam E; Rogers, Tom; Caligari, Peter D S; Wilkinson, Michael J

    2008-01-01

    * The provision of sequence-tagged site (STS) anchor points allows meaningful comparisons between mapping studies but can be a time-consuming process for nonmodel species or orphan crops. * Here, the first use of high-resolution melt analysis (HRM) to generate STS markers for use in linkage mapping is described. This strategy is rapid and low-cost, and circumvents the need for labelled primers or amplicon fractionation. * Using white lupin (Lupinus albus, x = 25) as a case study, HRM analysis was applied to identify 91 polymorphic markers from expressed sequence tag (EST)-derived and genomic libraries. Of these, 77 generated STS anchor points in the first fully resolved linkage map of the species. The map also included 230 amplified fragment length polymorphisms (AFLP) loci, spanned 1916 cM (84.2% coverage) and divided into the expected 25 linkage groups. * Quantitative trait loci (QTL) analyses performed on the population revealed genomic regions associated with several traits, including the agronomically important time to flowering (tf), alkaloid synthesis and stem height (Ph). Use of HRM-STS markers also allowed us to make direct comparisons between our map and that of the related crop, Lupinus angustifolius, based on the conversion of RFLP, microsatellite and single nucleotide polymorphism (SNP) markers into HRM markers.

  13. Arctic Research Mapping Application (ARMAP): 2D Maps and 3D Globes Support Arctic Science

    NASA Astrophysics Data System (ADS)

    Johnson, G.; Gaylord, A. G.; Brady, J. J.; Cody, R. P.; Aguilar, J. A.; Dover, M.; Garcia-Lavigne, D.; Manley, W.; Score, R.; Tweedie, C. E.

    2007-12-01

    The Arctic Research Mapping Application (ARMAP) is a suite of online services to provide support of Arctic science. These services include: a text based online search utility, 2D Internet Map Server (IMS); 3D globes and Open Geospatial Consortium (OGC) Web Map Services (WMS). With ARMAP's 2D maps and 3D globes, users can navigate to areas of interest, view a variety of map layers, and explore U.S. Federally funded research projects. Projects can be queried by location, year, funding program, discipline, and keyword. Links take you to specific information and other web sites associated with a particular research project. The Arctic Research Logistics Support Service (ARLSS) database is the foundation of ARMAP including US research funded by the National Science Foundation, National Aeronautics and Space Administration, National Oceanic and Atmospheric Administration, and the United States Geological Survey. Avoiding a duplication of effort has been a primary objective of the ARMAP project which incorporates best practices (e.g. Spatial Data Infrastructure and OGC standard web services and metadata) and off the shelf technologies where appropriate. The ARMAP suite provides tools for users of various levels of technical ability to interact with the data by importing the web services directly into their own GIS applications and virtual globes; performing advanced GIS queries; simply printing maps from a set of predefined images in the map gallery; browsing the layers in an IMS; or by choosing to "fly to" sites using a 3D globe. With special emphasis on the International Polar Year (IPY), ARMAP has targeted science planners, scientists, educators, and the general public. In sum, ARMAP goes beyond a simple map display to enable analysis, synthesis, and coordination of Arctic research. ARMAP may be accessed via the gateway web site at http://www.armap.org.

  14. Developing Vs30 site-condition maps by combining observations with geologic and topographic constraints

    USGS Publications Warehouse

    Thompson, E.M.; Wald, D.J.

    2012-01-01

    Despite obvious limitations as a proxy for site amplification, the use of time-averaged shear-wave velocity over the top 30 m (VS30) remains widely practiced, most notably through its use as an explanatory variable in ground motion prediction equations (and thus hazard maps and ShakeMaps, among other applications). As such, we are developing an improved strategy for producing VS30 maps given the common observational constraints. Using the abundant VS30 measurements in Taiwan, we compare alternative mapping methods that combine topographic slope, surface geology, and spatial correlation structure. The different VS30 mapping algorithms are distinguished by the way that slope and geology are combined to define a spatial model of VS30. We consider the globally applicable slope-only model as a baseline to which we compare two methods of combining both slope and geology. For both hybrid approaches, we model spatial correlation structure of the residuals using the kriging-with-a-trend technique, which brings the map into closer agreement with the observations. Cross validation indicates that we can reduce the uncertainty of the VS30 map by up to 16% relative to the slope-only approach.

  15. Mutation of a putative MAP kinase consensus site regulates NCAM endocytosis and NCAM-dependent neurite outgrowth.

    PubMed

    Goschzik, Tobias; Cremer, Harold; Gnanapragassam, Vinayaga S; Horstkorte, Rüdiger; Bork, Kaya; Diestel, Simone

    2017-07-01

    The cytoplasmic domain of the neural cell adhesion molecule NCAM contains several putative serine/threonine phosphorylation sites whose functions are largely unknown. Human NCAM140 (NCAM140) possesses a potential MAP kinase phosphorylation site at threonine (T) 803. The aim of this study was to analyze a possible phosphorylation of NCAM140 by MAP kinases and to identify the functional role of T803. We found that NCAM140 is phosphorylated by the MAP kinase ERK2 in vitro. Exchange of T803 to aspartic acid (D) which mimics constitutive phosphorylation at the respective position resulted in increased endocytosis compared to NCAM140 in neuroblastoma cells and primary neurons. Consistently, NCAM140 endocytosis was inhibited by the MEK inhibitor U0126 in contrast to NCAM140-T803D or NCAM140-T803A endocytosis supporting a role of a potential ERK2 mediated phosphorylation at this site in endocytosis. Furthermore, cells expressing NCAM140-T803D developed significantly shorter neurites than NCAM140 expressing cells indicating that a potential phosphorylation of NCAM by ERK2 also regulates NCAM-dependent neurite outgrowth. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  16. Construction of a high-density genetic map for grape using next generation restriction-site associated DNA sequencing

    PubMed Central

    2012-01-01

    Background Genetic mapping and QTL detection are powerful methodologies in plant improvement and breeding. Construction of a high-density and high-quality genetic map would be of great benefit in the production of superior grapes to meet human demand. High throughput and low cost of the recently developed next generation sequencing (NGS) technology have resulted in its wide application in genome research. Sequencing restriction-site associated DNA (RAD) might be an efficient strategy to simplify genotyping. Combining NGS with RAD has proven to be powerful for single nucleotide polymorphism (SNP) marker development. Results An F1 population of 100 individual plants was developed. In-silico digestion-site prediction was used to select an appropriate restriction enzyme for construction of a RAD sequencing library. Next generation RAD sequencing was applied to genotype the F1 population and its parents. Applying a cluster strategy for SNP modulation, a total of 1,814 high-quality SNP markers were developed: 1,121 of these were mapped to the female genetic map, 759 to the male map, and 1,646 to the integrated map. A comparison of the genetic maps to the published Vitis vinifera genome revealed both conservation and variations. Conclusions The applicability of next generation RAD sequencing for genotyping a grape F1 population was demonstrated, leading to the successful development of a genetic map with high density and quality using our designed SNP markers. Detailed analysis revealed that this newly developed genetic map can be used for a variety of genome investigations, such as QTL detection, sequence assembly and genome comparison. PMID:22908993

  17. Evaluation of Story Maps to Enhance Public Engagement and Communication at Legacy Management Sites – 17334

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

    Castillo, Darina; Carpenter, Cliff; Linard, Joshua

    Story Maps are being used in both public and private sectors to convey information to stakeholders, create enterprise platforms, and assist in decision making. Story Maps are web applications that combine maps, narrative text, images, and multimedia content to provide information. These applications provide a user-friendly platform to share the remarkable history of our sites, the complexity of their contamination and remediation, successes we achieve in our LTS&M activities, and even the challenges we face as we aim to fulfill our mission.

  18. CASPASE-9 CARD:CORE DOMAIN INTERACTIONS REQUIRE A PROPERLY-FORMED ACTIVE SITE

    PubMed Central

    Huber, Kristen L.; Serrano, Banyuhay P.; Hardy, Jeanne A.

    2018-01-01

    Caspase-9 is a critical factor in the initiation of apoptosis, and as a result is tightly regulated by a number of mechanisms. Caspase-9 contains a Caspase Activation and Recruitment Domain (CARD), which enables caspase-9 to form a tight interaction with the apoptosome, a heptameric activating platform. The caspase-9 CARD has been thought to be principally involved in recruitment to the apoptosome, but its roles outside this interaction have yet to be uncovered. In this work we show that the CARD is involved in physical interactions with the catalytic core of caspase-9 in the absence of the apoptosome; this interaction requires a properly formed caspase-9 active site. The active sites of caspases are composed of four extremely mobile loops. When the active-site loops are not properly ordered, the CARD and core domains of caspase-9 do not interact and behave independently, like loosely tethered beads. When the active-site loop bundle is properly ordered, the CARD domain interacts with the catalytic core, forming a single folding unit. Together these findings provide mechanistic insight into a new level of caspase-9 regulation, prompting speculation that the CARD may also play a role in the recruitment or recognition of substrate. PMID:29500231

  19. Interactions between white spruce and shrubby alders at three boreal forest sites in Alaska.

    Treesearch

    Tricia L. Wurtz

    2000-01-01

    To document possible soil nitrogen mosaics before timber harvesting on three boreal forest sites in Alaska, maps of the distribution of understory green (Alnus crispa (Ait.) Pursh) and Sitka alder (A. sitchensis(Reg.) Rydb.) stems were made. Understory alders were regularly distributed throughout the northernmost site (Standard...

  20. H 2 Adsorbed Site-to-Site Electronic Delocalization within IRMOF-1: Understanding Non-Negligible Interactions at High Pressure

    DOE PAGES

    Wu, Jian; Kucukkal, Mustafa U.; Clark, Aurora E.

    2016-07-15

    Isoreticular metal organic frameworks (IRMOFs) have shown high uptake capabilities for storage of H 2 (11.5 wt % at 77 K and 170 bar). A significant literature has employed fragment models and a single adsorbed H 2 to identify adsorption sites within IRMOFs, as well as the necessary adsorbate–adsorbent interactions needed to reach sufficient adsorption enthalpy for practical usage, however at high pressures it remains to be seen if H 2···H 2 intermolecular interactions may influence the energetics. This study focuses upon IRMOF-1 (also known as MOF-5), and examines the individual H 2 stabilization energies at different sites using Möller–Plessetmore » perturbation theory and density functional theory alongside chemical models that consist of isolated fragment models and a cubic super cell cluster consisting of both the face- and edge-cube’s of IRMOF-1. Optimization of twenty stable configurations of singly adsorbed H 2 in the super-cell cluster is observed to be essential to obtain energy ordering of the five primary sites consistent with experiment and prior benchmark calculations (α >> β > γ > δ ≈ ε). To examine site-to-site interactions that may occur in the high-pressure regime, 64 co-adsorbed H2 within a super-cell cluster have been studied (a theoretical maximum of all adsorption sites, 14 wt %). There, delocalization and/or charge transfer of electrons is observed from the σ orbitals of the H 2 bound at the γ positions into the σ* orbitals of H 2 bound at the α sites leads to stabilization of the interaction of H 2 at the γ, by 1.4 kJ/mol, respectively (using M06-2X/LANL2DZ). Furthermore, this effect has been confirmed to be charge transfer, and not a manifestation of enhanced dispersion at high loading, through natural bond order (NBO) analysis and by comparisons of the square of off-diagonal NBO Fock matrix elements for both density functionals that account for dispersion interactions and Hartree–Fock calculations that ignore

  1. Using 15N-Ammonium to Characterise and Map Potassium Binding Sites in Proteins by NMR Spectroscopy

    PubMed Central

    Werbeck, Nicolas D; Kirkpatrick, John; Reinstein, Jochen; Hansen, D Flemming

    2014-01-01

    A variety of enzymes are activated by the binding of potassium ions. The potassium binding sites of these enzymes are very specific, but ammonium ions can often replace potassium ions in vitro because of their similar ionic radii. In these cases, ammonium can be used as a proxy for potassium to characterise potassium binding sites in enzymes: the 1H,15N spin-pair of enzyme-bound 15NH4+ can be probed by 15N-edited heteronuclear NMR experiments. Here, we demonstrate the use of NMR spectroscopy to characterise binding of ammonium ions to two different enzymes: human histone deacetylase 8 (HDAC8), which is activated allosterically by potassium, and the bacterial Hsp70 homologue DnaK, for which potassium is an integral part of the active site. Ammonium activates both enzymes in a similar way to potassium, thus supporting this non-invasive approach. Furthermore, we present an approach to map the observed binding site onto the structure of HDAC8. Our method for mapping the binding site is general and does not require chemical shift assignment of the enzyme resonances. PMID:24520048

  2. Collaborative community hazard exposure mapping: Distant Early Warning radar sites in Alaska's North Slope

    NASA Astrophysics Data System (ADS)

    Brady, M.

    2015-12-01

    A method to produce hazard exposure maps that are developed in collaboration with local coastal communities is the focus of this research. Typically efforts to map community exposure to climate threats over large areas have limited consideration of local perspectives about associated risks, constraining their utility for local management. This problem is especially acute in remote locations such as the Arctic where there are unique vulnerabilities to coastal threats that can be fully understood only through inclusion of community stakeholders. Through collaboration with community members, this study identifies important coastal assets and places and surveys local perspectives of exposure to climate threats along Alaska's vast North Slope coastline spanning multiple municipalities. To model physical exposure, the study adapts the U.S. Geological Survey's (USGS) coastal vulnerability index (CVI) to the Arctic context by incorporating the effects of open water distance determined by sea ice extent, and assigning CVI values to coastal assets and places according to direction and proximity. The study found that in addition to concerns about exposed municipal and industrial assets, North Slope communities viewed exposure of traditional activity sites as presenting a particular risk for communities. Highly exposed legacy Cold War Distant Early Warning Line sites are of particular concern with impacts ranging from financial risk to contamination of sensitive coastal marine environments. This research demonstrates a method to collaboratively map community exposure to coastal climate threats to better understand local risks and produce locally usable exposure maps.

  3. Mapping as a visual health communication tool: promises and dilemmas.

    PubMed

    Parrott, Roxanne; Hopfer, Suellen; Ghetian, Christie; Lengerich, Eugene

    2007-01-01

    In the era of evidence-based public health promotion and planning, the use of maps as a form of evidence to communicate about the multiple determinants of cancer is on the rise. Geographic information systems and mapping technologies make future proliferation of this strategy likely. Yet disease maps as a communication form remain largely unexamined. This content analysis considers the presence of multivariate information, credibility cues, and the communication function of publicly accessible maps for cancer control activities. Thirty-six state comprehensive cancer control plans were publicly available in July 2005 and were reviewed for the presence of maps. Fourteen of the 36 state cancer plans (39%) contained map images (N = 59 static maps). A continuum of map inter activity was observed, with 10 states having interactive mapping tools available to query and map cancer information. Four states had both cancer plans with map images and interactive mapping tools available to the public on their Web sites. Of the 14 state cancer plans that depicted map images, two displayed multivariate data in a single map. Nine of the 10 states with interactive mapping capability offered the option to display multivariate health risk messages. The most frequent content category mapped was cancer incidence and mortality, with stage at diagnosis infrequently available. The most frequent communication function served by the maps reviewed was redundancy, as maps repeated information contained in textual forms. The social and ethical implications for communicating about cancer through the use of visual geographic representations are discussed.

  4. Interactive Maps on War and Peace: A WebGIS Application for Civic Education

    NASA Astrophysics Data System (ADS)

    Wirkus, Lars; Strunck, Alexander

    2013-04-01

    War and violent conflict are omnipresent-be it war in the Middle East, violent conflicts in failed states or increasing military expenditures and exports/ imports of military goods. To understand certain conflicts or peace processes and their possible interrelation, to conduct a well-founded political discussion and to support or influence decision-making, one matter is of special importance: easily accessible and, in particular, reliable data and information. Against this background, the Bonn International Center for Conversion (BICC) in close cooperation with the German Federal Agency for Civic Education (bpb) has been developing a map-based information portal on war and peace with various thematic modules for the latter's online service (http://sicherheitspolitik.bpb.de). The portal will eventually offer nine of such modules that are intended to give various target groups, such as interested members of the public, teachers and learners, policymakers and representatives of the media access to the required information in form of an interactive and country-based global overview or a comparison of different issues. Five thematic modules have been completed so far: War and conflict, peace and demobilization, military capacities, resources and conflict, conventional weapons. The portal offers a broad spectrum of different data processing and visualization tools. Its central feature is an interactive mapping component based on WebGIS and a relational database. Content and data provided through thematic maps in the form of WebGIS layers are generally supplemented by info graphics, data tables and short articles providing deeper knowledge on the respective issue. All modules and their sub-chapters are introduced by background texts. They put all interactive maps of a module into an appropriate context and help the users to also understand the interrelation between various layers. If a layer is selected, all corresponding texts and graphics are shown automatically below

  5. Mapping protein-protein interactions using yeast two-hybrid assays.

    PubMed

    Mehla, Jitender; Caufield, J Harry; Uetz, Peter

    2015-05-01

    Yeast two-hybrid (Y2H) screens are an efficient system for mapping protein-protein interactions and whole interactomes. The screens can be performed using random libraries or collections of defined open reading frames (ORFs) called ORFeomes. This protocol describes both library and array-based Y2H screening, with an emphasis on array-based assays. Array-based Y2H is commonly used to test a number of "prey" proteins for interactions with a single "bait" (target) protein or pool of proteins. The advantage of this approach is the direct identification of interacting protein pairs without further downstream experiments: The identity of the preys is known and does not require further confirmation. In contrast, constructing and screening a random prey library requires identification of individual prey clones and systematic retesting. Retesting is typically performed in an array format. © 2015 Cold Spring Harbor Laboratory Press.

  6. Image Analysis for Facility Siting: a Comparison of Lowand High-altitude Image Interpretability for Land Use/land Cover Mapping

    NASA Technical Reports Server (NTRS)

    Borella, H. M.; Estes, J. E.; Ezra, C. E.; Scepan, J.; Tinney, L. R.

    1982-01-01

    For two test sites in Pennsylvania the interpretability of commercially acquired low-altitude and existing high-altitude aerial photography are documented in terms of time, costs, and accuracy for Anderson Level II land use/land cover mapping. Information extracted from the imagery is to be used in the evaluation process for siting energy facilities. Land use/land cover maps were drawn at 1:24,000 scale using commercially flown color infrared photography obtained from the United States Geological Surveys' EROS Data Center. Detailed accuracy assessment of the maps generated by manual image analysis was accomplished employing a stratified unaligned adequate class representation. Both 'area-weighted' and 'by-class' accuracies were documented and field-verified. A discrepancy map was also drawn to illustrate differences in classifications between the two map scales. Results show that the 1:24,000 scale map set was more accurate (99% to 94% area-weighted) than the 1:62,500 scale set, especially when sampled by class (96% to 66%). The 1:24,000 scale maps were also more time-consuming and costly to produce, due mainly to higher image acquisition costs.

  7. In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

    PubMed Central

    Grey, Corinne; Clément, Julie A.J.; Buard, Jérôme; Leblanc, Benjamin; Gut, Ivo; Gut, Marta; Duret, Laurent

    2017-01-01

    In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner. Another subset reveals DSB-independent interactions between PRDM9 and genomic sites, such as the binding sites for the insulator protein CTCF. We propose that these DSB-independent sites result from interactions between hotspot-bound PRDM9 and genomic sequences located on the chromosome axis. PMID:28336543

  8. Investigation and identification of functional post-translational modification sites associated with drug binding and protein-protein interactions.

    PubMed

    Su, Min-Gang; Weng, Julia Tzu-Ya; Hsu, Justin Bo-Kai; Huang, Kai-Yao; Chi, Yu-Hsiang; Lee, Tzong-Yi

    2017-12-21

    Protein post-translational modification (PTM) plays an essential role in various cellular processes that modulates the physical and chemical properties, folding, conformation, stability and activity of proteins, thereby modifying the functions of proteins. The improved throughput of mass spectrometry (MS) or MS/MS technology has not only brought about a surge in proteome-scale studies, but also contributed to a fruitful list of identified PTMs. However, with the increase in the number of identified PTMs, perhaps the more crucial question is what kind of biological mechanisms these PTMs are involved in. This is particularly important in light of the fact that most protein-based pharmaceuticals deliver their therapeutic effects through some form of PTM. Yet, our understanding is still limited with respect to the local effects and frequency of PTM sites near pharmaceutical binding sites and the interfaces of protein-protein interaction (PPI). Understanding PTM's function is critical to our ability to manipulate the biological mechanisms of protein. In this study, to understand the regulation of protein functions by PTMs, we mapped 25,835 PTM sites to proteins with available three-dimensional (3D) structural information in the Protein Data Bank (PDB), including 1785 modified PTM sites on the 3D structure. Based on the acquired structural PTM sites, we proposed to use five properties for the structural characterization of PTM substrate sites: the spatial composition of amino acids, residues and side-chain orientations surrounding the PTM substrate sites, as well as the secondary structure, division of acidity and alkaline residues, and solvent-accessible surface area. We further mapped the structural PTM sites to the structures of drug binding and PPI sites, identifying a total of 1917 PTM sites that may affect PPI and 3951 PTM sites associated with drug-target binding. An integrated analytical platform (CruxPTM), with a variety of methods and online molecular docking

  9. EMMMA: A web-based system for environmental mercury mapping, modeling, and analysis

    USGS Publications Warehouse

    Hearn,, Paul P.; Wente, Stephen P.; Donato, David I.; Aguinaldo, John J.

    2006-01-01

    tissue, atmospheric emissions and deposition, stream sediments, soils, and coal) and mercuryrelated data (mine locations); 2) Interactively view and access predictions of the National Descriptive Model of Mercury in Fish (NDMMF) at 4,976 sites and 6,829 sampling events (events are unique combinations of site and sampling date) across the United States; and 3) Use interactive mapping and graphing capabilities to visualize spatial and temporal trends and study relationships between mercury and other variables.

  10. BAID: The Barrow Area Information Database - an interactive web mapping portal and cyberinfrastructure for scientific activities in the vicinity of Barrow, Alaska

    NASA Astrophysics Data System (ADS)

    Cody, R. P.; Kassin, A.; Gaylord, A.; Brown, J.; Tweedie, C. E.

    2012-12-01

    The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic. The Barrow Area Information Database (BAID, www.baidims.org) is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 9,600 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, and save or print maps and query results. Data are described with metadata that meet Federal Geographic Data Committee standards and are archived at the University Corporation for Atmospheric Research Earth Observing Laboratory (EOL) where non-proprietary BAID data can be freely downloaded. BAID has been used to: Optimize research site choice; Reduce duplication of science effort; Discover complementary and potentially detrimental research activities in an area of scientific interest; Re-establish historical research sites for resampling efforts assessing change in ecosystem structure and function over time; Exchange knowledge across disciplines and generations; Facilitate communication between western science and traditional ecological knowledge; Provide local residents access to science data that facilitates adaptation to arctic change; (and) Educate the next generation of environmental and computer scientists. This poster describes key activities that will be undertaken over the next three years to provide BAID users with novel software tools to interact with a current and diverse selection of information and data about the Barrow area. Key activities include: 1. Collecting data on research

  11. Optimizing Travel Time to Outpatient Interventional Radiology Procedures in a Multi-Site Hospital System Using a Google Maps Application.

    PubMed

    Mandel, Jacob E; Morel-Ovalle, Louis; Boas, Franz E; Ziv, Etay; Yarmohammadi, Hooman; Deipolyi, Amy; Mohabir, Heeralall R; Erinjeri, Joseph P

    2018-02-20

    The purpose of this study is to determine whether a custom Google Maps application can optimize site selection when scheduling outpatient interventional radiology (IR) procedures within a multi-site hospital system. The Google Maps for Business Application Programming Interface (API) was used to develop an internal web application that uses real-time traffic data to determine estimated travel time (ETT; minutes) and estimated travel distance (ETD; miles) from a patient's home to each a nearby IR facility in our hospital system. Hypothetical patient home addresses based on the 33 cities comprising our institution's catchment area were used to determine the optimal IR site for hypothetical patients traveling from each city based on real-time traffic conditions. For 10/33 (30%) cities, there was discordance between the optimal IR site based on ETT and the optimal IR site based on ETD at non-rush hour time or rush hour time. By choosing to travel to an IR site based on ETT rather than ETD, patients from discordant cities were predicted to save an average of 7.29 min during non-rush hour (p = 0.03), and 28.80 min during rush hour (p < 0.001). Using a custom Google Maps application to schedule outpatients for IR procedures can effectively reduce patient travel time when more than one location providing IR procedures is available within the same hospital system.

  12. Lipid Interaction Sites on Channels, Transporters and Receptors: Recent Insights from Molecular Dynamics Simulations

    PubMed Central

    Hedger, George; Sansom, Mark S. P.

    2017-01-01

    Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterisation of these sites is of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. PMID:26946244

  13. A Quantitative Chemotherapy Genetic Interaction Map Reveals Factors Associated with PARP Inhibitor Resistance.

    PubMed

    Hu, Hsien-Ming; Zhao, Xin; Kaushik, Swati; Robillard, Lilliane; Barthelet, Antoine; Lin, Kevin K; Shah, Khyati N; Simmons, Andy D; Raponi, Mitch; Harding, Thomas C; Bandyopadhyay, Sourav

    2018-04-17

    Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy. This quantitative map is predictive of interactions maintained in other cell lines, identifies DNA-repair factors, predicts cancer cell line responses to therapy, and prioritizes synergistic drug combinations. We identify that ARID1A loss confers resistance to PARP inhibitors in cells and ovarian cancer patients and that loss of GPBP1 causes resistance to cisplatin and PARP inhibitors through the regulation of genes involved in homologous recombination. This map helps navigate patient genomic data and optimize chemotherapeutic regimens by delineating factors involved in the response to specific types of DNA damage. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

    PubMed Central

    Jensen, Mikkel R. B.; Łopacińska, Joanna; Schmidt, Michael S.; Skolimowski, Maciej; Abeille, Fabien; Qvortrup, Klaus; Mølhave, Kristian

    2013-01-01

    Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells’ interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered. PMID:23326412

  15. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    NASA Astrophysics Data System (ADS)

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-08-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

  16. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    PubMed Central

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-01-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID:27561351

  17. Genomes as geography: using GIS technology to build interactive genome feature maps

    PubMed Central

    Dolan, Mary E; Holden, Constance C; Beard, M Kate; Bult, Carol J

    2006-01-01

    Background Many commonly used genome browsers display sequence annotations and related attributes as horizontal data tracks that can be toggled on and off according to user preferences. Most genome browsers use only simple keyword searches and limit the display of detailed annotations to one chromosomal region of the genome at a time. We have employed concepts, methodologies, and tools that were developed for the display of geographic data to develop a Genome Spatial Information System (GenoSIS) for displaying genomes spatially, and interacting with genome annotations and related attribute data. In contrast to the paradigm of horizontally stacked data tracks used by most genome browsers, GenoSIS uses the concept of registered spatial layers composed of spatial objects for integrated display of diverse data. In addition to basic keyword searches, GenoSIS supports complex queries, including spatial queries, and dynamically generates genome maps. Our adaptation of the geographic information system (GIS) model in a genome context supports spatial representation of genome features at multiple scales with a versatile and expressive query capability beyond that supported by existing genome browsers. Results We implemented an interactive genome sequence feature map for the mouse genome in GenoSIS, an application that uses ArcGIS, a commercially available GIS software system. The genome features and their attributes are represented as spatial objects and data layers that can be toggled on and off according to user preferences or displayed selectively in response to user queries. GenoSIS supports the generation of custom genome maps in response to complex queries about genome features based on both their attributes and locations. Our example application of GenoSIS to the mouse genome demonstrates the powerful visualization and query capability of mature GIS technology applied in a novel domain. Conclusion Mapping tools developed specifically for geographic data can be

  18. The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins.

    PubMed

    Takahara, Terunao; Inoue, Kuniko; Arai, Yumika; Kuwata, Keiko; Shibata, Hideki; Maki, Masatoshi

    2017-10-13

    Mobilization of intracellular calcium is essential for a wide range of cellular processes, including signal transduction, apoptosis, and vesicular trafficking. Several lines of evidence have suggested that apoptosis-linked gene 2 (ALG-2, also known as PDCD6 ), a calcium-binding protein, acts as a calcium sensor linking calcium levels with efficient vesicular trafficking, especially at the endoplasmic reticulum (ER)-to-Golgi transport step. However, how ALG-2 regulates these processes remains largely unclear. Here, we report that M APK1- i nteracting and s pindle- s tabilizing (MISS)- l ike (MISSL), a previously uncharacterized protein, interacts with ALG-2 in a calcium-dependent manner. Live-cell imaging revealed that upon a rise in intracellular calcium levels, GFP-tagged MISSL (GFP-MISSL) dynamically relocalizes in a punctate pattern and colocalizes with ALG-2. MISSL knockdown caused disorganization of the components of the ER exit site, the ER-Golgi intermediate compartment, and Golgi. Importantly, knockdown of either MISSL or ALG-2 attenuated the secretion of se creted a lkaline p hosphatase (SEAP), a model secreted cargo protein, with similar reductions in secretion by single- and double-protein knockdowns, suggesting that MISSL and ALG-2 act in the same pathway to regulate the secretion process. Furthermore, ALG-2 or MISSL knockdown delayed ER-to-Golgi transport of procollagen type I. We also found that ALG-2 and MISSL interact with microtubule-associated protein 1B (MAP1B) and that MAP1B knockdown reverts the reduced secretion of SEAP caused by MISSL or ALG-2 depletion. These results suggest that a change in the intracellular calcium level plays a role in regulation of the secretory pathway via interaction of ALG-2 with MISSL and MAP1B. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Access to Space Interactive Design Web Site

    NASA Technical Reports Server (NTRS)

    Leon, John; Cutlip, William; Hametz, Mark

    2000-01-01

    The Access To Space (ATS) Group at NASA's Goddard Space Flight Center (GSFC) supports the science and technology community at GSFC by facilitating frequent and affordable opportunities for access to space. Through partnerships established with access mode suppliers, the ATS Group has developed an interactive Mission Design web site. The ATS web site provides both the information and the tools necessary to assist mission planners in selecting and planning their ride to space. This includes the evaluation of single payloads vs. ride-sharing opportunities to reduce the cost of access to space. Features of this site include the following: (1) Mission Database. Our mission database contains a listing of missions ranging from proposed missions to manifested. Missions can be entered by our user community through data input tools. Data is then accessed by users through various search engines: orbit parameters, ride-share opportunities, spacecraft parameters, other mission notes, launch vehicle, and contact information. (2) Launch Vehicle Toolboxes. The launch vehicle toolboxes provide the user a full range of information on vehicle classes and individual configurations. Topics include: general information, environments, performance, payload interface, available volume, and launch sites.

  20. Concept Mapping as a Support for Mars Landing-Site Selection

    NASA Technical Reports Server (NTRS)

    Cabrol, Nathalie A.; Briggs, Geoffrey A.

    1999-01-01

    The NASA Ames' Center for Mars Exploration (CMEX) serves to coordinate Mars programmatic research at ARC in the sciences, in information technology and in aero-assist and other technologies. Most recently, CMEX has been working with the Institute for Human and Machine Cognition at the University of West Florida to develop a new kind of web browser based on the application of concept maps. These Cmaps, which are demonstrably effective in science teaching, can be used to provide a new kind of information navigation tool that can make web or CD based information more meaningful and more easily navigable. CMEX expects that its 1999 CD-ROM will have this new user interface. CMEX is also engaged with the Mars Surveyor Project Office at JPL in developing an Internet-based source of materials to support the process of selecting landing sites for the next series of Mars landers. This activity -- identifying the most promising sites from which to return samples relevant to the search for evidence of life -- is one that is expected to engage the general public as well as the science community. To make the landing site data easily accessible and meaningful to the public, CMEX is planning to use the IHMC Cmap browser as its user interface.

  1. MAPS of Cancer

    NASA Technical Reports Server (NTRS)

    Gray, Lincoln

    1998-01-01

    Our goal was to produce an interactive visualization from a mathematical model that successfully predicts metastases from head and neck cancer. We met this goal early in the project. The visualization is available for the public to view. Our work appears to fill a need for more information about this deadly disease. The idea of this project was to make an easily interpretable visualization based on what we call "functional maps" of disease. A functional map is a graphic summary of medical data, where distances between parts of the body are determined by the probability of disease, not by anatomical distances. Functional maps often beat little resemblance to anatomical maps, but they can be used to predict the spread of disease. The idea of modeling the spread of disease in an abstract multidimensional space is difficult for many people. Our goal was to make the important predictions easy to see. NASA must face this problem frequently: how to help laypersons and professionals see important trends in abstract, complex data. We took advantage of concepts perfected in NASA's graphics libraries. As an analogy, consider a functional map of early America. Suppose we choose travel times, rather than miles, as our measures of inter-city distances. For Abraham Lincoln, travel times would have been the more meaningful measure of separation between cities. In such a map New Orleans would be close to Memphis because of the Mississippi River. St. Louis would be close to Portland because of the Oregon Trail. Oklahoma City would be far from Little Rock because of the Cheyenne. Such a map would look puzzling to those of us who have always seen physical maps, but the functional map would be more useful in predicting the probabilities of inter-site transit. Continuing the analogy, we could predict the spread of social diseases such as gambling along the rivers and cattle rustling along the trails. We could simply print the functional map of America, but it would be more interesting

  2. TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network

    PubMed Central

    Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L.; Costanzo, Michael; Andrews, Brenda; Boone, Charles

    2017-01-01

    Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae. In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. PMID:28325812

  3. Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere.

    PubMed

    Chang, Edward F; Breshears, Jonathan D; Raygor, Kunal P; Lau, Darryl; Molinaro, Annette M; Berger, Mitchel S

    2017-01-01

    OBJECTIVE Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site. METHODS Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a "classic" or an "atypical" location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis. RESULTS Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance

  4. BAID: The Barrow Area Information Database - an interactive web mapping portal and cyberinfrastructure for scientific activities in the vicinity of Barrow, Alaska

    NASA Astrophysics Data System (ADS)

    Cody, R. P.; Kassin, A.; Gaylord, A. G.; Tweedie, C. E.

    2013-12-01

    In 2013, the Barrow Area Information Database (BAID, www.baid.utep.edu) project resumed field operations in Barrow, AK. The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic. BAID is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 11,000 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, and save or print maps and query results. Data are described with metadata that meet Federal Geographic Data Committee standards and are archived at the University Corporation for Atmospheric Research Earth Observing Laboratory (EOL) where non-proprietary BAID data can be freely downloaded. Highlights for the 2013 season include the addition of more than 2000 additional research sites, providing differential global position system (dGPS) support to visiting scientists, surveying over 80 miles of coastline to document rates of erosion, training of local GIS personal, deployment of a wireless sensor network, and substantial upgrades to the BAID website and web mapping applications.

  5. Prediction of Protein-Protein Interaction Sites by Random Forest Algorithm with mRMR and IFS

    PubMed Central

    Li, Bi-Qing; Feng, Kai-Yan; Chen, Lei; Huang, Tao; Cai, Yu-Dong

    2012-01-01

    Prediction of protein-protein interaction (PPI) sites is one of the most challenging problems in computational biology. Although great progress has been made by employing various machine learning approaches with numerous characteristic features, the problem is still far from being solved. In this study, we developed a novel predictor based on Random Forest (RF) algorithm with the Minimum Redundancy Maximal Relevance (mRMR) method followed by incremental feature selection (IFS). We incorporated features of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure and solvent accessibility. We also included five 3D structural features to predict protein-protein interaction sites and achieved an overall accuracy of 0.672997 and MCC of 0.347977. Feature analysis showed that 3D structural features such as Depth Index (DPX) and surface curvature (SC) contributed most to the prediction of protein-protein interaction sites. It was also shown via site-specific feature analysis that the features of individual residues from PPI sites contribute most to the determination of protein-protein interaction sites. It is anticipated that our prediction method will become a useful tool for identifying PPI sites, and that the feature analysis described in this paper will provide useful insights into the mechanisms of interaction. PMID:22937126

  6. Protein-protein interaction site predictions with minimum covariance determinant and Mahalanobis distance.

    PubMed

    Qiu, Zhijun; Zhou, Bo; Yuan, Jiangfeng

    2017-11-21

    Protein-protein interaction site (PPIS) prediction must deal with the diversity of interaction sites that limits their prediction accuracy. Use of proteins with unknown or unidentified interactions can also lead to missing interfaces. Such data errors are often brought into the training dataset. In response to these two problems, we used the minimum covariance determinant (MCD) method to refine the training data to build a predictor with better performance, utilizing its ability of removing outliers. In order to predict test data in practice, a method based on Mahalanobis distance was devised to select proper test data as input for the predictor. With leave-one-validation and independent test, after the Mahalanobis distance screening, our method achieved higher performance according to Matthews correlation coefficient (MCC), although only a part of test data could be predicted. These results indicate that data refinement is an efficient approach to improve protein-protein interaction site prediction. By further optimizing our method, it is hopeful to develop predictors of better performance and wide range of application. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network.

    PubMed

    Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles

    2017-05-05

    Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. Copyright © 2017 Usaj et al.

  8. Multiple Antigenic Sites Are Involved in Blocking the Interaction of GII.4 Norovirus Capsid with ABH Histo-Blood Group Antigens

    PubMed Central

    Parra, Gabriel I.; Abente, Eugenio J.; Sandoval-Jaime, Carlos; Sosnovtsev, Stanislav V.; Bok, Karin

    2012-01-01

    Noroviruses are major etiological agents of acute viral gastroenteritis. In 2002, a GII.4 variant (Farmington Hills cluster) spread so rapidly in the human population that it predominated worldwide and displaced previous GII.4 strains. We developed and characterized a panel of six monoclonal antibodies (MAbs) directed against the capsid protein of a Farmington Hills-like GII.4 norovirus strain that was associated with a large hospital outbreak in Maryland in 2004. The six MAbs reacted with high titers against homologous virus-like particles (VLPs) by enzyme-linked immunoassay but did not react with denatured capsid protein in immunoblots. The expression and self-assembly of newly developed genogroup I/II chimeric VLPs showed that five MAbs bound to the GII.4 protruding (P) domain of the capsid protein, while one recognized the GII.4 shell (S) domain. Cross-competition assays and mutational analyses showed evidence for at least three distinct antigenic sites in the P domain and one in the S domain. MAbs that mapped to the P domain but not the S domain were able to block the interaction of VLPs with ABH histo-blood group antigens (HBGA), suggesting that multiple antigenic sites of the P domain are involved in HBGA blocking. Further analysis showed that two MAbs mapped to regions of the capsid that had been associated with the emergence of new GII.4 variants. Taken together, our data map antibody and HBGA carbohydrate binding to proximal regions of the norovirus capsid, showing that evolutionary pressures on the norovirus capsid protein may affect both antigenic and carbohydrate recognition phenotypes. PMID:22532688

  9. Training site statistics from Landsat and Seasat satellite imagery registered to a common map base

    NASA Technical Reports Server (NTRS)

    Clark, J.

    1981-01-01

    Landsat and Seasat satellite imagery and training site boundary coordinates were registered to a common Universal Transverse Mercator map base in the Newport Beach area of Orange County, California. The purpose was to establish a spatially-registered, multi-sensor data base which would test the use of Seasat synthetic aperture radar imagery to improve spectral separability of channels used for land use classification of an urban area. Digital image processing techniques originally developed for the digital mosaics of the California Desert and the State of Arizona were adapted to spatially register multispectral and radar data. Techniques included control point selection from imagery and USGS topographic quadrangle maps, control point cataloguing with the Image Based Information System, and spatial and spectral rectifications of the imagery. The radar imagery was pre-processed to reduce its tendency toward uniform data distributions, so that training site statistics for selected Landsat and pre-processed Seasat imagery indicated good spectral separation between channels.

  10. Quantum Correlation in the XY Spin Model with Anisotropic Three-Site Interaction

    NASA Astrophysics Data System (ADS)

    Wang, Yao; Chai, Bing-Bing; Guo, Jin-Liang

    2018-05-01

    We investigate pairwise entanglement and quantum discord (QD) in the XY spin model with anisotropic three-site interaction at zero and finite temperatures. For both the nearest-neighbor spins and the next nearest-neighbor spins, special attention is paid to the dependence of entanglement and QD on the anisotropic parameter δ induced by the next nearest-neighbor spins. We show that the behavior of QD differs in many ways from entanglement under the influences of the anisotropic three-site interaction at finite temperatures. More important, comparing the effects of δ on the entanglement and QD, we find the anisotropic three-site interaction plays an important role in the quantum correlations at zero and finite temperatures. It is found that δ can strengthen the quantum correlation for both the nearest-neighbor spins and the next nearest-neighbor spins, especially for the nearest-neighbor spins at low temperature.

  11. MAP4 Mechanism that Stabilizes Mitochondrial Permeability Transition in Hypoxia: Microtubule Enhancement and DYNLT1 Interaction with VDAC1

    PubMed Central

    Zhang, Yi-ming; Zhang, Jia-ping; Hu, Jiong-yu; Zhang, Qiong; Dai, Xia; Teng, Miao; Zhang, Dong-xia; Huang, Yue-sheng

    2011-01-01

    Mitochondrial membrane permeability has received considerable attention recently because of its key role in apoptosis and necrosis induced by physiological events such as hypoxia. The manner in which mitochondria interact with other molecules to regulate mitochondrial permeability and cell destiny remains elusive. Previously we verified that hypoxia-induced phosphorylation of microtubule-associated protein 4 (MAP4) could lead to microtubules (MTs) disruption. In this study, we established the hypoxic (1% O2) cell models of rat cardiomyocytes, H9c2 and HeLa cells to further test MAP4 function. We demonstrated that increase in the pool of MAP4 could promote the stabilization of MT networks by increasing the synthesis and polymerization of tubulin in hypoxia. Results showed MAP4 overexpression could enhance cell viability and ATP content under hypoxic conditions. Subsequently we employed a yeast two-hybrid system to tag a protein interacting with mitochondria, dynein light chain Tctex-type 1 (DYNLT1), by hVDAC1 bait. We confirmed that DYNLT1 had protein-protein interactions with voltage-dependent anion channel 1 (VDAC1) using co-immunoprecipitation; and immunofluorescence technique showed that DYNLT1 was closely associated with MTs and VDAC1. Furthermore, DYNLT1 interactions with MAP4 were explored using a knockdown technique. We thus propose two possible mechanisms triggered by MAP4: (1) stabilization of MT networks, (2) DYNLT1 modulation, which is connected with VDAC1, and inhibition of hypoxia-induced mitochondrial permeabilization. PMID:22164227

  12. e23D: database and visualization of A-to-I RNA editing sites mapped to 3D protein structures.

    PubMed

    Solomon, Oz; Eyal, Eran; Amariglio, Ninette; Unger, Ron; Rechavi, Gidi

    2016-07-15

    e23D, a database of A-to-I RNA editing sites from human, mouse and fly mapped to evolutionary related protein 3D structures, is presented. Genomic coordinates of A-to-I RNA editing sites are converted to protein coordinates and mapped onto 3D structures from PDB or theoretical models from ModBase. e23D allows visualization of the protein structure, modeling of recoding events and orientation of the editing with respect to nearby genomic functional sites from databases of disease causing mutations and genomic polymorphism. http://www.sheba-cancer.org.il/e23D CONTACT: oz.solomon@live.biu.ac.il or Eran.Eyal@sheba.health.gov.il. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. MARs Tools for Interactive ANalysis (MARTIAN): Google Maps Tools for Visual Exploration of Geophysical Modeling on Mars

    NASA Astrophysics Data System (ADS)

    Dimitrova, L. L.; Haines, M.; Holt, W. E.; Schultz, R. A.; Richard, G.; Haines, A. J.

