Science.gov

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. |

  2. Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation.

    PubMed

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

    2015-10-16

    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 Ser(65) 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

  3. 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. PMID:26126123

  4. Site and Watershed Mapping.

    ERIC Educational Resources Information Center

    Institute for Environmental Education, Cleveland, OH.

    Presented as part of a larger unit on watershed investigations are a slideshow script and a map and compass unit intended to help high school students better visualize the relationship between a water sampling site, the entire stream, community, and watershed. The script discusses features of a topographical map, shows how to read one, and…

  5. Site and Watershed Mapping.

    ERIC Educational Resources Information Center

    Institute for Environmental Education, Cleveland, OH.

    Presented as part of a larger unit on watershed investigations are a slideshow script and a map and compass unit intended to help high school students better visualize the relationship between a water sampling site, the entire stream, community, and watershed. The script discusses features of a topographical map, shows how to read one, and

  6. Predicting Interaction Sites from the Energetics of Isolated Proteins: A New Approach to Epitope Mapping

    PubMed Central

    Scarabelli, Guido; Morra, Giulia; Colombo, Giorgio

    2010-01-01

    Abstract An increasing number of functional studies of proteins have shown that sequence and structural similarities alone may not be sufficient for reliable prediction of their interaction properties. This is particularly true for proteins recognizing specific antibodies, where the prediction of antibody-binding sites, called epitopes, has proven challenging. The antibody-binding properties of an antigen depend on its structure and related dynamics. Aiming to predict the antibody-binding regions of a protein, we investigate a new approach based on the integrated analysis of the dynamical and energetic properties of antigens, to identify nonoptimized, low-intensity energetic interaction networks in the protein structure isolated in solution. The method is based on the idea that recognition sites may correspond to localized regions with low-intensity energetic couplings with the rest of the protein, which allows them to undergo conformational changes, to be recognized by a binding partner, and to tolerate mutations with minimal energetic expense. Upon analyzing the results on isolated proteins and benchmarking against antibody complexes, it is found that the method successfully identifies binding sites located on the protein surface that are accessible to putative binding partners. The combination of dynamics and energetics can thus discriminate between epitopes and other substructures based only on physical properties. We discuss implications for vaccine design. PMID:20441761

  7. Native genomic blotting: high-resolution mapping of DNase I-hypersensitive sites and protein-DNA interactions

    SciTech Connect

    Pauli, U.; Chrysogelos, S.; Stein, J.; Stein, G.

    1988-01-01

    DNase I-hypersensitive sites are observed in the promoter regions of actively expressed genes, potentially active genes, and genes that were once active. The authors have developed an approach that greatly increases the resolution for mapping these sites by electrophoresing genomic DNA on native polyacrylamide gels prior to electroblotting and hybridization. This improved method has been used to scan the promoter and coding region of a cell-cycle-dependent human histone H4 gene with an accuracy of +/- 5-10 base pairs. Protein-DNA interactions can be seen in the autoradiograph as light areas and DNase I-hypersensitive sites as dark bands. Therefore, this method provides a rapid and relatively simple means to accurately localize protein-DNA interactions as well as DNase I-hypersensitive sites, thus directly displaying DNase I hypersensitivity and protein-DNA complexes on one autoradiograph. It also potentially allows the analysis of small changes in DNase I-hypersensitive sites under various biological conditions. With this technique rather large regions of DNA can be screened to determine areas that should be analyzed by more sophisticated methods, such as genomic sequencing or gel retardation assays.

  8. Interactive Metro Map Editing.

    PubMed

    Wang, Yu-Shuen; Peng, Wan-Yu

    2016-02-01

    Manual editing of a metro map is essential because many aesthetic and readability demands in map generation cannot be achieved by using a fully automatic method. In addition, a metro map should be updated when new metro lines are developed in a city. Considering that manually designing a metro map is time-consuming and requires expert skills, we present an interactive editing system that considers human knowledge and adjusts the layout to make it consistent with user expectations. In other words, only a few stations are controlled and the remaining stations are relocated by our system. Our system supports both curvilinear and octilinear layouts when creating metro maps. It solves an optimization problem, in which even spaces, route straightness, and maximum included angles at junctions are considered to obtain a curvilinear result. The system then rotates each edge to extend either vertically, horizontally, or diagonally while approximating the station positions provided by users to generate an octilinear layout. Experimental results, quantitative and qualitative evaluations, and user studies show that our editing system is easy to use and allows even non-professionals to design a metro map. PMID:26731455

  9. 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 success rate from different public web mapping sites was calculated and compared, and displayed by the means of diagram. And the answers from questionnaires were also classified and organized in this part. Moreover, based on the analysis, this paper expands the discussion about the layout, map visualization, map tools, search logic and etc. Finally, this paper closed with some valuable guidelines and suggestions for the design of public web mapping sites. Also, limitations for this research stated in the end.

  10. Electron microscopy analysis of the interaction between Escherichia coli DNA-dependent RNA polymerase and the replicative form of phage fd DNA. 1. Mapping of the binding sites.

    PubMed

    Giacomoni, P U; Delain, E; Le Pecq, J B

    1977-08-15

    The interaction of Escherichia coli DNA-dependent RNA polymerase (EC 2.7.7.6) with the replicative form of the DNA from the filamentous coliphage fd cleaved by the restriction endonuclease HindII has been studied by electron microscopy at low and high ionic strength. In the presence of ATP or GTP, and heparin, RNA polymerase binds to fd replicative-form DNA at a few specific sites which have been mapped. The map was oriented so that transcription is from right to left. Three main GTP initiator sites are found at 15%, 82% and 94% of the genome length. One main ATP initiator site is found which cannot be mapped with the same accuracy, and which is localized between 38% and 50%. In the absence of initiator triphosphates and heparin, the binding of the enzyme to fd DNA is much more heterogeneous and therefore the mapping is more difficult. Nevertheless it seems that the preferential binding regions correspond to the specific sites mapped in the presence of GTP or ATP. The mean number of polymerase molecules bound to DNA as a function of the molecular ratio enzyme to DNA present in the mixture has been determined. From these results a binding isotherm can be obtained. The apparent equilibrium constant (K approximately 10(9) M-1) which is derived certainly represents an under-estimated value, as discussed. PMID:334531

  11. Waste Site Mapping

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Old aircraft considered not restorable are melted down in on-site furnaces to reclaim the aluminum in their airframes. The process produces aluminum ingots and leaves a residue known as "dross." Because dross contains contaminants like lead silver cadmium and copper, Pima County, the dross dumping site, wanted to locate areas where dross had been dumped. Dr. Larry Lepley and Sandra L. Perry used the Landsat Thematic Mapper to screen for dross. A special two-step procedure was developed to separate the dross dumps (typically no larger than 50 meters across) from the desert background. The project has opened the door for similar applications.

  12. Mapping leptin-interacting sites in recombinant leptin-binding domain (LBD) subcloned from chicken leptin receptor.

    PubMed

    Niv-Spector, L; Raver, N; Friedman-Einat, M; Grosclaude, J; Gussakovsky, E E; Livnah, O; Gertler, A

    2005-09-01

    The binding domain of the chicken leptin receptor [chLBD (chicken leptin-binding domain)], subcloned from the full-size chicken leptin receptor and prepared in an Escherichia coli system, was subjected to site-directed mutagenesis to identify the amino acids involved in leptin binding. A total of 22 electrophoretically pure, >90% monomer-containing mutants were expressed, refolded and purified. The effects of the mutations were tested by the ability to form complexes with ovine leptin, and the kinetic parameters of interaction were determined by surface plasmon resonance. Six mutants were used to determine whether mutations of several amino acids that differ between chLBD and mammalian LBDs will affect affinity: none showed any such effect, except the mutant A105D (Ala(105)-->Asp), which exhibited some decrease in affinity. Surface plasmon resonance analysis identified six mutants in which binding activity was totally abolished (F73A, Y14A/F73A, V76A/F77A, L78A/L79A, V76A/F77A/L78A/L79A and A105D/D106V) and six mutants (Y14A, R41A, R41A/S42A/K43A, V103A, V135A/F136A and F136A) in which affinity for the hormone was reduced, mainly by increased dissociation rates. Gel-filtration experiments indicated the formation of a 1:1 ovine or human leptin-chLBD complex with a molecular mass of approx. 41 kDa. Gel-filtration experiments yielded 1:1 complexes with those mutants in which affinity had decreased, but not with the six mutants, which had totally lost their binding capacity. Modelling the leptin-chLBD complex indicated that the binding domain of the latter is located mainly in the L3 loop, which contributes nine amino acid residues interacting with leptin. Contact-surface analysis identified the residues having the highest contribution to the recognition site to be Phe73, Phe77 and Leu79. PMID:15842201

  13. 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

  14. Mapping the Interaction Sites between AMPA Receptors and TARPs Reveals a Role for the Receptor N-Terminal Domain in Channel Gating

    PubMed Central

    Cais, Ondrej; Herguedas, Beatriz; Krol, Karolina; Cull-Candy, Stuart G.; Farrant, Mark; Greger, Ingo H.

    2014-01-01

    Summary AMPA-type glutamate receptors (AMPARs) mediate fast neurotransmission at excitatory synapses. The extent and fidelity of postsynaptic depolarization triggered by AMPAR activation are shaped by AMPAR auxiliary subunits, including the transmembrane AMPAR regulatory proteins (TARPs). TARPs profoundly influence gating, an effect thought to be mediated by an interaction with the AMPAR ion channel and ligand binding domain (LBD). Here, we show that the distal N-terminal domain (NTD) contributes to TARP modulation. Alterations in the NTD-LBD linker result in TARP-dependent and TARP-selective changes in AMPAR gating. Using peptide arrays, we identify a TARP interaction region on the NTD and define the path of TARP contacts along the LBD surface. Moreover, we map key binding sites on the TARP itself and show that mutation of these residues mediates gating modulation. Our data reveal a TARP-dependent allosteric role for the AMPAR NTD and suggest that TARP binding triggers a drastic reorganization of the AMPAR complex. PMID:25373908

  15. Mapping the interaction sites between AMPA receptors and TARPs reveals a role for the receptor N-terminal domain in channel gating.

    PubMed

    Cais, Ondrej; Herguedas, Beatriz; Krol, Karolina; Cull-Candy, Stuart G; Farrant, Mark; Greger, Ingo H

    2014-10-23

    AMPA-type glutamate receptors (AMPARs) mediate fast neurotransmission at excitatory synapses. The extent and fidelity of postsynaptic depolarization triggered by AMPAR activation are shaped by AMPAR auxiliary subunits, including the transmembrane AMPAR regulatory proteins (TARPs). TARPs profoundly influence gating, an effect thought to be mediated by an interaction with the AMPAR ion channel and ligand binding domain (LBD). Here, we show that the distal N-terminal domain (NTD) contributes to TARP modulation. Alterations in the NTD-LBD linker result in TARP-dependent and TARP-selective changes in AMPAR gating. Using peptide arrays, we identify a TARP interaction region on the NTD and define the path of TARP contacts along the LBD surface. Moreover, we map key binding sites on the TARP itself and show that mutation of these residues mediates gating modulation. Our data reveal a TARP-dependent allosteric role for the AMPAR NTD and suggest that TARP binding triggers a drastic reorganization of the AMPAR complex. PMID:25373908

  16. 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

  17. Golgi: Interactive Online Brain Mapping.

    PubMed

    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

  18. 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

  19. Mapping NEHRP VS30 site classes

    USGS Publications Warehouse

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

    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.

  20. Site maps and facilities listings

    SciTech Connect

    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 for 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.

  1. 1884, 1889 & 1893 Site Maps Brookland Site Development ...

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

    1884, 1889 & 1893 Site Maps - Brookland Site Development Study, Brookland, bounded by B&O Railroad Tracks, Rhode Island & Brentwood Avenues on the south, 18th Street & South Dakota Avenue on the east, and Michigan Avenue on the North, Washington, District of Columbia, DC

  2. 23. Site plan, 1931 Photocopied from Sanborn Map Company, Insurance ...

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

    23. Site plan, 1931 Photocopied from Sanborn Map Company, Insurance Maps of New Haven, v. 5, map no. 540, 1924 updated to 1931. - Eli Whitney Armory, West of Whitney Avenue, Armory Street Vicinity, Hamden, New Haven County, CT

  3. 24. Site plan, 1924 Photocopied from Sanborn Map Company, Insurance ...

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

    24. Site plan, 1924 Photocopied from Sanborn Map Company, Insurance Maps of New Haven, v. 5, map no. 540, 1924 - Eli Whitney Armory, West of Whitney Avenue, Armory Street Vicinity, Hamden, New Haven County, CT

  4. Mapping of sites in forest stands.

    PubMed

    Netto, Sylvio Péllico; Stefanello, Flavio R; Pelissari, Allan L; David, Hassan C

    2014-12-01

    Generally, the forest companies use the total one year planting area as a minimum stratum of the total population and, consequently, the forest inventory processing has been conducted by applying the stratified random sampling to it. This study was carried out in the National Forest of Tres Barras, Brazil, and it aimed to classify and map the sites of Pinus elliottii stands. A systematic sampling was structured into clusters and applied independently by compartments. The clusters, in maltese cross, were composed of four sampling subunits, using Prodan sampling method with a fixed number of six trees. By analysis of the methodology it was possible to confirm the hypothesis: a) the selective thinning cause expressive increase of volumetric variability within compartments; b) the variation of sites within the compartments causes volumetric expansion of variance and this grows proportionally to the quality of the sites; c) the stratification in sites results in minimum variance within them; d) the stratification in sites resulted in until to 91% reduction of variances within them. PMID:25590737

  5. 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).

  6. 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.

  7. Mapping of a yeast G protein betagamma signaling interaction.

    PubMed Central

    Dowell, S J; Bishop, A L; Dyos, S L; Brown, A J; Whiteway, M S

    1998-01-01

    The mating pathway of Saccharomyces cerevisiae is widely used as a model system for G protein-coupled receptor-mediated signal transduction. Following receptor activation by the binding of mating pheromones, G protein betagamma subunits transmit the signal to a MAP kinase cascade, which involves interaction of Gbeta (Ste4p) with the MAP kinase scaffold protein Ste5p. Here, we identify residues in Ste4p required for the interaction with Ste5p. These residues define a new signaling interface close to the Ste20p binding site within the Gbetagamma coiled-coil. Ste4p mutants defective in the Ste5p interaction interact efficiently with Gpa1p (Galpha) and Ste18p (Ggamma) but cannot function in signal transduction because cells expressing these mutants are sterile. Ste4 L65S is temperature-sensitive for its interaction with Ste5p, and also for signaling. We have identified a Ste5p mutant (L196A) that displays a synthetic interaction defect with Ste4 L65S, providing strong evidence that Ste4p and Ste5p interact directly in vivo through an interface that involves hydrophobic residues. The correlation between disruption of the Ste4p-Ste5p interaction and sterility confirms the importance of this interaction in signal transduction. Identification of the Gbetagamma coiled-coil in Ste5p binding may set a precedent for Gbetagamma-effector interactions in more complex organisms. PMID:9832519

  8. Protein interaction mapping: a Drosophila case study.

    PubMed

    Formstecher, Etienne; Aresta, Sandra; Collura, Vincent; Hamburger, Alexandre; Meil, Alain; Trehin, Alexandra; Reverdy, Céline; Betin, Virginie; Maire, Sophie; Brun, Christine; Jacq, Bernard; Arpin, Monique; Bellaiche, Yohanns; Bellusci, Saverio; Benaroch, Philippe; Bornens, Michel; Chanet, Roland; Chavrier, Philippe; Delattre, Olivier; Doye, Valérie; Fehon, Richard; Faye, Gérard; Galli, Thierry; Girault, Jean-Antoine; Goud, Bruno; de Gunzburg, Jean; Johannes, Ludger; Junier, Marie-Pierre; Mirouse, Vincent; Mukherjee, Ashim; Papadopoulo, Dora; Perez, Franck; Plessis, Anne; Rossé, Carine; Saule, Simon; Stoppa-Lyonnet, Dominique; Vincent, Alain; White, Michael; Legrain, Pierre; Wojcik, Jérôme; Camonis, Jacques; Daviet, Laurent

    2005-03-01

    The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps. PMID:15710747

  9. Protein interaction mapping: A Drosophila case study

    PubMed Central

    Formstecher, Etienne; Aresta, Sandra; Collura, Vincent; Hamburger, Alexandre; Meil, Alain; Trehin, Alexandra; Reverdy, Céline; Betin, Virginie; Maire, Sophie; Brun, Christine; Jacq, Bernard; Arpin, Monique; Bellaiche, Yohanns; Bellusci, Saverio; Benaroch, Philippe; Bornens, Michel; Chanet, Roland; Chavrier, Philippe; Delattre, Olivier; Doye, Valérie; Fehon, Richard; Faye, Gérard; Galli, Thierry; Girault, Jean-Antoine; Goud, Bruno; de Gunzburg, Jean; Johannes, Ludger; Junier, Marie-Pierre; Mirouse, Vincent; Mukherjee, Ashim; Papadopoulo, Dora; Perez, Franck; Plessis, Anne; Rossé, Carine; Saule, Simon; Stoppa-Lyonnet, Dominique; Vincent, Alain; White, Michael; Legrain, Pierre; Wojcik, Jérôme; Camonis, Jacques; Daviet, Laurent

    2005-01-01

    The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps. PMID:15710747

  10. 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. The GSRM map tool will be demonstrated and latest model GSRM 1.1 results, containing important new data for Asia, Iran, western Pacific, and Southern California, will be presented.

  11. Interactive map of movable cultural heritage

    NASA Astrophysics Data System (ADS)

    Moscicka, A.; Marzec, M.

    2010-01-01

    The paper presents the results of a research project connected with using Geographic Information System (GIS) - as a technology and as a tool - to integrate different digital archival collections, present their content in one space and provide on-line access to them from one common level - from an on-line map. Digital archives contain a lot of movable heritage which content has no simple relation to geographic space: manuscripts or old prints can be created in one place, they can describe other places and now they can be stored still in another place. Moreover, each archival object could have been stored in many different places in the past. Presented paper propose the method of creating movable heritage map, based on all geographical places connected with digital collections. The starting point of the study was the international standards for describing digital collections. They provide metadata which are the source of spatial information about archival objects and about spatial, temporal, typological and semantic relations between them. All these aspects were integrated in the GIS and presented as the prototype of an on-line interactive map. Proposed solutions as well as practical applications of the map are presented in the paper.

  12. Beyond billboards: building interactive Web sites.

    PubMed

    Gilbert, J A

    1998-12-01

    More organizations are developing interactive Web sites that go beyond simple billboard-like advertising. These hospitals, integrated delivery systems, physician group practices and managed care organizations are finding that interactive Web sites are helping them improve service for a modest cost. PMID:10187488

  13. Drosophila Protein interaction Map (DPiM)

    PubMed Central

    Guruharsha, K.G.; Obar, Robert A.; Mintseris, Julian; Aishwarya, K.; Krishnan, R.T.; VijayRaghavan, K.; Artavanis-Tsakonas, Spyros

    2012-01-01

    Proteins perform essential cellular functions as part of protein complexes, often in conjunction with RNA, DNA, metabolites and other small molecules. The genome encodes thousands of proteins but not all of them are expressed in every cell type; and expressed proteins are not active at all times. Such diversity of protein expression and function accounts for the level of biological intricacy seen in nature. Defining protein-protein interactions in protein complexes, and establishing the when, what and where of potential interactions, is therefore crucial to understanding the cellular function of any protein—especially those that have not been well studied by traditional molecular genetic approaches. We generated a large-scale resource of affinity-tagged expression-ready clones and used co-affinity purification combined with tandem mass-spectrometry to identify protein partners of nearly 5,000 Drosophila melanogaster proteins. The resulting protein complex “map” provided a blueprint of metazoan protein complex organization. Here we describe how the map has provided valuable insights into protein function in addition to generating hundreds of testable hypotheses. We also discuss recent technological advancements that will be critical in addressing the next generation of questions arising from the map. PMID:23222005

  14. Groundwater maps of the Hanford Site, June 1993

    SciTech Connect

    Kasza, G.L.; Hartman, M.J.; Jordan, W.A.; Weekes, D.C.

    1994-02-01

    The Groundwater Maps of the Hanford Site, June 1993 is an update of the series of reports that document the configuration of the uppermost unconfined aquifer beneath the Hanford Site. This report series presents the semiannual water level measurements taken at site groundwater monitoring wells each June and December and the groundwater maps derived from these measurements. These reports document the changes in the groundwater level at Hanford as the site has transitioned from nuclear material production to environmental restoration and remediation. In addition, these reports provide water level data to support the various site characterization and groundwater monitoring programs currently in progress on the Hanford Site. Groundwater Maps of the Hanford Site are prepared for the US Department of Energy, Office of Environmental Restoration and Waste Management, by the Hanford Site Operations and Engineering Contractor, Westinghouse Hanford Company (WHC). This document fulfills reporting requirements specified in WHC (1993), Section 8.0 {open_quotes}Water Quality{close_quotes} and also described in the Environmental Monitoring Plan for the Hanford Site (DOE-RL 1991). Maps depicting the water table beneath the Hanford Site south of the Columbia River are presented in this report. Appendix A lists the well identification number, depth to water, casing elevating and the water level elevation for each well measured during June 1993. A summary discussion of the data is included with a well index map, the depth to water map and the contoured map of the water table surface for the Hanford Site and each of the three operational areas (the 100, 200, and 300-1100 Areas).

  15. Optimizing landfill site selection by using land classification maps.

    PubMed

    Eskandari, M; Homaee, M; Mahmoodi, S; Pazira, E; Van Genuchten, M Th

    2015-05-01

    Municipal solid waste disposal is a major environmental concern throughout the world. Proper landfill siting involves many environmental, economic, technical, and sociocultural challenges. In this study, a new quantitative method for landfill siting that reduces the number of evaluation criteria, simplifies siting procedures, and enhances the utility of available land evaluation maps was proposed. The method is demonstrated by selecting a suitable landfill site near the city of Marvdasht in Iran. The approach involves two separate stages. First, necessary criteria for preliminary landfill siting using four constraints and eight factors were obtained from a land classification map initially prepared for irrigation purposes. Thereafter, the criteria were standardized using a rating approach and then weighted to obtain a suitability map for landfill siting, with ratings in a 0-1 domain and divided into five suitability classes. Results were almost identical to those obtained with a more traditional environmental landfill siting approach. Because of far fewer evaluation criteria, the proposed weighting method was much easier to implement while producing a more convincing database for landfill siting. The classification map also considered land productivity. In the second stage, the six best alternative sites were evaluated for final landfill siting using four additional criteria. Sensitivity analyses were furthermore conducted to assess the stability of the obtained ranking. Results indicate that the method provides a precise siting procedure that should convince all pertinent stakeholders. PMID:25666474

  16. Coordinate Map of Rocks at Pathfinder Landing Site

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Mars-local-level (LL frame) coordinate map of rocks counted at the Mars Pathfinder landing site. Positions, apparent diameters (D), and heights (H) were measured to the nearest centimeter in the Mars map virtual reality environment constructed from the 'Monster Pan'

  17. A NEHRP Site Class Map for the Island of Hawaii

    NASA Astrophysics Data System (ADS)

    Knudsen, K. L.; Wong, I. G.; Terra, F.

    2008-12-01

    As demonstrated in the 2006 M 6.7 Kiholo Bay earthquake, where some strong motion stations recorded peak horizontal accelerations close to 1g, site response effects can be significant on the Big Island. As part of FEMA-supported studies following the earthquake, we have produced a new 1:100,000-scale map of site conditions for the Big Island of Hawaii. The mapping makes use of about 25 new SASW measurements (Wong et al., 2008) and 1:100,000-scale geologic mapping by Sherrod et al. (2007). An earlier 2006 site class map portrayed nearly all of the island as NEHRP site class B; however, based on about 20 SASW measurements in areas mapped as basalt, we believe that most of the island should be mapped as NEHRP C or D. Vs30 estimates for these basalt sites ranged from 844 to 1,812 ft/sec, spanning NEHRP classes C and D. The median value for these Vs30 estimates is 1,304 ft/sec, with a log mean of 1,274 ft/sec and a standard deviation of 274 ft/sec. The sites cover a range of basaltic rock conditions as depicted on the geologic map, including lava flows, scoria cones, littoral deposits, spatter or tuff cones, cinder cones, and lava domes. Other geologic map unit groups for which only a few Vs30 estimates were made from SASW data include alluvium, ash/tephra, and artificial fill. We assign to these map units NEHRP site class D?, C to E, and C to E, respectively. Geologic deposits for which we do not have quantitative velocity data and have made preliminary site class assignments are sand dunes (D?), landslide deposits (D?), and glacial deposits (D?). We also attempted to relate Vs30 estimates to mapped pedogenic soil units, ages of mapped basalt units, and source volcanoes for basalt units, but found little basis for making these correlations. This new map will be incorporated into ShakeMap and HAZUS, which are operational on the Big Island.

  18. INTERACTIVE NAME PLACEMENT FOR PROVISIONAL MAPS.

    USGS Publications Warehouse

    Goldberg, Jeffrey L.; Miller, Thomas C.

    1983-01-01

    Computer generation and placement of map type has been refined into a production mode at Mid-Continent Mapping Center (MCMC) for USGS 1:24,000- and 1:25,000-scale Provisional maps. The map collar program is written in FORTRAN using batch processing that allows the program to work in the background.

  19. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 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...

  20. 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...

  1. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 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...

  2. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 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...

  3. 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 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...

  4. Groundwater maps of the Hanford Site, June 1994

    SciTech Connect

    Serkowski, J.A.; Jordan, W.A.; Hartman, M.J.

    1994-12-01

    This report is a continuation of reports (Kasza et al., 1994) that document the configuration of the uppermost unconfined aquifer beneath the Hanford Site. This series presents the results of the semiannual water level measurement program and the water table maps generated from these measurements. The reports document the changes in the groundwater level at the Hanford Site during the transition from nuclear material production to environmental restoration and remediation. In addition, these reports provide water level data to support the various site characterization and ground water monitoring programs currently in progress on the Hanford Site. This report highlights the three major operations areas (the 100, 200, and 300/1100 Areas) where wastes were discharged to the soil. Each area includes a summary discussion of the data, a well index map, and a contoured map of the water table surface.

  5. Robotic Mapping of Cultural Heritage Sites

    NASA Astrophysics Data System (ADS)

    Borrmann, D.; Heß, R.; Houshiar, H. R.; Eck, D.; Schilling, K.; Nüchter, A.

    2015-02-01

    In archaeological studies the use of new technologies has moved into focus in the past years creating new challenges such as the processing of the massive amounts of data. In this paper we present steps and processes for smart 3D modelling of environments by use of the mobile robot Irma3D. A robot that is equipped with multiple sensors, most importantly a photo camera and a laser scanner, enables the automation of most of the processes, including data acquisition and registration. The robot was tested in two scenarios, Ostia Antica and the Würzburg Residence. The paper describes the steps for creating 3D color reconstructions of these renown cultural heritage sites.

  6. Groundwater maps of the Hanford Site, December 1993

    SciTech Connect

    Kasza, G.L.; Hartman, M.J.; Jordan, W.A.; Borghese, J.V.

    1994-07-01

    This report is an update to the series of reports that document the configuration of the uppermost unconfined aquifer beneath the Hanford Site. This series presents the latest results of the semiannual water level measurement program and the water table maps generated from these measurements. The reports document the changes in the groundwater level at the Hanford Site during the transition from nuclear material production to environmental restoration and remediation. In addition, these reports provide water level data to support the various site characterization and groundwater monitoring programs currently in progress on the Hanford Site. The three major operations areas (the 100, 200 and 300/1100 Areas) where wastes were discharged to the soil are covered in this update. The water level measurements from the wells in these areas are portrayed on a set of maps to illustrate the hydrologic conditions and are also tabulated in an appendix. A summary discussion of the data is included with the well index map, the depth to water map, and the contoured map of the water table surface for each of the three areas.

  7. 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.

  8. Hanford site Computer Automated Mapping Information System (CAMIS)

    SciTech Connect

    Rush, S.F.

    1995-09-01

    The Computer Automated Mapping Information System (CAMIS) provides sitewide, networked access to CAD based geographically referenced data. CAMIS allows multiple organizations to maintain and share their data. Information collected and managed according to site-wide standards, enables each organization to focus their limited resources on data issues tied to their own discipline without having to collect or manage reference data outside their respective domains. Sharing information also minimizes redundant data and helps improve the overall quality of the sites` data resources.

  9. 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

  10. Geologic mapping as a prerequisite to hazardous waste facility siting

    SciTech Connect

    LaMoreaux, P.E. )

    1993-03-01

    The nation's welfare is based on its capability to develop the mineral, water, and energy resources of the land. In addition, these resources must be developed with adequate consideration of environmental impact and the future welfare of the country. Geologic maps are an absolute necessity in the discovery and development of natural resources; for managing radioactive, toxic, and hazardous wastes; and for the assessment of hazards and risks such as those associated with volcanic action, earthquakes, landslides, and subsidence. Geologic maps are the basis for depicting rocks and rock materials, minerals, coal, oil, and water at or near the earth's surface. Hazardous waste facility projects require the preparation of detailed geologic maps. Throughout most of the USA, this type of mapping detail is not available. If these maps were available, it is estimated that the duration of an individual project could be reduced by at least one-fourth (1/4). Therefore, adequate site-specific mapping is required if one is to eliminate environmental problems associated with hazardous, toxic, radioactive, and municipal waste sites.

  11. S.M.A.R.T. map: Site map attribute retrieval technique

    SciTech Connect

    Brown-Rall, M.

    1995-03-29

    Plant Engineering`s Space and Site Planning (S&SP) organization at Lawrence Livermore National Laboratory (LLNL) has developed a new tool, which is a computerized mapping system that can graphically illustrate facility characteristics. The current ``base`` map being used is the LLNL Site Map prepared by Plant Engineering`s CADD Support group. Using current information in the Facility Information Tracking System (FITS) database, a Microsoft Excel spreadsheet, an electronic sort can be made, tying in the AutoCAD-generated site map to specific database fields. This link is accomplished by using a software overlay called the CadPLUS InfoEngine. The fields in the database include such things as, facility number, occupant program, population, facility age, facility quality, security level, etc. By selecting one or a combination of the fields, a map is generated, illustrating in color and hatch patterns the facilities or entities that are associated with the chosen fields. This process can be very useful for seeing the LLNL site at a glance, with highlighted characteristics for particular areas of interest. The generation of large complex graphics, using large-scale databases selectively, can be accomplished quickly. These extractions and links between data and graphics create a S.M.A.R.T. Map.

  12. Considerations for applying digital soil mapping to ecological sites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  13. Topographic Mapping and Rover Localization in MER 2003 Mission Landing Sites

    NASA Astrophysics Data System (ADS)

    Li, R.; di, K.; Matthies, L.; Maimone, M.; Arvidson, R.; Crumpler, L.; Xu, F.; Wang, J.; Niu, X.; Serafy, C.; Ming, D.; Richter, L.; Marais, D.; Golombek, M.; Squyres, S.; Johnson, J.; Bell, J.; Maki, J.; Malin, M.; Parker, T.; Edwards, L.; Sims, M.; Wang, A.; Garvin, J.; Soderblom, L.

    2004-05-01

    This presentation illustrates results of topographic mapping and rover localization in Spirit and Opportunity landing sites. MOC/NA images, DIMES descent images, and surface Pancam and Navcam images are used to map regional and local topographic features of the landing sites. A new bundle adjustment method builds an image network with improved visual odometric data to supply enhance pointing data that are essential for high accuracy mapping and rover localization. Special 3D mapping products of the crater where Opportunity spacecraft landed are produced first time using rover images acquired from inside of a planetary crater. Traverse maps will show the comparison result of rover positions computed from the rover telemetry data with those from the image-based localization method. Analysis of the differences will be performed considering wheel slippage, IMU drift, and other factors. High quality topographic mapping products such as orthoimage base maps, 3D digital terrain models, and 3D interactive viewing tools are developed to support a series of mission operations and outreach activities, including long term science planning, rover path planning, geological mapping, wheel track property investigation, rock distribution estimation, crater modeling, and TV simulation scenes.

  14. Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping

    PubMed Central

    Agostino, Mark; Yuriev, Elizabeth; Ramsland, Paul A.

    2012-01-01

    Modified gangliosides may be overexpressed in certain types of cancer, thus, they are considered a valuable target in cancer immunotherapy. Structural knowledge of their interaction with antibodies is currently limited, due to the large size and high flexibility of these ligands. In this study, we apply our previously developed site mapping technique to investigate the recognition of cancer-related gangliosides by anti-ganglioside antibodies. The results reveal a potential ganglioside-binding motif in the four antibodies studied, suggesting the possibility of structural convergence in the anti-ganglioside immune response. The structural basis of the recognition of ganglioside-mimetic peptides is also investigated using site mapping and compared to ganglioside recognition. The peptides are shown to act as structural mimics of gangliosides by interacting with many of the same binding site residues as the cognate carbohydrate epitopes. These studies provide important clues as to the structural basis of immunological mimicry of carbohydrates. PMID:22536387

  15. On-Site Semantic Mapping of Archaeological Excavation Areas

    NASA Astrophysics Data System (ADS)

    Houshiar, H.; Borrmann, D.; Elseberg, J.; Nüchter, A.; Näth, F.; Winkle, S.

    2013-07-01

    3D laser scanning is the state of the art in modeling archaeological excavation sites, historical sites and even entire cities or landscapes. The documentation of findings on an excavation site is an essential archaeological task. Automated systems accelerate this process and decrease the amount of error to a minimum. This paper presents a new documentation approach in industrial archaeology. It consists of a set of tools for recording and registering 3D data from excavation sites. We provide an efficient tool for visualization of acquired 3D point clouds in 3D and 2D modes. The main purpose of this software is to provide an easy to use, on-site semantic mapping tool for archaeologists. It includes functions for selecting and labeling findings. Additional information can be provided for each label. This data is exported to an XML format and serves as input for other systems and databases.

  16. Visualising interactive flood risk maps in a dynamic Geobrowser

    NASA Astrophysics Data System (ADS)

    Yaw Manful, Desmond; He, Yi; Cloke, Hannah; Pappenberger, Florian; Li, Zhijia; Wetterhall, Fredrik; Huang, Yingchun; Hu, Yuzhong

    2010-05-01

    Communicating flood forecast products effectively to end-users is the final step in the flood event simulation process. A prototype of the Novel Flood Early Warning System (NEWS) based on the TIGGE (THORPEX Interactive Grand Global Ensemble) database explores new avenues to visualise flood forecast products in a dynamic and interactive manner. One of the possibilities NEWS is currently assessing is Google Maps. Google Maps is a basic web mapping service application and technology provided by Google, free (for non-commercial use). It powers many map-based services including maps embedded on third-party websites via the Google Maps API. Creating a customized map interface requires adding the Google JavaScript code to a page, and then using Javascript functions to add points to the map. Flood maps allow end-users to visualise and navigate a world that is too large and complex to be seen directly. The NEWS software will attempt to deal with the following issues: • Uncertainty visualization in hazards maps • Visualizing uncertainty for sector specific risk managers • Uncertainty representation of point and linear data The objective is improve the information content of flood risk maps making them more useful to specific end-users.

  17. 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.

  18. Mapping Homing Endonuclease Cleavage Sites Using In Vitro Generated Protein

    PubMed Central

    Belfort, Marlene

    2015-01-01

    Mapping the precise position of endonucleolytic cleavage sites is a fundamental experimental technique used to describe the function of a homing endonuclease. However, these proteins are often recalcitrant to cloning and over-expression in biological systems because of toxicity induced by spurious DNA cleavage events. In this chapter we outline the steps to successfully express a homing endonuclease in vitro and use this product in nucleotide-resolution cleavage assays. PMID:24510259

  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. 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.

  1. 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

  2. A proteome-wide protein interaction map for Campylobacter jejuni

    PubMed Central

    Parrish, Jodi R; Yu, Jingkai; Liu, Guozhen; Hines, Julie A; Chan, Jason E; Mangiola, Bernie A; Zhang, Huamei; Pacifico, Svetlana; Fotouhi, Farshad; DiRita, Victor J; Ideker, Trey; Andrews, Phillip; Finley, Russell L

    2007-01-01

    Background Data from large-scale protein interaction screens for humans and model eukaryotes have been invaluable for developing systems-level models of biological processes. Despite this value, only a limited amount of interaction data is available for prokaryotes. Here we report the systematic identification of protein interactions for the bacterium Campylobacter jejuni, a food-borne pathogen and a major cause of gastroenteritis worldwide. Results Using high-throughput yeast two-hybrid screens we detected and reproduced 11,687 interactions. The resulting interaction map includes 80% of the predicted C. jejuni NCTC11168 proteins and places a large number of poorly characterized proteins into networks that provide initial clues about their functions. We used the map to identify a number of conserved subnetworks by comparison to protein networks from Escherichia coli and Saccharomyces cerevisiae. We also demonstrate the value of the interactome data for mapping biological pathways by identifying the C. jejuni chemotaxis pathway. Finally, the interaction map also includes a large subnetwork of putative essential genes that may be used to identify potential new antimicrobial drug targets for C. jejuni and related organisms. Conclusion The C. jejuni protein interaction map is one of the most comprehensive yet determined for a free-living organism and nearly doubles the binary interactions available for the prokaryotic kingdom. This high level of coverage facilitates pathway mapping and function prediction for a large number of C. jejuni proteins as well as orthologous proteins from other organisms. The broad coverage also facilitates cross-species comparisons for the identification of evolutionarily conserved subnetworks of protein interactions. PMID:17615063

  3. Cartographic Mapping of Mars Landing Sites: A Historical Perspective

    NASA Technical Reports Server (NTRS)

    Duxbury, Thomas C.

    2007-01-01

    Initial mapping of Mars began with the early Mariner 4, 6 and 7 flybys in the 1960's. Mariner 9 obtained the first global coverage of Mars in 1971. Viking Orbiters 1 and 2 added new and higher resolution global coverage. The US Geological Survey produced the first digital global cartographic map products in black and white and in color, the mosaicked digital image models (MDIMs). In 1989, the Phobos 88 mission added imaging as well as multispectral mapping of Mars in the equatorial region. The Mars Global Surveyor (MGS) added to the black and white and color global coverage. The most important development for Mars cartography occurred on MGS with its global coverage of Mars using the Mars Observer Laser Altimeter (MOL A) producing precision ground control in latitude, longitude and radius. The next version of the MDIM was produced at 230 m spatial resolution using MOLA precision cartographic control. The Mars Odyssey mission THEMIS instrument has completed its global infrared mapping of Mars at 100 m spatial resolution. The Mars Express mission is completing its global coverage of Mars in stereo at 100 m spatial resolution or better. MGS, Odyssey and Mars Express continue to provide limited surface coverage at the 1 to 20 m resolution. Currently the new Mars Reconnaissance Orbiter is producing images at the 10's of cm level. All of these datasets provide a rich and historic perspective of Mars covering nearly five decades and allow global cartographic map products to be produced in visual and infrared at the 100 m level with specialized cartographic maps being produced for landing sites at the meter or sub-meter spatial resolution level. This work was produced at the Jet Propulsion Laboratory, California Institute of Technology under contract to the National Aeronautics and Space Administration, NAS 7-7120.5d, within the NASA Mars Data Analysis Program and the MGS, Odyssey, Mars Express and MRO Participating Scientist Programs.

  4. Building protein interaction maps for Down's syndrome.

    PubMed

    Gardiner, Katheleen; Davisson, Muriel T; Crnic, Linda S

    2004-08-01

    Now that the complete sequences for human chromosome 21 and the orthologous mouse genomic regions are known, reasonably complete, conserved, protein-coding gene catalogues are also available. The central issue now facing Down's syndrome researchers is the correlation of increased expression of specific, normal, chromosome 21 genes with the development of specific deficits in learning and memory. Because of the number of candidate genes involved, the number of alternative splice variants of individual genes and the number of pathways in which these genes function, a pathway analysis approach will be critical to success. Here, three examples, both gene specific and pathway related, that would benefit from pathway analysis are discussed: (1) the potential roles of eight chromosome 21 proteins in RNA processing pathways; (2) the chromosome 21 protein intersectin 1 and its domain composition, alternative splicing, protein interactions and functions; and (3) the interactions of ten chromosome 21 proteins with components of the mitogen-activated protein kinase and the calcineurin signalling pathways. A productive approach to developing gene-phenotype correlations in Down's syndrome will make use of known and predicted functions and interactions of chromosome 21 genes to predict pathways that may be perturbed by their increased levels of expression. Investigations may then be targeted in animal models to specific interactions, intermediate steps or end-points of such pathways and the downstream - perhaps amplified - consequences of gene dosage directly assessed. Once pathway perturbations have been identified, the potential for rational design of therapeutics becomes practical. PMID:15355596

  5. Site classification map for Tbilisi using seismic prospecting methods

    NASA Astrophysics Data System (ADS)

    Goguadze, Nino; Gventcadze, Aleko; Arabidze, Vakhtang; Tsereteli, Emil; Gaphrindashvili, Giorgi

    2013-04-01

    This aspect deserves major attention since it plays considerable role in the definition of the seismic impact to be considered in the design and retrofitting of structures. The most important parameter of soil maps of seismic site conditions, the shear wave velocity in the upper 30 m section of the ground (VS30) on regional scales are relatively rare since they require substantial investment in geological and geotechnical data acquisition and interpretation. Work presented here was initiated by working package wp5 of regional projects EMME (Earthquake Model for Middle East Region). In the frame of the project geophysical field work were done in some parts of Tbilisi. Seismic prospecting measurements were done along some profiles. In seismic= prospecting RAS-24 was used and obtained data is processed by Winsism V.12 (refraction analysis ). Second version of soil classification for Tbilisi city was done on the basis of new geo-engineering map of 1: 25 000 scales. For this the number of engineering-geological researches and generalization on the territory of Tbilisi were processed, All the Geological and Engineer-geological reports, that were collected and processed. Since in the geological reports less attention is paid to the genesis of the quaternary sediments and their lithological description, and in this regard the territory of Tbilisi is very difficult and multi-spectrum, it was necessary to conduct additional field surveys in 10 districts to specify information. Finely combining information that comes from seismoprospecting measurements and geo-engineering map the new site classification map expressed in Vs30 were derived for Tbilisi city.

  6. 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 resolution GPS, LiDAR and hyperspectral imagery were also acquired. The LiDAR and hyperspectral data are being processed and will be added to the existing geo-referenced database as separate information layers for remote sensing analysis of surface features associated with the legacy test. By consolidating the various components of a VOB data point (coordinates, photo and item description) into a standalone database, searching or querying for other components or collects such as subsurface geophysical and/or airborne imagery is made much easier. Work by Los Alamos National Laboratory was sponsored by the National Nuclear Security Administration Award No. DE-AC52-06NA25946/NST10-NCNS-PD00. Work by National Security Technologies, LLC, was performed under Contract No. DE AC52 06NA25946 with the U.S. Department of Energy.

  7. MotifMap: a human genome-wide map of candidate regulatory motif sites

    PubMed Central

    Xie, Xiaohui; Rigor, Paul; Baldi, Pierre

    2009-01-01

    Motivation: Achieving a comprehensive map of all the regulatory elements encoded in the human genome is a fundamental challenge of biomedical research. So far, only a small fraction of the regulatory elements have been characterized, and there is great interest in applying computational techniques to systematically discover these elements. Such efforts, however, have been significantly hindered by the overwhelming size of non-coding DNA regions and the statistical variability and complex spatial organizations of mammalian regulatory elements. Results: Here we combine information from multiple mammalian genomes to derive the first fairly comprehensive map of regulatory elements in the human genome. We develop a procedure for identifying regulatory sites, with high levels of conservation across different species, using a new scoring scheme, the Bayesian branch length score (BBLS). Using BBLS, we predict 1.5 million regulatory sites, corresponding to 380 known regulatory motifs, with an estimated false discovery rate (FDR) of <50%. We demonstrate that the method is particularly effective for 155 motifs, for which 121 056 sites can be mapped with an estimated FDR of <10%. Over 28K SNPs are located in regions overlapping the 1.5 million predicted motif sites, suggesting potential functional implications for these SNPs. We have deposited these elements in a database and created a user-friendly web server for the retrieval, analysis and visualization of these elements. The initial map provides a systematic view of gene regulation in the genome, which will be refined as additional motifs become available. Availability: http://motifmap.ics.uci.edu Contact: xhx@ics.uci.edu; pfbaldi@ics.uci.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19017655

  8. 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

  9. Epstein–Barr virus and virus human protein interaction maps

    PubMed Central

    Calderwood, Michael A.; Venkatesan, Kavitha; Xing, Li; Chase, Michael R.; Vazquez, Alexei; Holthaus, Amy M.; Ewence, Alexandra E.; Li, Ning; Hirozane-Kishikawa, Tomoko; Hill, David E.; Vidal, Marc; Kieff, Elliott; Johannsen, Eric

    2007-01-01

    A comprehensive mapping of interactions among Epstein–Barr virus (EBV) proteins and interactions of EBV proteins with human proteins should provide specific hypotheses and a broad perspective on EBV strategies for replication and persistence. Interactions of EBV proteins with each other and with human proteins were assessed by using a stringent high-throughput yeast two-hybrid system. Overall, 43 interactions between EBV proteins and 173 interactions between EBV and human proteins were identified. EBV–EBV and EBV–human protein interaction, or “interactome” maps provided a framework for hypotheses of protein function. For example, LF2, an EBV protein of unknown function interacted with the EBV immediate early R transactivator (Rta) and was found to inhibit Rta transactivation. From a broader perspective, EBV genes can be divided into two evolutionary classes, “core” genes, which are conserved across all herpesviruses and subfamily specific, or “noncore” genes. Our EBV–EBV interactome map is enriched for interactions among proteins in the same evolutionary class. Furthermore, human proteins targeted by EBV proteins were enriched for highly connected or “hub” proteins and for proteins with relatively short paths to all other proteins in the human interactome network. Targeting of hubs might be an efficient mechanism for EBV reorganization of cellular processes. PMID:17446270

  10. Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.

    PubMed

    Kalamajski, Sebastian; Bihan, Dominique; Bonna, Arkadiusz; Rubin, Kristofer; Farndale, Richard W

    2016-04-01

    The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites. PMID:26893379

  11. Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase*

    PubMed Central

    Bihan, Dominique; Bonna, Arkadiusz; Rubin, Kristofer; Farndale, Richard W.

    2016-01-01

    The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites. PMID:26893379

  12. Site and Orbit Repeatabilities using Adaptive Mapping Functions

    NASA Astrophysics Data System (ADS)

    Desjardins, Camille; Gegout, Pascal; Soudarin, Laurent; Biancale, Richard; Perosanz, Felix

    2015-04-01

    The electromagnetic signals emitted by the satellite positioning systems travel at the speed of light in a straight line in a vacuum but are modified in their propagation through the neutral atmosphere by temporal and spatial changes of density, and composition and refractivity. These waves are slowed down and their trajectories are bent. This presentation summarizes the performances of the modeling of the tropospheric propagation by the ray tracing technique through the assimilations of the European Meteorological Centre (ECMWF) in the framework of realizing the geodetic reference frame. This goal is achieved by modeling the spatial variability of the propagation using the time variable three-dimensional physical parameters of the atmosphere. The tropospheric delays obtained by ray tracing in all directions throughout the meteorological model surrounding the geodetic site, are fitted by Adaptive Mapping Functions (AMF) parameterized by several tens of coefficients. The delays produced by the Horizon software are then experimented, kept unchanged or adjusted, when recovering a reference frame based on hundred sites using the GINS software. Without any adjustments of the tropospheric modeling, the subcentimetric performances of the AMF are demonstrated by the repeatability of sites positions and GPS satellites orbits. When some AMF coefficients are adjusted, the accuracy of orbits recovery in term of quadratic mean is 7 to 8 millimeters. This limit is imposed by the lack or deficiency of other models, such as non-tidal and tidal loading respectively. Hence the repeatability of the vertical position is not enhanced by changing the propagation model. At the contrary, the repeatability of the horizontal position of geodetic sites is greatly enhanced by accounting for the azimuthal variability provided by the realistic 3D shapes of the Atmosphere and the Earth and the rigorous interpolations of atmospheric parameters included in Adaptive Mapping Functions with respect to the standard approach.

  13. A geostatistical approach to mapping site response spectral amplifications

    USGS Publications Warehouse

    Thompson, E.M.; Baise, L.G.; Kayen, R.E.; Tanaka, Y.; Tanaka, H.

    2010-01-01

    If quantitative estimates of the seismic properties do not exist at a location of interest then the site response spectral amplifications must be estimated from data collected at other locations. Currently, the most common approach employs correlations of site class with maps of surficial geology. Analogously, correlations of site class with topographic slope can be employed where the surficial geology is unknown. Our goal is to identify and validate a method to estimate site response with greater spatial resolution and accuracy for regions where additional effort is warranted. This method consists of three components: region-specific data collection, a spatial model for interpolating seismic properties, and a theoretical method for computing spectral amplifications from the interpolated seismic properties. We consider three spatial interpolation schemes: correlations with surficial geology, termed the geologic trend (GT), ordinary kriging (OK), and kriging with a trend (KT). We estimate the spectral amplifications from seismic properties using the square root of impedance method, thereby linking the frequency-dependent spectral amplifications to the depth-dependent seismic properties. Thus, the range of periods for which this method is applicable is limited by the depth of exploration. A dense survey of near-surface S-wave slowness (Ss) throughout Kobe, Japan shows that the geostatistical methods give more accurate estimates of Ss than the topographic slope and GT methods, and the OK and KT methods perform equally well. We prefer the KT model because it can be seamlessly integrated with geologic maps that cover larger regions. Empirical spectral amplifications show that the region-specific data achieve more accurate estimates of observed median short-period amplifications than the topographic slope method. ?? 2010 Elsevier B.V.

  14. Protein-protein interaction site predictions with three-dimensional probability distributions of interacting atoms on protein surfaces.

    PubMed

    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 the physicochemical complementarity features based on the non-covalent interaction data derived from protein interiors. PMID:22701576

  15. 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 the physicochemical complementarity features based on the non-covalent interaction data derived from protein interiors. PMID:22701576

  16. Galaxy Interactions with FIRE: Mapping Star Formation

    NASA Astrophysics Data System (ADS)

    Moreno, Jorge

    2016-01-01

    We utilize a suite of 75 simulations of galaxies in idealised major mergers (stellar mass ratio ~2.5:1), with a wide range of orbital parameters, to investigate the spatial extent of interaction-induced star formation. Two versions are used, one based on a Kennicult-like subgrid model (Gadget, Springel & Hernquist 2003); the other based on the new Feedback In Realistic Environments model (FIRE, Hopkins et al. 2014). Although the total star formation in galaxy encounters is generally elevated relative to isolated galaxies, we find that this elevation is a combination of intense enhancements within the central kpc and moderately suppressed activity at large galacto-centric radii. This effect appears to be stronger in the older Gadget model. Suppression is the disk is also found in the FIRE runs, but at larger scales. This is because tidal torques are weaker in the newer FIRE model, leading to a more extended nuclear starburt. Our predictions of the radial dependence of triggered star formation, and specifically the suppression of star formation beyond kpc-scales, will be testable with the next generation of integral-field spectroscopic surveys.

  17. 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. PMID:19021113

  18. Interactive Maps from the Great Basin Center for Geothermal Energy

    DOE Data Explorer

    The Great Basin Center for Geothermal Energy, part of the University of Nevada, Reno, conducts research towards the establishment of geothermal energy as an economically viable energy source within the Great Basin. The Center specializes in collecting and synthesizing geologic, geochemical, geodetic, geophysical, and tectonic data, and using Geographic Information System (GIS) technology to view and analyze this data and to produce favorability maps of geothermal potential. The interactive maps are built with layers of spatial data that are also available as direct file downloads (see DDE00299). The maps allow analysis of these many layers, with various data sets turned on or off, for determining potential areas that would be favorable for geothermal drilling or other activity. They provide information on current exploration projects and leases, Bureau of Land Management land status, and map presentation of each type of scientific spatial data: geothermal, geophysical, geologic, geodetic, groundwater, and geochemical.

  19. Tangent map analysis of the beam-beam interaction

    SciTech Connect

    Lee, S.Y.; Tepikian, S.

    1989-01-01

    We studied the tangent map of the beam-beam interaction and found no evidence of beam-beam instability for /epsilon/ = 0.04. Tracking study with tune modulation shows however large emittance growth due to the sum resonances. The emittance growth is due to the multiple crossing of the sum resonances. 12 refs., 7 figs.

  20. Seismic site classification and site period mapping of Chennai City using geophysical and geotechnical data

    NASA Astrophysics Data System (ADS)

    Maheswari, R. Uma; Boominathan, A.; Dodagoudar, G. R.

    2010-11-01

    Subsurface conditions play a major role in the damage potential of earthquakes and the seismic soil amplification of a site which is a critical factor affecting the level of ground shaking. Shear wave velocity ( Vs) of the soil layer is an important parameter influencing the amplification behaviour of the site. Site characterization in calculating seismic hazards is usually based on the near-surface shear wave velocity values. The average shear wave velocity of the top 30 m of the soil, referred to as ( Vs) 30 is commonly adopted by competent building codes to classify the sites for earthquake resistant design of structures and in general it is widely used in microzonation studies. In the present study, the shear wave velocity of soil layers was measured at 30 locations in Chennai City by Multichannel Analysis of Surface Waves (MASW) test. In addition, nearly 300 borehole data were used to estimate Vs based on the correlations between Vs and SPT-N values for Chennai developed by authors earlier. Merging of MASW test results with borehole data yields sufficient coverage of Vs to develop a new site classification map for Chennai based on the NEHRP standard. It is found that part of the city belong to site D category (stiff soil). The developed site period map reveals that the fundamental site period varies in the range of 0.03 to 0.6 s, thus the soil conditions in Chennai pose a potential threat during earthquakes to low rise buildings (less than 6 storeys) which are densely distributed throughout the city.

