Sample records for activities site map

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

    PubMed Central

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

    2015-01-01

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

  2. Mapping NEHRP VS30 site classes

    USGS Publications Warehouse

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

    2005-01-01

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

  3. 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

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

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

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

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

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

    PubMed

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

    2007-05-22

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

  6. Methanopyrus kandleri topoisomerase V contains three distinct AP lyase active sites in addition to the topoisomerase active site

    PubMed Central

    Rajan, Rakhi; Osterman, Amy; Mondragón, Alfonso

    2016-01-01

    Topoisomerase V (Topo-V) is the only topoisomerase with both topoisomerase and DNA repair activities. The topoisomerase activity is conferred by a small alpha-helical domain, whereas the AP lyase activity is found in a region formed by 12 tandem helix-hairpin-helix ((HhH)2) domains. Although it was known that Topo-V has multiple repair sites, only one had been mapped. Here, we show that Topo-V has three AP lyase sites. The atomic structure and Small Angle X-ray Scattering studies of a 97 kDa fragment spanning the topoisomerase and 10 (HhH)2 domains reveal that the (HhH)2 domains extend away from the topoisomerase domain. A combination of biochemical and structural observations allow the mapping of the second repair site to the junction of the 9th and 10th (HhH)2 domains. The second site is structurally similar to the first one and to the sites found in other AP lyases. The 3rd AP lyase site is located in the 12th (HhH)2 domain. The results show that Topo-V is an unusual protein: it is the only known protein with more than one (HhH)2 domain, the only known topoisomerase with dual activities and is also unique by having three AP lyase repair sites in the same polypeptide. PMID:26908655

  7. Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy.

    PubMed

    Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling

    2015-12-01

    Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.

  8. 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

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

    PubMed Central

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

    2013-01-01

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

  10. Computer simulation of the active site of human serum cholinesterase

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

    Kefang Jiao; Song Li; Zhengzheng Lu

    1996-12-31

    The first 3D-structure of acetylchelinesterase from Torpedo California electric organ (T.AChE) was published by JL. Sussman in 1991. We have simulated 3D-structure of human serum cholinesterase (H.BuChE) and the active site of H.BuChE. It is discovered by experiment that the residue of H.BuChE is still active site after a part of H.BuChE is cut. For example, the part of 21KD + 20KD is active site of H.BuChE. The 20KD as it is. Studies on these peptides by Hemelogy indicate that two active peptides have same negative electrostatic potential maps diagram. These negative electrostatic areas attached by acetyl choline with positivemore » electrostatic potency. We predict that 147...236 peptide of AChE could be active site because it was as 20KD as with negative electrostatic potential maps. We look forward to proving from other ones.« less

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

    NASA Astrophysics Data System (ADS)

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

    2017-12-01

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

  12. Electrocorticographic high gamma activity versus electrical cortical stimulation mapping of naming.

    PubMed

    Sinai, Alon; Bowers, Christopher W; Crainiceanu, Ciprian M; Boatman, Dana; Gordon, Barry; Lesser, Ronald P; Lenz, Frederick A; Crone, Nathan E

    2005-07-01

    Subdural electrocorticographic (ECoG) recordings in patients undergoing epilepsy surgery have shown that functional activation is associated with event-related broadband gamma activity in a higher frequency range (>70 Hz) than previously studied in human scalp EEG. To investigate the utility of this high gamma activity (HGA) for mapping language cortex, we compared its neuroanatomical distribution with functional maps derived from electrical cortical stimulation (ECS), which remains the gold standard for predicting functional impairment after surgery for epilepsy, tumours or vascular malformations. Thirteen patients had undergone subdural electrode implantation for the surgical management of intractable epilepsy. Subdural ECoG signals were recorded while each patient verbally named sequentially presented line drawings of objects, and estimates of event-related HGA (80-100 Hz) were made at each recording site. Routine clinical ECS mapping used a subset of the same naming stimuli at each cortical site. If ECS disrupted mouth-related motor function, i.e. if it affected the mouth, lips or tongue, naming could not be tested with ECS at the same cortical site. Because naming during ECoG involved these muscles of articulation, the sensitivity and specificity of ECoG HGA were estimated relative to both ECS-induced impairments of naming and ECS disruption of mouth-related motor function. When these estimates were made separately for 12 electrode sites per patient (the average number with significant HGA), the specificity of ECoG HGA with respect to ECS was 78% for naming and 81% for mouth-related motor function, and equivalent sensitivities were 38% and 46%, respectively. When ECS maps of naming and mouth-related motor function were combined, the specificity and sensitivity of ECoG HGA with respect to ECS were 84% and 43%, respectively. This study indicates that event-related ECoG HGA during confrontation naming predicts ECS interference with naming and mouth-related motor

  13. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  15. 47 CFR 73.4108 - FM transmitter site map submissions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    Cancer.gov

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

  18. Mapping the spatial distribution and activity of (226)Ra at legacy sites through Machine Learning interpretation of gamma-ray spectrometry data.

    PubMed

    Varley, Adam; Tyler, Andrew; Smith, Leslie; Dale, Paul; Davies, Mike

    2016-03-01

    Radium ((226)Ra) contamination derived from military, industrial, and pharmaceutical products can be found at a number of historical sites across the world posing a risk to human health. The analysis of spectral data derived using gamma-ray spectrometry can offer a powerful tool to rapidly estimate and map the activity, depth, and lateral distribution of (226)Ra contamination covering an extensive area. Subsequently, reliable risk assessments can be developed for individual sites in a fraction of the timeframe compared to traditional labour-intensive sampling techniques: for example soil coring. However, local heterogeneity of the natural background, statistical counting uncertainty, and non-linear source response are confounding problems associated with gamma-ray spectral analysis. This is particularly challenging, when attempting to deal with enhanced concentrations of a naturally occurring radionuclide such as (226)Ra. As a result, conventional surveys tend to attribute the highest activities to the largest total signal received by a detector (Gross counts): an assumption that tends to neglect higher activities at depth. To overcome these limitations, a methodology was developed making use of Monte Carlo simulations, Principal Component Analysis and Machine Learning based algorithms to derive depth and activity estimates for (226)Ra contamination. The approach was applied on spectra taken using two gamma-ray detectors (Lanthanum Bromide and Sodium Iodide), with the aim of identifying an optimised combination of detector and spectral processing routine. It was confirmed that, through a combination of Neural Networks and Lanthanum Bromide, the most accurate depth and activity estimates could be found. The advantage of the method was demonstrated by mapping depth and activity estimates at a case study site in Scotland. There the method identified significantly higher activity (<3 Bq g(-1)) occurring at depth (>0.4m), that conventional gross counting algorithms

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

    PubMed

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

    2018-06-01

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

  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.

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

    USGS Publications Warehouse

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

    2011-01-01

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

  2. Nicotinamide Cofactors Suppress Active-Site Labeling of Aldehyde Dehydrogenases.

    PubMed

    Stiti, Naim; Chandrasekar, Balakumaran; Strubl, Laura; Mohammed, Shabaz; Bartels, Dorothea; van der Hoorn, Renier A L

    2016-06-17

    Active site labeling by (re)activity-based probes is a powerful chemical proteomic tool to globally map active sites in native proteomes without using substrates. Active site labeling is usually taken as a readout for the active state of the enzyme because labeling reflects the availability and reactivity of active sites, which are hallmarks for enzyme activities. Here, we show that this relationship holds tightly, but we also reveal an important exception to this rule. Labeling of Arabidopsis ALDH3H1 with a chloroacetamide probe occurs at the catalytic Cys, and labeling is suppressed upon nitrosylation and oxidation, and upon treatment with other Cys modifiers. These experiments display a consistent and strong correlation between active site labeling and enzymatic activity. Surprisingly, however, labeling is suppressed by the cofactor NAD(+), and this property is shared with other members of the ALDH superfamily and also detected for unrelated GAPDH enzymes with an unrelated hydantoin-based probe in crude extracts of plant cell cultures. Suppression requires cofactor binding to its binding pocket. Labeling is also suppressed by ALDH modulators that bind at the substrate entrance tunnel, confirming that labeling occurs through the substrate-binding cavity. Our data indicate that cofactor binding adjusts the catalytic Cys into a conformation that reduces the reactivity toward chloroacetamide probes.