    2006-12-01

    Interactive maps of surface-breaking faults and stress models on Mars provide important tools to engage undergraduate students, educators, and scientists with current geological and geophysical research. We have developed a map based on the Google Maps API -- an Internet based tool combining DHTML and AJAX, -- which allows very large maps to be viewed over the World Wide Web. Typically, small portions of the maps are downloaded as needed, rather than the entire image at once. This set-up enables relatively fast access for users with low bandwidth. Furthermore, Google Maps provides an extensible interactive interface making it ideal for visualizing multiple data sets at the user's choice. The Google Maps API works primarily with data referenced to latitudes and longitudes, which is then mapped in Mercator projection only. We have developed utilities for general cylindrical coordinate systems by converting these coordinates into equivalent Mercator projection before including them on the map. The MARTIAN project is available at http://rock.geo.sunysb.edu/~holt/Mars/MARTIAN/. We begin with an introduction to the Martian surface using a topography model. Faults from several datasets are classified by type (extension vs. compression) and by time epoch. Deviatoric stresses due to gravitational potential energy differences, calculated from the topography and crustal thickness, can be overlain. Several quantitative measures for the fit of the stress field to the faults are also included. We provide introductory text and exercises spanning a range of topics: how are faults identified, what stress is and how it relates to faults, what gravitational potential energy is and how variations in it produce stress, how the models are created, and how these models can be evaluated and interpreted. The MARTIAN tool is used at Stony Brook University in GEO 310: Introduction to Geophysics, a class geared towards junior and senior geosciences majors. Although this project is in its

  14. 3d interaction homology: The structurally known rotamers of tyrosine derive from a surprisingly limited set of information-rich hydropathic interaction environments described by maps.

    PubMed

    Ahmed, Mostafa H; Koparde, Vishal N; Safo, Martin K; Neel Scarsdale, J; Kellogg, Glen E

    2015-06-01

    Sidechain rotamer libraries are obtained through exhaustive statistical analysis of existing crystallographic structures of proteins and have been applied in multiple aspects of structural biology, for example, crystallography of relatively low-resolution structures, in homology model building and in biomolecular NMR. Little is known, however, about the driving forces that lead to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines reveals the environment around each, in terms of hydrophobic (π-π stacking, etc.) and polar (hydrogen bonding, etc.) interactions. After partitioning the tyrosines into backbone-dependent (ϕ, ψ) bins, a map similarity metric based on the correlation coefficient was applied to each map-map pair to build matrices suitable for clustering with k-means. The first bin (-200° ≤ ϕ < -155°; -205° ≤ ψ < -160°), representing 631 tyrosines, reduced to 14 unique hydropathic environments, with most diversity arising from favorable hydrophobic interactions with many different residue partner types. Polar interactions for tyrosine include surprisingly ubiquitous hydrogen bonding with the phenolic OH and a handful of unique environments surrounding the tyrosine backbone. The memberships of all but one of the 14 environments are dominated (>50%) by a single χ(1)/χ(2) rotamer. The last environment has weak or no interactions with the tyrosine ring and its χ(1)/χ(2) rotamer is indeterminate, which is consistent with it being composed of mostly surface residues. Each tyrosine residue attempts to fulfill its hydropathic valence and thus, structural water molecules are seen in a variety of roles throughout protein structure. © 2015 Wiley Periodicals, Inc.

  15. Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites.

    PubMed

    Asahi, M; Kimura, Y; Kurzydlowski, K; Tada, M; MacLennan, D H

    1999-11-12

    In an earlier study (Kimura, Y., Kurzydlowski, K., Tada, M., and MacLennan, D. H. (1997) J. Biol. Chem. 272, 15061-15064), mutation of amino acids on one face of the phospholamban (PLN) transmembrane helix led to loss of PLN inhibition of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) molecules. This helical face was proposed to form a site of PLN interaction with a transmembrane helix in SERCA molecules. To determine whether predicted transmembrane helices M4, M5, M6, or M8 in SERCA1a interact with PLN, SERCA1a mutants were co-expressed with wild-type PLN and effects on Ca(2+) dependence of Ca(2+) transport were measured. Wild-type inhibitory interactions shifted apparent Ca(2+) affinity of SERCA1a by an average of -0.34 pCa units, but four of the seven mutations in M4 led to a more inhibitory shift in apparent Ca(2+) affinity, averaging -0.53 pCa units. Seven mutations in M5 led to an average shift of -0.32 pCa units and seven mutations in M8 led to an average shift of -0.30 pCa units. Among 11 mutations in M6, 1, Q791A, increased the inhibitory shift (-0.59 pCa units) and 5, V795A (-0.11), L802A (-0.07), L802V (-0.04), T805A (-0.11), and F809A (-0.12), reduced the inhibitory shift, consistent with the view that Val(795), Leu(802), Thr(805), and Phe(809), located on one face of a predicted M6 helix, form a site in SERCA1a for interaction with PLN. Those mutations in M4, M6, or M8 of SERCA1a that enhanced PLN inhibitory function did not enhance PLN physical association with SERCA1a, but mutants V795A and L802A in M6, which decreased PLN inhibitory function, decreased physical association, as measured by co-immunoprecipitation. In related studies, those PLN mutants that gained inhibitory function also increased levels of co-immunoprecipitation of wild-type SERCA1a and those that lost inhibitory function also reduced association, correlating functional interaction sites with physical interaction sites. Thus, both functional and physical data confirm that PLN

  16. IRS-PCR-based genetic mapping of the huntingtin interacting protein gene (HIP1) on mouse chromosome 5.

    PubMed

    Himmelbauer, H; Wedemeyer, N; Haaf, T; Wanker, E E; Schalkwyk, L C; Lehrach, H

    1998-01-01

    Huntington's disease (HD) is a devastating central nervous system disorder. Even though the gene responsible has been positionally cloned recently, its etiology has remained largely unclear. To investigate potential disease mechanisms, we conducted a search for binding partners of the HD-protein huntingtin. With the yeast two-hybrid system, one such interacting factor, the huntingtin interacting protein-1 (HIP-1), was identified (Wanker et al. 1997; Kalchman et al. 1997) and the human gene mapped to 7q11.2. In this paper we demonstrate the localization of the HIP1 mouse homologue (Hip1) into a previously identified region of human-mouse synteny on distal mouse Chromosome (Chr) 5, both employing an IRS-PCR-based mapping strategy and traditional fluorescent in situ hybridization (FISH) mapping.

  17. Covariance of biophysical data with digital topograpic and land use maps over the FIFE site

    NASA Technical Reports Server (NTRS)

    Davis, F. W.; Schimel, D. S.; Friedl, M. A.; Michaelsen, J. C.; Kittel, T. G. F.; Dubayah, R.; Dozier, J.

    1992-01-01

    This paper discusses the biophysical stratification of the FIFE site, implementation of the stratification utilizing geographic information system methods, and validation of the stratification with respect to field measurements of biomass, Bowen ratio, soil moisture, and the greenness vegetation index (GVI) derived from TM satellite data. Maps of burning and topographic position were significantly associated with variation in GVI, biomass, and Bowen ratio. The stratified design did not significantly alter the estimated site-wide means for surface climate parameters but accounted for between 25 and 45 percent of the sample variance depending on the variable.

  18. Real-Time Mapping alert system; user's manual

    USGS Publications Warehouse

    Torres, L.A.

    1996-01-01

    The U.S. Geological Survey has an extensive hydrologic network that records and transmits precipitation, stage, discharge, and other water- related data on a real-time basis to an automated data processing system. Data values are recorded on electronic data collection platforms at field monitoring sites. These values are transmitted by means of orbiting satellites to receiving ground stations, and by way of telecommunication lines to a U.S. Geological Survey office where they are processed on a computer system. Data that exceed predefined thresholds are identified as alert values. These alert values can help keep water- resource specialists informed of current hydrologic conditions. The current alert status at monitoring sites is of critical importance during floods, hurricanes, and other extreme hydrologic events where quick analysis of the situation is needed. This manual provides instructions for using the Real-Time Mapping software, a series of computer programs developed by the U.S. Geological Survey for quick analysis of hydrologic conditions, and guides users through a basic interactive session. The software provides interactive graphics display and query of real-time information in a map-based, menu-driven environment.

  19. A 20-residue peptide of the inner membrane protein OutC mediates interaction with two distinct sites of the outer membrane secretin OutD and is essential for the functional type II secretion system in Erwinia chrysanthemi.

    PubMed

    Login, Frédéric H; Fries, Markus; Wang, Xiaohui; Pickersgill, Richard W; Shevchik, Vladimir E

    2010-05-01

    The type II secretion system (T2SS) is widely exploited by proteobacteria to secrete enzymes and toxins involved in bacterial survival and pathogenesis. The outer membrane pore formed by the secretin OutD and the inner membrane protein OutC are two key components of the secretion complex, involved in secretion specificity. Here, we show that the periplasmic regions of OutC and OutD interact directly and map the interaction site of OutC to a 20-residue peptide named OutCsip (secretin interacting peptide, residues 139-158). This peptide interacts in vitro with two distinct sites of the periplasmic region of OutD, one located on the N0 subdomain and another overlapping the N2-N3' subdomains. The two interaction sites of OutD have different modes of binding to OutCsip. A single substitution, V143S, located within OutCsip prevents its interaction with one of the two binding sites of OutD and fully inactivates the T2SS. We show that the N0 subdomain of OutD interacts also with a second binding site within OutC located in the region proximal to the transmembrane segment. We suggest that successive interactions between these distinct regions of OutC and OutD may have functional importance in switching the secretion machine.

  20. VS30 – A site-characterization parameter for use in building Codes, simplified earthquake resistant design, GMPEs, and ShakeMaps

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2012-01-01

    VS30, defined as the average seismic shear-wave velocity from the surface to a depth of 30 meters, has found wide-spread use as a parameter to characterize site response for simplified earthquake resistant design as implemented in building codes worldwide. VS30 , as initially introduced by the author for the US 1994 NEHRP Building Code, provides unambiguous definitions of site classes and site coefficients for site-dependent response spectra based on correlations derived from extensive borehole logging and comparative ground-motion measurement programs in California. Subsequent use of VS30 for development of strong ground motion prediction equations (GMPEs) and measurement of extensive sets of VS borehole data have confirmed the previous empirical correlations and established correlations of SVS30 with VSZ at other depths. These correlations provide closed form expressions to predict S30 V at a large number of additional sites and further justify S30 V as a parameter to characterize site response for simplified building codes, GMPEs, ShakeMap, and seismic hazard mapping.

  1. Vs30 mapping at selected sites within the Greater Accra Metropolitan Area

    NASA Astrophysics Data System (ADS)

    Nortey, Grace; Armah, Thomas K.; Amponsah, Paulina

    2018-06-01

    A large part of Accra is underlain by a complex distribution of shallow soft soils. Within seismically active zones, these soils hold the most potential to significantly amplify seismic waves and cause severe damage, especially to structures sited on soils lacking sufficient stiffness. This paper presents preliminary site classification for the Greater Accra Metropolitan Area of Ghana (GAMA), using experimental data from two-dimensional (2-D) Multichannel Analysis of Surface Wave (MASW) technique. The dispersive characteristics of fundamental mode Rayleigh type surface waves were utilized for imaging the shallow subsurface layers (approx. up to 30 m depth) by estimating the 1D (depth) and 2D (depth and surface location) shear wave velocities at 5 selected sites. The average shear wave velocity for 30 m depth (Vs30), which is critical in evaluating the site response of the upper 30 m, was estimated and used for the preliminary site classification of the GAM area, as per NEHRP (National Earthquake Hazards Reduction Program). Based on the Vs30 values obtained in the study, two common site types C, and D corresponding to shallow (>6 m < 30 m) weathered rock and deep (up 30 m thick) stiff soils respectively, have been identified within the study area. Lower velocity profiles are inferred for the residual soils (sandy to silty clays), derived from the Accraian Formation that lies mainly within Accra central. Stiffer soil sites lie to the north of Accra, and to the west near Nyanyano. The seismic response characteristics over the residual soils in the GAMA have become apparent using the MASW technique. An extensive site effect map and a more robust probabilistic seismic hazard analysis can now be efficiently built for the metropolis, by considering the site classes and design parameters obtained from this study.

  2. An interactive method for digitizing zone maps

    NASA Technical Reports Server (NTRS)

    Giddings, L. E.; Thompson, E. J.

    1975-01-01

    A method is presented for digitizing maps that consist of zones, such as contour or climatic zone maps. A color-coded map is prepared by any convenient process. The map is then read into memory of an Image 100 computer by means of its table scanner, using colored filters. Zones are separated and stored in themes, using standard classification procedures. Thematic data are written on magnetic tape and these data, appropriately coded, are combined to make a digitized image on tape. Step-by-step procedures are given for digitization of crop moisture index maps with this procedure. In addition, a complete example of the digitization of a climatic zone map is given.

  3. BAID: The Barrow Area Information Database - An Interactive Web Mapping Portal and Cyberinfrastructure Showcasing Scientific Activities in the Vicinity of Barrow, Arctic Alaska.

    NASA Astrophysics Data System (ADS)

    Escarzaga, S. M.; Cody, R. P.; Kassin, A.; Barba, M.; Gaylord, A. G.; Manley, W. F.; Mazza Ramsay, F. D.; Vargas, S. A., Jr.; Tarin, G.; Laney, C. M.; Villarreal, S.; Aiken, Q.; Collins, J. A.; Green, E.; Nelson, L.; Tweedie, C. E.

    2015-12-01

    The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic and the Barrow Area Information Database (BAID, www.barrowmapped.org) tracks and facilitates a gamut of research, management, and educational activities in the area. BAID is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 12,000 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, save or print maps and query results, and filter or view information by space, time, and/or other tags. Additionally, data are described with metadata that meet Federal Geographic Data Committee standards. Recent advances include the addition of more than 2000 new research sites, the addition of a query builder user interface allowing rich and complex queries, and provision of differential global position system (dGPS) and high-resolution aerial imagery support to visiting scientists. Recent field surveys include over 80 miles of coastline to document rates of erosion and the collection of high-resolution sonar data for bathymetric mapping of Elson Lagoon and near shore region of the Chukchi Sea. A network of five climate stations has been deployed across the peninsula to serve as a wireless net for the research community and to deliver near real time climatic data to the user community. Local GIS personal have also been trained to better make use of scientific data for local decision making. Links to Barrow area datasets are housed at national data archives and substantial upgrades have

  4. Systematic identification of phosphorylation-mediated protein interaction switches

    PubMed Central

    Wichmann, Oliver; Utz, Mathias; Andre, Timon; Minguez, Pablo; Parca, Luca; Roth, Frederick P.; Gavin, Anne-Claude; Bork, Peer; Russell, Robert B.

    2017-01-01

    Proteomics techniques can identify thousands of phosphorylation sites in a single experiment, the majority of which are new and lack precise information about function or molecular mechanism. Here we present a fast method to predict potential phosphorylation switches by mapping phosphorylation sites to protein-protein interactions of known structure and analysing the properties of the protein interface. We predict 1024 sites that could potentially enable or disable particular interactions. We tested a selection of these switches and showed that phosphomimetic mutations indeed affect interactions. We estimate that there are likely thousands of phosphorylation mediated switches yet to be uncovered, even among existing phosphorylation datasets. The results suggest that phosphorylation sites on globular, as distinct from disordered, parts of the proteome frequently function as switches, which might be one of the ancient roles for kinase phosphorylation. PMID:28346509

  5. Documentation for the 2008 Update of the United States National Seismic Hazard Maps

    USGS Publications Warehouse

    Petersen, Mark D.; Frankel, Arthur D.; Harmsen, Stephen C.; Mueller, Charles S.; Haller, Kathleen M.; Wheeler, Russell L.; Wesson, Robert L.; Zeng, Yuehua; Boyd, Oliver S.; Perkins, David M.; Luco, Nicolas; Field, Edward H.; Wills, Chris J.; Rukstales, Kenneth S.

    2008-01-01

    The 2008 U.S. Geological Survey (USGS) National Seismic Hazard Maps display earthquake ground motions for various probability levels across the United States and are applied in seismic provisions of building codes, insurance rate structures, risk assessments, and other public policy. This update of the maps incorporates new findings on earthquake ground shaking, faults, seismicity, and geodesy. The resulting maps are derived from seismic hazard curves calculated on a grid of sites across the United States that describe the frequency of exceeding a set of ground motions. The USGS National Seismic Hazard Mapping Project developed these maps by incorporating information on potential earthquakes and associated ground shaking obtained from interaction in science and engineering workshops involving hundreds of participants, review by several science organizations and State surveys, and advice from two expert panels. The National Seismic Hazard Maps represent our assessment of the 'best available science' in earthquake hazards estimation for the United States (maps of Alaska and Hawaii as well as further information on hazard across the United States are available on our Web site at http://earthquake.usgs.gov/research/hazmaps/).

  6. Functional mapping of protein-protein interactions in an enzyme complex by directed evolution.

    PubMed

    Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

    2014-01-01

    The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84-90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84-86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes.

  7. Functional Mapping of Protein-Protein Interactions in an Enzyme Complex by Directed Evolution

    PubMed Central

    Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

    2014-01-01

    The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84–90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84–86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes. PMID:25551646

  8. FragFit: a web-application for interactive modeling of protein segments into cryo-EM density maps.

    PubMed

    Tiemann, Johanna K S; Rose, Alexander S; Ismer, Jochen; Darvish, Mitra D; Hilal, Tarek; Spahn, Christian M T; Hildebrand, Peter W

    2018-05-21

    Cryo-electron microscopy (cryo-EM) is a standard method to determine the three-dimensional structures of molecular complexes. However, easy to use tools for modeling of protein segments into cryo-EM maps are sparse. Here, we present the FragFit web-application, a web server for interactive modeling of segments of up to 35 amino acids length into cryo-EM density maps. The fragments are provided by a regularly updated database containing at the moment about 1 billion entries extracted from PDB structures and can be readily integrated into a protein structure. Fragments are selected based on geometric criteria, sequence similarity and fit into a given cryo-EM density map. Web-based molecular visualization with the NGL Viewer allows interactive selection of fragments. The FragFit web-application, accessible at http://proteinformatics.de/FragFit, is free and open to all users, without any login requirements.

  9. PLASMAP: an interactive computational tool for storage, retrieval and device-independent graphic display of conventional restriction maps.

    PubMed Central

    Stone, B N; Griesinger, G L; Modelevsky, J L

    1984-01-01

    We describe an interactive computational tool, PLASMAP, which allows the user to electronically store, retrieve, and display circular restriction maps. PLASMAP permits users to construct libraries of plasmid restriction maps as a set of files which may be edited in the laboratory at any time. The display feature of PLASMAP quickly generates device-independent, artist-quality, full-color or monochrome, hard copies or CRT screens of complex, conventional circular restriction maps. PMID:6320096

  10. Contribution of physical modelling to climate-driven landslide hazard mapping: an alpine test site

    NASA Astrophysics Data System (ADS)

    Vandromme, R.; Desramaut, N.; Baills, A.; Hohmann, A.; Grandjean, G.; Sedan, O.; Mallet, J. P.

    2012-04-01

    The aim of this work is to develop a methodology for integrating climate change scenarios into quantitative hazard assessment and especially their precipitation component. The effects of climate change will be different depending on both the location of the site and the type of landslide considered. Indeed, mass movements can be triggered by different factors. This paper describes a methodology to address this issue and shows an application on an alpine test site. Mechanical approaches represent a solution for quantitative landslide susceptibility and hazard modeling. However, as the quantity and the quality of data are generally very heterogeneous at a regional scale, it is necessary to take into account the uncertainty in the analysis. In this perspective, a new hazard modeling method is developed and integrated in a program named ALICE. This program integrates mechanical stability analysis through a GIS software taking into account data uncertainty. This method proposes a quantitative classification of landslide hazard and offers a useful tool to gain time and efficiency in hazard mapping. However, an expertise approach is still necessary to finalize the maps. Indeed it is the only way to take into account some influent factors in slope stability such as heterogeneity of the geological formations or effects of anthropic interventions. To go further, the alpine test site (Barcelonnette area, France) is being used to integrate climate change scenarios into ALICE program, and especially their precipitation component with the help of a hydrological model (GARDENIA) and the regional climate model REMO (Jacob, 2001). From a DEM, land-cover map, geology, geotechnical data and so forth the program classifies hazard zones depending on geotechnics and different hydrological contexts varying in time. This communication, realized within the framework of Safeland project, is supported by the European Commission under the 7th Framework Programme for Research and Technological

  11. Validation of Innovative Exploration Technologies for Newberry Volcano: Drill Site Location Map 2010

    DOE Data Explorer

    Jaffe, Todd

    2012-01-01

    Newberry seeks to explore "blind" (no surface evidence) convective hydrothermal systems associated with a young silicic pluton on the flanks of Newberry Volcano. This project will employ a combination of innovative and conventional techniques to identify the location of subsurface geothermal fluids associated with the hot pluton. Newberry project drill site location map 2010. Once the exploration mythology is validated, it can be applied throughout the Cascade Range and elsewhere to locate and develop “blind” geothermal resources.

  12. Embodied Interaction Priority: Other's Body Part Affects Numeral-Space Mappings.

    PubMed

    You, Xuqun; Zhang, Yu; Zhu, Rongjuan; Guo, Yu

    2018-01-01

    Traditionally, the spatial-numerical association of response codes (SNARC) effect was presented in two-choice condition, in which only one individual reacted to both even (small) and odd (large) numbers. Few studies explored SNARC effect in a social situation. Moreover, there are many reference frames involved in SNARC effect, and it has not yet been investigated which reference frame is dominated when two participants perform the go-nogo task together. In the present study, we investigated which reference frame plays a primary role in SNARC effect when allocentric and egocentric reference frames were consistent or inconsistent in social settings. Furthermore, we explored how two actors corepresent number-space mapping interactively. Results of the two experiments demonstrated that egocentric reference frame was at work primarily when two reference frames were consistent and inconsistent. This shows that body-centered coordinate frames influence number-space mapping in social settings, and one actor may represent another actor's action and tasks.

  13. Topological phases in the Haldane model with spin–spin on-site interactions

    NASA Astrophysics Data System (ADS)

    Rubio-García, A.; García-Ripoll, J. J.

    2018-04-01

    Ultracold atom experiments allow the study of topological insulators, such as the non-interacting Haldane model. In this work we study a generalization of the Haldane model with spin–spin on-site interactions that can be implemented on such experiments. We focus on measuring the winding number, a topological invariant, of the ground state, which we compute using a mean-field calculation that effectively captures long-range correlations and a matrix product state computation in a lattice with 64 sites. Our main result is that we show how the topological phases present in the non-interacting model survive until the interactions are comparable to the kinetic energy. We also demonstrate the accuracy of our mean-field approach in efficiently capturing long-range correlations. Based on state-of-the-art ultracold atom experiments, we propose an implementation of our model that can give information about the topological phases.

  14. Calorimetric studies of the interactions of metalloenzyme active site mimetics with zinc-binding inhibitors.

    PubMed

    Robinson, Sophia G; Burns, Philip T; Miceli, Amanda M; Grice, Kyle A; Karver, Caitlin E; Jin, Lihua

    2016-07-19

    The binding of drugs to metalloenzymes is an intricate process that involves several interactions, including binding of the drug to the enzyme active site metal, as well as multiple interactions between the drug and the enzyme residues. In order to determine the free energy contribution of Zn(2+) binding by known metalloenzyme inhibitors without the other interactions, valid active site zinc structural mimetics must be formed and binding studies need to be performed in biologically relevant conditions. The potential of each of five ligands to form a structural mimetic with Zn(2+) was investigated in buffer using Isothermal Titration Calorimetry (ITC). All five ligands formed strong 1 : 1 (ligand : Zn(2+)) binary complexes. The complexes were used in further ITC experiments to study their interaction with 8-hydroxyquinoline (8-HQ) and/or acetohydroxamic acid (AHA), two bidentate anionic zinc-chelating enzyme inhibitors. It was found that tetradentate ligands were not suitable for creating zinc structural mimetics for inhibitor binding in solution due to insufficient coordination sites remaining on Zn(2+). A stable binary complex, [Zn(BPA)](2+), which was formed by a tridentate ligand, bis(2-pyridylmethyl)amine (BPA), was found to bind one AHA in buffer or a methanol : buffer mixture (60 : 40 by volume) at pH 7.25 or one 8-HQ in the methanol : buffer mixture at pH 6.80, making it an effective structural mimetic for the active site of zinc metalloenzymes. These results are consistent with the observation that metalloenzyme active site zinc ions have three residues coordinated to them, leaving one or two sites open for inhibitors to bind. Our findings indicate that Zn(BPA)X2 can be used as an active site structural mimetic for zinc metalloenzymes for estimating the free energy contribution of zinc binding to the overall inhibitor active site interactions. Such use will help aid in the rational design of inhibitors to a variety of zinc metalloenzymes.

  15. An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions

    PubMed Central

    Sengupta, Raghuvir N.; Van Schie, Sabine N.S.; Giambaşu, George; Dai, Qing; Yesselman, Joseph D.; York, Darrin; Piccirilli, Joseph A.; Herschlag, Daniel

    2016-01-01

    Biological catalysis hinges on the precise structural integrity of an active site that binds and transforms its substrates and meeting this requirement presents a unique challenge for RNA enzymes. Functional RNAs, including ribozymes, fold into their active conformations within rugged energy landscapes that often contain misfolded conformers. Here we uncover and characterize one such “off-pathway” species within an active site after overall folding of the ribozyme is complete. The Tetrahymena group I ribozyme (E) catalyzes cleavage of an oligonucleotide substrate (S) by an exogenous guanosine (G) cofactor. We tested whether specific catalytic interactions with G are present in the preceding E•S•G and E•G ground-state complexes. We monitored interactions with G via the effects of 2′- and 3′-deoxy (–H) and −amino (–NH2) substitutions on G binding. These and prior results reveal that G is bound in an inactive configuration within E•G, with the nucleophilic 3′-OH making a nonproductive interaction with an active site metal ion termed MA and with the adjacent 2′-OH making no interaction. Upon S binding, a rearrangement occurs that allows both –OH groups to contact a different active site metal ion, termed MC, to make what are likely to be their catalytic interactions. The reactive phosphoryl group on S promotes this change, presumably by repositioning the metal ions with respect to G. This conformational transition demonstrates local rearrangements within an otherwise folded RNA, underscoring RNA's difficulty in specifying a unique conformation and highlighting Nature's potential to use local transitions of RNA in complex function. PMID:26567314

  16. An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions.

    PubMed

    Sengupta, Raghuvir N; Van Schie, Sabine N S; Giambaşu, George; Dai, Qing; Yesselman, Joseph D; York, Darrin; Piccirilli, Joseph A; Herschlag, Daniel

    2016-01-01

    Biological catalysis hinges on the precise structural integrity of an active site that binds and transforms its substrates and meeting this requirement presents a unique challenge for RNA enzymes. Functional RNAs, including ribozymes, fold into their active conformations within rugged energy landscapes that often contain misfolded conformers. Here we uncover and characterize one such "off-pathway" species within an active site after overall folding of the ribozyme is complete. The Tetrahymena group I ribozyme (E) catalyzes cleavage of an oligonucleotide substrate (S) by an exogenous guanosine (G) cofactor. We tested whether specific catalytic interactions with G are present in the preceding E•S•G and E•G ground-state complexes. We monitored interactions with G via the effects of 2'- and 3'-deoxy (-H) and -amino (-NH(2)) substitutions on G binding. These and prior results reveal that G is bound in an inactive configuration within E•G, with the nucleophilic 3'-OH making a nonproductive interaction with an active site metal ion termed MA and with the adjacent 2'-OH making no interaction. Upon S binding, a rearrangement occurs that allows both -OH groups to contact a different active site metal ion, termed M(C), to make what are likely to be their catalytic interactions. The reactive phosphoryl group on S promotes this change, presumably by repositioning the metal ions with respect to G. This conformational transition demonstrates local rearrangements within an otherwise folded RNA, underscoring RNA's difficulty in specifying a unique conformation and highlighting Nature's potential to use local transitions of RNA in complex function. © 2015 Sengupta et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  17. Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase

    PubMed Central

    Lucas, James E; Siegel, Justin B

    2015-01-01

    Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240

  18. Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor.

    PubMed

    Hedger, George; Shorthouse, David; Koldsø, Heidi; Sansom, Mark S P

    2016-08-25

    Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. -40 to -4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins.

  19. Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor

    PubMed Central

    2016-01-01

    Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. −40 to −4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins. PMID:27109430

  20. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

    PubMed

    Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

    2016-08-18

    Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Analyzing Interactions by an IIS-Map-Based Method in Face-to-Face Collaborative Learning: An Empirical Study

    ERIC Educational Resources Information Center

    Zheng, Lanqin; Yang, Kaicheng; Huang, Ronghuai

    2012-01-01

    This study proposes a new method named the IIS-map-based method for analyzing interactions in face-to-face collaborative learning settings. This analysis method is conducted in three steps: firstly, drawing an initial IIS-map according to collaborative tasks; secondly, coding and segmenting information flows into information items of IIS; thirdly,…

  2. Mapping of chloroplast mutations conferring resistance to antibiotics in Chlamydomonas: evidence for a novel site of streptomycin resistance in the small subunit rRNA.

    PubMed

    Gauthier, A; Turmel, M; Lemieux, C

    1988-10-01

    A major obstacle to our understanding of the mechanisms governing the inheritance, recombination and segregation of chloroplast genes in Chlamydomonas is that the majority of antibiotic resistance mutations that have been used to gain insights into such mechanisms have not been physically localized on the chloroplast genome. We report here the physical mapping of two chloroplast antibiotic resistance mutations: one conferring cross-resistance to erythromycin and spiramycin in Chlamydomonas moewusii (er-nM1) and the other conferring resistance to streptomycin in the interfertile species C. eugametos (sr-2). The er-nM1 mutation results from a C to G transversion at a well-known site of macrolide resistance within the peptidyl transferase loop region of the large subunit rRNA gene. This locus, designated rib-2 in yeast mitochondrial DNA, corresponds to residue C-2611 in the 23 S rRNA of Escherichia coli. The sr-2 locus maps within the small subunit (SSU) rRNA gene at a site that has not been described previously. The mutation results from an A to C transversion at a position equivalent to residue A-523 in the E. coli 16 S rRNA. Although this region of the E. coli SSU rRNA has no binding affinity for streptomycin, it binds to ribosomal protein S4, a protein that has long been associated with the response of bacterial cells to this antibiotic. We propose that the sr-2 mutation indirectly affects the nearest streptomycin binding site through an altered interaction between a ribosomal protein and the SSU rRNA.

  3. Development and testing of a contamination potential mapping system for a portion of the General Separations Area, Savannah River Site, South Carolina

    USGS Publications Warehouse

    Rine, J.M.; Berg, R.C.; Shafer, J.M.; Covington, E.R.; Reed, J.K.; Bennett, C.B.; Trudnak, J.E.

    1998-01-01

    A methodology was developed to evaluate and map the contamination potential or aquifer sensitivity of the upper groundwater flow system of a portion of the General Separations Area (GSA) at the Department of Energy's Savannah River Site (SRS) in South Carolina. A Geographic Information System (GIS) was used to integrate diverse subsurface geologic data, soils data, and hydrology utilizing a stack-unit mapping approach to construct mapping layers. This is the first time that such an approach has been used to delineate the hydrogeology of a coastal plain environment. Unit surface elevation maps were constructed for the tops of six Tertiary units derived from over 200 boring logs. Thickness or isopach maps were created for five hydrogeologic units by differencing top and basal surface elevations. The geologic stack-unit map was created by stacking the five isopach maps and adding codes for each stack-unit polygon. Stacked-units were rated according to their hydrogeologic properties and ranked using a logarithmic approach (utility theory) to establish a contamination potential index. Colors were assigned to help display relative importance of stacked-units in preventing or promoting transport of contaminants. The sensitivity assessment included the effects of surface soils on contaminants which are particularly important for evaluating potential effects from surface spills. Hydrogeologic/hydrologic factors did not exhibit sufficient spatial variation to warrant incorporation into contamination potential assessment. Development of this contamination potential mapping system provides a useful tool for site planners, environmental scientists, and regulatory agencies.A methodology was developed to evaluate and map the contamination potential or aquifer sensitivity of the upper groundwater flow system of a portion of the General Separations Area (GSA) at the Department of Energy's Savannah River Site (SRS) in South Carolina. A Geographic Information System (GIS) was used to

  4. iMAR: An Interactive Web-Based Application for Mapping Herbicide Resistant Weeds.

    PubMed

    Panozzo, Silvia; Colauzzi, Michele; Scarabel, Laura; Collavo, Alberto; Rosan, Valentina; Sattin, Maurizio

    2015-01-01

    Herbicides are the major weed control tool in most cropping systems worldwide. However, the high reliance on herbicides has led to environmental issues as well as to the evolution of herbicide-resistant biotypes. Resistance is a major concern in modern agriculture and early detection of resistant biotypes is therefore crucial for its management and prevention. In this context, a timely update of resistance biotypes distribution is fundamental to devise and implement efficient resistance management strategies. Here we present an innovative web-based application called iMAR (interactive MApping of Resistance) for the mapping of herbicide resistant biotypes. It is based on open source software tools and translates into maps the data reported in the GIRE (Italian herbicide resistance working group) database of herbicide resistance at national level. iMAR allows an automatic, easy and cost-effective updating of the maps a nd provides two different systems, "static" and "dynamic". In the first one, the user choices are guided by a hierarchical tree menu, whereas the latter is more flexible and includes a multiple choice criteria (type of resistance, weed species, region, cropping systems) that permits customized maps to be created. The generated information can be useful to various stakeholders who are involved in weed resistance management: farmers, advisors, national and local decision makers as well as the agrochemical industry. iMAR is freely available, and the system has the potential to handle large datasets and to be used for other purposes with geographical implications, such as the mapping of invasive plants or pests.

  5. Building a Better Web Site: A Practical Guide to Interactivity for Libraries.

    ERIC Educational Resources Information Center

    Braun, Linda W.

    1998-01-01

    Describes selected commercial and academic Web sites providing interactive services (Amazon; Jones Library, Amherst, MA; Pine Crest Lower School, Ft. Lauderdale, FL; Barnes & Noble; Cal State's Information Literacy Tutorials; PBS's techknow site; K.I.D.S. Report), and argues that libraries that stop at links and policy statements miss…

  6. Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

    PubMed Central

    Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

    2016-01-01

    Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

  7. SH2 Binding Site Protection Assay: A Method for Identification of SH2 Domain Interaction Partners by Exploiting SH2 Mediated Phosphosite Protection.

    PubMed

    Jadwin, Joshua A

    2017-01-01

    Over the last two decades there has been a significant effort in the field to characterize the phosphosite binding specificities of SH2 domains with the goal of deciphering the pY signaling code. Although high throughput studies in various formats using most SH2 domains have collectively provided a rich resource of in vitro SH2-pTyr site specificity maps, this data can only be used approximate what is happening in the cell where protein concentrations and localization are not homogenous, as they are for in vitro experiments. Here we describe an in vivo approach, SH2 site protection assay, which can capture the pTyr binding specificity of SH2 domains in the cell. The basis of this approach is SH2-pY site protection, the ability of SH2 domains to prevent the PTP-dependent dephosphorylation of their pY site binding partners. We overexpress a tracer SH2 domain in cells and quantify the change in abundance of tyrosine phosphorylated sites using MS. Since the method is performed in vivo, it has the advantage of identifying SH2-pY interactions as they occur within in the cell.

  8. Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping.

    PubMed

    Henry, Roland G; Berman, Jeffrey I; Nagarajan, Srikantan S; Mukherjee, Pratik; Berger, Mitchel S

    2004-02-01

    The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.

  9. Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping

    PubMed Central

    Henry, Roland G.; Berman, Jeffrey I.; Nagarajan, Srikantan S.; Mukherjee, Pratik; Berger, Mitchel S.

    2014-01-01

    The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain. PMID:14980564

  10. Shear-wave velocity characterization of the USGS Hawaiian strong-motion network on the Island of Hawaii and development of an NEHRP site-class map

    USGS Publications Warehouse

    Wong, Ivan G.; Stokoe, Kenneth; Cox, Brady R.; Yuan, Jiabei; Knudsen, Keith L.; Terra, Fabia; Okubo, Paul G.; Lin, Yin-Cheng

    2011-01-01

    To assess the level and nature of ground shaking in Hawaii for the purposes of earthquake hazard mitigation and seismic design, empirical ground-motion prediction models are desired. To develop such empirical relationships, knowledge of the subsurface site conditions beneath strong-motion stations is critical. Thus, as a first step to develop ground-motion prediction models for Hawaii, spectral-analysis-of-surface-waves (SASW) profiling was performed at the 22 free-field U.S. Geological Survey (USGS) strong-motion sites on the Big Island to obtain shear-wave velocity (VS) data. Nineteen of these stations recorded the 2006 Kiholo Bay moment magnitude (M) 6.7 earthquake, and 17 stations recorded the triggered M 6.0 Mahukona earthquake. VS profiling was performed to reach depths of more than 100 ft. Most of the USGS stations are situated on sites underlain by basalt, based on surficial geologic maps. However, the sites have varying degrees of weathering and soil development. The remaining strong-motion stations are located on alluvium or volcanic ash. VS30 (average VS in the top 30 m) values for the stations on basalt ranged from 906 to 1908 ft/s [National Earthquake Hazards Reduction Program (NEHRP) site classes C and D], because most sites were covered with soil of variable thickness. Based on these data, an NEHRP site-class map was developed for the Big Island. These new VS data will be a significant input into an update of the USGS statewide hazard maps and to the operation of ShakeMap on the island of Hawaii.

  11. Site-directed DNA crosslinking of large multisubunit protein-DNA complexes.

    PubMed

    Persinger, Jim; Bartholomew, Blaine

    2009-01-01

    Several methods have been developed to site-specifically incorporate photoreactive nucleotide analogs into DNA for the purpose of identifying the proteins and their domains that are in contact with particular regions of DNA. The synthesis of several deoxynucleotide analogs that have a photoreactive group tethered to the nucleotide base and the incorporation of these analogs into DNA are described. In a second approach, oligonucleotide with a photoreactive group attached to the phosphate backbone is chemically synthesized. The photoreactive oligonucleotide is then enzymatically incorporated into DNA by annealing it to a complementary DNA template and extending with DNA polymerase. Both approaches have been effectively used to map protein-DNA interactions in large multisubunit complexes such as the eukaryotic transcription or ATP-dependent chromatin remodeling complexes. Not only do these techniques map the binding sites of the various subunits in these complexes, but when coupled with peptide mapping also determine the protein domain that is in close proximity to the different DNA sites. The strength of these techniques is the ability to scan a large number of potential sites by making combinations of different DNA probes and is facilitated by using an immobilized DNA template for synthesis.

  12. Comparative receptor mapping of serotoninergic 5-HT3 and 5-HT4 binding sites*

    NASA Astrophysics Data System (ADS)

    López-Rodríguez, María L.; Morcillo, María José; Benhamú, Bellinda; Rosado, María Luisa

    1997-11-01

    The clinical use of currently available drugs acting at the5-HT4 receptor has been hampered by their lack of selectivityover 5-HT3 binding sites. For this reason, there is considerableinterest in the medicinal chemistry of these serotonin receptor subtypes, andsignificant effort has been made towards the discovery of potent and selectiveligands. Computer-aided conformational analysis was used to characterizeserotoninergic 5-HT3 and 5-HT4 receptorrecognition. On the basis of the generally accepted model of the5-HT3 antagonist pharmacophore, we have performed a receptormapping of this receptor binding site, following the active analog approach(AAA) defined by Marshall. The receptor excluded volume was calculated as theunion of the van der Waals density maps of nine active ligands(pKi ≥ 8.9), superimposed in pharmacophoric conformations.Six inactive analogs (pKi < 7.0) were subsequently used todefine the essential volume, which in its turn can be used to define theregions of steric intolerance of the 5-HT3 receptor. Five activeligands (pKi ≥ 9.3) at 5-HT4 receptors wereused to construct an antagonist pharmacophore for this receptor, and todetermine its excluded volume by superimposition of pharmacophoricconformations. The volume defined by the superimposition of five inactive5-HT4 receptor analogs that possess the pharmacophoric elements(pKi ≤ 6.6) did not exceed the excluded volume calculated forthis receptor. In this case, the inactivity may be due to the lack of positiveinteraction of the amino moiety with a hypothetical hydrophobic pocket, whichwould interact with the voluminous substituents of the basic nitrogen ofactive ligands. The difference between the excluded volumes of both receptorshas confirmed that the main difference is indeed in the basic moiety. Thus,the 5-HT3 receptor can only accommodate small substituents inthe position of the nitrogen atom, whereas the 5-HT4 receptorrequires more voluminous groups. Also, the basic nitrogen is located at ca

  13. Magnetic Ground State Stabilized by Three-Site Interactions: Fe /Rh (111 )

    NASA Astrophysics Data System (ADS)

    Krönlein, Andreas; Schmitt, Martin; Hoffmann, Markus; Kemmer, Jeannette; Seubert, Nicolai; Vogt, Matthias; Küspert, Julia; Böhme, Markus; Alonazi, Bandar; Kügel, Jens; Albrithen, Hamad A.; Bode, Matthias; Bihlmayer, Gustav; Blügel, Stefan

    2018-05-01

    We report the direct observation of a theoretically predicted magnetic ground state in a monolayer Fe on Rh(111), which is referred to as an up-up-down-down (↑↑↓↓) double-row-wise antiferromagnetic spin structure, using spin-polarized scanning tunneling microscopy. This exotic phase, which exists in three orientational domains, is revealed by experiments with magnetic probe tips performed in external magnetic fields. It is shown that a hitherto unconsidered four-spin-three-site beyond-Heisenberg interaction distinctly contributes to the spin coupling of atoms with S ≥1 spins. The observation of the ↑↑↓↓ order substantiates the presence of higher-order, in particular, three-site interactions, in thin magnetic films of itinerant magnets.

  14. Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors

    PubMed Central

    Ciaccio, Mark F.; Chuu, Chih-pin; Jones, Richard B.

    2012-01-01

    First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This

  15. Suitability of oyster restoration sites along the Louisiana coast: Examining site and stock × site interaction

    USGS Publications Warehouse

    Schwarting Miller, Lindsay; La Peyre, Jerome F.; LaPeyre, Megan K.

    2017-01-01

    , seeding with stocks selected for best growth and survival under expected future environmental conditions could better ensure reef development by using oyster populations best suited to the predicted conditions. With rapidly changing estuarine conditions from anthropogenic activities and climate change, siting of oyster reef restoration incorporating both oyster population dynamics and in situ biotic and abiotic interactions is critical in better directing site selection for reef restoration efforts.

  16. Validation of a novel mapping system and utility for mapping complex atrial tachycardias.

    PubMed

    Honarbakhsh, S; Hunter, R J; Dhillon, G; Ullah, W; Keating, E; Providencia, R; Chow, A; Earley, M J; Schilling, R J

    2018-03-01

    This study sought to validate a novel wavefront mapping system utilizing whole-chamber basket catheters (CARTOFINDER, Biosense Webster). The system was validated in terms of (1) mapping atrial-paced beats and (2) mapping complex wavefront patterns in atrial tachycardia (AT). Patients undergoing catheter ablation for AT and persistent AF were included. A 64-pole-basket catheter was used to acquire unipolar signals that were processed by CARTOFINDER mapping system to generate dynamic wavefront propagation maps. The left atrium was paced from four sites to demonstrate focal activation. ATs were mapped with the mechanism confirmed by conventional mapping, entrainment, and response to ablation. Twenty-two patients were included in the study (16 with AT and 6 with AF initially who terminated to AT during ablation). In total, 172 maps were created with the mapping system. It correctly identified atrial-pacing sites in all paced maps. It accurately mapped 9 focal/microreentrant and 18 macroreentrant ATs both in the left and right atrium. A third and fourth observer independently identified the sites of atrial pacing and the AT mechanism from the CARTOFINDER maps, while being blinded to the conventional activation maps. This novel mapping system was effectively validated by mapping focal activation patterns from atrial-paced beats. The system was also effective in mapping complex wavefront patterns in a range of ATs in patients with scarred atria. The system may therefore be of practical use in the mapping and ablation of AT and could have potential for mapping wavefront activations in AF. © 2018 Wiley Periodicals, Inc.

  17. Mapping alpha-helical induced folding within the intrinsically disordered C-terminal domain of the measles virus nucleoprotein by site-directed spin-labeling EPR spectroscopy.