  1. Imputing and Predicting Quantitative Genetic Interactions in Epistatic MAPs

    PubMed Central

    Ryan, Colm; Cagney, Gerard; Krogan, Nevan; Cunningham, Pádraig; Greene, Derek

    2012-01-01

    Mapping epistatic (or genetic) interactions has emerged as an important network biology approach for establishing functional relationships among genes and proteins. Epistasis networks are complementary to physical protein interaction networks, providing valuable insight into both the function of individual genes and the overall wiring of the cell. A high-throughput method termed “epistatic mini array profiles” (E-MAPs) was recently developed in yeast to quantify alleviating or aggravating interactions between gene pairs. The typical output of an E-MAP experiment is a large symmetric matrix of interaction scores. One problem with this data is the large amount of missing values – interactions that cannot be measured during the high-throughput process or whose measurements were discarded due to quality filtering steps. These missing values can reduce the effectiveness of some data analysis techniques and prevent the use of others. Here, we discuss one solution to this problem, imputation using nearest neighbors, and give practical examples of the use of a freely available implementation of this method. PMID:21877290

  2. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... Considerations 3285.103 Site suitability with design zone maps. Prior to the initial installation of a new... indicated on the design zone maps provided with the home, are suitable for the site location where the...

  3. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... Considerations 3285.103 Site suitability with design zone maps. Prior to the initial installation of a new... indicated on the design zone maps provided with the home, are suitable for the site location where the...

  4. Mapping the sevoflurane-binding sites of calmodulin

    PubMed Central

    Brath, Ulrika; Lau, Kelvin; Van Petegem, Filip; Erdélyi, Máté

    2014-01-01

    General anesthetics, with sevoflurane (SF) being the first choice inhalational anesthetic agent, provide reversible, broad depressor effects on the nervous system yet have a narrow margin of safety. As characterization of low-affinity binding interactions of volatile substances is exceptionally challenging with the existing methods, none of the numerous cellular targets proposed as chief protagonists in anesthesia could yet be confirmed. The recognition that most critical functions modulated by volatile anesthetics are under the control of intracellular Ca2+ concentration, which in turn is primarily regulated by calmodulin (CaM), motivated us for characterization of the SF–CaM interaction. Solution NMR (Nuclear Magnetic Resonance) spectroscopy was used to identify SF-binding sites using chemical shift displacement, NOESY and heteronuclear Overhauser enhancement spectroscopy (HOESY) experiments. Binding affinities were measured using ITC (isothermal titration calorimetry). SF binds to both lobes of (Ca2+)4-CaM with low mmol/L affinity whereas no interaction was observed in the absence of Ca2+. SF does not affect the calcium binding of CaM. The structurally closely related SF and isoflurane are shown to bind to the same clefts. The SF-binding clefts overlap with the binding sites of physiologically relevant ion channels and bioactive small molecules, but the binding affinity suggests it could only interfere with very weak CaM targets. PMID:25505574

  5. MapZ beacons the division sites and positions FtsZ-rings in Streptococcus pneumoniae

    PubMed Central

    Zhao, Chao; Cluzel, Caroline; Lavergne, Jean-Pierre; Franz-Wachtel, Mirita; Macek, Boris; Combet, Christophe; Kuru, Erkin; VanNieuwenhze, Michael S.; Brun, Yves V.; Sherratt, David; Grangeasse, Christophe

    2014-01-01

    In every living organism, cell division requires accurate identification of the division site and placement of the division machinery. In bacteria, this process is traditionally considered to begin with the polymerization of the highly conserved tubulin-like protein FtsZ into a ring that locates precisely at midcell1. Over the last decades, several systems have been reported to regulate the spatiotemporal assembly and placement of the FtsZ-ring2-5. However, the human pathogen Streptococcus pneumoniae, as many other organisms, is devoid of these canonical systems and the mechanisms of positioning of the division machinery remain unknown4,6. Here we characterize a novel factor that locates at the division site before FtsZ and guides septum positioning in the pneumococcus. MapZ (Midcell Anchored Protein Z) forms ring structures at the cell equator and moves apart as the cell elongates, therefore behaving as a permanent beacon of division sites. MapZ then positions the FtsZ-ring through direct protein-protein interactions. MapZ-mediated control differs from previously described systems mostly based on negative regulation of FtsZ assembly. Further, MapZ is an endogenous target of the ser/thr-kinase StkP, which was recently shown to play a central role in cytokinesis and morphogenesis of the pneumococcus7-9. We show that both phosphorylated and non-phosphorylated forms of MapZ are required for proper Z-ring formation and dynamics. Altogether, this work uncovers a new mechanism for bacterial cell division that is regulated by phosphorylation and illustrates that nature has evolved a diversity of cell division mechanisms adapted to the different bacterial clades. PMID:25470041

  6. Value of simulated body surface potential maps as templates in localizing sites of ectopic activation for radiofrequency ablation.

    PubMed

    Hren, R; Horácek, B M

    1997-11-01

    Body surface potential maps recorded during catheter pace mapping can facilitate the localization of the site of origin of ventricular tachycardia. In this study, we investigated the value of a realistic computer model of the human ventricular myocardium in generating body surface potential maps as templates for identifying sites of ectopic activation. Our model features an anatomically accurate geometry and an anisotropy due to transmural fibre rotation, that were reconstructed with a spatial resolution of 0.5 mm. It simulates the electrotonic interactions of cardiac cells by solving a nonlinear parabolic partial differential equation, but it behaves as a cellular automaton when the transmembrane potential exceeds the threshold value. We successfully validated our model by comparing the simulated activation sequences--described by isochronal maps, epicardial potential maps and body surface potential maps--with the measured sequences of epicardial and body surface maps reported in the literature. By systematically pacing the left ventricular and right ventricular endocardial surfaces in our ventricular model, we generated a database of 155 QRS-integral maps, which provides a high-resolution reference frame for localizing distinct endocardial pacing sites. This database promises to be a useful tool in improving the performance of catheter pace mapping used in combination with body surface potential mapping. Overall, the results demonstrate that our computer model of the human ventricular myocardium is well suited for complementing a database of QRS-integral maps obtained during clinical pace mapping and can help enhance the efficacy of the ablative treatment of ventricular arrhythmias. PMID:9413870

  7. Mapping the dipole-dipole interaction among ultracold Rydberg atoms

    NASA Astrophysics Data System (ADS)

    Fahey, Donald P.; Carroll, Thomas J.; Noel, Michael W.

    2014-05-01

    A long-range dipole-dipole interaction couples the atoms in an ultracold Rydberg gas. This can lead to changes in the spatial configuration of states over an extended region. We discuss the use of selective field ionization with a spatially sensitive ion detector to directly map dipole-dipole interaction induced level shifts and energy exchange over large distances in a MOT. Experimental and simulation results will be presented. This material is based upon work supported by the National Science Foundation under Grant No. 1205895.

  8. Magnetic mapping and interpretation of an archaeological site in Syria

    NASA Astrophysics Data System (ADS)

    khatib alkontar, Rozan AL; Munschy, Marc; Castel, Corinne; Quenet, Philippe

    2014-05-01

    Among the subsurface methods of exploration that have been developed to meet the new requirements of archaeological research, geophysical methods offer a very wide range of applications in the study of buried deposits. In their latest developments, the prospecting method based on the measurement of the magnetic field is particularly effective at very different types of sites, ranging from prehistoric times to the most recent. The measured magnetic field observed at a place and at a time, results from the vector sum of the main regional field, the effect of subsurface structures, local disturbances such as power lines, buildings, fences, and the diurnal variation (solar influence). The principle of the magnetic method is, from magnetic measurements on a flat plane above the prospected surface, to study the three-dimensional variations of magnetization producing the magnetic anomalies. The use of magnetic surveys for archaeological prospecting is a well-established and versatile technique, and wide ranges of data processing routines are often applied to further enhance acquired data or derive source parameters. The main purpose of this work was to acquire new magnetic data on the field and to propose quantitative interpretations of magnetic maps obtained on three archaeological sites of Bronze Age in Syria (Badiyah ANR program). More precisely, some results are presented concerning one of the three sites, the Tell Al-Rawda-site which corresponds to a circular city of Early Bronze Age with a radius of about 200 m. Several profiles are used to characterize magnetizations. A large portion of archaeological geophysical data are concerned primarily with identifying the location and spatial extent of buried remains, although the data collected are likely to contain further information relating to the depth and geometry of anomalous features. A simple magnetic model corresponding to rectangular structures uniformly magnetized associated to walls cannot explain the magnetic anomalies. On contrary, the shape of the magnetic anomalies implies to propose magnetized or non-magnetized structures with a width of several meters. To fit completely the shape of the magnetic anomaly, an iterative algorithm is used consisting of modifying the shape of the top of the magnetized layer.

  9. Methods for Mapping of Interaction Networks Involving Membrane Proteins

    SciTech Connect

    Hooker, Brian S.; Bigelow, Diana J.; Lin, Chiann Tso

    2007-11-23

    Numerous approaches have been taken to study protein interactions, such as tagged protein complex isolation followed by mass spectrometry, yeast two-hybrid methods, fluorescence resonance energy transfer, surface plasmon resonance, site-directed mutagenesis, and crystallography. Membrane protein interactions pose significant challenges due to the need to solubilize membranes without disrupting protein-protein interactions. Traditionally, analysis of isolated protein complexes by high-resolution 2D gel electrophoresis has been the main method used to obtain an overall picture of proteome constituents and interactions. However, this method is time consuming, labor intensive, detects only abundant proteins and is not suitable for the coverage required to elucidate large interaction networks. In this review, we discuss the application of various methods to elucidate interactions involving membrane proteins. These techniques include methods for the direct isolation of single complexes or interactors as well as methods for characterization of entire subcellular and cellular interactomes.

  10. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps.

    PubMed

    Chi, Sung Wook; Zang, Julie B; Mele, Aldo; Darnell, Robert B

    2009-07-23

    MicroRNAs (miRNAs) have critical roles in the regulation of gene expression; however, as miRNA activity requires base pairing with only 6-8 nucleotides of messenger RNA, predicting target mRNAs is a major challenge. Recently, high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) has identified functional protein-RNA interaction sites. Here we use HITS-CLIP to covalently crosslink native argonaute (Ago, also called Eif2c) protein-RNA complexes in mouse brain. This produced two simultaneous data sets-Ago-miRNA and Ago-mRNA binding sites-that were combined with bioinformatic analysis to identify interaction sites between miRNA and target mRNA. We validated genome-wide interaction maps for miR-124, and generated additional maps for the 20 most abundant miRNAs present in P13 mouse brain. Ago HITS-CLIP provides a general platform for exploring the specificity and range of miRNA action in vivo, and identifies precise sequences for targeting clinically relevant miRNA-mRNA interactions. PMID:19536157

  11. Mapping protein binding sites on the biomolecular corona of nanoparticles

    NASA Astrophysics Data System (ADS)

    Kelly, Philip M.; Åberg, Christoffer; Polo, Ester; O'Connell, Ann; Cookman, Jennifer; Fallon, Jonathan; Krpetić, Željka; Dawson, Kenneth A.

    2015-05-01

    Nanoparticles in a biological milieu are known to form a sufficiently long-lived and well-organized ‘corona’ of biomolecules to confer a biological identity to the particle. Because this nanoparticle-biomolecule complex interacts with cells and biological barriers, potentially engaging with different biological pathways, it is important to clarify the presentation of functional biomolecular motifs at its interface. Here, we demonstrate that by using antibody-labelled gold nanoparticles, differential centrifugal sedimentation and various imaging techniques it is possible to identify the spatial location of proteins, their functional motifs and their binding sites. We show that for transferrin-coated polystyrene nanoparticles only a minority of adsorbed proteins exhibit functional motifs and the spatial organization appears random, which is consistent, overall, with a stochastic and irreversible adsorption process. Our methods are applicable to a wide array of nanoparticles and can offer a microscopic molecular description of the biological identity of nanoparticles.

  12. A protein interaction map of the LSU processome

    PubMed Central

    McCann, Kathleen L.; Charette, J. Michael; Vincent, Nicholas G.

    2015-01-01

    Maturation of the large ribosomal subunit (LSU) in eukaryotes is a complex and highly coordinated process that requires the concerted action of a large, dynamic, ribonucleoprotein complex, the LSU processome. While we know that >80 ribosome biogenesis factors are required throughout the course of LSU assembly, little is known about how these factors interact with each other within the LSU processome. To interrogate its organization and architecture, we took a systems biology approach and performed a semi-high-throughput, array-based, directed yeast two-hybrid assay. Assaying 4800 protein–protein interactions, we identified 232 high-confidence, binary-interacting protein pairs, representing a fourfold increase from current knowledge. The resulting LSU processome interactome map has enhanced our understanding of the organization and function of the biogenesis factors within the LSU processome, revealing both novel and previously identified subcomplexes and hub proteins, including Nop4. PMID:25877921

  13. Interaction sites of DivIVA and RodA from Corynebacterium glutamicum

    PubMed Central

    Sieger, Boris; Bramkamp, Marc

    2015-01-01

    Elongation growth in actinobacteria is localized at the cell poles. This is in contrast to many classical model organisms where insertion of new cell wall material is localized around the lateral site. We previously described a role of RodA from Corynebacterium glutamicum in apical cell growth and morphogenesis. Deletion of rodA had drastic effects on morphology and growth, likely a result from misregulation of penicillin-binding proteins and cell wall precursor delivery. We identified the interaction of RodA with the polar scaffold protein DivIVA, thus explaining subcellular localization of RodA to the cell poles. In this study, we describe this interaction in detail and map the interaction sites of DivIVA and RodA. A single amino acid residue in the N-terminal domain of DivIVA was found to be crucial for the interaction with RodA. The interaction site of RodA was mapped to its cytoplasmic, C-terminal domain, in a region encompassing the last 10 amino acids (AAs). Deletion of these 10 AAs significantly decreased the interaction efficiency with DivIVA. Our results corroborate the interaction of DivIVA and RodA, underscoring the important role of DivIVA as a spatial organizer of the elongation machinery in Corynebacterineae. PMID:25709601

  14. 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

  15. 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

  16. PTRcombiner: mining combinatorial regulation of gene expression from post-transcriptional interaction maps

    PubMed Central

    2014-01-01

    Background The progress in mapping RNA-protein and RNA-RNA interactions at the transcriptome-wide level paves the way to decipher possible combinatorial patterns embedded in post-transcriptional regulation of gene expression. Results Here we propose an innovative computational tool to extract clusters of mRNA trans-acting co-regulators (RNA binding proteins and non-coding RNAs) from pairwise interaction annotations. In addition the tool allows to analyze the binding site similarity of co-regulators belonging to the same cluster, given their positional binding information. The tool has been tested on experimental collections of human and yeast interactions, identifying modules that coordinate functionally related messages. Conclusions This tool is an original attempt to uncover combinatorial patterns using all the post-transcriptional interaction data available so far. PTRcombiner is available at http://disi.unitn.it/~passerini/software/PTRcombiner/. PMID:24758252

  17. Mapping of lamin A- and progerin-interacting genome regions.

    PubMed

    Kubben, Nard; Adriaens, Michiel; Meuleman, Wouter; Voncken, Jan Willem; van Steensel, Bas; Misteli, Tom

    2012-10-01

    Mutations in the A-type lamins A and C, two major components of the nuclear lamina, cause a large group of phenotypically diverse diseases collectively referred to as laminopathies. These conditions often involve defects in chromatin organization. However, it is unclear whether A-type lamins interact with chromatin in vivo and whether aberrant chromatin-lamin interactions contribute to disease. Here, we have used an unbiased approach to comparatively map genome-wide interactions of gene promoters with lamin A and progerin, the mutated lamin A isoform responsible for the premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS) in mouse cardiac myoytes and embryonic fibroblasts. We find that lamin A-associated genes are predominantly transcriptionally silent and that loss of lamin association leads to the relocation of peripherally localized genes, but not necessarily to their activation. We demonstrate that progerin induces global changes in chromatin organization by enhancing interactions with a specific subset of genes in addition to the identified lamin A-associated genes. These observations demonstrate disease-related changes in higher order genome organization in HGPS and provide novel insights into the role of lamin-chromatin interactions in chromatin organization. PMID:22610065

  18. Genome-wide map of regulatory interactions in the human genome

    PubMed Central

    Heidari, Nastaran; Phanstiel, Douglas H.; He, Chao; Grubert, Fabian; Jahanbani, Fereshteh; Kasowski, Maya; Zhang, Michael Q.

    2014-01-01

    Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer–promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus. PMID:25228660

  19. Genome-wide map of regulatory interactions in the human genome.

    PubMed

    Heidari, Nastaran; Phanstiel, Douglas H; He, Chao; Grubert, Fabian; Jahanbani, Fereshteh; Kasowski, Maya; Zhang, Michael Q; Snyder, Michael P

    2014-12-01

    Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer-promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus. PMID:25228660

  20. 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. PMID:19387483

  1. Synthetic protein interactions reveal a functional map of the cell.

    PubMed

    Berry, Lisa K; Ólafsson, Guðjón; Ledesma-Fernández, Elena; Thorpe, Peter H

    2016-01-01

    To understand the function of eukaryotic cells, it is critical to understand the role of protein-protein interactions and protein localization. Currently, we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations - a key requirement for the evolution of new protein functions. To answer this question, we fused every protein in the yeast Saccharomyces cerevisiae with a partner from each of the major cellular compartments and quantitatively assessed the effects upon growth. This analysis reveals that cells have a remarkable and unanticipated tolerance for forced protein associations, even if these associations lead to a proportion of the protein moving compartments within the cell. Furthermore, the interactions that do perturb growth provide a functional map of spatial protein regulation, identifying key regulatory complexes for the normal homeostasis of eukaryotic cells. PMID:27098839

  2. Synthetic protein interactions reveal a functional map of the cell

    PubMed Central

    Berry, Lisa K; Ólafsson, Guðjón; Ledesma-Fernández, Elena; Thorpe, Peter H

    2016-01-01

    To understand the function of eukaryotic cells, it is critical to understand the role of protein-protein interactions and protein localization. Currently, we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations – a key requirement for the evolution of new protein functions. To answer this question, we fused every protein in the yeast Saccharomyces cerevisiae with a partner from each of the major cellular compartments and quantitatively assessed the effects upon growth. This analysis reveals that cells have a remarkable and unanticipated tolerance for forced protein associations, even if these associations lead to a proportion of the protein moving compartments within the cell. Furthermore, the interactions that do perturb growth provide a functional map of spatial protein regulation, identifying key regulatory complexes for the normal homeostasis of eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.13053.001 PMID:27098839

  3. Cells-gene interactions simulation on a coupled map lattice.

    PubMed

    Bignone, F A

    1993-03-21

    A discontinuous mapping, developed to model gene expression inside cells and cellular interactions on a lattice, is described. Gene dynamics (considered here only as genetic trans regulations) are formulated in a way similar to the Boolean-neural network (BN) approach through a step function, and gene products are supposed to diffuse on a regular discrete lattice of cells, giving rise to nearest neighbour--cellular automata (CA) type--interactions. The time evolution of the model is discrete and synchronous. Despite its simple form the system shows a variegate pattern of behaviour, and certain regions in parameter space show a rich series of bifurcations and multistability already in the case of networks with two genes. The patterns of distribution of the products on the lattice are similar to the ring dynamics observed in CA following Wolfram's formulation and two-dimensional (torus) dynamics described in the Greenberg-Hasting model for excitable media. PMID:8331951

  4. Bayesian hidden Markov models to identify RNA-protein interaction sites in PAR-CLIP.

    PubMed

    Yun, Jonghyun; Wang, Tao; Xiao, Guanghua

    2014-06-01

    The photoactivatable ribonucleoside enhanced cross-linking immunoprecipitation (PAR-CLIP) has been increasingly used for the global mapping of RNA-protein interaction sites. There are two key features of the PAR-CLIP experiments: The sequence read tags are likely to form an enriched peak around each RNA-protein interaction site; and the cross-linking procedure is likely to introduce a specific mutation in each sequence read tag at the interaction site. Several ad hoc methods have been developed to identify the RNA-protein interaction sites using either sequence read counts or mutation counts alone; however, rigorous statistical methods for analyzing PAR-CLIP are still lacking. In this article, we propose an integrative model to establish a joint distribution of observed read and mutation counts. To pinpoint the interaction sites at single base-pair resolution, we developed a novel modeling approach that adopts non-homogeneous hidden Markov models to incorporate the nucleotide sequence at each genomic location. Both simulation studies and data application showed that our method outperforms the ad hoc methods, and provides reliable inferences for the RNA-protein binding sites from PAR-CLIP data. PMID:24571656

  5. Unambiguous Identification of miRNA:target site Interactions by Different Types of Ligation Reactions

    PubMed Central

    Manzano, Mark; Klironomos, Filippos; Schilling, Marcel; Herzog, Margareta; Gottwein, Eva; Rajewsky, Nikolaus

    2014-01-01

    SUMMARY To exert regulatory function, miRNAs guide Argonaute (AGO) proteins to partially complementary sites on target RNAs. Crosslinking and immunoprecipitation (“CLIP”) assays are state-of-the-art to map AGO binding sites, but assigning the targeting miRNA to these sites relies on bioinformatics predictions and is therefore indirect. To directly and unambiguously identify miRNA:target site interactions, we modified our CLIP methodology in C. elegans to experimentally ligate miRNAs to their target sites. Unexpectedly, ligation reactions also occurred in absence of the exogenous ligase. Our in vivo dataset and re-analysis of published mammalian AGO-CLIP data for miRNA-chimeras yielded ~17,000 miRNA:target site interactions. Analysis of interactions and extensive experimental validation of chimera-discovered targets of viral miRNAs suggest that our strategy identifies canonical, noncanonical, and nonconserved miRNA interactions. Our data suggest that ~80% of miRNA interactions have perfect or partial seed complementarity. In summary, analysis of miRNA:target chimeras enables the systematic, context-specific, in vivo discovery of miRNA binding. PMID:24857550

  6. Dissection of DNA damage responses using multiconditional genetic interaction maps.

    PubMed

    Gunol, Aude; Srivas, Rohith; Vreeken, Kees; Wang, Ze Zhong; Wang, Shuyi; Krogan, Nevan J; Ideker, Trey; van Attikum, Haico

    2013-01-24

    To protect the genome, cells have evolved a diverse set of pathways designed to sense, signal, and repair multiple types of DNA damage. To assess the degree of coordination and crosstalk among these pathways, we systematically mapped changes in the cell's genetic network across a panel of different DNA-damaging agents, resulting in ~1,800,000 differential measurements. Each agent was associated with a distinct interaction pattern, which, unlike single-mutant phenotypes or gene expression data, has high statistical power to pinpoint the specific repair mechanisms at work. The agent-specific networks revealed roles for the histone acetyltranferase Rtt109 in the mutagenic bypass of DNA lesions and the neddylation machinery in cell-cycle regulation and genome stability, while the network induced by multiple agents implicates Irc21, an uncharacterized protein, in checkpoint control and DNA repair. Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways. PMID:23273983

  7. Dissection of DNA Damage Responses Using Multiconditional Genetic Interaction Maps

    PubMed Central

    Guénolé, Aude; Srivas, Rohith; Vreeken, Kees; Wang, Ze Zhong; Wang, Shuyi; Krogan, Nevan J.; Ideker, Trey; van Attikum, Haico

    2013-01-01

    SUMMARY To protect the genome, cells have evolved a diverse set of pathways designed to sense, signal, and repair multiple types of DNA damage. To assess the degree of coordination and crosstalk among these pathways, we systematically mapped changes in the cell's genetic network across a panel of different DNA-damaging agents, resulting in ~1,800,000 differential measurements. Each agent was associated with a distinct interaction pattern, which, unlike single-mutant phenotypes or gene expression data, has high statistical power to pinpoint the specific repair mechanisms at work. The agent-specific networks revealed roles for the histone acetyltranferase Rtt109 in the mutagenic bypass of DNA lesions and the neddylation machinery in cell-cycle regulation and genome stability, while the network induced by multiple agents implicates Irc21, an uncharacterized protein, in checkpoint control and DNA repair. Our multiconditional genetic interaction map provides a unique resource that identifies agent-specific and general DNA damage response pathways. PMID:23273983

  8. Final report for the project "Improving the understanding of surface-atmosphere radiative interactions by mapping surface reflectance over the ARM CART site" (award DE-FG02-02ER63351)

    SciTech Connect

    Alexander P. Trishchenko; Yi Luo; Konstantin V. Khlopenkov, William M. Park; Zhanqing Li; Maureen Cribb

    2008-11-28

    Surface spectral reflectance (albedo) is a fundamental variable affecting the transfer of solar radiation and the Earth’s climate. It determines the proportion of solar energy absorbed by the surface and reflected back to the atmosphere. The International Panel on Climate Change (IPCC) identified surface albedo among key factors influencing climate radiative forcing. Accurate knowledge of surface reflective properties is important for advancing weather forecasting and climate change impact studies. It is also important for determining radiative impact and acceptable levels of greenhouse gases in the atmosphere, which makes this work strongly linked to major scientific objectives of the Climate Change Research Division (CCRD) and Atmospheric Radiation Measurement (ARM) Program. Most significant accomplishments of eth project are listed below. I) Surface albedo/BRDF datasets from 1995 to the end of 2004 have been produced. They were made available to the ARM community and other interested users through the CCRS public ftp site ftp://ftp.ccrs.nrcan.gc.ca/ad/CCRS_ARM/ and ARM IOP data archive under “PI data Trishchenko”. II) Surface albedo properties over the ARM SGP area have been described for 10-year period. Comparison with ECMWF data product showed some deficiencies in the ECMWF surface scheme, such as missing some seasonal variability and no dependence on sky-conditions which biases surface energy budget and has some influence of the diurnal cycle of upward radiation and atmospheric absorption. III) Four surface albedo Intensive Observation Period (IOP) Field Campaigns have been conducted for every season (August, 2002, May 2003, February 2004 and October 2004). Data have been prepared, documented and transferred to ARM IOP archive. Nine peer-reviewed journal papers and 26 conference papers have been published.

  9. Constructing 3D interaction maps from 1D epigenomes.

    PubMed

    Zhu, Yun; Chen, Zhao; Zhang, Kai; Wang, Mengchi; Medovoy, David; Whitaker, John W; Ding, Bo; Li, Nan; Zheng, Lina; Wang, Wei

    2016-01-01

    The human genome is tightly packaged into chromatin whose functional output depends on both one-dimensional (1D) local chromatin states and three-dimensional (3D) genome organization. Currently, chromatin modifications and 3D genome organization are measured by distinct assays. An emerging question is whether it is possible to deduce 3D interactions by integrative analysis of 1D epigenomic data and associate 3D contacts to functionality of the interacting loci. Here we present EpiTensor, an algorithm to identify 3D spatial associations within topologically associating domains (TADs) from 1D maps of histone modifications, chromatin accessibility and RNA-seq. We demonstrate that active promoter-promoter, promoter-enhancer and enhancer-enhancer associations identified by EpiTensor are highly concordant with those detected by Hi-C, ChIA-PET and eQTL analyses at 200 bp resolution. Moreover, EpiTensor has identified a set of interaction hotspots, characterized by higher chromatin and transcriptional activity as well as enriched TF and ncRNA binding across diverse cell types, which may be critical for stabilizing the local 3D interactions. PMID:26960733

  10. Global Mapping of Human RNA-RNA Interactions.

    PubMed

    Sharma, Eesha; Sterne-Weiler, Tim; O'Hanlon, Dave; Blencowe, Benjamin J

    2016-05-19

    The majority of the human genome is transcribed into non-coding (nc)RNAs that lack known biological functions or else are only partially characterized. Numerous characterized ncRNAs function via base pairing with target RNA sequences to direct their biological activities, which include critical roles in RNA processing, modification, turnover, and translation. To define roles for ncRNAs, we have developed a method enabling the global-scale mapping of RNA-RNA duplexes crosslinked in vivo, "LIGation of interacting RNA followed by high-throughput sequencing" (LIGR-seq). Applying this method in human cells reveals a remarkable landscape of RNA-RNA interactions involving all major classes of ncRNA and mRNA. LIGR-seq data reveal unexpected interactions between small nucleolar (sno)RNAs and mRNAs, including those involving the orphan C/D box snoRNA, SNORD83B, that control steady-state levels of its target mRNAs. LIGR-seq thus represents a powerful approach for illuminating the functions of the myriad of uncharacterized RNAs that act via base-pairing interactions. PMID:27184080

  11. Constructing 3D interaction maps from 1D epigenomes

    PubMed Central

    Zhu, Yun; Chen, Zhao; Zhang, Kai; Wang, Mengchi; Medovoy, David; Whitaker, John W.; Ding, Bo; Li, Nan; Zheng, Lina; Wang, Wei

    2016-01-01

    The human genome is tightly packaged into chromatin whose functional output depends on both one-dimensional (1D) local chromatin states and three-dimensional (3D) genome organization. Currently, chromatin modifications and 3D genome organization are measured by distinct assays. An emerging question is whether it is possible to deduce 3D interactions by integrative analysis of 1D epigenomic data and associate 3D contacts to functionality of the interacting loci. Here we present EpiTensor, an algorithm to identify 3D spatial associations within topologically associating domains (TADs) from 1D maps of histone modifications, chromatin accessibility and RNA-seq. We demonstrate that active promoter–promoter, promoter–enhancer and enhancer–enhancer associations identified by EpiTensor are highly concordant with those detected by Hi-C, ChIA-PET and eQTL analyses at 200 bp resolution. Moreover, EpiTensor has identified a set of interaction hotspots, characterized by higher chromatin and transcriptional activity as well as enriched TF and ncRNA binding across diverse cell types, which may be critical for stabilizing the local 3D interactions. PMID:26960733

  12. A genetic interaction map of cell cycle regulators.

    PubMed

    Billmann, Maximilian; Horn, Thomas; Fischer, Bernd; Sandmann, Thomas; Huber, Wolfgang; Boutros, Michael

    2016-04-15

    Cell-based RNA interference (RNAi) is a powerful approach to screen for modulators of many cellular processes. However, resulting candidate gene lists from cell-based assays comprise diverse effectors, both direct and indirect, and further dissecting their functions can be challenging. Here we screened a genome-wide RNAi library for modulators of mitosis and cytokinesis inDrosophilaS2 cells. The screen identified many previously known genes as well as modulators that have previously not been connected to cell cycle control. We then characterized ∼300 candidate modifiers further by genetic interaction analysis using double RNAi and a multiparametric, imaging-based assay. We found that analyzing cell cycle-relevant phenotypes increased the sensitivity for associating novel gene function. Genetic interaction maps based on mitotic index and nuclear size grouped candidates into known regulatory complexes of mitosis or cytokinesis, respectively, and predicted previously uncharacterized components of known processes. For example, we confirmed a role for theDrosophilaCCR4 mRNA processing complex componentl(2)NC136during the mitotic exit. Our results show that the combination of genome-scale RNAi screening and genetic interaction analysis using process-directed phenotypes provides a powerful two-step approach to assigning components to specific pathways and complexes. PMID:26912791

  13. Interactive exploration of data traffic with Hierarchical Network Maps.

    PubMed

    Mansmann, Florian; Vinnik, Svetlana

    2006-01-01

    Network communication has become indispensable in business, education, and government. With the pervasive role of the Internet as a means of sharing information across networks, its misuse for destructive purposes, such as spreading malicious code, compromising remote hosts, or damaging data through unauthorized access, has grown immensely in the recent years. The classical way of monitoring the operation of large network systems is by analyzing the system logs for detecting anomalies. In this work, we introduce Hierarchical Network Map, an interactive visualization technique for gaining a deeper insight into network flow behavior by means of user-driven visual exploration. Our approach is meant as an enhancement to conventional analysis methods based on statistics or machine learning. We use multidimensional modeling combined with position and display awareness to view source and target data of the hosts in a hierarchical fashion with the ability to interactively change the level of aggregation or apply filtering. The interdisciplinary approach integrating data warehouse technology, information visualization, and decision support, brings about the benefit of efficiently collecting the input data and aggregating over very large data sets, visualizing the results, and providing interactivity to facilitate analytical reasoning. PMID:17073367

  14. 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.

  15. Mapping protein-DNA interactions using ChIP-sequencing.

    PubMed

    Massie, Charles E; Mills, Ian G

    2012-01-01

    Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method.Chromatin immunoprecipitation (ChIP) allows enrichment of genomic regions which are associated with specific transcription factors, histone modifications, and indeed any other epitopes which are present on chromatin. The original ChIP methods used site-specific PCR and Southern blotting to confirm which regions of the genome were enriched, on a candidate basis. The combination of ChIP with genomic tiling arrays (ChIP-chip) allowed a more unbiased approach to map ChIP-enriched sites. However, limitations of microarray probe design and probe number have a detrimental impact on the coverage, resolution, sensitivity, and cost of whole-genome tiling microarray sets for higher eukaryotes with large genomes. The combination of ChIP with high-throughput sequencing technology has allowed more comprehensive surveys of genome occupancy, greater resolution, and lower cost for whole genome coverage. Herein, we provide a comparison of high-throughput sequencing platforms and a survey of ChIP-seq analysis tools, discuss experimental design, and describe a detailed ChIP-seq method. PMID:22113275

  16. Current approaches to fine mapping of antigen–antibody interactions

    PubMed Central

    Abbott, W Mark; Damschroder, Melissa M; Lowe, David C

    2014-01-01

    A number of different methods are commonly used to map the fine details of the interaction between an antigen and an antibody. Undoubtedly the method that is now most commonly used to give details at the level of individual amino acids and atoms is X-ray crystallography. The feasibility of undertaking crystallographic studies has increased over recent years through the introduction of automation, miniaturization and high throughput processes. However, this still requires a high level of sophistication and expense and cannot be used when the antigen is not amenable to crystallization. Nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA-based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids. It is quite common to use more than one method because of the limitations and even with a crystal structure it can be useful to use mutagenesis to tease apart the contribution of individual amino acids to binding affinity. PMID:24635566

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  18. 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

  19. Identification of the mitogen-activated protein kinase phosphorylation sites on human Sos1 that regulate interaction with Grb2.

    PubMed Central

    Corbalan-Garcia, S; Yang, S S; Degenhardt, K R; Bar-Sagi, D

    1996-01-01

    The Son of sevenless proteins (Sos) are guanine nucleotide exchange factors involved in the activation of Ras by cytoplasmic and receptor tyrosine kinases. Growth factor stimulation rapidly induces the phosphorylation of Sos on multiple serine and threonine sites. Previous studies have demonstrated that growth factor-induced Sos phosphorylation occurs at the C-terminal region of the protein and is mediated, in part, by mitogen-activated protein (MAP) kinase. In this report, we describe the identification of five MAP kinase sites (S-1137, S-1167, S-1178, S-1193, and S-1197) on hSos1. We demonstrate that four of these sites, S-1132, S-1167, S-1178, and S-1193, become phosphorylated following growth factor stimulation. The MAP kinase phosphorylation sites are clustered within a region encompassing three proline-rich SH3-binding sites in the C-terminal domain of hSos1. Replacing the MAP kinase phosphorylation sites with alanine residues results in an increase in the binding affinity of Grb2 to hSos1. Interestingly, hSos2 contains only one MAP kinase phosphorylation site and, as demonstrated previously, has an increased affinity toward Grb2 compared with hSos1. These results suggest a role for MAP kinase in the regulation of Grb2-Sos interactions. Since the binding of Grb2 is important for Sos function, the phosphorylation-dependent modulation of Grb2-Sos association may provide a means of controlling Ras activation. PMID:8816480

  20. Structure and mapping of spontaneous mutational sites of PyrR from Mycobacterium tuberculosis.

    PubMed

    Ghode, Pramila; Ramachandran, Sarath; Bifani, Pablo; Sivaraman, J

    2016-03-18

    The emergence of resistant Mycobacterium tuberculosis (Mtb) infection and the dearth of drugs against tuberculosis have made it imperative to identify and validate novel targets and classes of drugs for treatment. The pyrimidine operon regulatory protein (PyrR), a regulator of de novo pyrimidine synthesis, is an essential enzyme and a probable 5-fluorouracil (5-FU) target in Mtb, with mutations in PyrR attributable to 5-FU resistance. Here we report, for the first time, the co-crystal structure of the PyrR-5-FU complex along with mapping of spontaneous mutational sites of PyrR. A cluster of mutations in the presence of the drug usually indicates a plausible region of drug-target interaction. Notably, we observed that three of the mutated PyrR residues lie in close proximity to the 5-FU binding site, including the amino acid Val178, which is involved in water mediated hydrogen bonding contact with 5-FU. Computational modeling of the PyrR-5'-phosphoribosyl-α-1'-pyrophosphate (PRPP) complex revealed the location of several other mutations at the PRPP binding site of PyrR, indicating their probable role in resistance. Indeed, 5-FU-resistant strains harboring these mutations exhibited decreased susceptibility to 5-FU. Considering that pyrimidine analogs are predominantly regarded to inhibit PyrR, the present studies will be beneficial for the screening of appropriate inhibitors of PyrR and help provide insight into future TB drug design and development. PMID:26902118

  1. Mapping the Vertical Structure of the Lunar Regolith in Volcanic Regions and at Constellation Sites

    NASA Astrophysics Data System (ADS)

    Carter, L. M.; Ghent, R. R.; Bandfield, J. L.; Campbell, B. A.

    2014-12-01

    The upper ten meters of the lunar regolith contains stratigraphy that provides geologic insight, and these upper layers are also what future in-situ instruments will interact with. We use a combination of remote sensing data from ground-based radar observations (Arecibo and Green Bank Telescope at wavelengths of 12.6 cm and 70 cm) and the Lunar Reconnaissance Orbiter spacecraft (Diviner, Mini-RF) to determine how the regolith structure varies across volcanic terrains and possible future landing sites. Radar can detect buried units and provide a measure of roughness, while thermal infrared data provides complimentary information on the surface and near-surface rock abundance in the upper centimeters. Radar and infrared wavelengths are also sensitive to different sized rocks, which can be used to determine where there are increased numbers centimeter-sized rocks. A comparison of these data sets reveals significant differences in regolith stratigraphy across targets. For example, small rilles on the Aristarchus Plateau to the northeast of the Constellation Aristarchus 2 site are surrounded by rock-poor deposits and are likely a secondary source of pyroclastic materials. Some rilles, such as Rima Birt, are surrounded by pyroclastics that change in depth and/or embedded rock abundance along the length of the rille. We will present results from our data analysis and subsequent mapping, focusing on rilles, pyroclastic deposits, and Constellation Region of Interest targets including the Apollo sites.

  2. NMR Mapping of the IFNAR1-EC binding site on IFNα2 reveals allosteric changes in the IFNAR2-EC binding site

    PubMed Central

    Akabayov, Sabine Ruth; Biron, Zohar; Lamken, Peter; Piehler, Jacob; Anglister, Jacob

    2010-01-01

    All type I interferons (IFNs) bind to a common cell-surface receptor consisting of two subunits. IFNs initiate intracellular signal transduction cascades by simultaneous interaction with the extracellular domains of its receptor subunits IFNAR1 and IFNAR2. In this study we mapped the surface of IFNα2 interacting with the extracellular domain of IFNAR1 (IFNAR1-EC) by following changes in or the disappearance of the [1H,15N]-TROSY-HSQC cross peaks of IFNα2 caused by the binding of the extracellular domain of IFNAR1 (IFNAR1-EC) to the binary complex of IFNα2 with IFNAR2-EC. The NMR study on the 89 kDa complex was conducted at pH 8 and 308 K using an 800 MHz spectrometer. IFNAR1 binding affected a total of 47 out of 165 IFNα2 residues contained in two large patches on the face of the protein opposing the binding site for IFNAR2 and in a third patch located on the face containing the IFNAR2 binding site. The first two patches form the IFNAR1 binding site and one of these matches the IFNAR1 binding site previously identified by site-directed mutagenesis. The third patch partially matches the IFNα2 binding site for IFNAR2-EC indicating allosteric communication between the binding sites for the two receptor subunits. PMID:20047337

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

    DOE Data Explorer

    Jaffe, Todd

    2012-01-01

    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.

  4. Is it enough to have one ECa map for the site-specific management delineation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The soil apparent electrical conductivity (ECa) has been used to map soil spatial variability and to relate it to the variability of various soil properties thus delineating zones of site-specific management. Most often, a single ECa survey is done and the generated ECa map is considered to infer t...

  5. Preliminary Correlation Map of Geomorphic Surfaces in North-Central Frenchman Flat, Nevada Test Site

    SciTech Connect

    Bechtel Nevada

    2005-08-01

    This correlation map (scale = 1:12,000) presents the results of a mapping initiative that was part of the comprehensive site characterization required to operate the Area 5 Radioactive Waste Management Site, a low-level radioactive waste disposal facility located in northern Frenchman Flat at the Nevada Test Site. Eight primary map units are recognized for Quaternary surfaces: remnants of six alluvial fan or terrace surfaces, one unit that includes colluvial aprons associated with hill slopes, and one unit for anthropogenically disturbed surfaces. This surficial geology map provides fundamental data on natural processes for reconstruction of the Quaternary history of northern Frenchman Flat, which in turn will aid in the understanding of the natural processes that act to develop the landscape, and the time-frames involved in landscape development. The mapping was conducted using color and color-infrared aerial photographs and field verification of map unit composition and boundaries. Criteria for defining the map unit composition of geomorphic surface units are based on relative geomorphic position, landform morphology, and degree of preservation of surface morphology. The bedrock units identified on this map were derived from previous published mapping efforts and are included for completeness.

  6. Landing Site Selection and Surface Traverse Planning using the Lunar Mapping & Modeling Portal

    NASA Astrophysics Data System (ADS)

    Law, E.; Chang, G.; Bui, B.; Sadaqathullah, S.; Kim, R.; Dodge, K.; Malhotra, S.

    2013-12-01

    Introduction: The Lunar Mapping and Modeling Portal (LMMP), is a web-based Portal and a suite of interactive visualization and analysis tools for users to access mapped lunar data products (including image mosaics, digital elevation models, etc.) from past and current lunar missions (e.g., Lunar Reconnaissance Orbiter, Apollo, etc.), and to perform in-depth analyses to support lunar surface mission planning and system design for future lunar exploration and science missions. It has been widely used by many scientists mission planners, as well as educators and public outreach (e.g., Google Lunar XPRICE teams, RESOLVE project, museums etc.) This year, LMMP was used by the Lunar and Planetary Institute (LPI)'s Lunar Exploration internship program to perform lighting analysis and local hazard assessments, such as, slope, surface roughness and crater/boulder distribution to research landing sites and surface pathfinding and traversal. Our talk will include an overview of LMMP, a demonstration of the tools as well as a summary of the LPI Lunar Exploration summer interns' experience in using those tools.

  7. A Genetic Mapping System in Caenorhabditis Elegans Based on Polymorphic Sequence-Tagged Sites

    PubMed Central

    Williams, B. D.; Schrank, B.; Huynh, C.; Shownkeen, R.; Waterston, R. H.

    1992-01-01

    We devised an efficient genetic mapping system in the nematode Caenorhabditis elegans which is based upon the differences in number and location of the transposable element Tc1 between the Bristol and Bergerac strains. Using the nearly completed physical map of the C. elegans genome, we selected 40 widely distributed sites which contain a Tc1 element in the Bergerac strain, but not in the Bristol strain. For each site a polymerase chain reaction assay was designed that can distinguish between the Bergerac Tc1-containing site and the Bristol ``empty'' site. By combining appropriate assays in a single reaction, one can score multiple sites within single worms. This permits a mutation to be rapidly mapped, first to a linkage group and then to a chromosomal subregion, through analysis of only a small number of progeny from a single interstrain cross. PMID:1321065

  8. Mapping Functional Interactions in a Heterodimeric Phospholipid Pump*

    PubMed Central

    Puts, Catheleyne F.; Panatala, Radhakrishnan; Hennrich, Hanka; Tsareva, Alina; Williamson, Patrick; Holthuis, Joost C. M.

    2012-01-01

    Type 4 P-type ATPases (P4-ATPases) catalyze phospholipid transport to generate phospholipid asymmetry across membranes of late secretory and endocytic compartments, but their kinship to cation-transporting P-type transporters raised doubts about whether P4-ATPases alone are sufficient to mediate flippase activity. P4-ATPases form heteromeric complexes with Cdc50 proteins. Studies of the enzymatic properties of purified P4-ATPase·Cdc50 complexes showed that catalytic activity depends on direct and specific interactions between Cdc50 subunit and transporter, whereas in vivo interaction assays suggested that the binding affinity for each other fluctuates during the transport reaction cycle. The structural determinants that govern this dynamic association remain to be established. Using domain swapping, site-directed, and random mutagenesis approaches, we here show that residues throughout the subunit contribute to forming the heterodimer. Moreover, we find that a precise conformation of the large ectodomain of Cdc50 proteins is crucial for the specificity and functionality to transporter/subunit interactions. We also identified two highly conserved disulfide bridges in the Cdc50 ectodomain. Functional analysis of cysteine mutants that disrupt these disulfide bridges revealed an inverse relationship between subunit binding and P4-ATPase-catalyzed phospholipid transport. Collectively, our data indicate that a dynamic association between subunit and transporter is crucial for the transport reaction cycle of the heterodimer. PMID:22791719

  9. Orbital-science investigation: Part K: geologic sketch map of the candidate Proclus Apollo landing site

    USGS Publications Warehouse

    Lucchitta, Baerbel Koesters

    1972-01-01

    A panoramic camera frame (fig. 25-69) was used as the base for a geologic sketch map (fig. 25-70) of an area near Proclus Crater. The map was prepared to investigate the usefulness of the Apollo 15 panoramic camera photography in large-scale geologic mapping and to assess the geologic value of this area as a potential Apollo landing site. The area is being considered as a landing site because of the availability of smooth plains terrain and because of the scientific value of investigating plains materials, dark halo craters, and ancient rocks that may be present in the Proclus ray material.

  10. 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.

  11. Mapping of phosphorylation sites in polyomavirus large T antigen.

    PubMed Central

    Hassauer, M; Scheidtmann, K H; Walter, G

    1986-01-01

    The phosphorylation sites of polyomavirus large T antigen from infected or transformed cells were investigated. Tryptic digestion of large T antigen from infected, 32Pi-labeled cells revealed seven major phosphopeptides. Five of these were phosphorylated only at serine residues, and two were phosphorylated at serine and threonine residues. The overall ratio of phosphoserine to phosphothreonine was 6:1. The transformed cell line B4 expressed two polyomavirus-specific phosphoproteins: large T antigen, which was only weakly phosphorylated, and a truncated form of large T antigen of 34,000 molecular weight which was heavily phosphorylated. Both showed phosphorylation patterns similar to that of large T antigen from infected cells. Peptide analyses of large T antigens encoded by the deletion mutants dl8 and dl23 or of specific fragments of wild-type large T antigen indicated that the phosphorylation sites are located in an amino-terminal region upstream of residue 194. The amino acid composition of the phosphopeptides as revealed by differential labeling with various amino acids indicated that several phosphopeptides contain overlapping sequences and that all phosphorylation sites are located in four tryptic peptides derived from a region between Met71 and Arg191. Two of the potential phosphorylation sites were identified as Ser81 and Thr187. The possible role of this modification of large T antigen is discussed. Images PMID:3009889

  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. 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…

  14. Communication: Quantitative multi-site frequency maps for amide I vibrational spectroscopy.

    PubMed

    Reppert, Mike; Tokmakoff, Andrei

    2015-08-14

    An accurate method for predicting the amide I vibrational spectrum of a given protein structure has been sought for many years. Significant progress has been made recently by sampling structures from molecular dynamics simulations and mapping local electrostatic variables onto the frequencies of individual amide bonds. Agreement with experiment, however, has remained largely qualitative. Previously, we used dipeptide fragments and isotope-labeled constructs of the protein G mimic NuG2b as experimental standards for developing and testing amide I frequency maps. Here, we combine these datasets to test different frequency-map models and develop a novel method to produce an optimized four-site potential (4P) map based on the CHARMM27 force field. Together with a charge correction for glycine residues, the optimized map accurately describes both experimental datasets, with average frequency errors of 2-3 cm(-1). This 4P map is shown to be convertible to a three-site field map which provides equivalent performance, highlighting the viability of both field- and potential-based maps for amide I spectral modeling. The use of multiple sampling points for local electrostatics is found to be essential for accurate map performance. PMID:26277120

  15. Communication: Quantitative multi-site frequency maps for amide I vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Reppert, Mike; Tokmakoff, Andrei

    2015-08-01

    An accurate method for predicting the amide I vibrational spectrum of a given protein structure has been sought for many years. Significant progress has been made recently by sampling structures from molecular dynamics simulations and mapping local electrostatic variables onto the frequencies of individual amide bonds. Agreement with experiment, however, has remained largely qualitative. Previously, we used dipeptide fragments and isotope-labeled constructs of the protein G mimic NuG2b as experimental standards for developing and testing amide I frequency maps. Here, we combine these datasets to test different frequency-map models and develop a novel method to produce an optimized four-site potential (4P) map based on the CHARMM27 force field. Together with a charge correction for glycine residues, the optimized map accurately describes both experimental datasets, with average frequency errors of 2-3 cm-1. This 4P map is shown to be convertible to a three-site field map which provides equivalent performance, highlighting the viability of both field- and potential-based maps for amide I spectral modeling. The use of multiple sampling points for local electrostatics is found to be essential for accurate map performance.

  16. Complete Bouguer gravity map of the Nevada Test Site and vicinity, Nevada

    SciTech Connect

    Healey, D.L.; Harris, R.N.; Ponce, D.A.; Oliver, H.W.

    1987-12-31

    About 15,000 gravity stations were used to create the gravity map. Gravity studies at the Nevada Test Site were undertaken to help locate geologically favorable areas for underground nuclear tests and to help characterize potential high-level nuclear waste storage sites. 48 refs. (TEM)

  17. A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

    PubMed Central

    Nardini, Christine

    2010-01-01

    Background Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA). Methodology Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA. Significance We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being -at the moment- a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at ‘www.picb.ac.cn/ClinicalGenomicNTW/temp.html’ and ‘www.celldesigner.org’. PMID:20419126

  18. A site-specific factor interacts directly with its cognate RNA editing site in chloroplast transcripts.

    PubMed

    Miyamoto, Tetsuya; Obokata, Junichi; Sugiura, Masahiro

    2004-01-01

    RNA editing involves a variety of genetic systems and occurs by different mechanisms. In higher plant chloroplasts, specific sites of some transcripts are subject to C-to-U conversion. We have previously shown that site-specific trans-acting factors for psbE and petB mRNA editing bind corresponding cis-elements, which are located 5 nucleotides upstream from the editing site. Here we report that, by using mRNAs labeled either at the center of the upstream cis-element or at the editing site, the site-specific factors can be cross-linked with nucleotides at both positions. Mutations of nucleotides in the proximal region of the editing site revealed a correlation between editing activity and cross-linking efficiency of factors with the editing site, even though cross-linking with the upstream cis-element was unaffected. These observations suggest that the site-specific factor binds stably to the upstream ciselement, whereas it interacts weakly with the editing site. This finding raises the intriguing possibility that the site-specific factor is involved in both site-determination and C-to-U conversion in chloroplast RNA editing. PMID:14694196

  19. A site-specific factor interacts directly with its cognate RNA editing site in chloroplast transcripts

    PubMed Central

    Miyamoto, Tetsuya; Obokata, Junichi; Sugiura, Masahiro

    2004-01-01

    RNA editing involves a variety of genetic systems and occurs by different mechanisms. In higher plant chloroplasts, specific sites of some transcripts are subject to C-to-U conversion. We have previously shown that site-specific trans-acting factors for psbE and petB mRNA editing bind corresponding cis-elements, which are located 5 nucleotides upstream from the editing site. Here we report that, by using mRNAs labeled either at the center of the upstream cis-element or at the editing site, the site-specific factors can be cross-linked with nucleotides at both positions. Mutations of nucleotides in the proximal region of the editing site revealed a correlation between editing activity and cross-linking efficiency of factors with the editing site, even though cross-linking with the upstream cis-element was unaffected. These observations suggest that the site-specific factor binds stably to the upstream ciselement, whereas it interacts weakly with the editing site. This finding raises the intriguing possibility that the site-specific factor is involved in both site-determination and C-to-U conversion in chloroplast RNA editing. PMID:14694196

  20. Halogenated naphthyl methoxy piperidines for mapping serotonin transporter sites

    DOEpatents

    Goodman, M.M.; Faraj, B.

    1999-07-06

    Halogenated naphthyl methoxy piperidines having a strong affinity for the serotonin transporter are disclosed. Those compounds can be labeled with positron-emitting and/or gamma emitting halogen isotopes by a late step synthesis that maximizes the useable lifeterm of the label. The labeled compounds are useful for localizing serotonin transporter sites by positron emission tomography and/or single photon emission computed tomography.

  1. Halogenated naphthyl methoxy piperidines for mapping serotonin transporter sites

    DOEpatents

    Goodman, Mark M.; Faraj, Bahjat

    1999-01-01

    Halogenated naphthyl methoxy piperidines having a strong affinity for the serotonin transporter are disclosed. Those compounds can be labeled with positron-emitting and/or gamma emitting halogen isotopes by a late step synthesis that maximizes the useable lifeterm of the label. The labeled compounds are useful for localizing serotonin transporter sites by positron emission tomography and/or single photon emission computed tomography.

  2. Comparison of Kriging and coKriging for soil contamination mapping in abandoned mine sites

    NASA Astrophysics Data System (ADS)

    Lee, Hyeongyu; Choi, Yosoon

    2015-04-01

    Soil contamination mapping around abandoned mines is an important task for the planning and design of mine reclamation. This study compared the ordinary Kriging and the co-Kriging methods for the soil contamination mapping in abandoned mine sites. Four approaches were conducted as follows: (1) soil contamination mapping using the ordinary Kriging and Inductively Coupled Plasma (ICP) data only; (2) soil contamination mapping using the ordinary Kriging and Portable X-Ray Fluorescence (PXRF) data only; (3) soil contamination mapping using the ordinary Kriging and integrated data from ICP and PXRF; and (4) soil contamination mapping using the co-Kriging and integrated data from ICP and PXRF. Results indicate that the approach 3 provides substantial improvements over other three approaches including a more reasonable spatial pattern of soil contamination and reduction in the error of its estimates.

  3. Map model for nonlinear alpha particle interaction with toroidal Alfven waves

    SciTech Connect

    Berk, H.L.; Breizman, B.N.; Ye, H.