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

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

    Castillo, Darina; Carpenter, Cliff; Linard, Joshua

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

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

    PubMed Central

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

    2013-01-01

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

  5. Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation.

    PubMed

    Navara, Rachita; Leef, George; Shenasa, Fatemah; Kowalewski, Christopher; Rogers, Albert J; Meckler, Gabriela; Zaman, Junaid A B; Baykaner, Tina; Park, Shirley; Turakhia, Mintu P; Zei, Paul; Viswanathan, Mohan; Wang, Paul J; Narayan, Sanjiv M

    2018-01-29

    To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI). It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods. We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity. In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n  =  20) and focal (n  =  2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P < 0.001) with similar stability (P < 0.001). Vagal slowing was not observed at sites of AF termination. PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF. © 2018 Wiley Periodicals, Inc.

  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

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

    NASA Technical Reports Server (NTRS)

    2007-01-01

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

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

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

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  10. GIS walking maps to promote physical activity in low-income public housing communities: a qualitative examination.

    PubMed

    McNeill, Lorna H; Emmons, Karen

    2012-01-01

    Walking is the most commonly reported leisure-time activity. Members of racial/ethnic minority groups and people of low socioeconomic status disproportionately live in urban environments that are perceived to be unsafe, thereby reducing opportunities for engaging in walking. We examined the use of walking maps for increasing physical activity (PA) among low-income residents of public housing sites in Boston, Massachusetts. PA facilities, local businesses, and destinations in a walkable half-mile radius of the housing community were identified and plotted on maps by using geographic information systems technology. Four focus groups (n = 24) were conducted to learn how the walking maps were used by the residents and to understand map features that promoted use. Maps were used by participants to increase their PA, and use of the maps increased participants' awareness of community resources. Maps changed participants' perception of distances and were discussed as a means of fostering a sense of community. Use of the maps also increased participants' awareness of neighborhood incivilities. Barriers to map use were difficulty in interpreting the maps and lack of access to the maps. Walking maps that display PA opportunities and resources may be useful in increasing walking among residents of public housing sites.

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

    PubMed

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

    2018-03-01

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

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

    PubMed

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

    2018-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  14. 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.

  15. 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

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

    PubMed

    Burrough, P A; Swindell, J

    1997-01-01

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

  17. Active Fire Mapping Program

    MedlinePlus

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  18. Teaching Plate Tectonic Concepts using GeoMapApp Learning Activities

    NASA Astrophysics Data System (ADS)

    Goodwillie, A. M.; Kluge, S.

    2012-12-01

    GeoMapApp Learning Activities ( http://serc.carleton.edu/geomapapp/collection.html ) can help educators to expose undergraduate students to a range of earth science concepts using high-quality data sets in an easy-to-use map-based interface called GeoMapApp. GeoMapApp Learning Activities require students to interact with and analyse research-quality geoscience data as a means to explore and enhance their understanding of underlying content and concepts. Each activity is freely available through the SERC-Carleton web site and offers step-by-step student instructions and answer sheets. Also provided are annotated educator versions of the worksheets that include teaching tips, additional content and suggestions for further work. The activities can be used "off-the-shelf". Or, since the educator may require flexibility to tailor the activities, the documents are provided in Word format for easy modification. Examples of activities include one on the concept of seafloor spreading that requires students to analyse global seafloor crustal age data to calculate spreading rates in different ocean basins. Another activity has students explore hot spots using radiometric age dating of rocks along the Hawaiian-Emperor seamount chain. A third focusses upon the interactive use of contours and profiles to help students visualise 3-D topography on 2-D computer screens. A fourth activity provides a study of mass wasting as revealed through geomorphological evidence. The step-by-step instructions and guided inquiry approach reduce the need for teacher intervention whilst boosting the time that students can spend on productive exploration and learning. The activities can be used, for example, in a classroom lab with the educator present and as self-paced assignments in an out-of-class setting. GeoMapApp Learning Activities are funded through the NSF GeoEd program and are aimed at students in the introductory undergraduate, community college and high school levels. The activities are

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

    PubMed

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

    2018-03-28

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

  20. Active Site Mapping of Xylan-Deconstructing Enzymes with Arabinoxylan Oligosaccharides Produced by Automated Glycan Assembly.

    PubMed

    Senf, Deborah; Ruprecht, Colin; de Kruijff, Goswinus H M; Simonetti, Sebastian O; Schuhmacher, Frank; Seeberger, Peter H; Pfrengle, Fabian

    2017-03-02

    Xylan-degrading enzymes are crucial for the deconstruction of hemicellulosic biomass, making the hydrolysis products available for various industrial applications such as the production of biofuel. To determine the substrate specificities of these enzymes, we prepared a collection of complex xylan oligosaccharides by automated glycan assembly. Seven differentially protected building blocks provided the basis for the modular assembly of 2-substituted, 3-substituted, and 2-/3-substituted arabino- and glucuronoxylan oligosaccharides. Elongation of the xylan backbone relied on iterative additions of C4-fluorenylmethoxylcarbonyl (Fmoc) protected xylose building blocks to a linker-functionalized resin. Arabinofuranose and glucuronic acid residues have been selectively attached to the backbone using fully orthogonal 2-(methyl)naphthyl (Nap) and 2-(azidomethyl)benzoyl (Azmb) protecting groups at the C2 and C3 hydroxyls of the xylose building blocks. The arabinoxylan oligosaccharides are excellent tools to map the active site of glycosyl hydrolases involved in xylan deconstruction. The substrate specificities of several xylanases and arabinofuranosidases were determined by analyzing the digestion products after incubation of the oligosaccharides with glycosyl hydrolases. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

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

  2. Effects of Butyltins (BTs) on Mitogen-Activated-Protein Kinase Kinase Kinase (MAP3K) and Ras Activity in Human Natural Killer Cells

    PubMed Central

    Celada, Lindsay J.; Whalen, Margaret M.

    2013-01-01

    Butyltins (BTs) contaminate the environment and are found in human blood. BTs, tributyltin (TBT) and dibutyltin (DBT), diminish the cytotoxic function and levels of key proteins of human natural killer (NK) cells. NK cells are an initial immune defense against tumors, virally-infected cells and antibody-coated cells and thus critical to human health. The signaling pathways that regulate NK cell functions include mitogen-activated protein kinases (MAPKs). Studies have shown that exposure to BTs leads to the activation of specific MAPKs and MAPK kinases (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of MAP2Ks, which then activate MAPKs. The current study examined if BT-induced activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c-Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined for BT-induced alterations. Our results show significant activation of the MAP3K, c-Raf, in human NK cells within 10 minutes of TBT exposure and the MAP3K, ASK1, after one hour exposures to TBT. In addition, our results suggest that both TBT and DBT are impacting the regulation of c-Raf. PMID:24038145

  3. Site Map | USDA Plant Hardiness Zone Map

    Science.gov Websites

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

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

    PubMed Central

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

    2014-01-01

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

  5. Direct instrumental identification of catalytically active surface sites

    NASA Astrophysics Data System (ADS)

    Pfisterer, Jonas H. K.; Liang, Yunchang; Schneider, Oliver; Bandarenka, Aliaksandr S.

    2017-09-01

    The activity of heterogeneous catalysts—which are involved in some 80 per cent of processes in the chemical and energy industries—is determined by the electronic structure of specific surface sites that offer optimal binding of reaction intermediates. Directly identifying and monitoring these sites during a reaction should therefore provide insight that might aid the targeted development of heterogeneous catalysts and electrocatalysts (those that participate in electrochemical reactions) for practical applications. The invention of the scanning tunnelling microscope (STM) and the electrochemical STM promised to deliver such imaging capabilities, and both have indeed contributed greatly to our atomistic understanding of heterogeneous catalysis. But although the STM has been used to probe and initiate surface reactions, and has even enabled local measurements of reactivity in some systems, it is not generally thought to be suited to the direct identification of catalytically active surface sites under reaction conditions. Here we demonstrate, however, that common STMs can readily map the catalytic activity of surfaces with high spatial resolution: we show that by monitoring relative changes in the tunnelling current noise, active sites can be distinguished in an almost quantitative fashion according to their ability to catalyse the hydrogen-evolution reaction or the oxygen-reduction reaction. These data allow us to evaluate directly the importance and relative contribution to overall catalyst activity of different defects and sites at the boundaries between two materials. With its ability to deliver such information and its ready applicability to different systems, we anticipate that our method will aid the rational design of heterogeneous catalysts.