    PubMed

    Belle, Valérie; Rouger, Sabrina; Costanzo, Stéphanie; Liquière, Elodie; Strancar, Janez; Guigliarelli, Bruno; Fournel, André; Longhi, Sonia

    2008-12-01

    Using site-directed spin-labeling EPR spectroscopy, we mapped the region of the intrinsically disordered C-terminal domain of measles virus nucleoprotein (N(TAIL)) that undergoes induced folding. In addition to four spin-labeled N(TAIL) variants (S407C, S488C, L496C, and V517C) (Morin et al. (2006), J Phys Chem 110: 20596-20608), 10 new single-site cysteine variants were designed, purified from E. coli, and spin-labeled. These 14 spin-labeled variants enabled us to map in detail the gain of rigidity of N(TAIL) in the presence of either the secondary structure stabilizer 2,2,2-trifluoroethanol or the C-terminal domain X (XD) of the viral phosphoprotein. Different regions of N(TAIL) were shown to contribute to a different extent to the binding to XD, while the mobility of the spin labels grafted at positions 407 and 460 was unaffected upon addition of XD; that of the spin labels grafted within the 488-502 and the 505-522 regions was severely and moderately reduced, respectively. Furthermore, EPR experiments in the presence of 30% sucrose allowed us to precisely map to residues 488-502, the N(TAIL) region undergoing alpha-helical folding. The mobility of the 488-502 region was found to be restrained even in the absence of the partner, a behavior that could be accounted for by the existence of a transiently populated folded state. Finally, we show that the restrained motion of the 505-522 region upon binding to XD is due to the alpha-helical transition occurring within the 488-502 region and not to a direct interaction with XD.

  18. Spatial games with cyclic interactions: the response of empty sites

    NASA Astrophysics Data System (ADS)

    Brown, Bart; Pleimling, Michel

    2015-03-01

    Predator-prey models of the May-Leonard family employ empty sites in a spatial setting as an intermediate step in the reproduction process. This requirement makes the number and arrangement of empty sites important to the formation of space-time patterns. We study the density of empty sites in a stochastic predator-prey model in which the species compete in a cyclic way in two dimensions. In some cases systems of this type quickly form domains of neutral species after which all predation, and therefore, reproduction occur near the interface of competing domains. Using Monte Carlo simulations we investigate the relationship of this density of empty sites to the time-dependent domain length. We further explore the dynamics by introducing perturbations to the interaction rates of the system after which we measure the perturbed density, i.e. the response of empty sites, as the system relaxes. A dynamical scaling behavior is observed in the response of empty sites. This work is supported by the US National Science Foundation through Grant DMR-1205309.

  19. Enzyme Active Site Interactions by Raman/FTIR, NMR, and Ab Initio Calculations

    PubMed Central

    Deng, Hua

    2017-01-01

    Characterization of enzyme active site structure and interactions at high resolution is important for the understanding of the enzyme catalysis. Vibrational frequency and NMR chemical shift measurements of enzyme-bound ligands are often used for such purpose when X-ray structures are not available or when higher resolution active site structures are desired. This review is focused on how ab initio calculations may be integrated with vibrational and NMR chemical shift measurements to quantitatively determine high-resolution ligand structures (up to 0.001 Å for bond length and 0.01 Å for hydrogen bonding distance) and how interaction energies between bound ligand and its surroundings at the active site may be determined. Quantitative characterization of substrate ionic states, bond polarizations, tautomeric forms, conformational changes and its interactions with surroundings in enzyme complexes that mimic ground state or transition state can provide snapshots for visualizing the substrate structural evolution along enzyme-catalyzed reaction pathway. Our results have shown that the integration of spectroscopic studies with theoretical computation greatly enhances our ability to interpret experimental data and significantly increases the reliability of the theoretical analysis. PMID:24018325

  20. Discovery and Characterization of Non-ATP Site Inhibitors of the Mitogen Activated Protein (MAP) Kinases

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

    Comess, Kenneth M.; Sun, Chaohong; Abad-Zapatero, Cele

    Inhibition of protein kinases has validated therapeutic utility for cancer, with at least seven kinase inhibitor drugs on the market. Protein kinase inhibition also has significant potential for a variety of other diseases, including diabetes, pain, cognition, and chronic inflammatory and immunologic diseases. However, as the vast majority of current approaches to kinase inhibition target the highly conserved ATP-binding site, the use of kinase inhibitors in treating nononcology diseases may require great selectivity for the target kinase. As protein kinases are signal transducers that are involved in binding to a variety of other proteins, targeting alternative, less conserved sites onmore » the protein may provide an avenue for greater selectivity. Here we report an affinity-based, high-throughput screening technique that allows nonbiased interrogation of small molecule libraries for binding to all exposed sites on a protein surface. This approach was used to screen both the c-Jun N-terminal protein kinase Jnk-1 (involved in insulin signaling) and p38{alpha} (involved in the formation of TNF{alpha} and other cytokines). In addition to canonical ATP-site ligands, compounds were identified that bind to novel allosteric sites. The nature, biological relevance, and mode of binding of these ligands were extensively characterized using two-dimensional {sup 1}H/{sup 13}C NMR spectroscopy, protein X-ray crystallography, surface plasmon resonance, and direct enzymatic activity and activation cascade assays. Jnk-1 and p38{alpha} both belong to the MAP kinase family, and the allosteric ligands for both targets bind similarly on a ledge of the protein surface exposed by the MAP insertion present in the CMGC family of protein kinases and distant from the active site. Medicinal chemistry studies resulted in an improved Jnk-1 ligand able to increase adiponectin secretion in human adipocytes and increase insulin-induced protein kinase PKB phosphorylation in human hepatocytes

  1. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    PubMed Central

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D.

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1–2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand breaks are introduced at random wherever two translocating enzymes form a so-called collision complex following long-range communication between a pair of target sites in inverted (head-to-head) repeat. Paradoxically, structural models for collision suggest that the nuclease domains are too far apart (>30 bp) to dimerise and produce a double-strand DNA break using just two strand-cleavage events. Here, we examined the organisation of different collision complexes and how these lead to nuclease activation. We mapped DNA cleavage when a translocating enzyme collides with a static enzyme bound to its site. By following communication between sites in both head-to-head and head-to-tail orientations, we could show that motor activity leads to activation of the nuclease domains via distant interactions of the helicase or MTase-TRD. Direct nuclease dimerization is not required. To help explain the observed cleavage patterns, we also used exonuclease footprinting to demonstrate that individual Type ISP domains can swing off the DNA. This study lends further support to a model where DNA breaks are generated by multiple random nicks due to mobility of a collision complex with an overall DNA-binding footprint of ∼30 bp. PMID:26507855

  2. Capturing nonlocal interaction effects in the Hubbard model: Optimal mappings and limits of applicability

    NASA Astrophysics Data System (ADS)

    van Loon, E. G. C. P.; Schüler, M.; Katsnelson, M. I.; Wehling, T. O.

    2016-10-01

    We investigate the Peierls-Feynman-Bogoliubov variational principle to map Hubbard models with nonlocal interactions to effective models with only local interactions. We study the renormalization of the local interaction induced by nearest-neighbor interaction and assess the quality of the effective Hubbard models in reproducing observables of the corresponding extended Hubbard models. We compare the renormalization of the local interactions as obtained from numerically exact determinant quantum Monte Carlo to approximate but more generally applicable calculations using dual boson, dynamical mean field theory, and the random phase approximation. These more approximate approaches are crucial for any application with real materials in mind. Furthermore, we use the dual boson method to calculate observables of the extended Hubbard models directly and benchmark these against determinant quantum Monte Carlo simulations of the effective Hubbard model.

  3. BOREAS Hardcopy Maps

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nelson, Elizabeth; Newcomer, Jeffrey A.

    2000-01-01

    Boreal Ecosystem-Atmospheric Study (BOREAS) hardcopy maps are a collection of approximately 1,000 hardcopy maps representing the physical, climatological, and historical attributes of areas covering primarily the Manitoba and Saskatchewan provinces of Canada. These maps were collected by BOREAS Information System (BORIS) and Canada for Remote Sensing (CCRS) staff to provide basic information about site positions, manmade features, topography, geology, hydrology, land cover types, fire history, climate, and soils of the BOREAS study region. These maps are not available for distribution through the BOREAS project but may be used as an on-site resource. Information is provided within this document for individuals who want to order copies of these maps from the original map source. Note that the maps are not contained on the BOREAS CD-ROM set. An inventory listing file is supplied on the CD-ROM to inform users of the maps that are available. This inventory listing is available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). For hardcopies of the individual maps, contact the sources provided.

  4. "Where On Mars?": An Open Planetary Mapping Platform for Researchers, Educators, and the General Public

    NASA Astrophysics Data System (ADS)

    Manaud, Nicolas; Carter, John; Boix, Oriol

    2016-10-01

    The "Where On Mars?" project is essentially the evolution of an existing outreach product developed in collaboration between ESA and CartoDB; an interactive map visualisation of the ESA's ExoMars Rover candidate landing sites (whereonmars.co). Planetary imagery data and maps are increasingly produced by the scientific community, and shared typically as images, in scientific publications, presentations or public outreach websites. However, this media lacks of interactivity and contextual information available for further exploration, making it difficult for any audience to relate one location-based information to another. We believe that interactive web maps are a powerful way of telling stories, engaging with and educating people who, over the last decade, have become familiar with tools such as Google Maps. A few planetary web maps exist but they are either too complex for non-experts, or are closed-systems that do not allows anyone to publish and share content. The long-term vision for the project is to provide researchers, communicators, educators and a worldwide public with an open planetary mapping and social platform enabling them to create, share, communicate and consume research-based content. We aim for this platform to become the reference website everyone will go to learn about Mars and other planets in our Solar System; just like people head to Google Maps to find their bearings or any location-based information. The driver is clearly to create for people an emotional connection with Mars. The short-term objectives for the project are (1) to produce and curate an open repository of basemaps, geospatial data sets, map visualisations, and story maps; (2) to develop a beautifully crafted and engaging interactive map of Mars. Based on user-generated content, the underlying framework should (3) make it easy to create and share additional interactive maps telling specific stories.

  5. Efficient mapping of transgene integration sites and local structural changes in Cre transgenic mice using targeted locus amplification

    PubMed Central

    Cain-Hom, Carol; Splinter, Erik; van Min, Max; Simonis, Marieke; van de Heijning, Monique; Martinez, Maria; Asghari, Vida

    2017-01-01

    Abstract Cre/LoxP technology is widely used in the field of mouse genetics for spatial and/or temporal regulation of gene function. For Cre lines generated via pronuclear microinjection of a Cre transgene construct, the integration site is random and in most cases not known. Integration of a transgene can disrupt an endogenous gene, potentially interfering with interpretation of the phenotype. In addition, knowledge of where the transgene is integrated is important for planning of crosses between animals carrying a conditional allele and a given Cre allele in case the alleles are on the same chromosome. We have used targeted locus amplification (TLA) to efficiently map the transgene location in seven previously published Cre and CreERT2 transgenic lines. In all lines, transgene insertion was associated with structural changes of variable complexity, illustrating the importance of testing for rearrangements around the integration site. In all seven lines the exact integration site and breakpoint sequences were identified. Our methods, data and genotyping assays can be used as a resource for the mouse community and our results illustrate the power of the TLA method to not only efficiently map the integration site of any transgene, but also provide additional information regarding the transgene integration events. PMID:28053125

  6. Development of a novel 2D color map for interactive segmentation of histological images.

    PubMed

    Chaudry, Qaiser; Sharma, Yachna; Raza, Syed H; Wang, May D

    2012-05-01

    We present a color segmentation approach based on a two-dimensional color map derived from the input image. Pathologists stain tissue biopsies with various colored dyes to see the expression of biomarkers. In these images, because of color variation due to inconsistencies in experimental procedures and lighting conditions, the segmentation used to analyze biological features is usually ad-hoc. Many algorithms like K-means use a single metric to segment the image into different color classes and rarely provide users with powerful color control. Our 2D color map interactive segmentation technique based on human color perception information and the color distribution of the input image, enables user control without noticeable delay. Our methodology works for different staining types and different types of cancer tissue images. Our proposed method's results show good accuracy with low response and computational time making it a feasible method for user interactive applications involving segmentation of histological images.

  7. Rhodopsin TM6 Can Interact with Two Separate and Distinct Sites on Arrestin: Evidence for Structural Plasticity and Multiple Docking Modes in Arrestin–Rhodopsin Binding

    PubMed Central

    2015-01-01

    Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called “finger” loop (residues 67–79) and the other in the 160 loop (residues 155–165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin–rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin. PMID:24724832

  8. Rhodopsin TM6 can interact with two separate and distinct sites on arrestin: evidence for structural plasticity and multiple docking modes in arrestin-rhodopsin binding.

    PubMed

    Sinha, Abhinav; Jones Brunette, Amber M; Fay, Jonathan F; Schafer, Christopher T; Farrens, David L

    2014-05-27

    Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called "finger" loop (residues 67-79) and the other in the 160 loop (residues 155-165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin-rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin.

  9. Geoelectrical mapping of the Soil and Groundwater Contaminated Site: Case Study from Taiwan

    NASA Astrophysics Data System (ADS)

    Liu, H. C.; Lin, C. P.; Wang, T. P.

    2016-12-01

    In recent years, geophysical technology has been widely used in soil and groundwater investigation and remediation of contaminated sites assessments in Taiwan, such technology can securely work in either small or large sampler areas, and collect data from the traditional one-dimensional data to two-dimensional and three-dimensional data. In other words, geophysical technology helps provide more information to assist the data interpretation, and improves the overall effectiveness of soil and groundwater contamination surveys. Electrical Resistivity Tomography (ERT) is one of useful geophysical technology to the soil and groundwater contaminated sites. By estimating the groundwater flow direction and distribution of contaminations, we could establish monitoring or sampling wells in potential pollution areas. ERT survey could delineate the contaminated areas with high concentrations in relatively simple sites. Even in the seriously DNAPL leakage cases, it is possible to directly detect the DNAPL pool. In this study, we presented the investigation outcomes of electrical resistivity tomography (ERT) and ground-penetrating radar (GPR) at the DNAPLs-impacted site. Evaluation of ERT/GPR technique deployment in detecting buried DNAPLs and assessment of remediation efforts are also discussed. Results indicated zones with anomalously high resistivity to be associated with contaminated DNAPLs presence. Resistivity maps clearly outlined the subsurface distribution and the possible migration path of DNAPLs.

  10. Magnetic properties and energy-mapping analysis.

    PubMed

    Xiang, Hongjun; Lee, Changhoon; Koo, Hyun-Joo; Gong, Xingao; Whangbo, Myung-Hwan

    2013-01-28

    The magnetic energy levels of a given magnetic solid are closely packed in energy because the interactions between magnetic ions are weak. Thus, in describing its magnetic properties, one needs to generate its magnetic energy spectrum by employing an appropriate spin Hamiltonian. In this review article we discuss how to determine and specify a necessary spin Hamiltonian in terms of first principles electronic structure calculations on the basis of energy-mapping analysis and briefly survey important concepts and phenomena that one encounters in reading the current literature on magnetic solids. Our discussion is given on a qualitative level from the perspective of magnetic energy levels and electronic structures. The spin Hamiltonian appropriate for a magnetic system should be based on its spin lattice, i.e., the repeat pattern of its strong magnetic bonds (strong spin exchange paths), which requires one to evaluate its Heisenberg spin exchanges on the basis of energy-mapping analysis. Other weaker energy terms such as Dzyaloshinskii-Moriya (DM) spin exchange and magnetocrystalline anisotropy energies, which a spin Hamiltonian must include in certain cases, can also be evaluated by performing energy-mapping analysis. We show that the spin orientation of a transition-metal magnetic ion can be easily explained by considering its split d-block levels as unperturbed states with the spin-orbit coupling (SOC) as perturbation, that the DM exchange between adjacent spin sites can become comparable in strength to the Heisenberg spin exchange when the two spin sites are not chemically equivalent, and that the DM interaction between rare-earth and transition-metal cations is governed largely by the magnetic orbitals of the rare-earth cation.

  11. Active Interaction Mapping as a tool to elucidate hierarchical functions of biological processes.

    PubMed

    Farré, Jean-Claude; Kramer, Michael; Ideker, Trey; Subramani, Suresh

    2017-07-03

    Increasingly, various 'omics data are contributing significantly to our understanding of novel biological processes, but it has not been possible to iteratively elucidate hierarchical functions in complex phenomena. We describe a general systems biology approach called Active Interaction Mapping (AI-MAP), which elucidates the hierarchy of functions for any biological process. Existing and new 'omics data sets can be iteratively added to create and improve hierarchical models which enhance our understanding of particular biological processes. The best datatypes to further improve an AI-MAP model are predicted computationally. We applied this approach to our understanding of general and selective autophagy, which are conserved in most eukaryotes, setting the stage for the broader application to other cellular processes of interest. In the particular application to autophagy-related processes, we uncovered and validated new autophagy and autophagy-related processes, expanded known autophagy processes with new components, integrated known non-autophagic processes with autophagy and predict other unexplored connections.

  12. DARC 2.0: Improved Docking and Virtual Screening at Protein Interaction Sites

    PubMed Central

    Gowthaman, Ragul; Lyskov, Sergey; Karanicolas, John

    2015-01-01

    Over the past decade, protein-protein interactions have emerged as attractive but challenging targets for therapeutic intervention using small molecules. Due to the relatively flat surfaces that typify protein interaction sites, modern virtual screening tools developed for optimal performance against “traditional” protein targets perform less well when applied instead at protein interaction sites. Previously, we described a docking method specifically catered to the shallow binding modes characteristic of small-molecule inhibitors of protein interaction sites. This method, called DARC (Docking Approach using Ray Casting), operates by comparing the topography of the protein surface when “viewed” from a vantage point inside the protein against the topography of a bound ligand when “viewed” from the same vantage point. Here, we present five key enhancements to DARC. First, we use multiple vantage points to more accurately determine protein-ligand surface complementarity. Second, we describe a new scheme for rapidly determining optimal weights in the DARC scoring function. Third, we incorporate sampling of ligand conformers “on-the-fly” during docking. Fourth, we move beyond simple shape complementarity and introduce a term in the scoring function to capture electrostatic complementarity. Finally, we adjust the control flow in our GPU implementation of DARC to achieve greater speedup of these calculations. At each step of this study, we evaluate the performance of DARC in a “pose recapitulation” experiment: predicting the binding mode of 25 inhibitors each solved in complex with its distinct target protein (a protein interaction site). Whereas the previous version of DARC docked only one of these inhibitors to within 2 Å RMSD of its position in the crystal structure, the newer version achieves this level of accuracy for 12 of the 25 complexes, corresponding to a statistically significant performance improvement (p < 0.001). Collectively then, we

  13. Interactive flare sites within an active region complex

    NASA Technical Reports Server (NTRS)

    Poletto, G.; Gary, G. A.; Machado, M. E.

    1993-01-01

    We examine here a set of images of an active region complex, acquired on June 24-25, 1980, by the Hard X-ray Imaging Spectrometer on SMM, with the purpose of establishing whether there was any interplay between the frequent activity observed at different sites in the activity center and, in such a case, how the interaction was established. By analyzing both quiet and active orbits we show that, as a rule, activity originating in one region triggers the other region's activity. However, we find little unambiguous evidence for the presence of large-scale interconnecting loops. A comparison of X-ray images with magnetic field observations suggested that we interpret the active region behavior in terms of the interaction between different loop systems, in a scenario quite analogous to the interacting bipole representation of individual flares. We conclude that active region interplay provides an easily observable case to study the time-dependent topology and the mechanisms for the spreading of activity in transient events over all energy scales.

  14. Deconstructing the DGAT1 enzyme: membrane interactions at substrate binding sites.

    PubMed

    Lopes, Jose L S; Beltramini, Leila M; Wallace, Bonnie A; Araujo, Ana P U

    2015-01-01

    Diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the triacylglyceride synthesis pathway. Bovine DGAT1 is an endoplasmic reticulum membrane-bound protein associated with the regulation of fat content in milk and meat. The aim of this study was to evaluate the interaction of DGAT1 peptides corresponding to putative substrate binding sites with different types of model membranes. Whilst these peptides are predicted to be located in an extramembranous loop of the membrane-bound protein, their hydrophobic substrates are membrane-bound molecules. In this study, peptides corresponding to the binding sites of the two substrates involved in the reaction were examined in the presence of model membranes in order to probe potential interactions between them that might influence the subsequent binding of the substrates. Whilst the conformation of one of the peptides changed upon binding several types of micelles regardless of their surface charge, suggesting binding to hydrophobic domains, the other peptide bound strongly to negatively-charged model membranes. This binding was accompanied by a change in conformation, and produced leakage of the liposome-entrapped dye calcein. The different hydrophobic and electrostatic interactions observed suggest the peptides may be involved in the interactions of the enzyme with membrane surfaces, facilitating access of the catalytic histidine to the triacylglycerol substrates.

  15. User-Centric Secure Cross-Site Interaction Framework for Online Social Networking Services

    ERIC Educational Resources Information Center

    Ko, Moo Nam

    2011-01-01

    Social networking service is one of major technological phenomena on Web 2.0. Hundreds of millions of users are posting message, photos, and videos on their profiles and interacting with other users, but the sharing and interaction are limited within the same social networking site. Although users can share some content on a social networking site…

  16. Mapping of contact sites in complex formation between transducin and light-activated rhodopsin by covalent crosslinking: Use of a photoactivatable reagent

    PubMed Central

    Cai, Kewen; Itoh, Yoshiki; Khorana, H. Gobind

    2001-01-01

    Interaction of light-activated rhodopsin with transducin (T) is the first event in visual signal transduction. We use covalent crosslinking approaches to map the contact sites in interaction between the two proteins. Here we use a photoactivatable reagent, N-[(2-pyridyldithio)-ethyl], 4-azido salicylamide. The reagent is attached to the SH group of cytoplasmic monocysteine rhodopsin mutants by a disulfide-exchange reaction with the pyridylthio group, and the derivatized rhodopsin then is complexed with T by illumination at λ >495 nm. Subsequent irradiation of the complex at λ310 nm generates covalent crosslinks between the two proteins. Crosslinking was demonstrated between T and a number of single cysteine rhodopsin mutants. However, sites of crosslinks were investigated in detail only between T and the rhodopsin mutant S240C (cytoplasmic loop V-VI). Crosslinking occurred predominantly with Tα. For identification of the sites of crosslinks in Tα, the strategy used involved: (i) derivatization of all of the free cysteines in the crosslinked proteins with N-ethylmaleimide; (ii) reduction of the disulfide bond linking the two proteins and isolation of all of the Tα species carrying the crosslinked moiety with a free SH group; (iii) adduct formation of the latter with the N-maleimide moiety of the reagent, maleimido-butyryl-biocytin, containing a biotinyl group; (iv) trypsin degradation of the resulting Tα derivatives and isolation of Tα peptides carrying maleimido-butyryl-biocytin by avidin-agarose chromatography; and (v) identification of the isolated peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We found that crosslinking occurred mainly to two C-terminal peptides in Tα containing the amino acid sequences 310–313 and 342–345. PMID:11320237

  17. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria

    PubMed Central

    Hoppins, Suzanne; Collins, Sean R.; Cassidy-Stone, Ann; Hummel, Eric; DeVay, Rachel M.; Lackner, Laura L.; Westermann, Benedikt; Schuldiner, Maya

    2011-01-01

    To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane–associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria. PMID:21987634

  18. Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

    PubMed

    Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

    2017-07-24

    Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

  19. An Overview of Plume Tracker: Mapping Volcanic Emissions with Interactive Radiative Transfer Modeling

    NASA Astrophysics Data System (ADS)

    Realmuto, V. J.; Berk, A.; Guiang, C.

    2014-12-01

    Infrared remote sensing is a vital tool for the study of volcanic plumes, and radiative transfer (RT) modeling is required to derive quantitative estimation of the sulfur dioxide (SO2), sulfate aerosol (SO4), and silicate ash (pulverized rock) content of these plumes. In the thermal infrared, we must account for the temperature, emissivity, and elevation of the surface beneath the plume, plume altitude and thickness, and local atmospheric temperature and humidity. Our knowledge of these parameters is never perfect, and interactive mapping allows us to evaluate the impact of these uncertainties on our estimates of plume composition. To enable interactive mapping, the Jet Propulsion Laboratory is collaborating with Spectral Sciences, Inc., (SSI) to develop the Plume Tracker toolkit. This project is funded by a NASA AIST Program Grant (AIST-11-0053) to SSI. Plume Tracker integrates (1) retrieval procedures for surface temperature and emissivity, SO2, NH3, or CH4 column abundance, and scaling factors for H2O vapor and O3 profiles, (2) a RT modeling engine based on MODTRAN, and (3) interactive visualization and analysis utilities under a single graphics user interface. The principal obstacle to interactive mapping is the computational overhead of the RT modeling engine. Under AIST-11-0053 we have achieved a 300-fold increase in the performance of the retrieval procedures through the use of indexed caches of model spectra, optimization of the minimization procedures, and scaling of the effects of surface temperature and emissivity on model radiance spectra. In the final year of AIST-11-0053 we will implement parallel processing to exploit multi-core CPUs and cluster computing, and optimize the RT engine to eliminate redundant calculations when iterating over a range of gas concentrations. These enhancements will result in an additional 8 - 12X increase in performance. In addition to the improvements in performance, we have improved the accuracy of the Plume Tracker

  20. Social Networking Sites as Communication, Interaction, and Learning Environments: Perceptions and Preferences of Distance Education Students

    ERIC Educational Resources Information Center

    Bozkurt, Aras; Karadeniz, Abdulkadir; Kocdar, Serpil

    2017-01-01

    The advent of Web 2.0 technologies transformed online networks into interactive spaces in which user-generated content has become the core material. With the possibilities that emerged from Web 2.0, social networking sites became very popular. The capability of social networking sites promises opportunities for communication and interaction,…

  1. Contour Mapping

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In the early 1990s, the Ohio State University Center for Mapping, a NASA Center for the Commercial Development of Space (CCDS), developed a system for mobile mapping called the GPSVan. While driving, the users can map an area from the sophisticated mapping van equipped with satellite signal receivers, video cameras and computer systems for collecting and storing mapping data. George J. Igel and Company and the Ohio State University Center for Mapping advanced the technology for use in determining the contours of a construction site. The new system reduces the time required for mapping and staking, and can monitor the amount of soil moved.

  2. Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sites

    PubMed Central

    Song, Xiufeng; Gurevich, Eugenia V.; Gurevich, Vsevolod V.

    2008-01-01

    Arrestins are multi-functional regulators of G protein-coupled receptors. Receptor-bound arrestins interact with >30 remarkably diverse proteins and redirect the signaling to G protein-independent pathways. The functions of free arrestins are poorly understood, and the interaction sites of the non-receptor arrestin partners are largely unknown. In this study, we show that cone arrestin, the least studied member of the family, binds c-Jun N-terminal kinase (JNK3) and Mdm2 and regulates their subcellular distribution. Using arrestin mutants with increased or reduced structural flexibility, we demonstrate that arrestin in all conformations binds JNK3 comparably, whereas Mdm2 preferentially binds cone arrestin ‘frozen’ in the basal state. To localize the interaction sites, we expressed separate N- and C-domains of cone and rod arrestins and found that individual domains bind JNK3 and remove it from the nucleus as efficiently as full-length proteins. Thus, the arrestin binding site for JNK3 includes elements in both domains with the affinity of partial sites on individual domains sufficient for JNK3 relocalization. N-domain of rod arrestin binds Mdm2, which localizes its main interaction site to this region. Comparable binding of JNK3 and Mdm2 to four arrestin subtypes allowed us to identify conserved residues likely involved in these interactions. PMID:17680991

  3. Distinguishing time-delayed causal interactions using convergent cross mapping

    PubMed Central

    Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

    2015-01-01

    An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

  4. Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?

    PubMed

    Luther, Vishal; Qureshi, Norman; Lim, Phang Boon; Koa-Wing, Michael; Jamil-Copley, Shahnaz; Ng, Fu Siong; Whinnett, Zachary; Davies, D Wyn; Peters, Nicholas S; Kanagaratnam, Prapa; Linton, Nick

    2018-03-01

    Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach. © 2018 Wiley Periodicals, Inc.

  5. Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology.

    PubMed

    DeBlasio, Stacy L; Chavez, Juan D; Alexander, Mariko M; Ramsey, John; Eng, Jimmy K; Mahoney, Jaclyn; Gray, Stewart M; Bruce, James E; Cilia, Michelle

    2016-02-15

    Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus [PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in the Luteoviridae and with unrelated viruses in the Herpesviridae and Adenoviridae. Functional analysis of three PLRV-interacting host proteins in planta using a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection-hallmarks of host-pathogen interactions-were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies. The exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used protein interaction

  6. NHS-Esters As Versatile Reactivity-Based Probes for Mapping Proteome-Wide Ligandable Hotspots.

    PubMed

    Ward, Carl C; Kleinman, Jordan I; Nomura, Daniel K

    2017-06-16

    Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug discovery. Identifying previously unknown druggable hotspots in proteins would enable strategies for pharmacologically interrogating these sites with small molecules. Activity-based protein profiling (ABPP) has arisen as a powerful chemoproteomic strategy that uses reactivity-based chemical probes to map reactive, functional, and ligandable hotspots in complex proteomes, which has enabled inhibitor discovery against various therapeutic protein targets. Here, we report an alkyne-functionalized N-hydroxysuccinimide-ester (NHS-ester) as a versatile reactivity-based probe for mapping the reactivity of a wide range of nucleophilic ligandable hotspots, including lysines, serines, threonines, and tyrosines, encompassing active sites, allosteric sites, post-translational modification sites, protein interaction sites, and previously uncharacterized potential binding sites. Surprisingly, we also show that fragment-based NHS-ester ligands can be made to confer selectivity for specific lysine hotspots on specific targets including Dpyd, Aldh2, and Gstt1. We thus put forth NHS-esters as promising reactivity-based probes and chemical scaffolds for covalent ligand discovery.

  7. Efficient mapping of transgene integration sites and local structural changes in Cre transgenic mice using targeted locus amplification.

    PubMed

    Cain-Hom, Carol; Splinter, Erik; van Min, Max; Simonis, Marieke; van de Heijning, Monique; Martinez, Maria; Asghari, Vida; Cox, J Colin; Warming, Søren

    2017-05-05

    Cre/LoxP technology is widely used in the field of mouse genetics for spatial and/or temporal regulation of gene function. For Cre lines generated via pronuclear microinjection of a Cre transgene construct, the integration site is random and in most cases not known. Integration of a transgene can disrupt an endogenous gene, potentially interfering with interpretation of the phenotype. In addition, knowledge of where the transgene is integrated is important for planning of crosses between animals carrying a conditional allele and a given Cre allele in case the alleles are on the same chromosome. We have used targeted locus amplification (TLA) to efficiently map the transgene location in seven previously published Cre and CreERT2 transgenic lines. In all lines, transgene insertion was associated with structural changes of variable complexity, illustrating the importance of testing for rearrangements around the integration site. In all seven lines the exact integration site and breakpoint sequences were identified. Our methods, data and genotyping assays can be used as a resource for the mouse community and our results illustrate the power of the TLA method to not only efficiently map the integration site of any transgene, but also provide additional information regarding the transgene integration events. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. BAID: The Barrow Area Information Database - an interactive web mapping portal and cyberinfrastructure for scientific activities in the vicinity of Barrow, Alaska.

    NASA Astrophysics Data System (ADS)

    Cody, R. P.; Kassin, A.; Kofoed, K. B.; Copenhaver, W.; Laney, C. M.; Gaylord, A. G.; Collins, J. A.; Tweedie, C. E.

    2014-12-01

    The Barrow area of northern Alaska is one of the most intensely researched locations in the Arctic and the Barrow Area Information Database (BAID, www.barrowmapped.org) tracks and facilitates a gamut of research, management, and educational activities in the area. BAID is a cyberinfrastructure (CI) that details much of the historic and extant research undertaken within in the Barrow region in a suite of interactive web-based mapping and information portals (geobrowsers). The BAID user community and target audience for BAID is diverse and includes research scientists, science logisticians, land managers, educators, students, and the general public. BAID contains information on more than 12,000 Barrow area research sites that extend back to the 1940's and more than 640 remote sensing images and geospatial datasets. In a web-based setting, users can zoom, pan, query, measure distance, save or print maps and query results, and filter or view information by space, time, and/or other tags. Data are described with metadata that meet Federal Geographic Data Committee standards and are archived at the University Corporation for Atmospheric Research Earth Observing Laboratory (EOL) where non-proprietary BAID data can be freely downloaded. Recent advances include the addition of more than 2000 new research sites, provision of differential global position system (dGPS) and Unmanned Aerial Vehicle (UAV) support to visiting scientists, surveying over 80 miles of coastline to document rates of erosion, training of local GIS personal to better make use of science in local decision making, deployment and near real time connectivity to a wireless micrometeorological sensor network, links to Barrow area datasets housed at national data archives and substantial upgrades to the BAID website and web mapping applications.

  9. 183. Photocopy of map (Twin Falls Canal Company). TOPOGRAPHICAL MAP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    183. Photocopy of map (Twin Falls Canal Company). TOPOGRAPHICAL MAP OF MILNER DAM SITE, TWIN FALLS COUNTY, MILNER, IDAHO; MAP, LEFT SIDE ONLY. CROSS REFERENCE: ID-15-192. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  10. Real-Time Mapping alert system; characteristics and capabilities

    USGS Publications Warehouse

    Torres, L.A.; Lambert, S.C.; Liebermann, T.D.

    1995-01-01

    The U.S. Geological Survey has an extensive hydrologic network that records and transmits precipitation, stage, discharge, and other water-related data on a real-time basis to an automated data processing system. Data values are recorded on electronic data collection platforms at field sampling sites. These values are transmitted by means of orbiting satellites to receiving ground stations, and by way of telecommunication lines to a U.S. Geological Survey office where they are processed on a computer system. Data that exceed predefined thresholds are identified as alert values. The current alert status at monitoring sites within a state or region is of critical importance during floods, hurricanes, and other extreme hydrologic events. This report describes the characteristics and capabilities of a series of computer programs for real-time mapping of hydrologic data. The software provides interactive graphics display and query of hydrologic information from the network in a real-time, map-based, menu-driven environment.

  11. Posterior insular cortex - a site of vestibular-somatosensory interaction?

    PubMed

    Baier, Bernhard; Zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

    2013-09-01

    Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact.

  12. Integrating Databases with Maps: The Delivery of Cultural Data through TimeMap.

    ERIC Educational Resources Information Center

    Johnson, Ian

    TimeMap is a unique integration of database management, metadata and interactive maps, designed to contextualise and deliver cultural data through maps. TimeMap extends conventional maps with the time dimension, creating and animating maps "on-the-fly"; delivers them as a kiosk application or embedded in Web pages; links flexibly to…

  13. Short cell-penetrating peptides: a model of interactions with gene promoter sites.

    PubMed

    Khavinson, V Kh; Tarnovskaya, S I; Linkova, N S; Pronyaeva, V E; Shataeva, L K; Yakutseni, P P

    2013-01-01

    Analysis of the main parameters of molecular mechanics (number of hydrogen bonds, hydrophobic and electrostatic interactions, DNA-peptide complex minimization energy) provided the data to validate the previously proposed qualitative models of peptide-DNA interactions and to evaluate their quantitative characteristics. Based on these estimations, a three-dimensional model of Lys-Glu and Ala-Glu-Asp-Gly peptide interactions with DNA sites (GCAG and ATTTC) located in the promoter zones of genes encoding CD5, IL-2, MMP2, and Tram1 signal molecules.

  14. Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology

    PubMed Central

    DeBlasio, Stacy L.; Chavez, Juan D.; Alexander, Mariko M.; Ramsey, John; Eng, Jimmy K.; Mahoney, Jaclyn; Gray, Stewart M.; Bruce, James E.

    2015-01-01

    ABSTRACT Demonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus [PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in the Luteoviridae and with unrelated viruses in the Herpesviridae and Adenoviridae. Functional analysis of three PLRV-interacting host proteins in planta using a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection—hallmarks of host-pathogen interactions—were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies. IMPORTANCE The exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used

  15. Molecules to maps: tools for visualization and interaction in support of computational biology.

    PubMed

    Kraemer, E T; Ferrin, T E

    1998-01-01

    The volume of data produced by genome projects, X-ray crystallography, NMR spectroscopy, and electron and confocal microscopy present the bioinformatics community with new challenges for analyzing, understanding, and exchanging this data. At the 1998 Pacific Symposium on Biocomputing, a track entitled 'Molecules to Maps: Tools for Visualization and Interaction in Computational Biology' provided tool developers and users with the opportunity to discuss advances in tools and techniques to assist scientists in evaluating, absorbing, navigating, and correlating this sea of information, through visualization and user interaction. In this paper we present these advances and discuss some of the challenges that remain to be solved.

  16. Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings

    PubMed Central

    2016-01-01

    Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or “edge,” due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. PMID:26823515

  17. Recording and labeling at a site along the cochlea shows alignment of medial olivocochlear and auditory nerve tonotopic mappings.

    PubMed

    Brown, M Christian

    2016-03-01

    Medial olivocochlear (MOC) neurons provide an efferent innervation to outer hair cells (OHCs) of the cochlea, but their tonotopic mapping is incompletely known. In the present study of anesthetized guinea pigs, the MOC mapping was investigated using in vivo, extracellular recording, and labeling at a site along the cochlear course of the axons. The MOC axons enter the cochlea at its base and spiral apically, successively turning out to innervate OHCs according to their characteristic frequencies (CFs). Recordings made at a site in the cochlear basal turn yielded a distribution of MOC CFs with an upper limit, or "edge," due to usually absent higher-CF axons that presumably innervate more basal locations. The CFs at the edge, normalized across preparations, were equal to the CFs of the auditory nerve fibers (ANFs) at the recording sites (near 16 kHz). Corresponding anatomical data from extracellular injections showed spiraling MOC axons giving rise to an edge of labeling at the position of a narrow band of labeled ANFs. Overall, the edges of the MOC CFs and labeling, with their correspondences to ANFs, suggest similar tonotopic mappings of these efferent and afferent fibers, at least in the cochlear basal turn. They also suggest that MOC axons miss much of the position of the more basally located cochlear amplifier appropriate for their CF; instead, the MOC innervation may be optimized for protection from damage by acoustic overstimulation. Copyright © 2016 the American Physiological Society.

  18. Protein protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach

    NASA Astrophysics Data System (ADS)

    Keskin, Ozlem; Ma, Buyong; Rogale, Kristina; Gunasekaran, K.; Nussinov, Ruth

    2005-06-01

    Understanding and ultimately predicting protein associations is immensely important for functional genomics and drug design. Here, we propose that binding sites have preferred organizations. First, the hot spots cluster within densely packed 'hot regions'. Within these regions, they form networks of interactions. Thus, hot spots located within a hot region contribute cooperatively to the stability of the complex. However, the contributions of separate, independent hot regions are additive. Moreover, hot spots are often already pre-organized in the unbound (free) protein states. Describing a binding site through independent local hot regions has implications for binding site definition, design and parametrization for prediction. The compactness and cooperativity emphasize the similarity between binding and folding. This proposition is grounded in computation and experiment. It explains why summation of the interactions may over-estimate the stability of the complex. Furthermore, statistically, charge-charge coupling of the hot spots is disfavored. However, since within the highly packed regions the solvent is screened, the electrostatic contributions are strengthened. Thus, we propose a new description of protein binding sites: a site consists of (one or a few) self-contained cooperative regions. Since the residue hot spots are those conserved by evolution, proteins binding multiple partners at the same sites are expected to use all or some combination of these regions.

  19. Digital Geologic Map of the Nevada Test Site and Vicinity, Nye, Lincoln, and Clark Counties, Nevada, and Inyo County, California

    USGS Publications Warehouse

    Slate, Janet L.; Berry, Margaret E.; Rowley, Peter D.; Fridrich, Christopher J.; Morgan, Karen S.; Workman, Jeremiah B.; Young, Owen D.; Dixon, Gary L.; Williams, Van S.; McKee, Edwin H.; Ponce, David A.; Hildenbrand, Thomas G.; Swadley, W.C.; Lundstrom, Scott C.; Ekren, E. Bartlett; Warren, Richard G.; Cole, James C.; Fleck, Robert J.; Lanphere, Marvin A.; Sawyer, David A.; Minor, Scott A.; Grunwald, Daniel J.; Laczniak, Randell J.; Menges, Christopher M.; Yount, James C.; Jayko, Angela S.

    1999-01-01

    This digital geologic map of the Nevada Test Site (NTS) and vicinity, as well as its accompanying digital geophysical maps, are compiled at 1:100,000 scale. The map compilation presents new polygon (geologic map unit contacts), line (fault, fold axis, metamorphic isograd, dike, and caldera wall) and point (structural attitude) vector data for the NTS and vicinity, Nye, Lincoln, and Clark Counties, Nevada, and Inyo County, California. The map area covers two 30 x 60-minute quadrangles-the Pahute Mesa quadrangle to the north and the Beatty quadrangle to the south-plus a strip of 7.5-minute quadrangles on the east side-72 quadrangles in all. In addition to the NTS, the map area includes the rest of the southwest Nevada volcanic field, part of the Walker Lane, most of the Amargosa Desert, part of the Funeral and Grapevine Mountains, some of Death Valley, and the northern Spring Mountains. This geologic map improves on previous geologic mapping of the same area (Wahl and others, 1997) by providing new and updated Quaternary and bedrock geology, new geophysical interpretations of faults beneath the basins, and improved GIS coverages. Concurrent publications to this one include a new isostatic gravity map (Ponce and others, 1999) and a new aeromagnetic map (Ponce, 1999).

  20. Environmental Research Translation: Enhancing Interactions with Communities at Contaminated Sites

    NASA Astrophysics Data System (ADS)

    Ramirez-Andreotta, M.; Brusseau, M. L. L.; Artiola, J. F.; Maier, R. M.; Gandolfi, A. J.

    2015-12-01

    The characterization and remediation of contaminated sites are complex endeavors fraught with numerous challenges. One particular challenge that is receiving increased attention is the development and encouragement of full participation by communities and community members affected by a given site in all facets of decision-making. Many disciplines have been grappling with the challenges associated with environmental and risk communication, public participation in environmental data generation and decision-making, and increasing community capacity. The concepts and methods developed by these disciplines are reviewed, with a focus on their relevance to the specific dynamics associated with contaminated sites. The contributions of these disciplines are then synthesized and integrated to help develop Environmental Research Translation (ERT), a proposed framework for environmental scientists to promote interaction and communication among involved parties at contaminated sites. This holistic approach is rooted in public participation approaches to science, which includes: a transdisciplinary team, effective collaboration, information transfer, public participation in environmental projects, and a cultural model of risk communication. Although there are challenges associated with the implementation of ERT, it is anticipated that application of this proposed translational science method could promote more robust community participation at contaminated sites.

  1. Environmental Research Translation: Enhancing Interactions with Communities at Contaminated Sites

    PubMed Central

    Ramirez-Andreotta, Monica D.; Brusseau, Mark L.; Artiola, Janick F.; Maier, Raina M.; Gandolfi, A. Jay

    2014-01-01

    The characterization and remediation of contaminated sites are complex endeavors fraught with numerous challenges. One particular challenge that is receiving increased attention is the development and encouragement of full participation by communities and community members affected by a given site in all facets of decision-making. Many disciplines have been grappling with the challenges associated with environmental and risk communication, public participation in environmental data generation, and decision-making and increasing community capacity. The concepts and methods developed by these disciplines are reviewed, with a focus on their relevance to the specific dynamics associated with environmental contamination sites. The contributions of these disciplines are then synthesized and integrated to help develop Environmental Research Translation (ERT), a proposed framework for environmental scientists to promote interaction and communication among involved parties at contaminated sites. This holistic approach is rooted in public participation approaches to science, which includes: a transdisciplinary team, effective collaboration, information transfer, public participation in environmental projects, and a cultural model of risk communication. Although there are challenges associated with the implementation of ERT, it is anticipated that application of this proposed translational science method could promote more robust community participation at contaminated sites. PMID:25173762

  2. The Methodology of Interactive Parametric Modelling of Construction Site Facilities in BIM Environment

    NASA Astrophysics Data System (ADS)

    Kozlovská, Mária; Čabala, Jozef; Struková, Zuzana

    2014-11-01

    Information technology is becoming a strong tool in different industries, including construction. The recent trend of buildings designing is leading up to creation of the most comprehensive virtual building model (Building Information Model) in order to solve all the problems relating to the project as early as in the designing phase. Building information modelling is a new way of approaching to the design of building projects documentation. Currently, the building site layout as a part of the building design documents has a very little support in the BIM environment. Recently, the research of designing the construction process conditions has centred on improvement of general practice in planning and on new approaches to construction site layout planning. The state of art in field of designing the construction process conditions indicated an unexplored problem related to connection of knowledge system with construction site facilities (CSF) layout through interactive modelling. The goal of the paper is to present the methodology for execution of 3D construction site facility allocation model (3D CSF-IAM), based on principles of parametric and interactive modelling.