    1992-09-01

    A map model has been developed for studying the nonlinear interaction of alpha particles with the toroidal Alfven eigenmodes. The map is constructed by assuming a linear interaction during a single poloidal transit, which allows the study of the nonlinear interaction over many transits. By using this map, analytic expressions are obtained for the particle nonlinear bounce frequency, and the wave amplitude threshold for the onset of particle orbit stochasticity. The map model can also facilitate self-consistent simulations which incorporate the time variation of the waves.

  4. 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

    Developed by the Terrain Sciences Division (TSD) of the Geological Survey of Canada (GSC), an interactive map viewer, called GEOSERV (www.geoserv.org), is now available on the Internet. The purpose of this viewer is to provide engineers, planners, decision makers, and the general public with the geoscience information required for sound regional planning in densely populated areas, such as Canada's national capital, Ottawa (Ontario). Urban geology studies rely on diverse branches of earth sciences such as hydrology, engineering geology, geochemistry, stratigraphy, and geomorphology in order to build a three-dimensional model of the character of the land and to explain the geological processes involved in the dynamic equilibrium of the local environment. Over the past few years, TSD has compiled geoscientific information derived from various sources such as borehole logs, geological maps, hydrological reports and digital elevation models, compiled it in digital format and stored it in georeferenced databases in the form of point, linear, and polygonal data. This information constitutes the geoscience knowledge base which is then processed by Geographic Information Systems (GIS) to integrate the various sources of information and produce derived graphics, maps and models describing the geological infrastructure and response of the geological environment to human activities. Urban Geology of Canada's National Capital Area is a pilot project aiming at developing approaches, methodologies and standards that can be applied to other major urban centres of the country, while providing the geoscience knowledge required for sound regional planning and environmental protection of the National Capital Area. Based on an application developed by ESRI (Environmental System Research Institute), namely ArcIMS, the TSD has customized this web application to give free access to geoscience information of the Ottawa/Outaouais (Ontario/Québec) area including geological history, 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.

  5. Targeting Bax interaction sites reveals that only homo-oligomerization sites are essential for its activation

    PubMed Central

    Peng, R; Tong, J-S; Li, H; Yue, B; Zou, F; Yu, J; Zhang, L

    2013-01-01

    Bax is a proapoptotic Bcl-2 family member that has a central role in the initiation of mitochondria-dependent apoptosis. However, the mechanism of Bax activation during apoptosis remains unsettled. It is believed that the activation of Bax is mediated by either dissociation from prosurvival Bcl-2 family members, or direct association with BH3-only members. Several interaction sites on Bax that mediate its interactions with other Bcl-2 family members, as well as its proapoptotic activity, have been identified in previous studies by other groups. To rigorously investigate the functional role of these interaction sites, we knocked in their respective mutants using HCT116 colon cancer cells, in which apoptosis induced by several stimuli is strictly Bax-dependent. Bax-mediated apoptosis was intact upon knock-in (KI) of K21E and D33A, which were shown to block the interaction of Bax with BH3-only activators. Apoptosis was partially reduced by KI of D68R, which impairs the interaction of Bax with prosurvival members, and S184V, a constitutively mitochondria-targeting mutant. In contrast, apoptosis was largely suppressed by KI of L70A/D71A, which blocks homo-oligomerization of Bax and its binding to prosurvival Bcl-2 family proteins. Collectively, our results suggest that the activation of endogenous Bax in HCT116 cells is dependent on its homo-oligomerization sites, but not those previously shown to interact with BH3-only activators or prosurvival proteins only. We therefore postulate that critical interaction sites yet to be identified, or mechanisms other than protein-protein interactions, need to be pursued to delineate the mechanism of Bax activation during apoptosis. PMID:23392123

  6. Developing Exhibit-based, Interactive Web Sites to Communicate Science

    NASA Astrophysics Data System (ADS)

    Dusenbery, P. B.; Harold, J.

    2003-12-01

    New technologies are transforming the Web from a static medium to an interactive environment with tremendous potential for informal education and inquiry-based investigations. ASTC, the trade association of science museums, gave its 2000 innovation award to the Exploratorium's Web page rather than a physical exhibit. The increased power of the Web as an informal learning tool is partly the result of technologies (such as Java, Flash and Shockwave) that allow the development of inquiry-based, interactive experiences. Web site visitors can now "learn science by doing science." This report features two online projects funded by NSF and NASA: MarsQuest Online and the Space Weather Center. TERC, the Space Science Institute, and NASA's Jet Propulsion Laboratory are developing MarsQuest Online, an interactive, exploration-based Web site that extends the reach and scope of the MarsQuest exhibit. The Space Weather Center Web site is based on the Space Weather Center exhibit that was developed in partnership with scientists and educators at NASA/GSFC. Both exhibits represent a tremendous, collaborative effort by scientists, educators, and designers to communicate the essentials of Mars science and space weather to the public. As such, the graphics, text, and story developed for the exhibits represent a valuable resource that will provide the framework and base content for the public site. Given that framework, the Web sites can then expand both the content and audience of the exhibits in key ways. In particular, the sites will 1) extend the reach of the exhibit by making it available online, 2) extend the scope of the exhibit, linking to the latest imagery and results from ground and space-based missions, and 3) provide support and follow-up for the exhibit education programs, while making materials available to more teachers, parents, and museum educators and docents.

  7. Mapping Hfq-RNA interaction surfaces using tryptophan fluorescence quenching

    PubMed Central

    Robinson, Kirsten E.; Orans, Jillian; Kovach, Alexander R.; Link, Todd M.; Brennan, Richard G.

    2014-01-01

    Hfq is a posttranscriptional riboregulator and RNA chaperone that binds small RNAs and target mRNAs to effect their annealing and message-specific regulation in response to environmental stressors. Structures of Hfq-RNA complexes indicate that U-rich sequences prefer the proximal face and A-rich sequences the distal face; however, the Hfq-binding sites of most RNAs are unknown. Here, we present an Hfq-RNA mapping approach that uses single tryptophan-substituted Hfq proteins, all of which retain the wild-type Hfq structure, and tryptophan fluorescence quenching (TFQ) by proximal RNA binding. TFQ properly identified the respective distal and proximal binding of A15 and U6 RNA to Gram-negative Escherichia coli (Ec) Hfq and the distal face binding of (AA)3A, (AU)3A and (AC)3A to Gram-positive Staphylococcus aureus (Sa) Hfq. The inability of (GU)3G to bind the distal face of Sa Hfq reveals the (R-L)n binding motif is a more restrictive (A-L)n binding motif. Remarkably Hfq from Gram-positive Listeria monocytogenes (Lm) binds (GU)3G on its proximal face. TFQ experiments also revealed the Ec Hfq (A-R-N)n distal face-binding motif should be redefined as an (A-A-N)n binding motif. TFQ data also demonstrated that the 5′-untranslated region of hfq mRNA binds both the proximal and distal faces of Ec Hfq and the unstructured C-terminus. PMID:24288369

  8. Geologic sketch map of the candidate Proclus Apollo landing site, part K

    NASA Technical Reports Server (NTRS)

    Lucchitta, B. K.

    1972-01-01

    An Apollo 15 panoramic camera frame was used as a base for a geologic sketch map of an area near Proclus Crater. The map was prepared to investigate the usefulness of the panoramic camera photography in large-scale geologic mapping and to assess the geologic value of the area as a potential Apollo landing site. The photographs, taken under high solar illumination, resulted in good definition of albedo features, and stereoscopic viewing provided extreme clarity of topographic relief with terrain units easily delineated. The geological characteristics of the area as evidenced by the high-resolution photographs is discussed. It is concluded that the panoramic camera photographs reveal a wealth of detail and are eminently suited for geologic mapping purposes. In addition, the Proclus area, as a potential landing site, offers relatively rough plains terrain.

  9. Mapping Interactions between Germinants and Clostridium difficile Spores ▿

    PubMed Central

    Howerton, Amber; Ramirez, Norma; Abel-Santos, Ernesto

    2011-01-01

    Germination of Clostridium difficile spores is the first required step in establishing C. difficile-associated disease (CDAD). Taurocholate (a bile salt) and glycine (an amino acid) have been shown to be important germinants of C. difficile spores. In the present study, we tested a series of glycine and taurocholate analogs for the ability to induce or inhibit C. difficile spore germination. Testing of glycine analogs revealed that both the carboxy and amino groups are important epitopes for recognition and that the glycine binding site can accommodate compounds with more widely separated termini. The C. difficile germination machinery also recognizes other hydrophobic amino acids. In general, linear alkyl side chains are better activators of spore germination than their branched analogs. However, l-phenylalanine and l-arginine are also good germinants and are probably recognized by distinct binding sites. Testing of taurocholate analogs revealed that the 12-hydroxyl group of taurocholate is necessary, but not sufficient, to activate spore germination. In contrast, the 6- and 7-hydroxyl groups are required for inhibition of C. difficile spore germination. Similarly, C. difficile spores are able to detect taurocholate analogs with shorter, but not longer, alkyl amino sulfonic acid side chains. Furthermore, the sulfonic acid group can be partially substituted with other acidic groups. Finally, a taurocholate analog with an m-aminobenzenesulfonic acid side chain is a strong inhibitor of C. difficile spore germination. In conclusion, C. difficile spores recognize both amino acids and taurocholate through multiple interactions that are required to bind the germinants and/or activate the germination machinery. PMID:20971909

  10. Mapping protein interactions by combining antibody affinity maturation and mass spectrometry

    PubMed Central

    Dyson, Michael R.; Zheng, Yong; Zhang, Cunjie; Colwill, Karen; Pershad, Kritika; Kay, Brian K.; Pawson, Tony; McCafferty, John

    2011-01-01

    Mapping protein interactions by immunoprecipitation is limited by the availability of antibodies recognizing available native epitopes within protein complexes with sufficient affinity. Here we demonstrate a scalable approach for generation of such antibodies using phage display and affinity maturation. We combined antibody variable heavy (VH) genes from target-specific clones (recognizing Src homology 2 (SH2) domains of LYN, VAV1, NCK1, ZAP70, PTPN11, CRK, LCK, and SHC1) with a repertoire of 108 to 109 new variable light (VL) genes. Improved binders were isolated by stringent selections from these new chain-shuffled libraries. We also developed a predictive 96-well immunocapture screen and found that only 12% of antibodies had sufficient affinity/epitope availability to capture endogenous target from lysates. Using antibodies of different affinities to the same epitope, we show that affinity improvement was a key determinant for success and identified a clear affinity threshold value (60nM for SHC1) that must be breached for success in immunoprecipitation. By combining affinity capture using matured antibodies to SHC1 with mass spectrometry, we identified seven known binding partners and two known SHC1 phosphorylation sites in epidermal growth factor (EGF)-stimulated human breast cancer epithelial cells. These results demonstrate that antibodies capable of immunoprecipitation can be generated by chain shuffling, providing a scalable approach to mapping proteinprotein interaction networks. PMID:21704603

  11. Detecting site-specific biochemical constraints through substitution mapping.

    PubMed

    Dutheil, Julien

    2008-09-01

    The neutral theory of molecular evolution states that most mutations are deleterious or neutral. It results that the evolutionary rate of a given position in an alignment is a function of the level of constraint acting on this position. Inferring evolutionary rates from a set of aligned sequences is hence a powerful method to detect functionally and/or structurally important positions in a protein. Some positions, however, may be constrained while having a high substitution rate, providing these substitutions do not affect the biochemical property under constraint. Here, I introduce a new evolutionary rate measure accounting for the evolution of specific biochemical properties (e.g., volume, polarity, and charge). I then present a new statistical method based on the comparison of two rate measures: a site is said to be constrained for property X if it shows an unexpectedly high conservation of X knowing its total evolutionary rate. Compared to single-rate methods, the two-rate method offers several advantages: it (i) allows assessment of the significance of the constraint, (ii) provides information on the type of constraint acting on each position, and (iii) detects positions that are not proposed by previous methods. I apply this method to a 200-sequence data set of triosephosphate isomerase and report significant cases of positions constrained for polarity, volume, or charge. The three-dimensional localization of these positions shows that they are of potential interest to the molecular evolutionist and to the biochemist. PMID:18696030

  12. 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.

  13. Geomorphic Surface Maps of Northern Frenchman Flat, Nevada Test Site, Southern Nevada

    SciTech Connect

    Bechtel Nevada

    2005-08-01

    Large-scale (1:6000) surficial geology maps of northern Frenchman Flat were developed in 1995 as part of comprehensive site characterization required to operate a low-level radioactive waste disposal facility in that area. Seven surficial geology maps provide fundamental data on natural processes and are the platform needed to reconstruct the Quaternary history of northern Frenchman Flat. Reconstruction of the Quaternary history provides an understanding of the natural processes that act to develop the landscape, and the time-frames involved in landscape development. The mapping was conducted using color and color-infrared aerial photographs and field verification of map unit composition and boundaries. Criteria for defining the map unit composition of geomorphic surface units are based on relative geomorphic position, landform morphology, and degree of preservation of surface morphology. Seven geomorphic surfaces (Units 1 through 7) are recognized, spanning from the early Quaternary to present time.

  14. Benzodiazepine binding site-interactive flavones from Scutellaria baicalensis root.

    PubMed

    Liao, J F; Wang, H H; Chen, M C; Chen, C C; Chen, C F

    1998-08-01

    A benzodiazepine binding assay directed separation led to the identification of 3 flavones baicalein (1), oroxylin A (2), and skullcapflavone II (3) from the water extract of Scutellaria baicalensis root. Compounds 1, 2, and 3 interacted with the benzodiazepine binding site of GABAA receptors with a Ki value of 13.1, 14.6 and 0.36 micromol/L, respectively. PMID:9776664

  15. Perm-seq: Mapping Protein-DNA Interactions in Segmental Duplication and Highly Repetitive Regions of Genomes with Prior-Enhanced Read Mapping

    PubMed Central

    Zeng, Xin; Li, Bo; Welch, Rene; Rojo, Constanza; Zheng, Ye; Dewey, Colin N.; Keleş, Sündüz

    2015-01-01

    Segmental duplications and other highly repetitive regions of genomes contribute significantly to cells’ regulatory programs. Advancements in next generation sequencing enabled genome-wide profiling of protein-DNA interactions by chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq). However, interactions in highly repetitive regions of genomes have proven difficult to map since short reads of 50–100 base pairs (bps) from these regions map to multiple locations in reference genomes. Standard analytical methods discard such multi-mapping reads and the few that can accommodate them are prone to large false positive and negative rates. We developed Perm-seq, a prior-enhanced read allocation method for ChIP-seq experiments, that can allocate multi-mapping reads in highly repetitive regions of the genomes with high accuracy. We comprehensively evaluated Perm-seq, and found that our prior-enhanced approach significantly improves multi-read allocation accuracy over approaches that do not utilize additional data types. The statistical formalism underlying our approach facilitates supervising of multi-read allocation with a variety of data sources including histone ChIP-seq. We applied Perm-seq to 64 ENCODE ChIP-seq datasets from GM12878 and K562 cells and identified many novel protein-DNA interactions in segmental duplication regions. Our analysis reveals that although the protein-DNA interactions sites are evolutionarily less conserved in repetitive regions, they share the overall sequence characteristics of the protein-DNA interactions in non-repetitive regions. PMID:26484757

  16. Perm-seq: Mapping Protein-DNA Interactions in Segmental Duplication and Highly Repetitive Regions of Genomes with Prior-Enhanced Read Mapping.

    PubMed

    Zeng, Xin; Li, Bo; Welch, Rene; Rojo, Constanza; Zheng, Ye; Dewey, Colin N; Keleş, Sündüz

    2015-10-01

    Segmental duplications and other highly repetitive regions of genomes contribute significantly to cells' regulatory programs. Advancements in next generation sequencing enabled genome-wide profiling of protein-DNA interactions by chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq). However, interactions in highly repetitive regions of genomes have proven difficult to map since short reads of 50-100 base pairs (bps) from these regions map to multiple locations in reference genomes. Standard analytical methods discard such multi-mapping reads and the few that can accommodate them are prone to large false positive and negative rates. We developed Perm-seq, a prior-enhanced read allocation method for ChIP-seq experiments, that can allocate multi-mapping reads in highly repetitive regions of the genomes with high accuracy. We comprehensively evaluated Perm-seq, and found that our prior-enhanced approach significantly improves multi-read allocation accuracy over approaches that do not utilize additional data types. The statistical formalism underlying our approach facilitates supervising of multi-read allocation with a variety of data sources including histone ChIP-seq. We applied Perm-seq to 64 ENCODE ChIP-seq datasets from GM12878 and K562 cells and identified many novel protein-DNA interactions in segmental duplication regions. Our analysis reveals that although the protein-DNA interactions sites are evolutionarily less conserved in repetitive regions, they share the overall sequence characteristics of the protein-DNA interactions in non-repetitive regions. PMID:26484757

  17. 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

  18. 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.

  19. Chaotic scattering in solitary wave interactions: a singular iterated-map description.

    PubMed

    Goodman, Roy H

    2008-06-01

    We derive a family of singular iterated maps--closely related to Poincare maps--that describe chaotic interactions between colliding solitary waves. The chaotic behavior of such solitary-wave collisions depends on the transfer of energy to a secondary mode of oscillation, often an internal mode of the pulse. This map allows us to go beyond previous analyses and to understand the interactions in the case when this mode is excited prior to the first collision. The map is derived using Melnikov integrals and matched asymptotic expansions and generalizes a "multipulse" Melnikov integral. It allows one to find not only multipulse heteroclinic orbits, but exotic periodic orbits. The maps exhibit singular behavior, including regions of infinite winding. These maps are shown to be singular versions of the conservative Ikeda map from laser physics and connections are made with problems from celestial mechanics and fluid mechanics. PMID:18601480

  20. Chaotic scattering in solitary wave interactions: A singular iterated-map description

    SciTech Connect

    Goodman, Roy H.

    2008-06-15

    We derive a family of singular iterated maps--closely related to Poincare maps--that describe chaotic interactions between colliding solitary waves. The chaotic behavior of such solitary-wave collisions depends on the transfer of energy to a secondary mode of oscillation, often an internal mode of the pulse. This map allows us to go beyond previous analyses and to understand the interactions in the case when this mode is excited prior to the first collision. The map is derived using Melnikov integrals and matched asymptotic expansions and generalizes a ''multipulse'' Melnikov integral. It allows one to find not only multipulse heteroclinic orbits, but exotic periodic orbits. The maps exhibit singular behavior, including regions of infinite winding. These maps are shown to be singular versions of the conservative Ikeda map from laser physics and connections are made with problems from celestial mechanics and fluid mechanics.

  1. 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. PMID:21344013

  2. Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3.

    PubMed

    Zhou, Min; Sandercock, Alan M; Fraser, Christopher S; Ridlova, Gabriela; Stephens, Elaine; Schenauer, Matthew R; Yokoi-Fong, Theresa; Barsky, Daniel; Leary, Julie A; Hershey, John W; Doudna, Jennifer A; Robinson, Carol V

    2008-11-25

    The eukaryotic initiation factor 3 (eIF3) plays an important role in translation initiation, acting as a docking site for several eIFs that assemble on the 40S ribosomal subunit. Here, we use mass spectrometry to probe the subunit interactions within the human eIF3 complex. Our results show that the 13-subunit complex can be maintained intact in the gas phase, enabling us to establish unambiguously its stoichiometry and its overall subunit architecture via tandem mass spectrometry and solution disruption experiments. Dissociation takes place as a function of ionic strength to form three stable modules eIF3(c:d:e:l:k), eIF3(f:h:m), and eIF3(a:b:i:g). These modules are linked by interactions between subunits eIF3b:c and eIF3c:h. We confirmed our interaction map with the homologous yeast eIF3 complex that contains the five core subunits found in the human eIF3 and supplemented our data with results from immunoprecipitation. These results, together with the 27 subcomplexes identified with increasing ionic strength, enable us to define a comprehensive interaction map for this 800-kDa species. Our interaction map allows comparison of free eIF3 with that bound to the hepatitis C virus internal ribosome entry site (HCV-IRES) RNA. We also compare our eIF3 interaction map with related complexes, containing evolutionarily conserved protein domains, and reveal the location of subunits containing RNA recognition motifs proximal to the decoding center of the 40S subunit of the ribosome. PMID:18599441

  3. 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

  4. 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. PMID:26490728

  5. 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

  6. Exposing the Alkanesulfonate Monooxygenase Protein-Protein Interaction Sites.

    PubMed

    Dayal, Paritosh V; Singh, Harsimran; Busenlehner, Laura S; Ellis, Holly R

    2015-12-29

    The alkanesulfonate monooxygenase enzymes (SsuE and SsuD) catalyze the desulfonation of diverse alkanesulfonate substrates. The SsuE enzyme is an NADPH-dependent FMN reductase that provides reduced flavin to the SsuD monooxygenase enzyme. Previous studies have highlighted the presence of protein-protein interactions between SsuE and SsuD thought to be important in the flavin transfer event, but the putative interaction sites have not been identified. Protected sites on specific regions of SsuE and SsuD were identified by hydrogen-deuterium exchange mass spectrometry. An α-helix on SsuD containing conserved charged amino acids showed a decrease in percent deuteration in the presence of SsuE. The α-helical region of SsuD is part of an insertion sequence and is adjacent to the active site opening. A SsuD variant containing substitutions of the charged residues showed a 4-fold decrease in coupled assays that included SsuE to provide reduced FMN, but there was no activity observed with an SsuD variant containing a deletion of the α-helix under similar conditions. Desulfonation by the SsuD deletion variant was only observed with an increase in enzyme and substrate concentrations. Although activity was observed under certain conditions, there were no protein-protein interactions observed with the SsuD variants and SsuE in pull-down assays and fluorimetric titrations. The results from these studies suggest that optimal transfer of reduced flavin from SsuE to SsuD requires defined protein-protein interactions, but diffusion can occur under specified conditions. A basis is established for further studies to evaluate the structural features of the alkanesulfonate monooxygenase enzymes that promote desulfonation. PMID:26634408

  7. Interaction of anions with the active site of carboxypeptidase A.

    PubMed

    Bicknell, R; Schäffer, A; Bertini, I; Luchinat, C; Vallee, B L; Auld, D S

    1988-02-01

    Studies of azide inhibition of peptide hydrolysis catalyzed by cobalt(II) carboxypeptidase A identify two anion binding sites. Azide binding to the first site (KI = 35 mM) inhibits peptide hydrolysis in a partial competitive mode while binding at the second site (KI = 1.5 M) results in competitive inhibition. The cobalt electronic absorption spectrum is insensitive to azide binding at the first site but shows marked changes upon azide binding to the second site. Thus, azide elicits a spectral change with new lambda max (epsilon M) values of 590 (330) and 540 nm (190) and a KD of 1.4 M, equal to the second kinetic KI value for the cobalt enzyme, indicating that anion binding at the weaker site involves an interaction with the active-site metal. Remarkably, in the presence of the C-terminal products of peptide or ester hydrolysis or carboxylate inhibitor analogues, anion (e.g., azide, cyanate, and thiocyanate) binding is strongly synergistic; thus, KD for azide decreases to 4 mM in the presence of L-phenylalanine. These ternary complexes have characteristic absorption, CD, MCD, and EPR spectra. The absorption spectra of azide/carboxylate inhibitor ternary complexes with Co(II)CPD display a near-UV band between 305 and 310 nm with epsilon M values around 900-1250 M-1 cm-1. The lambda max values are close to the those of the charge-transfer band of an aquo Co(II)-azide complex (310 nm), consistent with the presence of a metal azide bond in the enzyme complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2835074

  8. 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 ephemeral washes dominated by Ash (Fraxinus), Walnut (Juglans) and Hackberry (Celtis) to drier upland sites typical of desert scrub and semi-desert grassland communities. These shrublands boast a diverse mixture of shrubs, succulents and perennial grasses. In many places the vegetation could be seen to echo the history of the fort site, with management of shrub encroachment apparent in the grasslands and the paucity of trees evidence of historic cutting for timber and fire wood. Seven of the 16 vegetation types were ‘accepted’ types within the NVC while the others have been described here as specific to FOBO and have proposed status within the NVC. The map was designed to facilitate ecologically-based natural resources management and research. The map is in digital format within a geodatabase structure that allows for complex relationships to be established between spatial and tabular data, and makes accessing the product easy and seamless. The GIS format allows user flexibility and will also enable updates to be made as new information becomes available (such as revised NVC codes or vegetation type names) or in the event of major disturbance events that could impact the vegetation.

  9. Algorithmic approaches to protein-protein interaction site prediction.

    PubMed

    Aumentado-Armstrong, Tristan T; Istrate, Bogdan; Murgita, Robert A

    2015-01-01

    Interaction sites on protein surfaces mediate virtually all biological activities, and their identification holds promise for disease treatment and drug design. Novel algorithmic approaches for the prediction of these sites have been produced at a rapid rate, and the field has seen significant advancement over the past decade. However, the most current methods have not yet been reviewed in a systematic and comprehensive fashion. Herein, we describe the intricacies of the biological theory, datasets, and features required for modern protein-protein interaction site (PPIS) prediction, and present an integrative analysis of the state-of-the-art algorithms and their performance. First, the major sources of data used by predictors are reviewed, including training sets, evaluation sets, and methods for their procurement. Then, the features employed and their importance in the biological characterization of PPISs are explored. This is followed by a discussion of the methodologies adopted in contemporary prediction programs, as well as their relative performance on the datasets most recently used for evaluation. In addition, the potential utility that PPIS identification holds for rational drug design, hotspot prediction, and computational molecular docking is described. Finally, an analysis of the most promising areas for future development of the field is presented. PMID:25713596

  10. Matrix model maps and reconstruction of AdS supergravity interactions

    SciTech Connect

    Cremonini, Sera; Mello Koch, Robert de; Jevicki, Antal

    2008-05-15

    We consider the question of reconstructing (cubic) SUGRA interactions in AdS/CFT. The method we introduce is based on the matrix model maps (MMP) which were previously successfully employed at the linearized level. The strategy is to start with the map for 1/2 BPS configurations, which is exactly known (to all orders) in the Hamiltonian framework. We then use the extension of the matrix model map with the corresponding Ward identities to completely specify the interaction. A central point in this construction is the nonvanishing of off-shell interactions (even for highest-weight states)

  11. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with apurinic/apyrimidinic sites in DNA.

    PubMed

    Kosova, Anastasiya A; Khodyreva, Svetlana N; Lavrik, Olga I

    2015-09-01

    Apurinic/apyrimidinic (AP) sites are some of the most frequent DNA damages and the key intermediates of base excision repair. Certain proteins can interact with the deoxyribose of the AP site to form a Schiff base, which can be stabilized by NaBH4 treatment. Several types of DNA containing the AP site were used to trap proteins in human cell extracts by this method. In the case of single-stranded AP DNA and AP DNA duplex with both 5' and 3' dangling ends, the major crosslinking product had an apparent molecular mass of 45 kDa. Using peptide mass mapping based on mass spectrometry data, we identified the protein forming this adduct as an isoform of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) called "uracil-DNA glycosylase". GAPDH is a glycolytic enzyme with many additional putative functions, which include interaction with nucleic acids, different DNA damages and DNA repair enzymes. We investigated interaction of GAPDH purified from HeLa cells and rabbit muscles with different AP DNAs. In spite of the ability to form a Schiff-base intermediate with the deoxyribose of the AP site, GAPDH does not display the AP lyase activity. In addition, along with the borohydride-dependent adducts with AP DNAs containing single-stranded regions, GAPDH was also shown to form the stable borohydride-independent crosslinks with these AP DNAs. GAPDH was proven to crosslink preferentially to AP DNAs cleaved via the β-elimination mechanism (spontaneously or by AP lyases) as compared to DNAs containing the intact AP site. The level of GAPDH-AP DNA adduct formation depends on oxidation of the protein SH-groups; disulfide bond reduction in GAPDH leads to the loss of its ability to form the adducts with AP DNA. A possible role of formation of the stable adducts with AP sites by GAPDH is discussed. PMID:26203648

  12. Overlapping drug interaction sites of human butyrylcholinesterase dissected by site-directed mutagenesis.

    PubMed

    Loewenstein-Lichtenstein, Y; Glick, D; Gluzman, N; Sternfeld, M; Zakut, H; Soreq, H

    1996-12-01

    Butyrylcholinesterase [BuChE (acylcholine acyl hydrolase); EC 3.1.1.8] limits the access of drugs, including tacrine, to other proteins. The "atypical" BuChE variant, in which Asp70 at the rim of the active site gorge is substituted by glycine, displayed a more drastically weakened interaction with tacrine than with cocaine, dibucaine, succinylcholine, BW284c51 [1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide], or alpha-solanine. To delineate the protein domains that are responsible for this phenomenon, we mutated residues within the rim of the active site gorge, the region parallel to the peripheral site in the homologous enzyme acetylcholinesterase [AChE (acetylcholine acetyl hydrolase); EC 3.1.1.7], the oxyanion hole, and the choline-binding site. When expressed in microinjected Xenopus laevis oocytes, all mutant DNAs yielded comparable amounts of immunoreactive protein products. Most mutants retained catalytic activity close to that of wild-type BuChE and were capable of binding ligands. However, certain modifications in and around the oxyanion hole caused a dramatic loss in activity. The affinities for tacrine were reduced more dramatically than for all other ligands, including cocaine, in both oxyanion hole and choline-binding site mutants. Modified ligand affinities further demonstrated a peripheral site in residues homologous with those of AChE. BuChE mutations that prevented tacrine interactions also hampered its ability to bind other drugs and inhibitors, which suggests a partial overlap of the binding sites. This predicts that in addition to their genetic predisposition to adverse responses to tacrine, homozygous carriers of "atypical" BuChE will be overly sensitive to additional anticholinesterases and especially so when exposed to several anticholinesterases in combination. PMID:8967962

  13. 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.

  14. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Site suitability with design zone maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban... HOUSING AND URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS...

  15. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Site suitability with design zone maps. 3285.103 Section 3285.103 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT...

  16. 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…

  17. 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

  18. Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome

    PubMed Central

    Schramm, Elizabeth C.; Roumenina, Lubka T.; Rybkine, Tania; Chauvet, Sophie; Vieira-Martins, Paula; Hue, Christophe; Maga, Tara; Valoti, Elisabetta; Wilson, Valerie; Jokiranta, Sakari; Smith, Richard J. H.; Noris, Marina; Goodship, Tim; Atkinson, John P.

    2015-01-01

    The pathogenesis of atypical hemolytic uremic syndrome (aHUS) is strongly linked to dysregulation of the alternative pathway of the complement system. Mutations in complement genes have been identified in about two-thirds of cases, with 5% to 15% being in C3. In this study, 23 aHUS-associated genetic changes in C3 were characterized relative to their interaction with the control proteins factor H (FH), membrane cofactor protein (MCP; CD46), and complement receptor 1 (CR1; CD35). In surface plasmon resonance experiments, 17 mutant recombinant proteins demonstrated a defect in binding to FH and/or MCP, whereas 2 demonstrated reduced binding to CR1. In the majority of cases, decreased binding affinity translated to a decrease in proteolytic inactivation (known as cofactor activity) of C3b via FH and MCP. These results were used to map the putative binding regions of C3b involved in the interaction with MCP and CR1 and interrogated relative to known FH binding sites. Seventy-six percent of patients with C3 mutations had low C3 levels that correlated with disease severity. This study expands our knowledge of the functional consequences of aHUS-associated C3 mutations relative to the interaction of C3 with complement regulatory proteins mediating cofactor activity. PMID:25608561

  19. 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.

  20. Geological map of the future: digital, interactive, and 3D

    NASA Astrophysics Data System (ADS)

    Thorleifson, H.

    2003-12-01

    Geological survey agencies are developing methods for government geological mapping in the post-paper map era. Surficial and bedrock maps are being digitized and reconciled, while multiple generations of legends are being made accessible in a categorized format. Regional 3D geological models that integrate soils and geology, surficial and bedrock geology, as well as onshore and offshore are increasingly in demand as the information, technology, and protocols to build them progress. Applications such as regional groundwater modelling require digitizing, reconciliation, and assembly of a digital elevation model, bathymetry, offshore geology, soils, surficial geology, public domain drillhole and geophysical data, bedrock maps, and existing stratigraphic models typically expressed as structure contours. New stratigraphic modelling, particularly required for surficial unconsolidated deposits in many regions, requires information from cored holes logged by geologists as well as geophysical surveys. These high-quality results are extrapolated laterally using drill hole data, commonly large quantities of water well data of varying resolution and reliability. Much effort is required to adequately georeference the drillhole data, and to parse large numbers of unique lithological descriptions. Stratigraphic modelling methods ideally use all data and an approach that permits judgement in the acceptance or rejection of data, while interpolation and extrapolation are guided by genetic insights. Models are best captured as a grid of predicted stratigraphy profiles that convey expert opinion on interpolation and extrapolation from the data points. Reconciliation of mapping with that of neighbouring jurisdictions is a key step, as is balancing subjective definition of strata with more objective geostatistical approaches to characterizing the heterogeneous physical properties of the strata. Progress is readily achievable in undeformed strata, while deformed strata present far greater challenges. Increasingly, databases of observations and measurements are being retained alongside the interpreted model, and models are being assigned varying confidence levels such that the result is seen not as an end but a means for prioritizing new mapping. Current activity is broadening our reliance not only from paper maps to digital models, but also from plan view maps, to drillhole databases, to 3D models, to dynamic models such as groundwater flow models. Pressing user requirements demand that geological survey work rapidly advance along this progression.

  1. CapsidMaps: protein-protein interaction pattern discovery platform for the structural analysis of virus capsids using Google Maps.

    PubMed

    Carrillo-Tripp, Mauricio; Montiel-García, Daniel Jorge; Brooks, Charles L; Reddy, Vijay S

    2015-04-01

    Structural analysis and visualization of protein-protein interactions is a challenging task since it is difficult to appreciate easily the extent of all contacts made by the residues forming the interfaces. In the case of viruses, structural analysis becomes even more demanding because several interfaces coexist and, in most cases, these are formed by hundreds of contacting residues that belong to multiple interacting coat proteins. CapsidMaps is an interactive analysis and visualization tool that is designed to benefit the structural virology community. Developed as an improved extension of the φ-ψ Explorer, here we describe the details of its design and implementation. We present results of analysis of a spherical virus to showcase the features and utility of the new tool. CapsidMaps also facilitates the comparison of quaternary interactions between two spherical virus particles by computing a similarity (S)-score. The tool can also be used to identify residues that are solvent exposed and in the process of locating antigenic epitope regions as well as residues forming the inside surface of the capsid that interact with the nucleic acid genome. CapsidMaps is part of the VIPERdb Science Gateway, and is freely available as a web-based and cross-browser compliant application at http://viperdb.scripps.edu. PMID:25697908

  2. CapsidMaps: Protein-protein interaction pattern discovery platform for the structural analysis of virus capsids using Google Maps

    PubMed Central

    Carrillo-Tripp, Mauricio; Montiel-García, Daniel Jorge; Brooks, Charles L.; Reddy, Vijay

    2016-01-01

    Structural analysis and visualization of protein-protein interactions is a challenging task since it is difficult to appreciate easily the extent of all contacts made by the residues forming the interfaces. In the case of viruses, structural analysis becomes even more demanding because several interfaces coexist and, in most cases, these are formed by hundreds of contacting residues that belong to multiple interacting coat proteins. CapsidMaps is an interactive analysis and visualization tool that is designed to benefit the structural virology community. Developed as an improved extension of the φ-ψ Explorer, here we describe the details of its design and implementation. We present results of analysis of a spherical virus to showcase the features and utility of the new tool. CapsidMaps also facilitates the comparison of quaternary interactions between two spherical virus particles by computing a similarity (S)-score. The tool can also be used to identify residues that are solvent exposed and in the process of locating antigenic epitope regions as well as residues forming the inside surface of the capsid that interact with the nucleic acid genome. CapsidMaps is part of the VIPERdb Science Gateway, and is freely available as a web-based and cross-browser compliant application at http://viperdb.scripps.edu. PMID:25697908

  3. Orthogonal electrode catheter array for mapping of endocardial focal site of ventricular activation

    SciTech Connect

    Desai, J.M.; Nyo, H.; Vera, Z.; Seibert, J.A.; Vogelsang, P.J. )

    1991-04-01

    Precise location of the endocardial site of origin of ventricular tachycardia may facilitate surgical and catheter ablation of this arrhythmia. The endocardial catheter mapping technique can locate the site of ventricular tachycardia within 4-8 cm2 of the earliest site recorded by the catheter. This report describes an orthogonal electrode catheter array (OECA) for mapping and radiofrequency ablation (RFA) of endocardial focal site of origin of a plunge electrode paced model of ventricular activation in dogs. The OECA is an 8 F five pole catheter with four peripheral electrodes and one central electrode (total surface area 0.8 cm{sup 2}). In eight mongrel dogs, mapping was performed by arbitrarily dividing the left ventricle (LV) into four segments. Each segment was mapped with OECA to find the earliest segment. Bipolar and unipolar electrograms were obtained. The plunge electrode (not visible on fluoroscopy) site was identified by the earliest wave front arrival times of -30 msec or earlier at two or more electrodes (unipolar electrograms) with reference to the earliest recorded surface ECG (I, AVF, and V1). Validation of the proximity of the five electrodes of the OECA to the plunge electrode was performed by digital radiography and RFA. Pathological examination was performed to document the proximity of the OECA to the plunge electrode and also for the width, depth, and microscopic changes of the ablation. To find the segment with the earliest LV activation a total of 10 {plus minus} 3 (mean {plus minus} SD) positions were mapped. Mean arrival times at the two earlier electrodes were -39 {plus minus} 4 msec and -35 {plus minus} 3 msec. Digital radiography showed the plunge electrode to be within the area covered by all five electrodes in all eight dogs. The plunge electrode was within 1 cm2 area of the region of RFA in all eight dogs.

  4. Shared-Screen Interaction: Engaging Groups in Map-Mediated Nonverbal Communication

    NASA Astrophysics Data System (ADS)

    Chorianopoulos, Konstantinos; Rieniets, Tim

    This chapter describes the design and development of an interactive video installation that allows participants to explore a map narrative, and engage in group interactions through a shared screen. For this purpose, several layers of cartographic information were employed in a computer application, which was programmed with motion-tracking libraries in the open source tool processing. The interactive video installation has been chosen as a medium to achieve the following aims: (1) The visualization of urban-conflict as an interactive map narrative, and (2) the encouragement of social encounters through a shared screen. The development process begins with the design of interaction between the system and the participants, as well as between the participants themselves. Then we map the interaction design concepts into multimedia and architectural design. Finally, we provide a discussion on the creative process and the collaboration between different disciplines, such as architecture, urban planning, cartography, computer engineering, and media studies.

  5. An approach to mapping haplotype-specific recombination sites in human MHC class III

    SciTech Connect

    Levo, A.; Westman, P.; Partanen, J.

    1996-12-31

    Studies of the major histocompatibility complex (MHC) in mouse indicate that the recombination sites are not randomly distributed and their occurrence is haplotype-dependent. No data concerning haplotype-specific recombination sites in human are available due to the low number of informative families. To investigate haplotype-specific recombination sites in human MHC, we describe an approach based on identification of recombinant haplotypes derived from one conserved haplotype at the population level. The recombination sites were mapped by comparing polymorphic markers between the recombinant and assumed original haplotypes. We tested this approach on the extended haplotype HLA A3; B47; Bf{sup *}F; C4A{sup *}1; C4B{sup *}Q0; DR7, which is most suitable for this analysis. First, it carries a number of rare markers, and second, the haplotype, albeit rare in the general population, is frequent in patients with 21-hydroxylase (21OH) defect. We observed recombinants derived from this haplotype in patients with 21OH defect. All these haplotypes had the centromeric part (from Bf to DR) identical to the original haplotype, but they differed in HLA A and B. We therefore assumed that they underwent recombinations in the segment that separates the Bf and HLA B genes. Polymorphic markers indicated that all break points mapped to two segments near the TNF locus. This approach makes possible the mapping of preferential recombination sites in different haplotypes. 20 refs., 1 fig., 1 tab.

  6. High precision landing site mapping and rover localization for Chang'e-3 mission

    NASA Astrophysics Data System (ADS)

    Liu, ZhaoQin; Di, KaiChang; Peng, Man; Wan, WenHui; Liu, Bin; Li, LiChun; Yu, TianYi; Wang, BaoFeng; Zhou, JianLiang; Chen, HongMin

    2015-01-01

    This paper presents the comprehensive results of landing site topographic mapping and rover localization in Chang'e-3 mission. High-precision topographic products of the landing site with extremely high resolutions (up to 0.05 m) were generated from descent images and registered to CE-2 DOM. Local DEM and DOM with 0.02 m resolution were produced routinely at each waypoint along the rover traverse. The lander location was determined to be (19.51256°W, 44.11884°N, -2615.451 m) using a method of DOM matching. In order to reduce error accumulation caused by wheel slippage and IMU drift in dead reckoning, cross-site visual localization and DOM matching localization methods were developed to localize the rover at waypoints; the overall traveled distance from the lander is 114.8 m from cross-site visual localization and 111.2 m from DOM matching localization. The latter is of highest accuracy and has been verified using a LRO NAC image where the rover trajeactory is directly identifiable. During CE-3 mission operations, landing site mapping and rover localization products including DEMs and DOMs, traverse maps, vertical traverse profiles were generated timely to support teleoperation tasks such as obstacle avoidance and rover path planning.

  7. Mapping of replication initiation sites in human ribosomal DNA by nascent-strand abundance analysis

    SciTech Connect

    Yoon, Y.; Sanchez, J.A.; Brun, C.

    1995-05-01

    New techniques for mapping mammalian DNA replication origins are needed. We have modified the existing nascent-strand size analysis technique to provide an independent means of studying replication initiation sites. We call the new method nascent-strand abundance analysis. We confirmed the validity of this method with replicating simian virus 40 DNA as a model. We then applied nascent-strand abundance and nascent-strand size analyses to mapping of initiation sites in human (HeLa) ribosomal DNA (rDNA), a region previously examined exclusively by two-dimensional gel electrophoresis methods. Our results partly confirm those obtained by two-dimensional gel electrophoresis techniques. Both studies suggest that replication initiates at relatively high frequency a few kilobase pairs upstream of the transcribed region and that many additional low-frequency initiation sites are distributed through most of the remainder of the ribosomal DNA repeat unit. 51 refs., 5 figs.

  8. Mapping Membrane Protein Backbone Dynamics: A Comparison of Site-Directed Spin Labeling with NMR 15N-Relaxation Measurements

    PubMed Central

    Lo, Ryan H.; Kroncke, Brett M.; Solomon, Tsega L.; Columbus, Linda

    2014-01-01

    The ability to detect nanosecond backbone dynamics with site-directed spin labeling (SDSL) in soluble proteins has been well established. However, for membrane proteins, the nitroxide appears to have more interactions with the protein surface, potentially hindering the sensitivity to backbone motions. To determine whether membrane protein backbone dynamics could be mapped with SDSL, a nitroxide was introduced at 55 independent sites in a model polytopic membrane protein, TM0026. Electron paramagnetic resonance spectral parameters were compared with NMR 15N-relaxation data. Sequential scans revealed backbone dynamics with the same trends observed for the R1 relaxation rate, suggesting that nitroxide dynamics remain coupled to the backbone on membrane proteins. PMID:25296323

  9. Phosphorylation of the Kinase Interaction Motif in Mitogen-activated Protein (MAP) Kinase Phosphatase-4 Mediates Cross-talk between Protein Kinase A and MAP Kinase Signaling Pathways*

    PubMed Central

    Dickinson, Robin J.; Delavaine, Laurent; Cejudo-Marín, Rocío; Stewart, Graeme; Staples, Christopher J.; Didmon, Mark P.; Trinidad, Antonio Garcia; Alonso, Andrés; Pulido, Rafael; Keyse, Stephen M.

    2011-01-01

    MAP kinase phosphatase 4 (DUSP9/MKP-4) plays an essential role during placental development and is one of a subfamily of three closely related cytoplasmic dual-specificity MAPK phosphatases, which includes the ERK-specific enzymes DUSP6/MKP-3 and DUSP7/MKP-X. However, unlike DUSP6/MKP-3, DUSP9/MKP-4 also inactivates the p38α MAP kinase both in vitro and in vivo. Here we demonstrate that inactivation of both ERK1/2 and p38α by DUSP9/MKP-4 is mediated by a conserved arginine-rich kinase interaction motif located within the amino-terminal non-catalytic domain of the protein. Furthermore, DUSP9/MKP-4 is unique among these cytoplasmic MKPs in containing a conserved PKA consensus phosphorylation site 55RRXSer-58 immediately adjacent to the kinase interaction motif. DUSP9/MKP-4 is phosphorylated on Ser-58 by PKA in vitro, and phosphorylation abrogates the binding of DUSP9/MKP-4 to both ERK2 and p38α MAP kinases. In addition, although mutation of Ser-58 to either alanine or glutamic acid does not affect the intrinsic catalytic activity of DUSP9/MKP-4, phospho-mimetic (Ser-58 to Glu) substitution inhibits both the interaction of DUSP9/MKP-4 with ERK2 and p38α in vivo and its ability to dephosphorylate and inactivate these MAP kinases. Finally, the use of a phospho-specific antibody demonstrates that endogenous DUSP9/MKP-4 is phosphorylated on Ser-58 in response to the PKA agonist forskolin and is also modified in placental tissue. We conclude that DUSP9/MKP-4 is a bona fide target of PKA signaling and that attenuation of DUSP9/MKP-4 function can mediate cross-talk between the PKA pathway and MAPK signaling through both ERK1/2 and p38α in vivo. PMID:21908610

  10. NATCARB Interactive Maps and the National Carbon Explorer: a National Look at Carbon Sequestration

    DOE Data Explorer

    NATCARB is a national look at carbon sequestration. The NATCARB home page, National Carbon Explorer (http://www.natcarb.org/) provides access to information and interactive maps on a national scale about climate change, DOE's carbon sequestration program and its partnerships, CO2 emissions, and sinks. This portal provides access to interactive maps based on the Carbon Sequestration Atlas of the United States and Canada.

  11. High Precision Topographic Mapping at Chang'E-3 Landing Site with Multi-Source Data

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Liu, B.; Xu, B.; Liu, Z.; Di, K.; Zhou, J.

    2014-04-01

    Chang'e-3 (CE-3) is the first lander and rover of China following the success of Chang'e-1 and Chang'e-2 (CE-2) orbiters. High precision topographic mapping can provide detailed terrain information to ensure the safety of the rover as well as to support scientific investigations. In this research, multi-source data are co-registered into a uniform geographic framework for high precision topographic mapping at the CE-3 landing site. CE-2 CCD images with 7 m- and 1.5 m- resolutions are registered using selfcalibration bundle adjustment method with ground control points (GCPs) selected from LRO WAC mosaic map and LOLA DTM. The trajectory of CE-3 descent images are recovered using self-calibration free net bundle adjustment, and then the topographic data is rectified by absolute orientation with GCPs selected from the adjusted CE-2 DEM and DOM. Finally, these topographic data are integrated into the same geographic framework for unified, multi-scale, high precision mapping of the CE-3 landing site. Key technologies and the mapping products of this research have been used to support the surface operations of CE-3 mission.

  12. Mapping

    ERIC Educational Resources Information Center

    Kinney, Douglas M.; McIntosh, Willard L.

    1978-01-01

    Geologic mapping in the United States increased by about one-quarter in the past year. Examinations of mapping trends were in the following categories: (1) Mapping at scales of 1:100, 000; (2) Metric-scale base maps; (3) International mapping, and (4) Planetary mapping. (MA)

  13. Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions.

    PubMed Central

    Jovanovic, J N; Benfenati, F; Siow, Y L; Sihra, T S; Sanghera, J S; Pelech, S L; Greengard, P; Czernik, A J

    1996-01-01

    The ability of neurotrophins to modulate the survival and differentiation of neuronal populations involves the Trk/MAP (mitogen-activated protein kinase) kinase signaling pathway. More recently, neurotrophins have also been shown to regulate synaptic transmission. The synapsins are a family of neuron-specific phosphoproteins that play a role in regulation of neurotransmitter release, in axonal elongation, and in formation and maintenance of synaptic contacts. We report here that synapsin I is a downstream effector for the neurotrophin/Trk/MAP kinase cascade. Using purified components, we show that MAP kinase stoichiometrically phosphorylated synapsin I at three sites (Ser-62, Ser-67, and Ser-549). Phosphorylation of these sites was detected in rat brain homogenates, in cultured cerebrocortical neurons, and in isolated presynaptic terminals. Brain-derived neurotrophic factor and nerve growth factor upregulated phosphorylation of synapsin I at MAP kinase-dependent sites in intact cerebrocortical neurons and PC12 cells, respectively, while KCl- induced depolarization of cultured neurons decreased the phosphorylation state at these sites. MAP kinase-dependent phosphorylation of synapsin I significantly reduced its ability to promote G-actin polymerization and to bundle actin filaments. The results suggest that MAP kinase-dependent phosphorylation of synapsin I may contribute to the modulation of synaptic plasticity by neurotrophins and by other signaling pathways that converge at the level of MAP kinase activation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8622996

  14. Mapping Out Atom-Wall Interaction with Atomic Clocks

    SciTech Connect

    Derevianko, A.; Obreshkov, B.; Dzuba, V. A.

    2009-09-25

    We explore the feasibility of probing atom-wall interaction with atomic clocks based on atoms trapped in engineered optical lattices. Optical lattice is normal to the wall. By monitoring the wall-induced clock shift at individual wells of the lattice, one would measure the dependence of the atom-wall interaction on the atom-wall separation. We find that the induced clock shifts are large and observable at already experimentally demonstrated levels of accuracy. We show that this scheme may uniquely probe the long-range atom-wall interaction in all three qualitatively distinct regimes of the interaction: van der Waals (image-charge interaction), Casimir-Polder (QED vacuum fluctuations), and Lifshitz (thermal-bath fluctuations) regimes.

  15. Repeated mapping of reefs constructed by Sabellaria spinulosa Leuckart 1849 at an offshore wind farm site

    NASA Astrophysics Data System (ADS)

    Pearce, Bryony; Fariñas-Franco, Jose M.; Wilson, Christian; Pitts, Jack; deBurgh, Angela; Somerfield, Paul J.

    2014-07-01

    Sabellaria spinulosa reefs are considered to be sensitive and of high conservation status. This article evaluates the feasibility of using remote sensing technology to delineate S. spinulosa reefs. S. spinulosa reef habitats associated with the Thanet Offshore Windfarm site were mapped using high resolution sidescan sonar (410 kHz) and multibeam echo sounder (<1 m2) data in 2005 (baseline), 2007 (pre-construction baseline) and 2012 (post-construction). The S. spinulosa reefs were identified in the acoustic data as areas of distinct irregular texturing. Maps created using acoustic data were validated using quantitative measures of reef quality, namely tube density (as a proxy for the density of live S. spinulosa), percentage cover of S. spinulosa structures (both living and dead) and associated macrofauna derived from seabed images taken across the development site. Statistically significant differences were observed in all physical measures of S. spinulosa as well the number (S) and diversity (H') of associated species, derived from seabed images classified according to the presence or absence of reef, validating the use of high resolution sidescan sonar to map these important biogenic habitats. High precision mapping in the early stages allowed for the micro-siting of wind turbines in a way that caused minimal damage to S. spinulosa reefs during construction. These habitats have since recovered and expanded in extent. The surveys undertaken at the Thanet Offshore Windfarm site demonstrate the importance of repeat mapping for this emerging industry, allowing habitat enhancement to be attributed to the development whilst preventing background habitat degradation from being wrongly attributed to the development.

  16. Geological mapping of the Oak Ridge K-25 Site, Oak Ridge, Tennessee

    SciTech Connect

    Lemiszki, P.J.

    1994-01-01

    The Oak Ridge K-25 Site (formerly known as the Oak Ridge Gaseous Diffusion Plant) is located in the southern Appalachian Valley and Ridge province of east Tennessee and overlies an area of folded and faulted Cambrian through Ordovician sedimentary rocks in the footwall of the Whiteoak Mountain fault. Environmental restoration plans for the area require that the geology of the site be well understood because various aspects of the groundwater system are directly influenced by stratigraphic and structural characteristics of the bedrock. This study involved mapping the bedrock geology of an 18-square mile area in and around the plant site. Field mapping focused on: (1) checking the accuracy of previously mapped stratigraphic and fault contacts, (2) dividing the bedrock into distinct stratigraphic units based on field criteria, (3) determining the geometry of map-scale folds and faults, and (4) documenting various aspects of the local fracture system. Besides accomplishing all of the above tasks, results from this study have led to a number of new hypotheses regarding various aspects of the site geology. First, faulting and folding within carbonates of the Chickamauga Supergroup in the plant area has repeated certain rock units, which requires that there be a thrust fault in the subsurface below them. This thrust fault may project to the surface with the Carters Limestone. Second, thrust slices of the Rome Formation that overlie the Chickamauga carbonates may be extremely thin and have a limited aerial extent. Third, part of the Knox Group on McKinney Ridge is folded into an anticline. Evaluating the above hypotheses will require information about the subsurface that can only be acquired through drilling and surface geophysical surveys. The geologic map produced from this study can be used to evaluate the location of coreholes that will more effectively intersect a combination of stratigraphic, structural, and hydrologic targets.

  17. Molecular Mapping of Restriction-Site Associated DNA Markers in Allotetraploid Upland Cotton

    PubMed Central

    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. PMID:25894395

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

    PubMed Central

    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. PMID:26064949

  19. 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.

  20. Statewide Repository and Interactive Map of Coastal Elevation Profiles for Alaska

    NASA Astrophysics Data System (ADS)

    Gould, A.; Kinsman, N.; Southerland, L.

    2014-12-01

    Beach elevation profiles are a type of temporal coastal data that can be used to better understand coastal environments, document change and assess hazard vulnerability. The value of these measurements increases when sites are revisited seasonally and/or interannually to capture the dynamic range of coastal landforms. Static measurements of the shoreface have been collected by a number of stakeholders in Alaska since the 1960s, but, have not historically been published or made readily accessible. In cooperation with the Alaska Ocean Observing System, the Alaska Division of Geological & Geophysical Surveys (DGGS) has designed a universal data repository to house these coastal measurements. This new database has an interactive map interface that enables easy access to existing profile locations to encourage repeat observations. Users can explore profile measurements collected by DGGS and others as time-series plots and location-based images of the shoreface environment. The database has been designed to accommodate datasets collected with differing techniques, including differential leveling, survey-grade GPS or extraction from lidar-derived digital elevation models. Non-DGGS profile measurements, including community-led efforts, University of Alaska project datasets, and archived United States Geological Survey coastal profiles have also been incorporated into the database and contributions from other entities are welcomed. In addition to exhibiting the new interactive map capabilities, we also provide a case study example from Yakutat, Alaska illustrating how this tool can be incorporated into broader investigations of coastal dynamics and how these measurements can augment shoreline change assessments. The readily accessible nature of this database also promotes local involvement in community-based coastal monitoring, also demonstrated in the Yakutat example.