  6. Topographic mapping of the Apollo 16 landing site

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2018-06-01

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

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

    PubMed Central

    Karl, Jason W.

    2017-01-01

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

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

    PubMed

    Maynard, Jonathan J; Karl, Jason W

    2017-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Brady, M.

    2015-12-01

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

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

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

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

  13. Considerations for applying digital soil mapping to ecological sites

    USDA-ARS?s Scientific Manuscript database

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

  14. Mutational Analysis of Escherichia coli MoeA: Two Functional Activities Map to the Active Site Cleft

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

    Nichols,J.; Xiang, S.; Schindelin, H.

    2007-01-01

    The molybdenum cofactor is ubiquitous in nature, and the pathway for Moco biosynthesis is conserved in all three domains of life. Recent work has helped to illuminate one of the most enigmatic steps in Moco biosynthesis, ligation of metal to molybdopterin (the organic component of the cofactor) to form the active cofactor. In Escherichia coli, the MoeA protein mediates ligation of Mo to molybdopterin while the MogA protein enhances this process in an ATP-dependent manner. The X-ray crystal structures for both proteins have been previously described as well as two essential MogA residues, Asp49 and Asp82. Here we describe amore » detailed mutational analysis of the MoeA protein. Variants of conserved residues at the putative active site of MoeA were analyzed for a loss of function in two different, previously described assays, one employing moeA{sup -} crude extracts and the other utilizing a defined system. Oddly, no correlation was observed between the activity in the two assays. In fact, our results showed a general trend toward an inverse relationship between the activity in each assay. Moco binding studies indicated a strong correlation between a variant's ability to bind Moco and its activity in the purified component assay. Crystal structures of the functionally characterized MoeA variants revealed no major structural changes, indicating that the functional differences observed are not due to disruption of the protein structure. On the basis of these results, two different functional areas were assigned to regions at or near the MoeA active site cleft.« less

  15. 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.

  16. 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.

  17. 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.

  18. 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).

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

    NASA Astrophysics Data System (ADS)

    Chakraborty, A.; Goto, H.

    2017-12-01

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

  20. 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.

  1. CsMAP34, a teleost MAP with dual role: A promoter of MASP-assisted complement activation and a regulator of immune cell activity.

    PubMed

    Li, Mo-Fei; Li, Jun; Sun, Li

    2016-12-23

    In teleost fish, the immune functions of mannan-binding lectin (MBL) associated protein (MAP) and MBL associated serine protease (MASP) are scarcely investigated. In the present study, we examined the biological properties both MAP (CsMAP34) and MASP (CsMASP1) molecules from tongue sole (Cynoglossus semilaevis). We found that CsMAP34 and CsMASP1 expressions occurred in nine different tissues and were upregulated by bacterial challenge. CsMAP34 protein was detected in blood, especially during bacterial infection. Recombinant CsMAP34 (rCsMAP34) bound C. semilaevis MBL (rCsBML) when the latter was activated by bacteria, while recombinant CsMASP1 (rCsMASP1) bound activated rCsBML only in the presence of rCsMAP34. rCsMAP34 stimulated the hemolytic and bactericidal activities of serum complement, whereas anti-CsMAP34 antibody blocked complement activities. Knockdown of CsMASP1 in C. semilaevis resulted in significant inhibition of complement activities. Furthermore, rCsMAP34 interacted directly with peripheral blood leukocytes (PBL) and enhanced the respiratory burst, acid phosphatase activity, chemotactic activity, and gene expression of PBL. These results indicate for the first time that a teleost MAP acts one hand as a regulator that promotes the lectin pathway of complement activation via its ability to recruit MBL to MASP, and other hand as a modulator of immune cell activity.

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

    Treesearch

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

    2017-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Clinton, J.

    2017-12-01

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

  4. Mapping Skills and Activities with Children's Literature

    ERIC Educational Resources Information Center

    Gandy, S. Kay

    2006-01-01

    In the primary grades, maps are useful tools to help the young reader put stories into perspective. This article presents 18 quality children's books that contain maps or lessons about maps, as well as activities to use in the classroom to teach map skills. A table is included with ratings of the usability of the maps.

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

    PubMed

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

    1999-02-12

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

  6. A Digital Tectonic Activity Map of the Earth

    NASA Technical Reports Server (NTRS)

    Lowman, Paul; Masuoka, Penny; Montgomery, Brian; OLeary, Jay; Salisbury, Demetra; Yates, Jacob

    1999-01-01

    The subject of neotectonics, covering the structures and structural activity of the last 5 million years (i.e., post-Miocene) is a well-recognized field, including "active tectonics," focussed on the last 500,000 years in a 1986 National Research Council report of that title. However, there is a cartographic gap between tectonic maps, generally showing all features regardless of age, and maps of current seismic or volcanic activity. We have compiled a map intended to bridge this gap, using modern data bases and computer-aided cartographic techniques. The maps presented here are conceptually descended from an earlier map showing tectonic and volcanic activity of the last one million years. Drawn by hand with the National Geographic Society's 1975 "The Physical World" map as a base, the 1981 map in various revisions has been widely reproduced in textbooks and various technical publications. However, two decades of progress call for a completely new map that can take advantage of new knowledge and cartographic techniques. The digital tectonic activity map (DTM), presented in shaded relief (Fig. 1) and schematic (Fig. 2) versions, is the result. The DTM is intended to show tectonism and volcanism of the last one million years, a period long enough to be representative of global activity, but short enough that features such as fault scarps and volcanos are still geomorphically recognizable. Data Sources and Cartographic Methods The DTM is based on a wide range of sources, summarized in Table 1. The most important is the digital elevation model, used to construct a shaded relief map. The bathymetry is largely from satellite altimetry, specifically the marine gravity compilations by Smith and Sandwell (1996). The shaded relief map was designed to match the new National Geographic Society world physical map (1992), although drawn independently, from the digital elevation model. The Robinson Projection is used instead of the earlier Van der Grinten one. Although neither

  7. BOREAS Hardcopy Maps

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  8. Mapping of Cardiac Electrical Activation with Electromechanical Wave Imaging: An in silico-in vivo Reciprocity Study

    PubMed Central

    Provost, Jean; Gurev, Viatcheslav; Trayanova, Natalia; Konofagou, Elisa E.

    2011-01-01

    Background Electromechanical Wave Imaging (EWI) is an entirely non-invasive, ultrasound-based imaging method capable of mapping the electromechanical activation sequence of the ventricles in vivo. Given the broad accessibility of ultrasound scanners in the clinic, the application of EWI could constitute a flexible surrogate for the 3D electrical activation. Objective The purpose of this report is to reproduce the electromechanical wave (EW) using an anatomically-realistic electromechanical model, and establish the capability of EWI to map the electrical activation sequence in vivo when pacing from different locations. Methods EWI was performed in one canine during pacing from three different sites. A high-resolution dynamic model of coupled cardiac electromechanics of the canine heart was used to predict the experimentally recorded electromechanical wave. The simulated 3D electrical activation sequence was then compared with the experimental EW. Results The electrical activation sequence and the EW were highly correlated for all pacing sites. The relationship between the electrical activation and the EW onset was found to be linear with a slope of 1.01 to 1.17 for different pacing schemes and imaging angles. Conclusions The accurate reproduction of the EW in simulations indicates that the model framework is capable of accurately representing the cardiac electromechanics and thus testing new hypotheses. The one-to-one correspondence between the electrical activation sequence and the EW indicates that EWI could be used to map the cardiac electrical activity. This opens the door for further exploration of the technique in assisting in the early detection, diagnosis and treatment monitoring of rhythm dysfunction. PMID:21185403

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

    PubMed

    Zhang, Zijun; Xing, Yi

    2017-09-19

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

  10. Tripolar Laplacian electrocardiogram and moment of activation isochronal mapping.

    PubMed

    Besio, W; Chen, T

    2007-05-01

    The electrocardiogram (ECG) provides useful global temporal assessment of the cardiac activity, but has limited spatial capabilities. The Laplacian electrocardiogram (LECG), an improvement over the ECG, provides high spatiotemporal distributed information about cardiac electrical activation. We designed and developed LECG tripolar concentric ring electrode active sensors based on the finite element algorithm 'nine-point method' (NPM). The active sensors were used in an array of 6 by 12 (72) locations to record bipolar and tripolar LECG from the body surface over the anterolateral chest. Compared to bipolar LECG, tripolar LECG showed significantly higher spatial selectivity which may be helpful in inferring information about cardiac activations detected on the body surface. In this study the moment of activation (MOA), an indicator of a depolarization wave passing below the active sensors, was used to surmise possible timing information of the cardiac electrical activation below the active sensors' recording sites. The MOA on the body surface was used to generate isochronal maps that may some day be used by clinicians in diagnosing arrhythmias and assessing the efficacy of therapies.