  3. Quantum mechanics study of the hydroxyethylamines-BACE-1 active site interaction energies

    NASA Astrophysics Data System (ADS)

    Gueto-Tettay, Carlos; Drosos, Juan Carlos; Vivas-Reyes, Ricardo

    2011-06-01

    The identification of BACE-1, a key enzyme in the production of Amyloid-β (Aβ) peptides, generated by the proteolytic processing of amyloid precursor protein, was a major advance in the field of Alzheimer's disease as this pathology is characterized by the presence of extracellular senile plaques, mainly comprised of Aβ peptides. Hydroxyethylamines have demonstrated a remarkable potential, like candidate drugs, for this disease using BACE-1 as target. Density Functional Theory calculations were employed to estimate interaction energies for the complexes formed between the hydroxyethylamine derivated inhibitors and 24 residues in the BACE-1 active site. The collected data offered not only a general but a particular quantitative description that gives a deep insight of the interactions in the active site, showing at the same time how ligand structural variations affect them. Polar interactions are the major energetic contributors for complex stabilization and those ones with charged aspartate residues are highlighted, as they contribute over 90% of the total attractive interaction energy. Ligand-ARG296 residue interaction reports the most repulsive value and decreasing of the magnitude of this repulsion can be a key feature for the design of novel and more potent BACE-1 inhibitors. Also it was explained why sultam derivated BACE-1 inhibitors are better ones than lactam based. Hydrophobic interactions concentrated at S1 zone and other relevant repulsions and attractions were also evaluated. The comparison of two different theory levels (X3LYP and M062X) allowed to confirm the relevance of the detected interactions as each theory level has its own strength to depict the forces involved, as is the case of M062X which is better describing the hydrophobic interactions. Those facts were also evaluated and confirmed by comparing the quantitative trend, of selected ligand-residue interactions, with MP2 theory level as reference standard method for electrostatic plus

  4. Quantum mechanics study of the hydroxyethylamines-BACE-1 active site interaction energies.

    PubMed

    Gueto-Tettay, Carlos; Drosos, Juan Carlos; Vivas-Reyes, Ricardo

    2011-06-01

    The identification of BACE-1, a key enzyme in the production of Amyloid-β (Aβ) peptides, generated by the proteolytic processing of amyloid precursor protein, was a major advance in the field of Alzheimer's disease as this pathology is characterized by the presence of extracellular senile plaques, mainly comprised of Aβ peptides. Hydroxyethylamines have demonstrated a remarkable potential, like candidate drugs, for this disease using BACE-1 as target. Density Functional Theory calculations were employed to estimate interaction energies for the complexes formed between the hydroxyethylamine derivated inhibitors and 24 residues in the BACE-1 active site. The collected data offered not only a general but a particular quantitative description that gives a deep insight of the interactions in the active site, showing at the same time how ligand structural variations affect them. Polar interactions are the major energetic contributors for complex stabilization and those ones with charged aspartate residues are highlighted, as they contribute over 90% of the total attractive interaction energy. Ligand-ARG296 residue interaction reports the most repulsive value and decreasing of the magnitude of this repulsion can be a key feature for the design of novel and more potent BACE-1 inhibitors. Also it was explained why sultam derivated BACE-1 inhibitors are better ones than lactam based. Hydrophobic interactions concentrated at S1 zone and other relevant repulsions and attractions were also evaluated. The comparison of two different theory levels (X3LYP and M062X) allowed to confirm the relevance of the detected interactions as each theory level has its own strength to depict the forces involved, as is the case of M062X which is better describing the hydrophobic interactions. Those facts were also evaluated and confirmed by comparing the quantitative trend, of selected ligand-residue interactions, with MP2 theory level as reference standard method for electrostatic plus

  5. Genotype to Phenotype Mapping of the E. coli lac Promoter

    NASA Astrophysics Data System (ADS)

    Otwinowski, Jakub; Nemenman, Ilya

    2014-03-01

    Genotype-to-phenotype maps and the related fitness landscapes that include epistatic interactions are difficult to measure because of their high dimensional structure. Here we construct such a map using the recently collected corpora of high-throughput sequence data from the 75 base pairs long mutagenized E. coli lac promoter region, where each sequence is associated with induced transcriptional activity measured by a fluorescent reporter. We find that the additive (non-epistatic) contributions of individual mutations account for about two-thirds of the explainable phenotype variance, while pairwise epistasis explains about 7% of the variance for the full mutagenized sequence and about 15% for the subsequence associated with protein binding sites. Surprisingly, there is no evidence for third order epistatic contributions, and our inferred fitness landscape is essentially single peaked, with a small amount of antagonistic epistasis. We identify transcription factor (CRP) and RNA polymerase binding sites in the promotor region and their interactions. We conclude with a cautionary note that inferred properties of fitness landscapes may be severely influenced by biases in the sequence data. Funded in part by HFSP and James S. McDonnell Foundation.

  6. [Protein interaction site of Toxoplasma gondii microneme protein 6 and aldolase determined by site-directed mutagenesis].

    PubMed

    Zheng, Bin; Yin, Zhi-Kui; Zhan, Xi-Mei

    2014-06-01

    To identify the protein interaction site of Toxoplasma gondii microneme protein 6 (MIC6) and aldolase by using site-directed mutagenesis. Based on Toxoplasma gondii MIC6 gene sequence (GenBank Accession No. AF110270), the specific primers were designed. Tryptophan (W)-348 of MIC6 C terminus (MIC6C) was mutated to valine (V) via site-directed mutagenesis. MIC6C W/V gene was obtained from cDNA library by PCR amplification and subcloned into pGEX-4T-1. The mutant protein GST-MIC6C W/V was expressed in E. coli, induced by 0.8 mmol/L IPTG, and purified by affinity chromatography. Glutathione sepharose beads were incubated with GST-MIC6C W/V and GST-MIC6C, respectively, and then incubated with T. gondii tachyzoites lysate, and bound proteins were eluted using sample buffer. Bound products were resolved by SDS-PAGE and Western blotting. Glutathione sepharose beads were incubated with GST-MIC6C W/V and GST-MIC6C, respectively, and then incubated with aldolase-His6. After incubation, the resin was washed and subjected to SDS-PAGE. The MIC6C W/N gene was obtained, and the recombinant plasmid MIC6C W/V/pGEX-4T-1 was successfully constructed. The mutant protein GST-MIC6C W/V was expressed and purified in vitro. SDS-PAGE analysis indicated that GST-MIC6C was co-precipitated with aldolase from T. gondii tachyzoites lysate or aldolase-His6, whereas GST-MIC6C W/V failed to precipitate aldolase from T. gondii tachyzoites lysate or aldolase-His6. Western blotting analysis using anti-aldolase antibody indicated that GST-MIC6C could pull-down aldolase from T. gondii tachyzoites lysate. Tryptophan (W348) was the interaction site of MIC6 and aldolase in T. gondii.

  7. Genome-wide Mapping of Cellular Protein–RNA Interactions Enabled by Chemical Crosslinking

    PubMed Central

    Li, Xiaoyu; Song, Jinghui; Yi, Chengqi

    2014-01-01

    RNA–protein interactions influence many biological processes. Identifying the binding sites of RNA-binding proteins (RBPs) remains one of the most fundamental and important challenges to the studies of such interactions. Capturing RNA and RBPs via chemical crosslinking allows stringent purification procedures that significantly remove the non-specific RNA and protein interactions. Two major types of chemical crosslinking strategies have been developed to date, i.e., UV-enabled crosslinking and enzymatic mechanism-based covalent capture. In this review, we compare such strategies and their current applications, with an emphasis on the technologies themselves rather than the biology that has been revealed. We hope such methods could benefit broader audience and also urge for the development of new methods to study RNA−RBP interactions. PMID:24747191

  8. Geovisualization in the HydroProg web map service

    NASA Astrophysics Data System (ADS)

    Spallek, Waldemar; Wieczorek, Malgorzata; Szymanowski, Mariusz; Niedzielski, Tomasz; Swierczynska, Malgorzata

    2016-04-01

    The HydroProg system, built at the University of Wroclaw (Poland) in frame of the research project no. 2011/01/D/ST10/04171 financed by the National Science Centre of Poland, has been designed for computing predictions of river stages in real time on a basis of multimodelling. This experimental system works on the upper Nysa Klodzka basin (SW Poland) above the gauge in the town of Bardo, with the catchment area of 1744 square kilometres. The system operates in association with the Local System for Flood Monitoring of Klodzko County (LSOP), and produces hydrograph prognoses as well as inundation predictions. For presenting the up-to-date predictions and their statistics in the online mode, the dedicated real-time web map service has been designed. Geovisualisation in the HydroProg map service concerns: interactive maps of study area, interactive spaghetti hydrograms of water level forecasts along with observed river stages, animated images of inundation. The LSOP network offers a high spatial and temporal resolution of observations, as the length of the sampling interval is equal to 15 minutes. The main environmental elements related to hydrological modelling are shown on the main map. This includes elevation data (hillshading and hypsometric tints), rivers and reservoirs as well as catchment boundaries. Furthermore, we added main towns, roads as well as political and administrative boundaries for better map understanding. The web map was designed as a multi-scale representation, with levels of detail and zooming according to scales: 1:100 000, 1:250 000 and 1:500 000. Observations of water level in LSOP are shown on interactive hydrographs for each gauge. Additionally, predictions and some of their statistical characteristics (like prediction errors and Nash-Sutcliffe efficiency) are shown for selected gauges. Finally, predictions of inundation are presented on animated maps which have been added for four experimental sites. The HydroProg system is a strictly

  9. Functional Interaction Map of Lyssavirus Phosphoprotein: Identification of the Minimal Transcription Domains

    PubMed Central

    Jacob, Yves; Real, Eléonore; Tordo, Noël

    2001-01-01

    Lyssaviruses, the causative agents of rabies encephalitis, are distributed in seven genotypes. The phylogenetically distant rabies virus (PV strain, genotype 1) and Mokola virus (genotype 3) were used to develop a strategy to identify functional homologous interactive domains from two proteins (P and N) which participate in the viral ribonucleoprotein (RNP) transcription-replication complex. This strategy combined two-hybrid and green fluorescent protein–reverse two-hybrid assays in Saccharomyces cerevisiae to analyze protein-protein interactions and a reverse genetic assay in mammalian cells to study the transcriptional activity of the reconstituted RNP complex. Lyssavirus P proteins contain two N-binding domains (N-BDs), a strong one encompassing amino acid (aa) 176 to the C terminus and a weak one in the 189 N-terminal aa. The N-terminal portion of P (aa 52 to 189) also contains a homomultimerization site. Here we demonstrate that N-P interactions, although weaker, are maintained between proteins of the different genotypes. A minimal transcriptional module of the P protein was obtained by fusing the first 60 N-terminal aa containing the L protein binding site to the C-terminal strong N-BD. Random mutation of the strong N-BD on P protein identified three highly conserved K residues crucial for N-P interaction. Their mutagenesis in full-length P induced a transcriptionally defective RNP. The analysis of homologous interactive domains presented here and previously reported dissections of the P protein allowed us to propose a model of the functional interaction network of the lyssavirus P protein. This model underscores the central role of P at the interface between L protein and N-RNA template. PMID:11559793

  10. ChiPPI: a novel method for mapping chimeric protein-protein interactions uncovers selection principles of protein fusion events in cancer.

    PubMed

    Frenkel-Morgenstern, Milana; Gorohovski, Alessandro; Tagore, Somnath; Sekar, Vaishnovi; Vazquez, Miguel; Valencia, Alfonso

    2017-07-07

    Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins. Mapping the influence of fusion proteins on cell metabolism and pathways reveals that ChiPPI networks often lose tumor suppressor proteins and gain oncoproteins. Furthermore, fusions often induce novel connections between non-interactors skewing interaction networks and signaling pathways. We compared fusion protein PPI networks in leukemia/lymphoma, sarcoma and solid tumors finding distinct enrichment patterns for each disease type. While certain pathways are enriched in all three diseases (Wnt, Notch and TGF β), there are distinct patterns for leukemia (EGFR signaling, DNA replication and CCKR signaling), for sarcoma (p53 pathway and CCKR signaling) and solid tumors (FGFR and EGFR signaling). Thus, the ChiPPI method represents a comprehensive tool for studying the anomaly of skewed cellular networks produced by fusion proteins in cancer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Expansion of Protein Farnesyltransferase Specificity Using “Tunable” Active Site Interactions

    PubMed Central

    Hougland, James L.; Gangopadhyay, Soumyashree A.; Fierke, Carol A.

    2012-01-01

    Post-translational modifications play essential roles in regulating protein structure and function. Protein farnesyltransferase (FTase) catalyzes the biologically relevant lipidation of up to several hundred cellular proteins. Site-directed mutagenesis of FTase coupled with peptide selectivity measurements demonstrates that molecular recognition is determined by a combination of multiple interactions. Targeted randomization of these interactions yields FTase variants with altered and, in some cases, bio-orthogonal selectivity. We demonstrate that FTase specificity can be “tuned” using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase variants enabling the creation of bioengineered parallel prenylation pathways with altered substrate selectivity within a cell. Engineered FTase variants provide a novel avenue for probing both the selectivity of prenylation pathway enzymes and the effects of prenylation pathway modifications on the cellular function of a protein. PMID:22992747

  12. Web GIS in practice VIII: HTML5 and the canvas element for interactive online mapping.

    PubMed

    Boulos, Maged N Kamel; Warren, Jeffrey; Gong, Jianya; Yue, Peng

    2010-03-03

    HTML5 is being developed as the next major revision of HTML (Hypertext Markup Language), the core markup language of the World Wide Web. It aims at reducing the need for proprietary, plug-in-based rich Internet application (RIA) technologies such as Adobe Flash. The canvas element is part of HTML5 and is used to draw graphics using scripting (e.g., JavaScript). This paper introduces Cartagen, an open-source, vector-based, client-side framework for rendering plug-in-free, offline-capable, interactive maps in native HTML5 on a wide range of Web browsers and mobile phones. Cartagen was developed at MIT Media Lab's Design Ecology group. Potential applications of the technology as an enabler for participatory online mapping include mapping real-time air pollution, citizen reporting, and disaster response, among many other possibilities.

  13. Web GIS in practice VIII: HTML5 and the canvas element for interactive online mapping

    PubMed Central

    2010-01-01

    HTML5 is being developed as the next major revision of HTML (Hypertext Markup Language), the core markup language of the World Wide Web. It aims at reducing the need for proprietary, plug-in-based rich Internet application (RIA) technologies such as Adobe Flash. The canvas element is part of HTML5 and is used to draw graphics using scripting (e.g., JavaScript). This paper introduces Cartagen, an open-source, vector-based, client-side framework for rendering plug-in-free, offline-capable, interactive maps in native HTML5 on a wide range of Web browsers and mobile phones. Cartagen was developed at MIT Media Lab's Design Ecology group. Potential applications of the technology as an enabler for participatory online mapping include mapping real-time air pollution, citizen reporting, and disaster response, among many other possibilities. PMID:20199681

  14. Bose-Fermi mapping and a multibranch spin-chain model for strongly interacting quantum gases in one dimension: Dynamics and collective excitations

    NASA Astrophysics Data System (ADS)

    Yang, Li; Pu, Han

    2016-09-01

    We show that the wave function in one spatial sector x1interaction, either bosonic or fermionic, can be mapped to the direct product of the wave function of a spinless Fermi gas with short-range p -wave interaction and that of a spin system governed by spin-parity projection operators. Applying this mapping to strongly interacting spinor gases, we obtain a generalized spin-chain model that captures both the static and dynamics properties of the system. Using this spin-chain model, we investigate the breathing-mode frequency and the quench dynamics of strongly interacting, harmonically trapped spinor gases.

  15. Calculating the habitable zones of multiple star systems with a new interactive Web site

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

    Müller, Tobias W. A.; Haghighipour, Nader

    We have developed a comprehensive methodology and an interactive Web site for calculating the habitable zone (HZ) of multiple star systems. Using the concept of spectral weight factor, as introduced in our previous studies of the calculations of HZ in and around binary star systems, we calculate the contribution of each star (based on its spectral energy distribution) to the total flux received at the top of the atmosphere of an Earth-like planet, and use the models of the HZ of the Sun to determine the boundaries of the HZ in multiple star systems. Our interactive Web site for carryingmore » out these calculations is publicly available at http://astro.twam.info/hz. We discuss the details of our methodology and present its application to some of the multiple star systems detected by the Kepler space telescope. We also present the instructions for using our interactive Web site, and demonstrate its capabilities by calculating the HZ for two interesting analytical solutions of the three-body problem.« less

  16. National Park Service Vegetation Mapping Inventory Program: Appalachian National Scenic Trail vegetation mapping project

    USGS Publications Warehouse

    Hop, Kevin D.; Strassman, Andrew C.; Hall, Mark; Menard, Shannon; Largay, Ery; Sattler, Stephanie; Hoy, Erin E.; Ruhser, Janis; Hlavacek, Enrika; Dieck, Jennifer

    2017-01-01

    The National Park Service (NPS) Vegetation Mapping Inventory (VMI) Program classifies, describes, and maps existing vegetation of national park units for the NPS Natural Resource Inventory and Monitoring (I&M) Program. The NPS VMI Program is managed by the NPS I&M Division and provides baseline vegetation information to the NPS Natural Resource I&M Program. The U.S. Geological Survey Upper Midwest Environmental Sciences Center, NatureServe, NPS Northeast Temperate Network, and NPS Appalachian National Scenic Trail (APPA) have completed vegetation classification and mapping of APPA for the NPS VMI Program.Mappers, ecologists, and botanists collaborated to affirm vegetation types within the U.S. National Vegetation Classification (USNVC) of APPA and to determine how best to map the vegetation types by using aerial imagery. Analyses of data from 1,618 vegetation plots were used to describe USNVC associations of APPA. Data from 289 verification sites were collected to test the field key to vegetation associations and the application of vegetation associations to a sample set of map polygons. Data from 269 validation sites were collected to assess vegetation mapping prior to submitting the vegetation map for accuracy assessment (AA). Data from 3,265 AA sites were collected, of which 3,204 were used to test accuracy of the vegetation map layer. The collective of these datasets affirmed 280 USNVC associations for the APPA vegetation mapping project.To map the vegetation and land cover of APPA, 169 map classes were developed. The 169 map classes consist of 150 that represent natural (including ruderal) vegetation types in the USNVC, 11 that represent cultural (agricultural and developed) vegetation types in the USNVC, 5 that represent natural landscapes with catastrophic disturbance or some other modification to natural vegetation preventing accurate classification in the USNVC, and 3 that represent nonvegetated water (non-USNVC). Features were interpreted from viewing 4

  17. Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

    PubMed Central

    Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

    2010-01-01

    The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

  18. RadMap

    EPA Pesticide Factsheets

    RadMap is an interactive desktop tool featuring a nationwide geographic information systems (GIS) map of long-term radiation monitoring locations across the United States with access to key information about the monitor and the area surrounding it.

  19. Understanding and Designing for Interactional Privacy Needs within Social Networking Sites

    ERIC Educational Resources Information Center

    Wisniewski, Pamela J.

    2012-01-01

    "Interpersonal boundary regulation" is a way to optimize social interactions when sharing and connecting through Social Networking Sites (SNSs). The theoretical foundation of much of my research comes from Altman's work on privacy management in the physical world. Altman believed that "we should attempt to design responsive…

  20. A triangular prism solid and shell interactive mapping element for electromagnetic sheet metal forming process

    NASA Astrophysics Data System (ADS)

    Cui, Xiangyang; Li, She; Feng, Hui; Li, Guangyao

    2017-05-01

    In this paper, a novel triangular prism solid and shell interactive mapping element is proposed to solve the coupled magnetic-mechanical formulation in electromagnetic sheet metal forming process. A linear six-node "Triprism" element is firstly proposed for transient eddy current analysis in electromagnetic field. In present "Triprism" element, shape functions are given explicitly, and a cell-wise gradient smoothing operation is used to obtain the gradient matrices without evaluating derivatives of shape functions. In mechanical field analysis, a shear locking free triangular shell element is employed in internal force computation, and a data mapping method is developed to transfer the Lorentz force on solid into the external forces suffered by shell structure for dynamic elasto-plasticity deformation analysis. Based on the deformed triangular shell structure, a "Triprism" element generation rule is established for updated electromagnetic analysis, which means inter-transformation of meshes between the coupled fields can be performed automatically. In addition, the dynamic moving mesh is adopted for air mesh updating based on the deformation of sheet metal. A benchmark problem is carried out for confirming the accuracy of the proposed "Triprism" element in predicting flux density in electromagnetic field. Solutions of several EMF problems obtained by present work are compared with experiment results and those of traditional method, which are showing excellent performances of present interactive mapping element.

  1. Three-dimensional mapping of equiprobable hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site

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

    Shirley, C.; Pohlmann, K.; Andricevic, R.

    1996-09-01

    Geological and geophysical data are used with the sequential indicator simulation algorithm of Gomez-Hernandez and Srivastava to produce multiple, equiprobable, three-dimensional maps of informal hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site. The upper 50 percent of the Tertiary volcanic lithostratigraphic column comprises the study volume. Semivariograms are modeled from indicator-transformed geophysical tool signals. Each equiprobable study volume is subdivided into discrete classes using the ISIM3D implementation of the sequential indicator simulation algorithm. Hydraulic conductivity is assigned within each class using the sequential Gaussian simulation method of Deutsch and Journel. The resulting maps show the contiguitymore » of high and low hydraulic conductivity regions.« less

  2. In vitro studies of the physical interactions between neurofilaments, microtubules and mitochondria isolated from the central nervous system

    NASA Astrophysics Data System (ADS)

    Leterrier, Jean-François; Eyer, Joël; Weiss, Dieter G.; Lindén, Monica

    1991-05-01

    In order to explore the molecular nature and the regulation of dense cytomatrix which interconnects MT, NF and membranous organelles in neurons (9), the interactions between NF, MT and each of these cytoskelatal elements with brain mitochondria were investigated in vitro using biochemical and viophysical methods. From these studies, the following conclusions were drawn: 1- Pure NF form in vitro a highly viscous gel, dependent upon the phosphorylation state of the side arms of the NF-H and M subunits which might participate directly to the interactions since antibodies specific of these phosphorylated sites inhibited efficiently the NF gelation. This process is modulated by both ATP hydrolysis and soluble molecules from nervous tissue and it might reflect the highly controled organization of NF bundles in axons. 2- In contrast with NF, low viscosity levels were detected in MT suspensions. However, the occurrence of weak interactions between MT were deduced from studies with taxol, ATP, AMP-PNP and Mg ions, which affected the viscosity and the organization of MT in vitro, possibly through MAPs mediated interactions. 3- Mitochondria associated permanently in vitro to few MT through cross-bridges involving MAPs, which bind to specific sites on the outer membrane (17). In addition, brain mitochondria (and not liver mitochondria) interact with NF in an ATP-dependent manner, through thin cross-bridges possibly involving the NF-H and M subunits since these molecules, when purified, compete efficiently with MAPs for the binding to membrane sites. These results suggest the participation of structure MAPs and of NF-H and M subunits in the spatial organization MT and NF and in anchoring mitochondria to the cytomatrix.

  3. From Open Geographical Data to Tangible Maps: Improving the Accessibility of Maps for Visually Impaired People

    NASA Astrophysics Data System (ADS)

    Ducasse, J.; Macé, M.; Jouffrais, C.

    2015-08-01

    Visual maps must be transcribed into (interactive) raised-line maps to be accessible for visually impaired people. However, these tactile maps suffer from several shortcomings: they are long and expensive to produce, they cannot display a large amount of information, and they are not dynamically modifiable. A number of methods have been developed to automate the production of raised-line maps, but there is not yet any tactile map editor on the market. Tangible interactions proved to be an efficient way to help a visually impaired user manipulate spatial representations. Contrary to raised-line maps, tangible maps can be autonomously constructed and edited. In this paper, we present the scenarios and the main expected contributions of the AccessiMap project, which is based on the availability of many sources of open spatial data: 1/ facilitating the production of interactive tactile maps with the development of an open-source web-based editor; 2/ investigating the use of tangible interfaces for the autonomous construction and exploration of a map by a visually impaired user.

  4. Digital mapping of the Mars Pathfinder landing site: Design, acquisition, and derivation of cartographic products for science applications

    USGS Publications Warehouse

    Gaddis, L.R.; Kirk, R.L.; Johnson, J. R.; Soderblom, L.A.; Ward, A.W.; Barrett, J.; Becker, K.; Decker, T.; Blue, J.; Cook, D.; Eliason, E.; Hare, T.; Howington-Kraus, E.; Isbell, C.; Lee, E.M.; Redding, B.; Sucharski, R.; Sucharski, T.; Smith, P.H.; Britt, D.T.

    1999-01-01

    The Imager for Mars Pathfinder (IMP) acquired more than 16,000 images and provided panoramic views of the surface of Mars at the Mars Pathfinder landing site in Ares Vallis. This paper describes the stereoscopic, multispectral IMP imaging sequences and focuses on their use for digital mapping of the landing site and for deriving cartographic products to support science applications of these data. Two-dimensional cartographic processing of IMP data, as performed via techniques and specialized software developed for ISIS (the U.S.Geological Survey image processing software package), is emphasized. Cartographic processing of IMP data includes ingestion, radiometric correction, establishment of geometric control, coregistration of multiple bands, reprojection, and mosaicking. Photogrammetric processing, an integral part of this cartographic work which utilizes the three-dimensional character of the IMP data, supplements standard processing with geometric control and topographic information [Kirk et al., this issue]. Both cartographic and photogrammetric processing are required for producing seamless image mosaics and for coregistering the multispectral IMP data. Final, controlled IMP cartographic products include spectral cubes, panoramic (360?? azimuthal coverage) and planimetric (top view) maps, and topographic data, to be archived on four CD-ROM volumes. Uncontrolled and semicontrolled versions of these products were used to support geologic characterization of the landing site during the nominal and extended missions. Controlled products have allowed determination of the topography of the landing site and environs out to ???60 m, and these data have been used to unravel the history of large- and small-scale geologic processes which shaped the observed landing site. We conclude by summarizing several lessons learned from cartographic processing of IMP data. Copyright 1999 by the American Geophysical Union.

  5. FAST TRACK COMMUNICATION: A Temperley-Lieb quantum chain with two- and three-site interactions

    NASA Astrophysics Data System (ADS)

    Ikhlef, Y.; Jacobsen, J. L.; Saleur, H.

    2009-07-01

    We study the phase diagram of a quantum chain of spin-1/2 particles whose world lines form a dense loop gas with loop weight n. In addition to the usual two-site interaction corresponding to the XXZ spin chain, we introduce a three-site interaction. The resulting model contains a Majumdar-Ghosh-like gapped phase and a new integrable point, which we solve exactly. We also locate a critical line realizing dilute O(n) criticality, without introducing explicit dilution in the loops. Our results have implications for anisotropic spin chains, as well as anyonic quantum chains.

  6. Near-field spatial mapping of strongly interacting multiple plasmonic infrared antennas.

    PubMed

    Grefe, Sarah E; Leiva, Daan; Mastel, Stefan; Dhuey, Scott D; Cabrini, Stefano; Schuck, P James; Abate, Yohannes

    2013-11-21

    Near-field dipolar plasmon interactions of multiple infrared antenna structures in the strong coupling limit are studied using scattering-type scanning near-field optical microscope (s-SNOM) and theoretical finite-difference time-domain (FDTD) calculations. We monitor in real-space the evolution of plasmon dipolar mode of a stationary antenna structure as multiple resonantly matched dipolar plasmon particles are closely approaching it. Interparticle separation, length and polarization dependent studies show that the cross geometry structure favors strong interparticle charge-charge, dipole-dipole and charge-dipole Coulomb interactions in the nanometer scale gap region, which results in strong field enhancement in cross-bowties and further allows these structures to be used as polarization filters. The nanoscale local field amplitude and phase maps show that due to strong interparticle Coulomb coupling, cross-bowtie structures redistribute and highly enhance the out-of-plane (perpendicular to the plane of the sample) plasmon near-field component at the gap region relative to ordinary bowties.

  7. RICH MAPS

    EPA Science Inventory

    Michael Goodchild recently gave eight reasons why traditional maps are limited as communication devices, and how interactive internet mapping can overcome these limitations. In the past, many authorities in cartography, from Jenks to Bertin, have emphasized the importance of sim...

  8. The Interaction of Integrin αIIbβ3 with Fibrin Occurs through Multiple Binding Sites in the αIIb β-Propeller Domain*

    PubMed Central

    Podolnikova, Nataly P.; Yakovlev, Sergiy; Yakubenko, Valentin P.; Wang, Xu; Gorkun, Oleg V.; Ugarova, Tatiana P.

    2014-01-01

    The currently available antithrombotic agents target the interaction of platelet integrin αIIbβ3 (GPIIb-IIIa) with fibrinogen during platelet aggregation. Platelets also bind fibrin formed early during thrombus growth. It was proposed that inhibition of platelet-fibrin interactions may be a necessary and important property of αIIbβ3 antagonists; however, the mechanisms by which αIIbβ3 binds fibrin are uncertain. We have previously identified the γ370–381 sequence (P3) in the γC domain of fibrinogen as the fibrin-specific binding site for αIIbβ3 involved in platelet adhesion and platelet-mediated fibrin clot retraction. In the present study, we have demonstrated that P3 can bind to several discontinuous segments within the αIIb β-propeller domain of αIIbβ3 enriched with negatively charged and aromatic residues. By screening peptide libraries spanning the sequence of the αIIb β-propeller, several sequences were identified as candidate contact sites for P3. Synthetic peptides duplicating these segments inhibited platelet adhesion and clot retraction but not platelet aggregation, supporting the role of these regions in fibrin recognition. Mutant αIIbβ3 receptors in which residues identified as critical for P3 binding were substituted for homologous residues in the I-less integrin αMβ2 exhibited reduced cell adhesion and clot retraction. These residues are different from those that are involved in the coordination of the fibrinogen γ404–411 sequence and from auxiliary sites implicated in binding of soluble fibrinogen. These results map the binding of fibrin to multiple sites in the αIIb β-propeller and further indicate that recognition specificity of αIIbβ3 for fibrin differs from that for soluble fibrinogen. PMID:24338009

  9. Maps | Geospatial Data Science | NREL

    Science.gov Websites

    Maps Maps NREL develops an array of maps to support renewable energy development and generation resource in the United States by county Geothermal Maps of geothermal power plants, resources for enhanced geothermal systems, and hydrothermal sites in the United States Hydrogen Maps of hydrogen production

  10. Mapping the binding site of snurportin 1 on native U1 snRNP by cross-linking and mass spectrometry

    PubMed Central

    Kühn-Hölsken, Eva; Lenz, Christof; Dickmanns, Achim; Hsiao, He-Hsuan; Richter, Florian M.; Kastner, Berthold; Ficner, Ralf; Urlaub, Henning

    2010-01-01

    Mass spectrometry allows the elucidation of molecular details of the interaction domains of the individual components in macromolecular complexes subsequent to cross-linking of the individual components. Here, we applied chemical and UV cross-linking combined with tandem mass-spectrometric analysis to identify contact sites of the nuclear import adaptor snurportin 1 to the small ribonucleoprotein particle U1 snRNP in addition to the known interaction of m3G cap and snurportin 1. We were able to define previously unknown sites of protein–protein and protein–RNA interactions on the molecular level within U1 snRNP. We show that snurportin 1 interacts with its central m3G-cap-binding domain with Sm proteins and with its extreme C-terminus with stem-loop III of U1 snRNA. The crosslinking data support the idea of a larger interaction area between snurportin 1 and U snRNPs and the contact sites identified prove useful for modeling the spatial arrangement of snurportin 1 domains when bound to U1 snRNP. Moreover, this suggests a functional nuclear import complex that assembles around the m3G cap and the Sm proteins only when the Sm proteins are bound and arranged in the proper orientation to the cognate Sm site in U snRNA. PMID:20421206

  11. The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis.

    PubMed

    Wu, Fan-Lin; Liu, Yin; Jiang, He-Wei; Luan, Yi-Zhao; Zhang, Hai-Nan; He, Xiang; Xu, Zhao-Wei; Hou, Jing-Li; Ji, Li-Yun; Xie, Zhi; Czajkowsky, Daniel M; Yan, Wei; Deng, Jiao-Yu; Bi, Li-Jun; Zhang, Xian-En; Tao, Sheng-Ce

    2017-08-01

    Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized. In this study, using a Mtb proteome microarray, we have globally identified the binding proteins in Mtb for all of the STPKs, and constructed the first STPK protein interaction (KPI) map that includes 492 binding proteins and 1,027 interactions. Bioinformatics analysis showed that the interacting proteins reflect diverse functions, including roles in two-component system, transcription, protein degradation, and cell wall integrity. Functional investigations confirmed that PknG regulates cell wall integrity through key components of peptidoglycan (PG) biosynthesis, e.g. MurC. The global STPK-KPIs network constructed here is expected to serve as a rich resource for understanding the key signaling pathways in Mtb, thus facilitating drug development and effective control of Mtb. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Google Maps: You Are Here

    ERIC Educational Resources Information Center

    Jacobsen, Mikael

    2008-01-01

    Librarians use online mapping services such as Google Maps, MapQuest, Yahoo Maps, and others to check traffic conditions, find local businesses, and provide directions. However, few libraries are using one of Google Maps most outstanding applications, My Maps, for the creation of enhanced and interactive multimedia maps. My Maps is a simple and…

  13. MapApp: A Java(TM) Applet for Accessing Geographic Databases

    NASA Astrophysics Data System (ADS)

    Haxby, W.; Carbotte, S.; Ryan, W. B.; OHara, S.

    2001-12-01

    MapApp (http://coast.ldeo.columbia.edu/help/MapApp.html) is a prototype Java(TM) applet that is intended to give easy and versatile access to geographic data sets through a web browser. It was developed initially to interface with the RIDGE Multibeam Synthesis. Subsequently, interfaces with other geophysical databases were added. At present, multibeam bathymetry grids, underway geophysics along ship tracks, and the LDEO Borehole Research Group's ODP well logging database are accessible through MapApp. We plan to add an interface with the Ridge Petrology Database in the near future. The central component of MapApp is a world physiographic map. Users may navigate around the map (zoom/pan) without waiting for HTTP requests to a remote server to be processed. A focus request loads image tiles from the server to compose a new map at the current viewing resolution. Areas in which multibeam grids are available may be focused to a pixel resolution of about 200 m. These areas may be identified by toggling a mask. Databases may be accessed through menus, and selected data objects may be loaded into MapApp by selecting items from tables. Once loaded, a bathymetry grid may be contoured or used to create bathymetric profiles; ship tracks and ODP sites may be overlain on the map and their geophysical data plotted in X-Y graphs. The advantage of applets over traditional web pages is that they permit dynamic interaction with data sets, while limiting time consuming interaction with a remote server. Users may customize the graphics display by modifying the scale, or the symbol or line characteristics of rendered data, contour interval, etc. The ease with which users can select areas, view the physiography of areas, and preview data sets and evaluate them for quality and applicability, makes MapApp a valuable tool for education and research.

  14. IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

    PubMed

    Jefferis, R; Lund, J; Pound, J D

    1998-06-01

    The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

  15. Mapping texts through dimensionality reduction and visualization techniques for interactive exploration of document collections

    NASA Astrophysics Data System (ADS)

    de Andrade Lopes, Alneu; Minghim, Rosane; Melo, Vinícius; Paulovich, Fernando V.

    2006-01-01

    The current availability of information many times impair the tasks of searching, browsing and analyzing information pertinent to a topic of interest. This paper presents a methodology to create a meaningful graphical representation of documents corpora targeted at supporting exploration of correlated documents. The purpose of such an approach is to produce a map from a document body on a research topic or field based on the analysis of their contents, and similarities amongst articles. The document map is generated, after text pre-processing, by projecting the data in two dimensions using Latent Semantic Indexing. The projection is followed by hierarchical clustering to support sub-area identification. The map can be interactively explored, helping to narrow down the search for relevant articles. Tests were performed using a collection of documents pre-classified into three research subject classes: Case-Based Reasoning, Information Retrieval, and Inductive Logic Programming. The map produced was capable of separating the main areas and approaching documents by their similarity, revealing possible topics, and identifying boundaries between them. The tool can deal with the exploration of inter-topics and intra-topic relationship and is useful in many contexts that need deciding on relevant articles to read, such as scientific research, education, and training.

  16. Mapping contacts between gRNA and mRNA in trypanosome RNA editing.

    PubMed

    Leung, S S; Koslowsky, D J

    1999-02-01

    All guide RNAs (gRNAs) identified to date have defined 5' anchor sequences, guiding sequences and a non-encoded 3' uridylate tail. The 5' anchor is required for in vitro editing and is thought to be responsible for selection and binding to the pre-edited mRNA. Little is known, however, about how the gRNAs are used to direct RNA editing. Utilizing the photo-reactive crosslinking agent, azidophenacyl (APA), attached to the 5'- or 3'-terminus of the gRNA, we have begun to map the structural relationships between the different defined regions of the gRNA with the pre-edited mRNA. Analyses of crosslinked conjugates produced with a 5'-terminal APA group confirm that the anchor of the gRNA is correctly positioning the interacting molecules. 3' Crosslinks (X-linker placed at the 3'-end of a U10tail) have also been mapped for three different gRNA/mRNA pairs. In all cases, analyses indicate that the U-tail can interact with a range of nucleotides located upstream of the first edited site. It appears that the U-tail prefers purine-rich sites, close to the first few editing sites. These results suggest that the U-tail may act in concert with the anchor to melt out secondary structure in the mRNA in the immediate editing domain, possibly increasing the accessibility of the editing complex to the proper editing sites.

  17. Tetragonal Lysozyme Interactions Studied by Site Directed Mutagenesis

    NASA Technical Reports Server (NTRS)

    Crawford, Lisa; Karr, Laurel J.; Nadarajah, Arunan; Pusey, Marc

    1999-01-01

    A number of recent experimental and theoretical studies have indicated that tetragonal lysozyme crystal growth proceeds by the addition of aggregates, formed by reversible self association of the solute molecules in the bulk solution. Periodic bond chain and atomic force microscopy studies have indicated that the probable growth unit is at minimum a 43 tetramer, and most likely an octamer composed of two complete turns about the 43 axis. If these results are correct, then there are intermolecular interactions which are only formed in the solution and others only formed at the joining of the growth unit to the crystal surface. We have set out to study these interactions, and the correctness of this hypothesis, using site directed mutagenesis of specific amino acid residues involved in the different bonds. We had initially expressed wild type lysozyme in S. cervasiae with yields of approximately 5 mg/L, which were eventually raised to approximately 40 mg/L. We are now moving the expression to the Pichia system, with anticipated yields of 300 to (3)500 mg/L, comparable to what can be obtained from egg whites. An additional advantage of using recombinant protein is the greater genetic homogeneity of the material obtained and the absence of any other contaminating egg proteins. The first mutation experiments are TYR 23 (Registered) PHE or ALA and ASN 113 (Registered) ALA or ASP. Both TYR 23 and ASN 113 form part of the postulated dimerization intermolecular binding site which lead to the formation of the 43 helix. Tyrosine also participates in an intermolecular hydrogen bond with ARG 114. The results of these and subsequent experiments will be discussed.

  18. Tetragonal Lysozyme Interactions Studied by Site Directed Mutagenesis

    NASA Technical Reports Server (NTRS)

    Crawford, Lisa; Karr, Laurel; Pusey, Marc

    1998-01-01

    A number of recent experimental and theoretical studies have indicated that tetragonal lysozyme crystal growth proceeds by the addition of aggregates, formed by reversible self association of the solute molecules in the bulk'solution. Periodic bond chain and atomic force microscopy studies have indicated that the probable growth unit is at minimum a 43 tetramer, and most likely an octamer composed of two complete turns about the 4(sub 3) axis. If these results are correct, then there are intermolecular interactions which are only formed in the solution and others only formed at the joining of the growth unit to the crystal surface. We have set out to study these interactions, and the correctness of this hypothesis, using site directed mutagenesis of specific amino acid residues involved in the different bonds. We had initially expressed wild type lysozyme in S. cervasiae with yields of approximately 5 mg/L, which were eventually raised to approximately 40 mg/L. We are now moving the expression to the Pichia system, with anticipated yields of 300 to greater than 500 mg/L, comparable to what can be obtained from egg whites. An additional advantage of using recombinant protein is the greater genetic homogeneity of the material obtained and the absence of any other contaminating egg proteins. The first mutation experiments are TYR 23 yields PHE or ALA and ASN 113 yields ALA or ASP. Both TYR 23 and ASN 113 form part of the postulated dimerization intermolecular binding site which lead to the formation of the 4(sub 3) helix. Tyrosine also participates in an intermolecular hydrogen bond with ARG 114. The results of these and subsequent experiments will be discussed.

  19. Potential Role of Land Use and Land Cover Information in Powerplant Siting: Example of Three Mile Island

    NASA Technical Reports Server (NTRS)

    Wray, J. R.

    1982-01-01

    Selecting a site for a nuclear powerplant can be helped by digitizing land use and land cover data, population data, and other pertinent data sets, and then placing them in a geographic information system. Such a system begins with a set of standardized maps for location reference and then provides for retrieval and analysis of spatial data keyed to the maps. This makes possible thematic mapping by computer, or interactive visual display for decisionmaking. It also permits correlating land use area measurements with census and other data (such as fallout dosages), and the updating of all data sets. The system is thus a tool for dealing with resource management problems and for analyzing the interaction between people and their environment. An explanation of a computer-plotted map of land use and cover for Three Mile Island and vicinity is given.

  20. Lunar Mapping and Modeling On-the-Go: A mobile framework for viewing and interacting with large geospatial datasets

    NASA Astrophysics Data System (ADS)

    Chang, G.; Kim, R.; Bui, B.; Sadaqathullah, S.; Law, E.; Malhotra, S.

    2012-12-01

    The Lunar Mapping and Modeling Portal (LMMP, https://www.lmmp.nasa.gov/) is a collaboration between four NASA centers, JPL, Marshall, Goddard, and Ames, along with the USGS and US Army to provide a centralized geospatial repository for storing processed lunar data collected from the Apollo missions to the latest data acquired by the Lunar Reconnaissance Orbiter (LRO). We offer various scientific and visualization tools to analyze rock and crater densities, lighting maps, thermal measurements, mineral concentrations, slope hazards, and digital elevation maps with the intention of serving not only scientists and lunar mission planners, but also the general public. The project has pioneered in leveraging new technologies and embracing new computing paradigms to create a system that is sophisticated, secure, robust, and scalable all the while being easy to use, streamlined, and modular. We have led innovations through the use of a hybrid cloud infrastructure, authentication through various sources, and utilizing an in-house GIS framework, TWMS (TiledWMS) as well as the commercial ArcGIS product from ESRI. On the client end, we also provide a Flash GUI framework as well as REST web services to interact with the portal. We have also developed a visualization framework on mobile devices, specifically Apple's iOS, which allows anyone from anywhere to interact with LMMP. At the most basic level, the framework allows users to browse LMMP's entire catalog of over 600 data imagery products ranging from global basemaps to LRO's Narrow Angle Camera (NAC) images that provide details of up to .5 meters/pixel. Users are able to view map metadata and can zoom in and out as well as pan around the entire lunar surface with the appropriate basemap. They can arbitrarily stack the maps and images on top of each other to show a layered view of the surface with layer transparency adjusted to suit the user's desired look. Once the user has selected a combination of layers, he can also

  1. Mapping of mosquito breeding sites in malaria endemic areas in Pos Lenjang, Kuala Lipis, Pahang, Malaysia.

    PubMed

    Ahmad, Rohani; Ali, Wan N W M; Nor, Zurainee M; Ismail, Zamree; Hadi, Azahari A; Ibrahim, Mohd N; Lim, Lee H

    2011-12-13

    The application of the Geographic Information Systems (GIS) to the study of vector transmitted diseases considerably improves the management of the information obtained from the field survey and facilitates the study of the distribution patterns of the vector species. As part of a study to assess remote sensing data as a tool for vector mapping, geographical features like rivers, small streams, forest, roads and residential area were digitized from the satellite images and overlaid with entomological data. Map of larval breeding habitats distribution and map of malaria transmission risk area were developed using a combination of field data, satellite image analysis and GIS technique. All digital data in the GIS were displayed in the WGS 1984 coordinate system. Six occasions of larval surveillance were also conducted to determine the species of mosquitoes, their characteristics and the abundance of habitats. Larval survey studies showed that anopheline and culicine larvae were collected and mapped from 79 and 67 breeding sites respectively. Breeding habitats were located at 100-400 m from human settlement. Map of villages with 400 m buffer zone visualizes that more than 80% of Anopheles maculatus s.s. immature habitats were found within the buffer zone. This study amplifies the need for a broadening of the GIS approach which is emphasized with the aim of rejuvenating the dynamic aspect of entomological studies in Malaysia. In fact, the use of such basic GIS platforms promote a more rational basis for strategic planning and management in the control of endemic diseases at the national level.