  1. Mapping Site Response Parameters on Cal Poly Pomona Campus Using the Spectral Ratio Method

    NASA Astrophysics Data System (ADS)

    HO, K. Y. K.; Polet, J.

    2014-12-01

    Site characteristics are an important factor in earthquake hazard assessment. To better understand site response differences on a small scale, as well as the seismic hazard of the area, we develop site response parameter maps of Cal Poly Pomona campus. Cal Poly Pomona is located in southern California about 40 km east of Los Angeles, within 50 km of San Andreas Fault. The campus is situated on top of the San Jose Fault. With about twenty two thousand students on campus, it is important to know the site response in this area. To this end, we apply the Horizontal-to-Vertical (H/V) spectral ratio technique, which is an empirical method that can be used in an urban environment with no environmental impact. This well-established method is based on the computation of the ratio of vertical ambient noise ground motion over horizontal ambient noise ground motion as a function of frequency. By applying the spectral ratio method and the criteria from Site Effects Assessment Using Ambient Excitations (SESAME) guidelines, we can determine fundamental frequency and a minimum site amplification factor. We installed broadband seismometers throughout the Cal Poly Pomona campus, with an initial number of about 15 sites. The sites are approximately 50 to 150 meters apart and about two hours of waveforms were recorded at each site. We used the Geopsy software to make measurements of the peak frequency and the amplitude of the main peak from the spectral ratio. These two parameters have been determined to be estimates of fundamental frequency and a minimum site amplification factor, respectively. Based on the geological map from the U.S. Geological Survey (USGS) and our data collected from Cal Poly Pomona campus, our preliminary results suggest that the area of campus that is covered by alluvial fan material tends to have a single significant spectral peak with a fundamental frequency of ~1Hz and a minimum amplification factor of ~3.7. The minimum depth of the surface layer is about 56 meters, as determined from the peak frequency and an estimate of the local shear wave velocity. We will present two preliminary site response parameter maps: one for fundamental frequency and one for minimum site amplification factor.

  2. Simple Ligand-Receptor Interaction Descriptor (SILIRID) for alignment-free binding site comparison.

    PubMed

    Chupakhin, Vladimir; Marcou, Gilles; Gaspar, Helena; Varnek, Alexandre

    2014-06-01

    We describe SILIRID (Simple Ligand-Receptor Interaction Descriptor), a novel fixed size descriptor characterizing protein-ligand interactions. SILIRID can be obtained from the binary interaction fingerprints (IFPs) by summing up the bits corresponding to identical amino acids. This results in a vector of 168 integer numbers corresponding to the product of the number of entries (20 amino acids and one cofactor) and 8 interaction types per amino acid (hydrophobic, aromatic face to face, aromatic edge to face, H-bond donated by the protein, H-bond donated by the ligand, ionic bond with protein cation and protein anion, and interaction with metal ion). Efficiency of SILIRID to distinguish different protein binding sites has been examined in similarity search in sc-PDB database, a druggable portion of the Protein Data Bank, using various protein-ligand complexes as queries. The performance of retrieval of structurally and evolutionary related classes of proteins was comparable to that of state-of-the-art approaches (ROC AUC ≈ 0.91). SILIRID can efficiently be used to visualize chemogenomic space covered by sc-PDB using Generative Topographic Mapping (GTM): sc-PDB SILIRID data form clusters corresponding to different protein types. PMID:25210596

  3. Inferring a protein interaction map of Mycobacterium tuberculosis based on sequences and interologs

    PubMed Central

    2012-01-01

    Background Mycobacterium tuberculosis is an infectious bacterium posing serious threats to human health. Due to the difficulty in performing molecular biology experiments to detect protein interactions, reconstruction of a protein interaction map of M. tuberculosis by computational methods will provide crucial information to understand the biological processes in the pathogenic microorganism, as well as provide the framework upon which new therapeutic approaches can be developed. Results In this paper, we constructed an integrated M. tuberculosis protein interaction network by machine learning and ortholog-based methods. Firstly, we built a support vector machine (SVM) method to infer the protein interactions of M. tuberculosis H37Rv by gene sequence information. We tested our predictors in Escherichia coli and mapped the genetic codon features underlying its protein interactions to M. tuberculosis. Moreover, the documented interactions of 14 other species were mapped to the interactome of M. tuberculosis by the interolog method. The ensemble protein interactions were validated by various functional relationships, i.e., gene coexpression, evolutionary relationship and functional similarity, extracted from heterogeneous data sources. The accuracy and validation demonstrate the effectiveness and efficiency of our framework. Conclusions A protein interaction map of M. tuberculosis is inferred from genetic codons and interologs. The prediction accuracy and numerically experimental validation demonstrate the effectiveness and efficiency of our method. Furthermore, our methods can be straightforwardly extended to infer the protein interactions of other bacterial species. PMID:22595003

  4. Combining Natural Sequence Variation with High Throughput Mutational Data to Reveal Protein Interaction Sites

    PubMed Central

    Melamed, Daniel; Young, David L.; Miller, Christina R.; Fields, Stanley

    2015-01-01

    Many protein interactions are conserved among organisms despite changes in the amino acid sequences that comprise their contact sites, a property that has been used to infer the location of these sites from protein homology. In an inter-species complementation experiment, a sequence present in a homologue is substituted into a protein and tested for its ability to support function. Therefore, substitutions that inhibit function can identify interaction sites that changed over evolution. However, most of the sequence differences within a protein family remain unexplored because of the small-scale nature of these complementation approaches. Here we use existing high throughput mutational data on the in vivo function of the RRM2 domain of the Saccharomyces cerevisiae poly(A)-binding protein, Pab1, to analyze its sites of interaction. Of 197 single amino acid differences in 52 Pab1 homologues, 17 reduce the function of Pab1 when substituted into the yeast protein. The majority of these deleterious mutations interfere with the binding of the RRM2 domain to eIF4G1 and eIF4G2, isoforms of a translation initiation factor. A large-scale mutational analysis of the RRM2 domain in a two-hybrid assay for eIF4G1 binding supports these findings and identifies peripheral residues that make a smaller contribution to eIF4G1 binding. Three single amino acid substitutions in yeast Pab1 corresponding to residues from the human orthologue are deleterious and eliminate binding to the yeast eIF4G isoforms. We create a triple mutant that carries these substitutions and other humanizing substitutions that collectively support a switch in binding specificity of RRM2 from the yeast eIF4G1 to its human orthologue. Finally, we map other deleterious substitutions in Pab1 to inter-domain (RRM2–RRM1) or protein-RNA (RRM2–poly(A)) interaction sites. Thus, the combined approach of large-scale mutational data and evolutionary conservation can be used to characterize interaction sites at single amino acid resolution. PMID:25671604

  5. The what, where, and why of priority maps and their interactions with visual working memory.

    PubMed

    Zelinsky, Gregory J; Bisley, James W

    2015-03-01

    Priority maps are winner-take-all neural mechanisms thought to guide the allocation of covert and overt attention. Here, we go beyond this standard definition and argue that priority maps play a much broader role in controlling goal-directed behavior. We start by defining what priority maps are and where they might be found in the brain; we then ask why they exist-the function that they serve. We propose that this function is to communicate a goal state to the different effector systems, thereby guiding behavior. Within this framework, we speculate on how priority maps interact with visual working memory and introduce our common source hypothesis, the suggestion that this goal state is maintained in visual working memory and used to construct all of the priority maps controlling the various motor systems. Finally, we look ahead and suggest questions about priority maps that should be asked next. PMID:25581477

  6. The what, where, and why of priority maps and their interactions with visual working memory

    PubMed Central

    Zelinsky, Gregory J.; Bisley, James W.

    2014-01-01

    Priority maps are winner-take-all neural mechanisms thought to guide the allocation of covert and overt attention. Here, we go beyond this standard definition and argue that priority maps play a much broader role in controlling goal-directed behavior. We start by defining what priority maps are and where they might be found in the brain; we then ask why they exist—the function that they serve. We propose that this function is to communicate a goal state to the different effector systems, thereby guiding behavior. Within this framework, we speculate on how priority maps interact with visual working memory and introduce our common source hypothesis, the suggestion that this goal state is maintained in visual working memory and used to construct all of the priority maps controlling the various motor systems. Finally, we look ahead and suggest questions about priority maps that should be asked next. PMID:25581477

  7. MAP Kinase Phosphatase 2 Regulates Macrophage-Adipocyte Interaction

    PubMed Central

    Jiao, Huipeng; Tang, Peng; Zhang, Yongliang

    2015-01-01

    Objective Inflammation is critical for the development of obesity-associated metabolic disorders. This study aims to investigate the role of mitogen-activated protein kinase phosphatase 2 (MKP-2) in inflammation during macrophage-adipocyte interaction. Methods White adipose tissues (WAT) from mice either on a high-fat diet (HFD) or normal chow (NC) were isolated to examine the expression of MKP-2. Murine macrophage cell line RAW264.7 stably expressing MKP-2 was used to study the regulation of MKP-2 in macrophages in response to saturated free fatty acid (FFA) and its role in macrophage M1/M2 activation. Macrophage-adipocyte co-culture system was employed to investigate the role of MKP-2 in regulating inflammation during adipocyte-macrophage interaction. c-Jun N-terminal kinase (JNK)- and p38-specific inhibitors were used to examine the mechanisms by which MKP-2 regulates macrophage activation and macrophage-adipocytes interaction. Results HFD changed the expression of MKP-2 in WAT, and MKP-2 was highly expressed in the stromal vascular cells (SVCs). MKP-2 inhibited the production of proinflammatory cytokines in response to FFA stimulation in macrophages. MKP-2 inhibited macrophage M1 activation through JNK and p38. In addition, overexpression of MKP-2 in macrophages suppressed inflammation during macrophage-adipocyte interaction. Conclusion MKP-2 is a negative regulator of macrophage M1 activation through JNK and p38 and inhibits inflammation during macrophage-adipocyte interaction. PMID:25816341

  8. 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.

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

    SciTech Connect

    Davis, F.W.; Schimel, D.S.; Friedl, M.A.; Michaelsen, J.C.; Kittel, T.G.F.; Dubayah, R.; Dozier, J. Colorado State Univ., Fort Collins Cooperative Inst. for Research in the Atmosphere, Fort Collins, CO Maryland Univ., College Park NASA, Goddard Space Flight Center, Greenbelt, MD )

    1992-11-01

    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. 30 refs.

  10. Salt Repository Project site study plan for surface geological mapping: Revision 1, December 22, 1987

    SciTech Connect

    Not Available

    1988-03-01

    This site study plan describes the Surface Geological Mapping field activities to be conducted during early stages of Site Characterization for the Deaf Smith County Site, Texas. The field program has been designed to provide data useful in addressing information and design data needs resulting from Federal/State/local regulatory requirements and repository program requirements. Air and ground surveys and an extensive literature search will be conducted to map areas within and hear proposed nuclear waste repository site in the Deaf Smith County. Findings from this study may identify additional areas requiring further investigation, for which a new site study plan will be prepared. The Salt Repository Project (SRP) Networks specify the schedule under which the program will operate. The Technical and Field Services Contractor (TFSC) is responsible for conducting the field program. Data will be handled and reported in accordance with established SRP procedures. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and the appropriate documentation is maintained. 27 refs., 13 figs., 5 tabs.

  11. Comparison of canine parvovirus with mink enteritis virus by restriction site mapping.

    PubMed Central

    McMaster, G K; Tratschin, J D; Siegl, G

    1981-01-01

    The genomes of canine parvovirus and mink enteritis virus were compared by restriction enzyme analysis of their replicative-form DNAs. Of 79 mapped sites, 68, or 86%, were found to be common for both types of DNA, indicating that canine parvovirus and mink enteritis virus are closely related viruses. Whether they evolved from a common precursor or whether canine parvovirus is derived from mink enteritis virus, however, cannot be deduced from our present data. Images PMID:6264109

  12. Comparative mapping of host-pathogen protein-protein interactions.

    PubMed

    Shah, Priya S; Wojcechowskyj, Jason A; Eckhardt, Manon; Krogan, Nevan J

    2015-10-01

    Pathogens usurp a variety of host pathways via protein-protein interactions to ensure efficient pathogen replication. Despite the existence of an impressive toolkit of systematic and unbiased approaches, we still lack a comprehensive list of these PPIs and an understanding of their functional implications. Here, we highlight the importance of harnessing genetic diversity of hosts and pathogens for uncovering the biochemical basis of pathogen restriction, virulence, fitness, and pathogenesis. We further suggest that integrating physical interaction data with orthogonal types of data will allow researchers to draw meaningful conclusions both for basic and translational science. PMID:26275922

  13. Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s)

    PubMed Central

    2015-01-01

    Undesirable side effects associated with orthosteric agonists/antagonists of cannabinoid 1 receptor (CB1R), a tractable target for treating several pathologies affecting humans, have greatly limited their translational potential. Recent discovery of CB1R negative allosteric modulators (NAMs) has renewed interest in CB1R by offering a potentially safer therapeutic avenue. To elucidate the CB1R allosteric binding motif and thereby facilitate rational drug discovery, we report the synthesis and biochemical characterization of first covalent ligands designed to bind irreversibly to the CB1R allosteric site. Either an electrophilic or a photoactivatable group was introduced at key positions of two classical CB1R NAMs: Org27569 (1) and PSNCBAM-1 (2). Among these, 20 (GAT100) emerged as the most potent NAM in functional assays, did not exhibit inverse agonism, and behaved as a robust positive allosteric modulator of binding of orthosteric agonist CP55,940. This novel covalent probe can serve as a useful tool for characterizing CB1R allosteric ligand-binding motifs. PMID:26529344

  14. Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions.

    PubMed Central

    Witherell, G W; Wimmer, E

    1994-01-01

    Translational initiation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal entry into the 5' nontranslated region of the EMCV mRNA, rather than by ribosomal scanning. Internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site (IRES). IRES elements have been proposed to be involved in the translation of picornavirus mRNAs and some cellular mRNAs. Internal ribosome binding likely requires the interaction of trans-acting factors that recognize both the mRNA and the ribosomal complex. Five cellular proteins (p52, p57, p70, p72, and p100) cross-link the EMCV IRES or fragments of the IRES. For one of these proteins, p57, binding to the IRES correlates with translation. Recently, p57 was identified to be very similar, if not identical, to polypyrimidine tract-binding protein. On the basis of cross-linking results with 21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides, consensus binding sites for p52, p57, p70, and p100 are proposed. It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence. Images PMID:8151781

  15. Competition between heavy fermion and Kondo interaction in isoelectronic A-site-ordered perovskites

    NASA Astrophysics Data System (ADS)

    Meyers, D.; Middey, S.; Cheng, J.-G.; Mukherjee, Swarnakamal; Gray, B. A.; Cao, Yanwei; Zhou, J.-S.; Goodenough, J. B.; Choi, Yongseong; Haskel, D.; Freeland, J. W.; Saha-Dasgupta, T.; Chakhalian, J.

    2014-12-01

    With current research efforts shifting towards the 4d and 5d transition metal oxides, understanding the evolution of the electronic and magnetic structure as one moves away from 3d materials is of critical importance. Here we perform X-ray spectroscopy and electronic structure calculations on A-site-ordered perovskites with Cu in the A-site and the B-sites descending along the ninth group of the periodic table to elucidate the emerging properties as d-orbitals change from partially filled 3d to 4d to 5d. The results show that when descending from Co to Ir, the charge transfers from the cuprate-like Zhang-Rice state on Cu to the t2g orbital of the B site. As the Cu d-orbital occupation approaches the Cu2+ limit, a mixed valence state in CaCu3Rh4O12 and heavy fermion state in CaCu3Ir4O12 are obtained. The investigated d-electron compounds are mapped onto the Doniach phase diagram of the competing RKKY and Kondo interactions developed for the f-electron systems.

  16. Site-wise manipulations induced phase transitions of interacting photons using superconducting circuit simulators

    NASA Astrophysics Data System (ADS)

    Deng, Xiuhao; Jia, Chunjing; Chien, Chih-Chun

    2015-03-01

    The Bose Hubbard model (BHM) of interacting bosons in a lattice has been a paradigm in many body physics. Here a quantum simulator of the BHM using a superconducting circuit is proposed. Specifically, a superconducting transmission line resonator supporting microwave photons is coupled to a charge qubit to form one site of the BHM, and adjacent sites are connected by a tunable coupler. To obtain a mapping from the superconducting circuit to the BHM, we focus on the dispersive regime where the excitations remain photon-like. Standard perturbation theory is implemented to locate the parameter range where the BHM can be simulated. This simulator allows single-site manipulations and we illustrate this feature by considering two scenarios where a single-site manipulation can drive a Mott insulator-superfluid transition. The critical point of the transition can be located by mean-field analyses and the exact diagonalization method was implemented to provide accurate results. The variance of the density and the fidelity metric clearly show signatures of this transition. Experimental realizations and other possible applications of this simulator are also discussed. The funding is supported by Graduate Scholarship of UC Merced. The computations were performed using the resources of the National Energy Research Scientific Computing Center (NERSC) supported by the U.S. Department of Energy, Office of Science, under.

  17. Competition between heavy fermion and Kondo interaction in isoelectronic A-site-ordered perovskites.

    PubMed

    Meyers, D; Middey, S; Cheng, J-G; Mukherjee, Swarnakamal; Gray, B A; Cao, Yanwei; Zhou, J-S; Goodenough, J B; Choi, Yongseong; Haskel, D; Freeland, J W; Saha-Dasgupta, T; Chakhalian, J

    2014-01-01

    With current research efforts shifting towards the 4d and 5d transition metal oxides, understanding the evolution of the electronic and magnetic structure as one moves away from 3d materials is of critical importance. Here we perform X-ray spectroscopy and electronic structure calculations on A-site-ordered perovskites with Cu in the A-site and the B-sites descending along the ninth group of the periodic table to elucidate the emerging properties as d-orbitals change from partially filled 3d to 4d to 5d. The results show that when descending from Co to Ir, the charge transfers from the cuprate-like Zhang-Rice state on Cu to the t(2g) orbital of the B site. As the Cu d-orbital occupation approaches the Cu(2+) limit, a mixed valence state in CaCu(3)Rh(4)O(12) and heavy fermion state in CaCu(3)Ir(4)O(12) are obtained. The investigated d-electron compounds are mapped onto the Doniach phase diagram of the competing RKKY and Kondo interactions developed for the f-electron systems. PMID:25517129

  18. Network Physiology: Mapping Interactions Between Networks of Physiologic Networks

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.; Bartsch, Ronny P.

    The human organism is an integrated network of interconnected and interacting organ systems, each representing a separate regulatory network. The behavior of one physiological system (network) may affect the dynamics of all other systems in the network of physiologic networks. Due to these interactions, failure of one system can trigger a cascade of failures throughout the entire network. We introduce a systematic method to identify a network of interactions between diverse physiologic organ systems, to quantify the hierarchical structure and dynamics of this network, and to track its evolution under different physiologic states. We find a robust relation between network structure and physiologic states: every state is characterized by specific network topology, node connectivity and links strength. Further, we find that transitions from one physiologic state to another trigger a markedly fast reorganization in the network of physiologic interactions on time scales of just a few minutes, indicating high network flexibility in response to perturbations. This reorganization in network topology occurs simultaneously and globally in the entire network as well as at the level of individual physiological systems, while preserving a hierarchical order in the strength of network links. Our findings highlight the need of an integrated network approach to understand physiologic function, since the framework we develop provides new information which can not be obtained by studying individual systems. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.

  19. 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 any area of interest. They can be easily customized, for example, adding placemarks or notes. Enrichment information can be added, using clickable icons, without cluttering the map. Best, the maps are fun to use. Digital interactive maps will be another effective tool for enhancing public understanding of urban creeks & watersheds.

  20. Stochastic Interaction between Neural Activity and Molecular Cues in the Formation of Topographic Maps.

    PubMed

    Owens, Melinda T; Feldheim, David A; Stryker, Michael P; Triplett, Jason W

    2015-09-23

    Topographic maps in visual processing areas maintain the spatial order of the visual world. Molecular cues and neuronal activity both play critical roles in map formation, but their interaction remains unclear. Here, we demonstrate that when molecular- and activity-dependent cues are rendered nearly equal in force, they drive topographic mapping stochastically. The functional and anatomical representation of azimuth in the superior colliculus of heterozygous Islet2-EphA3 knockin (Isl2(EphA3/+)) mice is variable: maps may be single, duplicated, or a combination of the two. This heterogeneity is not due to genetic differences, since map organizations in individual mutant animals often differ between colliculi. Disruption of spontaneous waves of retinal activity resulted in uniform map organization in Isl2(EphA3/+) mice, demonstrating that correlated spontaneous activity is required for map heterogeneity. Computational modeling replicates this heterogeneity, revealing that molecular- and activity-dependent forces interact simultaneously and stochastically during topographic map formation. PMID:26402608

  1. Mapping the Protein Interaction Network for TFIIB-Related Factor Brf1 in the RNA Polymerase III Preinitiation Complex

    PubMed Central

    Khoo, Seok-Kooi; Wu, Chih-Chien; Lin, Yu-Chun; Lee, Jin-Cheng

    2014-01-01

    TFIIB-related factor Brf1 is essential for RNA polymerase (Pol) III recruitment and open-promoter formation in transcription initiation. We site specifically incorporated a nonnatural amino acid cross-linker into Brf1 to map its protein interaction targets in the preinitiation complex (PIC). Our cross-linking analysis in the N-terminal domain of Brf1 indicated a pattern of multiple protein interactions reminiscent of TFIIB in the Pol active-site cleft. In addition to the TFIIB-like protein interactions, the Brf1 cyclin repeat subdomain is in contact with the Pol III-specific C34 subunit. With site-directed hydroxyl radical probing, we further revealed the binding between Brf1 cyclin repeats and the highly conserved region connecting C34 winged-helix domains 2 and 3. In contrast to the N-terminal domain of Brf1, the C-terminal domain contains extensive binding sites for TBP and Bdp1 to hold together the TFIIIB complex on the promoter. Overall, the domain architecture of the PIC derived from our cross-linking data explains how individual structural subdomains of Brf1 integrate the protein network from the Pol III active center to the promoter for transcription initiation. PMID:24277937

  2. Protein interaction mapping with ribosome-displayed using PLATO ORF libraries

    PubMed Central

    Zhu, Jian; Larman, H. Benjamin; Gao, Geng; Somwar, Romel; Zhang, Zijuan; Laserson, Uri; Ciccia, Alberto; Pavlova, Natalya; Church, George; Zhang, Wei; Kesari, Santosh; Elledge, Stephen J.

    2013-01-01

    Identifying physical interactions between proteins and other molecules is a critical aspect of biological analysis. Here we describe PLATO, an in vitro method for mapping such interactions by affinity enrichment of a library of full-length open reading frames displayed on ribosomes, followed by massively parallel analysis using DNA sequencing. We demonstrate the broad utility of the method by identifying known and new interacting partners of LYN kinase, patient autoantibodies and the small molecules gefitinib and dasatinib. PMID:24336473

  3. 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

  4. 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.

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

    PubMed

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

    2014-01-01

    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. PMID:25158696

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

    PubMed Central

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

    2014-01-01

    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. PMID:25158696

  7. Interacting damage models mapped onto ising and percolation models

    SciTech Connect

    Toussaint, Renaud; Pride, Steven R.

    2004-03-23

    The authors introduce a class of damage models on regular lattices with isotropic interactions between the broken cells of the lattice. Quasistatic fiber bundles are an example. The interactions are assumed to be weak, in the sense that the stress perturbation from a broken cell is much smaller than the mean stress in the system. The system starts intact with a surface-energy threshold required to break any cell sampled from an uncorrelated quenched-disorder distribution. The evolution of this heterogeneous system is ruled by Griffith's principle which states that a cell breaks when the release in potential (elastic) energy in the system exceeds the surface-energy barrier necessary to break the cell. By direct integration over all possible realizations of the quenched disorder, they obtain the probability distribution of each damage configuration at any level of the imposed external deformation. They demonstrate an isomorphism between the distributions so obtained and standard generalized Ising models, in which the coupling constants and effective temperature in the Ising model are functions of the nature of the quenched-disorder distribution and the extent of accumulated damage. In particular, they show that damage models with global load sharing are isomorphic to standard percolation theory, that damage models with local load sharing rule are isomorphic to the standard ising model, and draw consequences thereof for the universality class and behavior of the autocorrelation length of the breakdown transitions corresponding to these models. they also treat damage models having more general power-law interactions, and classify the breakdown process as a function of the power-law interaction exponent. Last, they also show that the probability distribution over configurations is a maximum of Shannon's entropy under some specific constraints related to the energetic balance of the fracture process, which firmly relates this type of quenched-disorder based damage model to standard statistical mechanics.

  8. Towards a proteome-scale map of the human protein-protein interaction network.

    PubMed

    Rual, Jean-Franois; Venkatesan, Kavitha; Hao, Tong; Hirozane-Kishikawa, Tomoko; Dricot, Amlie; Li, Ning; Berriz, Gabriel F; Gibbons, Francis D; Dreze, Matija; Ayivi-Guedehoussou, Nono; Klitgord, Niels; Simon, Christophe; Boxem, Mike; Milstein, Stuart; Rosenberg, Jennifer; Goldberg, Debra S; Zhang, Lan V; Wong, Sharyl L; Franklin, Giovanni; Li, Siming; Albala, Joanna S; Lim, Janghoo; Fraughton, Carlene; Llamosas, Estelle; Cevik, Sebiha; Bex, Camille; Lamesch, Philippe; Sikorski, Robert S; Vandenhaute, Jean; Zoghbi, Huda Y; Smolyar, Alex; Bosak, Stephanie; Sequerra, Reynaldo; Doucette-Stamm, Lynn; Cusick, Michael E; Hill, David E; Roth, Frederick P; Vidal, Marc

    2005-10-20

    Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project. PMID:16189514

  9. Interactive Web-based Access and Analysis Tools for the Western Climate Mapping Initiative (WestMap)

    NASA Astrophysics Data System (ADS)

    Comrie, A. C.; Redmond, K.; Glueck, M. F.; Reinbold, H.

    2006-12-01

    The Western Climate Mapping Consortium (WestMap) has developed a prototype web-based interactive access and resource interface to optimize public dissemination and usage of fine-scale spatial climate time series for the western United States. The western U.S. focus reflects the complex climate interactions and diverse geography that make resource management, policy considerations, and climate research challenging in this region. WestMap was conceived by a consortium comprised of the University of Arizona/CLIMAS, the Western Regional Climate Center (WRCC)/Desert Research Institute, and the PRISM group at Oregon State University, along with collaborators at Scripps Institute of Oceanography/California Applications Project, NOAA Climate Diagnostics Center, and the USDA Natural Resource Conservation Service. WestMap evolved in direct response to a multitude of requests to the WRCC and the RISAs from public and private stakeholder communities for lengthy time series of fine-scale spatial climate aggregated to user-specified domains, and related user-friendly web-based access and analysis tools. The WestMap interface is designed to link three stakeholder-driven components, 1) climate data development and operations (access, maintenance); 2) error assessment, data analysis, diagnostics, and related tools; and (3) data access, visualization, and educational resources. The 100-year PRISM 4km monthly temperature and precipitation series serve as the initial data archive, updating automatically once in operational mode. Operational user components are being designed to allow direct stakeholder access to user-specified data and resources most relevant to current needs in a timely manner. Requested resources currently in development and limited testing stages include clickable maps, regional aggregate capabilities, basic statistical analysis, time series visualization, error assessment, and download/print capability. Phased prototype testing, currently underway internally, will continue with broader stakeholder participation into Spring 2007. Operational release of the prototype interface is planned for late Summer 2007. At this meeting, we will share the latest developmental version of the WestMap interface with participants and invite feedback to help maximize the utility of the interface for the greater interdisciplinary climate community having interests in the western United States.

  10. Operation and research at the Ithaca MAP3S regional precipitation chemistry site

    SciTech Connect

    Butler, T.J.; Likens, G.E.

    1991-07-01

    Annual precipitation chemistry data from network start-up through 1988 is presented for the nine MAP3S sites. Time trends show significant negative linear regressions (P < 0.10) for SO{sub 4}{sup 2-} at 2 sites, H{sup +} at 4 sites, Ca{sup ++} at 1 site, and Na{sup +} at 1 site. Significant positive regressions over time include: NH{sub 4}{sup +} at 2 sites, Ca{sup ++} at 1 site, K{sup +} at 4 sites, and Cl{sup {minus}} at 2 sites. The Ithaca site shows the highest number of significant trends, with positive trends for Cl{sup {minus}}, NH{sub 4}{sup +}, Ca{sup ++}, and K{sup +}, and a negative trend for H{sup +}. Linear regressions of annual SO{sub 4}{sup 2-} concentrations on SO2 emissions show a significant positive relationship for Whiteface, Illinois, and Ohio at p < 0.10, 0.02, and 0.05 respectively. Overall for all MAP3S sites, plus Hubbard Brook a 25% decline in SO2 emissions over the region has been accompanied by a 16.5% decline in annual precipitation concentrations of SO{sub 4}{sup 2-}. For the region as a whole, a 20% decline in combined emissions has been accompanied to a 20% decline in H{sup +} concentrations. Thus a linear relationship exists between combined emissions and precipitation H{sup +} concentrations. No strong relationship exists for NOx emissions and precipitation NO{sub 3}{sup {minus}} concentration at the annual, seasonal or monthly level. Removing the NOx transportation sector, removing high and low precipitation values, or high pH values also does little to improve the NOx -- NO{sub 3}{sup {minus}} concentration relationships. Dry deposition components such a PAN, NO2, gaseous HNO{sub 3}, or aerosol NO{sub 3}{sup {minus}} should be included in the future with precipitation NO{sub 3}{sup {minus}} to relate emissions of NOx to nitrogen deposition. 11 refs., 27 figs.,1 tab.

  11. Site-response maps for the Los Angeles region based on earthquake ground motions

    USGS Publications Warehouse

    Hartzell, Stephen H.; Harmsen, Stephen C.; Frankel, Arthur D.; Carver, David L.; Cranswick, Edward; Meremonte, Mark E.; Michael, John A.

    1996-01-01

    Ground-motion records from aftershocks of the 1994 Northridge earthquake and main-shock records from the 1971 San Fernando, 1987 Whittier Narrows, 1991 Sierra Madre, and 1994 Northridge earthquakes are used to estimate site response in the urban Los Angeles, California, area. Two frequency bands are considered, 0.5-1.5 Hz and 2.0-6.0 Hz. Instrument characteristics prevented going to lower frequencies, and frequencies above 6.0 Hz are less important to the building inventory. Site response determined at the instrumented locations is associated with the surficial geology and contoured to produce a continuous spatial estimation of site response. The maps in this report are preliminary and will evolve as more data become available and more analysis is done.

  12. 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

  13. Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.

    PubMed

    Alessi, D R; Saito, Y; Campbell, D G; Cohen, P; Sithanandam, G; Rapp, U; Ashworth, A; Marshall, C J; Cowley, S

    1994-04-01

    Many growth factors whose receptors are protein tyrosine kinases stimulate the MAP kinase pathway by activating first the GTP-binding protein Ras and then the protein kinase p74raf-1. p74raf-1 phosphorylates and activates MAP kinase kinase (MAPKK). To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. This represents the first characterization of sites phosphorylated by this proto-oncogene product. Ser217 and Ser221 lie in a region of the catalytic domain where the activating phosphorylation sites of several other protein kinases are located. Among MAPKK family members, this region is the most conserved, suggesting that all members of the family are activated by the phosphorylation of these sites. A 'kinase-dead' MAPKK1 mutant was phosphorylated at the same residues as the wild-type enzyme, establishing that both sites are phosphorylated directly by p74raf-1, and not by autophosphorylation. Only the diphosphorylated form of MAPKK1 (phosphorylated at both Ser217 and Ser221) was detected, even when the stoichiometry of phosphorylation by p74raf-1 was low, indicating that phosphorylation of one of these sites is rate limiting, phosphorylation of the second then occurring extremely rapidly. Ser217 and Ser221 were both phosphorylated in vivo within minutes when PC12 cells were stimulated with nerve growth factor. Analysis of MAPKK1 mutants in which either Ser217 or Ser221 were changed to glutamic acid, and the finding that inactivation of maximally activated MAPKK1 required the dephosphorylation of both serines, shows that phosphorylation of either residue is sufficient for maximal activation. PMID:8157000

  14. Uncertainty in North America wet deposition isopleth maps: Effect of site selection and valid sample criteria

    SciTech Connect

    Simpson, J.C.; Olsen, A.R.

    1990-04-01

    This report considers several issues related to the preparation of isopleth maps for the display of spatial patterns of wet deposition. The valid sample criteria and data completeness rating used in the data summarization process are described. The data interpolation technique, kriging, is presented and it's derivation in terms of generalized least squares regression is given. Four different annual summaries for pH, sulfate concentration, and sulfate deposition in 1986 are prepared using either the Unified Deposition Database Committee (UDDC) definition of valid sample criteria or a relaxed valid sample criteria and the UDDC data completeness rating or a relaxed data completeness rating. The kriged estimates for the different annual summaries and the differences between these estimates are contoured. The effects of relaxing the valid sample criteria and data completeness rating are discussed. Conclusions are drawn about network operation, network design and the uncertainty of contour maps. It is recommended that in the case where the objective is contour maps to show regional patterns, the emphasis in most regions needs to be on the number of valid samples per site and the regional representativeness of the sites. 4 refs., 14 figs., 7 tabs.

  15. Applying nitrogen site-specifically using soil electrical conductivity maps and precision agriculture technology.

    PubMed

    Lund, E D; Wolcott, M C; Hanson, G P

    2001-10-16

    Soil texture varies significantly within many agricultural fields. The physical properties of soil, such as soil texture, have a direct effect on water holding capacity, cation exchange capacity, crop yield, production capability, and nitrogen (N) loss variations within a field. In short, mobile nutrients are used, lost, and stored differently as soil textures vary. A uniform application of N to varying soils results in a wide range of N availability to the crop. N applied in excess of crop usage results in a waste of the grower"s input expense, a potential negative effect on the environment, and in some crops a reduction of crop quality, yield, and harvestability. Inadequate N levels represent a lost opportunity for crop yield and profit. The global positioning system (GPS)-referenced mapping of bulk soil electrical conductivity (EC) has been shown to serve as an effective proxy for soil texture and other soil properties. Soils with a high clay content conduct more electricity than coarser textured soils, which results in higher EC values. This paper will describe the EC mapping process and provide case studies of site-specific N applications based on EC maps. Results of these case studies suggest that N can be managed site-specifically using a variety of management practices, including soil sampling, variable yield goals, and cropping history. PMID:12805883

  16. Identifying Potential Areas for Siting Interim Nuclear Waste Facilities Using Map Algebra and Optimization Approaches

    SciTech Connect

    Omitaomu, Olufemi A; Liu, Cheng; Cetiner, Sacit M; Belles, Randy; Mays, Gary T; Tuttle, Mark A

    2013-01-01

    The renewed interest in siting new nuclear power plants in the United States has brought to the center stage, the need to site interim facilities for long-term management of spent nuclear fuel (SNF). In this paper, a two-stage approach for identifying potential areas for siting interim SNF facilities is presented. In the first stage, the land area is discretized into grids of uniform size (e.g., 100m x 100m grids). For the continental United States, this process resulted in a data matrix of about 700 million cells. Each cell of the matrix is then characterized as a binary decision variable to indicate whether an exclusion criterion is satisfied or not. A binary data matrix is created for each of the 25 siting criteria considered in this study. Using map algebra approach, cells that satisfy all criteria are clustered and regarded as potential siting areas. In the second stage, an optimization problem is formulated as a p-median problem on a rail network such that the sum of the shortest distance between nuclear power plants with SNF and the potential storage sites from the first stage is minimized. The implications of obtained results for energy policies are presented and discussed.

  17. Comprehensive mapping of O-GlcNAc modification sites using a chemically cleavable tag.

    PubMed

    Griffin, Matthew E; Jensen, Elizabeth H; Mason, Daniel E; Jenkins, Courtney L; Stone, Shannon E; Peters, Eric C; Hsieh-Wilson, Linda C

    2016-05-24

    The post-translational modification of serine or threonine residues of proteins with a single N-acetylglucosamine monosaccharide (O-GlcNAcylation) is essential for cell survival and function. However, relatively few O-GlcNAc modification sites have been mapped due to the difficulty of enriching and detecting O-GlcNAcylated peptides from complex samples. Here we describe an improved approach to quantitatively label and enrich O-GlcNAcylated proteins for site identification. Chemoenzymatic labelling followed by copper(i)-catalysed azide-alkyne cycloaddition (CuAAC) installs a new mass spectrometry (MS)-compatible linker designed for facile purification of O-GlcNAcylated proteins from cell lysates. The linker also allows subsequent quantitative release of O-GlcNAcylated proteins for downstream MS analysis. We validate the approach by unambiguously identifying several established O-GlcNAc sites on the proteins α-crystallin and O-GlcNAc transferase (OGT), as well as discovering new, previously unreported sites on OGT. Notably, these novel sites on OGT lie in key functional domains of the protein, underscoring how this site identification method may reveal important biological insights into protein activity and regulation. PMID:27063346

  18. Bundling of microtubules in transfected cells does not involve an autonomous dimerization site on the MAP2 molecule.

    PubMed Central

    Burgin, K E; Ludin, B; Ferralli, J; Matus, A

    1994-01-01

    We have searched for putative dimerization sites in microtubule-associated protein 2 (MAP2) that may be involved in the bundling of microtubules. An overlapping series of fragments of the embryonic form MAP2c were created and immunologically "tagged" with an 11 amino acid sequence from human c-myc. Nonneuronal cells were transfected simultaneously with one of these myc-tagged fragments and with full-length native MAP2c. Immunolabeling with site-specific antibodies allowed the two transgene products to be located independently within the cytoplasm of a single double-transfected cell. All transfected cells contained bundled microtubules to which the full-length native MAP2 was bound. The distribution of the tagged MAP2 fragment relative to these MAP2-induced bundles was determined by the anti-myc staining. None of the fragments tested, representing all of the MAP2c sequence in overlapping pieces, were associated with MAP2-induced microtubule bundles. These results suggest that MAP2-induced bundle formation in cells does not involve an autonomous dimerization site within the MAP2 sequence. Images PMID:7919534

  19. New predictive equations and site amplification estimates for the next-generation Swiss ShakeMaps

    NASA Astrophysics Data System (ADS)

    Cauzzi, Carlo; Edwards, Benjamin; Fäh, Donat; Clinton, John; Wiemer, Stefan; Kästli, Philipp; Cua, Georgia; Giardini, Domenico

    2014-01-01

    We present a comprehensive scientific and technical update of the Swiss customization of United States Geological Survey ShakeMap, in use at the Swiss Seismological Service since 2007. The new Swiss ShakeMaps are based on predictive equations for peak ground-motions and response spectra derived from stochastic simulations tailored to Swiss seismicity. Using synthetics allows overcoming the difficulties posed by: (i) the paucity of strong-motion data recordings in Switzerland; (ii) the regional dependence of shear wave energy attenuation and focal depth distribution in the Swiss Alps and foreland; (iii) the depth dependence of stress parameters suggested by macroseismic and instrumental observations. In the new Swiss ShakeMaps, VS,30 is no longer used as proxy for site amplification at regional scale, and is replaced by macroseismic intensity increments for different soil classes, based on the recently revised earthquake catalogue of Switzerland (ECOS-09). The new implementation converts ground-motion levels into macroseismic intensity by means of ground-motion to intensity conversion equations based on the Italian strong-motion and intensity databanks and is therefore well constrained for intensities larger than VII. The new Swiss ShakeMaps show a satisfactory agreement with the macroseimic fields of both large historical events and recent well-recorded earthquakes of moderate magnitude. The new implementation is now fully consistent with the state-of-the-art in engineering seismology in Switzerland.

  20. A physical map of the X chromosome of Drosophila melanogaster: Cosmid contigs and sequence tagged sites

    SciTech Connect

    Madueno, E.; Modolell, J.; Papagiannakis, G.

    1995-04-01

    A physical map of the euchromatic X chromosome of Drosophila melanogaster has been constructed by assembling contiguous arrays of cosmids that were selected by screening a library with DNA isolated from microamplified chromosomal divisions. This map, consisting of 893 cosmids, covers {approximately}64% of the euchromatic part of the chromosome. In addition, 568 sequence tagged sites (STS), in aggregate representing 120 kb of sequenced DNA, were derived from selected cosmids. Most of these STSs, spaced at an average distance of {approximately} 35 kb along the euchromatic region of the chromosome, represent DNA tags that can be used as entry points to the fruitfly genome. Furthermore, 42 genes have been placed on the physical map, either through the hybridization of specific probes to the cosmids or through the fact that they were represented among the STSs. These provide a link between the physical and the genetic maps of D. melanogaster. Nine novel genes have been tentatively identified in Drosophila on the basis of matches between STS sequences and sequences from other species. 32 refs., 3 figs., 4 tabs.

  1. The FIRST experiment: interaction region and MAPS vertex detector

    NASA Astrophysics Data System (ADS)

    Spiriti, E.; de Napoli, M.; Romano, F.; FIRST Collaboration

    2011-06-01

    The improvement of the precision of the measurement of the nuclear cross-section, in order to fulfill the requirements of the actual Monte Carlo simulations for hadrontherapy and space radioprotection, is the main goal of the FIRST experiment. After a brief introduction on the treatment planning in hadrontherapy, this paper describes main characteristics and components of the experiment. The features of the interaction region detectors and their main needs (low material budget, high angular coverage, two tracks resolution and large trigger rate) are discussed. Special emphasis is devoted in discussing the new silicon pixel vertex detector, in particular its new developed data acquisition and its characterization with the first test results obtained with a prototype of the detector.

  2. MAP kinase-interacting kinases--emerging targets against cancer.

    PubMed

    Diab, Sarah; Kumarasiri, Malika; Yu, Mingfeng; Teo, Theodosia; Proud, Christopher; Milne, Robert; Wang, Shudong

    2014-04-24

    Mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) regulate the initiation of translation through phosphorylation of eukaryotic initiation factor 4E (eIF4E). Mnk-mediated eIF4E activation promotes cancer development and progression. While the phosphorylation of eIF4E is necessary for oncogenic transformation, the kinase activity of Mnks seems dispensable for normal development. For this reason, pharmacological inhibition of Mnks could represent an ideal mechanism-based and nontoxic therapeutic strategy for cancer treatment. In this review, we discuss the current understanding of Mnk biological roles, structures, and functions, as well as clinical implications. Importantly, we propose different strategies for identification of highly selective small molecule inhibitors of Mnks, including exploring a structural feature of their kinase domain, DFD motif, which is unique within the human kinome. We also argue that a combined targeting of Mnks and other pathways should be considered given the complexity of cancer. PMID:24613018

  3. Carbon Sequestration Atlas and Interactive Maps from the Southwest Regional Partnership on Carbon Sequestration

    DOE Data Explorer

    McPherson, Brian

    In November of 2002, DOE announced a global climate change initiative involving joint government-industry partnerships working together to find sensible, low cost solutions for reducing GHG emissions. As a result, seven regional partnerships were formed; the Southwest Regional Partnership on Carbon Sequestration (SWP) is one of those. These groups are utilizing their expertise to assess sequestration technologies to capture carbon emissions, identify and evaluate appropriate storage locations, and engage a variety of stakeholders in order to increase awareness of carbon sequestration. Stakeholders in this project are made up of private industry, NGOs, the general public, and government entities. There are a total of 44 current organizations represented in the partnership including electric utilities, oil and gas companies, state governments, universities, NGOs, and tribal nations. The SWP is coordinated by New Mexico Tech and encompasses New Mexico, Arizona, Colorado, Oklahoma, Utah, and portions of Kansas, Nevada, Texas, and Wyoming. Field test sites for the region are located in New Mexico (San Juan Basin), Utah (Paradox Basin), and Texas (Permian Basin).[Taken from the SWP C02 Sequestration Atlas] The SWP makes available at this website their CO2 Sequestration Atlas and an interactive data map.

  4. Competition between heavy-fermion and Kondo interaction in isoelectronic A-site ordered perovskites

    NASA Astrophysics Data System (ADS)

    Meyers, Derek; Middey, S.; Cheng, J.-G.; Mukherjee, S.; Gray, B. A.; Cao, Y.; Zhou, J.-S.; Goodenough, J. B.; Choi, Y.; Haskel, D.; Freeland, J. W.; Saha-Dasgupta, T.; Chakhalian, J.

    2015-03-01

    With current research efforts shifting towards the 4d and 5d transition metal oxides, understanding the evolution of the electronic and magnetic structure as one moves away from 3d materials is of critical importance. Here weX-ray spectroscopy and electronic structure calculations on A-site ordered perovskites with Cu in thesite and the B-sites descending along the 9th group of the periodic table to elucidate the emerging propertiesd-orbitals change from partially filled 3d, 4d, to 5d. The results show that when descending from Co to Ircharge transfers from the cuprate like Zhang-Rice state on Cu to the t2g orbital of the B site. As the Cuorbital occupation approaches the Cu2 + limit, a mixed-valence state in CaCu3Rh4O12 and heavy fermionin CaCu3Ir4O12 are obtained. The investigated d-electron compounds are mapped onto the Doniach phaseof the competing RKKY and Kondo interactions developed for f -electron systems.

  5. Reference interaction site model polaron theory of the hydrated electron

    NASA Astrophysics Data System (ADS)

    Laria, Daniel; Wu, David; Chandler, David

    1991-09-01

    We have extended the reference interaction site model (RISM)-polaron theory of Chandler et al. [J. Chem. Phys. 81, 1975 (1984)] to treat self-trapping and localized states of excess electrons in polar fluids. The extension is based on a new closure of the RISM equation presented herein. The theory is applied to the hydrated electron employing a simple class of electron-water pseudopotentials. Included in this class are models coinciding with those already examined by others using computer simulations. In those cases, the results for both structural and energetic properties compare well with those of simulation. The work function, or equivalently, the excess chemical potential of the hydrated electron are also computed; the theoretical result agrees with experiment to about 1%. Most interesting, however, is that as the parameter characterizing the pseudopotentials is varied, a critical parameter is found where the electron behavior changes essentially discontinuously from a trapped state to a ``super''-trapped state. This transition may have a direct bearing on theoretical efforts to explain the properties of solvated electrons.

  6. Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis.

    PubMed

    Takahashi, Kaneyoshi; Imai, Arisa; Iijima, Masumi; Yoshimoto, Nobuo; Maturana, Andrés D; Kuroda, Shun'ichi; Niimi, Tomoaki

    2015-12-21

    Neural epidermal growth factor-like (NEL)-like 1 (NELL1) is a secretory osteogenic protein comprising an N-terminal thrombospondin-1-like (TSPN) domain, four von Willebrand factor type C domains, and six epidermal growth factor-like repeats. NELL1 shows heparin-binding activity; however, the biological significance remains to be explored. In this report, we demonstrate that NELL1 binds to cell surface proteoglycans through its TSPN domain. Major heparin-binding sites were identified on the three-dimensional structural model of the TSPN domain of NELL1. Mutant analysis of the heparin-binding sites indicated that the heparin-binding activity of the TSPN domain is involved in interaction of NELL1 with cell surface proteoglycans. PMID:26627376

  7. 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.

  8. Detecting cell-adhesive sites in extracellular matrix using force spectroscopy mapping

    PubMed Central

    Chirasatitsin, Somyot; Engler, Adam J

    2010-01-01

    The cell microenvironment is composed of extracellular matrix (ECM), which contains specific binding sites that allow the cell to adhere to its surroundings. Cells employ focal adhesion proteins, which must be able to resist a variety of forces to bind to ECM. Current techniques for detecting the spatial arrangement of these adhesions, however, have limited resolution and those that detect adhesive forces lack sufficient spatial characterization or resolution. Using a unique application of force spectroscopy, we demonstrate here the ability to determine local changes in the adhesive property of a fibronectin substrate down to the resolution of the fibronectin antibody-functionalized tip diameter, ~20 nm. To verify the detection capabilities of force spectroscopy mapping (FSM), changes in loading rate and temperature were used to alter the bond dynamics and change the adhesion force. Microcontact printing was also used to pattern fluorescein isothiocyanate-conjugated fibronectin in order to mimic the discontinuous adhesion domains of native ECM. Fluorescent detection was used to identify the pattern while FSM was used to map cell adhesion sites in registry with the initial fluorescent image. The results show that FSM can be used to detect the adhesion domains at high resolution and may subsequently be applied to native ECM with randomly distributed cell adhesion sites. PMID:21152375

  9. MicroCT analysis of calcium/phosphorus ratio maps at different bone sites

    NASA Astrophysics Data System (ADS)

    Speller, R.; Pani, S.; Tzaphlidou, M.; Horrocks, J.

    2005-08-01

    The Ca/P ratio was measured in cortical bone samples from the femoral neck, front and rear tibia of rats, rabbits and lambs using synchrotron microCT. Use of a monoenergetic X-ray beam, as provided by the synchrotron facility, generates accurate 3-D maps of the linear attenuation coefficient within the sample and hence gives the ability to map different chemical components. Data were taken at 20 keV for each bone sample and calibration phantoms. From the 3-D data sets, multiple 2-D slices were reconstructed with a slice thickness of ˜28 μm and converted to Ca/P ratios using the calibration phantom results. Average values for each animal and bone site were estimated. Differences between the same bone sites from different animals are not significant (0.3< p<0.5) while those between different bone sites and different animals are highly significant ( p<10-3) demonstrating a dependence upon lifestyle and bone use. The spatial distribution of Ca/P was found to be non-uniform for some bones and some animals possibly indicating the structural mechanism for obtaining bone strength.

  10. Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites.

    PubMed

    Serrao, Erik; Cherepanov, Peter; Engelman, Alan N

    2016-01-01

    Retroviruses exhibit signature integration preferences on both the local and global scales. Here, we present a detailed protocol for (1) generation of diverse libraries of retroviral integration sites using ligation-mediated PCR (LM-PCR) amplification and next-generation sequencing (NGS), (2) mapping the genomic location of each virus-host junction using BEDTools, and (3) analyzing the data for statistical relevance. Genomic DNA extracted from infected cells is fragmented by digestion with restriction enzymes or by sonication. After suitable DNA end-repair, double-stranded linkers are ligated onto the DNA ends, and semi-nested PCR is conducted using primers complementary to both the long terminal repeat (LTR) end of the virus and the ligated linker DNA. The PCR primers carry sequences required for DNA clustering during NGS, negating the requirement for separate adapter ligation. Quality control (QC) is conducted to assess DNA fragment size distribution and adapter DNA incorporation prior to NGS. Sequence output files are filtered for LTR-containing reads, and the sequences defining the LTR and the linker are cropped away. Trimmed host cell sequences are mapped to a reference genome using BLAT and are filtered for minimally 97% identity to a unique point in the reference genome. Unique integration sites are scrutinized for adjacent nucleotide (nt) sequence and distribution relative to various genomic features. Using this protocol, integration site libraries of high complexity can be constructed from genomic DNA in three days. The entire protocol that encompasses exogenous viral infection of susceptible tissue culture cells to integration site analysis can therefore be conducted in approximately one to two weeks. Recent applications of this technology pertain to longitudinal analysis of integration sites from HIV-infected patients. PMID:27023428

  11. RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites

    PubMed Central

    Engreitz, Jesse M.; Sirokman, Klara; McDonel, Patrick; Shishkin, Alexander; Surka, Christine; Russell, Pamela; Grossman, Sharon R.; Chow, Amy Y.; Guttman, Mitchell; Lander, Eric S.

    2014-01-01

    Summary Intermolecular RNA-RNA interactions are used by many noncoding RNAs (ncRNAs) to achieve their diverse functions. To aid in identifying these contacts, we developed a method based on RNA Antisense Purification to systematically map RNA-RNA interactions (RAP-RNA) and applied it to investigate two ncRNAs implicated in RNA processing: U1 snRNA, a component of the spliceosome, and Malat1, a lncRNA that localizes to nuclear speckles. U1 and Malat1 interact with nascent transcripts through distinct targeting mechanisms. Using differential crosslinking, we confirmed that U1 directly hybridizes to both 5’ splice sites and 5’-splice-site motifs throughout introns and found that Malat1 interacts with pre-mRNAs indirectly through protein intermediates. Interactions with nascent pre-mRNAs cause U1 and Malat1 to localize proximally to chromatin at active genes, demonstrating that ncRNAs can use RNA-RNA interactions to target specific pre-mRNAs and genomic sites. RAP-RNA is sensitive to lower abundance RNAs as well, making it generally applicable for investigating ncRNAs. PMID:25259926

  12. 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 simultaneously and does not require any special software installation on users' systems. In addition, a javascript-based educational interface, dubbed "Exploring our Dynamic Planet", incorporates the map tool, explanatory material, background scientific material, and curricular activities that encourage users to explore Earth processes using the Jules Verne Voyager, Jr. tool. Exploring our Dynamic Planet can be viewed at http://www.dpc.ucar.edu/VoyagerJr/. Because of its flexibility, the map utilities can be used for hands-on exercises exploring plate interaction in a range of academic settings, from high school science classes to entry-level undergraduate to graduate-level tectonics courses.

  13. Development of Historical Water Table Maps of the 200 West Area of the Hanford Site (1950-1970)

    SciTech Connect

    Kinney, Teena M.; McDonald, John P.

    2006-09-15

    A series of detailed historical water-table maps for the 200-West Area of the Hanford Site was made to aid interpretation of contaminant distribution in the upper aquifer. The contaminants are the result of disposal of large volumes of waste to the ground during Hanford Site operations, which began in 1944 and continued into the mid-1990s. Examination of the contaminant plumes that currently exist on site shows that the groundwater beneath the 200-West Area has deviated from its pre-Hanford west-to-east flow direction during the past 50 years. By using historical water-level measurements from wells around the 200-West Area, it was possible to create water-table contour maps that show probable historic flow directions. These maps are more detailed than previously published water-table maps that encompass the entire Hanford Site.