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

    PubMed

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

    2018-05-05

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

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

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

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

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

    PubMed

    Forman, Stuart A; Miller, Keith W

    2016-11-01

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

  14. Whole-brain activity mapping onto a zebrafish brain atlas

    PubMed Central

    Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.

    2015-01-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

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

    NASA Astrophysics Data System (ADS)

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

    2018-06-01

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

  16. 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).

  17. 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

  18. The Microtubule-Associated Protein MAP18 Affects ROP2 GTPase Activity during Root Hair Growth1[OPEN

    PubMed Central

    Kang, Erfang; Zheng, Mingzhi; Zhang, Yan; Yuan, Ming; Fu, Ying

    2017-01-01

    Establishment and maintenance of the polar site are important for root hair tip growth. We previously reported that Arabidopsis (Arabidopsis thaliana) MICROTUBULE-ASSOCIATED PROTEIN18 (MAP18) functions in controlling the direction of pollen tube growth and root hair elongation. Additionally, the Rop GTPase ROP2 was reported as a positive regulator of both root hair initiation and tip growth in Arabidopsis. Both loss of function of ROP2 and knockdown of MAP18 lead to a decrease in root hair length, whereas overexpression of either MAP18 or ROP2 causes multiple tips or a branching hair phenotype. However, it is unclear whether MAP18 and ROP2 coordinately regulate root hair growth. In this study, we demonstrate that MAP18 and ROP2 interact genetically and functionally. MAP18 interacts physically with ROP2 in vitro and in vivo and preferentially binds to the inactive form of the ROP2 protein. MAP18 promotes ROP2 activity during root hair tip growth. Further investigation revealed that MAP18 competes with RhoGTPase GDP DISSOCIATION INHIBITOR1/SUPERCENTIPEDE1 for binding to ROP2, in turn affecting the localization of active ROP2 in the plasma membrane of the root hair tip. These results reveal a novel function of MAP18 in the regulation of ROP2 activation during root hair growth. PMID:28314794

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

  1. Whole-brain activity mapping onto a zebrafish brain atlas.

    PubMed

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

  2. Intercreativity: Mapping Online Activism

    NASA Astrophysics Data System (ADS)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  3. Echo Mapping of Active Galactic Nuclei

    NASA Technical Reports Server (NTRS)

    Peterson, B. M.; Horne, K.

    2004-01-01

    Echo mapping makes use of the intrinsic variability of the continuum source in active galactic nuclei to map out the distribution and kinematics of line-emitting gas from its light travel time-delayed response to continuum changes. Echo mapping experiments have yielded sizes for the broad line-emitting region in about three dozen AGNs. The dynamics of the line-emitting gas seem to be dominated by the gravity of the central black hole, enabling measurement of the black-hole masses in AGNs. We discuss requirements for future echo-mapping experiments that will yield the high quality velocity-delay maps of the broad-line region that are needed to determine its physical nature.

  4. GeoMapApp Learning Activities: Grab-and-go inquiry-based geoscience activities that bring cutting-edge technology to the classroom

    NASA Astrophysics Data System (ADS)

    Goodwillie, A. M.; Kluge, S.

    2011-12-01

    NSF-funded GeoMapApp Learning Activities (http://serc.carleton.edu/geomapapp) provide self-contained learning opportunities that are centred around the principles of guided inquiry. The activities allow students to interact with and analyse research-quality geoscience data to explore and enhance student understanding of underlying geoscience content and concepts. Each activity offers ready-to-use step-by-step student instructions and answer sheets that can be downloaded from the web page. Also provided are annotated teacher versions of the worksheets that include teaching tips, additional content and suggestions for further work. Downloadable pre- and post- quizzes tied to each activity help educators gauge the learning progression of their students. Short multimedia tutorials and details on content alignment with state and national teaching standards round out the package of material that comprises each "grab-and-go" activity. GeoMapApp Learning Activities expose students to content and concepts typically found at the community college, high school and introductory undergraduate levels. The activities are based upon GeoMapApp (http://www.geomapapp.org), a free, easy-to-use map-based data exploration and visualisation tool that allows students to access a wide range of geoscience data sets in a virtual lab-like environment. Activities that have so far been created under this project include student exploration of seafloor spreading rates, a study of mass wasting as revealed through geomorphological evidence, and an analysis of plate motion and hotspot traces. The step-by-step instructions and guided inquiry approach lead students through each activity, thus reducing the need for teacher intervention whilst also boosting the time that students can spend on productive exploration and learning. The activities can be used, for example, in a classroom lab with the educator present and as self-paced assignments in an out-of-class setting. GeoMapApp Learning Activities

  5. 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

  6. Site maps and facilities listings

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

    Not Available

    1993-11-01

    In September 1989, a Memorandum of Agreement among DOE offices regarding the environmental management of DOE facilities was signed by appropriate Assistant Secretaries and Directors. This Memorandum of Agreement established the criteria for EM line responsibility. It stated that EM would be responsible for all DOE facilities, operations, or sites (1) that have been assigned to DOE for environmental restoration and serve or will serve no future production need; (2) that are used for the storage, treatment, or disposal of hazardous, radioactive, and mixed hazardous waste materials that have been properly characterized, packaged, and labelled, but are not used formore » production; (3) that have been formally transferred to EM by another DOE office for the purpose of environmental restoration and the eventual return to service as a DOE production facility; or (4) that are used exclusively for long-term storage of DOE waste material and are not actively used for production, with the exception of facilities, operations, or sites under the direction of the DOE Office of Civilian Radioactive Waste Management. As part of the implementation of the Memorandum of Agreement, Field Offices within DOE submitted their listings of facilities, systems, operation, and sites for which EM would have line responsibility. It is intended that EM facility listings will be revised on a yearly basis so that managers at all levels will have a valid reference for the planning, programming, budgeting and execution of EM activities.« less

  7. Teaching Basic Geographical Skills: Map and Compass Activities.

    ERIC Educational Resources Information Center

    Trussell, Margaret Edith

    1986-01-01

    Presents a unit on map and compass activities which introduces compass direction, magnetic declination and conversion of map measurement to familiar units. Requires four, one-hour class meetings and may be followed by a half-day orienteering activity. (Author/JDH)

  8. The role of photogeologic mapping in traverse planning: Lessons from DRATS 2010 activities

    USGS Publications Warehouse

    Skinner, James A.; Fortezzo, Corey M.