  2. Mapping of mosquito breeding sites in malaria endemic areas in Pos Lenjang, Kuala Lipis, Pahang, Malaysia

    PubMed Central

    2011-01-01

    Background The application of the Geographic Information Systems (GIS) to the study of vector transmitted diseases considerably improves the management of the information obtained from the field survey and facilitates the study of the distribution patterns of the vector species. Methods As part of a study to assess remote sensing data as a tool for vector mapping, geographical features like rivers, small streams, forest, roads and residential area were digitized from the satellite images and overlaid with entomological data. Map of larval breeding habitats distribution and map of malaria transmission risk area were developed using a combination of field data, satellite image analysis and GIS technique. All digital data in the GIS were displayed in the WGS 1984 coordinate system. Six occasions of larval surveillance were also conducted to determine the species of mosquitoes, their characteristics and the abundance of habitats. Results Larval survey studies showed that anopheline and culicine larvae were collected and mapped from 79 and 67 breeding sites respectively. Breeding habitats were located at 100-400 m from human settlement. Map of villages with 400 m buffer zone visualizes that more than 80% of Anopheles maculatus s.s. immature habitats were found within the buffer zone. Conclusions This study amplifies the need for a broadening of the GIS approach which is emphasized with the aim of rejuvenating the dynamic aspect of entomological studies in Malaysia. In fact, the use of such basic GIS platforms promote a more rational basis for strategic planning and management in the control of endemic diseases at the national level. PMID:22166101

  3. Framing medical tourism: an examination of appeal, risk, convalescence, accreditation, and interactivity in medical tourism web sites.

    PubMed

    Mason, Alicia; Wright, Kevin B

    2011-02-01

    This exploratory study analyzed the content of medical tourism Web sites in an attempt to examine how they convey information about benefits and risks of medical procedures, how they frame credibility, and the degree to which these Web sites include interactive features for consumers. Drawing upon framing theory, the researchers content analyzed a sample of 66 medical tourism Web sites throughout the world. The results indicated that medical tourism Web sites largely promote the benefits of medical procedures while downplaying the risks, and relatively little information regarding the credibility of these services appears. In addition, the presentation of benefits/risks, credibility, and Web site interactivity were found to differ by region and type of facility. The authors discuss the implications of these findings concerning the framing of medical tourism Web site content, future directions for research, and limitations.

  4. Posterior insular cortex – a site of vestibular–somatosensory interaction?

    PubMed Central

    Baier, Bernhard; zu Eulenburg, Peter; Best, Christoph; Geber, Christian; Müller-Forell, Wibke; Birklein, Frank; Dieterich, Marianne

    2013-01-01

    Background In previous imaging studies the insular cortex (IC) has been identified as an essential part of the processing of a wide spectrum of perception and sensorimotor integration. Yet, there are no systematic lesion studies in a sufficient number of patients examining whether processing of vestibular and the interaction of somatosensory and vestibular signals take place in the IC. Methods We investigated acute stroke patients with lesions affecting the IC in order to fill this gap. In detail, we explored signs of a vestibular tone imbalance such as the deviation of the subjective visual vertical (SVV). We applied voxel-lesion behaviour mapping analysis in 27 patients with acute unilateral stroke. Results Our data demonstrate that patients with lesions of the posterior IC have an abnormal tilt of SVV. Furthermore, re-analysing data of 20 patients from a previous study, we found a positive correlation between thermal perception contralateral to the stroke and the severity of the SVV tilt. Conclusions We conclude that the IC is a sensory brain region where different modalities might interact. PMID:24392273

  5. Involvement of two classes of binding sites in the interactions of cyclophilin B with peripheral blood T-lymphocytes.

    PubMed

    Denys, A; Allain, F; Carpentier, M; Spik, G

    1998-12-15

    Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein, mainly associated with the secretory pathway, and is released in biological fluids. We recently reported that CyPB specifically binds to T-lymphocytes and promotes enhanced incorporation of CsA. The interactions with cellular binding sites involved, at least in part, the specific N-terminal extension of the protein. In this study, we intended to specify further the nature of the CyPB-binding sites on peripheral blood T-lymphocytes. We first provide evidence that the CyPB binding to heparin-Sepharose is prevented by soluble sulphated glycosaminoglycans (GAG), raising the interesting possibility that such interactions may occur on the T-cell surface. We then characterized CyPB binding to T-cell surface GAG and found that these interactions involved the N-terminal extension of CyPB, but not its conserved CsA-binding domain. In addition, we determined the presence of a second CyPB binding site, which we termed a type I site, in contrast with type II for GAG interactions. The two binding sites exhibit a similar affinity but the expression of the type I site was 3-fold lower. The conclusion that CyPB binding to the type I site is distinct from the interactions with GAG was based on the findings that it was (1) resistant to NaCl wash and GAG-degrading enzyme treatments, (2) reduced in the presence of CsA or cyclophilin C, and (3) unmodified in the presence of either the N-terminal peptide of CyPB or protamine. Finally, we showed that the type I binding sites were involved in an endocytosis process, supporting the hypothesis that they may correspond to a functional receptor for CyPB.

  6. BOREAS TE-23 Map Plot Data

    NASA Technical Reports Server (NTRS)

    Rich, Paul M.; Fournier, Robert; Hall, Forrest G. (Editor); Papagno, Andrea (Editor)

    2000-01-01

    The Boreal Ecosystem-Atmospheric Study (BOREAS) TE-23 (Terrestrial Ecology) team collected map plot data in support of its efforts to characterize and interpret information on canopy architecture and understory cover at the BOREAS tower flux sites and selected auxiliary sites from May to August 1994. Mapped plots (typical dimensions 50 m x 60 m) were set up and characterized at all BOREAS forested tower flux and selected auxiliary sites. Detailed measurement of the mapped plots included: (1) stand characteristics (location, density, basal area); (2) map locations diameter at breast height (DBH) of all trees; (3) detailed geometric measures of a subset of trees (height, crown dimensions); and (4) understory cover maps. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  7. The multiscale coarse-graining method. XI. Accurate interactions based on the centers of charge of coarse-grained sites

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

    Cao, Zhen; Voth, Gregory A., E-mail: gavoth@uchicago.edu

    It is essential to be able to systematically construct coarse-grained (CG) models that can efficiently and accurately reproduce key properties of higher-resolution models such as all-atom. To fulfill this goal, a mapping operator is needed to transform the higher-resolution configuration to a CG configuration. Certain mapping operators, however, may lose information related to the underlying electrostatic properties. In this paper, a new mapping operator based on the centers of charge of CG sites is proposed to address this issue. Four example systems are chosen to demonstrate this concept. Within the multiscale coarse-graining framework, CG models that use this mapping operatormore » are found to better reproduce the structural correlations of atomistic models. The present work also demonstrates the flexibility of the mapping operator and the robustness of the force matching method. For instance, important functional groups can be isolated and emphasized in the CG model.« less

  8. NASA Lunar and Planetary Mapping and Modeling

    NASA Astrophysics Data System (ADS)

    Day, B. H.; Law, E.

    2016-12-01

    NASA's Lunar and Planetary Mapping and Modeling Portals provide web-based suites of interactive visualization and analysis tools to enable mission planners, planetary scientists, students, and the general public to access mapped lunar data products from past and current missions for the Moon, Mars, and Vesta. New portals for additional planetary bodies are being planned. This presentation will recap significant enhancements to these toolsets during the past year and look forward to the results of the exciting work currently being undertaken. Additional data products and tools continue to be added to the Lunar Mapping and Modeling Portal (LMMP). These include both generalized products as well as polar data products specifically targeting potential sites for the Resource Prospector mission. Current development work on LMMP also includes facilitating mission planning and data management for lunar CubeSat missions, and working with the NASA Astromaterials Acquisition and Curation Office's Lunar Apollo Sample database in order to help better visualize the geographic contexts from which samples were retrieved. A new user interface provides, among other improvements, significantly enhanced 3D visualizations and navigation. Mars Trek, the project's Mars portal, has now been assigned by NASA's Planetary Science Division to support site selection and analysis for the Mars 2020 Rover mission as well as for the Mars Human Landing Exploration Zone Sites. This effort is concentrating on enhancing Mars Trek with data products and analysis tools specifically requested by the proposing teams for the various sites. Also being given very high priority by NASA Headquarters is Mars Trek's use as a means to directly involve the public in these upcoming missions, letting them explore the areas the agency is focusing upon, understand what makes these sites so fascinating, follow the selection process, and get caught up in the excitement of exploring Mars. The portals also serve as

  9. NASA Lunar and Planetary Mapping and Modeling

    NASA Astrophysics Data System (ADS)

    Day, Brian; Law, Emily

    2016-10-01

    NASA's Lunar and Planetary Mapping and Modeling Portals provide web-based suites of interactive visualization and analysis tools to enable mission planners, planetary scientists, students, and the general public to access mapped lunar data products from past and current missions for the Moon, Mars, and Vesta. New portals for additional planetary bodies are being planned. This presentation will recap some of the enhancements to these products during the past year and preview work currently being undertaken.New data products added to the Lunar Mapping and Modeling Portal (LMMP) include both generalized products as well as polar data products specifically targeting potential sites for the Resource Prospector mission. New tools being developed include traverse planning and surface potential analysis. Current development work on LMMP also includes facilitating mission planning and data management for lunar CubeSat missions. Looking ahead, LMMP is working with the NASA Astromaterials Office to integrate with their Lunar Apollo Sample database to help better visualize the geographic contexts of retrieved samples. All of this will be done within the framework of a new user interface which, among other improvements, will provide significantly enhanced 3D visualizations and navigation.Mars Trek, the project's Mars portal, has now been assigned by NASA's Planetary Science Division to support site selection and analysis for the Mars 2020 Rover mission as well as for the Mars Human Landing Exploration Zone Sites, and is being enhanced with data products and analysis tools specifically requested by the proposing teams for the various sites. NASA Headquarters is giving high priority to Mars Trek's use as a means to directly involve the public in these upcoming missions, letting them explore the areas the agency is focusing upon, understand what makes these sites so fascinating, follow the selection process, and get caught up in the excitement of exploring Mars.The portals also

  10. Normalization of a chromosomal contact map.

    PubMed

    Cournac, Axel; Marie-Nelly, Hervé; Marbouty, Martial; Koszul, Romain; Mozziconacci, Julien

    2012-08-30

    Chromatin organization has been increasingly studied in relation with its important influence on DNA-related metabolic processes such as replication or regulation of gene expression. Since its original design ten years ago, capture of chromosome conformation (3C) has become an essential tool to investigate the overall conformation of chromosomes. It relies on the capture of long-range trans and cis interactions of chromosomal segments whose relative proportions in the final bank reflect their frequencies of interactions, hence their spatial proximity in a population of cells. The recent coupling of 3C with deep sequencing approaches now allows the generation of high resolution genome-wide chromosomal contact maps. Different protocols have been used to generate such maps in various organisms. This includes mammals, drosophila and yeast. The massive amount of raw data generated by the genomic 3C has to be carefully processed to alleviate the various biases and byproducts generated by the experiments. Our study aims at proposing a simple normalization procedure to minimize the influence of these unwanted but inevitable events on the final results. Careful analysis of the raw data generated previously for budding yeast S. cerevisiae led to the identification of three main biases affecting the final datasets, including a previously unknown bias resulting from the circularization of DNA molecules. We then developed a simple normalization procedure to process the data and allow the generation of a normalized, highly contrasted, chromosomal contact map for S. cerevisiae. The same method was then extended to the first human genome contact map. Using the normalized data, we revisited the preferential interactions originally described between subsets of discrete chromosomal features. Notably, the detection of preferential interactions between tRNA in yeast and CTCF, PolII binding sites in human can vary with the normalization procedure used. We quantitatively reanalyzed the

  11. Construction of a high density SNP linkage map of kelp (Saccharina japonica) by sequencing Taq I site associated DNA and mapping of a sex determining locus.

    PubMed

    Zhang, Ning; Zhang, Linan; Tao, Ye; Guo, Li; Sun, Juan; Li, Xia; Zhao, Nan; Peng, Jie; Li, Xiaojie; Zeng, Liang; Chen, Jinsa; Yang, Guanpin

    2015-03-15

    Kelp (Saccharina japonica) has been intensively cultured in China for almost a century. Its genetic improvement is comparable with that of rice. However, the development of its molecular tools is extremely limited, thus its genes, genetics and genomics. Kelp performs an alternative life cycle during which sporophyte generation alternates with gametophyte generation. The gametophytes of kelp can be cloned and crossed. Due to these characteristics, kelp may serve as a reference for the biological and genetic studies of Volvox, mosses and ferns. We constructed a high density single nucleotide polymorphism (SNP) linkage map for kelp by restriction site associated DNA (RAD) sequencing. In total, 4,994 SNP-containing physical (tag-defined) RAD loci were mapped on 31 linkage groups. The map expanded a total genetic distance of 1,782.75 cM, covering 98.66% of the expected (1,806.94 cM). The length of RAD tags (85 bp) was extended to 400-500 bp with Miseq method, offering us an easiness of developing SNP chips and shifting SNP genotyping to a high throughput track. The number of linkage groups was in accordance with the documented with cytological methods. In addition, we identified a set of microsatellites (99 in total) from the extended RAD tags. A gametophyte sex determining locus was mapped on linkage group 2 in a window about 9.0 cM in width, which was 2.66 cM up to marker_40567 and 6.42 cM down to marker_23595. A high density SNP linkage map was constructed for kelp, an intensively cultured brown alga in China. The RAD tags were also extended so that a SNP chip could be developed. In addition, a set of microsatellites were identified among mapped loci, and a gametophyte sex determining locus was mapped. This map will facilitate the genetic studies of kelp including for example the evaluation of germplasm and the decipherment of the genetic bases of economic traits.

  12. Mapping the distribution of specific antibody interaction forces on individual red blood cells

    NASA Astrophysics Data System (ADS)

    Yeow, Natasha; Tabor, Rico F.; Garnier, Gil

    2017-02-01

    Current blood typing methods rely on the agglutination of red blood cells (RBCs) to macroscopically indicate a positive result. An indirect agglutination mechanism is required when blood typing with IgG forms of antibodies. To date, the interaction forces between anti-IgG and IgG antibodies have been poorly quantified, and blood group related antigens have never been quantified with the atomic force microscope (AFM). Instead, the total intensity resulting from fluorescent-tagged antibodies adsorbed on RBC has been measured to calculate an average antigen density on a series of RBCs. In this study we mapped specific antibody interaction forces on the RBC surface. AFM cantilever tips functionalized with anti-IgG were used to probe RBCs incubated with specific IgG antibodies. This work provides unique insight into antibody-antigen interactions in their native cell-bound location, and crucially, on a per-cell basis rather than an ensemble average set of properties. Force profiles obtained from the AFM directly provide not only the anti-IgG - IgG antibody interaction force, but also the spatial distribution and density of antigens over a single cell. This new understanding might be translated into the development of very selective and quantitative interactions that underpin the action of drugs in the treatment of frontier illnesses.

  13. Antarctic Sea Ice-Atmosphere Interactions: A Self-organizing Map-based Perspective

    NASA Astrophysics Data System (ADS)

    Reusch, D. B.

    2005-12-01

    Interactions between the ocean, sea ice and the atmosphere are a significant component of the dynamic nature of the Earth's climate system. Self-organizing maps (SOMs), an analysis tool from the field of artificial neural networks, have been used to study variability in Antarctic sea ice extent and the West Antarctic atmospheric circulation, plus the relationship and interactions between these two systems. Self-organizing maps enable unsupervised classification of large, multivariate/multidimensional data sets, e.g., time series of the atmospheric circulation or sea-ice extent, into a fixed number of distinct generalized states or modes, organized spatially as a two-dimensional grid, that are representative of the input data. When applied to atmospheric data, the analysis yields a nonlinear classification of the continuum of atmospheric conditions. In contrast to principal component analysis, SOMs do not force orthogonality or require subjective rotations to produce interpretable patterns. Twenty four years (1973-96) of monthly sea ice extent data (10 deg longitude bands; Simmonds and Jacka, 1995) were analyzed with a 30-node SOM. The resulting set of generalized patterns concisely captures the spatial and temporal variability in this data. An example of the former is variability in the longitudinal region of greatest extent. The SOM patterns readily show that there are multiple spatial patterns corresponding to "greatest extent conditions". Temporal variability is examined by creating frequency maps (i.e., which patterns occur most often) by month. With the annual cycle still in the data, the monthly frequency maps show a cycle moving from least extent, through expansion to greatest extent and back through retreat. When plotted in "SOM space", month-to-month transitions occur at different rates of change, suggesting that there is variability in the rate of change in extent at different times of the year, e.g., retreat in January is faster than November. Twenty

  14. Unmasking tandem site interaction in human acetylcholinesterase. Substrate activation with a cationic acetanilide substrate.

    PubMed

    Johnson, Joseph L; Cusack, Bernadette; Davies, Matthew P; Fauq, Abdul; Rosenberry, Terrone L

    2003-05-13

    Acetylcholinesterase (AChE) contains a narrow and deep active site gorge with two sites of ligand binding, an acylation site (or A-site) at the base of the gorge, and a peripheral site (or P-site) near the gorge entrance. The P-site contributes to catalytic efficiency by transiently binding substrates on their way to the acylation site, where a short-lived acyl enzyme intermediate is produced. A conformational interaction between the A- and P-sites has recently been found to modulate ligand affinities. We now demonstrate that this interaction is of functional importance by showing that the acetylation rate constant of a substrate bound to the A-site is increased by a factor a when a second molecule of substrate binds to the P-site. This demonstration became feasible through the introduction of a new acetanilide substrate analogue of acetylcholine, 3-(acetamido)-N,N,N-trimethylanilinium (ATMA), for which a = 4. This substrate has a low acetylation rate constant and equilibrates with the catalytic site, allowing a tractable algebraic solution to the rate equation for substrate hydrolysis. ATMA affinities for the A- and P-sites deduced from the kinetic analysis were confirmed by fluorescence titration with thioflavin T as a reporter ligand. Values of a >1 give rise to a hydrolysis profile called substrate activation, and the AChE site-specific mutant W86F, and to a lesser extent wild-type human AChE itself, showed substrate activation with acetylthiocholine as the substrate. Substrate activation was incorporated into a previous catalytic scheme for AChE in which a bound P-site ligand can also block product dissociation from the A-site, and two additional features of the AChE catalytic pathway were revealed. First, the ability of a bound P-site ligand to increase the substrate acetylation rate constant varied with the structure of the ligand: thioflavin T accelerated ATMA acetylation by a factor a(2) of 1.3, while propidium failed to accelerate. Second, catalytic rate

  15. AAPG-CSD geologic provinces code map

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

    Meyer, R.F.; Wallace, L.G.; Wagner, F.J. Jr.

    1991-10-01

    This article provides the history of a revised geologic map which was drawn based on both surface geology and petroleum occurrence. The map includes offshore maps for California and the Gulf Coast of Texas and Louisiana. For onshore sites it provides geologic province boundaries which were drawn along county boundaries to approximate their position relative to oil and gas production. The offshore sites are drawn based on the universal transverse Mercator system.

  16. TSEMA: interactive prediction of protein pairings between interacting families

    PubMed Central

    Izarzugaza, José M. G.; Juan, David; Pons, Carles; Ranea, Juan A. G.; Valencia, Alfonso; Pazos, Florencio

    2006-01-01

    An entire family of methodologies for predicting protein interactions is based on the observed fact that families of interacting proteins tend to have similar phylogenetic trees due to co-evolution. One application of this concept is the prediction of the mapping between the members of two interacting protein families (which protein within one family interacts with which protein within the other). The idea is that the real mapping would be the one maximizing the similarity between the trees. Since the exhaustive exploration of all possible mappings is not feasible for large families, current approaches use heuristic techniques which do not ensure the best solution to be found. This is why it is important to check the results proposed by heuristic techniques and to manually explore other solutions. Here we present TSEMA, the server for efficient mapping assessment. This system calculates an initial mapping between two families of proteins based on a Monte Carlo approach and allows the user to interactively modify it based on performance figures and/or specific biological knowledge. All the explored mappings are graphically shown over a representation of the phylogenetic trees. The system is freely available at . Standalone versions of the software behind the interface are available upon request from the authors. PMID:16845017

  17. Ablation of post-surgical intra-atrial reentrant tachycardia. Predilection target sites and mapping approach.

    PubMed

    Anné, W; van Rensburg, H; Adams, J; Ector, H; Van de Werf, F; Heidbüchel, H

    2002-10-01

    Atrial arrhythmias are a frequent complication of atrial surgery. The location of these tachycardias is very diverse due to the individual difference in the original anatomy, surgical corrections, and effects of atrial fibrosis. Nevertheless some recurrent patterns are emerging. Forty-five patients underwent 51 ablation procedures between September 1995 and March 2001 using conventional mapping and temperature-controlled ablation. A duadecapolar catheter was swept from anterior to posterior in the right (and/or left) atrium, allowing for rapid mapping followed by entrainment confirmation. Twenty-eight patients had corrected congenital heart disease, 17 surgery for acquired heart disease. One hundred and sixteen arrhythmias were found, 86 circuits were targeted, 81 with success (94%). Despite the heterogeneous anatomy, the same targets were often encountered: the posterior isthmus between the inferior vena cava and the tricuspid ring (62%), the gap between the inferior vena cava and the atriotomy scar (49%), and the region around the atriopulmonary connection in Fontans (two out of four patients). After a mean follow-up of 24 months, 13 patients had a recurrent arrhythmia (29%) after their last procedure. There was a significant association between the number of circuits found during the initial procedure and the likelihood of recurrent arrhythmias. Knowledge of anatomical predilection sites and mapping the right (and/or left) atrium with a 'sweeping Halo technique' allow for effective ablation of most post-surgical atrial tachycardias. Severely damaged atria with multiple arrhythmias may require 'preventive' ablation of all recognizable channels.

  18. Mapping of interaction domains between human repair proteins ERCC1 and XPF.

    PubMed

    de Laat, W L; Sijbers, A M; Odijk, H; Jaspers, N G; Hoeijmakers, J H

    1998-09-15

    ERCC1-XPF is a heterodimeric protein complexinvolved in nucleotide excision repair and recombinational processes. Like its homologous complex in Saccharomyces cerevisiae , Rad10-Rad1, it acts as a structure-specific DNA endonuclease, cleaving at duplex-single-stranded DNA junctions. In repair, ERCC1-XPF and Rad10-Rad1 make an incision on the the 5'-side of the lesion. No humans with a defect in the ERCC1 subunit of this protein complex have been identified and ERCC1-deficient mice suffer from severe developmental problems and signs of premature aging on top of a repair-deficient phenotype. Xeroderma pigmentosum group F patients carry mutations in the XPF subunit and generally show the clinical symptoms of mild DNA repair deficiency. All XP-F patients examined demonstrate reduced levels of XPF and ERCC1 protein, suggesting that proper complex formation is required for stability of the two proteins. To better understand the molecular and clinical consequences of mutations in the ERCC1-XPF complex, we decided to map the interaction domains between the two subunits. The XPF-binding domain comprises C-terminal residues 224-297 of ERCC1. Intriguingly, this domain resides outside the region of homology with its yeast Rad10 counterpart. The ERCC1-binding domain in XPF maps to C-terminal residues 814-905. ERCC1-XPF complex formation is established by a direct interaction between these two binding domains. A mutation from an XP-F patient that alters the ERCC1-binding domain in XPF indeed affects complex formation with ERCC1.

  19. Mapping of interaction domains between human repair proteins ERCC1 and XPF.

    PubMed Central

    de Laat, W L; Sijbers, A M; Odijk, H; Jaspers, N G; Hoeijmakers, J H

    1998-01-01

    ERCC1-XPF is a heterodimeric protein complexinvolved in nucleotide excision repair and recombinational processes. Like its homologous complex in Saccharomyces cerevisiae , Rad10-Rad1, it acts as a structure-specific DNA endonuclease, cleaving at duplex-single-stranded DNA junctions. In repair, ERCC1-XPF and Rad10-Rad1 make an incision on the the 5'-side of the lesion. No humans with a defect in the ERCC1 subunit of this protein complex have been identified and ERCC1-deficient mice suffer from severe developmental problems and signs of premature aging on top of a repair-deficient phenotype. Xeroderma pigmentosum group F patients carry mutations in the XPF subunit and generally show the clinical symptoms of mild DNA repair deficiency. All XP-F patients examined demonstrate reduced levels of XPF and ERCC1 protein, suggesting that proper complex formation is required for stability of the two proteins. To better understand the molecular and clinical consequences of mutations in the ERCC1-XPF complex, we decided to map the interaction domains between the two subunits. The XPF-binding domain comprises C-terminal residues 224-297 of ERCC1. Intriguingly, this domain resides outside the region of homology with its yeast Rad10 counterpart. The ERCC1-binding domain in XPF maps to C-terminal residues 814-905. ERCC1-XPF complex formation is established by a direct interaction between these two binding domains. A mutation from an XP-F patient that alters the ERCC1-binding domain in XPF indeed affects complex formation with ERCC1. PMID:9722633

  20. PDB-Explorer: a web-based interactive map of the protein data bank in shape space.

    PubMed

    Jin, Xian; Awale, Mahendra; Zasso, Michaël; Kostro, Daniel; Patiny, Luc; Reymond, Jean-Louis

    2015-10-23

    The RCSB Protein Data Bank (PDB) provides public access to experimentally determined 3D-structures of biological macromolecules (proteins, peptides and nucleic acids). While various tools are available to explore the PDB, options to access the global structural diversity of the entire PDB and to perceive relationships between PDB structures remain very limited. A 136-dimensional atom pair 3D-fingerprint for proteins (3DP) counting categorized atom pairs at increasing through-space distances was designed to represent the molecular shape of PDB-entries. Nearest neighbor searches examples were reported exemplifying the ability of 3DP-similarity to identify closely related biomolecules from small peptides to enzyme and large multiprotein complexes such as virus particles. The principle component analysis was used to obtain the visualization of PDB in 3DP-space. The 3DP property space groups proteins and protein assemblies according to their 3D-shape similarity, yet shows exquisite ability to distinguish between closely related structures. An interactive website called PDB-Explorer is presented featuring a color-coded interactive map of PDB in 3DP-space. Each pixel of the map contains one or more PDB-entries which are directly visualized as ribbon diagrams when the pixel is selected. The PDB-Explorer website allows performing 3DP-nearest neighbor searches of any PDB-entry or of any structure uploaded as protein-type PDB file. All functionalities on the website are implemented in JavaScript in a platform-independent manner and draw data from a server that is updated daily with the latest PDB additions, ensuring complete and up-to-date coverage. The essentially instantaneous 3DP-similarity search with the PDB-Explorer provides results comparable to those of much slower 3D-alignment algorithms, and automatically clusters proteins from the same superfamilies in tight groups. A chemical space classification of PDB based on molecular shape was obtained using a new atom-pair 3

  1. Mapping the Sea Floor of the Historic Area Remediation Site (HARS) Offshore of New York City

    USGS Publications Warehouse

    Butman, Bradford

    2002-01-01

    The area offshore of New York City has been used for the disposal of dredged material for over a century. The area has also been used for the disposal of other materials such as acid waste, industrial waste, municipal sewage sludge, cellar dirt, and wood. Between 1976 and 1995, the New York Bight Dredged Material Disposal Site, also known as the Mud Dump Site (MDS), received on average about 6 million cubic yards of dredged material annually. In September 1997 the MDS was closed as a disposal site, and it and the surrounding area were designated as the Historic Area Remediation Site (HARS). The sea floor of the HARS, approximately 9 square nautical miles in area, currently is being remediated by placing a minimum 1-m-thick cap of clean dredged material on top of the surficial sediments that are contaminated from previous disposal of dredged and other materials. The U.S. Geological Survey (USGS) is working cooperatively with the U.S. Army Corps of Engineers (USACE) to map the sea floor geology of the HARS and changes in the characteristics of the surficial sediments over time.

  2. Using Web Maps to Analyze the Construction of Global Scale Cognitive Maps

    ERIC Educational Resources Information Center

    Pingel, Thomas J.

    2018-01-01

    Game-based Web sites and applications are changing the ways in which students learn the world map. In this study, a Web map-based digital learning tool was used as a study aid for a university-level geography course in order to examine the way in which global scale cognitive maps are constructed. A network analysis revealed that clicks were…

  3. Concept mapping One-Carbon Metabolism to model future ontologies for nutrient-gene-phenotype interactions.

    PubMed

    Joslin, A C; Green, R; German, J B; Lange, M C

    2014-09-01

    Advances in the development of bioinformatic tools continue to improve investigators' ability to interrogate, organize, and derive knowledge from large amounts of heterogeneous information. These tools often require advanced technical skills not possessed by life scientists. User-friendly, low-barrier-to-entry methods of visualizing nutrigenomics information are yet to be developed. We utilized concept mapping software from the Institute for Human and Machine Cognition to create a conceptual model of diet and health-related data that provides a foundation for future nutrigenomics ontologies describing published nutrient-gene/polymorphism-phenotype data. In this model, maps containing phenotype, nutrient, gene product, and genetic polymorphism interactions are visualized as triples of two concepts linked together by a linking phrase. These triples, or "knowledge propositions," contextualize aggregated data and information into easy-to-read knowledge maps. Maps of these triples enable visualization of genes spanning the One-Carbon Metabolism (OCM) pathway, their sequence variants, and multiple literature-mined associations including concepts relevant to nutrition, phenotypes, and health. The concept map development process documents the incongruity of information derived from pathway databases versus literature resources. This conceptual model highlights the importance of incorporating information about genes in upstream pathways that provide substrates, as well as downstream pathways that utilize products of the pathway under investigation, in this case OCM. Other genes and their polymorphisms, such as TCN2 and FUT2, although not directly involved in OCM, potentially alter OCM pathway functionality. These upstream gene products regulate substrates such as B12. Constellations of polymorphisms affecting the functionality of genes along OCM, together with substrate and cofactor availability, may impact resultant phenotypes. These conceptual maps provide a foundational

  4. Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution

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

    Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.

    1994-09-01

    Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less

  5. Mapping site index and volume increment from forest inventory, Landsat, and ecological variables in Tahoe National Forest, California, USA

    USGS Publications Warehouse

    Huang, Shengli; Ramirez, Carlos; Conway, Scott; Kennedy, Kama; Kohler, Tanya; Liu, Jinxun

    2016-01-01

    High-resolution site index (SI) and mean annual increment (MAI) maps are desired for local forest management. We integrated field inventory, Landsat, and ecological variables to produce 30 m SI and MAI maps for the Tahoe National Forest (TNF) where different tree species coexist. We converted species-specific SI using adjustment factors. Then, the SI map was produced by (i) intensifying plots to expand the training sets to more climatic, topographic, soil, and forest reflective classes, (ii) using results from a stepwise regression to enable a weighted imputation that minimized the effects of outlier plots within classes, and (iii) local interpolation and strata median filling to assign values to pixels without direct imputations. The SI (reference age is 50 years) map had an R2 of 0.7637, a root-mean-square error (RMSE) of 3.60, and a mean absolute error (MAE) of 3.07 m. The MAI map was similarly produced with an R2 of 0.6882, an RMSE of 1.73, and a MAE of 1.20 m3·ha−1·year−1. Spatial patterns and trends of SI and MAI were analyzed to be related to elevation, aspect, slope, soil productivity, and forest type. The 30 m SI and MAI maps can be used to support decisions on fire, plantation, biodiversity, and carbon.

  6. Mapping burn severity, pine beetle infestation, and their interaction at the High Park Fire

    NASA Astrophysics Data System (ADS)

    Stone, Brandon

    North America's western forests are experiencing wildfire and mountain pine beetle (MPB) disturbances that are unprecedented in the historic record, but it remains unclear whether and how MPB infestation influences post-infestation fire behavior. The 2012 High Park Fire burned in an area that's estimated to have begun a MPB outbreak cycle within five years before the wildfire, resulting in a landscape in which disturbance interactions can be studied. A first step in studying these interactions is mapping regions of beetle infestation and post-fire disturbance. We implemented an approach for mapping beetle infestation and burn severity using as source data three 5 m resolution RapidEye satellite images (two pre-fire, one post-fire). A two-tiered methodology was developed to overcome the spatial limitations of many classification approaches through explicit analyses at both pixel and plot level. Major land cover classes were photo-interpreted at the plot-level and their spectral signature used to classify 5 m images. A new image was generated at 25 m resolution by tabulating the fraction of coincident 5 m pixels in each cover class. The original photo interpretation was then used to train a second classification using as its source image the new 25 m image. Maps were validated using k-fold analysis of the original photo interpretation, field data collected immediately post-fire, and publicly available classifications. To investigate the influence of pre-fire beetle infestation on burn severity within the High Park Fire, we fit a log-linear model of conditional independence to our thematic maps after controlling for forest cover class and slope aspect. Our analysis revealed a high co-occurrence of severe burning and beetle infestation within high elevation lodgepole pine stands, but did not find statistically significant evidence that infected stands were more likely to burn severely than similar uninfected stands. Through an inspection of the year-to-year changes in

  7. Multigraph: Interactive Data Graphs on the Web

    NASA Astrophysics Data System (ADS)

    Phillips, M. B.

    2010-12-01

    Many aspects of geophysical science involve time dependent data that is often presented in the form of a graph. Considering that the web has become a primary means of communication, there are surprisingly few good tools and techniques available for presenting time-series data on the web. The most common solution is to use a desktop tool such as Excel or Matlab to create a graph which is saved as an image and then included in a web page like any other image. This technique is straightforward, but it limits the user to one particular view of the data, and disconnects the graph from the data in a way that makes updating a graph with new data an often cumbersome manual process. This situation is somewhat analogous to the state of mapping before the advent of GIS. Maps existed only in printed form, and creating a map was a laborious process. In the last several years, however, the world of mapping has experienced a revolution in the form of web-based and other interactive computer technologies, so that it is now commonplace for anyone to easily browse through gigabytes of geographic data. Multigraph seeks to bring a similar ease of access to time series data. Multigraph is a program for displaying interactive time-series data graphs in web pages that includes a simple way of configuring the appearance of the graph and the data to be included. It allows multiple data sources to be combined into a single graph, and allows the user to explore the data interactively. Multigraph lets users explore and visualize "data space" in the same way that interactive mapping applications such as Google Maps facilitate exploring and visualizing geography. Viewing a Multigraph graph is extremely simple and intuitive, and requires no instructions. Creating a new graph for inclusion in a web page involves writing a simple XML configuration file and requires no programming. Multigraph can read data in a variety of formats, and can display data from a web service, allowing users to "surf

  8. An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase

    DOE PAGES

    Murphy, Jesse R.; Donini, Stefano; Kappock, T. Joseph

    2015-10-01

    Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open'more » structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. In conclusion, as a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.« less

  9. An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase.

    PubMed

    Murphy, Jesse R; Donini, Stefano; Kappock, T Joseph

    2015-10-01

    Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open' structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. As a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.

  10. Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy.

    PubMed

    Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling

    2015-12-01

    Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.

  11. Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions.

    PubMed

    Turner, Leslie M; Harr, Bettina

    2014-12-09

    Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.

  12. Site maps and facilities listings

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

    Not Available

    1993-11-01

    In September 1989, a Memorandum of Agreement among DOE offices regarding the environmental management of DOE facilities was signed by appropriate Assistant Secretaries and Directors. This Memorandum of Agreement established the criteria for EM line responsibility. It stated that EM would be responsible for all DOE facilities, operations, or sites (1) that have been assigned to DOE for environmental restoration and serve or will serve no future production need; (2) that are used for the storage, treatment, or disposal of hazardous, radioactive, and mixed hazardous waste materials that have been properly characterized, packaged, and labelled, but are not used formore » production; (3) that have been formally transferred to EM by another DOE office for the purpose of environmental restoration and the eventual return to service as a DOE production facility; or (4) that are used exclusively for long-term storage of DOE waste material and are not actively used for production, with the exception of facilities, operations, or sites under the direction of the DOE Office of Civilian Radioactive Waste Management. As part of the implementation of the Memorandum of Agreement, Field Offices within DOE submitted their listings of facilities, systems, operation, and sites for which EM would have line responsibility. It is intended that EM facility listings will be revised on a yearly basis so that managers at all levels will have a valid reference for the planning, programming, budgeting and execution of EM activities.« less

  13. New insights into the interaction between pyrrolyl diketoacids and HIV-1 integrase active site and comparison with RNase H.

    PubMed

    Corona, Angela; di Leva, Francesco Saverio; Rigogliuso, Giuseppe; Pescatori, Luca; Madia, Valentina Noemi; Subra, Frederic; Delelis, Olivier; Esposito, Francesca; Cadeddu, Marta; Costi, Roberta; Cosconati, Sandro; Novellino, Ettore; di Santo, Roberto; Tramontano, Enzo

    2016-10-01

    HIV-1 integrase (IN) inhibitors are one of the most recent innovations in the treatment of HIV infection. The selection of drug resistance viral strains is however a still open issue requiring constant efforts to identify new anti-HIV-1 drugs. Pyrrolyl diketo acid (DKA) derivatives inhibit HIV-1 replication by interacting with the Mg 2+ cofactors within the HIV-1 IN active site or within the HIV-1 reverse-transcriptase associated ribonuclease H (RNase H) active site. While the interaction mode of pyrrolyl DKAs with the RNase H active site has been recently reported and substantiated by mutagenesis experiments, their interaction within the IN active site still lacks a detailed understanding. In this study, we investigated the binding mode of four pyrrolyl DKAs to the HIV-1 IN active site by molecular modeling coupled with site-directed mutagenesis studies showing that the DKA pyrrolyl scaffold primarily interacts with the IN amino residues P145, Q146 and Q148. Importantly, the tested DKAs demonstrated good effectiveness against HIV-1 Raltegravir resistant Y143A and N155H INs, thus showing an interaction pattern with relevant differences if compared with the first generation IN inhibitors. These data provide precious insights for the design of new HIV inhibitors active on clinically selected Raltegravir resistant variants. Furthermore, this study provides new structural information to modulate IN and RNase H inhibitory activities for development of dual-acting anti-HIV agents. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Quantification and site-specification of the support practice factor when mapping soil erosion risk associated with olive plantations in the Mediterranean island of Crete.

    PubMed

    Karydas, Christos G; Sekuloska, Tijana; Silleos, Georgios N

    2009-02-01

    Due to inappropriate agricultural management practices, soil erosion is becoming one of the most dangerous forms of soil degradation in many olive farming areas in the Mediterranean region, leading to significant decrease of soil fertility and yield. In order to prevent further soil degradation, proper measures are necessary to be locally implemented. In this perspective, an increase in the spatial accuracy of remote sensing datasets and advanced image analysis are significant tools necessary and efficient for mapping soil erosion risk on a fine scale. In this study, the Revised Universal Soil Loss Equation (RUSLE) was implemented in the spatial domain using GIS, while a very high resolution satellite image, namely a QuickBird image, was used for deriving cover management (C) and support practice (P) factors, in order to map the risk of soil erosion in Kolymvari, a typical olive farming area in the island of Crete, Greece. The results comprised a risk map of soil erosion when P factor was taken uniform (conventional approach) and a risk map when P factor was quantified site-specifically using object-oriented image analysis. The results showed that the QuickBird image was necessary in order to achieve site-specificity of the P factor and therefore to support fine scale mapping of soil erosion risk in an olive cultivation area, such as the one of Kolymvari in Crete. Increasing the accuracy of the QB image classification will further improve the resulted soil erosion mapping.

  15. Influence of long-range Coulomb interaction in velocity map imaging.

    PubMed

    Barillot, T; Brédy, R; Celep, G; Cohen, S; Compagnon, I; Concina, B; Constant, E; Danakas, S; Kalaitzis, P; Karras, G; Lépine, F; Loriot, V; Marciniak, A; Predelus-Renois, G; Schindler, B; Bordas, C

    2017-07-07

    The standard velocity-map imaging (VMI) analysis relies on the simple approximation that the residual Coulomb field experienced by the photoelectron ejected from a neutral or ion system may be neglected. Under this almost universal approximation, the photoelectrons follow ballistic (parabolic) trajectories in the externally applied electric field, and the recorded image may be considered as a 2D projection of the initial photoelectron velocity distribution. There are, however, several circumstances where this approximation is not justified and the influence of long-range forces must absolutely be taken into account for the interpretation and analysis of the recorded images. The aim of this paper is to illustrate this influence by discussing two different situations involving isolated atoms or molecules where the analysis of experimental images cannot be performed without considering long-range Coulomb interactions. The first situation occurs when slow (meV) photoelectrons are photoionized from a neutral system and strongly interact with the attractive Coulomb potential of the residual ion. The result of this interaction is the formation of a more complex structure in the image, as well as the appearance of an intense glory at the center of the image. The second situation, observed also at low energy, occurs in the photodetachment from a multiply charged anion and it is characterized by the presence of a long-range repulsive potential. Then, while the standard VMI approximation is still valid, the very specific features exhibited by the recorded images can be explained only by taking into consideration tunnel detachment through the repulsive Coulomb barrier.

  16. Geological mapping in northwestern Saudi Arabia using LANDSAT multispectral techniques

    NASA Technical Reports Server (NTRS)

    Blodget, H. W.; Brown, G. F.; Moik, J. G.

    1975-01-01

    Various computer enhancement and data extraction systems using LANDSAT data were assessed and used to complement a continuing geologic mapping program. Interactive digital classification techniques using both the parallel-piped and maximum-likelihood statistical approaches achieve very limited success in areas of highly dissected terrain. Computer enhanced imagery developed by color compositing stretched MSS ratio data was constructed for a test site in northwestern Saudi Arabia. Initial results indicate that several igneous and sedimentary rock types can be discriminated.

  17. Mapping specificity landscapes of RNA-protein interactions by high throughput sequencing.

    PubMed

    Jankowsky, Eckhard; Harris, Michael E

    2017-04-15

    To function in a biological setting, RNA binding proteins (RBPs) have to discriminate between alternative binding sites in RNAs. This discrimination can occur in the ground state of an RNA-protein binding reaction, in its transition state, or in both. The extent by which RBPs discriminate at these reaction states defines RBP specificity landscapes. Here, we describe the HiTS-Kin and HiTS-EQ techniques, which combine kinetic and equilibrium binding experiments with high throughput sequencing to quantitatively assess substrate discrimination for large numbers of substrate variants at ground and transition states of RNA-protein binding reactions. We discuss experimental design, practical considerations and data analysis and outline how a combination of HiTS-Kin and HiTS-EQ allows the mapping of RBP specificity landscapes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Dynamic map labeling.

    PubMed

    Been, Ken; Daiches, Eli; Yap, Chee

    2006-01-01

    We address the problem of filtering, selecting and placing labels on a dynamic map, which is characterized by continuous zooming and panning capabilities. This consists of two interrelated issues. The first is to avoid label popping and other artifacts that cause confusion and interrupt navigation, and the second is to label at interactive speed. In most formulations the static map labeling problem is NP-hard, and a fast approximation might have O(nlogn) complexity. Even this is too slow during interaction, when the number of labels shown can be several orders of magnitude less than the number in the map. In this paper we introduce a set of desiderata for "consistent" dynamic map labeling, which has qualities desirable for navigation. We develop a new framework for dynamic labeling that achieves the desiderata and allows for fast interactive display by moving all of the selection and placement decisions into the preprocessing phase. This framework is general enough to accommodate a variety of selection and placement algorithms. It does not appear possible to achieve our desiderata using previous frameworks. Prior to this paper, there were no formal models of dynamic maps or of dynamic labels; our paper introduces both. We formulate a general optimization problem for dynamic map labeling and give a solution to a simple version of the problem. The simple version is based on label priorities and a versatile and intuitive class of dynamic label placements we call "invariant point placements". Despite these restrictions, our approach gives a useful and practical solution. Our implementation is incorporated into the G-Vis system which is a full-detail dynamic map of the continental USA. This demo is available through any browser.

  19. NASA's Solar System Treks: Online Portals for Planetary Mapping and Modeling

    NASA Astrophysics Data System (ADS)

    Day, B. H.; Law, E.