  14. 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 Development, Area "Environment", Activity 1.3.3.1 "Prediction of triggering and risk assessment for landslides".

  15. Does an Interactive WebCT Site Help Students Learn?

    ERIC Educational Resources Information Center

    Elicker, Joelle D.; O'Malley, Alison L.; Williams, Christine M.

    2008-01-01

    We examined whether students with access to a supplemental course Web site enhanced with e-mail, discussion boards, and chat room capability reacted to it more positively than students who used a Web site with the same content but no communication features. Students used the Web sites on a voluntary basis. At the end of the semester, students…

  16. Mapping Topoisomerase IV Binding and Activity Sites on the E. coli Genome

    PubMed Central

    Lebailly, Elise; Pages, Carine; Cornet, Francois; Cosentino Lagomarsino, Marco

    2016-01-01

    Catenation links between sister chromatids are formed progressively during DNA replication and are involved in the establishment of sister chromatid cohesion. Topo IV is a bacterial type II topoisomerase involved in the removal of catenation links both behind replication forks and after replication during the final separation of sister chromosomes. We have investigated the global DNA-binding and catalytic activity of Topo IV in E. coli using genomic and molecular biology approaches. ChIP-seq revealed that Topo IV interaction with the E. coli chromosome is controlled by DNA replication. During replication, Topo IV has access to most of the genome but only selects a few hundred specific sites for its activity. Local chromatin and gene expression context influence site selection. Moreover strong DNA-binding and catalytic activities are found at the chromosome dimer resolution site, dif, located opposite the origin of replication. We reveal a physical and functional interaction between Topo IV and the XerCD recombinases acting at the dif site. This interaction is modulated by MatP, a protein involved in the organization of the Ter macrodomain. These results show that Topo IV, XerCD/dif and MatP are part of a network dedicated to the final step of chromosome management during the cell cycle. PMID:27171414

  17. 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.

  18. Large-scale mapping of human protein–protein interactions by mass spectrometry

    PubMed Central

    Ewing, Rob M; Chu, Peter; Elisma, Fred; Li, Hongyan; Taylor, Paul; Climie, Shane; McBroom-Cerajewski, Linda; Robinson, Mark D; O'Connor, Liam; Li, Michael; Taylor, Rod; Dharsee, Moyez; Ho, Yuen; Heilbut, Adrian; Moore, Lynda; Zhang, Shudong; Ornatsky, Olga; Bukhman, Yury V; Ethier, Martin; Sheng, Yinglun; Vasilescu, Julian; Abu-Farha, Mohamed; Lambert, Jean-Philippe; Duewel, Henry S; Stewart, Ian I; Kuehl, Bonnie; Hogue, Kelly; Colwill, Karen; Gladwish, Katharine; Muskat, Brenda; Kinach, Robert; Adams, Sally-Lin; Moran, Michael F; Morin, Gregg B; Topaloglou, Thodoros; Figeys, Daniel

    2007-01-01

    Mapping protein–protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein–protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24 540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein–protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations. PMID:17353931

  19. Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli

    PubMed Central

    Impens, Francis; Radoshevich, Lilliana; Cossart, Pascale; Ribet, David

    2014-01-01

    SUMOylation is an essential ubiquitin-like modification involved in important biological processes in eukaryotic cells. Identification of small ubiquitin-related modifier (SUMO)-conjugated residues in proteins is critical for understanding the role of SUMOylation but remains experimentally challenging. We have set up a powerful and high-throughput method combining quantitative proteomics and peptide immunocapture to map SUMOylation sites and have analyzed changes in SUMOylation in response to stimuli. With this technique we identified 295 SUMO1 and 167 SUMO2 sites on endogenous substrates of human cells. We further used this strategy to characterize changes in SUMOylation induced by listeriolysin O, a bacterial toxin that impairs the host cell SUMOylation machinery, and identified several classes of host proteins specifically deSUMOylated in response to this toxin. Our approach constitutes an unprecedented tool, broadly applicable to various SUMO-regulated cellular processes in health and disease. PMID:25114211

  20. High Resolution Multibeam Sonar Mapping of the Lost City Hydrothermal Site with the Autonomous Benthic Explorer

    NASA Astrophysics Data System (ADS)

    Jakuba, M. V.; Yoerger, D. R.; Bradley, A. M.; Kelley, D. S.; Karson, J. A.

    2003-12-01

    The Autonomous Benthic Explorer (ABE) of the Woods Hole Oceanographic Institution (WHOI) collected high-resolution multibeam sonar bathymetry of the Atlantis Massif and the Lost City vent site in May 2003. A Simrad Mesotech SM 2000 multibeam sonar has been fully integrated into the vehicle for this purpose. The challenging topography of the Lost City site demanded careful AUV survey planning, but also afforded the opportunity to try new survey techniques, particularly side-looking surveys along steep slopes. The quality of post-processed navigation has been improved with the addition of a model-based smoother. To aid in processing the large volume of sonar data generated during surveys, we have developed a high-level user interface in the form of a MATLAB GUI that allows users to inspect sonar images and the corresponding bathymetry concurrently. Using these techniques, bathymetric maps gridded on 2 m regular grids are visually free of trackline artifacts.

  1. MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations.

    PubMed

    Lander, E S; Green, P; Abrahamson, J; Barlow, A; Daly, M J; Lincoln, S E; Newberg, L A; Newburg, L

    1987-10-01

    With the advent of RFLPs, genetic linkage maps are now being assembled for a number of organisms including both inbred experimental populations such as maize and outbred natural populations such as humans. Accurate construction of such genetic maps requires multipoint linkage analysis of particular types of pedigrees. We describe here a computer package, called MAPMAKER, designed specifically for this purpose. The program uses an efficient algorithm that allows simultaneous multipoint analysis of any number of loci. MAPMAKER also includes an interactive command language that makes it easy for a geneticist to explore linkage data. MAPMAKER has been applied to the construction of linkage maps in a number of organisms, including the human and several plants, and we outline the mapping strategies that have been used. PMID:3692487

  2. P78-T Solid-Phase Strategy for Phosphorylation/ Glycosylation Site Mapping

    PubMed Central

    Nika, H.; Angeletti, R. Hogue

    2007-01-01

    Chemically induced β-elimination of phosphate from serine and threonine coupled with Michael addition has emerged as a chemical strategy to address both the ion suppression and the gas-phase lability of the phosphate group. In previous work, we have adopted the chemistry to solid-phase derivatization on C18 ZipTip pipette tips using barium hydroxide as elimination base and 2-amino-ethanethiol as nucleophile.1 The utility of the protocol for improved phosphopeptide detection by signal enhancement was demonstrated with low-level amounts of tryptic protein digests, and the resultant increased MS/MS spectral information content greatly facilitated mapping of the site of phosphorylation. In this report, we have focused on chemistry optimization of O-phospho and O-GlcNAc modified peptides reported as resistant to β-elimination, i.e., those containing the modified residues followed by proline. Conclusive mapping of these phosphorylation sites has become increasingly important in view of the fact that phosphorylated Ser/Thr-Pro motifs are substrates for prolyl cis/trans isomerase Pin1.2 Similarly, unambiguous site determination of O-GlcNAc modifications has more recently attracted considerable interest because of the global and often site-specific reciprocal relationship between O-GlcNAc and O-phosphate in many cellular responses.3 We have used a panel of model peptides to define the optimal reaction conditions for both concurrent and consecutive elimination/Michael addition reactions and employed carbon/C18 mixed-phase ZipTips to afford efficient binding of small hydrophilic peptides.

  3. Inclusive Composite Interval Mapping of QTL by Environment Interactions in Biparental Populations

    PubMed Central

    Li, Shanshan; Wang, Jiankang; Zhang, Luyan

    2015-01-01

    Identification of environment-specific QTL and stable QTL having consistent genetic effects across a wide range of environments is of great importance in plant breeding. Inclusive Composite Interval Mapping (ICIM) has been proposed for additive, dominant and epistatic QTL mapping in biparental populations for single environment. In this study, ICIM was extended to QTL by environment interaction (QEI) mapping for multi-environmental trials, where the QTL average effect and QEI effects could be properly estimated. Stepwise regression was firstly applied in each environment to identify the most significant marker variables which were then used to adjust the phenotypic values. One-dimensional scanning was then conducted on the adjusted phenotypic values across the environments in order to detect QTL with either average effect or QEI effects, or both average effect and QEI effects. In this way, the genetic background could be well controlled while the conventional interval mapping was applied. An empirical method to determine the threshold of logarithm of odds was developed, and the efficiency of the ICIM QEI mapping was demonstrated in simulated populations under different genetic models. One actual recombinant inbred line population was used to compare mapping results between QEI mapping and single-environment analysis. PMID:26161656

  4. RE Atlas: The U.S. Atlas of Renewable Resources (Interactive Map, GIS Data)

    DOE Data Explorer

    This interactive data map allows a user to explore the locations across the U.S. of many different basic, renewable energy resources. The many layers can be activated one at a time or in multiple combinations and the GIS display draws from a rich combination of data collections.

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

    SciTech Connect

    Comess, Kenneth M.; Sun, Chaohong; Abad-Zapatero, Cele; Goedken, Eric R.; Gum, Rebecca J.; Borhani, David W.; Argiriadi, Maria; Groebe, Duncan R.; Jia, Yong; Clampit, Jill E.; Haasch, Deanna L.; Smith, Harriet T.; Wang, Sanyi; Song, Danying; Coen, Michael L.; Cloutier, Timothy E.; Tang, Hua; Cheng, Xueheng; Quinn, Christopher; Liu, Bo; Xin, Zhili; Liu, Gang; Fry, Elizabeth H.; Stoll, Vincent; Ng, Teresa I.; Banach, David; Marcotte, Doug; Burns, David J.; Calderwood, David J.; Hajduk, Philip J.

    2012-03-02

    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 on 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, in similar fashion to Jnk-1 siRNA and to rosiglitazone treatment. Together, the data suggest that these new ligand series bind to a novel, allosteric, and physiologically relevant site and therefore represent a unique approach to identify kinase inhibitors.

  6. 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. PMID:24973612

  7. Adjustment of footprint correction for airborne flux mapping over the FIFE site

    NASA Technical Reports Server (NTRS)

    Schuepp, P. H.; Macpherson, J. I.; Desjardins, R. L.

    1992-01-01

    A meaningful interpretation of airborne flux estimates over nonuniform terrain must consider local advection from nonhomogeneous source distributions (footprint correction). An empirical procedure for footprint correction of airborne flux data obtained in the First ISLSCP Field Experiment (FIFE) 1989 is presented, based on simple analytical solutions of the diffusion equation which have been adjusted to approximate more realistic solutions. Optimized estimates of surface flux 'maps' derived from airborne observations are then constructed for maximum correlation between flux estimates and independently observed surface characteristics. This paper also includes an analysis of resolution for the given procedure, in terms of amplitude recovery of hypothetical square-wave distributions of surface flux density, and discusses its implications for the interpretation of the optimized estimates of FIFE surface flux maps. Results show that corrected spatial sink distributions are obtained by the current empirical procedure at the cost of considerable reduction in amplitude recovery of small-scale variations in surface flux density. The high spatial correlation observed between corrected flux maps and surface characteristics such as greenness or surface temperature excess is ascribed to the approximately correct positioning of the main flux gradients across the site, which can be expected to have been reproduced with amplitude recovery equal to or greater than 60 percent.

  8. The gross architecture of an antibody-combining site as determined by spin-label mapping

    PubMed Central

    Sutton, Brian J.; Gettins, Peter; Givol, David; Marsh, Derek; Wain-Hobson, Simon; Willan, Keith J.; Dwek, Raymond A.

    1977-01-01

    1. A series of Dnp (dinitrophenyl) nitroxide spin labels was used to map the dimensions of the combining site of the Dnp-binding immunoglobulin A myeloma protein MOPC 315. The method compares the observed e.s.r. (electron-spin-resonance) hyperfine splittings with those calculated on the basis of different postulated motions for the spin label. The analysis is complicated by the sensitivity of the e.s.r. hyperfine splitting to the overall `tumbling' time of the antibody–hapten complex and the polarity of the spin-label's environment. When these effects are considered quantitatively, it is then possible to determine the degree of mobility of each hapten which is allowed by the shape of the combining site. 2. The dinitrophenyl ring is rigidly held, and the depth of the site is 1.1–1.2nm and has lateral dimensions at the entrance to the site ≥0.6nm×0.9nm. The analysis of the results for spin-labelled haptens with chiral centres allows these lateral dimensions to be refined to 0.8nm and 1.1nm, and it is shown that the site is asymmetric with respect to the plane of the dinitrophenyl ring. 3. A polarity profile of the combining site was also obtained and a positively charged amino acid residue, possibly arginine-95L (light chain), was located at the entrance to the site. 4. The binding of Gd(III) to the antibody–hapten complexes results in quenching of the e.s.r. signal of the nitroxide. By using La(III) as a control, the paramagnetic contribution to the quenching is measured. 5. Analysis of the differential quenchings of the enantiomers of two five-membered nitroxide ring spin labels gives two possible locations of the metal-binding site. One of these is equidistant (0.7nm) from each of the three dinitrophenyl aromatic protons, and nuclear-magnetic-resonance relaxation studies, at 270MHz, on solutions of dinitrobenzene, Gd(III) and the Fv fragment (variable region of heavy and light chain) from protein MOPC 315 support this location for the metal site. 6. The e.s.r. and metal-binding data were then compared with the results of a model of the combining site constructed on the basis of framework invariance in immunoglobulins [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol. 41, in the press]. The overall agreement is very good. Assignments of possible chelating groups for the metal can be made. PMID:200219

  9. Mapping of impediments to contamination flow using multicomponent reflection seismology at the Savannah River Site

    SciTech Connect

    Dickenson, O.A.; Steensma, G.J.; Boyd, T.M.

    1996-11-01

    A major obstacle to the remediation of contaminated aquifers at the Savannah River Site in Aiken, South Carolina is the presence of discontinuous sand and clay lenses that are difficult to map effectively using geologic and geophysical well logs. In order to map these discontinuous sand and clay lenses we acquire two perpendicular nine-component (9C) seismic lines, a 9C Vertical Seismic Profile, (VSP) and p-wave and s-wave sonic logs in a borehole south of the Old Burial Ground at the Savannah River Site within which were available natural gamma ray and interpreted geology logs. P-wave reflections are interpreted as originating from water table, the Tan Clay, the Green Clay, the top of the Ellenton Clay, and a calcareous sediment layer within the Barnwell/McBean aquifer. Along the east-west trending line, reflectors are generally continuous except for the occurrence of a discontinuity in the upper reflectors near the east end of the line. This discontinuity could be interpreted as a sediment slump feature possibly related to the dissolution of the calcareous sediment layer, or as the eastern terminus of a large scour feature. Along the north-south trending line, reflectors are spatially less continuous and are interpreted as being cut by several channel/scour features.

  10. 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.

  11. Genetic Mapping of Specific Interactions between Aedes aegypti Mosquitoes and Dengue Viruses

    PubMed Central

    Diancourt, Laure; Caro, Valrie; Thaisomboonsuk, Butsaya; Richardson, Jason H.; Jarman, Richard G.; Ponlawat, Alongkot; Lambrechts, Louis

    2013-01-01

    Specific interactions between host genotypes and pathogen genotypes (GG interactions) are commonly observed in invertebrate systems. Such specificity challenges our current understanding of invertebrate defenses against pathogens because it contrasts the limited discriminatory power of known invertebrate immune responses. Lack of a mechanistic explanation, however, has questioned the nature of host factors underlying GG interactions. In this study, we aimed to determine whether GG interactions observed between dengue viruses and their Aedes aegypti vectors in nature can be mapped to discrete loci in the mosquito genome and to document their genetic architecture. We developed an innovative genetic mapping strategy to survey GG interactions using outbred mosquito families that were experimentally exposed to genetically distinct isolates of two dengue virus serotypes derived from human patients. Genetic loci associated with vector competence indices were detected in multiple regions of the mosquito genome. Importantly, correlation between genotype and phenotype was virus isolate-specific at several of these loci, indicating GG interactions. The relatively high percentage of phenotypic variation explained by the markers associated with GG interactions (ranging from 7.8% to 16.5%) is consistent with large-effect host genetic factors. Our data demonstrate that GG interactions between dengue viruses and mosquito vectors can be assigned to physical regions of the mosquito genome, some of which have a large effect on the phenotype. This finding establishes the existence of tangible host genetic factors underlying specific interactions between invertebrates and their pathogens in a natural system. Fine mapping of the uncovered genetic loci will elucidate the molecular mechanisms of mosquito-virus specificity. PMID:23935524

  12. 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.

  13. 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

  14. 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).

  15. 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.

  16. Quantitative analysis of anthropogenic relief features: automated mapping of charcoal kiln sites from high-resolution ALS data

    NASA Astrophysics Data System (ADS)

    Schneider, Anna; Takla, Melanie; Nicolay, Alexander; Raab, Alexandra; Raab, Thomas

    2014-05-01

    High-resolution digital elevation data from airborne laser scanning (ALS) allow for identification and mapping of so far unknown small-scale relief features that are hidden by forest cover. Especially as a result of historic land use, small anthropogenic landforms can occur, e.g., remains of charcoal kilns on sites that were used for charcoal production or ridge and furrow systems in former farmland areas. Mapping such relief features and analyzing their spatial distribution patterns can help to understand past land-use systems and their effects on landscapes. To efficiently detect and quantify small-scale relief features from high-resolution DEMs for larger areas, (semi-) automated mapping routines are required. In order to describe the number and spatial distribution of historic charcoal kiln sites in the area around Cottbus, Germany, we developed a GIS-based routine for the detection and mapping of kiln remnants from ALS elevation models with a resolution of 1 or 2 meters. The method is based on a template matching algorithm, using a combination of morphometric parameters, and is implemented within ArcGIS. The mapping results could be validated against a comprehensive database of kiln sites and diameters recorded from archaeological excavations in the forefield of the opencast mine Jänschwalde and from manual digitization of kiln remnants from Shaded Relief maps for the Jänschwalder Heide and the Tauersche Forst, north of Cottbus. A considerably high number of charcoal kiln sites could be detected in ALS data, and the diameters of the identified charcoal kilns are remarkable large in the area. For the Jänschwalder Heide, more than 5000 kiln sites in an area of 32 km2 were detected by manual digitization, with 1355 kiln sites that are wider than 12 m. These relatively large kiln sites could be mapped with detection rates that are close to those of manual digitization using the automated mapping routine. Detection quality was improved by the combination of several morphometric parameters used for template matching, as compared to a mapping based on elevation values only. In comparison to manual digitization, a combination of the described detection routine and a manual removal of falsely detected sites can considerably facilitate the mapping and distribution analysis of kiln sites or other small-scale relief features.

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

    PubMed

    Rooklin, David; Wang, Cheng; Katigbak, Joseph; Arora, Paramjit S; Zhang, Yingkai

    2015-08-24

    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

  18. Gitools: Analysis and Visualisation of Genomic Data Using Interactive Heat-Maps

    PubMed Central

    Perez-Llamas, Christian; Lopez-Bigas, Nuria

    2011-01-01

    Intuitive visualization of data and results is very important in genomics, especially when many conditions are to be analyzed and compared. Heat-maps have proven very useful for the representation of biological data. Here we present Gitools (http://www.gitools.org), an open-source tool to perform analyses and visualize data and results as interactive heat-maps. Gitools contains data import systems from several sources (i.e. IntOGen, Biomart, KEGG, Gene Ontology), which facilitate the integration of novel data with previous knowledge. PMID:21602921

  19. Mapping Single Cell-Substrate Interactions by Surface Plasmon Resonance Microscopy

    PubMed Central

    Wang, Wei; Wang, Shaopeng; Liu, Qiang; Wu, Jie; Tao, Nongjian

    2013-01-01

    We report on imaging of cell-substrate adhesion of a single cell with sub-cellular spatial resolution. Osmotic pressure was introduced to provide a controllable mechanical stimulation to the cell attached to a substrate, and high-resolution surface plasmon resonance microscopy was used to map the response of the cell, from which local cell-substrate adhesion was determined. In addition to high spatial resolution, the approach is non-invasive and fast, and allows for continuously mapping of cell-substrate interactions and single cell movements. PMID:22920036

  20. Allosteric sites can be identified based on the residue-residue interaction energy difference.

    PubMed

    Ma, Xiaomin; Qi, Yifei; Lai, Luhua

    2015-08-01

    Allosteric drugs act at a distance to regulate protein functions. They have several advantages over conventional orthosteric drugs, including diverse regulation types and fewer side effects. However, the rational design of allosteric ligands remains a challenge, especially when it comes to the identification allosteric binding sites. As the binding of allosteric ligands may induce changes in the pattern of residue-residue interactions, we calculated the residue-residue interaction energies within the allosteric site based on the molecular mechanics generalized Born surface area energy decomposition scheme. Using a dataset of 17 allosteric proteins with structural data for both the apo and the ligand-bound state available, we used conformational ensembles generated by molecular dynamics simulations to compute the differences in the residue-residue interaction energies in known allosteric sites from both states. For all the known sites, distinct interaction energy differences (>25%) were observed. We then used CAVITY, a binding site detection program to identify novel putative allosteric sites in the same proteins. This yielded a total of 31 "druggable binding sites," of which 21 exhibited >25% difference in residue interaction energies, and were hence predicted as novel allosteric sites. Three of the predicted allosteric sites were supported by recent experimental studies. All the predicted sites may serve as novel allosteric sites for allosteric ligand design. Our study provides a computational method for identifying novel allosteric sites for allosteric drug design. PMID:25185787

  1. Functional mapping of neural sites mediating prolactin-induced hyperphagia in doves.

    PubMed

    Hnasko, R M; Buntin, J D

    1993-10-01

    Microinjections of prolactin (PRL) into the ventromedial nucleus of the hypothalamus (VMN) or the preoptic area (POA) have been previously shown to increase food intake and body weight in ring doves. In an attempt to corroborate these results and to provide a more complete map of PRL-sensitive brain sites mediating the orexigenic action of PRL, a microinjection procedure was employed in the present study that delivered PRL or saline vehicle in extremely small volumes (10 nl/injection) to a variety of diencephalic sites in dove brain that had been previously demonstrated to contain high concentrations of PRL receptors. Estimates obtained from one female subject given a single 10 nl injection of [125I]ovine PRL into the VMN supported the claim that such injection volumes resulted in limited diffusion, as 80% of the tissue radioactivity was found within a 280 mm area surrounding the injection site at 30 min after injection. Food intake of cannulated male doves in the mapping study was monitored daily during a 6 day baseline period, an initial 4 day treatment period, a 6-12 day post-treatment recovery period, and a second 4 day treatment period. Approximately half of the birds received PRL injections (50 ng/10 nl twice daily) and saine vehicle injections (10 nl twice daily) during the first and second treatment periods, respectively, while remaining birds received these treatments in the reverse order. No significant changes in food intake across baseline, vehicle, post-treatment, or PRL treatment periods were observed in birds with injection sites in the lateral POA, paraventricular nucleus of the hypothalamus (PVN), or the medial-basal hypothalamic region between the tuberal hypothalamus (TU) and VMN. In contrast, injections of PRL into the VMN area, medial POA, or TU resulted in average daily food intake values that significantly exceeded those recorded during other periods. The most robust feeding response was seen in the VMN group, where PRL injections resulted in a 58% increase in food intake over that recorded during injection of vehicle. This increase was significantly greater than that observed following PRL injections into the mPOA (26%) or the TU (32%). These findings suggest that the VMN may be a primary site of PRL action in promoting hyperphagia in this species, although PRL effects at other diencephalic loci, such as the mPOA and TU, may also contribute to the orexigenic action of this hormone. PMID:8221107

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

    NASA Astrophysics Data System (ADS)

    Cabrol, Nathalie A.; Briggs, Geoffrey A.

    1999-06-01

    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.

  3. Global transcriptional start site mapping using differential RNA sequencing reveals novel antisense RNAs in Escherichia coli.

    PubMed

    Thomason, Maureen K; Bischler, Thorsten; Eisenbart, Sara K; Förstner, Konrad U; Zhang, Aixia; Herbig, Alexander; Nieselt, Kay; Sharma, Cynthia M; Storz, Gisela

    2015-01-01

    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

  4. 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.

  5. 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).

  6. Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data

    PubMed Central

    Scott, David L; Diez, Gerold; Goldmann, Wolfgang H

    2006-01-01

    Background Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein. Results We have developed a novel computational program that predicts a protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling, Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD spectroscopy and calorimetry experiments confirm that the interfaces predicted for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and vinculin) partially insert into lipid aggregates. The validity of these predictions is supported by an analysis of the available three-dimensional structural data. The lipid interfaces predicted by our algorithm generally contain energetically favorable secondary structures (e.g., an amphipathic alpha-helix flanked by a flexible hinge or loop region), are solvent-exposed in the intact protein, and possess favorable local or global electrostatic properties. Conclusion At present, there are few reliable methods to determine the region of a protein that mediates biologically important interactions with lipids or lipid aggregates. Our matrix-based algorithm predicts lipid interaction sites that are consistent with the available biochemical and structural data. To determine whether these sites are indeed correctly identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography. PMID:16569237

  7. 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

  8. Mapping the complex morphology of cell interactions with nanowire substrates using FIB-SEM.

    PubMed

    Wierzbicki, Rafał; Købler, Carsten; Jensen, Mikkel R B; Lopacińska, 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

  9. 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

  10. Mapping of noise impact provoked by the execution of foundation piles at high rise building sites.

    PubMed

    de Araújo, Adolpho Guido; Gusmão, Alexandre Duarte; Rabbani, Emilia Rahnemay Kohman; Fucale, Stela Paulino

    2012-01-01

    The objective of this work is to map, in a limited area inside and outside of the worksite, the environmental impact generated by sound pollution coming from the driving of foundation piles for high rise buildings, as well as to observe and check if the noise levels produced by the emitting source are tolerable in the urban environment. The methodology of the work includes a survey of technical references about the subject; measurement of noises surrounding the worksite during the foundation phase for four distinct buildings, with different types of piles: prefabricated piles, continuous helical displacement piles , traditional compaction piles and Terra Probe compaction piles. A grid of points was built due to the time of driving and after that the measurements of environmental noises were performed emitted by the execution of each type of pile using a sound level meter. The interpretation of the measurements and their impacts on the neighborhood of the building were performed using the computational tool Suffer for creating noise level contours. The X and Y axes of the grid represent the distances in meters of the area studied and the Z axis represents the noise measured in dB. The contours developed represent the mapping of the noise at the worksites and their surroundings. The mapping of the urban impact of noise, the measurement of its dimensions, and the examination of its propagation around the building are important subsides to adequate individual and collective protection procedures. Seventy one points were measured at four building sites with different types of piles, and the results showed that at only three points was the noise within the limits of the Municipal Law of Recife of 70 dB, which proves the relevance of the research. Finally, the comparative analysis between the four types of piles shows that the continuous helical displacement pile emits the lowest noise level among the four pile types studied. PMID:22317218

  11. Molecular epidemiology and restriction site mapping of adenovirus type 3 genome types.

    PubMed Central

    Adrian, T; Best, B; Hierholzer, J C; Wigand, R

    1989-01-01

    One hundred thirty-eight strains of adenovirus type 3 isolated from patients in the United States, West Germany, and other regions between 1961 and 1984 were analyzed with six restriction endonucleases; 18 genome types were found. BglII was the most discriminative enzyme. Mapping of altered restriction sites was also performed for all six enzymes. The genome types D1 (like the prototype) and D3 prevailed among 45 and 47 strains, respectively. All genome types could be divided into two groups related to D1 or D3. Several clusters of infections by strains with the same genome type were observed. Only hints of differences were found in the pathogenicities of individual genome types. D1 strains were present in the United States and in Europe; group D3 prevailed almost exclusively in the United States. Images PMID:2546977

  12. Using Hadoop File System and MapReduce in a small/medium Grid site

    NASA Astrophysics Data System (ADS)

    Riahi, H.; Donvito, G.; Fanò, L.; Fasi, M.; Marzulli, G.; Spiga, D.; Valentini, A.

    2012-12-01

    Data storage and data access represent the key of CPU-intensive and data-intensive high performance Grid computing. Hadoop is an open-source data processing framework that includes fault-tolerant and scalable distributed data processing model and execution environment, named MapReduce, and distributed File System, named Hadoop distributed File System (HDFS). HDFS was deployed and tested within the Open Science Grid (OSG) middleware stack. Efforts have been taken to integrate HDFS with gLite middleware. We have tested the File System thoroughly in order to understand its scalability and fault-tolerance while dealing with small/medium site environment constraints. To benefit entirely from this File System, we made it working in conjunction with Hadoop Job scheduler to optimize the executions of the local physics analysis workflows. The performance of the analysis jobs which used such architecture seems to be promising, making it useful to follow up in the future.

  13. Geologic map of the Mine Mountain area, Nevada Test Site, southern Nevada

    SciTech Connect

    Cashman, P.H.; Cole, J.C.

    1998-10-05

    The Mine Mountain area is a small range of hills on the west side of the central Yucca Flat basin on the Nevada Test Site, Nye County, Nevada. This map portrays the very complex relationships among the pre-Tertiary stratigraphic units of the region. Rocks and structures of the Mine Mountain area record the compounded effects of: (1) eastward-directed, foreland-vergent thrusting; (2) younger folds and thrusts formed by hinterland vergence in a general westerly direction; and (3) low-angle normal faulting formed by extension along a northeast-southwest trend. All of these structures are older than the oldest middle Miocene volcanic rocks that were deposited on the flanks of the Mine Mountain terrane. High-angle faults that post-date these volcanic rocks locally show displacements of several hundred meters, but do not strongly affect patterns in the pre-Tertiary rocks.

  14. Mapping and consensus sequence identification for multiple vinculin binding sites within the talin rod.

    PubMed

    Gingras, Alexandre R; Ziegler, Wolfgang H; Frank, Ronald; Barsukov, Igor L; Roberts, Gordon C K; Critchley, David R; Emsley, Jonas

    2005-11-01

    The interaction between the cytoskeletal proteins talin and vinculin plays a key role in integrin-mediated cell adhesion and migration. Three vinculin binding sites (VBS1-3) have previously been identified in the talin rod using a yeast two-hybrid assay. To extend these studies, we spot-synthesized a series of peptides spanning all the alpha-helical regions predicted for the talin rod and identified eight additional VBSs, two of which overlap key functional regions of the rod, including the integrin binding site and C-terminal actin binding site. The talin VBS alpha-helices bind to a hydrophobic cleft in the N-terminal vinculin Vd1 domain. We have defined the specificity of this interaction by spot-synthesizing a series of 25-mer talin VBS1 peptides containing substitutions with all the commonly occurring amino acids. The consensus for recognition is LXXAAXXVAXX- VXXLIXXA with distinct classes of hydrophobic side chains at positions 1, 4, 5, 8, 9, 12, 15, and 16 required for vinculin binding. Positions 1, 8, 12, 15, and 16 require an aliphatic residue and will not tolerate alanine, whereas positions 4, 5, and 9 are less restrictive. These preferences are common to all 11 VBS sequences with a minor variation occurring in one case. A crystal structure of this variant VBS peptide in complex with the vinculin Vd1 domain reveals a subtly different mode of vinculin binding. PMID:16135522

  15. 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 evaluate their students based on pre-determined criteria. The IMAPS activities are developed in partnerships with the Department of Earth Sciences at Western University, Sports Western, the Thames Valley District School Board, and Dimentians Web Marketing and Design. We are continually looking for new collaborators to help design or test our inquiry- and web-based activities, provide feedback on our programs, or volunteer with us. Please contact cpsxoutreach@uwo.ca if you are interested.

  16. MAPPING MOLECULAR FLEXIBILITY OF PROTEINS WITH SITE DIRECTED SPIN LABELING: A CASE STUDY OF MYOGLOBIN‡

    PubMed Central

    López, Carlos J.; Oga, Shirley; Hubbell, Wayne L.

    2012-01-01

    Site directed spin labeling (SDSL) has potential for mapping protein flexibility under physiological conditions. The purpose of the present study was to explore this potential using 38 singly spin-labeled mutants of myoglobin distributed throughout the sequence. Correlation of the EPR spectra with protein structure provides new evidence that the site dependent variation in lineshape, and hence motion of the spin label, is due largely to differences in mobility of the helical backbone in the ns time range. Fluctuations between conformational substates, typically in the μs-ms time range, are slow on the EPR time scale and the spectra provide a snapshot of conformational equilibria frozen in time as revealed by multiple components in the spectra. A recent study showed that osmolyte perturbation can positively identify conformational exchange as the origin of multicomponent spectra (Lopez et al. (2009), Protein Sci. 18, 1637). In the present study this new strategy is employed in combination with lineshape analysis and pulsed-EPR interspin distance measurements to investigate the conformation and flexibility of myoglobin in three folded and partially folded states. The regions identified to be in conformational exchange in the three forms agree remarkably well with those assigned by NMR, but the faster time scale of EPR allows characterization of localized states not detected in NMR. Collectively, the results suggest that SDSL-EPR and osmolyte perturbation provide a facile means for mapping the amplitude of fast backbone fluctuations and for detecting sequences in slow conformational exchange in folded and partially folded protein sequences. PMID:22809279

  17. Application of time domain induced polarization to the mapping of lithotypes in a landfill site

    NASA Astrophysics Data System (ADS)

    Gazoty, A.; Fiandaca, G.; Pedersen, J.; Auken, E.; Christiansen, A. V.; Pedersen, J. K.

    2012-06-01

    A direct current (DC) resistivity and time domain induced polarization (TDIP) survey was undertaken at a decommissioned landfill site situated in Hørløkke, Denmark, for the purpose of mapping the waste deposits and to discriminate important geological units that control the hydrology of the surrounding area. It is known that both waste deposits and clay have clear signatures in TDIP data, making it possible to enhance the resolution of geological structures compared to DC surveys alone. Four DC/TDIP profiles were carried out crossing the landfill, and another seven profiles in the surroundings provide a sufficiently dense coverage of the entire area. The whole dataset was inverted using a 1-D laterally constrained inversion scheme, recently implemented for TDIP data, in order to use the entire decay curves for reconstructing the electrical parameters of the soil in terms of the Cole-Cole polarization model. Results show that it is possible to resolve both the geometry of the buried waste body and key geological structures. In particular, it was possible to find a silt/clay lens at depth that correlates with the flow direction of the pollution plume spreading out from the landfill and to map a shallow sandy layer rich in clay that likely has a strong influence on the hydrology of the site. This interpretation of the geophysical findings was constrained by borehole data, in terms of geology and gamma ray logging. The results of this study are important for the impact of the resolved geological units on the hydrology of the area, making it possible to construct more realistic scenarios of the variation of the pollution plume as a function of the climate change.

  18. Application of time domain induced polarization to the mapping of lithotypes in a landfill site

    NASA Astrophysics Data System (ADS)

    Gazoty, A.; Fiandaca, G.; Pedersen, J.; Auken, E.; Christiansen, A. V.; Pedersen, J. K.

    2012-01-01

    A DC resistivity (DC) and Time Domain Induced Polarization (TDIP) survey was undertaken at a decommissioned landfill site situated in Hørløkke, Denmark, for the purpose of mapping the waste deposits and to discriminate important geological units that control the hydrology of the surrounding area. It is known that both waste deposits and clay have clear signatures in TDIP data, making possible to enhance the resolution of geological structures, when compared to DC surveys alone. Four DC/TDIP profiles were carried out crossing the landfill and another seven profiles in the surroundings, giving a dense coverage over the entire area. The whole dataset was inverted using a 1-D Laterally Constrained Inversion scheme, recently implemented for IP data, in order to use the entire decay curves for reconstructing the electrical parameters of the soil in terms of the Cole-Cole polarization model. Results show that it is possible to both resolve the geometry of the buried waste body and key geological structures. In particular, it was possible to find a silt/clay lens at depth, which correlates with the flow direction of the pollution plume spreading out from the landfill, and to map a shallow sandy layer rich in clay that likely has a strong influence on the hydrology of the site. This interpretation of the geophysical findings was constrained by boreholes data, in terms of geology and gamma ray logging. The results of this study are important for the impact that the resolved geological units have in the hydrology of the area, making it possible to construct more realistic scenarios of the variation of the pollution plume as a function of the climate change.

  19. An integrated study of spatial multicriteria analysis and mathematical modelling for managed aquifer recharge site suitability mapping and site ranking at Northern Gaza coastal aquifer.

    PubMed

    Rahman, Mohammad Azizur; Rusteberg, Bernd; Uddin, Mohammad Salah; Lutz, Annegret; Saada, Muath Abu; Sauter, Martin

    2013-07-30

    This paper describes an integrated approach of site suitability mapping and ranking of the most suitable sites, for the implementation of Managed Aquifer Recharge (MAR) projects, using spatial multicriteria decision analysis (SMCDA) techniques and mathematical modelling. The SMCDA procedure contains constraint mapping, site suitability analysis with criteria standardization and weighting, criteria overlay by analytical hierarchy process (AHP) combined with weighted linear combination (WLC) and ordered weighted averaging (OWA), and sensitivity analysis. The hydrogeological impacts of the selected most suitable sites were quantified by using groundwater flow and transport modelling techniques. Finally, ranking of the selected sites was done with the WLC method. The integrated approach is demonstrated by a case study in the coastal aquifer of North Gaza. Constraint mapping shows that 50% of the total study area is suitable for MAR implementation. About 25% of the total area is "very good" and 25% percent is "good" for MAR, according to the site suitability analysis. Six locations were selected and ranked against six representative decision criteria. Long term (year 2003 to year 2040) groundwater flow and transport simulations were performed to quantify the selected criteria under MAR project operation conditions at the selected sites. Finally, the suitability mapping and hydrogeological investigation recommends that the location of the existing infiltration ponds, constructed near the planned North Gaza Wastewater Treatment Plant (NGWWTP) is most suitable for MAR project implementation. This paper concludes that mathematical modelling should be combined with the SMCDA technique in order to select the best location for MAR project implementation. Besides MAR project implementation, the generalised approach can be applicable for any other water resources development project that deals with site selection and implementation. PMID:23603773

  20. Improving the Apollo 12 landing site mapping with Chandrayaan M3 data

    NASA Astrophysics Data System (ADS)

    Chemin, Yann; Crawford, Ian; Bugiolacchi, Roberto; Irfan, Huma; Alexander, Louise

    2014-05-01

    The geology of the Apollo 12 landing site has been the subject of many studies, including recently by Korotev et al. (2011) and Snape et al. (2013). This research attempts to bring additional understanding from a remote sensing perspective using the Moon Mineralogy Mapper (M3) sensor data, onboard the Chandrayaan lunar orbiter. This has a higher spatial-spectral resolution sensor than the Clementine UV-Vis sensor and provides the opportunity to study the lunar surface with detailed spectral signatures. Mapping of FeO (wt%) and TiO2 (wt%) is done using the methods of Lucey et al. (2000) and Wilcox et al. (2005). A FeO & TiO2 processing module (i.feotio2) is made specifically for this research within the Free & Open Source Software GRASS GIS. Attempts will be made to estimate the lava flow thickness using the method of Bugiolacchi et al. (2006) and individual lava layers thicknesses (Weider et al., 2010). Integration of this new information will be put in perspective and integrated with previous work. Analysis from the combined higher spatial and spectral resolutions will improve the accuracy of the geological mapping at the Apollo 12 landing site. References Bugiolacchi, R., Spudis, P.D., Guest, J.E., 2006. Stratigraphy and composition of lava flows in Mare Nubium and Mare Cognitum. Meteoritics & Planetary Science. 41(2):285-304. Korotev, R.L., Jolliff, B.L., Zeigler, R.A., Seddio, S.M., Haskin, L.A., 2011. Apollo 12 revisited. Geochimica et Cosmochimica Acta. 75(6):1540-1573. Lucey, P.G., Blewett, D.T., Jolliff, B.L., 2000. Lunar iron and titanium abundance algorithms based on final processing of Clementine ultraviolet-visible images. J. Geophys. Res. 105(E8): 20297-20305. Snape, J.F., Alexander, L., Crawford, I.A., Joy, K.H., 2013. Basaltic Regolith Sample 12003,314: A New Member of the Apollo 12 Feldspathic Basalt Suite? Lunar and Planetary Institute Science Conference Abstracts 44:1044. Weider, S.Z., Crawford, I.A. and Joy, K.H., "Individual lava flow thicknesses in Oceanus Procellarum and Mare Serenitatis determined from Clementine multi-spectral data," Icarus, 209, 323-336, (2010). Wilcox, B.B., Lucey, P.G., Gillis, J.J., 2005. Mapping iron in the lunar mare: An improved approach. J. Geophys. Res. 110(E11):2156-2202.

  1. Construction and application for QTL analysis of a Restriction Site Associated DNA (RAD) linkage map in barley

    PubMed Central

    2011-01-01

    Background Linkage maps are an integral resource for dissection of complex genetic traits in plant and animal species. Canonical map construction follows a well-established workflow: an initial discovery phase where genetic markers are mined from a small pool of individuals, followed by genotyping of selected mapping populations using sets of marker panels. A newly developed sequence-based marker technology, Restriction site Associated DNA (RAD), enables synchronous single nucleotide polymorphism (SNP) marker discovery and genotyping using massively parallel sequencing. The objective of this research was to assess the utility of RAD markers for linkage map construction, employing barley as a model system. Using the published high density EST-based SNP map in the Oregon Wolfe Barley (OWB) mapping population as a reference, we created a RAD map using a limited set of prior markers to establish linakge group identity, integrated the RAD and prior data, and used both maps for detection of quantitative trait loci (QTL). Results Using the RAD protocol in tandem with the Illumina sequence by synthesis platform, a total of 530 SNP markers were identified from initial scans of the OWB parental inbred lines - the "dominant" and "recessive" marker stocks - and scored in a 93 member doubled haploid (DH) mapping population. RAD sequence data from the structured population was converted into allele genotypes from which a genetic map was constructed. The assembled RAD-only map consists of 445 markers with an average interval length of 5 cM, while an integrated map includes 463 RAD loci and 2383 prior markers. Sequenced RAD markers are distributed across all seven chromosomes, with polymorphic loci emanating from both coding and noncoding regions in the Hordeum genome. Total map lengths are comparable and the order of common markers is identical in both maps. The same large-effect QTL for reproductive fitness traits were detected with both maps and the majority of these QTL were coincident with a dwarfing gene (ZEO) and the VRS1 gene, which determines the two-row and six-row germplasm groups of barley. Conclusions We demonstrate how sequenced RAD markers can be leveraged to produce high quality linkage maps for detection of single gene loci and QTLs. By combining SNP discovery and genotyping into parallel sequencing events, RAD markers should be a useful molecular breeding tool for a range of crop species. Expected improvements in cost and throughput of second and third-generation sequencing technologies will enable more powerful applications of the sequenced RAD marker system, including improvements in de novo genome assembly, development of ultra-high density genetic maps and association mapping. PMID:21205322

  2. 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.

  3. Unraveling the nature of the segmentation clock: Intrinsic disorder of clock proteins and their interaction map

    PubMed Central

    Roy, Sourav; Schnell, Santiago; Radivojac, Predrag

    2007-01-01

    Vertebrate segmentation has been proved to be under a strict temporal control governed by a biological clock, known as the segmentation clock. The present experimental evidence suggests that the segmentation clock initiates and maintains its periodic cycle by the periodic activation or inhibition of the Notch signaling pathway as well as the periodic autoregulation of the cyclic genes themselves. In this paper, we investigate the structural and evolutionary properties of the Notch pathway proteins involved in the mice segmentation clock and computationally identify the interaction map within the Notch signaling pathway. The results of our analysis strongly indicate that most of the pathway proteins are intrinsically disordered and that the mechanism of their interaction likely involves helical molecular recognition elements, short loosely structured segments within disordered regions which are directly involved in protein–protein interactions. Predicted interactions are in agreement with gene knock-out studies available in the literature. PMID:16798096

  4. Influence of the interaction volume on the kinetic energy resolution of a velocity map imaging spectrometer

    NASA Astrophysics Data System (ADS)

    Peng, Zhang; Zheng-Peng, Feng; Si-Qiang, Luo; Zhe, Wang

    2016-03-01

    We investigate the influence of the interaction volume on the energy resolution of a velocity map imaging spectrometer. The simulation results show that the axial interaction size has a significant influence on the resolution. This influence is increased for a higher kinetic energy. We further show that the radial interaction size has a minor influence on the energy resolution for the electron or ion with medium energy, but it is crucial for the resolution of the electron or ion with low kinetic energy. By tracing the flight trajectories we show how the electron or ion energy resolution is influenced by the interaction size. Project supported by the National Natural Science Foundation of China (Grant Nos. 11234004 and 61275126).

  5. Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells.

    PubMed

    Hulce, Jonathan J; Cognetta, Armand B; Niphakis, Micah J; Tully, Sarah E; Cravatt, Benjamin F

    2013-03-01

    Cholesterol is an essential structural component of cellular membranes and serves as a precursor for several classes of signaling molecules. Cholesterol exerts its effects and is, itself, regulated in large part by engagement in specific interactions with proteins. The full complement of sterol-binding proteins that exist in mammalian cells, however, remains unknown. Here we describe a chemoproteomic strategy that uses clickable, photoreactive sterol probes in combination with quantitative mass spectrometry to globally map cholesterol-protein interactions directly in living cells. We identified over 250 cholesterol-binding proteins, including receptors, channels and enzymes involved in many established and previously unreported interactions. Prominent among the newly identified interacting proteins were enzymes that regulate sugars, glycerolipids and cholesterol itself as well as proteins involved in vesicular transport and protein glycosylation and degradation, pointing to key nodes in biochemical pathways that may couple sterol concentrations to the control of other metabolites and protein localization and modification. PMID:23396283

  6. Mapping Plant Interactomes Using Literature Curated and Predicted ProteinProtein Interaction Data Sets[W

    PubMed Central

    Lee, KiYoung; Thorneycroft, David; Achuthan, Premanand; Hermjakob, Henning; Ideker, Trey

    2010-01-01

    Most cellular processes are enabled by cohorts of interacting proteins that form dynamic networks within the plant proteome. The study of these networks can provide insight into protein function and provide new avenues for research. This article informs the plant science community of the currently available sources of protein interaction data and discusses how they can be useful to researchers. Using our recently curated IntAct Arabidopsis thaliana proteinprotein interaction data set as an example, we discuss potentials and limitations of the plant interactomes generated to date. In addition, we present our efforts to add value to the interaction data by using them to seed a proteome-wide map of predicted protein subcellular locations. PMID:20371643

  7. Mapping Dynamic Protein Interactions to Insulin Secretory Granule Behavior with TIRF-FRET

    PubMed Central

    Lam, Alice D.; Ismail, Sahar; Wu, Ray; Yizhar, Ofer; Passmore, Daniel R.; Ernst, Stephen A.; Stuenkel, Edward L.

    2010-01-01

    Biological processes are governed by extensive networks of dynamic molecular interactions. Yet, establishing a spatial and temporal map of these interactions and their direct relationship to specific cell functions has remained a challenge. Here, we implement sensitized emission Förster resonance energy transfer (FRET) stoichiometry under total internal reflection fluorescence (TIRF) microscopy. We demonstrate through quantitative analysis and modeling that evanescent fields must be precisely matched between FRET excitation wavelengths to isolate dynamic interactions between bimolecular FRET pairs that are not entirely membrane-delimited. We then use TIRF-FRET to monitor the behavior of individual insulin-containing secretory granules at the plasma membrane of living cells, while simultaneously tracking the dynamic interaction between the GTPase Rab27A and its effector Slp4A, on those same granules. Notably, insulin granules that underwent exocytosis demonstrated a specific increase in Rab27A-GTP/Slp4A FRET in the 5 s before membrane fusion, which coincided temporally with an increase in granule displacement and mobility. These results demonstrate an initial spatiotemporal mapping of a dynamic protein-protein interaction on individual secretory granules that is linked to a specific granule behavior in living cells. PMID:20713017

  8. 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

  9. Comprehensive Polyadenylation Site Maps in Yeast and Human Reveal Pervasive Alternative Polyadenylation

    PubMed Central

    Ozsolak, Fatih; Kapranov, Philipp; Foissac, Sylvain; Kim, Sang Woo; Fishilevich, Elane; Monaghan, A. Paula; John, Bino; Milos, Patrice M.

    2010-01-01

    Summary The emerging discoveries on the link between polyadenylation and disease states underline the need to fully characterize genome-wide polyadenylation states. Here, we report comprehensive maps of global polyadenylation events in human and yeast generated using refinements to the Direct RNA Sequencing technology. This direct approach provides a quantitative view of genome-wide polyadenylation states in a strand-specific manner and requires only attomole RNA quantities. The polyadenylation profiles revealed an abundance of unannotated polyadenylation sites, alternative polyadenylation patterns, and regulatory element-associated polyA+ RNAs. We observed differences in sequence composition surrounding canonical and non-canonical human polyadenylation sites, suggesting novel non-coding RNA-specific polyadenylation mechanisms in humans. Furthermore, we observed the correlation level between sense and antisense transcripts to depend on gene expression levels, supporting the view that overlapping transcription from opposite strands may play a regulatory role. Our data provide a comprehensive view of the polyadenylation state and overlapping transcription. PMID:21145465

  10. Geophysical Applications in Mapping the Subsurface Structure of Archaeological Site at Lembah Bujang, Kedah, Malaysia

    NASA Astrophysics Data System (ADS)

    Sapiai, Sarmiza M.; Saad, Rosli; Nawawi, M. N. M.; Shyeh, S. K.; Saidin, Mohd Mokhtar

    2010-07-01

    Lembah Bujang is one of Peninsular Malaysia's most important areas for archaeology as excavations in this area have revealed many traces of Malaysia's prehistory. The site is one of the oldest known place human activities the Peninsula. The aim of this study is to map and understand the subsurface structure of the survey area which is one of the archaeologically interesting areas. Geophysical methods are used because it is nondestructive and do not disturb the site. The methods are relatively quick and the results are used as a guide for subsequent excavation work. So it can greatly help in setting the digging priorities as geophysical surveying can reveal, for instance, important subsurface features like monuments, tunnels, voids, or buried walls. The geophysical methods used in this study were the magnetic gradiometer, 2-D electrical resistivity and ground penetrating radar (GPR) method. The integration of these three methods can be beneficial as each method has its strength and limitation. The specific area of study is in Sungai Batu and the results show that the sedimentation consists of sandy clay, alluvium and boulders with a depth of between 0 m to 15 m.

  11. Geologic map of Paleozoic rocks in the Calico Hills, Nevada Test Site, southern Nevada

    SciTech Connect

    Cole, J.C.; Cashman, P.H.

    1998-11-01

    The Calico Hills area in the southwestern part of the Nevada Test Site, Nye County, Nevada, exposes a core of pre-Tertiary rocks surrounded by middle Miocene volcanic strata. This map portrays the very complex relationships among the pre-Tertiary stratigraphic units of the region. The Devonian and Mississippian rocks of the Calico Hills are distinct from age-equivalent carbonate-shelf or submarine-fan strata in other parts of the Nevada Test Site. The Calico Hills strata are interpreted to have been deposited beyond the continental shelf edge from alternating silicic and carbonate clastic sources. Structures of the Calico Hills area record the compounded effects of: (1) eastward-directed, foreland-vergent thrusting; (2) younger folds, kink zones, and thrusts formed by hinterland-vergent deformation toward northwesterly and northerly directions; and (3) low-angle normal faults that displaced blocks of Middle Paleozoic carbonate strata across the contractionally deformed terrane. All of these structures are older than any of the middle Miocene volcanic rocks that were erupted across the Calico Hills.

  12. Mapping of contamination at Savannah River Site FBWU by INEEL trolley

    SciTech Connect

    Carpenter, M.V.; Gehrke, R.J.; Helmer, R.G.; Josten, N.

    1998-01-01

    The Ford Building Waste Unit (FBWU) 643-11G is a Resource Conservation and Recovery Act/Comprehensive Environmental Response Compensation and Liability Act (RCRA/CERCLA) designated site at the Savannah River Site (SRS) in Aiken, South Carolina. Pre-Work Plan Characterization at the FBWU in May 1996 indicated that radiological contamination was present in surface and near surface soils and identified cesium-137, {sup 137}Cs, the unit specific contaminant, as being primarily in the top 15 cm of soil. The Idaho National Engineering and Environmental Laboratory (INEEL) sent the dig-face trolley system to SRS where it demonstrated its capability over a 6.1-m (20 ft.) x 9.6-m (30 ft.) area to rapidly map the contamination on-line with its large area plastic scintillation detector. Also, an extended-range (10 keV to 3 MeV) Ge detector was used at selected locations to identify and quantify the {sup 137}Cs contamination. The coordinate locations of each measurement acquired in either the scanning or fixed position mode was obtained with a survey system based on radial encoders. Topography measurements were also made during measurements to permit correction of field of view and activity concentrations for changes in the ground to detector distance.

  13. Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation.

    PubMed Central

    DiDonato, J; Mercurio, F; Rosette, C; Wu-Li, J; Suyang, H; Ghosh, S; Karin, M

    1996-01-01

    Extracellular stimuli that activate the transcription factor NF-kappaB cause rapid phosphorylation of the IkappaBalpha inhibitor, which retains NF-kappaB in the cytoplasm of nonstimulated cells. Phosphorylation of IkappaBalpha is followed by its rapid degradation, the inhibition of which prevents NF-kappaB activation. To determine the relationship between these events, we mapped the inducible phosphorylation sites of IkappaBalpha. We found that two residues, serines 32 and 36, were phosphorylated in response to either tumor necrosis factor, interleukin-1, or phorbol ester. Substitution of either serine blocks or slows down induction of IkappaBalpha degradation. Substitutions of the homologous sites in IkappaBbeta, serines 19 and 23, also prevent inducible IkappaBbeta degradation. We suggest that activation of a single IkappaB kinas e or closely related IkappaB kinases is the first cr itical step in NF-kappaB activation. Once phosphorylated, IkappaB is ubiquitinated. Unlike wild-type IkappaBalpha, the phosphorylation-defective mutants do not undergo inducible polyubiquitination. As substitution of a conserved lysine residue slows down the ubiquitination and degradation of IkappaBalpha without affecting its phosphorylation, polyubiquitination is required for inducible IkappaB degradation. PMID:8657102

  14. Near-surface gas mapping studies of salt geologic features at Weeks Island and other sites

    SciTech Connect

    Molecke, M.A.; Carney, K.R.; Autin, W.J.; Overton, E.B.