    2013-01-01

    We produced a 1:24,000 scale photogeologic map of the Desert Research and Technology Studies (DRATS) 2010 simulated lunar mission traverse area and surrounding environments located within the northeastern part of the San Francisco Volcanic Field (SFVF), north-central Arizona. To mimic an exploratory mission, we approached the region “blindly” by rejecting prior knowledge or preconceived notions of the regional geologic setting and focused instead only on image and topographic base maps that were intended to be equivalent to pre-cursor mission “orbital returns”. We used photogeologic mapping techniques equivalent to those employed during the construction of modern planetary geologic maps. Based on image and topographic base maps, we identified 4 surficial units (talus, channel, dissected, and plains units), 5 volcanic units (older cone, younger cone, older flow, younger flow, and block field units), and 5 basement units (grey-toned mottled, red-toned platy, red-toned layered, light-toned slabby, and light-toned layered units). Comparison of our remote-based map units with published field-based map units indicates that the two techniques yield pervasively similar results of contrasting detail, with higher accuracies linked to remote-based units that have high topographic relief and tonal contrast relative to adjacent units. We list key scientific questions that remained after photogeologic mapping and prior to DRATS activities and identify 13 specific observations that the crew and science team would need to make in order to address those questions and refine the interpreted geologic context. We translated potential observations into 62 recommended sites for visitation and observation during the mission traverse. The production and use of a mission-specific photogeologic map for DRATS 2010 activities resulted in strategic and tactical recommendations regarding observational context and hypothesis tracking over the course of an exploratory mission.

  9. Mixture model based joint-MAP reconstruction of attenuation and activity maps in TOF-PET

    NASA Astrophysics Data System (ADS)

    Hemmati, H.; Kamali-Asl, A.; Ghafarian, P.; Ay, M. R.

    2018-06-01

    A challenge to have quantitative positron emission tomography (PET) images is to provide an accurate and patient-specific photon attenuation correction. In PET/MR scanners, the nature of MR signals and hardware limitations have led to a real challenge on the attenuation map extraction. Except for a constant factor, the activity and attenuation maps from emission data on TOF-PET system can be determined by the maximum likelihood reconstruction of attenuation and activity approach (MLAA) from emission data. The aim of the present study is to constrain the joint estimations of activity and attenuation approach for PET system using a mixture model prior based on the attenuation map histogram. This novel prior enforces non-negativity and its hyperparameters can be estimated using a mixture decomposition step from the current estimation of the attenuation map. The proposed method can also be helpful on the solving of scaling problem and is capable to assign the predefined regional attenuation coefficients with some degree of confidence to the attenuation map similar to segmentation-based attenuation correction approaches. The performance of the algorithm is studied with numerical and Monte Carlo simulations and a phantom experiment and was compared with MLAA algorithm with and without the smoothing prior. The results demonstrate that the proposed algorithm is capable of producing the cross-talk free activity and attenuation images from emission data. The proposed approach has potential to be a practical and competitive method for joint reconstruction of activity and attenuation maps from emission data on PET/MR and can be integrated on the other methods.

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

    PubMed

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

    2015-01-01

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

  11. BOREAS TE-23 Map Plot Data

    NASA Technical Reports Server (NTRS)

    Rich, Paul M.; Fournier, Robert; Hall, Forrest G. (Editor); Papagno, Andrea (Editor)

    2000-01-01

    The Boreal Ecosystem-Atmospheric Study (BOREAS) TE-23 (Terrestrial Ecology) team collected map plot data in support of its efforts to characterize and interpret information on canopy architecture and understory cover at the BOREAS tower flux sites and selected auxiliary sites from May to August 1994. Mapped plots (typical dimensions 50 m x 60 m) were set up and characterized at all BOREAS forested tower flux and selected auxiliary sites. Detailed measurement of the mapped plots included: (1) stand characteristics (location, density, basal area); (2) map locations diameter at breast height (DBH) of all trees; (3) detailed geometric measures of a subset of trees (height, crown dimensions); and (4) understory cover maps. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  12. Sentinel-1 data exploitation for geohazard activity map generation

    NASA Astrophysics Data System (ADS)

    Barra, Anna; Solari, Lorenzo; Béjar-Pizarro, Marta; Monserrat, Oriol; Herrera, Gerardo; Bianchini, Silvia; Crosetto, Michele; María Mateos, Rosa; Sarro, Roberto; Moretti, Sandro

    2017-04-01

    This work is focused on geohazard mapping and monitoring by exploiting Sentinel-1 (A and B) data and the DInSAR (Differential interferometric SAR (Synthetic Aperture Radar)) techniques. Sometimes the interpretation of the DInSAR derived product (like the velocity map) can be complex, mostly for a final user who do not usually works with radar. The aim of this work is to generate, in a rapid way, a clear product to be easily exploited by the authorities in the geohazard management: intervention planning and prevention activities. Specifically, the presented methodology has been developed in the framework of the European project SAFETY, which is aimed at providing Civil Protection Authorities (CPA) with the capability of periodically evaluating and assessing the potential impact of geohazards (volcanic activity, earthquakes, landslides and subsidence) on urban areas. The methodology has three phases, the interferograms generation, the activity map generation, in terms of velocity and accumulated deformation (with time-series), and the Active Deformation Area (ADA) map generation. The last one is the final product, derived from the original activity map by analyzing the data in a Geographic Information System (GIS) environment, which isolate only the true deformation areas over the noise. This product can be more easily read by the authorities than the original activity map, i.e. can be better exploited to integrate other information and analysis. This product also permit an easy monitoring of the active areas.

  13. Usefulness of ventricular endocardial electric reconstruction from body surface potential maps to noninvasively localize ventricular ectopic activity in patients

    NASA Astrophysics Data System (ADS)

    Lai, Dakun; Sun, Jian; Li, Yigang; He, Bin

    2013-06-01

    As radio frequency (RF) catheter ablation becomes increasingly prevalent in the management of ventricular arrhythmia in patients, an accurate and rapid determination of the arrhythmogenic site is of important clinical interest. The aim of this study was to test the hypothesis that the inversely reconstructed ventricular endocardial current density distribution from body surface potential maps (BSPMs) can localize the regions critical for maintenance of a ventricular ectopic activity. Patients with isolated and monomorphic premature ventricular contractions (PVCs) were investigated by noninvasive BSPMs and subsequent invasive catheter mapping and ablation. Equivalent current density (CD) reconstruction (CDR) during symptomatic PVCs was obtained on the endocardial ventricular surface in six patients (four men, two women, years 23-77), and the origin of the spontaneous ectopic activity was localized at the location of the maximum CD value. Compared with the last (successful) ablation site (LAS), the mean and standard deviation of localization error of the CDR approach were 13.8 and 1.3 mm, respectively. In comparison, the distance between the LASs and the estimated locations of an equivalent single moving dipole in the heart was 25.5 ± 5.5 mm. The obtained CD distribution of activated sources extending from the catheter ablation site also showed a high consistency with the invasively recorded electroanatomical maps. The noninvasively reconstructed endocardial CD distribution is suitable to predict a region of interest containing or close to arrhythmia source, which may have the potential to guide RF catheter ablation.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed

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

    2015-12-01

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

  16. 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

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

    DOE PAGES

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

    2017-12-15

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

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

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

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

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

  19. GeoMapApp Learning Activities: A Virtual Lab Environment for Student-Centred Engagement with Geoscience Data

    NASA Astrophysics Data System (ADS)

    Kluge, S.; Goodwillie, A. M.

    2012-12-01

    As STEM learning requirements enter the mainstream, there is benefit to providing the tools necessary for students to engage with research-quality geoscience data in a cutting-edge, easy-to-use map-based interface. Funded with an NSF GeoEd award, GeoMapApp Learning Activities ( http://serc.carleton.edu/geomapapp/collection.html ) are being created to help in that endeavour. GeoMapApp Learning Activities offer step-by-step instructions within a guided inquiry approach that enables students to dictate the pace of learning. Based upon GeoMapApp (http://www.geomapapp.org), a free, easy-to-use map-based data exploration and visualisation tool, each activity furnishes the educator with an efficient package of downloadable documents. This includes step-by-step student instructions and answer sheet; an educator's annotated worksheet containing teaching tips, additional content and suggestions for further work; and, quizzes for use before and after the activity to assess learning. Examples of activities so far created involve calculation and analysis of the rate of seafloor spreading; compilation of present-day evidence for huge ancient landslides on the seafloor around the Hawaiian islands; a study of radiometrically-dated volcanic rocks to help understand the concept of hotspots; and, the optimisation of contours as a means to aid visualisation of 3-D data sets on a computer screen. The activities are designed for students at the introductory undergraduate, community college and high school levels, and present a virtual lab-like environment to expose students to content and concepts typically found in those educational settings. The activities can be used in the classroom or out of class, and their guided nature means that the requirement for teacher intervention is reduced thus allowing students to spend more time analysing and understanding geoscience data, content and concepts. Each activity is freely available through the SERC-Carleton web site.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    USGS Publications Warehouse

    Malpeli, Katherine C.; Chirico, Peter G.