    2017-12-01

    NASA's Solar System Treks are a suite of web-based of lunar and planetary mapping and modeling portals providing interactive visualization and analysis tools enabling mission planners, planetary scientists, students, and the general public to access mapped lunar data products from past and current missions for the Moon, Mars, Vesta, and more. New portals for additional planetary bodies are being planned. This presentation will recap significant enhancements to these toolsets during the past year and look ahead to future features and releases. Moon Trek is a new portal replacing its predecessor, the Lunar Mapping and Modeling Portal (LMMP), that significantly upgrades and builds upon the capabilities of LMMP. It features greatly improved navigation, 3D visualization, fly-overs, performance, and reliability. Additional data products and tools continue to be added. These include both generalized products as well as polar data products specifically targeting potential sites for NASA's Resource Prospector mission as well as for missions being planned by NASA's international partners. The latest release of Mars Trek includes new tools and data products requested by NASA's Planetary Science Division to support site selection and analysis for Mars Human Landing Exploration Zone Sites. Also being given very high priority by NASA Headquarters is Mars Trek's use as a means to directly involve the public in upcoming missions, letting them explore the areas the agency is focusing upon, understand what makes these sites so fascinating, follow the selection process, and get caught up in the excitement of exploring Mars. Phobos Trek, the latest effort in the Solar System Treks suite, is being developed in coordination with the International Phobos/Deimos Landing Site Working Group, with landing site selection and analysis for JAXA's MMX mission as a primary driver.

  20. NASA's Solar System Treks: Online Portals for Planetary Mapping and Modeling

    NASA Technical Reports Server (NTRS)

    Day, Brian

    2017-01-01

    NASA's Solar System Treks are a suite of web-based of lunar and planetary mapping and modeling portals providing interactive visualization and analysis tools enabling mission planners, planetary scientists, students, and the general public to access mapped lunar data products from past and current missions for the Moon, Mars, Vesta, and more. New portals for additional planetary bodies are being planned. This presentation will recap significant enhancements to these toolsets during the past year and look ahead to future features and releases. Moon Trek is a new portal replacing its predecessor, the Lunar Mapping and Modeling Portal (LMMP), that significantly upgrades and builds upon the capabilities of LMMP. It features greatly improved navigation, 3D visualization, fly-overs, performance, and reliability. Additional data products and tools continue to be added. These include both generalized products as well as polar data products specifically targeting potential sites for NASA's Resource Prospector mission as well as for missions being planned by NASA's international partners. The latest release of Mars Trek includes new tools and data products requested by NASA's Planetary Science Division to support site selection and analysis for Mars Human Landing Exploration Zone Sites. Also being given very high priority by NASA Headquarters is Mars Trek's use as a means to directly involve the public in upcoming missions, letting them explore the areas the agency is focusing upon, understand what makes these sites so fascinating, follow the selection process, and get caught up in the excitement of exploring Mars. Phobos Trek, the latest effort in the Solar System Treks suite, is being developed in coordination with the International Phobos/Deimos Landing Site Working Group, with landing site selection and analysis for JAXA's MMX (Martian Moons eXploration) mission as a primary driver.

  1. Semantic Data And Visualization Techniques Applied To Geologic Field Mapping

    NASA Astrophysics Data System (ADS)

    Houser, P. I. Q.; Royo-Leon, M.; Munoz, R.; Estrada, E.; Villanueva-Rosales, N.; Pennington, D. D.

    2015-12-01

    Geologic field mapping involves the use of technology before, during, and after visiting a site. Geologists utilize hardware such as Global Positioning Systems (GPS) connected to mobile computing platforms such as tablets that include software such as ESRI's ArcPad and other software to produce maps and figures for a final analysis and report. Hand written field notes contain important information and drawings or sketches of specific areas within the field study. Our goal is to collect and geo-tag final and raw field data into a cyber-infrastructure environment with an ontology that allows for large data processing, visualization, sharing, and searching, aiding in connecting field research with prior research in the same area and/or aid with experiment replication. Online searches of a specific field area return results such as weather data from NOAA and QuakeML seismic data from USGS. These results that can then be saved to a field mobile device and searched while in the field where there is no Internet connection. To accomplish this we created the GeoField ontology service using the Web Ontology Language (OWL) and Protégé software. Advanced queries on the dataset can be made using reasoning capabilities can be supported that go beyond a standard database service. These improvements include the automated discovery of data relevant to a specific field site and visualization techniques aimed at enhancing analysis and collaboration while in the field by draping data over mobile views of the site using augmented reality. A case study is being performed at University of Texas at El Paso's Indio Mountains Research Station located near Van Horn, Texas, an active multi-disciplinary field study site. The user can interactively move the camera around the study site and view their data digitally. Geologist's can check their data against the site in real-time and improve collaboration with another person as both parties have the same interactive view of the data.

  2. Near-Atomic Three-Dimensional Mapping for Site-Specific Chemistry of 'Superbugs'.

    PubMed

    Adineh, Vahid R; Marceau, Ross K W; Velkov, Tony; Li, Jian; Fu, Jing

    2016-11-09

    Emergence of multidrug resistant Gram-negative bacteria has caused a global health crisis and last-line class of antibiotics such as polymyxins are increasingly used. The chemical composition at the cell surface plays a key role in antibiotic resistance. Unlike imaging the cellular ultrastructure with well-developed electron microscopy, the acquisition of a high-resolution chemical map of the bacterial surface still remains a technological challenge. In this study, we developed an atom probe tomography (APT) analysis approach to acquire mass spectra in the pulsed-voltage mode and reconstructed the 3D chemical distribution of atoms and molecules in the subcellular domain at the near-atomic scale. Using focused ion beam (FIB) milling together with micromanipulation, site-specific samples were retrieved from a single cell of Acinetobacter baumannii prepared as needle-shaped tips with end radii less than 60 nm, followed by a nanoscale coating of silver in the order of 10 nm. The significantly elevated conductivity provided by the metallic coating enabled successful and routine field evaporation of the biological material, with all the benefits of pulsed-voltage APT. In parallel with conventional cryo-TEM imaging, our novel approach was applied to investigate polymyxin-susceptible and -resistant strains of A. baumannii after treatment of polymyxin B. Acquired atom probe mass spectra from the cell envelope revealed characteristic fragments of phosphocholine from the polymyxin-susceptible strain, but limited signals from this molecule were detected in the polymyxin-resistant strain. This study promises unprecedented capacity for 3D nanoscale imaging and chemical mapping of bacterial cells at the ultimate 3D spatial resolution using APT.

  3. Smart "geomorphological" map browsing - a tale about geomorphological maps and the internet

    NASA Astrophysics Data System (ADS)

    Geilhausen, M.; Otto, J.-C.

    2012-04-01

    With the digital production of geomorphological maps, the dissemination of research outputs now extends beyond simple paper products. Internet technologies can contribute to both, the dissemination of geomorphological maps and access to geomorphologic data and help to make geomorphological knowledge available to a greater public. Indeed, many national geological surveys employ end-to-end digital workflows from data capture in the field to final map production and dissemination. This paper deals with the potential of web mapping applications and interactive, portable georeferenced PDF maps for the distribution of geomorphological information. Web mapping applications such as Google Maps have become very popular and widespread and increased the interest and access to mapping. They link the Internet with GIS technology and are a common way of presenting dynamic maps online. The GIS processing is performed online and maps are visualised in interactive web viewers characterised by different capabilities such as zooming, panning or adding further thematic layers, with the map refreshed after each task. Depending on the system architecture and the components used, advanced symbology, map overlays from different applications and sources and their integration into a Desktop GIS are possible. This interoperability is achieved through the use of international open standards that include mechanisms for the integration and visualisation of information from multiple sources. The portable document format (PDF) is commonly used for printing and is a standard format that can be processed by many graphic software and printers without loss of information. A GeoPDF enables the sharing of geospatial maps and data in PDF documents. Multiple, independent map frames with individual spatial reference systems are possible within a GeoPDF, for example, for map overlays or insets. Geospatial functionality of a GeoPDF includes scalable map display, layer visibility control, access to attribute

  4. Geospatial Augmented Reality for the interactive exploitation of large-scale walkable orthoimage maps in museums

    NASA Astrophysics Data System (ADS)

    Wüest, Robert; Nebiker, Stephan

    2018-05-01

    In this paper we present an app framework for augmenting large-scale walkable maps and orthoimages in museums or public spaces using standard smartphones and tablets. We first introduce a novel approach for using huge orthoimage mosaic floor prints covering several hundred square meters as natural Augmented Reality (AR) markers. We then present a new app architecture and subsequent tests in the Swissarena of the Swiss National Transport Museum in Lucerne demonstrating the capabilities of accurately tracking and augmenting different map topics, including dynamic 3d data such as live air traffic. The resulting prototype was tested with everyday visitors of the museum to get feedback on the usability of the AR app and to identify pitfalls when using AR in the context of a potentially crowded museum. The prototype is to be rolled out to the public after successful testing and optimization of the app. We were able to show that AR apps on standard smartphone devices can dramatically enhance the interactive use of large-scale maps for different purposes such as education or serious gaming in a museum context.

  5. A Look Inside HIV Resistance through Retroviral Protease Interaction Maps

    PubMed Central

    Kontijevskis, Aleksejs; Prusis, Peteris; Petrovska, Ramona; Yahorava, Sviatlana; Mutulis, Felikss; Mutule, Ilze; Komorowski, Jan; Wikberg, Jarl E. S

    2007-01-01

    Retroviruses affect a large number of species, from fish and birds to mammals and humans, with global socioeconomic negative impacts. Here the authors report and experimentally validate a novel approach for the analysis of the molecular networks that are involved in the recognition of substrates by retroviral proteases. Using multivariate analysis of the sequence-based physiochemical descriptions of 61 retroviral proteases comprising wild-type proteases, natural mutants, and drug-resistant forms of proteases from nine different viral species in relation to their ability to cleave 299 substrates, the authors mapped the physicochemical properties and cross-dependencies of the amino acids of the proteases and their substrates, which revealed a complex molecular interaction network of substrate recognition and cleavage. The approach allowed a detailed analysis of the molecular–chemical mechanisms involved in substrate cleavage by retroviral proteases. PMID:17352531

  6. Protein Interaction Analysis Provides a Map of the Spatial and Temporal Organization of the Ciliary Gating Zone.

    PubMed

    Takao, Daisuke; Wang, Liang; Boss, Allison; Verhey, Kristen J

    2017-08-07

    The motility and signaling functions of the primary cilium require a unique protein and lipid composition that is determined by gating mechanisms localized at the base of the cilium. Several protein complexes localize to the gating zone and may regulate ciliary protein composition; however, the mechanisms of ciliary gating and the dynamics of the gating components are largely unknown. Here, we used the BiFC (bimolecular fluorescence complementation) assay and report for the first time on the protein-protein interactions that occur between ciliary gating components and transiting cargoes during ciliary entry. We find that the nucleoporin Nup62 and the C termini of the nephronophthisis (NPHP) proteins NPHP4 and NPHP5 interact with the axoneme-associated kinesin-2 motor KIF17 and thus spatially map to the inner region of the ciliary gating zone. Nup62 and NPHP4 exhibit rapid turnover at the transition zone and thus define dynamic components of the gate. We find that B9D1, AHI1, and the N termini of NPHP4 and NPHP5 interact with the transmembrane protein SSTR3 and thus spatially map to the outer region of the ciliary gating zone. B9D1, AHI1, and NPHP5 exhibit little to no turnover at the transition zone and thus define components of a stable gating structure. These data provide the first comprehensive map of the molecular orientations of gating zone components along the inner-to-outer axis of the ciliary gating zone. These results advance our understanding of the functional roles of gating zone components in regulating ciliary protein composition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

    PubMed

    Mizejewski, G J

    2016-09-01

    The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

  8. Kinetics and binding sites for interaction of the prefoldin with a group II chaperonin: contiguous non-native substrate and chaperonin binding sites in the archaeal prefoldin.

    PubMed

    Okochi, Mina; Nomura, Tomoko; Zako, Tamotsu; Arakawa, Takatoshi; Iizuka, Ryo; Ueda, Hiroshi; Funatsu, Takashi; Leroux, Michel; Yohda, Masafumi

    2004-07-23

    Prefoldin is a jellyfish-shaped hexameric co-chaperone of the group II chaperonins. It captures a protein folding intermediate and transfers it to a group II chaperonin for completion of folding. The manner in which prefoldin interacts with its substrates and cooperates with the chaperonin is poorly understood. In this study, we have examined the interaction between a prefoldin and a chaperonin from hyperthermophilic archaea by immunoprecipitation, single molecule observation, and surface plasmon resonance. We demonstrate that Pyrococcus prefoldin interacts most tightly with its cognate chaperonin, and vice versa, suggesting species specificity in the interaction. Using truncation mutants, we uncovered by kinetic analyses that this interaction is multivalent in nature, consistent with multiple binding sites between the two chaperones. We present evidence that both N- and C-terminal regions of the prefoldin beta sub-unit are important for molecular chaperone activity and for the interaction with a chaperonin. Our data are consistent with substrate and chaperonin binding sites on prefoldin that are different but in close proximity, which suggests a possible handover mechanism of prefoldin substrates to the chaperonin.

  9. Engaging Students through Mapping Local History

    PubMed Central

    Mitchell, Katharyne; Elwood, Sarah

    2015-01-01

    This article argues that the integration of local history and geography through collaborative digital mapping can lead to greater interest in civic participation by early adolescent learners. In the study, twenty-nine middle school students were asked to research, represent, and discuss local urban sites of historical significance on an interactive Web platform. As students learned more about local community events, people, and historical forces, they became increasingly engaged with the material and enthusiastic about making connections to larger issues and processes. In the final session, students expressed interest in participating in their own communities through joining nonprofit organizations and educating others about community history and daily life. PMID:25635145

  10. Engaging Students through Mapping Local History.

    PubMed

    Mitchell, Katharyne; Elwood, Sarah

    2012-07-01

    This article argues that the integration of local history and geography through collaborative digital mapping can lead to greater interest in civic participation by early adolescent learners. In the study, twenty-nine middle school students were asked to research, represent, and discuss local urban sites of historical significance on an interactive Web platform. As students learned more about local community events, people, and historical forces, they became increasingly engaged with the material and enthusiastic about making connections to larger issues and processes. In the final session, students expressed interest in participating in their own communities through joining nonprofit organizations and educating others about community history and daily life.

  11. The Microtubule-Associated Protein MAP18 Affects ROP2 GTPase Activity during Root Hair Growth1[OPEN

    PubMed Central

    Kang, Erfang; Zheng, Mingzhi; Zhang, Yan; Yuan, Ming; Fu, Ying

    2017-01-01

    Establishment and maintenance of the polar site are important for root hair tip growth. We previously reported that Arabidopsis (Arabidopsis thaliana) MICROTUBULE-ASSOCIATED PROTEIN18 (MAP18) functions in controlling the direction of pollen tube growth and root hair elongation. Additionally, the Rop GTPase ROP2 was reported as a positive regulator of both root hair initiation and tip growth in Arabidopsis. Both loss of function of ROP2 and knockdown of MAP18 lead to a decrease in root hair length, whereas overexpression of either MAP18 or ROP2 causes multiple tips or a branching hair phenotype. However, it is unclear whether MAP18 and ROP2 coordinately regulate root hair growth. In this study, we demonstrate that MAP18 and ROP2 interact genetically and functionally. MAP18 interacts physically with ROP2 in vitro and in vivo and preferentially binds to the inactive form of the ROP2 protein. MAP18 promotes ROP2 activity during root hair tip growth. Further investigation revealed that MAP18 competes with RhoGTPase GDP DISSOCIATION INHIBITOR1/SUPERCENTIPEDE1 for binding to ROP2, in turn affecting the localization of active ROP2 in the plasma membrane of the root hair tip. These results reveal a novel function of MAP18 in the regulation of ROP2 activation during root hair growth. PMID:28314794

  12. Analysis of In Vivo Chromatin and Protein Interactions of Arabidopsis Transcript Elongation Factors.

    PubMed

    Pfab, Alexander; Antosz, Wojciech; Holzinger, Philipp; Bruckmann, Astrid; Griesenbeck, Joachim; Grasser, Klaus D

    2017-01-01

    A central step to elucidate the function of proteins commonly comprises the analysis of their molecular interactions in vivo. For nuclear regulatory proteins this involves determining protein-protein interactions as well as mapping of chromatin binding sites. Here, we present two protocols to identify protein-protein and chromatin interactions of transcript elongation factors (TEFs) in Arabidopsis. The first protocol (Subheading 3.1) describes protein affinity-purification coupled to mass spectrometry (AP-MS) that utilizes suspension cultured cells as experimental system. This approach provides an unbiased view of proteins interacting with epitope-tagged TEFs. The second protocol (Subheading 3.2) depicts details about a chromatin immunoprecipitation (ChIP) procedure to characterize genomic binding sites of TEFs. These methods should be valuable tools for the analysis of a broad variety of nuclear proteins.

  13. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins

    NASA Astrophysics Data System (ADS)

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

  14. Site-conditions map for Portugal based on VS measurements: methodology and final model

    NASA Astrophysics Data System (ADS)

    Vilanova, Susana; Narciso, João; Carvalho, João; Lopes, Isabel; Quinta Ferreira, Mario; Moura, Rui; Borges, José; Nemser, Eliza; Pinto, carlos

    2017-04-01

    In this paper we present a statistically significant site-condition model for Portugal based on shear-wave velocity (VS) data and surface geology. We also evaluate the performance of commonly used Vs30 proxies based on exogenous data and analyze the implications of using those proxies for calculating site amplification in seismic hazard assessment. The dataset contains 161 Vs profiles acquired in Portugal in the context of research projects, technical reports, academic thesis and academic papers. The methodologies involved in characterizing the Vs structure at the sites in the database include seismic refraction, multichannel analysis of seismic waves and refraction microtremor. Invasive measurements were performed in selected locations in order to compare the Vs profiles obtained from both invasive and non-invasive techniques. In general there was good agreement in the subsurface structure of Vs30 obtained from the different methodologies. The database flat-file includes information on Vs30, surface geology at 1:50.000 and 1:500.000 scales, elevation and topographic slope and based on SRTM30 topographic dataset. The procedure used to develop the site-conditions map is based on a three-step process that includes defining a preliminary set of geological units based on the literature, performing statistical tests to assess whether or not the differences in the distributions of Vs30 are statistically significant, and merging of the geological units accordingly. The dataset was, to some extent, affected by clustering and/or preferential sampling and therefore a declustering algorithm was applied. The final model includes three geological units: 1) Igneous, metamorphic and old (Paleogene and Mesozoic) sedimentary rocks; 2) Neogene and Pleistocene formations, and 3) Holocene formations. The evaluation of proxies indicates that although geological analogues and topographic slope are in general unbiased, the latter shows significant bias for particular geological units and

  15. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Cancer.gov

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  16. CPC - Monitoring & Data: Regional Climate Maps

    Science.gov Websites

    Weather Service NWS logo - Click to go to the NWS home page Climate Prediction Center Site Map News Information CPC Web Team HOME > Monitoring and Data > Global Climate Data & Maps > Global Regional Climate Maps Regional Climate Maps Banner The Monthly regional analyses products are usually

  17. High-resolution mapping of transcription factor binding sites on native chromatin

    PubMed Central

    Kasinathan, Sivakanthan; Orsi, Guillermo A.; Zentner, Gabriel E.; Ahmad, Kami; Henikoff, Steven

    2014-01-01

    Sequence-specific DNA-binding proteins including transcription factors (TFs) are key determinants of gene regulation and chromatin architecture. Formaldehyde cross-linking and sonication followed by Chromatin ImmunoPrecipitation (X-ChIP) is widely used for profiling of TF binding, but is limited by low resolution and poor specificity and sensitivity. We present a simple protocol that starts with micrococcal nuclease-digested uncross-linked chromatin and is followed by affinity purification of TFs and paired-end sequencing. The resulting ORGANIC (Occupied Regions of Genomes from Affinity-purified Naturally Isolated Chromatin) profiles of Saccharomyces cerevisiae Abf1 and Reb1 provide highly accurate base-pair resolution maps that are not biased toward accessible chromatin, and do not require input normalization. We also demonstrate the high specificity of our method when applied to larger genomes by profiling Drosophila melanogaster GAGA Factor and Pipsqueak. Our results suggest that ORGANIC profiling is a widely applicable high-resolution method for sensitive and specific profiling of direct protein-DNA interactions. PMID:24336359

  18. Web GIS in practice II: interactive SVG maps of diagnoses of sexually transmitted diseases by Primary Care Trust in London, 1997 – 2003

    PubMed Central

    Boulos, Maged N Kamel; Russell, Chris; Smith, Michael

    2005-01-01

    Background The rates of Sexually transmitted diseases (STDs) in England have been rising steadily since the mid 1990s, making them a major public health concern. In 2003, 672,718 people were diagnosed with an STD in England, and around one third of those cases were diagnosed in London. Results Using GeoReveal v1.1 for Windows, we produced Web-based interactive choropleth maps of diagnoses of STDs by Primary Care Trust (PCT) in London for the years from 1997 to 2003 . These maps are in Scalable Vector Graphics (SVG) format and require a freely available Adobe SVG browser plug-in to be displayed. They are based on data obtained from the House of Commons Hansard Written Answers for 15 October 2004. They show steadily rising rates of STDs in London over the covered seven-year period. Also, one can clearly see on the maps that PCTs located in central London had the highest numbers of STD diagnoses throughout the mapped seven years. A companion bar chart allows users to instantly compare the STD figure of a given PCT for a given year against the average figure for all 25 mapped PCTs for the same year, and also compare those figures across all seven years. The maps offer users a rich set of useful features and functions, including the ability to change the classification method in use, the number of ranges in the map, and the colour theme, among others. Conclusions Wizard-driven tools like GeoReveal have made it very easy to transform complex raw data into valuable decision support information products (interactive Web maps) in very little time and without requiring much expertise. The resultant interactive maps have the potential of further supporting health planners and decision makers in their planning and management tasks by allowing them to graphically interrogate data, instantly spot trends, and make quick and effective visual comparisons of geographically differentiated phenomena between different geographical areas and over time. SVG makes an ideal format for such

  19. IntegratedMap: a Web interface for integrating genetic map data.

    PubMed

    Yang, Hongyu; Wang, Hongyu; Gingle, Alan R

    2005-05-01

    IntegratedMap is a Web application and database schema for storing and interactively displaying genetic map data. Its Web interface includes a menu for direct chromosome/linkage group selection, a search form for selection based on mapped object location and linkage group displays. An overview display provides convenient access to the full range of mapped and anchored object types with genetic locus details, such as numbers, types and names of mapped/anchored objects displayed in a compact scrollable list box that automatically updates based on selected map location and object type. Also, multilinkage group and localized map views are available along with links that can be configured for integration with other Web resources. IntegratedMap is implemented in C#/ASP.NET and the package, including a MySQL schema creation script, is available from http://cggc.agtec.uga.edu/Data/download.asp

  20. Final report: Mapping Interactions in Hybrid Systems with Active Scanning Probes

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

    Berezovsky, Jesse

    2017-09-29

    This project aimed to study and map interactions between components of hybrid nanodevices using a novel scanning probe approach. To enable this work, we initially constructed a flexible experimental apparatus allowing for simultaneous scanning probe and confocal optical microscopy measurements. This setup was first used for all-optical measurements of nanostructures, with the focus then shifting to hybrid devices in which single coherent electron spins are coupled to micron-scale ferromagnetic elements, which may prove useful for addressing single spins, enhanced sensing, or spin-wave-mediated coupling of spins for quantum information applications. A significant breakthrough was the realization that it is not necessarymore » to fabricate a magnetic structure on a scanning probe – instead a ferromagnetic vortex core can act as an integrated, solid state, scanning probe. The core of the vortex produces a very strong, localized fringe field which can be used analogously to an MFM tip. Unlike a traditional MFM tip, however, the vortex core is scanned within an integrated device (eliminating drift), and can be moved on vastly faster timescales. This approach allows the detailed investigation of interactions between single spins and complex driven ferromagnetic dynamics.« less

  1. LC-MS/MS Peptide Mapping with Automated Data Processing for Routine Profiling of N-Glycans in Immunoglobulins

    NASA Astrophysics Data System (ADS)

    Shah, Bhavana; Jiang, Xinzhao Grace; Chen, Louise; Zhang, Zhongqi

    2014-06-01

    Protein N-Glycan analysis is traditionally performed by high pH anion exchange chromatography (HPAEC), reversed phase liquid chromatography (RPLC), or hydrophilic interaction liquid chromatography (HILIC) on fluorescence-labeled glycans enzymatically released from the glycoprotein. These methods require time-consuming sample preparations and do not provide site-specific glycosylation information. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) peptide mapping is frequently used for protein structural characterization and, as a bonus, can potentially provide glycan profile on each individual glycosylation site. In this work, a recently developed glycopeptide fragmentation model was used for automated identification, based on their MS/MS, of N-glycopeptides from proteolytic digestion of monoclonal antibodies (mAbs). Experimental conditions were optimized to achieve accurate profiling of glycoforms. Glycan profiles obtained from LC-MS/MS peptide mapping were compared with those obtained from HPAEC, RPLC, and HILIC analyses of released glycans for several mAb molecules. Accuracy, reproducibility, and linearity of the LC-MS/MS peptide mapping method for glycan profiling were evaluated. The LC-MS/MS peptide mapping method with fully automated data analysis requires less sample preparation, provides site-specific information, and may serve as an alternative method for routine profiling of N-glycans on immunoglobulins as well as other glycoproteins with simple N-glycans.

  2. Genome-wide mapping of DNase I hypersensitive sites in rare cell populations using single-cell DNase sequencing.

    PubMed

    Cooper, James; Ding, Yi; Song, Jiuzhou; Zhao, Keji

    2017-11-01

    Increased chromatin accessibility is a feature of cell-type-specific cis-regulatory elements; therefore, mapping of DNase I hypersensitive sites (DHSs) enables the detection of active regulatory elements of transcription, including promoters, enhancers, insulators and locus-control regions. Single-cell DNase sequencing (scDNase-seq) is a method of detecting genome-wide DHSs when starting with either single cells or <1,000 cells from primary cell sources. This technique enables genome-wide mapping of hypersensitive sites in a wide range of cell populations that cannot be analyzed using conventional DNase I sequencing because of the requirement for millions of starting cells. Fresh cells, formaldehyde-cross-linked cells or cells recovered from formalin-fixed paraffin-embedded (FFPE) tissue slides are suitable for scDNase-seq assays. To generate scDNase-seq libraries, cells are lysed and then digested with DNase I. Circular carrier plasmid DNA is included during subsequent DNA purification and library preparation steps to prevent loss of the small quantity of DHS DNA. Libraries are generated for high-throughput sequencing on the Illumina platform using standard methods. Preparation of scDNase-seq libraries requires only 2 d. The materials and molecular biology techniques described in this protocol should be accessible to any general molecular biology laboratory. Processing of high-throughput sequencing data requires basic bioinformatics skills and uses publicly available bioinformatics software.

  3. Global Mapping of Transcription Factor Binding Sites by Sequencing Chromatin Surrogates: a Perspective on Experimental Design, Data Analysis, and Open Problems.

    PubMed

    Wei, Yingying; Wu, George; Ji, Hongkai

    2013-05-01

    Mapping genome-wide binding sites of all transcription factors (TFs) in all biological contexts is a critical step toward understanding gene regulation. The state-of-the-art technologies for mapping transcription factor binding sites (TFBSs) couple chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip). These technologies have limitations: they are low-throughput with respect to surveying many TFs. Recent advances in genome-wide chromatin profiling, including development of technologies such as DNase-seq, FAIRE-seq and ChIP-seq for histone modifications, make it possible to predict in vivo TFBSs by analyzing chromatin features at computationally determined DNA motif sites. This promising new approach may allow researchers to monitor the genome-wide binding sites of many TFs simultaneously. In this article, we discuss various experimental design and data analysis issues that arise when applying this approach. Through a systematic analysis of the data from the Encyclopedia Of DNA Elements (ENCODE) project, we compare the predictive power of individual and combinations of chromatin marks using supervised and unsupervised learning methods, and evaluate the value of integrating information from public ChIP and gene expression data. We also highlight the challenges and opportunities for developing novel analytical methods, such as resolving the one-motif-multiple-TF ambiguity and distinguishing functional and non-functional TF binding targets from the predicted binding sites. The online version of this article (doi:10.1007/s12561-012-9066-5) contains supplementary material, which is available to authorized users.

  4. Patient-oriented interactive E-health tools on U.S. hospital Web sites.

    PubMed

    Huang, Edgar; Chang, Chiu-Chi Angela

    2012-01-01

    The purpose of this study is to provide evidence for strategic planning regarding e-health development in U.S. hospitals. A content analysis of a representative sample of the U.S. hospital Web sites has revealed how U.S. hospitals have taken advantage of the 21 patient-oriented interactive tools identified in this study. Significant gaps between various types of hospitals have also been found. It is concluded that although the majority of the U.S. hospitals have adopted traditional functional tools, they need to make significant inroad in implementing the core e-business tools to serve their patients/users, making their Web sites more efficient marketing tools.

  5. Cartographic mapping study

    NASA Technical Reports Server (NTRS)

    Wilson, C.; Dye, R.; Reed, L.

    1982-01-01

    The errors associated with planimetric mapping of the United States using satellite remote sensing techniques are analyzed. Assumptions concerning the state of the art achievable for satellite mapping systems and platforms in the 1995 time frame are made. An analysis of these performance parameters is made using an interactive cartographic satellite computer model, after first validating the model using LANDSAT 1 through 3 performance parameters. An investigation of current large scale (1:24,000) US National mapping techniques is made. Using the results of this investigation, and current national mapping accuracy standards, the 1995 satellite mapping system is evaluated for its ability to meet US mapping standards for planimetric and topographic mapping at scales of 1:24,000 and smaller.

  6. Binding sites for interaction of peroxiredoxin 6 with surfactant protein A.

    PubMed

    Krishnaiah, Saikumari Y; Dodia, Chandra; Sorokina, Elena M; Li, Haitao; Feinstein, Sheldon I; Fisher, Aron B

    2016-04-01

    Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction. Docking of SPA and Prdx6 was modeled using the ZDOCK (zlab.bu.edu) program in order to predict molecular sites for binding of the two proteins. The predicted peptide sequences were evaluated for binding to the opposite protein using isothermal titration calorimetry and circular dichroism measurement followed by determination of the effect of the SP-A peptide on the PLA2 activity of Prdx6. The sequences 195EEEAKKLFPK204.in the Prdx6 helix and 83DEELQTELYEIKHQIL99 in SP-A were identified as the sites for hydrophobic interaction and H(+)-bonding between the 2 proteins. Treatment of mouse endothelial cells with the SP-A peptide inhibited their recovery from lipid peroxidation associated with oxidative stress indicating inhibition of Prdx6 activity by the peptide in the intact cell. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Binding sites for interaction of peroxiredoxin 6 with surfactant protein A

    PubMed Central

    Krishnaiah, Saikumari Y; Dodia, Chandra; Sorokina, Elena M; Li, Haitao; Feinstein, Sheldon I; Fisher, Aron B

    2016-01-01

    Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction. Docking of SPA and Prdx6 was modeled using the ZDOCK (zlab.bu.edu) program in order to predict molecular sites for binding of the two proteins. The predicted peptide sequences were evaluated for binding to the opposite protein using isothermal titration calorimetry and circular dichroism measurement followed by determination of the effect of the SP-A peptide on the PLA2 activity of Prdx6. The sequences 195EEEAKKLFPK204.in the Prdx6 helix and 83DEELQTELYEIKHQIL99 in SP-A were identified as the sites for hydrophobic interaction and H+-bonding between the 2 proteins. Treatment of mouse endothelial cells with the SP-A peptide inhibited their recovery from lipid peroxidation associated with oxidative stress indicating inhibition of Prdx6 activity by the peptide in the intact cell. PMID:26723227

  8. Combining solvent thermodynamic profiles with functionality maps of the Hsp90 binding site to predict the displacement of water molecules.

    PubMed

    Haider, Kamran; Huggins, David J

    2013-10-28

    Intermolecular interactions in the aqueous phase must compete with the interactions between the two binding partners and their solvating water molecules. In biological systems, water molecules in protein binding sites cluster at well-defined hydration sites and can form strong hydrogen-bonding interactions with backbone and side-chain atoms. Displacement of such water molecules is only favorable when the ligand can form strong compensating hydrogen bonds. Conversely, water molecules in hydrophobic regions of protein binding sites make only weak interactions, and the requirements for favorable displacement are less stringent. The propensity of water molecules for displacement can be identified using inhomogeneous fluid solvation theory (IFST), a statistical mechanical method that decomposes the solvation free energy of a solute into the contributions from different spatial regions and identifies potential binding hotspots. In this study, we employed IFST to study the displacement of water molecules from the ATP binding site of Hsp90, using a test set of 103 ligands. The predicted contribution of a hydration site to the hydration free energy was found to correlate well with the observed displacement. Additionally, we investigated if this correlation could be improved by using the energetic scores of favorable probe groups binding at the location of hydration sites, derived from a multiple copy simultaneous search (MCSS) method. The probe binding scores were not highly predictive of the observed displacement and did not improve the predictivity when used in combination with IFST-based hydration free energies. The results show that IFST alone can be used to reliably predict the observed displacement of water molecules in Hsp90. However, MCSS can augment IFST calculations by suggesting which functional groups should be used to replace highly displaceable water molecules. Such an approach could be very useful in improving the hit-to-lead process for new drug targets.

  9. A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities

    PubMed Central

    Vizeacoumar, Franco J; Arnold, Roland; Vizeacoumar, Frederick S; Chandrashekhar, Megha; Buzina, Alla; Young, Jordan T F; Kwan, Julian H M; Sayad, Azin; Mero, Patricia; Lawo, Steffen; Tanaka, Hiromasa; Brown, Kevin R; Baryshnikova, Anastasia; Mak, Anthony B; Fedyshyn, Yaroslav; Wang, Yadong; Brito, Glauber C; Kasimer, Dahlia; Makhnevych, Taras; Ketela, Troy; Datti, Alessandro; Babu, Mohan; Emili, Andrew; Pelletier, Laurence; Wrana, Jeff; Wainberg, Zev; Kim, Philip M; Rottapel, Robert; O'Brien, Catherine A; Andrews, Brenda; Boone, Charles; Moffat, Jason

    2013-01-01

    Improved efforts are necessary to define the functional product of cancer mutations currently being revealed through large-scale sequencing efforts. Using genome-scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co-culture competition assays to generate a high-confidence genetic interaction network of differentially essential or differential essentiality (DiE) genes. The network uncovered examples of conserved genetic interactions, densely connected functional modules derived from comparative genomics with model systems data, functions for uncharacterized genes in the human genome and targetable vulnerabilities. Finally, we demonstrate a general applicability of DiE gene signatures in determining genetic dependencies of other non-isogenic cancer cell lines. For example, the PTEN−/− DiE genes reveal a signature that can preferentially classify PTEN-dependent genotypes across a series of non-isogenic cell lines derived from the breast, pancreas and ovarian cancers. Our reference network suggests that many cancer vulnerabilities remain to be discovered through systematic derivation of a network of differentially essential genes in an isogenic cancer cell model. PMID:24104479

  10. Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions

    PubMed Central

    Turner, Leslie M; Harr, Bettina

    2014-01-01

    Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone. DOI: http://dx.doi.org/10.7554/eLife.02504.001 PMID:25487987

  11. Analysis of functional importance of binding sites in the Drosophila gap gene network model.

    PubMed

    Kozlov, Konstantin; Gursky, Vitaly V; Kulakovskiy, Ivan V; Dymova, Arina; Samsonova, Maria

    2015-01-01

    The statistical thermodynamics based approach provides a promising framework for construction of the genotype-phenotype map in many biological systems. Among important aspects of a good model connecting the DNA sequence information with that of a molecular phenotype (gene expression) is the selection of regulatory interactions and relevant transcription factor bindings sites. As the model may predict different levels of the functional importance of specific binding sites in different genomic and regulatory contexts, it is essential to formulate and study such models under different modeling assumptions. We elaborate a two-layer model for the Drosophila gap gene network and include in the model a combined set of transcription factor binding sites and concentration dependent regulatory interaction between gap genes hunchback and Kruppel. We show that the new variants of the model are more consistent in terms of gene expression predictions for various genetic constructs in comparison to previous work. We quantify the functional importance of binding sites by calculating their impact on gene expression in the model and calculate how these impacts correlate across all sites under different modeling assumptions. The assumption about the dual interaction between hb and Kr leads to the most consistent modeling results, but, on the other hand, may obscure existence of indirect interactions between binding sites in regulatory regions of distinct genes. The analysis confirms the previously formulated regulation concept of many weak binding sites working in concert. The model predicts a more or less uniform distribution of functionally important binding sites over the sets of experimentally characterized regulatory modules and other open chromatin domains.

  12. Arabidopsis Microtubule-Associated Protein MAP65-3 Cross-Links Antiparallel Microtubules toward Their Plus Ends in the Phragmoplast via Its Distinct C-Terminal Microtubule Binding Domain[W

    PubMed Central

    Ho, Chin-Min Kimmy; Lee, Yuh-Ru Julie; Kiyama, Lindsay D.; Dinesh-Kumar, Savithramma P.; Liu, Bo

    2012-01-01

    Plant cytokinesis is brought about by the phragmoplast, which contains an antiparallel microtubule (MT) array. The MT-associated protein MAP65-3 acts as an MT-bundling factor that specifically cross-links antiparallel MTs near their plus ends. MAP65 family proteins contain an N-terminal dimerization domain and C-terminal MT interaction domain. Compared with other MAP65 isoforms, MAP65-3 contains an extended C terminus. A MT binding site was discovered in the region between amino acids 496 and 588 and found to be essential for the organization of phragmoplast MTs. The frequent cytokinetic failure caused by loss of MAP65-3 was not rescued by ectopic expression of MAP65-1 under the control of the MAP65-3 promoter, indicating nonoverlapping functions between the two isoforms. In the presence of MAP65-3, however, ectopic MAP65-1 appeared in the phragmoplast midline. We show that MAP65-1 could acquire the function of MAP65-3 when the C terminus of MAP65-3, which contains the MT binding site, was grafted to it. Our results also show that MAP65-1 and MAP65-3 may share redundant functions in MT stabilization. Such a stabilization effect was likely brought about by MT binding and bundling. We conclude that MAP65-3 contains a distinct C-terminal MT binding site with a specific role in cross-linking antiparallel MTs toward their plus ends in the phragmoplast. PMID:22570443

  13. Memory matters: influence from a cognitive map on animal space use.

    PubMed

    Gautestad, Arild O

    2011-10-21

    A vertebrate individual's cognitive map provides a capacity for site fidelity and long-distance returns to favorable patches. Fractal-geometrical analysis of individual space use based on collection of telemetry fixes makes it possible to verify the influence of a cognitive map on the spatial scatter of habitat use and also to what extent space use has been of a scale-specific versus a scale-free kind. This approach rests on a statistical mechanical level of system abstraction, where micro-scale details of behavioral interactions are coarse-grained to macro-scale observables like the fractal dimension of space use. In this manner, the magnitude of the fractal dimension becomes a proxy variable for distinguishing between main classes of habitat exploration and site fidelity, like memory-less (Markovian) Brownian motion and Levy walk and memory-enhanced space use like Multi-scaled Random Walk (MRW). In this paper previous analyses are extended by exploring MRW simulations under three scenarios: (1) central place foraging, (2) behavioral adaptation to resource depletion (avoidance of latest visited locations) and (3) transition from MRW towards Levy walk by narrowing memory capacity to a trailing time window. A generalized statistical-mechanical theory with the power to model cognitive map influence on individual space use will be important for statistical analyses of animal habitat preferences and the mechanics behind site fidelity and home ranges. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. CrowdMapping: A Crowdsourcing-Based Terminology Mapping Method for Medical Data Standardization.

    PubMed

    Mao, Huajian; Chi, Chenyang; Huang, Boyu; Meng, Haibin; Yu, Jinghui; Zhao, Dongsheng

    2017-01-01

    Standardized terminology is the prerequisite of data exchange in analysis of clinical processes. However, data from different electronic health record systems are based on idiosyncratic terminology systems, especially when the data is from different hospitals and healthcare organizations. Terminology standardization is necessary for the medical data analysis. We propose a crowdsourcing-based terminology mapping method, CrowdMapping, to standardize the terminology in medical data. CrowdMapping uses a confidential model to determine how terminologies are mapped to a standard system, like ICD-10. The model uses mappings from different health care organizations and evaluates the diversity of the mapping to determine a more sophisticated mapping rule. Further, the CrowdMapping model enables users to rate the mapping result and interact with the model evaluation. CrowdMapping is a work-in-progress system, we present initial results mapping terminologies.

  15. Identification and mapping of natural vegetation on a coastal site using a Worldview-2 satellite image.

    PubMed

    Rapinel, Sébastien; Clément, Bernard; Magnanon, Sylvie; Sellin, Vanessa; Hubert-Moy, Laurence

    2014-11-01

    Identification and mapping of natural vegetation are major issues for biodiversity management and conservation. Remotely sensed data with very high spatial resolution are currently used to study vegetation, but most satellite sensors are limited to four spectral bands, which is insufficient to identify some natural vegetation formations. The study objectives are to discriminate natural vegetation and identify natural vegetation formations using a Worldview-2 satellite image. The classification of the Worldview-2 image and ancillary thematic data was performed using a hybrid pixel-based and object-oriented approach. A hierarchical scheme using three levels was implemented, from land cover at a field scale to vegetation formation. This method was applied on a 48 km² site located on the French Atlantic coast which includes a classified NATURA 2000 dune and marsh system. The classification accuracy was very high, the Kappa index varying between 0.90 and 0.74 at land cover and vegetation formation levels respectively. These results show that Wordlview-2 images are suitable to identify natural vegetation. Vegetation maps derived from Worldview-2 images are more detailed than existing ones. They provide a useful medium for environmental management of vulnerable areas. The approach used to map natural vegetation is reproducible for a wider application by environmental managers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue.

    PubMed

    Pless, Stephan A; Millen, Kat S; Hanek, Ariele P; Lynch, Joseph W; Lester, Henry A; Lummis, Sarah C R; Dougherty, Dennis A

    2008-10-22

    Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-pi interaction with the agonist, whereas in GABA(A) receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-pi interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC(50) value and the cation-pi binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-pi interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-pi interaction between Phe and a neurotransmitter.

  17. RadMap Installation Instructions

    EPA Pesticide Factsheets

    RadMap is an interactive desktop tool featuring a nationwide geographic information systems (GIS) map of long-term radiation monitoring locations across the United States with access to key information about the monitor and the area surrounding it.

  18. Mapping hydration dynamics and coupled water-protein fluctuations around a protein surface

    NASA Astrophysics Data System (ADS)

    Zhang, Luyuan; Wang, Lijuan; Kao, Ya-Ting; Qiu, Weihong; Yang, Yi; Okobiah, Oghaghare; Zhong, Dongping

    2009-03-01

    Elucidation of the molecular mechanism of water-protein interactions is critical to understanding many fundamental aspects of protein science, such as protein folding and misfolding and enzyme catalysis. We recently carried out a global mapping of protein-surface hydration dynamics around a globular α-helical protein apomyoglobin. The intrinsic optical probe tryptophan was employed to scan the protein surface one at a time by site-specific mutagenesis. With femtosecond resolution, we mapped out the dynamics of water-protein interactions with more than 20 mutants and for two states, native and molten globular. A robust bimodal distribution of time scales was observed, representing two types of water motions: local relaxation and protein-coupled fluctuations. The time scales show a strong correlation with the local protein structural rigidity and chemical identity. We also resolved two distinct contributions to the overall Stokes-shifts from the two time scales. These results are significant to understanding the role of hydration water on protein structural stability, dynamics and function.

  19. Language Mapping with Navigated Repetitive TMS: Proof of Technique and Validation

    PubMed Central

    Tarapore, Phiroz E.; Findlay, Anne M.; Honma, Susanne M.; Mizuiri, Danielle; Houde, John F.; Berger, Mitchel S.; Nagarajan, Srikantan S.

    2013-01-01

    Objective Lesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS. Methods Subjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared. Results nTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects

  20. Interactive Mapping of Inundation Metrics Using Cloud Computing for Improved Floodplain Conservation and Management

    NASA Astrophysics Data System (ADS)

    Bulliner, E. A., IV; Lindner, G. A.; Bouska, K.; Paukert, C.; Jacobson, R. B.