    1996-10-01

    Field sampling and rapid gas analysis techniques were used to survey near-surface soil gases for geotechnical diagnostic purposes at the Weeks Island Strategic Petroleum Reserve (SPR) site and other salt dome locations in southern Louisiana. This report presents the complete data, results and interpretations obtained during 1995. Weeks Island 1994 gas survey results are also briefly summarized; this earlier study did not find a definitive correlation between sinkhole No. 1 and soil gases. During 1995, several hundred soil gas samples were obtained and analyzed in the field by gas chromatography, for profiling low concentrations and gas anomalies at ppm to percent levels. The target gases included hydrogen, methane, ethane and ethylene. To supplement the field data, additional gas samples were collected at various site locations for laboratory analysis of target gases at ppb levels. Gases in the near-surface soil originate predominantly from the oil, from petrogenic sources within the salt, or from surface microbial activity. Surveys were conducted across two Weeks Island sinkholes, several mapped anomalous zones in the salt, and over the SPR repository site and its perimeter. Samples were also taken at other south Louisiana salt dome locations for comparative purposes. Notable results from these studies are that elevated levels of hydrogen and methane (1) were positively associated with anomalous gassy or shear zones in the salt dome(s) and (2) are also associated with suspected salt fracture (dilatant) zones over the edges of the SPR repository. Significantly elevated areas of hydrogen, methane, plus some ethane, were found over anomalous shear zones in the salt, particularly in a location over high pressure gas pockets in the salt, identified in the mine prior to SPR operations. Limited stable isotope ratio analyses, SIRA, were also conducted and determined that methane samples were of petrogenic origin, not biogenic.

  15. Mapping the Vif-A3G interaction using peptide arrays: a basis for anti-HIV lead peptides.

    PubMed

    Reingewertz, Tali H; Britan-Rosich, Elena; Rotem-Bamberger, Shahar; Viard, Mathias; Jacobs, Amy; Miller, Abigail; Lee, Ji Youn; Hwang, Jeeseong; Blumenthal, Robert; Kotler, Moshe; Friedler, Assaf

    2013-06-15

    Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3G (A3G) is a cytidine deaminase that restricts retroviruses, endogenous retro-elements and DNA viruses. A3G plays a key role in the anti-HIV-1 innate cellular immunity. The HIV-1 Vif protein counteracts A3G mainly by leading A3G towards the proteosomal machinery and by direct inhibition of its enzymatic activity. Both activities involve direct interaction between Vif and A3G. Disrupting the interaction between A3G and Vif may rescue A3G antiviral activity and inhibit HIV-1 propagation. Here, mapping the interaction sites between A3G and Vif by peptide array screening revealed distinct regions in Vif important for A3G binding, including the N-terminal domain (NTD), C-terminal domain (CTD) and residues 83-99. The Vif-binding sites in A3G included 12 different peptides that showed strong binding to either full-length Vif, Vif CTD or both. Sequence similarity was found between Vif-binding peptides from the A3G CTD and NTD. A3G peptides were synthesized and tested for their ability to counteract Vif action. A3G 211-225 inhibited HIV-1 replication in cell culture and impaired Vif dependent A3G degradation. In vivo co-localization of full-length Vif with A3G 211-225 was demonstrated by use of FRET. This peptide has the potential to serve as an anti-HIV-1 lead compound. Our results suggest a complex interaction between Vif and A3G that is mediated by discontinuous binding regions with different affinities. PMID:23545135

  16. A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

    PubMed Central

    Cardó-Vila, Marina; Zurita, Amado J.; Giordano, Ricardo J.; Sun, Jessica; Rangel, Roberto; Guzman-Rojas, Liliana; Anobom, Cristiane D.; Valente, Ana P.; Almeida, Fábio C. L.; Lahdenranta, Johanna; Kolonin, Mikhail G.; Arap, Wadih; Pasqualini, Renata

    2008-01-01

    Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs. PMID:18941632

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

    PubMed Central

    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. PMID:26266545

  18. 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. PMID:26266545

  19. A combined binary interaction and phenotypic map of C. elegans cell polarity proteins.

    PubMed

    Koorman, Thijs; Klompstra, Diana; van der Voet, Monique; Lemmens, Irma; Ramalho, João J; Nieuwenhuize, Susan; van den Heuvel, Sander; Tavernier, Jan; Nance, Jeremy; Boxem, Mike

    2016-03-01

    The establishment of cell polarity is an essential process for the development of multicellular organisms and the functioning of cells and tissues. Here, we combine large-scale protein interaction mapping with systematic phenotypic profiling to study the network of physical interactions that underlies polarity establishment and maintenance in the nematode Caenorhabditis elegans. Using a fragment-based yeast two-hybrid strategy, we identified 439 interactions between 296 proteins, as well as the protein regions that mediate these interactions. Phenotypic profiling of the network resulted in the identification of 100 physically interacting protein pairs for which RNAi-mediated depletion caused a defect in the same polarity-related process. We demonstrate the predictive capabilities of the network by showing that the physical interaction between the RhoGAP PAC-1 and PAR-6 is required for radial polarization of the C. elegans embryo. Our network represents a valuable resource of candidate interactions that can be used to further our insight into cell polarization. PMID:26780296

  20. Network structure beyond food webs: mapping non-trophic and trophic interactions on Chilean rocky shores.

    PubMed

    Sonia Kéfi; Berlow, Eric L; Wieters, Evie A; Joppa, Lucas N; Wood, Spencer A; Brose, Ulrich; Navarrete, Sergio A

    2015-01-01

    How multiple types of non-trophic interactions map onto trophic networks in real communities remains largely unknown. We present the first effort, to our knowledge, describing a comprehensive ecological network that includes all known trophic and diverse non-trophic links among >100 coexisting species for the marine rocky intertidal community of the central Chilean coast. Our results suggest that non-trophic interactions exhibit highly nonrandom structures both alone and with respect to food web structure. The occurrence of different types of interactions, relative to all possible links, was well predicted by trophic structure and simple traits of the source and target species. In this community, competition for space and positive interactions related to habitat/refuge provisioning by sessile and/or basal species were by far the most abundant non-trophic interactions. If these patterns are orroborated in other ecosystems, they may suggest potentially important dynamic constraints on the combined architecture of trophic and non-trophic interactions. The nonrandom patterning of non-trophic interactions suggests a path forward for developing a more comprehensive ecological network theory to predict the functioning and resilience of ecological communities. PMID:26236914

  1. Construction and Application of a Protein Interaction Map for White Spot Syndrome Virus (WSSV)*

    PubMed Central

    Sangsuriya, Pakkakul; Huang, Jiun-Yan; Chu, Yu-Fei; Phiwsaiya, Kornsunee; Leekitcharoenphon, Pimlapas; Meemetta, Watcharachai; Senapin, Saengchan; Huang, Wei-Pang; Withyachumnarnkul, Boonsirm; Flegel, Timothy W.; Lo, Chu-Fang

    2014-01-01

    White spot syndrome virus (WSSV) is currently the most serious global threat for cultured shrimp production. Although its large, double-stranded DNA genome has been completely characterized, most putative protein functions remain obscure. To provide more informative knowledge about this virus, a proteomic-scale network of WSSV-WSSV protein interactions was carried out using a comprehensive yeast two-hybrid analysis. An array of yeast transformants containing each WSSV open reading frame fused with GAL4 DNA binding domain and GAL4 activation domain was constructed yielding 187 bait and 182 prey constructs, respectively. On screening of ∼28,000 pairwise combinations, 710 interactions were obtained from 143 baits. An independent coimmunoprecipitation assay (co-IP) was performed to validate the selected protein interaction pairs identified from the yeast two-hybrid approach. The program Cytoscape was employed to create a WSSV protein–protein interaction (PPI) network. The topology of the WSSV PPI network was based on the Barabási-Albert model and consisted of a scale-free network that resembled other established viral protein interaction networks. Using the RNA interference approach, knocking down either of two candidate hub proteins gave shrimp more protection against WSSV than knocking down a nonhub gene. The WSSV protein interaction map established in this study provides novel guidance for further studies on shrimp viral pathogenesis, host-viral protein interaction and potential targets for therapeutic and preventative antiviral strategies in shrimp aquaculture. PMID:24217020

  2. Mapping the Genetic Basis of Symbiotic Variation in Legume-Rhizobium Interactions in Medicago truncatula

    PubMed Central

    Gorton, Amanda J.; Heath, Katy D.; Pilet-Nayel, Marie-Laure; Baranger, Alain

    2012-01-01

    Mutualisms are known to be genetically variable, where the genotypes differ in the fitness benefits they gain from the interaction. To date, little is known about the loci that underlie such genetic variation in fitness or whether the loci influencing fitness are partner specific, and depend on the genotype of the interaction partner. In the legume-rhizobium mutualism, one set of potential candidate genes that may influence the fitness benefits of the symbiosis are the plant genes involved in the initiation of the signaling pathway between the two partners. Here we performed quantitative trait loci (QTL) mapping in Medicago truncatula in two different rhizobium strain treatments to locate regions of the genome influencing plant traits, assess whether such regions are dependent on the genotype of the rhizobial mutualist (QTL × rhizobium strain), and evaluate the contribution of sequence variation at known symbiosis signaling genes. Two of the symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting average fruit weight and leaf number, suggesting that natural variation in nodulation genes may potentially influence plant fitness. In both rhizobium strain treatments, there were QTL that influenced multiple traits, indicative of either tight linkage between loci or pleiotropy, including one QTL with opposing effects on growth and reproduction. There was no evidence for QTL × rhizobium strain or genotype × genotype interactions, suggesting either that such interactions are due to small-effect loci or that more genotype-genotype combinations need to be tested in future mapping studies. PMID:23173081

  3. 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 prediction MCC was 0.49. Independent tests on anti-carbohydrate antibodies showed that the carbohydrate antigen binding sites were predicted with comparable accuracy. These results demonstrate that the predictors are among the best in carbohydrate binding site predictions to date. PMID:22848404

  4. 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 ?-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. PMID:21876146

  5. 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 the map. Data tables are offered if the copyright of datasets allows such use. All data of all thematic modules is presented in country profiles in a consolidated manner. The portal has been created with Open Source Software. PostgreSQL and PostGIS, MapServer, OpenLayers, MapProxy and cmsmadesimple are combined to manipulate and transform global data sets into interactive thematic maps. A purpose-programmed layer selection menu enables users to select single layers or to combine up to three matching layers from all possible pre-set layer combinations. This applies both to fields of topics within a module and across various modules. Due to the complexity of the structure and visualization constraints, no more than three layers can be combined. The WebGIS-based information portal on war and peace is an excellent example of how GIS technologies can be used for education and outreach. Not only can they play a crucial role in supporting the educational mandate and mission of certain institutions. They can also directly support various target groups in obtaining the knowledge needed by providing a collection of straight forward designed, ready-to-use data, info graphics and maps.

  6. Mapping intended spinal site of care from the upright to prone position: an interexaminer reliability study

    PubMed Central

    2014-01-01

    Background Upright examination procedures like radiology, thermography, manual muscle testing, and spinal motion palpation may lead to spinal interventions with the patient prone. The reliability and accuracy of mapping upright examination findings to the prone position is unknown. This study had 2 primary goals: (1) investigate how erroneous spine-scapular landmark associations may lead to errors in treating and charting spine levels; and (2) study the interexaminer reliability of a novel method for mapping upright spinal sites to the prone position. Methods Experiment 1 was a thought experiment exploring the consequences of depending on the erroneous landmark association of the inferior scapular tip with the T7 spinous process upright and T6 spinous process prone (relatively recent studies suggest these levels are T8 and T9, respectively). This allowed deduction of targeting and charting errors. In experiment 2, 10 examiners (2 experienced, 8 novice) used an index finger to maintain contact with a mid-thoracic spinous process as each of 2 participants slowly moved from the upright to the prone position. Interexaminer reliability was assessed by computing Intraclass Correlation Coefficient, standard error of the mean, root mean squared error, and the absolute value of the mean difference for each examiner from the 10 examiner mean for each of the 2 participants. Results The thought experiment suggesting that using the (inaccurate) scapular tip landmark rule would result in a 3 level targeting and charting error when radiological findings are mapped to the prone position. Physical upright exam procedures like motion palpation would result in a 2 level targeting error for intervention, and a 3 level error for charting. The reliability experiment showed examiners accurately maintained contact with the same thoracic spinous process as the participant went from upright to prone, ICC (2,1) = 0.83. Conclusions As manual therapists, the authors have emphasized how targeting errors may impact upon manual care of the spine. Practitioners in other fields that need to accurately locate spinal levels, such as acupuncture and anesthesiology, would also be expected to draw important conclusions from these findings. PMID:24904747

  7. 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

  8. 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. PMID:25934935

  9. Genome-wide mapping of promoter-anchored interactions with close to single-enhancer resolution.

    PubMed

    Sahlén, Pelin; Abdullayev, Ilgar; Ramsköld, Daniel; Matskova, Liudmila; Rilakovic, Nemanja; Lötstedt, Britta; Albert, Thomas J; Lundeberg, Joakim; Sandberg, Rickard

    2015-01-01

    Although the locations of promoters and enhancers have been identified in several cell types, we still have limited information on their connectivity. We developed HiCap, which combines a 4-cutter restriction enzyme Hi-C with sequence capture of promoter regions. Applying the method to mouse embryonic stem cells, we identified promoter-anchored interactions involving 15,905 promoters and 71,984 distal regions. The distal regions were enriched for enhancer marks and transcription, and had a mean fragment size of only 699 bp--close to single-enhancer resolution. High-resolution maps of promoter-anchored interactions with HiCap will be important for detailed characterizations of chromatin interaction landscapes. PMID:26313521

  10. 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.

  11. An Online Interactive Map Service for Displaying Ground-Water Conditions in Arizona

    USGS Publications Warehouse

    Tillman, Fred D; Leake, Stanley A.; Flynn, Marilyn E.; Cordova, Jeffrey T.; Schonauer, Kurt T.

    2007-01-01

    Monitoring the availability of the nation's ground-water supplies is of critical importance to planners and water managers. The general public also has an interest in understanding the status of ground-water conditions, especially in the semi-arid Southwestern United States where much of the water used by municipalities and agriculture comes from the subsurface. Unlike surface-water indicators such as stage or discharge, ground-water conditions may be more difficult to assess and present. Individual well observations may only represent conditions in a limited area surrounding the well and wells may be screened over single or multiple aquifers, further complicating single-well measurement interpretations. Additionally, changes in ground-water conditions may involve time scales ranging from days to many years, depending on recharge, soil properties and depth to the water table. This lack of an easily identifiable ground-water property indicative of current conditions combined with differing time scales of water-level changes makes the presentation of ground-water conditions a difficult task, particularly on a regional basis. One approach is to spatially present several indicators of ground-water conditions that address different time scales and attributes of the aquifer systems. In this report, we describe a publicly-available online interactive map service that presents several different layers of ground-water-conditions information for the alluvial basins in the Lower Colorado River Basin in Arizona (http://montezuma.wr.usgs.gov/website/azgwconditions/). These data layers include wells experiencing water-level decline, wells experiencing water-level rise, recent trends in ground-water levels, change in water level since predevelopment and change in storage since predevelopment. Recent pumpage totals and projected population numbers are also provided for ground-water basins and counties in the region of the Lower Colorado River in Arizona along with a bibliography of U.S. Geological Survey reports for those seeking further information. The methods used to create these data layers are explained with illustrations of example information available on the Web site.

  12. Prediction of Protein-Protein Interaction Sites Based on Naive Bayes Classifier

    PubMed Central

    Geng, Haijiang; Lu, Tao; Lin, Xiao; Liu, Yu; Yan, Fangrong

    2015-01-01

    Protein functions through interactions with other proteins and biomolecules and these interactions occur on the so-called interface residues of the protein sequences. Identifying interface residues makes us better understand the biological mechanism of protein interaction. Meanwhile, information about the interface residues contributes to the understanding of metabolic, signal transduction networks and indicates directions in drug designing. In recent years, researchers have focused on developing new computational methods for predicting protein interface residues. Here we creatively used a 181-dimension protein sequence feature vector as input to the Naive Bayes Classifier- (NBC-) based method to predict interaction sites in protein-protein complexes interaction. The prediction of interaction sites in protein interactions is regarded as an amino acid residue binary classification problem by applying NBC with protein sequence features. Independent test results suggested that Naive Bayes Classifier-based method with the protein sequence features as input vectors performed well. PMID:26697220

  13. Coexistence and competition of on-site and intersite Coulomb interactions in Mott-molecular-dimers

    NASA Astrophysics Data System (ADS)

    Juliano, R. C.; de Arruda, A. S.; Craco, L.

    2016-02-01

    We reveal the interplay between on-site (U) and intersite (V) Coulomb interactions in the extended two-site Hubbard model. Due to its atomic-like form quantum correlations intrinsic to Mott-molecular-dimers are exactly computed. Our results for physical quantities such as double occupancy and specific heat are consistent with those obtained for the one-band Hubbard model, suggesting that a two-site dimer model is able to capture the essential thermodynamic properties of strongly interacting electron systems. It is noted that intersite Coulomb interactions promote the formation of doublons, which compete with the spin-singlet state induced by the on-site Coulomb repulsion. Our results are expected to be relevant for understanding electronic and thermodynamical properties of interacting electrons in systems with strongly coupled magnetic atoms.

  14. Mapping of the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor.

    PubMed Central

    Neumann, D; Barchan, D; Safran, A; Gershoni, J M; Fuchs, S

    1986-01-01

    Synthetic peptides and their respective antibodies have been used in order to map the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor. By using antibodies to a synthetic peptide corresponding to residues 169-181 of the alpha subunit, we demonstrate that this sequence is included within the 18-kDa toxin binding fragment previously reported. Furthermore, the 18-kDa fragment was also found to bind a monoclonal antibody (5.5) directed against the cholinergic binding site. Sequential proteolysis of the acetylcholine receptor with trypsin, prior to Staphylococcus aureus V8 protease digestion, resulted in a 15-kDa toxin binding fragment that is included within the 18-kDa fragment but is shorter than it only at its carboxyl terminus. This 15-kDa fragment therefore initiates beyond Asp-152 and terminates in the region of Arg-313/Lys-314. In addition, experiments are reported that indicate that in the intact acetylcholine receptor, Cys-128 and/or Cys-142 are not crosslinked by disulfide bridges with any of the cysteines (at positions 192, 193, and 222) that reside in the 15-kDa toxin binding fragment. Finally, the synthetic dodecapeptide Lys-His-Trp-Val-Tyr-Tyr-Thr-Cys-Cys-Pro-Asp-Thr, which is present in the 15-kDa fragment (corresponding to residues 185-196 of the alpha subunit) was shown to bind alpha-bungarotoxin directly. This binding was completely inhibited by competition with d-tubocurarine. Images PMID:3458258

  15. Mapping of the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor.

    PubMed

    Neumann, D; Barchan, D; Safran, A; Gershoni, J M; Fuchs, S

    1986-05-01

    Synthetic peptides and their respective antibodies have been used in order to map the alpha-bungarotoxin binding site within the alpha subunit of the acetylcholine receptor. By using antibodies to a synthetic peptide corresponding to residues 169-181 of the alpha subunit, we demonstrate that this sequence is included within the 18-kDa toxin binding fragment previously reported. Furthermore, the 18-kDa fragment was also found to bind a monoclonal antibody (5.5) directed against the cholinergic binding site. Sequential proteolysis of the acetylcholine receptor with trypsin, prior to Staphylococcus aureus V8 protease digestion, resulted in a 15-kDa toxin binding fragment that is included within the 18-kDa fragment but is shorter than it only at its carboxyl terminus. This 15-kDa fragment therefore initiates beyond Asp-152 and terminates in the region of Arg-313/Lys-314. In addition, experiments are reported that indicate that in the intact acetylcholine receptor, Cys-128 and/or Cys-142 are not crosslinked by disulfide bridges with any of the cysteines (at positions 192, 193, and 222) that reside in the 15-kDa toxin binding fragment. Finally, the synthetic dodecapeptide Lys-His-Trp-Val-Tyr-Tyr-Thr-Cys-Cys-Pro-Asp-Thr, which is present in the 15-kDa fragment (corresponding to residues 185-196 of the alpha subunit) was shown to bind alpha-bungarotoxin directly. This binding was completely inhibited by competition with d-tubocurarine. PMID:3458258

  16. Comprehensive Human Transcription Factor Binding Site Map for Combinatory Binding Motifs Discovery

    PubMed Central

    Müller-Molina, Arnoldo J.; Schöler, Hans R.; Araúzo-Bravo, Marcos J.

    2012-01-01

    To know the map between transcription factors (TFs) and their binding sites is essential to reverse engineer the regulation process. Only about 10%–20% of the transcription factor binding motifs (TFBMs) have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory “DNA words.” From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%—far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of “DNA words,” newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters. PMID:23209563

  17. Mapping the Interactions between the NS4B and NS3 Proteins of Dengue Virus

    PubMed Central

    Zou, Jing; Lee, Le Tian; Wang, Qing Yin; Xie, Xuping; Lu, Siyan; Yau, Yin Hoe; Yuan, Zhiming; Geifman Shochat, Susana; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus RNA synthesis is mediated by a multiprotein complex associated with the endoplasmic reticulum membrane, named the replication complex (RC). Within the flavivirus RC, NS4B, an integral membrane protein with a role in virulence and regulation of the innate immune response, binds to the NS3 protease-helicase. NS4B modulates the RNA helicase activity of NS3, but the molecular details of their interaction remain elusive. Here, we used dengue virus (DENV) to map the determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV-infected cells and cells coexpressing both proteins. Surface plasmon resonance demonstrated that subdomains 2 and 3 of the NS3 helicase region and the cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible, with a tendency to form a three-turn α-helix and two short β-strands. Upon binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B exhibited line broadening, suggesting a participation in the interaction. Sequence alignment showed that 4 of these 12 residues are strictly conserved across different flaviviruses. Mutagenesis analysis showed that three (Q134, G140, and N144) of the four evolutionarily conserved NS4B residues are essential for DENV replication. The mapping of the NS3/NS4B-interacting regions described here can assist the design of inhibitors that disrupt their interface for antiviral therapy. IMPORTANCE NS3 and NS4B are essential components of the flavivirus RC. Using DENV as a model, we mapped the interaction between the viral NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the cytoplasmic loop of NS4B are critical for the interaction. Functional analysis delineated residues within the NS4B cytoplasmic loop that are crucial for DENV replication. Our findings reveal molecular details of how flavivirus NS3 protein cooperates with NS4B within the RC. In addition, this study has established the rationale and assays to search for inhibitors disrupting the NS3-NS4B interaction for antiviral drug discovery. PMID:25589636

  18. 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.

  19. 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,…

  20. 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,

  1. Mapping of the Lunokhod-1 Landing Site: A Case Study for Future Lunar Exploration

    NASA Astrophysics Data System (ADS)

    Karachevtseva, I.; Oberst, J.; Konopikhin, A.; Shingareva, K.; Gusakova, E.; Kokhanov, A.; Baskakova, M.; Peters, O.; Scholten, F.; Wählisch, M.; Robinson, M.

    2012-04-01

    Introduction. Luna-17 landed on November 17, 1970 and deployed Lunokhod-1, the first remotely operated roving vehicle ever to explore a planetary surface. Within 332 days, the vehicle conquered a traverse of approx. 10 km. The rover was equipped with a navigation camera system as well as a scanner camera with which panoramic images were obtained. From separated stations, stereoscopic views were obtained. The history of the Lunokhods came back into focus recently, when the Lunar Reconnaissance Orbiter [1] obtained images from orbit at highest resolutions of 0.5-0.25 m/pixel. The Luna-17 landing platform as well as the roving vehicles at their final resting positions can clearly be identified. In addition, the rover tracks are clearly visible in most areas. From LRO stereo images, digital elevation model (DEM) of the Lunokhod-1 landing site areas have been derived [2]. These are useful to study the topographic profile and slopes of the traverse. The data are also useful to study the 3-D morphology of craters in the surroundings. Methodology. Lunokhod-1 area mapping have been done using GIS techniques. With CraterTools [3] we digitized craters in the Lunokhod-1 traverse area and created a geodatabase, which consists at this moment of about 45,000 craters including their diameters and depths, obtained from the DEM [4]. The LRO DEM also was used to measure traverse. We used automatic GIS functions for calculating various surface parameters of the Lunokhod-1 area surface including slopes, roughness, crater cumulative and spatial densities, and prepared respective thematic maps. We also measured relative depth (ratio D/H) and inner slopes of craters and classified craters by their morphological type using automatic and visual methods. Vertical profiles through several craters using the high resolution DEM have been done, and the results show good agreement with the topographic models with contours in 10cm that have been obtained from the Lunokhod-1 stereo images [5]. The preliminary results of crater morphology show that highest H/D for studied craters of the Lunokhod 1 area is ~0.14, that is noticeably smaller than that for very fresh well studied small craters, for example, in the Apollo 14 [6]. At present more detailed geomorphology analyses using orthoimages with different illumination is in progress and will be shown at the conference. Conclusions and future works. While new missions to the Lunar surface are being planned, it is of utmost importance to identify and make available for access all Lunar surface data. We show that these data can be used for large-scale mapping and surface studies of landing sites for future lunar missions, for example LUNA-GLOB and LUNA-RESOURCE. Acknowledgments: This research was partly funded by the Ministry of Education and Science of the Russian Federation (MEGA-GRANT, Project name: "Geodesy, cartography and the study of planets and satellites", contract No. 11.G34.31.0021).

  2. Expression patterns of FLAGELLIN SENSING 2 map to bacterial entry sites in plant shoots and roots

    PubMed Central

    Beck, Martina; Wyrsch, Ines; Strutt, James; Wimalasekera, Rinukshi; Webb, Alex; Boller, Thomas; Robatzek, Silke

    2014-01-01

    Pathogens can colonize all plant organs and tissues. To prevent this, each cell must be capable of autonomously triggering defence. Therefore, it is generally assumed that primary sensors of the immune system are constitutively present. One major primary sensor against bacterial infection is the FLAGELLIN SENSING 2 (FLS2) pattern recognition receptor (PRR). To gain insights into its expression pattern, the FLS2 promoter activity in β-glucuronidase (GUS) reporter lines was monitored. The data show that pFLS2::GUS activity is highest in cells and tissues vulnerable to bacterial entry and colonization, such as stomata, hydathodes, and lateral roots. GUS activity is also high in the vasculature and, by monitoring Ca2+ responses in the vasculature, it was found that this tissue contributes to flg22-induced Ca2+ burst. The FLS2 promoter is also regulated in a tissue- and cell type-specific manner and is responsive to hormones, damage, and biotic stresses. This results in stimulus-dependent expansion of the FLS2 expression domain. In summary, a tissue- and cell type-specific map of FLS2 expression has been created correlating with prominent entry sites and target tissues of plant bacterial pathogens. PMID:25205577

  3. A remote characterization system for subsurface mapping of buried waste sites

    SciTech Connect

    Sandness, G.A.; Bennett, D.W.

    1992-10-01

    Mapping of buried objects and regions of chemical and radiological contamination is required at US Department of Energy (DOE) buried waste sites. The DOE Office of Technology Development Robotics Integrated Program has initiated a project to develop and demonstrate a remotely controlled subsurface sensing system, called the Remote Characterization System (RCS). This project, a collaborative effort by five of the National Laboratories, involves the development of a unique low-signature survey vehicle, a base station, radio telemetry data links, satellite-based vehicle tracking, stereo vision, and sensors for non-invasive inspection of the surface and subsurface. To minimize interference with on-board sensors, the survey vehicle has been constructed predominatantly of non-metallic materials. The vehicle is self-propelled and will be guided by an operator located at a remote base station. The RCS sensors will be environmentally sealed and internally cooled to preclude contamination during use. Ground-penetrating radar, magnetometers, and conductivity devices are planned for geophysical surveys. Chemical and radiological sensors will be provided to locate hot spots and to provide isotopic concentration data.

  4. Spirit rover localization and topographic mapping at the landing site of Gusev crater, Mars

    USGS Publications Warehouse

    Li, R.; Archinal, B.A.; Arvidson, R. E.; Bell, J.; Christensen, P.; Crumpler, L.; Des Marais, D.J.; Di, K.; Duxbury, T.; Golombek, M.P.; Grant, J. A.; Greeley, R.; Guinn, J.; Johnson, Aaron H.; Kirk, R.L.; Maimone, M.; Matthies, L.H.; Malin, M.; Parker, T.; Sims, M.; Thompson, S.; Squyres, S. W.; Soderblom, L.A.

    2006-01-01

    By sol 440, the Spirit rover has traversed a distance of 3.76 km (actual distance traveled instead of odometry). Localization of the lander and the rover along the traverse has been successfully performed at the Gusev crater landing site. We localized the lander in the Gusev crater using two-way Doppler radio positioning and cartographic triangulations through landmarks visible in both orbital and ground images. Additional high-resolution orbital images were used to verify the determined lander position. Visual odometry and bundle adjustment technologies were applied to compensate for wheel slippage, azimuthal angle drift, and other navigation errors (which were as large as 10.5% in the Husband Hill area). We generated topographic products, including 72 ortho maps and three-dimensional (3-D) digital terrain models, 11 horizontal and vertical traverse profiles, and one 3-D crater model (up to sol 440). Also discussed in this paper are uses of the data for science operations planning, geological traverse surveys, surveys of wind-related features, and other science applications. Copyright 2006 by the American Geophysical Union.

  5. Predicting and mapping potential Whooping Crane stopover habitat to guide site selection for wind energy projects.

    PubMed

    Belaire, J Amy; Kreakie, Betty J; Keitt, Timothy; Minor, Emily

    2014-04-01

    Migratory stopover habitats are often not part of planning for conservation or new development projects. We identified potential stopover habitats within an avian migratory flyway and demonstrated how this information can guide the site-selection process for new development. We used the random forests modeling approach to map the distribution of predicted stopover habitat for the Whooping Crane (Grus americana), an endangered species whose migratory flyway overlaps with an area where wind energy development is expected to become increasingly important. We then used this information to identify areas for potential wind power development in a U.S. state within the flyway (Nebraska) that minimize conflicts between Whooping Crane stopover habitat and the development of clean, renewable energy sources. Up to 54% of our study area was predicted to be unsuitable as Whooping Crane stopover habitat and could be considered relatively low risk for conflicts between Whooping Cranes and wind energy development. We suggest that this type of analysis be incorporated into the habitat conservation planning process in areas where incidental take permits are being considered for Whooping Cranes or other species of concern. Field surveys should always be conducted prior to construction to verify model predictions and understand baseline conditions. PMID:24372936

  6. Immunocytochemical mapping of the hemoglobin biosynthesis site in amphibian erythroid cells.

    PubMed

    Cianciarullo, A M; Beçak, W; Soares, M J

    1999-06-01

    During the past 25 years, several studies have attempted to determine the site of integration of the heme and the four globin chains in vertebrate erythroid cells that is important in the formation of the hemoglobin molecule. Mitochondrion-like organelles or hemosomes were pointed out as responsible for this task. We performed several experiments to investigate this hypothesis. The intracellular distribution of hemoglobin in amphibian erythroid cells was detected by post-embedding immuno-electron microscopy, using a polyclonal anti-human hemoglobin-proteinA-gold complex. Hemoglobin mapping showed an intense labeling in the cell cytoplasm, but none in cytoplasmic structures such as endoplasmic reticulum, mitochondria, mitochondrion-like organelles, Golgi complex, ribosomes or ferruginous inclusions. The mitochondrial fraction obtained according to the protocol described for some authors, showed by ultrastructural examination that this fraction has a heterogeneous content, also composed by microvesicles rich in cytoplasmic hemoglobin, an artifact generated by mechanical action during cell fractionation. Thus, when this fraction is lysed and its content submitted to electrophoresis, hemoglobin bands would be found inevitably, causing false-positive results, erroneously attributed to hemoglobin content of mitochondrion-like organelles. Our data do not confirm the hypothesis that the final hemoglobin biosynthesis occurs inside mitochondrion-like organelles. They suggest that the hemoglobin molecule be assembled in the erythrocyte cytoplasm outside of mitochondria or hemosomes. PMID:10481306

  7. A terrain-based site characterization map of California with implications for the contiguous United States

    USGS Publications Warehouse

    Yong, Alan K.; Hough, Susan E.; Iwahashi, Junko; Braverman, Amy

    2012-01-01

    We present an approach based on geomorphometry to predict material properties and characterize site conditions using the VS30 parameter (time‐averaged shear‐wave velocity to a depth of 30 m). Our framework consists of an automated terrain classification scheme based on taxonomic criteria (slope gradient, local convexity, and surface texture) that systematically identifies 16 terrain types from 1‐km spatial resolution (30 arcsec) Shuttle Radar Topography Mission digital elevation models (SRTM DEMs). Using 853 VS30 values from California, we apply a simulation‐based statistical method to determine the mean VS30 for each terrain type in California. We then compare the VS30 values with models based on individual proxies, such as mapped surface geology and topographic slope, and show that our systematic terrain‐based approach consistently performs better than semiempirical estimates based on individual proxies. To further evaluate our model, we apply our California‐based estimates to terrains of the contiguous United States. Comparisons of our estimates with 325 VS30 measurements outside of California, as well as estimates based on the topographic slope model, indicate our method to be statistically robust and more accurate. Our approach thus provides an objective and robust method for extending estimates of VS30 for regions where in situ measurements are sparse or not readily available.

  8. Combined geophysical methods for mapping infiltration pathways at the Aurora Water Aquifer recharge and recovery site

    NASA Astrophysics Data System (ADS)

    Jasper, Cameron A.

    Although aquifer recharge and recovery systems are a sustainable, decentralized, low cost, and low energy approach for the reclamation, treatment, and storage of post- treatment wastewater, they can suffer from poor infiltration rates and the development of a near-surface clogging layer within infiltration ponds. One such aquifer recharge and recovery system, the Aurora Water site in Colorado, U.S.A, functions at about 25% of its predicted capacity to recharge floodplain deposits by flooding infiltration ponds with post-treatment wastewater extracted from river bank aquifers along the South Platte River. The underwater self-potential method was developed to survey self-potential signals at the ground surface in a flooded infiltration pond for mapping infiltration pathways. A method for using heat as a groundwater tracer within the infiltration pond used an array of in situ high-resolution temperature sensing probes. Both relatively positive and negative underwater self-potential anomalies are consistent with observed recovery well pumping rates and specific discharge estimates from temperature data. Results from electrical resistivity tomography and electromagnetics surveys provide consistent electrical conductivity distributions associated with sediment textures. A lab method was developed for resistivity tests of near-surface sediment samples. Forward numerical modeling synthesizes the geophysical information to best match observed self- potential anomalies and provide permeability distributions, which is important for effective aquifer recharge and recovery system design, and optimization strategy development.

  9. Bayesian Mapping of Genomewide Interacting Quantitative Trait Loci for Ordinal Traits

    PubMed Central

    Yi, Nengjun; Banerjee, Samprit; Pomp, Daniel; Yandell, Brian S.

    2007-01-01

    Development of statistical methods and software for mapping interacting QTL has been the focus of much recent research. We previously developed a Bayesian model selection framework, based on the composite model space approach, for mapping multiple epistatic QTL affecting continuous traits. In this study we extend the composite model space approach to complex ordinal traits in experimental crosses. We jointly model main and epistatic effects of QTL and environmental factors on the basis of the ordinal probit model (also called threshold model) that assumes a latent continuous trait underlies the generation of the ordinal phenotypes through a set of unknown thresholds. A data augmentation approach is developed to jointly generate the latent data and the thresholds. The proposed ordinal probit model, combined with the composite model space framework for continuous traits, offers a convenient way for genomewide interacting QTL analysis of ordinal traits. We illustrate the proposed method by detecting new QTL and epistatic effects for an ordinal trait, dead fetuses, in a F2 intercross of mice. Utility and flexibility of the method are also demonstrated using a simulated data set. Our method has been implemented in the freely available package R/qtlbim, which greatly facilitates the general usage of the Bayesian methodology for genomewide interacting QTL analysis for continuous, binary, and ordinal traits in experimental crosses. PMID:17507680

  10. Spa2p functions as a scaffold-like protein to recruit the Mpk1p MAP kinase module to sites of polarized growth.

    PubMed

    van Drogen, Frank; Peter, Matthias

    2002-10-01

    Scaffold proteins play a major role in regulating MAP kinase pathways. In yeast, the Mpk1p-MAP kinase pathway functions to maintain the integrity of the cytoskeleton and the cell wall. In this module, the MEKK Bck1p functions upstream of the MEKs Mkk1p and Mkk2p, which in turn activate the MAP kinase Mpk1p. Mpk1p regulates several nuclear targets, including the transcription factors Rlm1p and SBF, and the two HMG1-like proteins NHP6A and NHP6B. Here we show that Mpk1p constitutively shuttles between the nucleus and the cytoplasm, and both Mpk1p and Mkk1p localize to sites of polarized growth in a Spa2p-dependent manner. Spa2p belongs to a group of proteins that includes Bni1p, Bud6p, and Pea2p, which are involved in the dynamic organization of the actin cytoskeleton during polarized growth. FRAP analysis shows that Spa2p-GFP is stably anchored at bud tips, whereas Mpk1p binds transiently. Spa2p interacts with Mkk1p and Mpk1p, and membrane bound Spa2p is sufficient to recruit Mkk1p and Mpk1p but not other MAP kinases to the cell cortex. Taken together, these results suggest that Spa2p functions as a scaffold-like protein for the cell wall integrity pathway during polarized growth. PMID:12361575

  11. Interactions between cochlear implant electrode insertion depth and frequency-place mapping

    NASA Astrophysics Data System (ADS)

    Başkent, Deniz; Shannon, Robert V.

    2005-03-01

    While new electrode designs allow deeper insertion and wider coverage in the cochlea, there is still considerable variation in the insertion depth of the electrode array among cochlear implant users. The present study measures speech recognition as a function of insertion depth, varying from a deep insertion of 10 electrodes at 28.8 mm to a shallow insertion of a single electrode at 7.2 mm, in four Med-El Combi 40+ users. Short insertion depths were simulated by inactivating apical electrodes. Speech recognition increased with deeper insertion, reaching an asymptotic level at 21.6 or 26.4 mm depending on the frequency-place map used. Başkent and Shannon [J. Acoust. Soc. Am. 116, 3130-3140 (2004)] showed that speech recognition by implant users was best when the acoustic input frequency was matched onto the cochlear location that normally processes that frequency range, minimizing the spectral distortions in the map. However, if an electrode array is not fully inserted into the cochlea, a matched map will result in the loss of considerable low-frequency information. The results show a strong interaction between the optimal frequency-place mapping and electrode insertion depth. Consistent with previous studies, frequency-place matching produced better speech recognition than compressing the full speech range onto the electrode array for full insertion ranges (20 to 25 mm from the round window). For shallower insertions (16.8 and 19.2 mm) a mild amount of frequency-place compression was better than truncating the frequency range to match the basal cochlear location. These results show that patients with shallow electrode insertions might benefit from a map that assigns a narrower frequency range than patients with full insertions. .

  12. Thermal dissociation of protein-oligosaccharide complexes in the gas phase: mapping the intrinsic intermolecular interactions.

    PubMed

    Kitova, Elena N; Bundle, David R; Klassen, John S

    2002-05-22

    Blackbody infrared radiative dissociation (BIRD) and functional group replacement are used to map the location and strength of hydrogen bonds between an antibody single chain fragment (scFv) and its natural trisaccharide receptor, alpha-D-Galp (1-->2)[alpha-D-Abep (1-->3)]alpha-D-Manp1-->OMe (1), in the gaseous, multiply protonated complex. Arrhenius activation parameters (E(a) and A) are reported for the loss of 1 and a series of monodeoxy trisaccharide congeners (5-8 identical with tri) from the (scFv + tri + 10H)(+10) complex. The energetic contribution of the specific oligosaccharide OH groups to the stability of the (scFv + 1 + 10H)(+10) complex is determined from the differences in E(a) measured for the trisaccharide analogues and 1 (55.2 kcal/mol). A decrease of 6 to 11 kcal/mol in E(a), measured for the monodeoxy trisaccharides, indicates that the deleted OH groups interact strongly with the scFv and that they account for a majority of the stabilizing intermolecular interactions. A partial map of the hydrogen bond donor/acceptor groups of 1 and the strength of the interactions is presented for the protonated +10 complex. A comparison of the gas-phase map with the crystal structure indicates that significant structural differences exist. The hydroxyl groups located outside of the binding pocket, and exposed to solvent in solution, participate in new protein-oligosaccharide hydrogen bonds in the gas phase. The decrease in kinetic and energetic stability of the (scFv + 2 + nH)(n)()(+) complex with increasing charge-state is attributed to conformational differences in the binding region induced by electrostatic repulsion. The similarity in the Arrhenius parameters for the +9 and +10 charge states suggests that repulsion effects on the structure of the binding region are negligible below +11. PMID:12010066

  13. The interaction of high-resolution electrophoresis and computational analysis in genome mapping

    SciTech Connect

    Carrano, A.V.; Branscomb, E.W.; de Jong, P.J.; Mohrenweiser, H.; Olsen, A.; Slezak, T.

    1990-07-26

    The construction of physical maps and the determination of the DNA sequence of chromosome-size segments of the human genome is a complex, multidisciplinary undertaking. The approach we have taken to construct a physical map and sequence of human chromosome 19 typifies these interactions. We exploit the power of both acrylamide and agarose gel electrophoresis to provide a simple and versatile method for DNA fingerprinting and the creation of contigs or sets of overlapping genomic clones. Cosmid libraries are constructed from Yeast Artificial Chromosomes (YAC) clones or from flow-sorted chromosomes. Cosmid DNA isolated from the screened library array is cut with a combination of five restriction enzymes and the fragment ends labeled with one of four different fluorochromes. Our approach to contig construction uses a robotic system to label restriction fragments from cosmids with fluorochromes, use of an automated DNA sequencer to capture fragment mobility data in a high resolution multiplex mode processes the mobility data to determine fragment length and provide a statistical measure of overlap among cosmids; and display the contigs and underlying cosmids for operator interaction and access to a database. Data analyses and interactions are conducted over a network of SUN workstations using a set of software tools that we developed and coupled to a commercially available database. Applying these methods, we have analyzed 5154 cosmid clones and assembled 515 contigs for chromosome 19. Some of these contigs have been identified with known genes and many have been mapped to the chromosome by fluorescence in situ hybridization. Existing contigs are being extended by a combination of walking and fingerprinting. 21 refs., 2 figs.

  14. 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

  15. The Importance of Synchronous Interaction for Student Satisfaction with Course Web Sites

    ERIC Educational Resources Information Center

    Cao, Qidong; Griffin, Thomas E.; Bai, Xue

    2009-01-01

    As more affordable synchronous communications are becoming available, the use of synchronous interactions has not been noted in course Web sites as often as asynchronous communications. Previous research indicated that the integration of synchronous tools into course Web sites has made a positive impact on students. While most of the previous…

  16. 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…

  17. The Internet and Public Participation: State Legislature Web Sites and the Many Definitions of Interactivity

    ERIC Educational Resources Information Center

    Ferber, Paul; Foltz, Franz; Pugliese, Rudy

    2005-01-01

    The interactive nature of the Internet is seen by some as a technological innovation that might boost participation in politics and civic affairs. That potential, however, is clouded by imprecise definitions of interactivity found among scholars and practitioners alike. Evaluation of state legislature Web sites found them to not be very…

  18. The Internet and Public Participation: State Legislature Web Sites and the Many Definitions of Interactivity

    ERIC Educational Resources Information Center

    Ferber, Paul; Foltz, Franz; Pugliese, Rudy

    2005-01-01

    The interactive nature of the Internet is seen by some as a technological innovation that might boost participation in politics and civic affairs. That potential, however, is clouded by imprecise definitions of interactivity found among scholars and practitioners alike. Evaluation of state legislature Web sites found them to not be very

  19. RefSOFI for Mapping Nanoscale Organization of Protein-protein Interactions in Living cells

    PubMed Central

    Hertel, Fabian; Mo, Gary C. H.; Duwé, Sam; Dedecker, Peter; Zhang, Jin

    2015-01-01

    Summary It has become increasingly clear that protein-protein interactions (PPIs) are compartmentalized in nanoscale domains that define the biochemical architecture of the cell. Despite tremendous advances in super-resolution imaging, strategies to observe PPIs at sufficient resolution to discern their organization are just emerging. Here we describe a strategy in which PPIs induce reconstitution of fluorescent proteins (FPs) that are capable of exhibiting single-molecule fluctuations suitable for Stochastic Optical Fluctuation Imaging (SOFI). Subsequently, spatial maps of these interactions can be resolved in super-resolution in living cells. Using this strategy, termed reconstituted fluorescence-based SOFI (refSOFI), we investigated the interaction between the endoplasmic reticulum Ca2+ sensor STIM1 and the pore-forming channel subunit ORAI1, a crucial process in store-operated Ca2+ entry (SOCE). Stimulating SOCE does not appear to change the size of existing STIM1/ORAI1 interaction puncta at the ER-plasma membrane junctions, but results in an apparent increase in the number of interaction puncta. PMID:26748717

  20. Mapping of synergistic components of weakly interacting protein-protein motifs using arrays of paired peptides.

    PubMed

    Espanel, Xavier; Wälchli, Sébastien; Rückle, Thomas; Harrenga, Axel; Huguenin-Reggiani, Martine; Hooft van Huijsduijnen, Rob

    2003-04-25

    Protein-protein recognition usually involves multiple interactions among different motifs that are scattered over protein surfaces. To identify such weak interactions, we have developed a novel double peptide synthesis (DS) method. This method allows us to map protein-protein interactions that involve two linear dis- continuous components from a polypeptide by the use of spatially addressable synergistic pairs of synthetic peptides. The DS procedure is based on the "SPOT" membrane-bound peptide synthesis technique, but to synthesize a mixture of two peptides, it uses both Fmoc (N-(9-fluorenyl)methoxycarbonyl))-alanine and Alloc-alanine at the first cycle. This allows their selective deprotection by either piperidine or tributyltin/palladium treatment, respectively. Using SPOT DS, we confirmed as a proof of principle that Elk-1 Ser(383) phosphorylation by ERK-2 kinase is stimulated by the presence of the Elk-1-docking domain. SPOT DS can also be used to dissect protein-protein motifs that define phosphatase substrate affinity. Using this technique, we identified three new regions in the insulin receptor that stimulate the dephosphorylation of the receptor by protein-tyrosine phosphatase (PTP) 1B and presumably increase the selectivity of PTP for this substrate. These data demonstrate that the SPOT DS technique allows the identification of non-linear weakly interacting protein motifs, which are an important determinant of protein kinase and phosphatase substrate specificity and of protein-protein interactions in general. PMID:12551909

  1. RefSOFI for Mapping Nanoscale Organization of Protein-Protein Interactions in Living Cells.

    PubMed

    Hertel, Fabian; Mo, Gary C H; Duwé, Sam; Dedecker, Peter; Zhang, Jin

    2016-01-12

    It has become increasingly clear that protein-protein interactions (PPIs) are compartmentalized in nanoscale domains that define the biochemical architecture of the cell. Despite tremendous advances in super-resolution imaging, strategies to observe PPIs at sufficient resolution to discern their organization are just emerging. Here we describe a strategy in which PPIs induce reconstitution of fluorescent proteins (FPs) that are capable of exhibiting single-molecule fluctuations suitable for stochastic optical fluctuation imaging (SOFI). Subsequently, spatial maps of these interactions can be resolved in super-resolution in living cells. Using this strategy, termed reconstituted fluorescence-based SOFI (refSOFI), we investigated the interaction between the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the pore-forming channel subunit ORAI1, a crucial process in store-operated Ca(2+) entry (SOCE). Stimulating SOCE does not appear to change the size of existing STIM1/ORAI1 interaction puncta at the ER-plasma membrane junctions, but results in an apparent increase in the number of interaction puncta. PMID:26748717

  2. Mapping the lipoylation site of Arabidopsis thaliana plastidial dihydrolipoamide S-acetyltransferase using mass spectrometry and site-directed mutagenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The catalytic enhancement achieved by the pyruvate dehydrogenase complex (PDC) results from a combination of substrate channeling plus active-site coupling. The mechanism for active-site coupling involves lipoic acid prosthetic groups covalently attached to Lys residues in the primary ...

  3. First-generation site-response maps for the Los Angeles region based on earthquake ground motions

    USGS Publications Warehouse

    Hartzell, S.; Harmsen, S.; Frankel, A.; Carver, D.; Cranswick, E.; Meremonte, M.; Michael, J.

    1998-01-01

    Ground-motion records from aftershocks of the 1994 Northridge earthquake and mainshock records from the 1971 San Fernando, 1987 Whittier Narrows, 1991 Sierra Madre, and 1994 Northridge earthquakes are used to estimate site response relative to a rock site for the urban Los Angeles area. Site response is estimated at 232 mainshock and 201 aftershock sites relative to a low-amplitude site in the Santa Monica Mountains. Average amplification values are calculated for the frequency bands: 1 to 3, 3 to 5, and 5 to 7 Hz. These bands are chosen based on limitations in aftershock recording equipment at lower frequencies and reduced significance to the building inventory at higher frequencies. Site amplification factors determined at the instrumented locations are grouped by the surficial geology and contoured to produce a continuous spatial estimation of amplification. The maps in this article represent the first attempt to produce estimates of site amplification based on observations of ground motion for such a large areal extent of the Los Angeles region. These maps are expected to evolve as more data become available and more analysis is done.

  4. Using integrated geospatial mapping and conceptual site models to guide risk-based environmental clean-up decisions.

    PubMed

    Mayer, Henry J; Greenberg, Michael R; Burger, Joanna; Gochfield, Michael; Powers, Charles; Kosson, David; Keren, Roger; Danis, Christine; Vyas, Vikram

    2005-04-01

    Government and private sector organizations are increasingly turning to the use of maps and other visual models to provide a depiction of environmental hazards and the potential risks they represent to humans and ecosystems. Frequently, the graphic presentation is tailored to address a specific contaminant, its location and possible exposure pathways, and potential receptors. Its format is usually driven by the data available, choice of graphics technology, and the audience being served. A format that is effective for displaying one contaminant at one scale at one site, however, may be ineffective in accurately portraying the circumstances surrounding a different contaminant at the same site, or the same contaminant at a different site, because of limitations in available data or the graphics technology being used. This is the daunting challenge facing the U.S. Department of Energy (DOE), which is responsible for the nation's legacy wastes from nuclear weapons research, testing, and production at over 100 sites in the United States. In this article, we discuss the development and use of integrated geospatial mapping and conceptual site models to identify hazards and evaluate alternative long-term environmental clean-up strategies at DOE sites located across the United States. While the DOE probably has the greatest need for such information, the Department of Defense and other public and private responsible parties for many large and controversial National Priority List or Superfund sites would benefit from a similar approach. PMID:15876215

  5. Site-directed mutagenesis for quantitation of base-base interactions at defined sites.

    PubMed

    Singer, B; Dosanjh, M K

    1990-01-01

    Two alkylation products implicated in initiation of carcinogenesis are O6-alkylguanine (m6G) and O4-alkylthymine (m4T). We have used site-specific insertion of these derivatives into oligonucleotides and measured the kinetic constants of various pairings, using both prokaryotic and eukaryotic polymerases for replication. Preliminary data are also reported for another carcinogen product, N2,3-ethenodeoxyguanosine ( epsilon G). The immediate neighbor bases play an important role in determining the frequency of specific changed basepairing and subsequent elongation of the annealed primer. However, both m4T and m6G prefer to form a type of G.T pairing which would lead to the transitions: G.C----A.T or T.A----C.G. The enzymes were the Klenow fragment of E. coli DNA polymerase I (Kf), engineered 3'----5' exonuclease-free Kf (exo-free Kf), polymerase alpha-primase complex from Drosophila melanogaster or calf thymus, and human immunodeficient virus-I reverse transcriptase (HIV-I RT). All enzymes led to approximately the same frequency of transitions. It is postulated that the mutation frequency at a given site is primarily a function of the structure of the sequence around the target site. PMID:2233812

  6. Mapping Microbial Populations Relative to Sites of Ongoing Serpentinization: Results from the Tablelands Ophiolite Complex, Canada

    NASA Astrophysics Data System (ADS)

    Schrenk, M. O.; Brazelton, W. J.; Woodruff, Q.; Szponar, N.; Morrill, P. L.

    2010-12-01

    The aqueous alteration of ultramafic rocks (serpentinization) has been suggested to be a favorable process for the habitability of astrobodies in our solar system including subsurface environments of Mars and Europa. Serpentinization produces copious quantities of hydrogen and small organic molecules, and leads to highly reducing, highly alkaline conditions (up to pH 12) and a lack of dissolved inorganic carbon, which both stimulates and challenges microbial activities. Several environments on Earth provide insight into the relationships between serpentinization and microbial life including slow-spreading mid-ocean ridges, subduction zones, and ophiolite materials emplaced along continental margins. The Tablelands, an ophiolite in western Newfoundland, Canada provides an opportunity to carefully document and map the relationships between geochemical energy, microbial growth, and physiology. Alkaline fluids at the Tablelands originate from 500-million year old oceanic crust and accumulate in shallow pools or seep from beneath serpentinized talus. Fluids, rocks, and gases were collected from the Tablelands during a series of field excursions in 2009 and 2010, and geochemical, microscopic, molecular, and cultivation-based approaches were used to study the serpentinite microbial ecosystem. These samples provide an opportunity to generate a comprehensive map of microbial communities and their activities in space and time. Data indicate that a low but detectable stock of microorganisms inhabit high pH pools associated with end-member serpentinite fluids. Enrichment cultures yielded brightly pigmented colonies related to Alphaproteobacteria, presumably carrying out anoxygenic photosynthesis, and Firmicutes, presumably catalyzing the fermentation of organic matter. Culture-independent analyses of SSU rRNA using T-RFLP indicated low diversity communities of Firmicutes and Archaea in standing alkaline pools, communities of Beta- and Gammaproteobacteria at high pH seeps, and assemblages consisting of diverse taxa at neutral pH background sites. Terrestrial serpentinite-hosted microbial ecosystems with their accessibility, their low phylogenetic diversity, and limited range of energetic resources provide an excellent opportunity to explore the interplay between geochemical energy and life and to elucidate the native serpentinite subsurface biosphere. From the perspective of Mars exploration, studies of serpentinite ecosystems provide the opportunity to pinpoint the organisms and physiological adaptations specifically associated with serpentinization and to directly measure their geochemical impacts. Both of these results will inform modeling and life detection efforts of the Martian subsurface environment.