    2015-01-01

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

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

    NASA Technical Reports Server (NTRS)

    2007-01-01

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

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

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

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

  3. 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.

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed

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

    2014-08-27

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

  6. Normal Modes Expose Active Sites in Enzymes.

    PubMed

    Glantz-Gashai, Yitav; Meirson, Tomer; Samson, Abraham O

    2016-12-01

    Accurate prediction of active sites is an important tool in bioinformatics. Here we present an improved structure based technique to expose active sites that is based on large changes of solvent accessibility accompanying normal mode dynamics. The technique which detects EXPOsure of active SITes through normal modEs is named EXPOSITE. The technique is trained using a small 133 enzyme dataset and tested using a large 845 enzyme dataset, both with known active site residues. EXPOSITE is also tested in a benchmark protein ligand dataset (PLD) comprising 48 proteins with and without bound ligands. EXPOSITE is shown to successfully locate the active site in most instances, and is found to be more accurate than other structure-based techniques. Interestingly, in several instances, the active site does not correspond to the largest pocket. EXPOSITE is advantageous due to its high precision and paves the way for structure based prediction of active site in enzymes.

  7. Normal Modes Expose Active Sites in Enzymes

    PubMed Central

    Glantz-Gashai, Yitav; Samson, Abraham O.

    2016-01-01

    Accurate prediction of active sites is an important tool in bioinformatics. Here we present an improved structure based technique to expose active sites that is based on large changes of solvent accessibility accompanying normal mode dynamics. The technique which detects EXPOsure of active SITes through normal modEs is named EXPOSITE. The technique is trained using a small 133 enzyme dataset and tested using a large 845 enzyme dataset, both with known active site residues. EXPOSITE is also tested in a benchmark protein ligand dataset (PLD) comprising 48 proteins with and without bound ligands. EXPOSITE is shown to successfully locate the active site in most instances, and is found to be more accurate than other structure-based techniques. Interestingly, in several instances, the active site does not correspond to the largest pocket. EXPOSITE is advantageous due to its high precision and paves the way for structure based prediction of active site in enzymes. PMID:28002427

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

    PubMed

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

    2000-01-01

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

  9. Three-dimensional representations of salt-dome margins at four active strategic petroleum reserve sites.

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

    Rautman, Christopher Arthur; Stein, Joshua S.

    2003-01-01

    Existing paper-based site characterization models of salt domes at the four active U.S. Strategic Petroleum Reserve sites have been converted to digital format and visualized using modern computer software. The four sites are the Bayou Choctaw dome in Iberville Parish, Louisiana; the Big Hill dome in Jefferson County, Texas; the Bryan Mound dome in Brazoria County, Texas; and the West Hackberry dome in Cameron Parish, Louisiana. A new modeling algorithm has been developed to overcome limitations of many standard geological modeling software packages in order to deal with structurally overhanging salt margins that are typical of many salt domes. Thismore » algorithm, and the implementing computer program, make use of the existing interpretive modeling conducted manually using professional geological judgement and presented in two dimensions in the original site characterization reports as structure contour maps on the top of salt. The algorithm makes use of concepts of finite-element meshes of general engineering usage. Although the specific implementation of the algorithm described in this report and the resulting output files are tailored to the modeling and visualization software used to construct the figures contained herein, the algorithm itself is generic and other implementations and output formats are possible. The graphical visualizations of the salt domes at the four Strategic Petroleum Reserve sites are believed to be major improvements over the previously available two-dimensional representations of the domes via conventional geologic drawings (cross sections and contour maps). Additionally, the numerical mesh files produced by this modeling activity are available for import into and display by other software routines. The mesh data are not explicitly tabulated in this report; however an electronic version in simple ASCII format is included on a PC-based compact disk.« less

  10. Mapping recent chikungunya activity in the Americas

    USDA-ARS?s Scientific Manuscript database

    To better understand chikungunya activity in the America we mapped recent chikungunya activity in the Americas. This activity is needed to better understand that the relationships between climatic factors and disease outbreak patters are critical to the design and constructing of predictive models....

  11. International Map Year: Results and Implications

    NASA Astrophysics Data System (ADS)

    Rystedt, Bengt; Ormeling, Ferjan; Buckley, Aileen; Coetzee, Serena; Voženilek, Vit; Fairbairn, David; Kagawa, Ayako

    2018-05-01

    IMY was a worldwide celebration of maps and their unique role in our world. Supported by the United Nations, IMY provides opportunities to demonstrate, follow, and get involved in the art, science, and technology of making and using maps and geographic information. International Map Year (IMY) started in Paris 2011 when the General Assembly of the International Cartographic Association (ICA) asked the ICA Executive Committee (EC) to follow up on the proposal given in a motion from the Swedish Cartographic Society. An IMY Working Group (WG) was constituted - it defined the IMY goals and the activities required to reach them, and it proposed a suitable time period for the IMY to the ICA EC. IMY commenced in August 2015 and ended in December 2016. The success of IMY was dependent on all member nations of the ICA participating in an effort to broaden the knowledge of cartography and geographic information in society in general, especially among citizens and school children. Member nations of the ICA were responsible for organizing IMY activities, such as a national Map Day, through national IMY committees tasked to engage national organizations and spearheading collaboration. The IMY WG set up an IMY web site with general information on IMY, guidelines for how to organize Map Days, suggestions relating to activities aimed at general map awareness, and more. The web site also provides access to the electronic book The World of Maps, which has been translated from English into five other languages.

  12. Cardiac conduction velocity estimation from sequential mapping assuming known Gaussian distribution for activation time estimation error.

    PubMed

    Shariat, Mohammad Hassan; Gazor, Saeed; Redfearn, Damian

    2016-08-01

    In this paper, we study the problem of the cardiac conduction velocity (CCV) estimation for the sequential intracardiac mapping. We assume that the intracardiac electrograms of several cardiac sites are sequentially recorded, their activation times (ATs) are extracted, and the corresponding wavefronts are specified. The locations of the mapping catheter's electrodes and the ATs of the wavefronts are used here for the CCV estimation. We assume that the extracted ATs include some estimation errors, which we model with zero-mean white Gaussian noise values with known variances. Assuming stable planar wavefront propagation, we derive the maximum likelihood CCV estimator, when the synchronization times between various recording sites are unknown. We analytically evaluate the performance of the CCV estimator and provide its mean square estimation error. Our simulation results confirm the accuracy of the proposed method and the error analysis of the proposed CCV estimator.

  13. Spatial resolution of pace mapping of idiopathic ventricular tachycardia/ectopy originating in the right ventricular outflow tract.

    PubMed

    Bogun, Frank; Taj, Majid; Ting, Michael; Kim, Hyungjin Myra; Reich, Stephen; Good, Eric; Jongnarangsin, Krit; Chugh, Aman; Pelosi, Frank; Oral, Hakan; Morady, Fred

    2008-03-01

    Pace mapping has been used to identify the site of origin of focal ventricular arrhythmias. The spatial resolution of pace mapping has not been adequately quantified using currently available three-dimensional mapping systems. The purpose of this study was to determine the spatial resolution of pace mapping in patients with idiopathic ventricular tachycardia or premature ventricular contractions originating in the right ventricular outflow tract. In 16 patients with idiopathic ventricular tachycardia/ectopy from the right ventricular outflow tract, comparisons and classifications of pace maps were performed by two observers (good pace map: match >10/12 leads; inadequate pace map: match < or =10/12 leads) and a customized MATLAB 6.0 program (assessing correlation coefficient and normalized root mean square of the difference (nRMSd) between test and template signals). With an electroanatomic mapping system, the correlation coefficient of each pace map was correlated with the distance between the pacing site and the effective ablation site. The endocardial area within the 10-ms activation isochrone was measured. The ablation procedure was effective in all patients. Sites with good pace maps had a higher correlation coefficient and lower nRMSd than sites with inadequate pace maps (correlation coefficient: 0.96 +/- 0.03 vs 0.76 +/- 0.18, P <.0001; nRMSd: 0.41 +/- 0.16 vs 0.89 +/- 0.39, P <.0001). Using receiver operating characteristic curves, appropriate cutoff values were >0.94 for correlation coefficient (sensitivity 81%, specificity 89%) and < or =0.54 for nRMSd (sensitivity 76%, specificity 80%). Good pace maps were located a mean of 7.3 +/- 5.0 mm from the effective ablation site and had a mean activation time of -24 +/- 7 ms. However, in 3 (18%) of 16 patients, the best pace map was inadequate at the effective ablation site, with an endocardial activation time at these sites of -25 +/- 12 ms. Pace maps with correlation coefficient > or =0.94 were confined to an

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

    PubMed

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

    2017-07-03

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

  15. A global tectonic activity map with orbital photographic supplement

    NASA Technical Reports Server (NTRS)

    Lowman, P. D., Jr.