    2017-12-01

    Within large-river ecosystems, floodplains serve a variety of important ecological functions. A recent survey of 80 managers of floodplain conservation lands along the Upper and Middle Mississippi and Lower Missouri Rivers in the central United States found that the most critical information needed to improve floodplain management centered on metrics for characterizing depth, extent, frequency, duration, and timing of inundation. These metrics can be delivered to managers efficiently through cloud-based interactive maps. To calculate these metrics, we interpolated an existing one-dimensional hydraulic model for the Lower Missouri River, which simulated water surface elevations at cross sections spaced (<1 km) to sufficiently characterize water surface profiles along an approximately 800 km stretch upstream from the confluence with the Mississippi River over an 80-year record at a daily time step. To translate these water surface elevations to inundation depths, we subtracted a merged terrain model consisting of floodplain LIDAR and bathymetric surveys of the river channel. This approach resulted in a 29000+ day time series of inundation depths across the floodplain using grid cells with 30 m spatial resolution. Initially, we used these data on a local workstation to calculate a suite of nine spatially distributed inundation metrics for the entire model domain. These metrics are calculated on a per pixel basis and encompass a variety of temporal criteria generally relevant to flora and fauna of interest to floodplain managers, including, for example, the average number of days inundated per year within a growing season. Using a local workstation, calculating these metrics for the entire model domain requires several hours. However, for the needs of individual floodplain managers working at site scales, these metrics may be too general and inflexible. Instead of creating a priori a suite of inundation metrics able to satisfy all user needs, we present the usage of

  1. Towards adaptable, interactive and quantitative paleogeographic maps

    NASA Astrophysics Data System (ADS)

    Wright, N.; Zahirovic, S.; Müller, R. D.; Seton, M.

    2012-07-01

    A variety of paleogeographic atlases have been constructed, with applications from paleoclimate, ocean circulation and faunal radiation models to resource exploration; yet their uncertainties remain difficult to assess, as they are generally presented as low-resolution static maps. We present a methodology for ground-truthing paleogeographic maps, by linking the GPlates plate reconstruction tool to the global Paleobiology Database and a Phanerozoic plate motion model. We develop a spatio-temporal data mining workflow to compare a Phanerozoic Paleogeographic Atlas of Australia with biogeographic indicators. The agreement between fossil data and paleogeographic maps is quite good, but the methodology also highlights key inconsistencies. The Early Devonian paleogeography of southeastern Australia insufficiently describes the Emsian inundation that is supported by biogeography. Additionally, the Cretaceous inundation of eastern Australia retreats by 110 Ma according to the paleogeography, but the biogeography indicates that inundation prevailed until at least 100 Ma. Paleobiogeography can also be used to refine Gondwana breakup and the extent of pre-breakup Greater India can be inferred from the southward limit of inundation along western Australia. Although paleobiology data provide constraints only for paleoenvironments with high preservation potential of organisms, our approach enables the use of additional proxy data to generate improved paleogeographic reconstructions.

  2. Interactive segmentation of tongue contours in ultrasound video sequences using quality maps

    NASA Astrophysics Data System (ADS)

    Ghrenassia, Sarah; Ménard, Lucie; Laporte, Catherine

    2014-03-01

    Ultrasound (US) imaging is an effective and non invasive way of studying the tongue motions involved in normal and pathological speech, and the results of US studies are of interest for the development of new strategies in speech therapy. State-of-the-art tongue shape analysis techniques based on US images depend on semi-automated tongue segmentation and tracking techniques. Recent work has mostly focused on improving the accuracy of the tracking techniques themselves. However, occasional errors remain inevitable, regardless of the technique used, and the tongue tracking process must thus be supervised by a speech scientist who will correct these errors manually or semi-automatically. This paper proposes an interactive framework to facilitate this process. In this framework, the user is guided towards potentially problematic portions of the US image sequence by a segmentation quality map that is based on the normalized energy of an active contour model and automatically produced during tracking. When a problematic segmentation is identified, corrections to the segmented contour can be made on one image and propagated both forward and backward in the problematic subsequence, thereby improving the user experience. The interactive tools were tested in combination with two different tracking algorithms. Preliminary results illustrate the potential of the proposed framework, suggesting that the proposed framework generally improves user interaction time, with little change in segmentation repeatability.

  3. Genomic maps of lincRNA occupancy reveal principles of RNA-chromatin interactions

    PubMed Central

    Chu, Ci; Qu, Kun; Zhong, Franklin; Artandi, Steven E.; Chang, Howard Y.

    2011-01-01

    SUMMARY Long intergenic noncoding RNAs (lincRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lincRNAs with bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of three lincRNAs reveal that RNA occupancy sites in the genome are focal, sequence-specific, and numerous. Drosophila roX2 RNA occupies male X-linked gene bodies with increasing tendency toward the 3’ end, peaking at CES sites. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lincRNA preferentially occupies a GA-rich DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, suggesting the order of RNA guidance of Polycomb occupancy. ChIRP-seq is generally applicable to illuminate the intersection of RNA and chromatin with newfound precision genome-wide. PMID:21963238

  4. The Effectiveness of Interactive Computer Assisted Modeling in Teaching Study Strategies and Concept Mapping of College Textbook Material.

    ERIC Educational Resources Information Center

    Mikulecky, Larry

    A study evaluated the effectiveness of a series of print materials and interactive computer-guided study programs designed to lead undergraduate students to apply basic textbook reading and concept mapping strategies to the study of science and social science textbooks. Following field testing with 25 learning skills students, 50 freshman biology…

  5. Application of molecular docking and ONIOM methods for the description of interactions between anti-quorum sensing active (AHL) analogues and the Pseudomonas aeruginosa LasR binding site.

    PubMed

    Ahumedo, Maicol; Drosos, Juan Carlos; Vivas-Reyes, Ricardo

    2014-05-01

    Molecular docking methods were applied to simulate the coupling of a set of nineteen acyl homoserine lactone analogs into the binding site of the transcriptional receptor LasR. The best pose of each ligand was explored and a qualitative analysis of the possible interactions present in the complex was performed. From the results of the protein-ligand complex analysis, it was found that residues Tyr-64 and Tyr-47 are involved in important interactions, which mainly determine the antagonistic activity of the AHL analogues considered for this study. The effect of different substituents on the aromatic ring, the common structure to all ligands, was also evaluated focusing on how the interaction with the two previously mentioned tyrosine residues was affected. Electrostatic potential map calculations based on the electron density and the van der Waals radii were performed on all ligands to graphically aid in the explanation of the variation of charge density on their structures when the substituent on the aromatic ring is changed through the elements of the halogen group series. A quantitative approach was also considered and for that purpose the ONIOM method was performed to estimate the energy change in the different ligand-receptor complex regions. Those energy values were tested for their relationship with the corresponding IC50 in order to establish if there is any correlation between energy changes in the selected regions and the biological activity. The results obtained using the two approaches may contribute to the field of quorum sensing active molecules; the docking analysis revealed the role of some binding site residues involved in the formation of a halogen bridge with ligands. These interactions have been demonstrated to be responsible for the interruption of the signal propagation needed for the quorum sensing circuit. Using the other approach, the structure-activity relationship (SAR) analysis, it was possible to establish which structural characteristics

  6. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity

    PubMed Central

    Miller, Megan B.; Yan, Yan; Machida, Kazuya; Kiraly, Drew D.; Levy, Aaron D.; Wu, Yi I.; Lam, TuKiet T.; Abbott, Thomas; Koleske, Anthony J.; Eipper, Betty A.; Mains, Richard E.

    2017-01-01

    Kalirin7 (Kal7), a postsynaptic Rho GDP/GTP exchange factor (RhoGEF), plays a crucial role in long term potentiation and in the effects of cocaine on behavior and spine morphology. The KALRN gene has been linked to schizophrenia and other disorders of synaptic function. Mass spectrometry was used to quantify phosphorylation at 26 sites in Kal7 from individual adult rat nucleus accumbens and prefrontal cortex before and after exposure to acute or chronic cocaine. Region- and isoform-specific phosphorylation was observed along with region-specific effects of cocaine on Kal7 phosphorylation. Evaluation of the functional significance of multi-site phosphorylation in a complex protein like Kalirin is difficult. With the identification of five tyrosine phosphorylation (pY) sites, a panel of 71 SH2 domains was screened, identifying subsets that interacted with multiple pY sites in Kal7. In addition to this type of reversible interaction, endoproteolytic cleavage by calpain plays an essential role in long-term potentiation. Calpain cleaved Kal7 at two sites, separating the N-terminal domain, which affects spine length, and the PDZ binding motif from the GEF domain. Mutations preventing phosphorylation did not affect calpain sensitivity or GEF activity; phosphomimetic mutations at specific sites altered protein stability, increased calpain sensitivity and reduced GEF activity. PMID:28418645

  7. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    PubMed

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  8. The Future of Web Maps in Next Generation Textbooks

    NASA Astrophysics Data System (ADS)

    DiBiase, D.; Prasad, S.

    2014-12-01

    The reformation of the "Object Formerly Known as Textbook" (coined by the Chronicle of Higher Education) toward a digital future is underway. Emerging nextgen texts look less like electronic books ("ebooks") and more like online courseware. In addition to text and illustrations, nextgen textbooks for STEM subjects are likely to combine quizzes, grade management tools, support for social learning, and interactive media including web maps. Web maps are interactive, multi-scale, online maps that enable teachers and learners to explore, interrogate, and mash up the wide variety of map layers available in the cloud. This presentation will show how web maps coupled with interactive quizzes enable students' purposeful explorations and interpretations of spatial patterns related to humankind's interactions with the earth. Attendees will also learn about Esri's offer to donate ArcGIS Online web mapping subscriptions to every U.S. school as part of the President Obama's ConnectED initiative.

  9. PRMT7 Interacts with ASS1 and Citrullinemia Mutations Disrupt the Interaction.

    PubMed

    Verma, Mamta; Charles, Ramya Chandar M; Chakrapani, Baskar; Coumar, Mohane Selvaraj; Govindaraju, Gayathri; Rajavelu, Arumugam; Chavali, Sreenivas; Dhayalan, Arunkumar

    2017-07-21

    Protein arginine methyltransferase 7 (PRMT7) catalyzes the introduction of monomethylation marks at the arginine residues of substrate proteins. PRMT7 plays important roles in the regulation of gene expression, splicing, DNA damage, paternal imprinting, cancer and metastasis. However, little is known about the interaction partners of PRMT7. To address this, we performed yeast two-hybrid screening of PRMT7 and identified argininosuccinate synthetase (ASS1) as a potential interaction partner of PRMT7. We confirmed that PRMT7 directly interacts with ASS1 using pull-down studies. ASS1 catalyzes the rate-limiting step of arginine synthesis in urea cycle and citrulline-nitric oxide cycle. We mapped the interface of PRMT7-ASS1 complex through computational approaches and validated the predicted interface in vivo by site-directed mutagenesis. Evolutionary analysis revealed that the ASS1 residues important for PRMT7-ASS1 interaction have co-evolved with PRMT7. We showed that ASS1 mutations linked to type I citrullinemia disrupt the ASS1-PRMT7 interaction, which might explain the molecular pathogenesis of the disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Continuum mesoscopic framework for multiple interacting species and processes on multiple site types and/or crystallographic planes.

    PubMed

    Chatterjee, Abhijit; Vlachos, Dionisios G

    2007-07-21

    While recently derived continuum mesoscopic equations successfully bridge the gap between microscopic and macroscopic physics, so far they have been derived only for simple lattice models. In this paper, general deterministic continuum mesoscopic equations are derived rigorously via nonequilibrium statistical mechanics to account for multiple interacting surface species and multiple processes on multiple site types and/or different crystallographic planes. Adsorption, desorption, reaction, and surface diffusion are modeled. It is demonstrated that contrary to conventional phenomenological continuum models, microscopic physics, such as the interaction potential, determines the final form of the mesoscopic equation. Models of single component diffusion and binary diffusion of interacting particles on single-type site lattice and of single component diffusion on complex microporous materials' lattices consisting of two types of sites are derived, as illustrations of the mesoscopic framework. Simplification of the diffusion mesoscopic model illustrates the relation to phenomenological models, such as the Fickian and Maxwell-Stefan transport models. It is demonstrated that the mesoscopic equations are in good agreement with lattice kinetic Monte Carlo simulations for several prototype examples studied.

  11. National Park Service Vegetation Mapping Inventory Program: Natchez Trace Parkway vegetation mapping project report

    USGS Publications Warehouse

    Hop, Kevin D.; Strassman, Andrew C.; Nordman, Carl; Pyne, Milo; White, Rickie; Jakusz, Joseph; Hoy, Erin E.; Dieck, Jennifer

    2016-01-01

    The National Park Service (NPS) Vegetation Mapping Inventory (VMI) Program is an effort to classify, describe, and map existing vegetation of national park units for the NPS Natural Resource Inventory and Monitoring (I&M) Program. The NPS VMI Program is managed by the NPS I&M Division and provides baseline vegetation information to the NPS Natural Resource I&M Program. The U.S. Geological Survey Upper Midwest Environmental Sciences Center, NatureServe, NPS Gulf Coast Network, and NPS Natchez Trace Parkway (NATR; also referred to as Parkway) have completed vegetation classification and mapping of NATR for the NPS VMI Program.Mappers, ecologists, and botanists collaborated to affirm vegetation types within the U.S. National Vegetation Classification (USNVC) of NATR and to determine how best to map them by using aerial imagery. Analyses of data from 589 vegetation plots had been used to describe an initial 99 USNVC associations in the Parkway; this classification work was completed prior to beginning this NATR vegetation mapping project. Data were collected during this project from another eight quick plots to support new vegetation types not previously identified at the Parkway. Data from 120 verification sites were collected to test the field key to vegetation associations and the application of vegetation associations to a sample set of map polygons. Furthermore, data from 900 accuracy assessment (AA) sites were collected (of which 894 were used to test accuracy of the vegetation map layer). The collective of all these datasets resulted in affirming 122 USNVC associations at NATR.To map the vegetation and open water of NATR, 63 map classes were developed. including the following: 54 map classes represent natural (including ruderal) vegetation types in the USNVC, 5 map classes represent cultural (agricultural and developed) vegetation types in the USNVC, 3 map classes represent nonvegetation open-water bodies (non-USNVC), and 1 map class represents landscapes that

  12. Can we trust cancer information on the Internet?--A comparison of interactive cancer risk sites.

    PubMed

    Ekman, Alexandra; Hall, Per; Litton, Jan-Eric

    2005-08-01

    To investigate the prevalence and quality of interactive cancer risk sites on the Internet. A cancer risk site was defined as a website that gave an estimate of the individual risk of developing cancer. Six search engines and one Meta crawler were used to search the Internet for cancer risk sites (including breast, prostate, colon, and lung cancer). A set of defined quality criteria for health related websites was used to evaluate the websites during 2001 and 2002. The number of cancer risk sites, as defined above, increased by 50% between 2001 and 2002. Only two out of 22 cancer risk sites fulfilled the quality criteria adequately. No signs of a change in trend (with regard to the quality criteria met) were noted in January 2005. The overall quality of the documentation on the cancer risk sites was poor and no improvement was seen during the study period. The majority of the cancer risk sites do not give reliable risk estimates.

  13. Comparison of RS/GIS analysis with classic mapping approaches for siting low-yield boreholes for hand pumps in crystalline terrains. An application to rural communities of the Caimbambo province, Angola

    NASA Astrophysics Data System (ADS)

    Martín-Loeches, Miguel; Reyes-López, Jaime; Ramírez-Hernández, Jorge; Temiño-Vela, Javier; Martínez-Santos, Pedro

    2018-02-01

    In poverty-stricken regions of Sub-Saharan Africa, groundwater for supply is often obtained by means of hand pumps, which means that low-yield boreholes are acceptable. However, boreholes are often sited without sufficient hydrogeological information due to budget constraints, which leads to high failure rates. Cost-effective techniques for borehole siting need to be developed in order to maximize the success rate. In regions underlain by granite, weathered formations are usually targeted for drilling, as these are generally presented as a better cost-benefit ratio than the fractured basement. Within this context, this research focuses on a granite region of Angola. A comparison of two mapping techniques for borehole siting-groundwater prospect is presented. A classic hydrogeomorphological map was developed first based on aerial photographs, field mapping and a geophysical survey. This map represents a considerable time investment and was developed by qualified technicians. The second map (RS/GIS) is considerably simpler and more cost-effective. It was developed by the integration in a GIS platform of six maps of equal importance-slope, drainage density, vegetation vigor, presence of clay in the soil, lineaments and rock outcrops-prepared from Landsat 8 imagery and a Digital Elevation Model (DEM). Similar results were obtained in both cases. By means of a supervised classification of Landsat images, RS/GIS analysis allows for the identification of granitic outcrops, house clusters and sandy alluvial valleys. This in turn allows for the delineation of low-interest or contamination-prone areas, thus contributing additional qualitative information. The position of a well that is going to be powered by a handpump is chosen also upon social and local matters as the distance to the stakeholders, information that are not difficult to integrate in the GIS. Although the second map needs some field inputs (i.e. surveys to determine the thickness of the weathered pack

  14. Functional-to-form mapping for assembly design automation

    NASA Astrophysics Data System (ADS)

    Xu, Z. G.; Liu, W. M.; Shen, W. D.; Yang, D. Y.; Liu, T. T.

    2017-11-01

    Assembly-level function-to-form mapping is the most effective procedure towards design automation. The research work mainly includes: the assembly-level function definitions, product network model and the two-step mapping mechanisms. The function-to-form mapping is divided into two steps, i.e. mapping of function-to-behavior, called the first-step mapping, and the second-step mapping, i.e. mapping of behavior-to-structure. After the first step mapping, the three dimensional transmission chain (or 3D sketch) is studied, and the feasible design computing tools are developed. The mapping procedure is relatively easy to be implemented interactively, but, it is quite difficult to finish it automatically. So manual, semi-automatic, automatic and interactive modification of the mapping model are studied. A mechanical hand F-F mapping process is illustrated to verify the design methodologies.

  15. Genetic interaction analysis of point mutations enables interrogation of gene function at a residue-level resolution

    PubMed Central

    Braberg, Hannes; Moehle, Erica A.; Shales, Michael; Guthrie, Christine; Krogan, Nevan J.

    2014-01-01

    We have achieved a residue-level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. PMID:24842270

  16. Genome contact map explorer: a platform for the comparison, interactive visualization and analysis of genome contact maps

    PubMed Central

    Kumar, Rajendra; Sobhy, Haitham

    2017-01-01

    Abstract Hi-C experiments generate data in form of large genome contact maps (Hi-C maps). These show that chromosomes are arranged in a hierarchy of three-dimensional compartments. But to understand how these compartments form and by how much they affect genetic processes such as gene regulation, biologists and bioinformaticians need efficient tools to visualize and analyze Hi-C data. However, this is technically challenging because these maps are big. In this paper, we remedied this problem, partly by implementing an efficient file format and developed the genome contact map explorer platform. Apart from tools to process Hi-C data, such as normalization methods and a programmable interface, we made a graphical interface that let users browse, scroll and zoom Hi-C maps to visually search for patterns in the Hi-C data. In the software, it is also possible to browse several maps simultaneously and plot related genomic data. The software is openly accessible to the scientific community. PMID:28973466

  17. Landslide susceptibility mapping using decision-tree based CHi-squared automatic interaction detection (CHAID) and Logistic regression (LR) integration

    NASA Astrophysics Data System (ADS)

    Althuwaynee, Omar F.; Pradhan, Biswajeet; Ahmad, Noordin

    2014-06-01

    This article uses methodology based on chi-squared automatic interaction detection (CHAID), as a multivariate method that has an automatic classification capacity to analyse large numbers of landslide conditioning factors. This new algorithm was developed to overcome the subjectivity of the manual categorization of scale data of landslide conditioning factors, and to predict rainfall-induced susceptibility map in Kuala Lumpur city and surrounding areas using geographic information system (GIS). The main objective of this article is to use CHi-squared automatic interaction detection (CHAID) method to perform the best classification fit for each conditioning factor, then, combining it with logistic regression (LR). LR model was used to find the corresponding coefficients of best fitting function that assess the optimal terminal nodes. A cluster pattern of landslide locations was extracted in previous study using nearest neighbor index (NNI), which were then used to identify the clustered landslide locations range. Clustered locations were used as model training data with 14 landslide conditioning factors such as; topographic derived parameters, lithology, NDVI, land use and land cover maps. Pearson chi-squared value was used to find the best classification fit between the dependent variable and conditioning factors. Finally the relationship between conditioning factors were assessed and the landslide susceptibility map (LSM) was produced. An area under the curve (AUC) was used to test the model reliability and prediction capability with the training and validation landslide locations respectively. This study proved the efficiency and reliability of decision tree (DT) model in landslide susceptibility mapping. Also it provided a valuable scientific basis for spatial decision making in planning and urban management studies.

  18. Special-Status Plant Species Surveys and Vegetation Mapping at Lawrence Livermore National Laboratory

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

    Preston, R E

    This report presents the results of Jones & Stokes special-status plant surveys and vegetation mapping for the University of California, Lawrence Livermore National Laboratory (LLNL). Special-status plant surveys were conducted at Site 300 in April to May 1997 and in March to April 2002. Eight special-status plants were identified at Site 300: large-flowered fiddleneck, big tarplant, diamond-petaled poppy, round-leaved filaree, gypsum-loving larkspur, California androsace, stinkbells, and hogwallow starfish. Maps identifying the locations of these species, a discussion of the occurrence of these species at Site 300, and a checklist of the flora of Site 300 are presented. A reconnaissance surveymore » of the LLNL Livermore Site was conducted in June 2002. This survey concluded that no special-status plants occur at the Livermore Site. Vegetation mapping was conducted in 2001 at Site 300 to update a previous vegetation study done in 1986. The purpose of the vegetation mapping was to update and to delineate more precisely the boundaries between vegetation types and to map vegetation types that previously were not mapped. The vegetation map is presented with a discussion of the vegetation classification used.« less

  19. WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTION DOMAINS BETWEEN XPG AND WRN

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

    Rangaraj, K.; Cooper, P.K.; Trego, K.S.

    The rapid recognition and repair of DNA damage is essential for the maintenance of genomic integrity and cellular survival. Multiple complex and interconnected DNA damage responses exist within cells to preserve the human genome, and these repair pathways are carried out by a specifi c interplay of protein-protein interactions. Thus a failure in the coordination of these processes, perhaps brought about by a breakdown in any one multifunctional repair protein, can lead to genomic instability, developmental and immunological abnormalities, cancer and premature aging. This study demonstrates a novel interaction between two such repair proteins, Xeroderma pigmentosum group G protein (XPG)more » and Werner syndrome helicase (WRN), that are both highly pleiotropic and associated with inherited genetic disorders when mutated. XPG is a structure-specifi c endonuclease required for the repair of UV-damaged DNA by nucleotide excision repair (NER), and mutations in XPG result in the diseases Xeroderma pigmentosum (XP) and Cockayne syndrome (CS). A loss of XPG incision activity results in XP, whereas a loss of non-enzymatic function(s) of XPG causes CS. WRN is a multifunctional protein involved in double-strand break repair (DSBR), and consists of 3’–5’ DNA-dependent helicase, 3’–5’ exonuclease, and single-strand DNA annealing activities. Nonfunctional WRN protein leads to Werner syndrome, a premature aging disorder with increased cancer incidence. Far Western analysis was used to map the interacting domains between XPG and WRN by denaturing gel electrophoresis, which separated purifi ed full length and recombinant XPG and WRN deletion constructs, based primarily upon the length of each polypeptide. Specifi c interacting domains were visualized when probed with the secondary protein of interest which was then detected by traditional Western analysis using the antibody of the secondary protein. The interaction between XPG and WRN was mapped to the C

  20. Geophysical logging and geologic mapping data in the vicinity of the GMH Electronics Superfund site near Roxboro, North Carolina

    USGS Publications Warehouse

    Chapman, Melinda J.; Clark, Timothy W.; Williams, John H.

    2013-01-01

    Geologic mapping, the collection of borehole geophysical logs and images, and passive diffusion bag sampling were conducted by the U.S. Geological Survey North Carolina Water Science Center in the vicinity of the GMH Electronics Superfund site near Roxboro, North Carolina, during March through October 2011. The study purpose was to assist the U.S. Environmental Protection Agency in the development of a conceptual groundwater model for the assessment of current contaminant distribution and future migration of contaminants. Data compilation efforts included geologic mapping of more than 250 features, including rock type and secondary joints, delineation of more than 1,300 subsurface features (primarily fracture orientations) in 15 open borehole wells, and the collection of passive diffusion-bag samples from 42 fracture zones at various depths in the 15 wells.

  1. Using Concept Maps as Instructional Materials to Foster the Understanding of the Atomic Model and Matter-Energy Interaction

    ERIC Educational Resources Information Center

    Aguiar, Joana G.; Correia, Paulo R. M.

    2016-01-01

    In this paper, we explore the use of concept maps (Cmaps) as instructional materials prepared by teachers, to foster the understanding of chemistry. We choose fireworks as a macroscopic event to teach basic chemical principles related to the Bohr atomic model and matter-energy interaction. During teachers' Cmap navigation, students can experience…

  2. Across-site patterns of modulation detection: Relation to speech recognitiona)

    PubMed Central

    Garadat, Soha N.; Zwolan, Teresa A.; Pfingst, Bryan E.

    2012-01-01

    The aim of this study was to identify across-site patterns of modulation detection thresholds (MDTs) in subjects with cochlear implants and to determine if removal of sites with the poorest MDTs from speech processor programs would result in improved speech recognition. Five hundred millisecond trains of symmetric-biphasic pulses were modulated sinusoidally at 10 Hz and presented at a rate of 900 pps using monopolar stimulation. Subjects were asked to discriminate a modulated pulse train from an unmodulated pulse train for all electrodes in quiet and in the presence of an interleaved unmodulated masker presented on the adjacent site. Across-site patterns of masked MDTs were then used to construct two 10-channel MAPs such that one MAP consisted of sites with the best masked MDTs and the other MAP consisted of sites with the worst masked MDTs. Subjects’ speech recognition skills were compared when they used these two different MAPs. Results showed that MDTs were variable across sites and were elevated in the presence of a masker by various amounts across sites. Better speech recognition was observed when the processor MAP consisted of sites with best masked MDTs, suggesting that temporal modulation sensitivity has important contributions to speech recognition with a cochlear implant. PMID:22559376

  3. Looking for an old map

    USGS Publications Warehouse

    ,

    1996-01-01

    Many people want maps that show an area of the United States as it existed many years ago. These are called historical maps, and there are two types. The most common type consists of special maps prepared by commercial firms to show such historical features as battle-fields, military routes, or the paths taken by famous travelers. Typically, these maps are for sale to tourists at the sites of historical events. The other type is the truly old map--one compiled by a surveyor or cartographer many years ago. Lewis and Clark, for example, made maps of their journeys into the Northwest Territories in 1803-6, and originals of some of these maps still exist.

  4. Genetic Mapping and QTL Analysis of Growth-Related Traits in Pinctada fucata Using Restriction-Site Associated DNA Sequencing

    PubMed Central

    Li, Yaoguo; He, Maoxian

    2014-01-01

    The pearl oyster, Pinctada fucata (P. fucata), is one of the marine bivalves that is predominantly cultured for pearl production. To obtain more genetic information for breeding purposes, we constructed a high-density linkage map of P. fucata and identified quantitative trait loci (QTL) for growth-related traits. One F1 family, which included the two parents, 48 largest progeny and 50 smallest progeny, was sampled to construct a linkage map using restriction site-associated DNA sequencing (RAD-Seq). With low coverage data, 1956.53 million clean reads and 86,342 candidate RAD loci were generated. A total of 1373 segregating SNPs were used to construct a sex-average linkage map. This spanned 1091.81 centimorgans (cM), with 14 linkage groups and an average marker interval of 1.41 cM. The genetic linkage map coverage, Coa, was 97.24%. Thirty-nine QTL-peak loci, for seven growth-related traits, were identified using the single-marker analysis, nonparametric mapping Kruskal-Wallis (KW) test. Parameters included three for shell height, six for shell length, five for shell width, four for hinge length, 11 for total weight, eight for soft tissue weight and two for shell weight. The QTL peak loci for shell height, shell length and shell weight were all located in linkage group 6. The genotype frequencies of most QTL peak loci showed significant differences between the large subpopulation and the small subpopulation (P<0.05). These results highlight the effectiveness of RAD-Seq as a tool for generation of QTL-targeted and genome-wide marker data in the non-model animal, P. fucata, and its possible utility in marker-assisted selection (MAS). PMID:25369421

  5. Engineered bi-histidine metal chelation sites map the structure of the mechanical unfolding transition state of an elastomeric protein domain GB1.

    PubMed

    Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin

    2012-08-22

    Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The φ(M2+)(U)-value is defined as ΔΔG(‡-N)/ΔΔG(U-N), which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG(‡-N)) relative to its thermodynamic stability (ΔG(U-N)) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify φ(M2+)(U)-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1's mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs

  6. Six Landing Sites on Mars

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The landing site chosen for NASA's Phoenix Mars Lander, at about 68 degrees north latitude, is much farther north than the sites where previous spacecraft have landed on Mars.

    Color coding on this map indicates relative elevations based on data from the Mars Orbiter Laser Altimeter on NASA's Mars Global Surveyor. Red is higher elevation; blue is lower elevation. In longitude, the map extends from 70 degrees (north) to minus 70 degrees (south).

  7. Mapping epitopes and antigenicity by site-directed masking

    NASA Astrophysics Data System (ADS)

    Paus, Didrik; Winter, Greg

    2006-06-01

    Here we describe a method for mapping the binding of antibodies to the surface of a folded antigen. We first created a panel of mutant antigens (-lactamase) in which single surface-exposed residues were mutated to cysteine. We then chemically tethered the cysteine residues to a solid phase, thereby masking a surface patch centered on each cysteine residue and blocking the binding of antibodies to this region of the surface. By these means we mapped the epitopes of several mAbs directed to -lactamase. Furthermore, by depleting samples of polyclonal antisera to the masked antigens and measuring the binding of each depleted sample of antisera to unmasked antigen, we mapped the antigenicity of 23 different epitopes. After immunization of mice and rabbits with -lactamase in Freund's adjuvant, we found that the antisera reacted with both native and denatured antigen and that the antibody response was mainly directed to an exposed and flexible loop region of the native antigen. By contrast, after immunization in PBS, we found that the antisera reacted only weakly with denatured antigen and that the antibody response was more evenly distributed over the antigenic surface. We suggest that denatured antigen (created during emulsification in Freund's adjuvant) elicits antibodies that bind mainly to the flexible regions of the native protein and that this explains the correlation between antigenicity and backbone flexibility. Denaturation of antigen during vaccination or natural infections would therefore be expected to focus the antibody response to the flexible loops. backbone flexibility | Freund's adjuvant | conformational epitope | antisera

  8. Identification of residue pairing in interacting β-strands from a predicted residue contact map.

    PubMed

    Mao, Wenzhi; Wang, Tong; Zhang, Wenxuan; Gong, Haipeng

    2018-04-19

    Despite the rapid progress of protein residue contact prediction, predicted residue contact maps frequently contain many errors. However, information of residue pairing in β strands could be extracted from a noisy contact map, due to the presence of characteristic contact patterns in β-β interactions. This information may benefit the tertiary structure prediction of mainly β proteins. In this work, we propose a novel ridge-detection-based β-β contact predictor to identify residue pairing in β strands from any predicted residue contact map. Our algorithm RDb 2 C adopts ridge detection, a well-developed technique in computer image processing, to capture consecutive residue contacts, and then utilizes a novel multi-stage random forest framework to integrate the ridge information and additional features for prediction. Starting from the predicted contact map of CCMpred, RDb 2 C remarkably outperforms all state-of-the-art methods on two conventional test sets of β proteins (BetaSheet916 and BetaSheet1452), and achieves F1-scores of ~ 62% and ~ 76% at the residue level and strand level, respectively. Taking the prediction of the more advanced RaptorX-Contact as input, RDb 2 C achieves impressively higher performance, with F1-scores reaching ~ 76% and ~ 86% at the residue level and strand level, respectively. In a test of structural modeling using the top 1 L predicted contacts as constraints, for 61 mainly β proteins, the average TM-score achieves 0.442 when using the raw RaptorX-Contact prediction, but increases to 0.506 when using the improved prediction by RDb 2 C. Our method can significantly improve the prediction of β-β contacts from any predicted residue contact maps. Prediction results of our algorithm could be directly applied to effectively facilitate the practical structure prediction of mainly β proteins. All source data and codes are available at http://166.111.152.91/Downloads.html or the GitHub address of https://github.com/wzmao/RDb2C .

  9. Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor.

    PubMed

    Wang, Jinti; Yarov-Yarovoy, Vladimir; Kahn, Roy; Gordon, Dalia; Gurevitz, Michael; Scheuer, Todd; Catterall, William A

    2011-09-13

    The α-scorpions toxins bind to the resting state of Na(+) channels and inhibit fast inactivation by interaction with a receptor site formed by domains I and IV. Mutants T1560A, F1610A, and E1613A in domain IV had lower affinities for Leiurus quinquestriatus hebraeus toxin II (LqhII), and mutant E1613R had ~73-fold lower affinity. Toxin dissociation was accelerated by depolarization and increased by these mutations, whereas association rates at negative membrane potentials were not changed. These results indicate that Thr1560 in the S1-S2 loop, Phe1610 in the S3 segment, and Glu1613 in the S3-S4 loop in domain IV participate in toxin binding. T393A in the SS2-S6 loop in domain I also had lower affinity for LqhII, indicating that this extracellular loop may form a secondary component of the receptor site. Analysis with the Rosetta-Membrane algorithm resulted in a model of LqhII binding to the voltage sensor in a resting state, in which amino acid residues in an extracellular cleft formed by the S1-S2 and S3-S4 loops in domain IV interact with two faces of the wedge-shaped LqhII molecule. The conserved gating charges in the S4 segment are in an inward position and form ion pairs with negatively charged amino acid residues in the S2 and S3 segments of the voltage sensor. This model defines the structure of the resting state of a voltage sensor of Na(+) channels and reveals its mode of interaction with a gating modifier toxin.

  10. Analysis of the interactions between GMF and Arp2/3 complex in two binding sites by molecular dynamics simulation.

    PubMed

    Popinako, A; Antonov, M; Dibrova, D; Chemeris, A; Sokolova, O S

    2018-02-05

    The Arp2/3 complex plays a key role in nucleating actin filaments branching. The glia maturation factor (GMF) competes with activators for interacting with the Arp2/3 complex and initiates the debranching of actin filaments. In this study, we performed a comparative analysis of interactions between GMF and the Arp2/3 complex and identified new amino acid residues involved in GMF binding to the Arp2/3 complex at two separate sites, revealed by X-ray and single particle EM techniques. Using molecular dynamics simulations we demonstrated the quantitative and qualitative changes in hydrogen bonds upon binding with GMF. We identified the specific amino acid residues in GMF and Arp2/3 complex that stabilize the interactions and estimated the mean force profile for the GMF using umbrella sampling. Phylogenetic and structural analyses of the recently defined GMF binding site on the Arp3 subunit indicate a new mechanism for Arp2/3 complex inactivation that involves interactions between the Arp2/3 complex and GMF at two binding sites. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Cloud computing for protein-ligand binding site comparison.

    PubMed

    Hung, Che-Lun; Hua, Guan-Jie

    2013-01-01

    The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

  12. Digital geologic map of the Nevada Test Site and vicinity, Nye, Lincoln, and Clark Counties, Nevada, and Inyo County, California

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

    Slate, J.L.; Berry, M.E.; Rowley, P.D.

    2000-03-08

    This digital geologic map of the Nevada Test Site (NTS) and vicinity, as well as its accompanying digital geophysical maps, are compiled at 1:100,000 scale. The map area covers two 30 {times} 60-minute quadrangles-the Pahute Mesa quadrangle to the north and the Beatty quadrangle to the south-plus a strip of 7 1/2-minute quadrangles on the east side. In addition to the NTS, the map area includes the rest of the southwest Nevada volcanic field, part of the Walker Lane, most of the Amargosa Desert, part of the Funeral and Grapevine Mountains, some of Death Valley, and the northern Spring Mountains.more » This geologic map improves on previous geologic mapping of the same area by providing new and updated Quaternary and bedrock geology, new geophysical interpretations of faults beneath the basins, and improved GIS coverages. This publication also includes a new isostatic gravity map and a new aeromagnetic map. The primary purpose of the three maps is to provide an updated geologic framework to aid interpretation of ground-water flow through and off the NTS. The NTS is centrally located within the area of the Death Valley regional ground-water flow system of southwestern Nevada and adjacent California. During the last 40 years, DOE and its predecessor agencies have conducted about 900 nuclear tests on the NTS, of which 100 were atmospheric tests and the rest were underground tests. More than 200 of the tests were detonated at or beneath the water table, which commonly is about 500 to 600 m below the surface. Because contaminants introduced by these test may move into water supplies off the NTS, rates and directions of ground-water flow must be determined. Knowledge about the ground water also is needed to properly appraise potential future effects of the possible nuclear waste repository at Yucca Mountain, adjacent to the NTS.« less

  13. SfiI genomic cleavage map of Escherichia coli K-12 strain MG1655.

    PubMed Central

    Perkins, J D; Heath, J D; Sharma, B R; Weinstock, G M

    1992-01-01

    An SfiI restriction map of Escherichia coli K-12 strain MG1655 is presented. The map contains thirty-one cleavage sites separating fragments ranging in size from 407 kb to 3.7 kb. Several techniques were used in the construction of this map, including CHEF pulsed field gel electrophoresis; physical analysis of a set of twenty-six auxotrophic transposon insertions; correlation with the restriction map of Kohara and coworkers using the commercially available E. coli Gene Mapping Membranes; analysis of publicly available sequence information; and correlation of the above data with the combined genetic and physical map developed by Rudd, et al. The combination of these techniques has yielded a map in which all but one site can be localized within a range of +/- 2 kb, and over half the sites can be localized precisely by sequence data. Two sites present in the EcoSeq5 sequence database are not cleaved in MG1655 and four sites are noted to be sensitive to methylation by the dcm methylase. This map, combined with the NotI physical map of MG1655, can aid in the rapid, precise mapping of several different types of genetic alterations, including transposon mediated mutations and other insertions, inversions, deletions and duplications. Images PMID:1312707

  14. Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.

    PubMed

    Xia, Yitian; Shang, Yuan; Zhang, Rongguang; Zhu, Jinwei

    2017-08-10

    The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-Å resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  15. Use of Bedrock and Geomorphic Mapping Compilations in Assessing Geologic Hazards at Recreation Sites on National Forests in NW California

    NASA Astrophysics Data System (ADS)

    de La Fuente, J. A.; Bell, A.; Elder, D.; Mowery, R.; Mikulovsky, R.; Klingel, H.; Stevens, M.

    2010-12-01

    coverage is a compilation of the best available mapping for all National Forests in California. The geomorphic coverage includes features such as active and dormant landslides, alluvial fans, headwall basins, glacial features, and valley inner gorge. Criteria will be developed which utilize elements of this data to evaluate geologic hazards in the vicinity of developed recreation sites. The second phase will be conducted later and involves site specific analyses focusing on areas identified as higher hazard in the first phase, along with verification and updating of phase 1 findings. The third phase will complete any site level geologic or hydrologic investigations, and wrap up the hazard assessment process. A summary report with hazard maps and recommendations will be prepared at the end of each phase. The overriding goal of this project is to provide sound geologic information to managers so they can use a science-based approach in recognizing and managing geologic hazards at recreation sites.

  16. A Quantitative Chemotherapy Genetic Interaction Map Reveals Factors Associated with PARP Inhibitor Resistance. | Office of Cancer Genomics

    Cancer.gov

    Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy.

  17. GPU-Based Interactive Exploration and Online Probability Maps Calculation for Visualizing Assimilated Ocean Ensembles Data

    NASA Astrophysics Data System (ADS)

    Hoteit, I.; Hollt, T.; Hadwiger, M.; Knio, O. M.; Gopalakrishnan, G.; Zhan, P.

    2016-02-01

    Ocean reanalyses and forecasts are nowadays generated by combining ensemble simulations with data assimilation techniques. Most of these techniques resample the ensemble members after each assimilation cycle. Tracking behavior over time, such as all possible paths of a particle in an ensemble vector field, becomes very difficult, as the number of combinations rises exponentially with the number of assimilation cycles. In general a single possible path is not of interest but only the probabilities that any point in space might be reached by a particle at some point in time. We present an approach using probability-weighted piecewise particle trajectories to allow for interactive probability mapping. This is achieved by binning the domain and splitting up the tracing process into the individual assimilation cycles, so that particles that fall into the same bin after a cycle can be treated as a single particle with a larger probability as input for the next cycle. As a result we loose the possibility to track individual particles, but can create probability maps for any desired seed at interactive rates. The technique is integrated in an interactive visualization system that enables the visual analysis of the particle traces side by side with other forecast variables, such as the sea surface height, and their corresponding behavior over time. By harnessing the power of modern graphics processing units (GPUs) for visualization as well as computation, our system allows the user to browse through the simulation ensembles in real-time, view specific parameter settings or simulation models and move between different spatial or temporal regions without delay. In addition our system provides advanced visualizations to highlight the uncertainty, or show the complete distribution of the simulations at user-defined positions over the complete time series of the domain.

  18. Glossary of Common Site Terms

    MedlinePlus

    ... Maps Downloading Content for Analysis About Site What's New ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking to This Site Terms and ...

  19. A new strategy for developing Vs30 maps

    USGS Publications Warehouse

    Wald, David J.; McWhirter, Leslie; Thompson, Eric; Hering, Amanda S.

    2011-01-01

    Despite obvious limitations as a proxy for site amplification, the use of time-averaged shear-wave velocity over the top 30m (Vs30) is useful and widely practiced, most notably through its use as an explanatory variable in ground motion prediction equations (and thus hazard maps and ShakeMaps, among other applications). Local, regional, and global Vs30 maps thus have diverse and fundamental uses in earthquake and engineering seismology. As such, we are developing an improved strategy for producing Vs30 maps given the common observational constraints available in any region for various spatial scales. We investigate a hierarchical approach to mapping Vs30, where the baseline model is derived from topographic slope because it is available globally, but geological maps and Vs30 observations contribute, where available. Using the abundant measured Vs30 values in Taiwan as an example, we analyze Vs30 versus slope per geologic unit and observe minor trends that indicate potential interaction of geologic and slope terms. We then regress Vs30 for the geologic Vs30 medians, topographic-slope, and cross-term coefficients for a hybrid model. The residuals of this hybrid model still exhibit a strong spatial correlation structure, so we use the kriging-with-a-trend method (the trend is the hybrid model) to further refine the Vs30 map so as to honor the Vs30 observations. Unlike the geology or slope models alone, this strategytakes advantage of the predictive capabilities of the two models, yet effectively defaults to ordinary kriging in the vicinity of the observed data, thereby achieving consistency with the observed data.

  20. Site-occupation embedding theory using Bethe ansatz local density approximations

    NASA Astrophysics Data System (ADS)

    Senjean, Bruno; Nakatani, Naoki; Tsuchiizu, Masahisa; Fromager, Emmanuel

    2018-06-01

    Site-occupation embedding theory (SOET) is an alternative formulation of density functional theory (DFT) for model Hamiltonians where the fully interacting Hubbard problem is mapped, in principle exactly, onto an impurity-interacting (rather than a noninteracting) one. It provides a rigorous framework for combining wave-function (or Green function)-based methods with DFT. In this work, exact expressions for the per-site energy and double occupation of the uniform Hubbard model are derived in the context of SOET. As readily seen from these derivations, the so-called bath contribution to the per-site correlation energy is, in addition to the latter, the key density functional quantity to model in SOET. Various approximations based on Bethe ansatz and perturbative solutions to the Hubbard and single-impurity Anderson models are constructed and tested on a one-dimensional ring. The self-consistent calculation of the embedded impurity wave function has been performed with the density-matrix renormalization group method. It has been shown that promising results are obtained in specific regimes of correlation and density. Possible further developments have been proposed in order to provide reliable embedding functionals and potentials.

  1. Restriction site polymorphism-based candidate gene mapping for seedling drought tolerance in cowpea [Vigna unguiculata (L.) Walp.].