  7. Digital geologic map of the Nevada Test Site and vicinity, Nye, Lincoln, and Clark Counties, Nevada, and Inyo County, California

    SciTech Connect

    Slate, J.L.; Berry, M.E.; Rowley, P.D.; Fridrich, C.J.; Morgan, K.S.; Workman, J.B.; Young, O.D.; Dixon, G.L.; Williams, V.S.; McKee, E.H.; Ponce, D.A.; Hildenbrand, T.G.; Swadley, W.C.; Lundstrom, S.C.; Ekren, E.B.; Warren, R.G.; Cole, J.C.; Fleck, R.J.; Lanphere, M.A.; Sawyer, D.A.; Minor, S.A.; Grunwald, D.J.; Laczniak, R.J.; Menges, C.M.; Yount, J.C.; Jayko, A.S.

    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. 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.

  8. Accurate thermodynamics for short-ranged truncations of Coulomb interactions in site-site molecular models

    NASA Astrophysics Data System (ADS)

    Rodgers, Jocelyn M.; Weeks, John D.

    2009-12-01

    Coulomb interactions are present in a wide variety of all-atom force fields. Spherical truncations of these interactions permit fast simulations but are problematic due to their incorrect thermodynamics. Herein we demonstrate that simple analytical corrections for the thermodynamics of uniform truncated systems are possible. In particular, results for the simple point charge/extended (SPC/E) water model treated with spherically truncated Coulomb interactions suggested by local molecular field theory [J. M. Rodgers and J. D. Weeks, Proc. Natl. Acad. Sci. U.S.A. 105, 19136 (2008)] are presented. We extend the results developed by Chandler [J. Chem. Phys. 65, 2925 (1976)] so that we may treat the thermodynamics of mixtures of flexible charged and uncharged molecules simulated with spherical truncations. We show that the energy and pressure of spherically truncated bulk SPC/E water are easily corrected using exact second-moment-like conditions on long-ranged structure. Furthermore, applying the pressure correction as an external pressure removes the density errors observed by other research groups in NPT simulations of spherically truncated bulk species.

  9. Topographic Mapping Of The Ocular Fundus By Laser Contour Angiography : The Man-Machine Interaction

    NASA Astrophysics Data System (ADS)

    Shapiro, Jerrold M.

    1980-07-01

    Laser contour angiography is a new technique which was developed by the author for topographically mapping the retina and optic nerve head of the eye. A striped pattern of laser light is projected onto the ocular fundus through one side of the patient's dilated pupil. Photographs, taken through the opposite side of the pupil, reveal the topography as parallactic displacements of the stripes. A topographic map is constructed from tracings of the stripes. The method was shown to produce highly reproducible maps. In order to further improve the reproducibility of the topographic measurements, the effects of the man-machine interaction during the stripe tracing process on measurement error were investigated. The tracing strategy of the operator is to estimate the position along the edge of a stripe at which the perceived light intensity is halfway between the local maximum and minimum. The relationship of errors in the estimates of position to those in perceived intensity was established using a theoretical model. The predictive ability of the model was tested using repeated measurements on the laser contour angiogram of a human eye. The model predicted a position error (standard deviation) of 4.3 micrometers. This agreed remarkably well with the experimental result of 4.5 micrometers. The results indicated that film grain noise and defocussing of the projected pattern are the primary contributors to measurement error. We now use a finer grain film, and have further reduced the position error to 3.4 micrometers.

  10. 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

  11. 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 the class fraction signatures of pixels classified as MPB infestation, we were able to observe increases in infection extent and intensity in the year before the fire. The resulting maps will help to increase our understanding of the process that contributed to the High Park Fire, and we believe that the novel classification approach will allow for improved characterization of forest disturbances.

  12. Metallicity at the explosion sites of interacting transients

    NASA Astrophysics Data System (ADS)

    Taddia, F.; Sollerman, J.; Fremling, C.; Pastorello, A.; Leloudas, G.; Fransson, C.; Nyholm, A.; Stritzinger, M. D.; Ergon, M.; Roy, R.; Migotto, K.

    2015-08-01

    Context. Some circumstellar-interacting (CSI) supernovae (SNe) are produced by the explosions of massive stars that have lost mass shortly before the SN explosion. There is evidence that the precursors of some SNe IIn were luminous blue variable (LBV) stars. For a small number of CSI SNe, outbursts have been observed before the SN explosion. Eruptive events of massive stars are named SN impostors (SN IMs) and whether they herald a forthcoming SN or not is still unclear. The large variety of observational properties of CSI SNe suggests the existence of other progenitors, such as red supergiant (RSG) stars with superwinds. Furthermore, the role of metallicity in the mass loss of CSI SN progenitors is still largely unexplored. Aims: Our goal is to gain insight into the nature of the progenitor stars of CSI SNe by studying their environments, in particular the metallicity at their locations. Methods: We obtain metallicity measurements at the location of 60 transients (including SNe IIn, SNe Ibn, and SN IMs) via emission-line diagnostic on optical spectra obtained at the Nordic Optical Telescope and through public archives. Metallicity values from the literature complement our sample. We compare the metallicity distributions among the different CSI SN subtypes, and to those of other core-collapse SN types. We also search for possible correlations between metallicity and CSI SN observational properties. Results: We find that SN IMs tend to occur in environments with lower metallicity than those of SNe IIn. Among SNe IIn, SN IIn-L(1998S-like) SNe show higher metallicities, similar to those of SNe IIL/P, whereas long-lasting SNe IIn (1988Z-like) show lower metallicities, similar to those of SN IMs. The metallicity distribution of SNe IIn can be reproduced by combining the metallicity distributions of SN IMs (which may be produced by major outbursts of massive stars like LBVs) and SNe IIP (produced by RSGs). The same applies to the distributions of the normalized cumulative rank (NCR) values, which quantifies the SN association to H ii regions. For SNe IIn, we find larger mass-loss rates and higher CSM velocities at higher metallicities. The luminosity increment in the optical bands during SN IM outbursts tend to be larger at higher metallicity, whereas the SN IM quiescent optical luminosities tend to be lower. Conclusions: The difference in metallicity between SNe IIn and SN IMs indicates that LBVs are only one of the progenitor channels for SNe IIn, with 1988Z-like and 1998S-like SNe possibly arising from LBVs and RSGs, respectively. Finally, even though line-driven winds likely do not primarily drive the late mass-loss of CSI SN progenitors, metallicity has some impact on the observational properties of these transients. Based on observations performed at the Nordic Optical Telescope (Proposal numbers: P45-004, P49-016; PI: F. Taddia), La Palma, Spain.Tables 1-3, 5-7 and Figs. 4-7, 11-14 are available in electronic form at http://www.aanda.org

  13. Identification of the Interaction Sites of Inhibitor-3 for Protein Phosphatase-1

    PubMed Central

    Zhang, Lifang; Qi, Zhiqing; Gao, Yan; Lee, Ernest Y.C.

    2008-01-01

    Inhibitor-3 is a potent inhibitor of protein phosphatase-1, with an IC50 in the nanomolar range for the inhibition of the dephosphorylation of phosphorylase a. Human Inhibitor-3 possesses a putative protein phosphatase-1 binding motif, 39KKVEW43. We provide direct evidence that this sequence is involved in PP1 interaction by examining the effects of site-directed mutations of Inhibitor-3 on its ability to inhibit protein phosphatase-1. A second interaction site whose deletion led to loss of inhibitory potency was identified between residues 65–77. The existence of two interaction sites is consistent with the high inhibitory potency of Inhibitor-3, and with current models for other inhibitor and targeting proteins that interact with protein phosphatase-1 with high affinity. PMID:18951879

  14. Construction of High-Density Genetic Map in Barley through Restriction-Site Associated DNA Sequencing

    PubMed Central

    Zhou, Gaofeng; Zhang, Qisen; Zhang, Xiao-qi; Tan, Cong; Li, Chengdao

    2015-01-01

    Genetic maps in barley are usually constructed from a limited number of molecular markers such as SSR (simple sequence repeat) and DarT (diversity arrays technology). These markers must be first developed before being used for genotyping. Here, we introduce a new strategy based on sequencing progeny of a doubled haploid population from Baudin × AC Metcalfe to construct a genetic map in barley. About 13,547 polymorphic SNP tags with >93% calling rate were selected to construct the genetic map. A total of 12,998 SNP tags were anchored to seven linkage groups which spanned a cumulative 967.6 cM genetic distance. The high-density genetic map can be used for QTL mapping and the assembly of WGS and BAC contigs. The genetic map was evaluated for its effectiveness and efficiency in QTL mapping and candidate gene identification. A major QTL for plant height was mapped at 105.5 cM on chromosome 3H. This QTL with LOD value of 13.01 explained 44.5% of phenotypic variation. This strategy will enable rapid and efficient establishment of high-density genetic maps in other species. PMID:26182149

  15. Sequence-based prediction of protein-protein interaction sites with L1-logreg classifier.

    PubMed

    Dhole, Kaustubh; Singh, Gurdeep; Pai, Priyadarshini P; Mondal, Sukanta

    2014-05-01

    Protein-protein interactions are of central importance for virtually every process in a living cell. Information about the interaction sites in proteins improves our understanding of disease mechanisms and can provide the basis for new therapeutic approaches. Since a multitude of unique residue-residue contacts facilitate the interactions, protein-protein interaction sites prediction has become one of the most important and challenging problems of computational biology. Although much progress in this field has been reported, this problem is yet to be satisfactorily solved. Here, a novel method (LORIS: L1-regularized LOgistic Regression based protein-protein Interaction Sites predictor) is proposed, that identifies interaction residues, using sequence features and is implemented via the L1-logreg classifier. Results show that LORIS is not only quite effective, but also, performs better than existing state-of-the art methods. LORIS, available as standalone package, can be useful for facilitating drug-design and targeted mutation related studies, which require a deeper knowledge of protein interactions sites. PMID:24486250

  16. 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

  17. 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 retrievals through refinements in the description of surface emissivity and use of vector projection to define the misfit between model and observed spectra. Portions of this research were conducted at the Jet Propulsion Laboratory, California Institute of Technology, under contract to the National Aeronautics and Space Administration.

  18. Construction of High-Density Linkage Maps of Populus deltoides × P. simonii Using Restriction-Site Associated DNA Sequencing

    PubMed Central

    Tong, Chunfa; Li, Huogen; Wang, Ying; Li, Xuran; Ou, Jiajia; Wang, Deyuan; Xu, Houxi; Ma, Chao; Lang, Xianye; Liu, Guangxin; Zhang, Bo; Shi, Jisen

    2016-01-01

    Although numerous linkage maps have been constructed in the genus Populus, they are typically sparse and thus have limited applications due to low throughput of traditional molecular markers. Restriction-site associated DNA sequencing (RADSeq) technology allows us to identify a large number of single nucleotide polymorphisms (SNP) across genomes of many individuals in a fast and cost-effective way, and makes it possible to construct high-density genetic linkage maps. We performed RADSeq for 299 progeny and their two parents in an F1 hybrid population generated by crossing the female Populus deltoides ‘I-69’ and male Populus simonii ‘L3’. A total of 2,545 high quality SNP markers were obtained and two parent-specific linkage maps were constructed. The female genetic map contained 1601 SNPs and 20 linkage groups, spanning 4,249.12 cM of the genome with an average distance of 2.69 cM between adjacent markers, while the male map consisted of 940 SNPs and also 20 linkage groups with a total length of 3,816.24 cM and an average marker interval distance of 4.15 cM. Finally, our analysis revealed that synteny and collinearity are highly conserved between the parental linkage maps and the reference genome of P. trichocarpa. We demonstrated that RAD sequencing is a powerful technique capable of rapidly generating a large number of SNPs for constructing genetic maps in outbred forest trees. The high-quality linkage maps constructed here provided reliable genetic resources to facilitate locating quantitative trait loci (QTLs) that control growth and wood quality traits in the hybrid population. PMID:26964097

  19. Construction of High-Density Linkage Maps of Populus deltoides × P. simonii Using Restriction-Site Associated DNA Sequencing.

    PubMed

    Tong, Chunfa; Li, Huogen; Wang, Ying; Li, Xuran; Ou, Jiajia; Wang, Deyuan; Xu, Houxi; Ma, Chao; Lang, Xianye; Liu, Guangxin; Zhang, Bo; Shi, Jisen

    2016-01-01

    Although numerous linkage maps have been constructed in the genus Populus, they are typically sparse and thus have limited applications due to low throughput of traditional molecular markers. Restriction-site associated DNA sequencing (RADSeq) technology allows us to identify a large number of single nucleotide polymorphisms (SNP) across genomes of many individuals in a fast and cost-effective way, and makes it possible to construct high-density genetic linkage maps. We performed RADSeq for 299 progeny and their two parents in an F1 hybrid population generated by crossing the female Populus deltoides 'I-69' and male Populus simonii 'L3'. A total of 2,545 high quality SNP markers were obtained and two parent-specific linkage maps were constructed. The female genetic map contained 1601 SNPs and 20 linkage groups, spanning 4,249.12 cM of the genome with an average distance of 2.69 cM between adjacent markers, while the male map consisted of 940 SNPs and also 20 linkage groups with a total length of 3,816.24 cM and an average marker interval distance of 4.15 cM. Finally, our analysis revealed that synteny and collinearity are highly conserved between the parental linkage maps and the reference genome of P. trichocarpa. We demonstrated that RAD sequencing is a powerful technique capable of rapidly generating a large number of SNPs for constructing genetic maps in outbred forest trees. The high-quality linkage maps constructed here provided reliable genetic resources to facilitate locating quantitative trait loci (QTLs) that control growth and wood quality traits in the hybrid population. PMID:26964097

  20. 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

  1. Geologic structure mapping database Spent Fuel Test - Climax, Nevada Test Site

    SciTech Connect

    Yow, J.L. Jr.

    1984-12-04

    Information on over 2500 discontinuities mapped at the SFT-C is contained in the geologic structure mapping database. Over 1800 of these features include complete descriptions of their orientations. This database is now available for use by other researchers. 6 references, 3 figures, 2 tables.

  2. Using JournalMap to link spatial information with ecological site descriptions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Dynamic prescription maps for site-specific variable rate irrigation of cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTION DOMAINS BETWEEN XPG AND WRN

    SciTech Connect

    Rangaraj, K.; Cooper, P.K.; Trego, K.S.

    2009-01-01

    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) 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-terminal region of XPG as well as the C-terminal region of WRN. The physical interaction between XPG and WRN links NER, (made evident by the disease XP) with DSBR, which imparts additional knowledge of the overlapping nature of these two proteins and the previously distinct DNA repair pathways they are associated with. Since genomic integrity is constantly threatened by both endogenous and exogenous (internal and external) damage, understanding the roles of these proteins in coordinating DNA repair processes with replication will signifi cantly further understanding how defects instigate physiological consequences in response to various DNA damaging sources. This ultimately contributes to our understanding of cancer and premature aging.

  5. 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 bookmark those layers for quick access in subsequent sessions. A search tool is also provided to allow users to quickly find points of interests on the moon and to view the auxiliary data associated with that feature. More advanced features include the ability to interact with the data. Using the services provided by the portal, users will be able to log in and access the same scientific analysis tools provided on the web site including measuring between two points, generating subsets, and running other analysis tools, all by using a customized touch interface that are immediately familiar to users of these smart mobile devices. Users can also access their own storage on the portal and view or send the data to other users. Finally, there are features that will utilize functionality that can only be enabled by mobile devices. This includes the use of the gyroscopes and motion sensors to provide a haptic interface visualize lunar data in 3D, on the device as well as potentially on a large screen. The mobile framework that we have developed for LMMP provides a glimpse of what is possible in visualizing and manipulating large geospatial data on small portable devices. While the framework is currently tuned to our portal, we hope that we can generalize the tool to use data sources from any type of GIS services.

  6. Equilibrium states of rigid bodies with multiple interaction sites: Application to protein helices

    NASA Astrophysics Data System (ADS)

    Erman, B.; Bahar, I.; Jernigan, R. L.

    1997-08-01

    Equilibrium configurations of rigid building blocks with multiple embedded interaction sites are investigated, as a coarse-grained approach for conformational sampling of protein structures with known secondary structure. First, hypothetical structures of asymmetric shapes, and pairs of rods composed of multiple interaction sites are considered. The rods are either disconnected or joined by a flexible loop. The sites are assumed to interact with a classical 6-12 Lennard-Jones potential. Subsequently, the investigation is extended to the study of two disconnected ? helices composed of homogeneous interaction sites and to the ROP monomer, a small protein consisting of two heterogeneous ? helices connected by a loop. Residue-specific long-range and short-range potentials extracted from a protein database are used. A Monte Carlo procedure combined with an energy minimization algorithm, originally developed by Li and Scheraga [Proc. Natl. Acad. Sci. USA 84, 6611 (1987)] is used to generate a set of low energy conformations over the full conformational space. Results show that: (i) The potential of mean force between two rods as a whole exhibits an inverse linear dependence on the separation between rods despite the individual sites interacting via a 6-12 Lennard-Jones potential. (ii) As the length of the rods (or helices) increases, they tend to align parallel to one other. (iii) This tendency to become parallel is enhanced when the density of interaction sites is higher. (iv) The angle between the principal axes of the rods is found to scale as n-5/3 with the number n of sites. (v) The native conformation of the ROP monomer, including the detailed rotational states of the virtual bonds located in the loop connecting the ? helices is correctly predicted. This lends support to the adoption of such a coarse-grained model and its parameters for future simulations.

  7. 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 (-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

  8. Orbital-science investigation: Part J: preliminary geologic map of the region around the candidate Proclus Apollo landing site

    USGS Publications Warehouse

    Wilhelms, Don E.

    1972-01-01

    The Proclus Crater region was mapped to test the value, for photogeologic mapping purposes, of Apollo 15 metric photographs and to estimate the scientific value of the area as a potential landing site. A metric photographic frame (fig. 25-67) serves as a base for a map of the region around the Proclus Crater (fig. 25-68), and adjacent frames were overlapped with the base frame to provide stereographic images. The excellent stereocoverage allows easy simultaneous observation of topography and albedo. The large forward overlap and the extensive areal photographic coverage provide the best photogeologic data available to date. Brief study has already refined earlier interpretations of the area (refs. 25-7 and 25-32). Although volcanic units have been shown to be extensive in this region, mass wasting apparently has been more important than volcanism in shaping terra landforms.

  9. Interaction of Antiparallel Microtubules in the Phragmoplast Is Mediated by the Microtubule-Associated Protein MAP65-3 in Arabidopsis[W

    PubMed Central

    Ho, Chin-Min Kimmy; Hotta, Takashi; Guo, Fengli; Roberson, Robert W.; Lee, Yuh-Ru Julie; Liu, Bo

    2011-01-01

    In plant cells, microtubules (MTs) in the cytokinetic apparatus phragmoplast exhibit an antiparallel array and transport Golgi-derived vesicles toward MT plus ends located at or near the division site. By transmission electron microscopy, we observed that certain antiparallel phragmoplast MTs overlapped and were bridged by electron-dense materials in Arabidopsis thaliana. Robust MT polymerization, reported by fluorescently tagged End Binding1c (EB1c), took place in the phragmoplast midline. The engagement of antiparallel MTs in the central spindle and phragmoplast was largely abolished in mutant cells lacking the MT-associated protein, MAP65-3. We found that endogenous MAP65-3 was selectively detected on the middle segments of the central spindle MTs at late anaphase. When MTs exhibited a bipolar appearance with their plus ends placed in the middle, MAP65-3 exclusively decorated the phragmoplast midline. A bacterially expressed MAP65-3 protein was able to establish the interdigitation of MTs in vitro. MAP65-3 interacted with antiparallel microtubules before motor Kinesin-12 did during the establishment of the phragmoplast MT array. Thus, MAP65-3 selectively cross-linked interdigitating MTs (IMTs) to allow antiparallel MTs to be closely engaged in the phragmoplast. Although the presence of IMTs was not essential for vesicle trafficking, they were required for the phragmoplast-specific motors Kinesin-12 and Phragmoplast-Associated Kinesin-Related Protein2 to interact with MT plus ends. In conclusion, we suggest that the phragmoplast contains IMTs and highly dynamic noninterdigitating MTs, which work in concert to bring about cytokinesis in plant cells. PMID:21873565

  10. A novel method for protein-protein interaction site prediction using phylogenetic substitution models

    PubMed Central

    La, David; Kihara, Daisuke

    2011-01-01

    Protein-protein binding events mediate many critical biological functions in the cell. Typically, functionally important sites in proteins can be well identified by considering sequence conservation. However, protein-protein interaction sites exhibit higher sequence variation than other functional regions, such as catalytic sites of enzymes. Consequently, the mutational behavior leading to weak sequence conservation poses significant challenges to the protein-protein interaction site prediction. Here, we present a phylogenetic framework to capture critical sequence variations that favor the selection of residues essential for protein-protein binding. Through the comprehensive analysis of diverse protein families, we show that protein binding interfaces exhibit distinct amino acid substitution as compared with other surface residues. Based on this analysis, we have developed a novel method, BindML, which utilizes the substitution models to predict protein-protein binding sites of protein with unknown interacting partners. BindML estimates the likelihood that a phylogenetic tree of a local surface region in a query protein structure follows the substitution patterns of protein binding interface and non-binding surfaces. BindML is shown to perform well compared to alternative methods for protein binding interface prediction. The methodology developed in this study is very versatile in the sense that it can be generally applied for predicting other types of functional sites, such as DNA, RNA, and membrane binding sites in proteins. PMID:21989996

  11. Effects of sudden changes in cycle length and pacing site on canine cardiac surface QRST isoarea maps.

    PubMed

    Hirai, M; Burgess, M J

    1991-07-01

    The effects of changes in paced cycle length alone and changes in both paced cycle length and site of pacing on canine cardiac surface QRST isoarea maps were studied. The correlations between QRST isoarea maps acquired during right ventricular pacing at 900 ms and 700 ms averaged 0.97. The correlations between maps acquired during RV pacing at 900 ms and 500 ms averaged 0.94. The root mean square value of QRST areas progressively decreased as cycle length was decreased from 900 ms to 700 ms and then to 500 ms. This suggests that the pattern of distribution of repolarization properties remained the same and the magnitude of difference in repolarization properties decreased as cycle length was decreased. The correlation coefficients of QRST isoarea maps acquired during RV pacing at 900 ms and those acquired during left ventricular pacing at 700 ms and 500 ms averaged 0.74 +/- 0.01 and 0.68 +/- 0.03, respectively. These correlations were lower than those associated with a change in pacing cycle length alone. Root mean square differences in QRST areas recorded during changes in both pacing site and pacing cycle length were greater than the differences associated with change in cycle length alone. This suggests that changes in activation sequence altered repolarization properties more than they were altered by changes in cycle length alone. QRST isoarea maps have been proposed for assessing arrhythmia vulnerability. The results of this study provide a framework for interpreting QRST isoarea maps acquired during supraventricular tachycardias, premature ventricular complexes, and sustained ventricular tachycardias. PMID:1919381

  12. A map of the cleavage sites for endonuclease AvaI in the chromosome of bacteriophage lambda.

    PubMed Central

    Hughes, S G

    1977-01-01

    The linear order of nine fragments generated by the action of endonuclease AvaI on the DNA of bacteriophage lambda was determined from the altered fragmentation patterns of bacteriophages containing known deletions and of hybrids of bacteriophages lambda and phi80. Digestion of 5'-terminally 32P-labelled bacteriophage-lambda DNA was used to identify the terminal fragments. Measurement of relative fragment lengths permitted rough mapping of the endonuclease-AvaI cleavage sites relative to the ends of the bacteriophage-lambda chromosome. The fragment order was confirmed and the map refined by analysis of the fragmentation of derivative phages containing single cleavage sites for endonuclease EcoRI. Images PLATE 1 PLATE 2 PMID:880215

  13. Automated analysis of viral integration sites in gene therapy research using the SeqMap web resource

    PubMed Central

    Peters, Brandon; Dirscherl, Sara; Dantzer, Jessica; Nowacki, Jonathan; Cross, Scott; Li, Xiaoman; Cornetta, Kenneth; Dinauer, Mary C.; Mooney, Sean D.

    2009-01-01

    Research in gene therapy involving genome integrating vectors, now often includes analysis of vector integration sites across the genome using methods such as ligation mediated (LM)-PCR or linear amplification-mediated (LAM)-PCR. To help researchers analyze these sites and the functions of nearby genes, we have developed SeqMap (http://seqmap.compbio.iupui.edu/) a secure, web-based comprehensive vector integration site management tool that automatically analyzes and annotates large numbers of vector integration sites derived from LM-PCR experiments in human and model organisms upon a common genome database. We believe use of this resource will enable better reproducibility and understanding of this important data. PMID:18580967

  14. LISE: a server using ligand-interacting and site-enriched protein triangles for prediction of ligand-binding sites.

    PubMed

    Xie, Zhong-Ru; Liu, Chuan-Kun; Hsiao, Fang-Chih; Yao, Adam; Hwang, Ming-Jing

    2013-07-01

    LISE is a web server for a novel method for predicting small molecule binding sites on proteins. It differs from a number of servers currently available for such predictions in two aspects. First, rather than relying on knowledge of similar protein structures, identification of surface cavities or estimation of binding energy, LISE computes a score by counting geometric motifs extracted from sub-structures of interaction networks connecting protein and ligand atoms. These network motifs take into account spatial and physicochemical properties of ligand-interacting protein surface atoms. Second, LISE has now been more thoroughly tested, as, in addition to the evaluation we previously reported using two commonly used small benchmark test sets and targets of two community-based experiments on ligand-binding site predictions, we now report an evaluation using a large non-redundant data set containing >2000 protein-ligand complexes. This unprecedented test, the largest ever reported to our knowledge, demonstrates LISE's overall accuracy and robustness. Furthermore, we have identified some hard to predict protein classes and provided an estimate of the performance that can be expected from a state-of-the-art binding site prediction server, such as LISE, on a proteome scale. The server is freely available at http://lise.ibms.sinica.edu.tw. PMID:23609546

  15. Risk map and spatial determinants of pancreas disease in the marine phase of Norwegian Atlantic salmon farming sites

    PubMed Central

    2012-01-01

    Background Outbreaks of pancreas disease (PD) greatly contribute to economic losses due to high mortality, control measures, interrupted production cycles, reduced feed conversion and flesh quality in the aquaculture industries in European salmon-producing countries. The overall objective of this study was to evaluate an effect of potential factors contributing to PD occurrence accounting for spatial congruity of neighboring infected sites, and then create quantitative risk maps for predicting PD occurrence. The study population included active Atlantic salmon farming sites located in the coastal area of 6 southern counties of Norway (where most of PD outbreaks have been reported so far) from 1 January 2009 to 31 December 2010. Results Using a Bayesian modeling approach, with and without spatial component, the final model included site latitude, site density, PD history, and local biomass density. Clearly, the PD infected sites were spatially clustered; however, the cluster was well explained by the covariates of the final model. Based on the final model, we produced a map presenting the predicted probability of the PD occurrence in the southern part of Norway. Subsequently, the predictive capacity of the final model was validated by comparing the predicted probabilities with the observed PD outbreaks in 2011. Conclusions The framework of the study could be applied for spatial studies of other infectious aquatic animal diseases. PMID:23006469

  16. 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.

  17. On-site screened Coulomb interactions for localized electrons in transition metal oxides and defect systems

    NASA Astrophysics Data System (ADS)

    Shih, Bi-Ching; Zhang, Peihong; Department of Physics Team

    2011-03-01

    Electronic and structural properties of strongly correlated material systems are largely determined by the strength of the on-site Coulomb interaction. Theoretical models devised to capture the physics of strongly correlated materials usually involve screened Coulomb interactions as adjustable parameters. We present first-principles results for the screened on-site Coulomb and exchange energy for transition metal oxides. The dielectric screening is calculated within the random phase approximation and the localized electrons are represented by maximally localized Wannier functions. We further extend our study to calculate on-site Coulomb interactions for localized defect states in semiconductors. We acknowledge the computational support provided by the Center for Computational Research at the University at Buffalo, SUNY. This work is supported by the National Science Foundation under Grant No. DMR-0946404 and by the Department of Energy under Grant No. DE-SC0002623.

  18. Systematic analysis of the Hmga2 3? UTR identifies many independent regulatory sequences and a novel interaction between distal sites

    PubMed Central

    Kristjnsdttir, Katla; Fogarty, Elizabeth A.

    2015-01-01

    The 3? untranslated regions (3? UTRs) of mRNAs regulate transcripts by serving as binding sites for regulatory factors, including microRNAs and RNA binding proteins. Binding of such trans-acting factors can control the rates of mRNA translation, decay, and other aspects of mRNA biology. To better understand the role of 3? UTRs in gene regulation, we performed a detailed analysis of a model mammalian 3? UTR, that of Hmga2, with the principal goals of identifying the complete set of regulatory elements within a single 3? UTR, and determining the extent to which elements interact with and affect one another. Hmga2 is an oncogene whose overexpression in cancers often stems from mutations that remove 3?-UTR regulatory sequences. We used reporter assays in cultured cells to generate maps of cis-regulatory information across the Hmga2 3? UTR at different resolutions, ranging from 50 to 400 nt. We found many previously unidentified regulatory sites, a large number of which were up-regulating. Importantly, the overall location and impact of regulatory sites was conserved between different species (mouse, human, and chicken). By systematically comparing the regulatory impact of 3?-UTR segments of different sizes we were able to determine that the majority of regulatory sequences function independently; only a very small number of segments showed evidence of any interactions. However, we discovered a novel interaction whereby terminal 3?-UTR sequences induced internal up-regulating elements to convert to repressive elements. By fully characterizing one 3? UTR, we hope to better understand the principles of 3?-UTR-mediated gene regulation. PMID:25999317

  19. Application of DLVO energy map to evaluate interactions between spherical colloids and rough surfaces.

    PubMed

    Shen, Chongyang; Wang, Feng; Li, Baoguo; Jin, Yan; Wang, Lian-Ping; Huang, Yuanfang

    2012-10-16

    This study theoretically evaluated interactions between spherical colloids and rough surfaces in three-dimensional space using Derjaguin-Landau-Verwey- Overbeek (DLVO) energy/force map and curve. The rough surfaces were modeled as a flat surface covered by hemispherical protrusions. A modified Derjaguin approach was employed to calculate the interaction energies and forces. Results show that more irreversible attachments in primary minima occur at higher ionic strengths, which theoretically explains the observed hysteresis of colloid attachment and detachment during transients in solution chemistry. Secondary minimum depths can be increased significantly in concave regions (e.g., areas aside of asperities or between asperities) due to sidewall interactions. Through comparing the tangential attractive forces from asperities and the hydrodynamic drag forces in three-dimensional space, we showed that attachment in secondary minima can be located on open collector surfaces of a porous medium. This result challenges the usual belief that the attachment in secondary minima only occurs in stagnation point regions of the porous medium and is absent in shear flow systems such as parallel plate flow chamber and impinging jet apparatus. Despite the argument about the role of secondary minima in colloid attachment remained, our study theoretically justified the existence of attachment in secondary minima in the presence of surface roughness. Further, our study implied that the presence of surface roughness is more favorable for attachment in secondary minima than in primary minima under unfavorable chemical conditions. PMID:23006065

  20. 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.

  1. Linking tumor mutations to drug responses via a quantitative chemical-genetic interaction map

    PubMed Central

    Martins, Maria M.; Zhou, Alicia Y.; Corella, Alexandra; Horiuchi, Dai; Yau, Christina; Rakshandehroo, Taha; Gordan, John D.; Levin, Rebecca S.; Johnson, Jeff; Jascur, John; Shales, Mike; Sorrentino, Antonio; Cheah, Jaime; Clemons, Paul A.; Shamji, Alykhan F.; Schreiber, Stuart L.; Krogan, Nevan J.; Shokat, Kevan M.; McCormick, Frank; Goga, Andrei; Bandyopadhyay, Sourav

    2014-01-01

    There is an urgent need in oncology to link molecular aberrations in tumors with therapeutics that can be administered in a personalized fashion. One approach identifies synthetic-lethal genetic interactions or dependencies that cancer cells acquire in the presence of specific mutations. Using engineered isogenic cells, we generated a systematic and quantitative chemical-genetic interaction map that charts the influence of 51 aberrant cancer genes on 90 drug responses. The dataset strongly predicts drug responses found in cancer cell line collections, indicating that isogenic cells can model complex cellular contexts. Applied to triple-negative breast cancer, we report clinically actionable interactions with the MYC oncogene including resistance to AKT/PI3K pathway inhibitors and an unexpected sensitivity to dasatinib through LYN inhibition in a synthetic-lethal manner, providing new drug and biomarker pairs for clinical investigation. This scalable approach enables the prediction of drug responses from patient data and can accelerate the development of new genotype-directed therapies. PMID:25501949

  2. Molecular interaction maps of bioregulatory networks: a general rubric for systems biology.

    PubMed

    Kohn, Kurt W; Aladjem, Mirit I; Weinstein, John N; Pommier, Yves

    2006-01-01

    A standard for bioregulatory network diagrams is urgently needed in the same way that circuit diagrams are needed in electronics. Several graphical notations have been proposed, but none has become standard. We have prepared many detailed bioregulatory network diagrams using the molecular interaction map (MIM) notation, and we now feel confident that it is suitable as a standard. Here, we describe the MIM notation formally and discuss its merits relative to alternative proposals. We show by simple examples how to denote all of the molecular interactions commonly found in bioregulatory networks. There are two forms of MIM diagrams. "Heuristic" MIMs present the repertoire of interactions possible for molecules that are colocalized in time and place. "Explicit" MIMs define particular models (derived from heuristic MIMs) for computer simulation. We show also how pathways or processes can be highlighted on a canonical heuristic MIM. Drawing a MIM diagram, adhering to the rules of notation, imposes a logical discipline that sharpens one's understanding of the structure and function of a network. PMID:16267266

  3. 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. PMID:26823515

  4. Interaction between beta-adrenergic receptors and guanine nucleotide sites in turkey erythrocyte membranes.

    PubMed Central

    Vauquelin, G; Bottari, S; Andre, C; Jacobsson, B; Strosberg, A D

    1980-01-01

    beta 1-Adrenergic receptors from turkey erythrocyte membranes have been identified by specific binding of the radiolabeled antagonist (-)-[3H]dihydroalprenolol. These receptors are inactivated by the alkylating agent N-ethylmaleimide when occupied by beta-adrenergic agonists but not when occupied by antagonists or when unoccupied. A time-dependent decrease of the number of receptor sites is observed. Inactivation affects 45-60% of the sites, regardless of the agonist or N-ethylmaleimide concentration. The guanine nucleotides GTP and 5'-guanylyl imidodiphosphate effectively protect the receptors against agonist-mediated inactivation by N-ethylmaleimide. Protection by ATP necessitates a 100-fold higher concentration; 10 mM NaF is ineffective. The guanine nucleotide effect is reversible and occurs via interaction with N-ethylmaleimide-insensitive sites. These observations establish that guanine nucleotide sites interact with and caused structural modification of the agonist-occupied beta-adrenergic receptors in turkey erythrocyte membranes. PMID:6253990

  5. Active Learning Centre: utilization patterns of an interactive educational World Wide Web site.

    PubMed Central

    Turchin, A.; Lehmann, C. U.

    1999-01-01

    The advent of the World Wide Web (WWW) provides unique opportunities to transform medical education. Interactive computer assisted instruction has shown promising results but its growth has been impeded by logistical barriers. We designed an interactive WWW site--Active Learning Centre (ALC)--that offers a novel approach to these problems, combining remotely authored databases with computer-generated self-assessment tests. This study analyzes utilization and user assessment of the site. The site was found to be patronized mostly by students and health professionals from English-speaking countries. Users have been pleased with their experience and suggest further expansion of the ALC. Our data have also tentatively shown that their knowledge improved with repeated visits to the site. PMID:10566435

  6. Mapping the interaction between factor VIII and von Willebrand factor by electron microscopy and mass spectrometry.

    PubMed

    Chiu, Po-Lin; Bou-Assaf, George M; Chhabra, Ekta Seth; Chambers, Melissa G; Peters, Robert T; Kulman, John D; Walz, Thomas

    2015-08-20

    Association with the D'D3 domain of von Willebrand factor (VWF) stabilizes factor VIII (FVIII) in the circulation and maintains it at a level sufficient to prevent spontaneous bleeding. We used negative-stain electron microscopy (EM) to visualize complexes of FVIII with dimeric and monomeric forms of the D'D3 domain. The EM averages show that FVIII interacts with the D'D3 domain primarily through its C1 domain, with the C2 domain providing a secondary attachment site. Hydrogen-deuterium exchange mass spectrometry corroborated the importance of the C1 domain in D'D3 binding and implicates additional surface regions on FVIII in the interaction. Together, our results establish that the C1 domain is the major binding site on FVIII for VWF, reiterate the importance of the a3 acidic peptide in VWF binding, and suggest that the A3 and C2 domains play ancillary roles in this interaction. PMID:26065652

  7. Large-Scale Mapping of Transposable Element Insertion Sites Using Digital Encoding of Sample Identity

    PubMed Central

    Gohl, Daryl M.; Freifeld, Limor; Silies, Marion; Hwa, Jennifer J.; Horowitz, Mark; Clandinin, Thomas R.

    2014-01-01

    Determining the genomic locations of transposable elements is a common experimental goal. When mapping large collections of transposon insertions, individualized amplification and sequencing is both time consuming and costly. We describe an approach in which large numbers of insertion lines can be simultaneously mapped in a single DNA sequencing reaction by using digital error-correcting codes to encode line identity in a unique set of barcoded pools. PMID:24374352

  8. Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain

    NASA Astrophysics Data System (ADS)

    Smith, Frank J.; Pau, Victor P. T.; Cingolani, Gino; Rothberg, Brad S.

    2013-10-01

    Ligand binding sites within proteins can interact by allosteric mechanisms to modulate binding affinities and control protein function. Here we present crystal structures of the regulator of K+ conductance (RCK) domain from a K+ channel, MthK, which reveal the structural basis of allosteric coupling between two Ca2+ regulatory sites within the domain. Comparison of RCK domain crystal structures in a range of conformations and with different numbers of regulatory Ca2+ ions bound, combined with complementary electrophysiological analysis of channel gating, suggests chemical interactions that are important for modulation of ligand binding and subsequent channel opening.

  9. An interactive program for computer-aided map design, display, and query: EM APKGS2

    NASA Astrophysics Data System (ADS)

    Pouch, Gregory W.

    1997-04-01

    EM APKGS2 is a user-friendly, PC-based electronic mapping tool for use in hydrogeologic exploration and appraisal. EM APKGS2 allows the analyst to construct maps interactively from data stored in a relational database, perform point-oriented spatial queries such as locating all wells within a specified radius, perform geographic overlays, and export the data to other programs for further analysis. EM APKGS2 runs under Microsoft R Windows 3.1 and compatible operating systems. EM APKGS2 is a public domain program available from the Kansas Geological Survey. EM APKGS2 is the centerpiece of WHEAT, the Windows-based Hydrogeologic Exploration and Appraisal Toolkit, a suite of user-friendly Microsoft R Windows programs for natural resource exploration and management. The principal goals in development of WHEAT have been ease of use, hardware independence, low cost, and end-user extensibility. WHEAT's native data format is a Microsoft R Access R database. WHEAT stores a feature's geographic coordinates as attributes so they can be accessed easily by the user. The WHEAT programs are designed to be used in conjunction with other Microsoft R Windows software to allow the natural resource scientist to perform work easily and effectively. WHEAT and EM APKGS have been used at several of Kansas' Groundwater Management Districts and the Kansas Geological Survey on groundwater management operations, groundwater modeling projects, and geologic exploration projects.

  10. An interactive program for computer-aided map design, display, and query: EMAPKGS2

    USGS Publications Warehouse

    Pouch, G.W.

    1997-01-01

    EMAPKGS2 is a user-friendly, PC-based electronic mapping tool for use in hydrogeologic exploration and appraisal. EMAPKGS2 allows the analyst to construct maps interactively from data stored in a relational database, perform point-oriented spatial queries such as locating all wells within a specified radius, perform geographic overlays, and export the data to other programs for further analysis. EMAPKGS2 runs under Microsoft?? Windows??? 3.1 and compatible operating systems. EMAPKGS2 is a public domain program available from the Kansas Geological Survey. EMAPKGS2 is the centerpiece of WHEAT, the Windows-based Hydrogeologic Exploration and Appraisal Toolkit, a suite of user-friendly Microsoft?? Windows??? programs for natural resource exploration and management. The principal goals in development of WHEAT have been ease of use, hardware independence, low cost, and end-user extensibility. WHEAT'S native data format is a Microsoft?? Access?? database. WHEAT stores a feature's geographic coordinates as attributes so they can be accessed easily by the user. The WHEAT programs are designed to be used in conjunction with other Microsoft?? Windows??? software to allow the natural resource scientist to perform work easily and effectively. WHEAT and EMAPKGS have been used at several of Kansas' Groundwater Management Districts and the Kansas Geological Survey on groundwater management operations, groundwater modeling projects, and geologic exploration projects. ?? 1997 Elsevier Science Ltd.

  11. An improved interolog mapping-based computational prediction of protein-protein interactions with increased network coverage.

    PubMed

    Folador, Edson Luiz; Hassan, Syed Shah; Lemke, Ney; Barh, Debmalya; Silva, Artur; Ferreira, Rafaela Salgado; Azevedo, Vasco

    2014-11-01

    Automated and efficient methods that map ortholog interactions from several organisms and public databases (pDB) are needed to identify new interactions in an organism of interest (interolog mapping). When computational methods are applied to predict interactions, it is important that these methods be validated and their efficiency proven. In this study, we compare six Blast+ metrics over three datasets to identify the best metric for protein-protein interaction predictions. Using Blast+ to align the protein pairs, the ortholog interactions from DIP were mapped to String, Intact and Psibase pDBs. For each interaction mapped to each pDBs, we retrieved the alignment score, e-value, bitscore, similarity, identity and coverage. We evaluated these Blast+ values, and combinations thereof, with the Receiver Operating Characteristic (ROC) curves and computed the Area Under Curve (AUC). To validate these predictions, we used a subset of the Database of Interacting Proteins (DIP) composed of experimental interactions curated by the International Molecular Exchange (IMEx). The cut-off point for each metric/pDB was computed aiming to identify the best one that separates the true and false predicted interactions. In contrast to other methods that only compute the first Blast hit, we considered the first 20 hits, thus increasing the number of predicted interaction pairs. In addition, we identified the contribution of each individual pDB, as well as their combined contribution to the prediction. The best metric had an AUC of 0.96 for a single pDB and AUC of 0.93 for combined pDBs. Compared to other studies, with a cut-off point of 0.70 representing a specificity of 0.95 and a sensitivity of 0.90 for individual pDB, our method efficiently predicts protein-protein interactions. PMID:25209055

  12. Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

    PubMed Central

    Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J.; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F.; Emili, Andrew

    2011-01-01

    As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. PMID:22125496

  13. The role of TFIIB–RNA polymerase II interaction in start site selection in yeast cells

    PubMed Central

    Zhang, Dong-Yi; Carson, Daniel J.; Ma, Jun

    2002-01-01

    Previous studies have established a critical role of both TFIIB and RNA polymerase II (RNAPII) in start site selection in the yeast Saccharomyces cerevisiae. However, it remains unclear how the TFIIB–RNAPII interaction impacts on this process since such an interaction can potentially influence both preinitiation complex (PIC) stability and conformation. In this study, we further investigate the role of TFIIB in start site selection by characterizing our newly generated TFIIB mutants, two of which exhibit a novel upstream shift of start sites in vivo. We took advantage of an artificial recruitment system in which an RNAPII holoenzyme component is covalently linked to a DNA-binding domain for more direct and stable recruitment. We show that TFIIB mutations can exert their effects on start site selection in such an artificial recruitment system even though it has a relaxed requirement for TFIIB. We further show that these TFIIB mutants have normal affinity for RNAPII and do not alter the promoter melting/scanning step. Finally, we show that overexpressing the genetically isolated TFIIB mutant E62K, which has a reduced affinity for RNAPII, can correct its start site selection defect. We discuss a model in which the TFIIB–RNAPII interaction controls the start site selection process by influencing the conformation of PIC prior to or during PIC assembly, as opposed to PIC stability. PMID:12136090

  14. PRECISE: a Database of Predicted and Consensus Interaction Sites in Enzymes

    PubMed Central

    Sheu, Shu-Hsien; Lancia, David R.; Clodfelter, Karl H.; Landon, Melissa R.; Vajda, Sandor

    2005-01-01

    PRECISE (Predicted and Consensus Interaction Sites in Enzymes) is a database of interactions between the amino acid residues of an enzyme and its ligands (substrate and transition state analogs, cofactors, inhibitors and products). It is available online at http://precise.bu.edu/. In the current version, all information on interactions is extracted from the enzyme–ligand complexes in the Protein Data Bank (PDB) by performing the following steps: (i) clustering homologous enzyme chains such that, in each cluster, the proteins have the same EC number and all sequences are similar; (ii) selecting a representative chain for each cluster; (iii) selecting ligand types; (iv) finding non-bonded interactions and hydrogen bonds; and (v) summing the interactions for all chains within the cluster. The output of the search is the color-coded sequence of the representative. The colors indicate the total number of interactions found at each amino acid position in all chains of the cluster. Clicking on a residue displays a detailed list of interactions for that residue. Optional filters allow restricting the output to selected chains in the cluster, to non-bonded or hydrogen bonding interactions, and to selected ligand types. The binding site information is essential for understanding and altering substrate specificity and for the design of enzyme inhibitors. PMID:15608178

  15. Mapping of the Allosteric Site in Cholesterol Hydroxylase CYP46A1 for Efavirenz, a Drug That Stimulates Enzyme Activity.

    PubMed

    Anderson, Kyle W; Mast, Natalia; Hudgens, Jeffrey W; Lin, Joseph B; Turko, Illarion V; Pikuleva, Irina A

    2016-05-27

    Cytochrome P450 46A1 (CYP46A1) is a microsomal enzyme and cholesterol 24-hydroxylase that controls cholesterol elimination from the brain. This P450 is also a potential target for Alzheimer disease because it can be activated pharmacologically by some marketed drugs, as exemplified by efavirenz, the anti-HIV medication. Previously, we suggested that pharmaceuticals activate CYP46A1 allosterically through binding to a site on the cytosolic protein surface, which is different from the enzyme active site facing the membrane. Here we identified this allosteric site for efavirenz on CYP46A1 by using a combination of hydrogen-deuterium exchange coupled to MS, computational modeling, site-directed mutagenesis, and analysis of the CYP46A1 crystal structure. We also mapped the binding region for the CYP46A1 redox partner oxidoreductase and found that the allosteric and redox partner binding sites share a common border. On the basis of the data obtained, we propose the mechanism of CYP46A1 allostery and the pathway for the signal transmission from the P450 allosteric site to the active site. PMID:27056331

  16. Interacted QTL Mapping in Partial NCII Design Provides Evidences for Breeding by Design

    PubMed Central

    Yi, Can; Wen, Jia; Jinxing, Tu; Zhang, Yuan Ming

    2015-01-01

    The utilization of heterosis in rice, maize and rapeseed has revolutionized crop production. Although elite hybrid cultivars are mainly derived from the F1 crosses between two groups of parents, named NCII mating design, little has been known about the methodology of how interacted effects influence quantitative trait performance in the population. To bridge genetic analysis with hybrid breeding, here we integrated an interacted QTL mapping approach with breeding by design in partial NCII mating design. All the potential main and interacted effects were included in one full model. If the number of the effects is huge, bulked segregant analysis were used to test which effects were associated with the trait. All the selected effects were further shrunk by empirical Bayesian, so significant effects could be identified. A series of Monte Carlo simulations was performed to validate the new method. Furthermore, all the significant effects were used to calculate genotypic values of all the missing F1 hybrids, and all these F1 phenotypic or genotypic values were used to predict elite parents and parental combinations. Finally, the new method was adopted to dissect the genetic foundation of oil content in 441 rapeseed parents and 284 F1 hybrids. As a result, 8 main-effect QTL and 37 interacted QTL were found and used to predict 10 elite restorer lines, 10 elite sterile lines and 10 elite parental crosses. Similar results across various methods and in previous studies and a high correlation coefficient (0.76) between the predicted and observed phenotypes validated the proposed method in this study. PMID:25822501

  17. Predicting target-ligand interactions using protein ligand-binding site and ligand substructures

    PubMed Central

    2015-01-01

    Background Cell proliferation, differentiation, Gene expression, metabolism, immunization and signal transduction require the participation of ligands and targets. It is a great challenge to identify rules governing molecular recognition between chemical topological substructures of ligands and the binding sites of the targets. Methods We suppose that the ligand-target interactions are determined by ligand substructures as well as the physical-chemical properties of the binding sites. Therefore, we propose a fragment interaction model (FIM) to describe the interactions between ligands and targets, with the purpose of facilitating the chemical interpretation of ligand-target binding. First we extract target-ligand complexes from sc-PDB database, based on which, we get the target binding sites and the ligands. Then we represent each binding site as a fragment vector based on a target fragment dictionary that is composed of 199 clusters (denoted as fragements in this work) obtained by clustering 4200 trimers according to their physical-chemical properties. And then, we represent each ligand as a substructure vector based on a dictionary containing 747 substructures. Finally, we build the FIM by generating the interaction matrix M (representing the fragment interaction network), and the FIM can later be used for predicting unknown ligand-target interactions as well as providing the binding details of the interactions. Results The five-fold cross validation results show that the proposed model can get higher AUC score (92%) than three prevalence algorithms CS-PD (80%), BLM-NII (85%) and RF (85%), demonstrating the remarkable predictive ability of FIM. We also show that the ligand binding sites (local information) overweight the sequence similarities (global information) in ligand-target binding, and introducing too much global information would be harmful to the predictive ability. Moreover, The derived fragment interaction network can provide the chemical insights on the interactions. Conclusions The target and ligand bindings are local events, and the local information dominate the binding ability. Though integrating of the global information can promote the predictive ability, the role is very limited. The fragment interaction network is helpful for understanding the mechanism of the ligand-target interaction. PMID:25707321

  18. Mapping of phosphorylation sites of gel-isolated proteins by nanoelectrospray tandem mass spectrometry: potentials and limitations.

    PubMed

    Neubauer, G; Mann, M

    1999-01-01

    Precursor ion scans have proven to be extremely useful for the characterization of unseparated peptide mixtures. In conjunction with the nanoelectrospray source, precursor ion scans provide a sensitive tool for the detection of posttranslationally modified peptides and have been used to determine phosphorylation sites of proteins digested in solution. In this report, we extend our previous work to the determination of protein phosphorylation sites of gel-isolated proteins. The in-gel digestion procedure developed in our laboratory for protein microsequencing was found to be suitable for phosphorylation mapping as well. The risk of losing hydrophilic peptides in the desalting step was decreased by using column packing material designed for the purification of oligonucleotides and by adjusting the pH conditions to the needs of phosphopeptide analysis. With this method, the tryptic phosphopeptides of beta-casein were detected after in-gel digestion at a sensitivity of 250 fmol of protein applied to the gel. The phosphorylation sites of two other proteins, Src-delta U and Op18, have similarly been mapped. Subpicomole to low-picomole amounts of protein starting material are needed in general, although we and others have reported attomole sensitivity for the detection of model phosphopeptides using precursor ion scans. This indicates that the success in determining phosphorylation sites depends crucially on the digestion, extraction, and detection efficiency for individual phosphopeptides. PMID:9921130

  19. Mapping divalent metal ion binding sites in a group II intron by Mn(2+)- and Zn(2+)-induced site-specific RNA cleavage.

    PubMed

    Hertweck, M; Mueller, M W

    2001-09-01

    The function of group II introns depends on positively charged divalent metal ions that stabilize the ribozyme structure and may be directly involved in catalysis. We investigated Mn2+- and Zn2+-induced site-specific RNA cleavage to identify metal ions that fit into binding pockets within the structurally conserved bI1 group II intron domains (DI-DVI), which might fulfill essential roles in intron function. Ten cleavage sites were identified in DI, two sites in DIII and two in DVI. All cleavage sites are located in the center or close to single-stranded and flexible RNA structures. Strand scissions mediated by Mn2+/Zn2+ are competed for by Mg2+, indicating the existence of Mg2+ binding pockets in physical proximity to the observed Mn2+-/Zn2+-induced cleavage positions. To distinguish between metal ions with a role in structure stabilization and those that play a more specific and critical role in the catalytic process of intron splicing, we combined structural and functional assays, comparing wild-type precursor and multiple splicing-deficient mutants. We identified six regions with binding pockets for Mg2+ ions presumably playing an important role in bI1 structure stabilization. Remarkably, assays with DI deletions and branch point mutants revealed the existence of one Mg2+ binding pocket near the branching A, which is involved in first-step catalysis. This pocket formation depends on precise interaction between the branching nucleotide and the 5' splice site, but does not require exon-binding site 1/intron binding site 1 interaction. This Mg2+ ion might support the correct placing of the branching A into the 'first-step active site'. PMID:11531997

  20. Analysis of the Interaction of the Eg5 Loop5 with the Nucleotide Site

    SciTech Connect

    Harrington, Timothy D.; Naber, Nariman; Larson, Adam G.; Cooke, Roger; Rice, Sarah E.; Pate, Edward F.