    1981-01-01

    A three part map showing equatorial and polar regions was compiled showing tectonic and volcanic activity of the past one million years, including the present. Features shown include actively spreading ridges, spreading rates, major active faults, subduction zones, well defined plates, and volcanic areas active within the past one million years. Activity within this period was inferred from seismicity (instrumental and historic), physiography, and published literature. The tectonic activity map was used for planning global geodetic programs of satellite laser ranging and very long base line interferometry and for geologic education.

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

    PubMed

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

    2008-01-01

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

  17. 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.

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

    PubMed

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

    2017-07-01

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

  19. Microstructure-scaled active sites imaging of a solid oxide fuel cell composite cathode

    NASA Astrophysics Data System (ADS)

    Nagasawa, Tsuyoshi; Hanamura, Katsunori

    2017-11-01

    Active sites for oxygen reduction reaction in strontium-doped lanthanum manganite (LSM)/scandia-stabilized zirconia (ScSZ) composite cathode of solid oxide fuel cell (SOFC) is visualized in microstructure scale by oxygen isotope labeling. In order to quench a reaction, a SOFC power generation equipment with a nozzle for direct helium gas impinging jet to the cell is prepared. A typical electrolyte-supported cell is operated by supplying 18O2 at 1073 K and abruptly quenched to room temperature. During the quench, the temperature of the cell is decreased from 1073 K to 673 K in 1 s. The 18O concentration distribution in the cross section of the quenched cathode is obtained by secondary ion mass spectrometry (SIMS) with a spatial resolution of 50 nm. The obtained 18O mapping gives the first visualization of highly distributed active sites in the composite cathode both in macroscopic and particle scales.

  20. Mapping International Cancer Activities – Global Cancer Project Map Launch

    Cancer.gov

    CGH’s Dr. Sudha Sivaram, Dr. Makeda Williams, and Ms. Kalina Duncan have partnered with Drs. Ami Bhatt and Franklin Huang at Global Oncology, Inc. (GO) to develop the Global Cancer Project Map - a web-based tool designed to facilitate cancer research and control activity planning.

  1. Active-site monovalent cations revealed in a 1.55-Å-resolution hammerhead ribozyme structure.

    PubMed

    Anderson, Michael; Schultz, Eric P; Martick, Monika; Scott, William G

    2013-10-23

    We have obtained a 1.55-Å crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni under conditions that permit detailed observations of Na(+) ion binding in the ribozyme's active site. At least two such Na(+) ions are observed. The first Na(+) ion binds to the N7 of G10.1 and the adjacent A9 phosphate in a manner identical with that previously observed for divalent cations. A second Na(+) ion binds to the Hoogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissipating the negative charge of the catalytically active enolate form of the nucleotide base. A potential but more ambiguous third site bridges the A9 and scissile phosphates in a manner consistent with that of previous predictions. Hammerhead ribozymes have been observed to be active in the presence of high concentrations of monovalent cations, including Na(+), but the mechanism by which monovalent cations substitute for divalent cations in hammerhead catalysis remains unclear. Our results enable us to suggest that Na(+) directly and specifically substitutes for divalent cations in the hammerhead active site. The detailed geometry of the pre-catalytic active-site complex is also revealed with a new level of precision, thanks to the quality of the electron density maps obtained from what is currently the highest-resolution ribozyme structure in the Protein Data Bank. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. 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

  3. Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues.

    PubMed

    Molenaar, Remco J; Khurshed, Mohammed; Hira, Vashendriya V V; Van Noorden, Cornelis J F

    2018-05-26

    Altered cellular metabolism is a hallmark of many diseases, including cancer, cardiovascular diseases and infection. The metabolic motor units of cells are enzymes and their activity is heavily regulated at many levels, including the transcriptional, mRNA stability, translational, post-translational and functional level. This complex regulation means that conventional quantitative or imaging assays, such as quantitative mRNA experiments, Western Blots and immunohistochemistry, yield incomplete information regarding the ultimate activity of enzymes, their function and/or their subcellular localization. Quantitative enzyme cytochemistry and histochemistry (i.e., metabolic mapping) show in-depth information on in situ enzymatic activity and its kinetics, function and subcellular localization in an almost true-to-nature situation. We describe a protocol to detect the activity of dehydrogenases, which are enzymes that perform redox reactions to reduce cofactors such as NAD(P) + and FAD. Cells and tissue sections are incubated in a medium that is specific for the enzymatic activity of one dehydrogenase. Subsequently, the dehydrogenase that is the subject of investigation performs its enzymatic activity in its subcellular site. In a chemical reaction with the reaction medium, this ultimately generates blue-colored formazan at the site of the dehydrogenase's activity. The formazan's absorbance is therefore a direct measure of the dehydrogenase's activity and can be quantified using monochromatic light microscopy and image analysis. The quantitative aspect of this protocol enables researchers to draw statistical conclusions from these assays. Besides observational studies, this technique can be used for inhibition studies of specific enzymes. In this context, studies benefit from the true-to-nature advantages of metabolic mapping, giving in situ results that may be physiologically more relevant than in vitro enzyme inhibition studies. In all, metabolic mapping is an

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

    PubMed Central

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

    2015-01-01

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

  5. Susceptibility-based functional brain mapping by 3D deconvolution of an MR-phase activation map.

    PubMed

    Chen, Zikuan; Liu, Jingyu; Calhoun, Vince D

    2013-05-30

    The underlying source of T2*-weighted magnetic resonance imaging (T2*MRI) for brain imaging is magnetic susceptibility (denoted by χ). T2*MRI outputs a complex-valued MR image consisting of magnitude and phase information. Recent research has shown that both the magnitude and the phase images are morphologically different from the source χ, primarily due to 3D convolution, and that the source χ can be reconstructed from complex MR images by computed inverse MRI (CIMRI). Thus, we can obtain a 4D χ dataset from a complex 4D MR dataset acquired from a brain functional MRI study by repeating CIMRI to reconstruct 3D χ volumes at each timepoint. Because the reconstructed χ is a more direct representation of neuronal activity than the MR image, we propose a method for χ-based functional brain mapping, which is numerically characterised by a temporal correlation map of χ responses to a stimulant task. Under the linear imaging conditions used for T2*MRI, we show that the χ activation map can be calculated from the MR phase map by CIMRI. We validate our approach using numerical simulations and Gd-phantom experiments. We also analyse real data from a finger-tapping visuomotor experiment and show that the χ-based functional mapping provides additional activation details (in the form of positive and negative correlation patterns) beyond those generated by conventional MR-magnitude-based mapping. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Black and Brown Bear Activity at Selected Coastal Sites in Glacier Bay National Park and Preserve, Alaska: A Preliminary Assessment Using Noninvasive Procedures

    USGS Publications Warehouse

    Partridge, Steve; Smith, Tom; Lewis, Tania

    2009-01-01

    A number of efforts in recent years have sought to predict bear activity in various habitats to minimize human disturbance and bear/human conflicts. Alaskan coastal areas provide important foraging areas for bears (Ursus americanus and U. arctos), particularly following den emergence when there may be no snow-free foraging alternatives. Additionally, coastal areas provide important food items for bears throughout the year. Glacier Bay National Park and Preserve (GLBA) in southeastern Alaska has extensive coastal habitats, and the National Park Service (NPS) has been long interested in learning more about the use of these coastal habitats by bears because these same habitats receive extensive human use by park visitors, especially kayaking recreationists. This study provides insight regarding the nature and intensity of bear activity at selected coastal sites within GLBA. We achieved a clearer understanding of bear/habitat relationships within GLBA by analyzing bear activity data collected with remote cameras, bear sign mapping, scat collections, and genetic analysis of bear hair. Although we could not quantify actual levels of bear activity at study sites, agreement among measures of activity (for example, sign counts, DNA analysis, and video record) lends support to our qualitative site assessments. This work suggests that habitat evaluation, bear sign mapping, and periodic scat counts can provide a useful index of bear activity for sites of interest.