    PubMed

    Muchero, Wellington; Ehlers, Jeffrey D; Roberts, Philip A

    2010-02-01

    Quantitative trait loci (QTL) studies provide insight into the complexity of drought tolerance mechanisms. Molecular markers used in these studies also allow for marker-assisted selection (MAS) in breeding programs, enabling transfer of genetic factors between breeding lines without complete knowledge of their exact nature. However, potential for recombination between markers and target genes limit the utility of MAS-based strategies. Candidate gene mapping offers an alternative solution to identify trait determinants underlying QTL of interest. Here, we used restriction site polymorphisms to investigate co-location of candidate genes with QTL for seedling drought stress-induced premature senescence identified previously in cowpea. Genomic DNA isolated from 113 F(2:8) RILs of drought-tolerant IT93K503-1 and drought susceptible CB46 genotypes was digested with combinations of EcoR1 and HpaII, Mse1, or Msp1 restriction enzymes and amplified with primers designed from 13 drought-responsive cDNAs. JoinMap 3.0 and MapQTL 4.0 software were used to incorporate polymorphic markers onto the AFLP map and to analyze their association with the drought response QTL. Seven markers co-located with peaks of previously identified QTL. Isolation, sequencing, and blast analysis of these markers confirmed their significant homology with drought or other abiotic stress-induced expressed sequence tags (EST) from cowpea and other plant systems. Further, homology with coding sequences for a multidrug resistance protein 3 and a photosystem I assembly protein ycf3 was revealed in two of these candidates. These results provide a platform for the identification and characterization of genetic trait determinants underlying seedling drought tolerance in cowpea.

  2. Calculating Water Thermodynamics in the Binding Site of Proteins - Applications of WaterMap to Drug Discovery.

    PubMed

    Cappel, Daniel; Sherman, Woody; Beuming, Thijs

    2017-01-01

    The ability to accurately characterize the solvation properties (water locations and thermodynamics) of biomolecules is of great importance to drug discovery. While crystallography, NMR, and other experimental techniques can assist in determining the structure of water networks in proteins and protein-ligand complexes, most water molecules are not fully resolved and accurately placed. Furthermore, understanding the energetic effects of solvation and desolvation on binding requires an analysis of the thermodynamic properties of solvent involved in the interaction between ligands and proteins. WaterMap is a molecular dynamics-based computational method that uses statistical mechanics to describe the thermodynamic properties (entropy, enthalpy, and free energy) of water molecules at the surface of proteins. This method can be used to assess the solvent contributions to ligand binding affinity and to guide lead optimization. In this review, we provide a comprehensive summary of published uses of WaterMap, including applications to lead optimization, virtual screening, selectivity analysis, ligand pose prediction, and druggability assessment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Allosteric binding sites in Rab11 for potential drug candidates

    PubMed Central

    2018-01-01

    Rab11 is an important protein subfamily in the RabGTPase family. These proteins physiologically function as key regulators of intracellular membrane trafficking processes. Pathologically, Rab11 proteins are implicated in many diseases including cancers, neurodegenerative diseases and type 2 diabetes. Although they are medically important, no previous study has found Rab11 allosteric binding sites where potential drug candidates can bind to. In this study, by employing multiple clustering approaches integrating principal component analysis, independent component analysis and locally linear embedding, we performed structural analyses of Rab11 and identified eight representative structures. Using these representatives to perform binding site mapping and virtual screening, we identified two novel binding sites in Rab11 and small molecules that can preferentially bind to different conformations of these sites with high affinities. After identifying the binding sites and the residue interaction networks in the representatives, we computationally showed that these binding sites may allosterically regulate Rab11, as these sites communicate with switch 2 region that binds to GTP/GDP. These two allosteric binding sites in Rab11 are also similar to two allosteric pockets in Ras that we discovered previously. PMID:29874286

  4. Using JournalMap to link spatial information with ecological site descriptions

    USDA-ARS?s Scientific Manuscript database

    JournalMap is a scientific literature search engine that empowers you to find relevant research based on location and biophysical variables as well as traditional keyword searches. All publications are geotagged based on reported location information and plotted on a world map showing where the rese...

  5. Geoinquiries: Maps and Data for Everyone

    ERIC Educational Resources Information Center

    Baker, Thomas R.

    2015-01-01

    Ever want to take a quick, deep-dive into a map found in students' textbooks? Ever want to use a web-based map to bring that static, print map to life? Maybe the map would be better with interactive or near real-time data. This article discusses the new Earth Science GeoInquiries! Earth Science GeoInquiries from Esri are instructional resources…

  6. Dynamic prescription maps for site-specific variable rate irrigation of cotton

    USDA-ARS?s Scientific Manuscript database

    A prescription map is a set of instructions that controls a variable rate irrigation (VRI) system. These maps, which may be based on prior yield, soil texture, topography, or soil electrical conductivity data, are often manually applied at the beginning of an irrigation season and remain static. The...

  7. Map Learning with a 3D Printed Interactive Small-Scale Model: Improvement of Space and Text Memorization in Visually Impaired Students.

    PubMed

    Giraud, Stéphanie; Brock, Anke M; Macé, Marc J-M; Jouffrais, Christophe

    2017-01-01

    Special education teachers for visually impaired students rely on tools such as raised-line maps (RLMs) to teach spatial knowledge. These tools do not fully and adequately meet the needs of the teachers because they are long to produce, expensive, and not versatile enough to provide rapid updating of the content. For instance, the same RLM can barely be used during different lessons. In addition, those maps do not provide any interactivity, which reduces students' autonomy. With the emergence of 3D printing and low-cost microcontrollers, it is now easy to design affordable interactive small-scale models (SSMs) which are adapted to the needs of special education teachers. However, no study has previously been conducted to evaluate non-visual learning using interactive SSMs. In collaboration with a specialized teacher, we designed a SSM and a RLM representing the evolution of the geography and history of a fictitious kingdom. The two conditions were compared in a study with 24 visually impaired students regarding the memorization of the spatial layout and historical contents. The study showed that the interactive SSM improved both space and text memorization as compared to the RLM with braille legend. In conclusion, we argue that affordable home-made interactive small scale models can improve learning for visually impaired students. Interestingly, they are adaptable to any teaching situation including students with specific needs.

  8. Map Learning with a 3D Printed Interactive Small-Scale Model: Improvement of Space and Text Memorization in Visually Impaired Students

    PubMed Central

    Giraud, Stéphanie; Brock, Anke M.; Macé, Marc J.-M.; Jouffrais, Christophe

    2017-01-01

    Special education teachers for visually impaired students rely on tools such as raised-line maps (RLMs) to teach spatial knowledge. These tools do not fully and adequately meet the needs of the teachers because they are long to produce, expensive, and not versatile enough to provide rapid updating of the content. For instance, the same RLM can barely be used during different lessons. In addition, those maps do not provide any interactivity, which reduces students’ autonomy. With the emergence of 3D printing and low-cost microcontrollers, it is now easy to design affordable interactive small-scale models (SSMs) which are adapted to the needs of special education teachers. However, no study has previously been conducted to evaluate non-visual learning using interactive SSMs. In collaboration with a specialized teacher, we designed a SSM and a RLM representing the evolution of the geography and history of a fictitious kingdom. The two conditions were compared in a study with 24 visually impaired students regarding the memorization of the spatial layout and historical contents. The study showed that the interactive SSM improved both space and text memorization as compared to the RLM with braille legend. In conclusion, we argue that affordable home-made interactive small scale models can improve learning for visually impaired students. Interestingly, they are adaptable to any teaching situation including students with specific needs. PMID:28649209

  9. Binding Site and Potency Prediction of Teixobactin and other Lipid II Ligands by Statistical Base Scoring of Conformational Space Maps.

    PubMed

    Lungu, Claudiu N; Diudea, Mircea V

    2018-01-01

    Lipid II, a peptidoglycan, is a precursor in bacterial cell synthesis. It has both hydrophilic and lipophilic properties. The molecule translocates a bacterial membrane to deliver and incorporate "building blocks" from disaccharide-pentapeptide into the peptidoglican wall. Lipid II is a valid antibiotic target. A receptor binding pocket may be occupied by a ligand in various plausible conformations, among which only few ones are energetically related to a biological activity in the physiological efficiency domain. This paper reports the mapping of the conformational space of Lipid II in its interaction with Teixobactin and other Lipid II ligands. In order to study computationally the complex between Lipid II and ligands, a docking study was first carried on. Docking site was retrieved form literature. After docking, 5 ligand conformations and further 5 complexes (denoted 00 to 04) for each molecule were taken into account. For each structure, conformational studies were performed. Statistical analysis, conformational analysis and molecular dynamics based clustering were used to predict the potency of these compounds. A score for potency prediction was developed. Appling lipid II classification according to Lipid II conformational energy, a conformation of Teixobactin proved to be energetically favorable, followed by Oritravicin, Dalbavycin, Telvanicin, Teicoplamin and Vancomycin, respectively. Scoring of molecules according to cluster band and PCA produced the same result. Molecules classified according to standard deviations showed Dalbavycin as the most favorable conformation, followed by Teicoplamin, Telvanicin, Teixobactin, Oritravicin and Vancomycin, respectively. Total score showing best energetic efficiency of complex formation shows Teixobactin to have the best conformation (a score of 15 points) followed by Dalbavycin (14 points), Oritravicin (12v points), Telvanicin (10 points), Teicoplamin (9 points), Vancomycin (3 points). Statistical analysis of

  10. Social interaction facilitates word learning in preverbal infants: Word-object mapping and word segmentation.

    PubMed

    Hakuno, Yoko; Omori, Takahide; Yamamoto, Jun-Ichi; Minagawa, Yasuyo

    2017-08-01

    In natural settings, infants learn spoken language with the aid of a caregiver who explicitly provides social signals. Although previous studies have demonstrated that young infants are sensitive to these signals that facilitate language development, the impact of real-life interactions on early word segmentation and word-object mapping remains elusive. We tested whether infants aged 5-6 months and 9-10 months could segment a word from continuous speech and acquire a word-object relation in an ecologically valid setting. In Experiment 1, infants were exposed to a live tutor, while in Experiment 2, another group of infants were exposed to a televised tutor. Results indicate that both younger and older infants were capable of segmenting a word and learning a word-object association only when the stimuli were derived from a live tutor in a natural manner, suggesting that real-life interaction enhances the learning of spoken words in preverbal infants. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Brownfields Road Map

    EPA Pesticide Factsheets

    The Brownfields Road Map publication and companion website provide a general outline of how to assess and clean up a brownfields site and introduce stakeholders to a range of technology options and available resources.

  12. Geomorphic Mapping and Paleoterrain Generation for use in Modeling Holocene (8,000 1,500 yr) Agropastoral Landuse and Landscape Interactions in Southeast Spain

    NASA Astrophysics Data System (ADS)

    Arrowsmith, J. R.; Dimaggio, E. N.; Barton, C. M.; Sarjoughian, H. S.; Fall, P.; Falconer, S. E.; Ullah, I. I.

    2006-12-01

    Dramatic changes in land use were associated with the rise of agriculture in the mid Holocene. Both the surface properties and the drainage networks were changed. Along with the direct modifications to surface properties (vegetation change, sediment liberation, and compaction) and drainage network alteration (terracing, canals), up and downstream responses in the watersheds communicated these changes throughout the landscape. The magnitude, rate, and feedbacks with the growing human populations are critical questions in our effort to assess human-landscape interactions. Our interdisciplinary team has focused on two field sites around the Mediterranean for model development and testing. We are combining high resolution process- based models of landscape change implemented within the GRASS GIS with agent based models of agropastoral behavior and driven by high resolution climate and vegetation models. In the Spanish field area (Penaguila Valley, 38.41 N 0.23 W), we have produced detailed (1:10,000) geomorphic maps which we combine with high resolution Digital Elevation Models (DEMs) on which we can run the surface process models to assess the portions of the landscape that are most sensitive to the postulated agropastoral landuse changes. To support this modeling we have produced the 1 m DEMs from softcopy photogrammetry. This DEM has greatly improved our overall spatial resolution to permit more accurate terrace correlations and improved quantitative assessment of morphologic processes (e.g. channel erosion, slope stability). In stereo, we have mapped overall landscape morphology that emphasizes areas of active erosion and alluvial terrace surfaces. Alluvial terraces are crucial to this research because they record periods of past stable topography and those of mid Holocene age were settled and farmed. We have correlated mapped terraces across the landscape using elevation and morphological distinctions. Using ArcGIS, we interpolated surfaces across equivalent

  13. MC EMiNEM Maps the Interaction Landscape of the Mediator

    PubMed Central

    Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C.; Martin, Dietmar E.; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

    2012-01-01

    The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors. PMID:22737066

  14. MC EMiNEM maps the interaction landscape of the Mediator.

    PubMed

    Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C; Martin, Dietmar E; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

    2012-01-01

    The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

  15. Segmental allotetraploidy and allelic interactions in buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.) as revealed by genome mapping.

    PubMed

    Jessup, R W; Burson, B L; Burow, O; Wang, Y W; Chang, C; Li, Z; Paterson, A H; Hussey, M A

    2003-04-01

    Linkage analyses increasingly complement cytological and traditional plant breeding techniques by providing valuable information regarding genome organization and transmission genetics of complex polyploid species. This study reports a genome map of buffelgrass (Pennisetum ciliare (L.) Link syn. Cenchrus ciliaris L.). Maternal and paternal maps were constructed with restriction fragment length polymorphisms (RFLPs) segregating in 87 F1 progeny from an intraspecific cross between two heterozygous genotypes. A survey of 862 heterologous cDNAs and gDNAs from across the Poaceae, as well as 443 buffelgrass cDNAs, yielded 100 and 360 polymorphic probes, respectively. The maternal map included 322 RFLPs, 47 linkage groups, and 3464 cM, whereas the paternal map contained 245 RFLPs, 42 linkage groups, and 2757 cM. Approximately 70 to 80% of the buffelgrass genome was covered, and the average marker spacing was 10.8 and 11.3 cM on the respective maps. Preferential pairing was indicated between many linkage groups, which supports cytological reports that buffelgrass is a segmental allotetraploid. More preferential pairing (disomy) was found in the maternal than paternal parent across linkage groups (55 vs. 38%) and loci (48 vs. 15%). Comparison of interval lengths in 15 allelic bridges indicated significantly less meiotic recombination in paternal gametes. Allelic interactions were detected in four regions of the maternal map and were absent in the paternal map.

  16. POLYSITE - An interactive package for the selection and refinement of Landsat image training sites

    NASA Technical Reports Server (NTRS)

    Mack, Marilyn J. P.

    1986-01-01

    A versatile multifunction package, POLYSITE, developed for Goddard's Land Analysis System, is described which simplifies the process of interactively selecting and correcting the sites used to study Landsat TM and MSS images. Image switching between the zoomed and nonzoomed image, color and shape cursor change and location display, and bit plane erase or color change, are global functions which are active at all times. Local functions possibly include manipulation of intensive study areas, new site definition, mensuration, and new image copying. The program is illustrated with the example of a full TM maser scene of metropolitan Washington, DC.

  17. Ab initio study of the Coulomb interaction in NbxCo clusters: Strong on-site versus weak nonlocal screening

    NASA Astrophysics Data System (ADS)

    Peters, L.; Şaşıoǧlu, E.; Mertig, I.; Katsnelson, M. I.

    2018-01-01

    By means of ab initio calculations in conjunction with the random-phase approximation (RPA) within the full-potential linearized augmented plane wave method, we study the screening of the Coulomb interaction in NbxCo (1 ≤x ≤9 ) clusters. In addition, these results are compared with pure bcc Nb bulk. We find that for all clusters the on-site Coulomb interaction in RPA is strongly screened, whereas the intersite nonlocal Coulomb interaction is weakly screened and for some clusters it is unscreened or even antiscreened. This is in strong contrast with pure Nb bulk, where the intersite Coulomb interaction is almost completely screened. Furthermore, constrained RPA calculations reveal that the contribution of the Co 3 d → 3 d channel to the total screening of the Co 3 d electrons is small. Moreover, we find that both the on-site and intersite Coulomb interaction parameters decrease in a reasonable approximation linearly with the cluster size and for clusters having more than 20 Nb atoms a transition from 0D to 3D screening is expected to take place.

  18. THREaD Mapper Studio: a novel, visual web server for the estimation of genetic linkage maps

    PubMed Central

    Cheema, Jitender; Ellis, T. H. Noel; Dicks, Jo

    2010-01-01

    The estimation of genetic linkage maps is a key component in plant and animal research, providing both an indication of the genetic structure of an organism and a mechanism for identifying candidate genes associated with traits of interest. Because of this importance, several computational solutions to genetic map estimation exist, mostly implemented as stand-alone software packages. However, the estimation process is often largely hidden from the user. Consequently, problems such as a program crashing may occur that leave a user baffled. THREaD Mapper Studio (http://cbr.jic.ac.uk/threadmapper) is a new web site that implements a novel, visual and interactive method for the estimation of genetic linkage maps from DNA markers. The rationale behind the web site is to make the estimation process as transparent and robust as possible, while also allowing users to use their expert knowledge during analysis. Indeed, the 3D visual nature of the tool allows users to spot features in a data set, such as outlying markers and potential structural rearrangements that could cause problems with the estimation procedure and to account for them in their analysis. Furthermore, THREaD Mapper Studio facilitates the visual comparison of genetic map solutions from third party software, aiding users in developing robust solutions for their data sets. PMID:20494977

  19. Interactive Videodisc Learning Systems.

    ERIC Educational Resources Information Center

    Currier, Richard L.

    1983-01-01

    Discussion of capabilities of interactive videodisc, which combines video images recorded on disc and random-access, highlights interactivity; teaching techniques with videodiscs (including masking, disassembly, movie maps, tactical maps, action code, and simulation); costs; and games. Illustrative material is provided. (High Technology, P. O. Box…

  20. High-Resolution Coarse-Grained Modeling Using Oriented Coarse-Grained Sites.

    PubMed

    Haxton, Thomas K

    2015-03-10

    We introduce a method to bring nearly atomistic resolution to coarse-grained models, and we apply the method to proteins. Using a small number of coarse-grained sites (about one per eight atoms) but assigning an independent three-dimensional orientation to each site, we preferentially integrate out stiff degrees of freedom (bond lengths and angles, as well as dihedral angles in rings) that are accurately approximated by their average values, while retaining soft degrees of freedom (unconstrained dihedral angles) mostly responsible for conformational variability. We demonstrate that our scheme retains nearly atomistic resolution by mapping all experimental protein configurations in the Protein Data Bank onto coarse-grained configurations and then analytically backmapping those configurations back to all-atom configurations. This roundtrip mapping throws away all information associated with the eliminated (stiff) degrees of freedom except for their average values, which we use to construct optimal backmapping functions. Despite the 4:1 reduction in the number of degrees of freedom, we find that heavy atoms move only 0.051 Å on average during the roundtrip mapping, while hydrogens move 0.179 Å on average, an unprecedented combination of efficiency and accuracy among coarse-grained protein models. We discuss the advantages of such a high-resolution model for parametrizing effective interactions and accurately calculating observables through direct or multiscale simulations.

  1. MOLA-Based Landing Site Characterization

    NASA Technical Reports Server (NTRS)

    Duxbury, T. C.; Ivanov, A. B.

    2001-01-01

    The Mars Global Surveyor (MGS) Mars Orbiter Laser Altimeter (MOLA) data provide the basis for site characterization and selection never before possible. The basic MOLA information includes absolute radii, elevation and 1 micrometer albedo with derived datasets including digital image models (DIM's illuminated elevation data), slopes maps and slope statistics and small scale surface roughness maps and statistics. These quantities are useful in downsizing potential sites from descent engineering constraints and landing/roving hazard and mobility assessments. Slope baselines at the few hundred meter level and surface roughness at the 10 meter level are possible. Additionally, the MOLA-derived Mars surface offers the possibility to precisely register and map project other instrument datasets (images, ultraviolet, infrared, radar, etc.) taken at different resolution, viewing and lighting geometry, building multiple layers of an information cube for site characterization and selection. Examples of direct MOLA data, data derived from MOLA and other instruments data registered to MOLA arc given for the Hematite area.

  2. Interactive Mapping of the Planets: An Online Activity Using the Google Earth Platform

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Gilbert, A.; Harrison, T. N.; Mader, M. M.; Shankar, B.; Tornabene, L. L.

    2013-12-01

    With funding from the Natural Sciences and Engineering Research Council of Canada's PromoScience program and support from the Department of Earth Sciences at The University of Western Ontario, the Centre for Planetary Science and Exploration (CPSX) has developed a new web-based initiative called Interactive Mapping of the Planets (IMAPS). Additional components include in person school visits to deliver inquiry-based workshops, week-long summer camps, and pre-prepared impact rock lending kits, all framed around the IMAPS activity. IMAPS will is now in beta testing mode and will be demonstrated in this session. The general objective of the online activity is for participants to plan and design a rover mission to Mars based on a given mission goal - e.g., to find evidence for past water flow. The activity begins with participants receiving image-analysis training to learn about the different landforms on Mars and which ones are potentially caused by water flow. They then need to pass a short test to show they can consistently identify Martian landforms. From there, the participants choose a landing site and plan a traverse - utilizing the free Google Earth plug-in - and taking into account factors such as hazards and their sites of interest. A mission control blog will provide updates on the status of their mission and a 'choose your rover' option provides the opportunity to unlock more advanced rovers by collaborating with other scientists and rating their missions. Indeed, evaluation of missions will be done using a crowd-sourcing method. In addition to being fully accessible online, CPSX will also target primary- and secondary-school grades in which astronomy and space science is taught. Teachers in K-12 classrooms will be able to sign-up for the activity ahead of time in order to receive a workshop package, which will guide them on how to use the IMAPS online activity with their class. Teachers will be able to set up groups for their classroom so that they can

  3. Candidate Mars Surveyor Landing Sites Near Apollinaris Patera

    NASA Astrophysics Data System (ADS)

    Gulick, Virginia C.

    1999-06-01

    Regions near Apollinaris Patera are proposed for consideration as Mars Surveyor landing sites. Gulick (1998) proposed this region at the First Mars Surveyor Landing Site workshop; Bulmer and Gregg (1998) provided additional support. Apollinaris Patera is situated on the highlands/lowlands boundary at 8.5S, 186W. The volcano itself has been mapped as Hesperian in age. The regions surrounding Apollinaris show evidence for volcanism, volcano-ice interactions, and erosion by water. Numerous valleys modified by fluvial processes dissect a large fan structure emanating from the southern flank of the volcano. Sapping valleys have formed along the southern terminus of the fan structure. Regions near Apollinaris Patera provide a unique opportunity to sample outcrop lithologies ranging from highland Noachian basement rocks, to Hesperian aged lava flows, channel and flood plain materials, to Amazonian volcanic, ash and channel deposits.

  4. Candidate Mars Surveyor Landing Sites Near Apollinaris Patera

    NASA Technical Reports Server (NTRS)

    Gulick, Virginia C.

    1999-01-01

    Regions near Apollinaris Patera are proposed for consideration as Mars Surveyor landing sites. Gulick (1998) proposed this region at the First Mars Surveyor Landing Site workshop; Bulmer and Gregg (1998) provided additional support. Apollinaris Patera is situated on the highlands/lowlands boundary at 8.5S, 186W. The volcano itself has been mapped as Hesperian in age. The regions surrounding Apollinaris show evidence for volcanism, volcano-ice interactions, and erosion by water. Numerous valleys modified by fluvial processes dissect a large fan structure emanating from the southern flank of the volcano. Sapping valleys have formed along the southern terminus of the fan structure. Regions near Apollinaris Patera provide a unique opportunity to sample outcrop lithologies ranging from highland Noachian basement rocks, to Hesperian aged lava flows, channel and flood plain materials, to Amazonian volcanic, ash and channel deposits.

  5. Novel Genes Affecting the Interaction between the Cabbage Whitefly and Arabidopsis Uncovered by Genome-Wide Association Mapping

    PubMed Central

    Broekgaarden, Colette; Bucher, Johan; Bac-Molenaar, Johanna; Keurentjes, Joost J. B.; Kruijer, Willem; Voorrips, Roeland E.; Vosman, Ben

    2015-01-01

    Plants have evolved a variety of ways to defend themselves against biotic attackers. This has resulted in the presence of substantial variation in defense mechanisms among plants, even within a species. Genome-wide association (GWA) mapping is a useful tool to study the genetic architecture of traits, but has so far only had limited exploitation in studies of plant defense. Here, we study the genetic architecture of defense against the phloem-feeding insect cabbage whitefly (Aleyrodes proletella) in Arabidopsis thaliana. We determined whitefly performance, i.e. the survival and reproduction of whitefly females, on 360 worldwide selected natural accessions and subsequently performed GWA mapping using 214,051 SNPs. Substantial variation for whitefly adult survival and oviposition rate (number of eggs laid per female per day) was observed between the accessions. We identified 39 candidate SNPs for either whitefly adult survival or oviposition rate, all with relatively small effects, underpinning the complex architecture of defense traits. Among the corresponding candidate genes, i.e. genes in linkage disequilibrium (LD) with candidate SNPs, none have previously been identified as a gene playing a role in the interaction between plants and phloem-feeding insects. Whitefly performance on knock-out mutants of a number of candidate genes was significantly affected, validating the potential of GWA mapping for novel gene discovery in plant-insect interactions. Our results show that GWA analysis is a very useful tool to gain insight into the genetic architecture of plant defense against herbivorous insects, i.e. we identified and validated several genes affecting whitefly performance that have not previously been related to plant defense against herbivorous insects. PMID:26699853

  6. Nonlinear Time Domain Seismic Soil-Structure Interaction (SSI) Deep Soil Site Methodology Development

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

    Spears, Robert Edward; Coleman, Justin Leigh

    Currently the Department of Energy (DOE) and the nuclear industry perform seismic soil-structure interaction (SSI) analysis using equivalent linear numerical analysis tools. For lower levels of ground motion, these tools should produce reasonable in-structure response values for evaluation of existing and new facilities. For larger levels of ground motion these tools likely overestimate the in-structure response (and therefore structural demand) since they do not consider geometric nonlinearities (such as gaping and sliding between the soil and structure) and are limited in the ability to model nonlinear soil behavior. The current equivalent linear SSI (SASSI) analysis approach either joins the soilmore » and structure together in both tension and compression or releases the soil from the structure for both tension and compression. It also makes linear approximations for material nonlinearities and generalizes energy absorption with viscous damping. This produces the potential for inaccurately establishing where the structural concerns exist and/or inaccurately establishing the amplitude of the in-structure responses. Seismic hazard curves at nuclear facilities have continued to increase over the years as more information has been developed on seismic sources (i.e. faults), additional information gathered on seismic events, and additional research performed to determine local site effects. Seismic hazard curves are used to develop design basis earthquakes (DBE) that are used to evaluate nuclear facility response. As the seismic hazard curves increase, the input ground motions (DBE’s) used to numerically evaluation nuclear facility response increase causing larger in-structure response. As ground motions increase so does the importance of including nonlinear effects in numerical SSI models. To include material nonlinearity in the soil and geometric nonlinearity using contact (gaping and sliding) it is necessary to develop a nonlinear time domain methodology

  7. Web GIS in practice V: 3-D interactive and real-time mapping in Second Life

    PubMed Central

    Boulos, Maged N Kamel; Burden, David

    2007-01-01

    This paper describes technologies from Daden Limited for geographically mapping and accessing live news stories/feeds, as well as other real-time, real-world data feeds (e.g., Google Earth KML feeds and GeoRSS feeds) in the 3-D virtual world of Second Life, by plotting and updating the corresponding Earth location points on a globe or some other suitable form (in-world), and further linking those points to relevant information and resources. This approach enables users to visualise, interact with, and even walk or fly through, the plotted data in 3-D. Users can also do the reverse: put pins on a map in the virtual world, and then view the data points on the Web in Google Maps or Google Earth. The technologies presented thus serve as a bridge between mirror worlds like Google Earth and virtual worlds like Second Life. We explore the geo-data display potential of virtual worlds and their likely convergence with mirror worlds in the context of the future 3-D Internet or Metaverse, and reflect on the potential of such technologies and their future possibilities, e.g. their use to develop emergency/public health virtual situation rooms to effectively manage emergencies and disasters in real time. The paper also covers some of the issues associated with these technologies, namely user interface accessibility and individual privacy. PMID:18042275

  8. Integrated platform for genome-wide screening and construction of high-density genetic interaction maps in mammalian cells

    PubMed Central

    Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

    2013-01-01

    A major challenge of the postgenomic era is to understand how human genes function together in normal and disease states. In microorganisms, high-density genetic interaction (GI) maps are a powerful tool to elucidate gene functions and pathways. We have developed an integrated methodology based on pooled shRNA screening in mammalian cells for genome-wide identification of genes with relevant phenotypes and systematic mapping of all GIs among them. We recently demonstrated the potential of this approach in an application to pathways controlling the susceptibility of human cells to the toxin ricin. Here we present the complete quantitative framework underlying our strategy, including experimental design, derivation of quantitative phenotypes from pooled screens, robust identification of hit genes using ultra-complex shRNA libraries, parallel measurement of tens of thousands of GIs from a single double-shRNA experiment, and construction of GI maps. We describe the general applicability of our strategy. Our pooled approach enables rapid screening of the same shRNA library in different cell lines and under different conditions to determine a range of different phenotypes. We illustrate this strategy here for single- and double-shRNA libraries. We compare the roles of genes for susceptibility to ricin and Shiga toxin in different human cell lines and reveal both toxin-specific and cell line-specific pathways. We also present GI maps based on growth and ricin-resistance phenotypes, and we demonstrate how such a comparative GI mapping strategy enables functional dissection of physical complexes and context-dependent pathways. PMID:23739767

  9. LiDAR-Derived Flood-Inundation Maps for Real-Time Flood-Mapping Applications, Tar River Basin, North Carolina

    USGS Publications Warehouse

    Bales, Jerad D.; Wagner, Chad R.; Tighe, Kirsten C.; Terziotti, Silvia

    2007-01-01

    Flood-inundation maps were created for selected streamgage sites in the North Carolina Tar River basin. Light detection and ranging (LiDAR) data with a vertical accuracy of about 20 centimeters, provided by the Floodplain Mapping Information System of the North Carolina Floodplain Mapping Program, were processed to produce topographic data for the inundation maps. Bare-earth mass point LiDAR data were reprocessed into a digital elevation model with regularly spaced 1.5-meter by 1.5-meter cells. A tool was developed as part of this project to connect flow paths, or streams, that were inappropriately disconnected in the digital elevation model by such features as a bridge or road crossing. The Hydraulic Engineering Center-River Analysis System (HEC-RAS) model, developed by the U.S. Army Corps of Engineers, was used for hydraulic modeling at each of the study sites. Eleven individual hydraulic models were developed for the Tar River basin sites. Seven models were developed for reaches with a single gage, and four models were developed for reaches of the Tar River main stem that receive flow from major gaged tributaries, or reaches in which multiple gages were near one another. Combined, the Tar River hydraulic models included 272 kilometers of streams in the basin, including about 162 kilometers on the Tar River main stem. The hydraulic models were calibrated to the most current stage-discharge relations at 11 long-term streamgages where rating curves were available. Medium- to high-flow discharge measurements were made at some of the sites without rating curves, and high-water marks from Hurricanes Fran and Floyd were available for high-stage calibration. Simulated rating curves matched measured curves over the full range of flows. Differences between measured and simulated water levels for a specified flow were no more than 0.44 meter and typically were less. The calibrated models were used to generate a set of water-surface profiles for each of the 11 modeled

  10. Global Transcriptional Start Site Mapping Using Differential RNA Sequencing Reveals Novel Antisense RNAs in Escherichia coli

    PubMed Central

    Thomason, Maureen K.; Bischler, Thorsten; Eisenbart, Sara K.; Förstner, Konrad U.; Zhang, Aixia; Herbig, Alexander; Nieselt, Kay

    2014-01-01

    While the model organism Escherichia coli has been the subject of intense study for decades, the full complement of its RNAs is only now being examined. Here we describe a survey of the E. coli transcriptome carried out using a differential RNA sequencing (dRNA-seq) approach, which can distinguish between primary and processed transcripts, and an automated prediction algorithm for transcriptional start sites (TSS). With the criterion of expression under at least one of three growth conditions examined, we predicted 14,868 TSS candidates, including 5,574 internal to annotated genes (iTSS) and 5,495 TSS corresponding to potential antisense RNAs (asRNAs). We examined expression of 14 candidate asRNAs by Northern analysis using RNA from wild-type E. coli and from strains defective for RNases III and E, two RNases reported to be involved in asRNA processing. Interestingly, nine asRNAs detected as distinct bands by Northern analysis were differentially affected by the rnc and rne mutations. We also compared our asRNA candidates with previously published asRNA annotations from RNA-seq data and discuss the challenges associated with these cross-comparisons. Our global transcriptional start site map represents a valuable resource for identification of transcription start sites, promoters, and novel transcripts in E. coli and is easily accessible, together with the cDNA coverage plots, in an online genome browser. PMID:25266388

  11. University of California San Francisco (UCSF-1): Chemical-Genetic Interaction Mapping Strategy | Office of Cancer Genomics

    Cancer.gov

    The CTD2 Center at University of California San Francisco (UCSF-1) developed a chemical-genetic interaction mapping strategy to uncover the impact of cancer gene expression on responses to a panel of emerging therapeutics. To study the impact of aberrant gene activity in isolation, they developed an isogenic model of triple-negative breast cancer (TNBC) using the hormone receptor negative MCF10A non-tumorigenic cell line derived from healthy breast tissue which is diploid and largely devoid of somatic alterations.

  12. Soils maps supplement to soil moisture ground truth, Lafayette, Indiana, site St. Charles, Missouri, site

    NASA Technical Reports Server (NTRS)

    Jones, E. B.; Olt, S. E.

    1975-01-01

    A compilation of soils information obtained as the result of a library search of data on the Lafayette, Indiana, site and St. Charles, Missouri, site is presented. Soils data for the Lafayette, Indiana, site are shown in Plates 1 and 2; and soils data for the St. Charles, Missouri, site are shown in Plates 3 and 4.

  13. Digital Aeromagnetic Map of the Nevada Test Site and Vicinity, Nye, Lincoln, and Clark Counties, Nevada, and Inyo County, California

    USGS Publications Warehouse

    Ponce, David A.

    2000-01-01

    An aeromagnetic map of the Nevada Test Site area was prepared from publicly available aeromagnetic data described by McCafferty and Grauch (1997). Magnetic surveys were processed using standard techniques. Southwest Nevada is characterized by magnetic anomalies that reflect the distribution of thick sequences of volcanic rocks, magnetic sedimentary rocks, and the occurrence of granitic rocks. In addition, aeromagnetic data reveal the presence of linear features that reflect faulting at both regional and local scales.

  14. Genome Wide Association Mapping of Grain Arsenic, Copper, Molybdenum and Zinc in Rice (Oryza sativa L.) Grown at Four International Field Sites

    PubMed Central

    Norton, Gareth J.; Douglas, Alex; Lahner, Brett; Yakubova, Elena; Guerinot, Mary Lou; Pinson, Shannon R. M.; Tarpley, Lee; Eizenga, Georgia C.; McGrath, Steve P.; Zhao, Fang-Jie; Islam, M. Rafiqul; Islam, Shofiqul; Duan, Guilan; Zhu, Yongguan; Salt, David E.; Meharg, Andrew A.; Price, Adam H.

    2014-01-01

    The mineral concentrations in cereals are important for human health, especially for individuals who consume a cereal subsistence diet. A number of elements, such as zinc, are required within the diet, while some elements are toxic to humans, for example arsenic. In this study we carry out genome-wide association (GWA) mapping of grain concentrations of arsenic, copper, molybdenum and zinc in brown rice using an established rice diversity panel of ∼300 accessions and 36.9 k single nucleotide polymorphisms (SNPs). The study was performed across five environments: one field site in Bangladesh, one in China and two in the US, with one of the US sites repeated over two years. GWA mapping on the whole dataset and on separate subpopulations of rice revealed a large number of loci significantly associated with variation in grain arsenic, copper, molybdenum and zinc. Seventeen of these loci were detected in data obtained from grain cultivated in more than one field location, and six co-localise with previously identified quantitative trait loci. Additionally, a number of candidate genes for the uptake or transport of these elements were located near significantly associated SNPs (within 200 kb, the estimated global linkage disequilibrium previously employed in this rice panel). This analysis highlights a number of genomic regions and candidate genes for further analysis as well as the challenges faced when mapping environmentally-variable traits in a highly genetically structured diversity panel. PMID:24586963

  15. Interactions of divalent cations with calcium binding sites of BK channels reveal independent motions within the gating ring.

    PubMed

    Miranda, Pablo; Giraldez, Teresa; Holmgren, Miguel

    2016-12-06

    Large-conductance voltage- and calcium-activated K + (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca 2+ and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. In contrast to Ca 2+ that binds to both RCK domains, Mg 2+ , Cd 2+ , or Ba 2+ interact preferentially with either one or the other. Interaction of cations with their binding sites causes molecular rearrangements of the gating ring, but how these motions occur remains elusive. We have assessed the separate contributions of each RCK domain to the cation-induced gating-ring structural rearrangements, using patch-clamp fluorometry. Here we show that Mg 2+ and Ba 2+ selectively induce structural movement of the RCK2 domain, whereas Cd 2+ causes motions of RCK1, in all cases substantially smaller than those elicited by Ca 2+ By combining divalent species interacting with unique sites, we demonstrate that RCK1 and RCK2 domains move independently when their specific binding sites are occupied. Moreover, binding of chemically distinct cations to both RCK domains is additive, emulating the effect of fully occupied Ca 2+ binding sites.

  16. ATP and AMP Mutually Influence Their Interaction with the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) at Separate Binding Sites*

    PubMed Central

    Randak, Christoph O.; Dong, Qian; Ver Heul, Amanda R.; Elcock, Adrian H.; Welsh, Michael J.

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel in the ATP-binding cassette (ABC) transporter protein family. In the presence of ATP and physiologically relevant concentrations of AMP, CFTR exhibits adenylate kinase activity (ATP + AMP ⇆ 2 ADP). Previous studies suggested that the interaction of nucleotide triphosphate with CFTR at ATP-binding site 2 is required for this activity. Two other ABC proteins, Rad50 and a structural maintenance of chromosome protein, also have adenylate kinase activity. All three ABC adenylate kinases bind and hydrolyze ATP in the absence of other nucleotides. However, little is known about how an ABC adenylate kinase interacts with ATP and AMP when both are present. Based on data from non-ABC adenylate kinases, we hypothesized that ATP and AMP mutually influence their interaction with CFTR at separate binding sites. We further hypothesized that only one of the two CFTR ATP-binding sites is involved in the adenylate kinase reaction. We found that 8-azidoadenosine 5′-triphosphate (8-N3-ATP) and 8-azidoadenosine 5′-monophosphate (8-N3-AMP) photolabeled separate sites in CFTR. Labeling of the AMP-binding site with 8-N3-AMP required the presence of ATP. Conversely, AMP enhanced photolabeling with 8-N3-ATP at ATP-binding site 2. The adenylate kinase active center probe P1,P5-di(adenosine-5′) pentaphosphate interacted simultaneously with an AMP-binding site and ATP-binding site 2. These results show that ATP and AMP interact with separate binding sites but mutually influence their interaction with the ABC adenylate kinase CFTR. They further indicate that the active center of the adenylate kinase comprises ATP-binding site 2. PMID:23921386

  17. Usability Assessment of the Missouri Cancer Registry's Published Interactive Mapping Reports: Round One.

    PubMed

    Ben Ramadan, Awatef Ahmed; Jackson-Thompson, Jeannette; Schmaltz, Chester Lee

    2017-08-04

     Many users of spatial data have difficulty interpreting information in health-related spatial reports. The Missouri Cancer Registry and Research Center (MCR-ARC) has produced interactive reports for several years. These reports have never been tested for usability.  The aims of this study were to: (1) conduct a multi-approach usability testing study to understand ease of use (user friendliness) and user satisfaction; and (2) evaluate the usability of MCR-ARC's published InstantAtlas reports.   An institutional review board (IRB) approved mixed methodology usability testing study using a convenience sample of health professionals. A recruiting email was sent to faculty in the Master of Public Health program and to faculty and staff in the Department of Health Management and Informatics at the University of Missouri-Columbia. The study included 7 participants. The test included a pretest questionnaire, a multi-task usability test, and the System Usability Scale (SUS). Also, the researchers collected participants' comments about the tested maps immediately after every trial. Software was used to record the computer screen during the trial and the participants' spoken comments. Several performance and usability metrics were measured to evaluate the usability of MCR-ARC's published mapping reports. Of the 10 assigned tasks, 6 reached a 100% completion success rate, and this outcome was relative to the complexity of the tasks. The simple tasks were handled more efficiently than the complicated tasks. The SUS score ranged between 20-100 points, with an average of 62.7 points and a median of 50.5 points. The tested maps' effectiveness outcomes were better than the efficiency and satisfaction outcomes. There was a statistically significant relationship between the subjects' performance on the study test and the users' previous experience with geographic information system (GIS) tools (P=.03). There were no statistically significant relationships between users

  18. Analysis of capsid portal protein and terminase functional domains: interaction sites required for DNA packaging in bacteriophage T4.

    PubMed

    Lin, H; Rao, V B; Black, L W

    1999-06-04

    Bacteriophage DNA packaging results from an ATP-driven translocation of concatemeric DNA into the prohead by the phage terminase complexed with the portal vertex dodecamer of the prohead. Functional domains of the bacteriophage T4 terminase and portal gene 20 product (gp20) were determined by mutant analysis and sequence localization within the structural genes. Interaction regions of the portal vertex and large terminase subunit (gp17) were determined by genetic (terminase-portal intergenic suppressor mutations), biochemical (column retention of gp17 and inhibition of in vitro DNA packaging by gp20 peptides), and immunological (co-immunoprecipitation of polymerized gp20 peptide and gp17) studies. The specificity of the interaction was tested by means of a phage T4 HOC (highly antigenicoutercapsid protein) display system in which wild-type, cs20, and scrambled portal peptide sequences were displayed on the HOC protein of phage T4. Binding affinities of these recombinant phages as determined by the retention of these phages by a His-tag immobilized gp17 column, and by co-immunoprecipitation with purified terminase supported the specific nature of the portal protein and terminase interaction sites. In further support of specificity, a gp20 peptide corresponding to a portion of the identified site inhibited packaging whereas the scrambled sequence peptide did not block DNA packaging in vitro. The portal interaction site is localized to 28 residues in the central portion of the linear sequence of gp20 (524 residues). As judged by two pairs of intergenic portal-terminase suppressor mutations, two separate regions of the terminase large subunit gp17 (central and COOH-terminal) interact through hydrophobic contacts at the portal site. Although the terminase apparently interacts with this gp20 portal peptide, polyclonal antibody against the portal peptide appears unable to access it in the native structure, suggesting intimate association of gp20 and gp17 possibly

  19. Experimental mapping of DNA duplex shape enabled by global lineshape analyses of a nucleotide-independent nitroxide probe

    PubMed Central

    Ding, Yuan; Zhang, Xiaojun; Tham, Kenneth W.; Qin, Peter Z.

    2014-01-01

    Sequence-dependent variation in structure and dynamics of a DNA duplex, collectively referred to as ‘DNA shape’, critically impacts interactions between DNA and proteins. Here, a method based on the technique of site-directed spin labeling was developed to experimentally map shapes of two DNA duplexes that contain response elements of the p53 tumor suppressor. An R5a nitroxide spin label, which was covalently attached at a specific phosphate group, was scanned consecutively through the DNA duplex. X-band continuous-wave electron paramagnetic resonance spectroscopy was used to monitor rotational motions of R5a, which report on DNA structure and dynamics at the labeling site. An approach based on Pearson's coefficient analysis was developed to collectively examine the degree of similarity among the ensemble of R5a spectra. The resulting Pearson's coefficients were used to generate maps representing variation of R5a mobility along the DNA duplex. The R5a mobility maps were found to correlate with maps of certain DNA helical parameters, and were capable of revealing similarity and deviation in the shape of the two closely related DNA duplexes. Collectively, the R5a probe and the Pearson's coefficient-based lineshape analysis scheme yielded a generalizable method for examining sequence-dependent DNA shapes. PMID:25092920

  20. A quantitative chemotherapy genetic interaction map reveals new factors associated with PARP inhibitor resistance | Office of Cancer Genomics

    Cancer.gov

    Nearly every cancer patient is treated with chemotherapy yet our understanding of factors that dictate response and resistance to such agents remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells that charts the impact of knockdown of 625 cancer and DNA repair related genes on sensitivity to 29 drugs, covering all classes of cancer chemotherapeutics.