    2011-11-21

    Loop 5 (L5) is a conserved loop that projects from the α2-helix adjacent to the nucleotide site of all kinesin-family motors. L5 is critical to the function of the mito tickinesin-5 family motors and is the binding site for several kinesin-5 inhibitors that are currently in clinical trials. Its conformational dynamics and its role in motor function are not fully understood. Our previous work using EPR spectroscopy suggested that L5 alters the nucleotide pocket conformation of the kinesin-5 motor Eg5 (Larsonetal.,2010). EPR spectra of a spin-labeled nucleotide analog bound at the nucleotide site of Eg5 display a highly immobilized component that is absent if L5 is shortened or if the inhibitor STLC is added (Larson etal.,2010), which X-ray structures suggest stabilizes an L5 conformation pointing away from the nucleotide site. These data, coupled with the proximity of L5 to the nucleotide site suggest L5 could interact with a bound nucleotide, modulating function. Here we use molecular dynamics (MD) simulations of Eg5 to explore the interaction of L5 with the nucleotide site in greater detail. We performed MD simulations in which the L5-domain of the Eg5•ADP X-ray structure was manually deformed via backbone bond rotations. The L5-domain of Eg5 was sufficiently lengthy that portions of L5 could belocated in proximity to bound ADP. The MD simulations evolved to thermodynamically stable structures at 300K showing that L5 can interact directly with bound nucleotide with significant impingement on the ribosehydroxyls, consistent with the EPR spectroscopy results. Taken together, these data provide support for the hypothes is that L5 modulates Eg5 function via interaction with the nucleotide-binding site.

  1. Acoustic mapping of diffuse flow at a seafloor hydrothermal site: Monolith Vent, Juan de Fuca Ridge

    NASA Astrophysics Data System (ADS)

    Rona, P. A.; Jackson, D. R.; Wen, T.; Jones, C.; Mitsuzawa, K.; Bemis, K. G.; Dworski, J. G.

    Diffuse flow of hydrothermal solutions commonly occurs in patchy areas up to tens of meters in diameter in seafloor hydrothermal fields. It is recognized as a quantitatively significant component of thermal and chemical fluxes, yet is elusive to map. We report a new acoustic method to detect and map areas of diffuse flow using phase-coherent correlation techniques. The sonar system was modified to record phase information and mounted on DSV SEA CLIFF. The submersible occupied a stationary position on the seafloor and the transducer scanned the seafloor surrounding Monolith Vent, a sulfide edifice venting black smokers, at a nominal range of 17 m at a depth of 2249 m on the Juan de Fuca Ridge. Patchy areas of uncorrelated returns clearly stood out from a background of returns that exhibited ping-to-ping correlation. The areas of uncorrelated returns coincided with areas of diffuse flow as mapped by a video survey with the Navy's Advanced Tethered Vehicle (ATV). Correlated returns were backscattered from invariant seafloor. Uncorrelated returns were distorted by index of refraction inhomogeneities as they passed through diffuse flow between the seafloor and the transducer. The acoustic method presented can synoptically map areas of diffuse flow. When combined with standard in situ measurement and sampling methods the acoustic mapping will facilitate accurate determination of diffuse thermal and chemical fluxes in seafloor hydrothermal fields.

  2. Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast.

    PubMed

    Patrick, Kristin L; Ryan, Colm J; Xu, Jiewei; Lipp, Jesse J; Nissen, Kelly E; Roguev, Assen; Shales, Michael; Krogan, Nevan J; Guthrie, Christine

    2015-03-01

    Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated, the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear. To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, we constructed an epistatic mini-array profile (E-MAP) and discovered many new connections between chromatin and splicing. Notably, the nucleosome remodeler SWI/SNF had strong genetic interactions with components of the U2 snRNP SF3 complex. Overexpression of SF3 components in ΔSWI/SNF cells led to inefficient splicing of many fission yeast introns, predominantly those with non-consensus splice sites. Deletion of SWI/SNF decreased recruitment of the splicing ATPase Prp2, suggesting that SWI/SNF promotes co-transcriptional spliceosome assembly prior to first step catalysis. Importantly, defects in SWI/SNF as well as SF3 overexpression each altered nucleosome occupancy along intron-containing genes, illustrating that the chromatin landscape both affects--and is affected by--co-transcriptional splicing. PMID:25825871

  3. Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast

    PubMed Central

    Patrick, Kristin L.; Ryan, Colm J.; Xu, Jiewei; Lipp, Jesse J.; Nissen, Kelly E.; Roguev, Assen; Shales, Michael; Krogan, Nevan J.; Guthrie, Christine

    2015-01-01

    Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated, the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear. To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, we constructed an epistatic mini-array profile (E-MAP) and discovered many new connections between chromatin and splicing. Notably, the nucleosome remodeler SWI/SNF had strong genetic interactions with components of the U2 snRNP SF3 complex. Overexpression of SF3 components in ΔSWI/SNF cells led to inefficient splicing of many fission yeast introns, predominantly those with non-consensus splice sites. Deletion of SWI/SNF decreased recruitment of the splicing ATPase Prp2, suggesting that SWI/SNF promotes co-transcriptional spliceosome assembly prior to first step catalysis. Importantly, defects in SWI/SNF as well as SF3 overexpression each altered nucleosome occupancy along intron-containing genes, illustrating that the chromatin landscape both affects—and is affected by—co-transcriptional splicing. PMID:25825871

  4. Mapping the interactions between flavodoxin and its physiological partners flavodoxin reductase and cobalamin-dependent methionine synthase

    PubMed Central

    Hall, Diane A.; Vander Kooi, Craig W.; Stasik, Chad N.; Stevens, Shawn Y.; Zuiderweg, Erik R. P.; Matthews, Rowena G.

    2001-01-01

    Flavodoxins are electron-transfer proteins that contain the prosthetic group flavin mononucleotide. In Escherichia coli, flavodoxin is reduced by the FAD-containing protein NADPH:ferredoxin (flavodoxin) oxidoreductase; flavodoxins serve as electron donors in the reductive activation of anaerobic ribonucleotide reductase, biotin synthase, pyruvate formate lyase, and cobalamin-dependent methionine synthase. In addition, domains homologous to flavodoxin are components of the multidomain flavoproteins cytochrome P450 reductase, nitric oxide synthase, and methionine synthase reductase. Although three-dimensional structures are known for many of these proteins and domains, very little is known about the structural aspects of their interactions. We address this issue by using NMR chemical shift mapping to identify the surfaces on flavodoxin that bind flavodoxin reductase and methionine synthase. We find that these physiological partners bind to unique overlapping sites on flavodoxin, precluding the formation of ternary complexes. We infer that the flavodoxin-like domains of the cytochrome P450 reductase family form mutually exclusive complexes with their electron-donating and -accepting partners, complexes that require conformational changes for interconversion. PMID:11493691

  5. CANCER MORTALITY MAPS AND GRAPHS

    EPA Science Inventory

    The Cancer Mortality Maps & Graph Web Site provides interactive maps, graphs (which are accessible to the blind and visually-impaired), text, tables and figures showing geographic patterns and time trends of cancer death rates for the time period 1950-1994 for more than 40 cancer...

  6. Ithaca MAP3S regional precipitation chemistry site. Annual progress report, 1 November 1984-31 October 1985

    SciTech Connect

    Butler, T.J.; Likens, G.E.

    1986-07-01

    Samples were collected at the MAP3S Regional Precipitation Chemistry Site located 15 km southwest of Ithaca, New York (Lat. 42/sup 0/ 24', Long. 76/sup 0/ 39') at an elevation of 503 m. The surrounding area is rural in nature and consists of gently rolling terrain, vegetated by deciduous forest, abandoned fields, pasture and some agricultural land. Local point sources of combustion products include a 250 mw coal-fired power plant, 23 km NNE of the site and the Cornell University steam-generating plant 16 km ENE of the site. The latter produces emissions of SO/sub 2/ and particulates comparable to a 50 mw coal-fired power plant. Both of these plants are in a quadrant that is consistently downwind of the sampling station. Other local potential sources of particles are from agricultural activity, road dust, and road salt during the winter. Data are collected September 1984 through September 1985.

  7. Forest Types in the Lower Suwannee River Floodplain, Florida?-A Report and Interactive Map

    USGS Publications Warehouse

    Darst, M.R.; Light, H.M.; Lewis, L.J.; Sepulveda, A.A.

    2003-01-01

    A map of forest types in the lower Suwannee River floodplain, Florida, was created during a study conducted from 1996 to 2000 by the U.S. Geological Survey in cooperation with the Suwannee River Water Management District. The map is presented with this report on a compact disc with interactive viewing software. The forest map can be used by scientists for ecological studies in the floodplain based on land cover types and by landowners and management personnel making land use decisions. The study area is the 10-year floodplain of the lower Suwannee River from its confluence with the Santa Fe River to the lower limit of forests near the Gulf of Mexico. The floodplain is divided into three reaches: riverine (non-tidal), upper tidal, and lower tidal, due to changes in hydrology, vegetation, and soils with proximity to the coast. The 10-year floodplain covers about 21,170 hectares; nearly 88 percent of this area (18,580 hectares) is mapped as 14 major forest types. Approximately 29 percent (5,319 hectares) of these forests have been altered by agriculture or development. About 75 percent of the area of major forest types (13,994 hectares) is wetland forests and about 25 percent (4,586 hectares) is upland forests. Tidal wetland forests (8,955 hectares) cover a much greater area than riverine wetland forests (5,039 hectares). Oak/pine upland forests are present in the riverine and upper tidal reaches of the floodplain on elevations that are inundated only briefly during the highest floods. High bottomland hardwoods are present on the higher levees, ridges, and flats of the riverine reach where soils are usually sandy. Low bottomland hardwood forests are present in the riverine reach on swamp margins and low levees and flats that are flooded continuously for several weeks or longer every 1 to 3 years. Riverine swamps are present in the lowest and wettest areas of the non-tidal floodplain that are either inundated or saturated most of the time. Upper tidal bottomland hardwood forests are present on sandy soils on high flats and in transitional areas between upland forests and swamps. Upper tidal mixed forests are found on low levees or between swamps and higher forest types. Upper tidal swamps are present at elevations below median monthly high stage and usually have surface soils that are permanently saturated mucks. Lower tidal hammocks are found on higher elevations that do not receive regular tidal inundation but have a high water table and are briefly inundated by storm surges several times a decade. Lower tidal mixed forests include swamps with numerous small hummocks or less common larger hummocks. Lower tidal swamps are found on deep muck soils that are below the elevation of the median daily or monthly high stage. Seven additional land cover types (2,590 hectares) are mapped. Water in the main channel of the lower Suwannee River (1,767 hectares) was mapped separately from open water in the floodplain (239 hectares). Other land cover types are: seepage slopes (70 hectares), isolated forested wetlands (19 hectares), marshes upstream of the tree line (505 hectares), beds of emergent aquatic vegetation (21 hectares), and floodplain glades (46 hectares)

  8. A Method for Place Name Display Considering User Locating Habits in Map Sites

    NASA Astrophysics Data System (ADS)

    Liu, X. C.; Li, X.; Wang, L.; Wang, P.

    2013-11-01

    The traditional researches for cartographic lettering and display focus on conflict among labels and overlap between labels and features. But these two issues are not significant in web maps. It is worthwhile to concern about how to improve labels' readability considering user locating habits for enhancing user experience. This paper has established a new method for place name display called "the gravitational field". This method is appropriate for the display of dotted place names from the national level (approximately 1:20 million) to city level (approximately 1:250 thousand) in web maps. We have conducted a usability test which used all nationwide provincial capitals, autonomous regions, municipalities, prefecture-level cities, municipal districts, countries and part of the townships dotted names. The results show that this rule improves web map's legibility, and can significantly enhance the user experience.

  9. 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.

  10. 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…

  11. 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

  12. Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein

    NASA Technical Reports Server (NTRS)

    Gaucher, Eric A.; Miyamoto, Michael M.; Benner, Steven A.

    2003-01-01

    The Leptin protein is central to the regulation of energy metabolism in mammals. By integrating evolutionary, structural, and biochemical information, a surface segment, outside of its known receptor contacts, is predicted as a second interaction site that may help to further define its roles in energy balance and its functional differences between humans and other mammals.

  13. 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. PMID:24097054

  14. Process maps for plasma spray: Part 1: Plasma-particle interactions

    SciTech Connect

    GILMORE,DELWYN L.; NEISER JR.,RICHARD A.; WAN,YUEPENG; SAMPATH,SANJAY

    2000-01-26

    This is the first paper of a two part series based on an integrated study carried out at Sandia National Laboratories and the State University of New York at Stony Brook. The aim of the study is to develop a more fundamental understanding of plasma-particle interactions, droplet-substrate interactions, deposit formation dynamics and microstructural development as well as final deposit properties. The purpose is to create models that can be used to link processing to performance. Process maps have been developed for air plasma spray of molybdenum. Experimental work was done to investigate the importance of such spray parameters as gun current, auxiliary gas flow, and powder carrier gas flow. In-flight particle diameters, temperatures, and velocities were measured in various areas of the spray plume. Samples were produced for analysis of microstructures and properties. An empirical model was developed, relating the input parameters to the in-flight particle characteristics. Multi-dimensional numerical simulations of the plasma gas flow field and in-flight particles under different operating conditions were also performed. In addition to the parameters which were experimentally investigated, the effect of particle injection velocity was also considered. The simulation results were found to be in good general agreement with the experimental data.

  15. Mapping Strain-rate Dependent Dislocation-Defect Interactions by Atomistic Simulations

    SciTech Connect

    Fan, Yue; Osetskiy, Yury N; Yip, Sidney; Yildiz-Botterud, Bilge

    2013-01-01

    Probing the mechanisms of defect-defect interactions at strain rates lower than 106 s-1 is an unresolved challenge to date to molecular dynamics (MD) techniques. Here we propose a novel atomistic approach based on transition state theory and the concept of a strain-dependent effective activation barrier that is capable of simulating the kinetics of dislocation-defect interactions at virtually any strain rate, exemplified within 10-7 to 107 s-1. We apply this approach to the problem of an edge dislocation colliding with a cluster of self-interstitial atoms (SIA) under shear deformation. Using an activation-relaxation algorithm (1), we uncover a unique strain-rate dependent trigger mechanism that allows the SIA cluster to be absorbed during the process leading to dislocation climb. Guided by this finding, we determine the activation barrier of the trigger mechanism as a function of shear strain, and use that in a coarse-graining rate equation formulation for constructing a mechanism map in the phase space of strain-rate and temperature. Our predictions of a crossover from a defect recovery at the low strain rate regime to defect absorption behavior in the high strain-rate regime are validated against our own independent, direct MD simulations at 105 to 107 s-1. Implications of the present approach for probing molecular-level mechanisms in strain-rate regimes previously considered inaccessible to atomistic simulations are discussed.

  16. Fractionation profiling: a fast and versatile approach for mapping vesicle proteomes and protein–protein interactions

    PubMed Central

    Borner, Georg H. H.; Hein, Marco Y.; Hirst, Jennifer; Edgar, James R.; Mann, Matthias; Robinson, Margaret S.

    2014-01-01

    We developed “fractionation profiling,” a method for rapid proteomic analysis of membrane vesicles and protein particles. The approach combines quantitative proteomics with subcellular fractionation to generate signature protein abundance distribution profiles. Functionally associated groups of proteins are revealed through cluster analysis. To validate the method, we first profiled >3500 proteins from HeLa cells and identified known clathrin-coated vesicle proteins with >90% accuracy. We then profiled >2400 proteins from Drosophila S2 cells, and we report the first comprehensive insect clathrin-coated vesicle proteome. Of importance, the cluster analysis extends to all profiled proteins and thus identifies a diverse range of known and novel cytosolic and membrane-associated protein complexes. We show that it also allows the detailed compositional characterization of complexes, including the delineation of subcomplexes and subunit stoichiometry. Our predictions are presented in an interactive database. Fractionation profiling is a universal method for defining the clathrin-coated vesicle proteome and may be adapted for the analysis of other types of vesicles and particles. In addition, it provides a versatile tool for the rapid generation of large-scale protein interaction maps. PMID:25165137

  17. Mapping strain rate dependence of dislocation-defect interactions by atomistic simulations

    PubMed Central

    Fan, Yue; Osetskiy, Yuri N.; Yip, Sidney; Yildiz, Bilge

    2013-01-01

    Probing the mechanisms of defect–defect interactions at strain rates lower than 106 s−1 is an unresolved challenge to date to molecular dynamics (MD) techniques. Here we propose an original atomistic approach based on transition state theory and the concept of a strain-dependent effective activation barrier that is capable of simulating the kinetics of dislocation–defect interactions at virtually any strain rate, exemplified within 10−7 to 107 s−1. We apply this approach to the problem of an edge dislocation colliding with a cluster of self-interstitial atoms (SIAs) under shear deformation. Using an activation–relaxation algorithm [Kushima A, et al. (2009) J Chem Phys 130:224504], we uncover a unique strain-rate–dependent trigger mechanism that allows the SIA cluster to be absorbed during the process, leading to dislocation climb. Guided by this finding, we determine the activation barrier of the trigger mechanism as a function of shear strain, and use that in a coarse-graining rate equation formulation for constructing a mechanism map in the phase space of strain rate and temperature. Our predictions of a crossover from a defect recovery at the low strain-rate regime to defect absorption behavior in the high strain-rate regime are validated against our own independent, direct MD simulations at 105 to 107 s−1. Implications of the present approach for probing molecular-level mechanisms in strain-rate regimes previously considered inaccessible to atomistic simulations are discussed. PMID:24114271

  18. Fractionation profiling: a fast and versatile approach for mapping vesicle proteomes and protein-protein interactions.

    PubMed

    Borner, Georg H H; Hein, Marco Y; Hirst, Jennifer; Edgar, James R; Mann, Matthias; Robinson, Margaret S

    2014-10-15

    We developed "fractionation profiling," a method for rapid proteomic analysis of membrane vesicles and protein particles. The approach combines quantitative proteomics with subcellular fractionation to generate signature protein abundance distribution profiles. Functionally associated groups of proteins are revealed through cluster analysis. To validate the method, we first profiled >3500 proteins from HeLa cells and identified known clathrin-coated vesicle proteins with >90% accuracy. We then profiled >2400 proteins from Drosophila S2 cells, and we report the first comprehensive insect clathrin-coated vesicle proteome. Of importance, the cluster analysis extends to all profiled proteins and thus identifies a diverse range of known and novel cytosolic and membrane-associated protein complexes. We show that it also allows the detailed compositional characterization of complexes, including the delineation of subcomplexes and subunit stoichiometry. Our predictions are presented in an interactive database. Fractionation profiling is a universal method for defining the clathrin-coated vesicle proteome and may be adapted for the analysis of other types of vesicles and particles. In addition, it provides a versatile tool for the rapid generation of large-scale protein interaction maps. PMID:25165137

  19. Mapping the Interactions between Shocks and Mixing Layers in a 3-Stream Supersonic Jet

    NASA Astrophysics Data System (ADS)

    Lewalle, Jacques; Ruscher, Christopher; Kan, Pinqing; Tenney, Andrew; Gogineni, Sivaram; Kiel, Barry

    2015-11-01

    Pressure is obtained from an LES calculation of the supersonic jet (Ma1 = 1 . 6) issuing from a rectangular nozzle in a low-subsonic co-flow; a tertiary flow, also rectangular with Ma3 = 1 insulates the primary jet from an aft-deck plate. The developing jet exhibits complex three-dimensional interactions between oblique shocks, multiple mixing layers and corner vortices, which collectively act as a skeleton for the flow. Our study is based on several plane sections through the pressure field, with short signals (0.1 s duration at 80 kHz sampling rate). Using wavelet-based band-pass filtering and cross-correlations, we map the directions of propagation of information among the various ``bones'' in the skeleton. In particular, we identify upstream propagation in some frequency bands, 3-dimensional interactions between the various shear layers, and several key bones from which the pressure signals, when taken as reference, provide dramatic phase-locking for parts of the skeleton. We acknowledge the support of AFRL through an SBIR grant.

  20. A genetic map in the Mimulus guttatus species complex reveals transmission ratio distortion due to heterospecific interactions.

    PubMed Central

    Fishman, L; Kelly, A J; Morgan, E; Willis, J H

    2001-01-01

    As part of a study of the genetics of floral adaptation and speciation in the Mimulus guttatus species complex, we constructed a genetic linkage map of an interspecific cross between M. guttatus and M. nasutus. We genotyped an F(2) mapping population (N = 526) at 255 AFLP, microsatellite, and gene-based markers and derived a framework map through repeated rounds of ordering and marker elimination. The final framework map consists of 174 marker loci on 14 linkage groups with a total map length of 1780 cM Kosambi. Genome length estimates (2011-2096 cM) indicate that this map provides thorough coverage of the hybrid genome, an important consideration for QTL mapping. Nearly half of the markers in the full data set (49%) and on the framework map (48%) exhibited significant transmission ratio distortion (alpha = 0.05). We localized a minimum of 11 transmission ratio distorting loci (TRDLs) throughout the genome, 9 of which generate an excess of M. guttatus alleles and a deficit of M. nasutus alleles. This pattern indicates that the transmission ratio distortion results from particular interactions between the heterospecific genomes and suggests that substantial genetic divergence has occurred between these Mimulus species. We discuss possible causes of the unequal representation of parental genomes in the F(2) generation. PMID:11779808

  1. POWER TO DETECT HIGHER-ORDER EPISTATIC INTERACTIONS IN A METABOLIC PATHWAY USING NESTED ASSOCIATION MAPPING AND DIALLEL ASSOCIATION MAPPING

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epistatic interactions among quantitative trait loci (QTL) contribute substantially to the variation in complex traits. The main objectives of this study were to (i) compare two- vs. four-step genome scans to identify four-way interactions among QTL belonging to a metabolic pathway, (ii) investigat...

  2. The nuclear quadrupole interaction at inequivalent lattice sites in ammonium paramolybdate: A TDPAC study

    NASA Astrophysics Data System (ADS)

    Das, S. K.; Heinrich, F.; Butz, T.

    2006-09-01

    A nuclear quadrupole interaction (NQI) study using the time differential perturbed angular correlation (TDPAC) technique on ammonium paramolybdate (APM) has shown three inequivalent molybdenum sites in this compound which consists of seven MoO 6 polyhedra connected through edges. In this study the nuclear probe 99Mo was used to measure the ?- ? perturbed angular correlation of 99Tc on Mo-sites to obtain the quadrupole interaction parameters. The quadrupole interaction frequencies ( ?Q) for the three sites are 0.0224, 0.0386 and 0.0434 rad/ns and the asymmetry parameters ( ?) of the electric field gradient (EFG) are 0.45, 0.18, and 0.58, respectively. The site assignment is based on the population ratios 4:2:1. The Mo atoms with the highest population show the lowest ?Q indicating that this set of polyhedra is "least" distorted or condensed. Besides the least squares fit, a cross-correlation algorithm has been used to analyze the experimental data to corroborate the fitted parameters and quoted errors. The derived NQI-parameters can be used for site assignments in other compounds built from condensed Mo-O octahedra.

  3. Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas fir. III. Quantitative trait loci-by-environment interactions.

    PubMed

    Jermstad, Kathleen D; Bassoni, Daniel L; Jech, Keith S; Ritchie, Gary A; Wheeler, Nicholas C; Neale, David B

    2003-11-01

    Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir (Pseudotsuga menziesii var. menziesii [Mirb.] Franco) for complex traits controlling the timing of growth initiation and growth cessation. QTL were estimated under controlled environmental conditions to identify QTL interactions with photoperiod, moisture stress, winter chilling, and spring temperatures. A three-generation mapping population of 460 cloned progeny was used for genetic mapping and phenotypic evaluations. An all-marker interval mapping method was used for scanning the genome for the presence of QTL and single-factor ANOVA was used for estimating QTL-by-environment interactions. A modest number of QTL were detected per trait, with individual QTL explaining up to 9.5% of the phenotypic variation. Two QTL-by-treatment interactions were found for growth initiation, whereas several QTL-by-treatment interactions were detected among growth cessation traits. This is the first report of QTL interactions with specific environmental signals in forest trees and will assist in the identification of candidate genes controlling these important adaptive traits in perennial plants. PMID:14668397

  4. Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas fir. III. Quantitative trait loci-by-environment interactions.

    PubMed Central

    Jermstad, Kathleen D; Bassoni, Daniel L; Jech, Keith S; Ritchie, Gary A; Wheeler, Nicholas C; Neale, David B

    2003-01-01

    Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir (Pseudotsuga menziesii var. menziesii [Mirb.] Franco) for complex traits controlling the timing of growth initiation and growth cessation. QTL were estimated under controlled environmental conditions to identify QTL interactions with photoperiod, moisture stress, winter chilling, and spring temperatures. A three-generation mapping population of 460 cloned progeny was used for genetic mapping and phenotypic evaluations. An all-marker interval mapping method was used for scanning the genome for the presence of QTL and single-factor ANOVA was used for estimating QTL-by-environment interactions. A modest number of QTL were detected per trait, with individual QTL explaining up to 9.5% of the phenotypic variation. Two QTL-by-treatment interactions were found for growth initiation, whereas several QTL-by-treatment interactions were detected among growth cessation traits. This is the first report of QTL interactions with specific environmental signals in forest trees and will assist in the identification of candidate genes controlling these important adaptive traits in perennial plants. PMID:14668397

  5. Mapping substrate interactions of the human membrane-associated neuraminidase, NEU3, using STD NMR.

    PubMed

    Albohy, Amgad; Richards, Michele R; Cairo, Christopher W

    2015-03-01

    Saturation transfer difference (STD) nuclear magnetic resonance (NMR) is a powerful technique which can be used to investigate interactions between proteins and their substrates. The method identifies specific sites of interaction found on a small molecule ligand when in complex with a protein. The ability of STD NMR to provide specific insight into binding interactions in the absence of other structural data is an attractive feature for its use with membrane proteins. We chose to employ STD NMR in our ongoing investigations of the human membrane-associated neuraminidase NEU3 and its interaction with glycolipid substrates (e.g., GM3). In order to identify critical substrate-enzyme interactions, we performed STD NMR with a catalytically inactive form of the enzyme, NEU3(Y370F), containing an N-terminal maltose-binding protein (MBP)-affinity tag. In the absence of crystallographic data on the enzyme, these data represent a critical experimental test of proposed homology models, as well as valuable new structural data. To aid interpretation of the STD NMR data, we compared the results with molecular dynamics (MD) simulations of the enzyme-substrate complexes. We find that the homology model is able to predict essential features of the experimental data, including close contact of the hydrophobic aglycone and the Neu5Ac residue with the enzyme. Additionally, the model and STD NMR data agree on the facial recognition of the galactose and glucose residues of the GM3-analog studied. We conclude that the homology model of NEU3 can be used to predict substrate recognition, but our data indicate that unstructured portions of the NEU3 model may require further refinement. PMID:25294388

  6. [Cloning-idependent mapping technology for genomic fidelity, contig linking, C-DNA site analysis, and gene detection]. Final report

    SciTech Connect

    Lerman, L.S.

    1994-12-25

    The project was designed to develop and apply a novel unconventional approach to genome mapping based on physical properties of DNA that are a sensitive function of the base sequence, and so does not depend on the clonability of the sequences to be mapped nor on the presence of particular restriction sites. We have shown that a broad array of DNA fragments are retarded at nearly the same level in denaturing gradient gel electrophoresis (DGGE) if the segment with the lowest thermal stability has the same melting temperature, regardless of the length of the fragment. The retarded pattern remain steady in the gel, changing little with continued field exposure. Mapping proceeds by the analysis of two-dimensional patterns produced by random fragmentation of genomic DNA and denaturing gradient gel electrophoresis. Random fragments are first separated according to length by conventional agarose electrophoresis. The result is a two- dimensional pattern which can be idealized as an array of nearly parallel, mostly separated lines of DNA. The pattern is blotted onto a membrane and probed sequentially with oligos or relevant DNA or RNA fragments. The endpoints on the fragment length scale of each line hybridizing with each probe, the distribution along each line, and the depth in the gradient constitute specific map information.

  7. Mapping protein-protein interactions by localized oxidation: consequences of the reach of hydroxyl radical.

    PubMed

    Cheal, Sarah M; Ng, Mindy; Barrios, Brianda; Miao, Zheng; Kalani, Amir K; Meares, Claude F

    2009-06-01

    Hydroxyl radicals generated from a variety of methods, including not only synchrotron radiation but also Fenton reactions involving chelated iron, have become an accepted macromolecular footprinting tool. Hydroxyl radicals react with proteins via multiple mechanisms that lead to both polypeptide backbone cleavage events and side chain modifications (e.g., hydroxylation and carbonyl formation). The use of site-specifically tethered iron chelates can reveal protein-protein interactions, but the interpretation of such experiments will be strengthened by improving our understanding of how hydroxyl radicals produced at a point on a protein react with other protein sites. We have developed methods for monitoring carbonyl formation on proteins as a function of distance from a hydroxyl generator, iron-(S)-1-[p-(bromoacetamido)benzyl]EDTA (FeBABE), conjugated to an engineered cysteine residue. After activation of the chelated iron with ascorbate and peroxide produces new protein carbonyl groups, their positions can be identified using element-coded affinity tagging (ECAT), with carbonyl-specific tags {e.g., rare earth chelates of (S)-2-[4-(2-aminooxy)acetamidobenzyl]-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (AOD)} that allow for affinity purification, identification, and relative quantitation of oxidation sites using mass spectrometry. Intraprotein oxidation of single-cysteine mutants of Escherichia coli sigma(70) by tethered FeBABE was used to calibrate the reach of hydroxyl radical by comparison to the crystal structure; the application to protein-protein interactions was demonstrated using the same sigma(70) FeBABE conjugates in complexes with the RNA polymerase core enzyme. The results provide fundamental information for interpreting protein footprinting experiments in other systems. PMID:19354299

  8. 24 CFR 3285.103 - Site suitability with design zone maps.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... is to be installed. The design zone maps are those identified in part 3280 of this chapter. (a) Wind zone. Manufactured homes must not be installed in a wind zone that exceeds the design wind loads for which the home has been designed, as evidenced by the wind zone indicated on the home's data plate...

  9. An Interactive Barnes Objective Map Analysis Scheme for Use with Satellite and Conventional Data.

    NASA Astrophysics Data System (ADS)

    Koch, Steven E.; Desjardins, Mary; Kocin, Paul J.

    1983-09-01

    An objective analysis scheme based on the Barnes technique and designed for use on an interactive computer is described. In order to meet the specific needs of the research meteorologist, the interactive Barnes scheme allows real-time assessments both of the quality of the resulting analyses and of the impact of satellite-derived data upon various meteorological data sets. Display of a number of statistical and mapped analysis quality control indicators aid the impact assessments. Simple means for taking account of the spatially clustered nature typical of satellite data are included in the internal computations of the relative weights of data at grid point locations.An analyst is allowed the capability of modifying values of certain input parameters to the interactive Barnes scheme within internally set limits. These constraints were objectively determined and tested in a number of different situations prior to implementation. The following constraints are employed: 1) calculation of the weights as a function of a data spacing representative of the data distribution; 2) automatic elimination of detail at wavelengths smaller than twice the representative data spacing; 3) placement of bounds upon the grid spacing by the data spacing; and 4) setting of a fixed limit on the number of passes through the data to achieve rapid and sufficient convergence of the analyzed values to the observed ones. A mathematical analysis of the convergence properties of the Barnes technique is presented to support the validity of the latter constraint.Despite these constraints, the interactive Barnes scheme remains versatile because it accepts limited inputs to the data and grid display areas, to the data and grid spacings, and to the rate of convergence of the analysis to the observations. Input parameter values are entered through a series of questions displayed on a computer video terminal and by manipulation of display function devices. The analyst immediately sees a plot of the data, the contoured grid values, superimposed in various colors if desired, and the effects of choice of analysis options. Examples of both meteorological and satellite data analyses are presented to demonstrate the objectivity, versatility and practicality of the interactive Barnes scheme.

  10. Bioflavonoid interaction with rat uterine type II binding sites and cell growth inhibition.

    PubMed

    Markaverich, B M; Roberts, R R; Alejandro, M A; Johnson, G A; Middleditch, B S; Clark, J H

    1988-01-01

    Competition analysis with a number of known bioflavonoids demonstrated that these compounds (luteolin, quercetin, pelargonin) compete for [3H]estradiol binding to cytosol and nuclear type II sites in rat uterine preparations. The inhibition of [3H]estradiol binding to type II sites was specific and these bioflavonoids did not interact with the rat uterine estrogen receptor. Since estradiol stimulation of nuclear type II sites in the rat uterus is highly correlated with cellular hypertrophy and hyperplasia, we assessed the effects of these compounds on the growth of MCF-7 human breast cancer cells in culture and on estradiol stimulation of uterine growth in the immature rat. The data demonstrated that addition of quercetin (5-10 micrograms/ml) to MCF-7 cell cultures resulted in a dose-dependent inhibition of cell growth (DNA/flask). This effect was reversible by removal of quercetin from the culture medium, or by the addition of 10 nM estradiol-17 beta to these cell cultures containing this bioflavonoid. Since estradiol-17 beta (10 nM) stimulated nuclear type II sites and proliferation of MCF-7 cells, we believe bioflavonoid inhibition of MCF-7 cell growth may be mediated through an interaction with nuclear type II sites. This hypothesis was confirmed by in vivo studies which demonstrated that injection of luteolin or quercetin blocked estradiol stimulation of nuclear type II sites in the immature rat uterus and this correlated with an inhibition of uterine growth (wet and dry weight). These studies suggest bioflavonoids, through an interaction with type II sites, may be involved in cell growth regulation. PMID:3386279

  11. Three-dimensional mapping of equiprobable hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site

    SciTech Connect

    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 contiguity of high and low hydraulic conductivity regions.

  12. 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.

  13. Human papillomavirus DNA: physical mapping of the cleavage sites of Bacillus amyloliquefaciens (BamI) and Haemophilus parainfluenzae (HpaII) endonucleases and evidence for partial heterogeneity.

    PubMed Central

    Favre, M; Orth, G; Croissant, O; Yaniv, M

    1977-01-01

    The DNA of human papillomavirus (HPV) obtained from a pool of plantar warts is cleaved by bacillus amyloliquefaciens (BamI) and Haemophilus parainfluenzae (HpaII) restriction endonucleases at one and four specific sites, respectively. These sites were localized on the previously established cleavage map of HPV DNA, using the Hind, HindIII, HpaI, and EcoRI endonuclease restriction sites as reference. The four HpaII sites were mapped, clockwise, at 1.4, 41.1, 44.3, and 52.8% of the genome length from the unique BamI cleavage site taken as point zero. The HpaII site mapped at 1.4% of the genome length was absent in 40 to 50% of the molecules, thus showing a genetic heterogeneity of HPV DNA. Images PMID:191644

  14. Hydrogen-bonding interactions in the active sites of cytochrome P450cam and its site-directed mutants.

    PubMed

    Deng, T; Macdonald, I D; Simianu, M C; Sykora, M; Kincaid, J R; Sligar, S G

    2001-01-17

    Resonance Raman spectroscopy is applied to the cyanide adducts of cytochrome P450cam and its T252A and D251N site-directed mutants, both in their substrate-free and camphor-bound forms, to probe active-site heme structure and, in particular, interactions of the FeCN fragment with potential active-site H-bond donors. In contrast to the ferrous CO and ferric NO adducts, which form only essentially linear (slightly distorted) FeXY fragments, the spectra of the ferric CN(-) adducts provide clear evidence the for the existence of an additional, rather highly bent, conformer; that is, the cyanide complexes form both linear and bent conformers in both the substrate-free and substrate-bound forms. Formation of this bent conformer is most reasonably attributed to the presence of off-axis H-bond donors, which induce distortion on the FeCN fragment but not the FeCO and FeNO fragments, which are poorer H-bond acceptors. For all three proteins, the substrate-free form exhibits a complex spectral pattern which arises because one of the modes associated with the FeCN fragment is coupled with two heme macrocycle deformation modes. Significantly, no evidence for such coupling is observed in the spectra of the camphor-bound forms. While various unknown factors may possibly give rise to selective activation of such coupling in the substrate-free derivative, given the known facts about the active-site architecture of this enzyme, a plausible explanation is that the bent conformer is oriented toward the water-filled substrate-binding site in the substrate-free form, but oppositely, toward the proposed proton delivery shuttle, in the substrate-bound form. Sensitivity of the FeCN modes to H(2)O/D(2)O exchange in the two camphor-bound mutants, which is apparently absent for the camphor-bound native protein, is most reasonably attributed to the known presence of extra water in the active sites of these mutants. PMID:11456513

  15. COREMAP: Graphical user interface for displaying reactor core data in an interactive hexagon map

    SciTech Connect

    Muscat, F.L.; Derstine, K.L.

    1995-06-01

    COREMAP is a Graphical User Interface (GUI) designed to assist users read and check reactor core data from multidimensional neutronic simulation models in color and/or as text in an interactive 2D planar grid of hexagonal subassemblies. COREMAP is a complete GEODST/RUNDESC viewing tool which enables the user to access multi data set files (e.g. planes, moments, energy groups ,... ) and display up to two data sets simultaneously, one as color and the other as text. The user (1) controls color scale characteristics such as type (linear or logarithmic) and range limits, (2) controls the text display based upon conditional statements on data spelling, and value. (3) chooses zoom features such as core map size, number of rings and surrounding subassemblies, and (4) specifies the data selection for supplied popup subwindows which display a selection of data currently off-screen for a selected cell, as a list of data and/or as a graph. COREMAP includes a RUNDESC file editing tool which creates ``proposed`` Run-description files by point and click revisions to subassembly assignments in an existing EBRII Run-description file. COREMAP includes a fully automated printing option which creates high quality PostScript color or greyscale images of the core map independent of the monitor used, e.g. color prints can be generated with a session from a color or monochrome monitor. The automated PostScript output is an alternative to the xgrabsc based printing option. COREMAP includes a plotting option which creates graphs related to a selected cell. The user specifies the X and Y coordinates types (planes, moment, group, flux ,... ) and a parameter, P, when displaying several curves for the specified (X, Y) pair COREMAP supports hexagonal geometry reactor core configurations specified by: the GEODST file and binary Standard Interface Files and the RUNDESC ordering.

  16. 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. PMID:24070451

  17. Combining Solvent Thermodynamic Profiles with Functionality Maps of the Hsp90 Binding Site to Predict the Displacement of Water Molecules

    PubMed Central

    2013-01-01

    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. PMID:24070451

  18. DamID-seq: Genome-wide Mapping of Protein-DNA Interactions by High Throughput Sequencing of Adenine-methylated DNA Fragments.

    PubMed

    Wu, Feinan; Olson, Brennan G; Yao, Jie

    2016-01-01

    The DNA adenine methyltransferase identification (DamID) assay is a powerful method to detect protein-DNA interactions both locally and genome-wide. It is an alternative approach to chromatin immunoprecipitation (ChIP). An expressed fusion protein consisting of the protein of interest and the E. coli DNA adenine methyltransferase can methylate the adenine base in GATC motifs near the sites of protein-DNA interactions. Adenine-methylated DNA fragments can then be specifically amplified and detected. The original DamID assay detects the genomic locations of methylated DNA fragments by hybridization to DNA microarrays, which is limited by the availability of microarrays and the density of predetermined probes. In this paper, we report the detailed protocol of integrating high throughput DNA sequencing into DamID (DamID-seq). The large number of short reads generated from DamID-seq enables detecting and localizing protein-DNA interactions genome-wide with high precision and sensitivity. We have used the DamID-seq assay to study genome-nuclear lamina (NL) interactions in mammalian cells, and have noticed that DamID-seq provides a high resolution and a wide dynamic range in detecting genome-NL interactions. The DamID-seq approach enables probing NL associations within gene structures and allows comparing genome-NL interaction maps with other functional genomic data, such as ChIP-seq and RNA-seq. PMID:26862720

  19. Interaction between Solar Wind and Lunar Magnetic Anomalies observed by Kaguya MAP-PACE

    NASA Astrophysics Data System (ADS)

    Saito, Yoshifumi; Yokota, Shoichiro; Tanaka, Takaaki; Asamura, Kazushi; Nishino, Masaki; Yamamoto, Tadateru; Uemura, Kota; Tsunakawa, Hideo

    2010-05-01

    It is known that Moon has neither global intrinsic magnetic field nor thick atmosphere. Different from the Earth's case where the intrinsic global magnetic field prevents the solar wind from penetrating into the magnetosphere, solar wind directly impacts the lunar surface. Since the discovery of the lunar crustal magnetic field in 1960s, several papers have been published concerning the interaction between the solar wind and the lunar magnetic anomalies. MAG/ER on Lunar Prospector found heating of the solar wind electrons presumably due to the interaction between the solar wind and the lunar magnetic anomalies and the existence of the mini-magnetosphere was suggested. However, the detailed mechanism of the interaction has been unclear mainly due to the lack of the in-situ observed data of low energy ions. MAgnetic field and Plasma experiment - Plasma energy Angle and Composition Experiment (MAP-PACE) on Kaguya (SELENE) completed its ˜1.5-year observation of the low energy charged particles around the Moon on 10 June, 2009. Kaguya was launched on 14 September 2007 by H2A launch vehicle from Tanegashima Space Center in Japan. Kaguya was inserted into a circular lunar polar orbit of 100km altitude and continued observation for nearly 1.5 years till it impacted the Moon on 10 June 2009. During the last 5 months, the orbit was lowered to ˜50km-altitude between January 2009 and April 2009, and some orbits had further lower perilune altitude of ˜10km after April 2009. MAP-PACE consisted of 4 sensors: ESA (Electron Spectrum Analyzer)-S1, ESA-S2, IMA (Ion Mass Analyzer), and IEA (Ion Energy Analyzer). All the sensors performed quite well as expected from the laboratory experiment carried out before launch. Since each sensor had hemispherical field of view, two electron sensors and two ion sensors that were installed on the spacecraft panels opposite to each other could cover full 3-dimensional phase space of low energy electrons and ions. One of the ion sensors IMA was an energy mass spectrometer. IMA measured mass identified ion energy spectra that had never been obtained at 100km altitude polar orbit around the Moon. When Kaguya flew over South Pole Aitken region, where strong magnetic anomalies exist, solar wind ions reflected by magnetic anomalies were observed. These ions had much higher flux than the solar wind protons scattered at the lunar surface. The magnetically reflected ions had nearly the same energy as the incident solar wind ions while the solar wind protons scattered at the lunar surface had slightly lower energy than the incident solar wind ions. At 100km altitude, when the reflected ions were observed, the simultaneously measured electrons were often heated and the incident solar wind ions were sometimes slightly decelerated. At ~50km altitude, when the reflected ions were observed, proton scattering at the lunar surface clearly disappeared. It suggests that there exists an area on the lunar surface where solar wind does not impact. At ~10km altitude, the interaction between the solar wind ions and the lunar magnetic anomalies was remarkable with clear deceleration of the incident solar wind ions and heating of the reflected ions as well as significant heating of the electrons. Calculating velocity moments including density, velocity, temperature of the ions and electrons, we have found that there exists 100km scale regions over strong magnetic anomalies where plasma parameters are quite different from the outside. Solar wind ions observed at 10km altitude show several different behaviors such as deceleration without heating and heating in a limited region inside the magnetic anomalies that may be caused by the magnetic field structure. The deceleration of the solar wind has the same ΔE/q (ΔE : deceleration energy, q: charge) for different species, which constraints the possible mechanisms of the interaction between solar wind and magnetic anomalies.

  20. 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 dispersion energies. PMID:21691813

  1. An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

    PubMed Central

    Lu, Yan; Chen, Jianjun; Xiao, Min; Li, Wei

    2013-01-01

    Tubulin dynamics is a promising target for new chemotherapeutic agents. The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity. CBSIs have been modified as to chemical structure as well as pharmacokinetic properties, and tested in order to find a highly potent, low toxicity agent for treatment of cancers. CBSIs are believed to act by a common mechanism via binding to the colchicine site on tubulin. The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs. PMID:22814904

  2. 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.

  3. Reconstructing Genome-Wide Protein–Protein Interaction Networks Using Multiple Strategies with Homologous Mapping

    PubMed Central

    Lo, Yu-Shu; Huang, Sing-Han; Luo, Yong-Chun; Lin, Chun-Yu; Yang, Jinn-Moon

    2015-01-01

    Background One of the crucial steps toward understanding the biological functions of a cellular system is to investigate protein–protein interaction (PPI) networks. As an increasing number of reliable PPIs become available, there is a growing need for discovering PPIs to reconstruct PPI networks of interesting organisms. Some interolog-based methods and homologous PPI families have been proposed for predicting PPIs from the known PPIs of source organisms. Results Here, we propose a multiple-strategy scoring method to identify reliable PPIs for reconstructing the mouse PPI network from two well-known organisms: human and fly. We firstly identified the PPI candidates of target organisms based on homologous PPIs, sharing significant sequence similarities (joint E-value ≤ 1 × 10−40), from source organisms using generalized interolog mapping. These PPI candidates were evaluated by our multiple-strategy scoring method, combining sequence similarities, normalized ranks, and conservation scores across multiple organisms. According to 106,825 PPI candidates in yeast derived from human and fly, our scoring method can achieve high prediction accuracy and outperform generalized interolog mapping. Experiment results show that our multiple-strategy score can avoid the influence of the protein family size and length to significantly improve PPI prediction accuracy and reflect the biological functions. In addition, the top-ranked and conserved PPIs are often orthologous/essential interactions and share the functional similarity. Based on these reliable predicted PPIs, we reconstructed a comprehensive mouse PPI network, which is a scale-free network and can reflect the biological functions and high connectivity of 292 KEGG modules, including 216 pathways and 76 structural complexes. Conclusions Experimental results show that our scoring method can improve the predicting accuracy based on the normalized rank and evolutionary conservation from multiple organisms. Our predicted PPIs share similar biological processes and cellular components, and the reconstructed genome-wide PPI network can reflect network topology and modularity. We believe that our method is useful for inferring reliable PPIs and reconstructing a comprehensive PPI network of an interesting organism. PMID:25602759

  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. In vivo interaction of the Escherichia coli integration host factor with its specific binding sites.

    PubMed Central

    Engelhorn, M; Boccard, F; Murtin, C; Prentki, P; Geiselmann, J

    1995-01-01

    The histone-like protein integration host factor (IHF) of Escherichia coli binds to specific binding sites on the chromosome or on mobile genetic elements, and is involved in many cellular processes. We have analyzed the interaction of IHF with five different binding sites in vitro and in vivo using UV laser footprinting, a technique that probes the immediate environment and conformation of a segment of DNA. Using this generally applicable technique we can directly compare the binding modes and interaction strengths of a DNA binding protein in its physiological environment within the cell to measurements performed in vitro. We conclude that the interactions between IHF and its specific binding sites are identical in vitro and in vivo. The footprinting signal is consistent with the model of IHF-binding to DNA proposed by Yang and Nash (1989). The occupancy of binding sites varies with the concentration of IHF in the cell and allows to estimate the concentration of free IHF protein in the cell. Images PMID:7659518

  6. NMR mapping of RANTES surfaces interacting with CCR5 using linked extracellular domains.

    PubMed

    Schnur, Einat; Kessler, Naama; Zherdev, Yuri; Noah, Eran; Scherf, Tali; Ding, Fa-Xiang; Rabinovich, Svetlana; Arshava, Boris; Kurbatska, Victoria; Leonciks, Ainars; Tsimanis, Alexander; Rosen, Osnat; Naider, Fred; Anglister, Jacob

    2013-05-01

    Chemokines constitute a large family of small proteins that regulate leukocyte trafficking to the site of inflammation by binding to specific cell-surface receptors belonging to the G-protein-coupled receptor (GPCR) superfamily. The interactions between N-terminal (Nt-) peptides of these GPCRs and chemokines have been studied extensively using NMR spectroscopy. However, because of the lower affinities of peptides representing the three extracellular loops (ECLs) of chemokine receptors to their respective chemokine ligands, information concerning these interactions is scarce. To overcome the low affinity of ECL peptides to chemokines, we linked two or three CC chemokine receptor 5 (CCR5) extracellular domains using either biosynthesis in Escherichia coli or chemical synthesis. Using such chimeras, CCR5 binding to RANTES was followed using (1)H-(15)N-HSQC spectra to monitor titration of the chemokine with peptides corresponding to the extracellular surface of the receptor. Nt-CCR5 and ECL2 were found to be the major contributors to CCR5 binding to RANTES, creating an almost closed ring around this protein by interacting with opposing faces of the chemokine. A RANTES positively charged surface involved in Nt-CCR5 binding resembles the positively charged surface in HIV-1 gp120 formed by the C4 and the base of the third variable loop of gp120 (V3). The opposing surface on RANTES, composed primarily of β2-β3 hairpin residues, binds ECL2 and was found to be analogous to a surface in the crown of the gp120 V3. The chemical and biosynthetic approaches for linking GPCR surface regions discussed herein should be widely applicable to the investigation of interactions of extracellular segments of chemokine receptors with their respective ligands. PMID:23480650

  7. 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. PMID:12723046

  8. Using Student Interactions to Foster Rule-Diagram Mapping during Problem Solving in an Intelligent Tutoring System

    ERIC Educational Resources Information Center

    Butcher, Kirsten R.; Aleven, Vincent

    2013-01-01

    In many domains, problem solving involves the application of general domain principles to specific problem representations. In 3 classroom studies with an intelligent tutoring system, we examined the impact of (learner-generated) interactions and (tutor-provided) visual cues designed to facilitate rule-diagram mapping (where students connect…

  9. A Structure-Based Classification and Analysis of Protein Domain Family Binding Sites and Their Interactions

    PubMed Central

    Ghoorah, Anisah W.; Devignes, Marie-Dominique; Alborzi, Seyed Ziaeddin; Smaïl-Tabbone, Malika; Ritchie, David W.

    2015-01-01

    While the number of solved 3D protein structures continues to grow rapidly, the structural rules that distinguish protein-protein interactions between different structural families are still not clear. Here, we classify and analyse the secondary structural features and promiscuity of a comprehensive non-redundant set of domain family binding sites (DFBSs) and hetero domain-domain interactions (DDIs) extracted from our updated KBDOCK resource. We have partitioned 4001 DFBSs into five classes using their propensities for three types of secondary structural elements (“α” for helices, “β” for strands, and “γ” for irregular structure) and we have analysed how frequently these classes occur in DDIs. Our results show that β elements are not highly represented in DFBSs compared to α and γ elements. At the DDI level, all classes of binding sites tend to preferentially bind to the same class of binding sites and α/β contacts are significantly disfavored. Very few DFBSs are promiscuous: 80% of them interact with just one Pfam domain. About 50% of our Pfam domains bear only one single-partner DFBS and are therefore monogamous in their interactions with other domains. Conversely, promiscuous Pfam domains bear several DFBSs among which one or two are promiscuous, thereby multiplying the promiscuity of the concerned protein. PMID:25860777

  10. Multivariate PLS Modeling of Apicomplexan FabD-Ligand Interaction Space for Mapping Target-Specific Chemical Space and Pharmacophore Fingerprints

    PubMed Central

    Surolia, Avadhesha

    2015-01-01

    Biomolecular recognition underlying drug-target interactions is determined by both binding affinity and specificity. Whilst, quantification of binding efficacy is possible, determining specificity remains a challenge, as it requires affinity data for multiple targets with the same ligand dataset. Thus, understanding the interaction space by mapping the target space to model its complementary chemical space through computational techniques are desirable. In this study, active site architecture of FabD drug target in two apicomplexan parasites viz. Plasmodium falciparum (PfFabD) and Toxoplasma gondii (TgFabD) is explored, followed by consensus docking calculations and identification of fifteen best hit compounds, most of which are found to be derivatives of natural products. Subsequently, machine learning techniques were applied on molecular descriptors of six FabD homologs and sixty ligands to induce distinct multivariate partial-least square models. The biological space of FabD mapped by the various chemical entities explain their interaction space in general. It also highlights the selective variations in FabD of apicomplexan parasites with that of the host. Furthermore, chemometric models revealed the principal chemical scaffolds in PfFabD and TgFabD as pyrrolidines and imidazoles, respectively, which render target specificity and improve binding affinity in combination with other functional descriptors conducive for the design and optimization of the leads. PMID:26535573

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

    PubMed

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

    2015-12-01

    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

  12. Building disease-specific drug-protein connectivity maps from molecular interaction networks and PubMed abstracts.

    PubMed

    Li, Jiao; Zhu, Xiaoyan; Chen, Jake Yue

    2009-07-01

    The recently proposed concept of molecular connectivity maps enables researchers to integrate experimental measurements of genes, proteins, metabolites, and drug compounds under similar biological conditions. The study of these maps provides opportunities for future toxicogenomics and drug discovery applications. We developed a computational framework to build disease-specific drug-protein connectivity maps. We integrated gene/protein and drug connectivity information based on protein interaction networks and literature mining, without requiring gene expression profile information derived from drug perturbation experiments on disease samples. We described the development and application of this computational framework using Alzheimer's Disease (AD) as a primary example in three steps. First, molecular interaction networks were incorporated to reduce bias and improve relevance of AD seed proteins. Second, PubMed abstracts were used to retrieve enriched drug terms that are indirectly associated with AD through molecular mechanistic studies. Third and lastly, a comprehensive AD connectivity map was created by relating enriched drugs and related proteins in literature. We showed that this molecular connectivity map development approach outperformed both curated drug target databases and conventional information retrieval systems. Our initial explorations of the AD connectivity map yielded a new hypothesis that diltiazem and quinidine may be investigated as candidate drugs for AD treatment. Molecular connectivity maps derived computationally can help study molecular signature differences between different classes of drugs in specific disease contexts. To achieve overall good data coverage and quality, a series of statistical methods have been developed to overcome high levels of data noise in biological networks and literature mining results. Further development of computational molecular connectivity maps to cover major disease areas will likely set up a new model for drug development, in which therapeutic/toxicological profiles of candidate drugs can be checked computationally before costly clinical trials begin. PMID:19649302

  13. Distribution of single-nucleotide variants on protein-protein interaction sites and its relationship with minor allele frequency.

    PubMed

    Nishi, Hafumi; Nakata, Junichi; Kinoshita, Kengo

    2016-02-01

    Recent advances in DNA sequencing techniques have identified rare single-nucleotide variants with less than 1% minor allele frequency. Despite the growing interest and physiological importance of rare variants in genome sciences, less attention has been paid to the allele frequency of variants in protein sciences. To elucidate the characteristics of genetic variants on protein interaction sites, from the viewpoints of the allele frequency and the structural position of variants, we mapped about 20,000 human SNVs onto protein complexes. We found tha