  7. Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation.

    PubMed

    Zaman, Junaid A B; Sauer, William H; Alhusseini, Mahmood I; Baykaner, Tina; Borne, Ryan T; Kowalewski, Christopher A B; Busch, Sonia; Zei, Paul C; Park, Shirley; Viswanathan, Mohan N; Wang, Paul J; Brachmann, Johannes; Krummen, David E; Miller, John M; Rappel, Wouter Jan; Narayan, Sanjiv M; Peters, Nicholas S

    2018-01-01

    The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation. We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms. Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation. © 2018 American Heart Association, Inc.

  8. Language Mapping with Navigated Repetitive TMS: Proof of Technique and Validation

    PubMed Central

    Tarapore, Phiroz E.; Findlay, Anne M.; Honma, Susanne M.; Mizuiri, Danielle; Houde, John F.; Berger, Mitchel S.; Nagarajan, Srikantan S.

    2013-01-01

    Objective Lesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS. Methods Subjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared. Results nTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects

  9. Activities for Plate Tectonics using GeoMapApp

    NASA Astrophysics Data System (ADS)

    Goodwillie, A. M.

    2016-12-01

    The concept of plate tectonics is a fundamental component of our understanding of how Earth works yet authentic, high-quality geoscience data related to plate tectonics may not be readily available to all students. To compound matters, when data is accessible, students may not possess the skills or resources necessary to explore and analyse it. As a result, much emphasis at federal and state level is now placed upon encouraging students to work with more data and more technology more often and more rigourously. Easy-to-use digital platforms offer much potential for promoting inquiry-based learning at all levels of education. GeoMapApp is one such tool. Developed at Columbia University's Lamont-Doherty Earth Observatory, GeoMapApp (http://www.geomapapp.org) is a free resource that integrates a wide range of research-grade geoscience data in one intuitive map-based interface. Simple strategies for data manipulation, visualisation and presentation allow uses to explore the data in meaningful ways. Layering and transparency capabilities further allow learners to use GeoMapApp to compare multiple data sets at once, and high-impact Save Session functionality allows a GeoMapApp project to be saved for sharing or later use. In this presentation, activities related to plate tectonics will be highlighted. One GeoMapApp activity helps students investigate plate boundaries by exploring earthquake and volcano locations. Another requires students to calculate the rate of seafloor spreading using crustal age data in various ocean basins. A third uses the GeoMapApp layering technique to explore the influence of geological forces in shaping the landscape. Each activity shown can be done by students on an individual basis, as pairs, or as groups. Educators report that student use of GeoMapApp fosters an increased sense of data "ownership" amongst students, promotes STEM skills, and provides them with access to authentic research-grade geoscience data using the same cutting

  10. LUNAR SITE MAP (APOLLO XV) - MSC

    NASA Image and Video Library

    1971-07-16

    S71-40085 (July 1971) --- An enlarged Lunar Orbiter photograph of the Apollo 15 landing area in the Hadley-Apennine region on the nearside of the moon. The overlay indicates the location of the numerous informally-named surface features. These names will facilitate understanding the verbal descriptions from the astronauts during their lunar surface extravehicular activity (EVA). This is an August 1967, Lunar Orbiter V photograph of Site 26.1.

  11. Genome-wide mapping of autonomous promoter activity in human cells

    PubMed Central

    van Arensbergen, Joris; FitzPatrick, Vincent D.; de Haas, Marcel; Pagie, Ludo; Sluimer, Jasper; Bussemaker, Harmen J.; van Steensel, Bas

    2017-01-01

    Previous methods to systematically characterize sequence-intrinsic activity of promoters have been limited by relatively low throughput and the length of sequences that could be tested. Here we present Survey of Regulatory Elements (SuRE), a method to assay more than 108 DNA fragments, each 0.2–2kb in size, for their ability to drive transcription autonomously. In SuRE, a plasmid library is constructed of random genomic fragments upstream of a 20bp barcode and decoded by paired-end sequencing. This library is then transfected into cells and transcribed barcodes are quantified in the RNA by high throughput sequencing. When applied to the human genome, we achieved a 55-fold genome coverage, allowing us to map autonomous promoter activity genome-wide. By computational modeling we delineated subregions within promoters that are relevant for their activity. For instance, we show that antisense promoter transcription is generally dependent on the sense core promoter sequences, and that most enhancers and several families of repetitive elements act as autonomous transcription initiation sites. PMID:28024146

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

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  13. Genome-wide mapping of DNase I hypersensitive sites in rare cell populations using single-cell DNase sequencing.

    PubMed

    Cooper, James; Ding, Yi; Song, Jiuzhou; Zhao, Keji

    2017-11-01

    Increased chromatin accessibility is a feature of cell-type-specific cis-regulatory elements; therefore, mapping of DNase I hypersensitive sites (DHSs) enables the detection of active regulatory elements of transcription, including promoters, enhancers, insulators and locus-control regions. Single-cell DNase sequencing (scDNase-seq) is a method of detecting genome-wide DHSs when starting with either single cells or <1,000 cells from primary cell sources. This technique enables genome-wide mapping of hypersensitive sites in a wide range of cell populations that cannot be analyzed using conventional DNase I sequencing because of the requirement for millions of starting cells. Fresh cells, formaldehyde-cross-linked cells or cells recovered from formalin-fixed paraffin-embedded (FFPE) tissue slides are suitable for scDNase-seq assays. To generate scDNase-seq libraries, cells are lysed and then digested with DNase I. Circular carrier plasmid DNA is included during subsequent DNA purification and library preparation steps to prevent loss of the small quantity of DHS DNA. Libraries are generated for high-throughput sequencing on the Illumina platform using standard methods. Preparation of scDNase-seq libraries requires only 2 d. The materials and molecular biology techniques described in this protocol should be accessible to any general molecular biology laboratory. Processing of high-throughput sequencing data requires basic bioinformatics skills and uses publicly available bioinformatics software.

  14. Collaborative Concept Mapping Activities in a Classroom Scenario

    ERIC Educational Resources Information Center

    Elorriaga, J. A.; Arruarte, A.; Calvo, I.; Larrañaga, M.; Rueda, U.; Herrán, E.

    2013-01-01

    The aim of this study is to test collaborative concept mapping activities using computers in a classroom scenario and to evaluate the possibilities that Elkar-CM offers for collaboratively learning non-technical topics. Elkar-CM is a multi-lingual and multi-media software program designed for drawing concept maps (CMs) collaboratively. Concept…

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

    PubMed

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

    2017-02-01

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

  16. A gratuitous β-Lactamase inducer uncovers hidden active site dynamics of the Staphylococcus aureus BlaR1 sensor domain.

    PubMed

    Frederick, Thomas E; Peng, Jeffrey W

    2018-01-01

    Increasing evidence shows that active sites of proteins have non-trivial conformational dynamics. These dynamics include active site residues sampling different local conformations that allow for multiple, and possibly novel, inhibitor binding poses. Yet, active site dynamics garner only marginal attention in most inhibitor design efforts and exert little influence on synthesis strategies. This is partly because synthesis requires a level of atomic structural detail that is frequently missing in current characterizations of conformational dynamics. In particular, while the identity of the mobile protein residues may be clear, the specific conformations they sample remain obscure. Here, we show how an appropriate choice of ligand can significantly sharpen our abilities to describe the interconverting binding poses (conformations) of protein active sites. Specifically, we show how 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid (CBAP) exposes otherwise hidden dynamics of a protein active site that binds β-lactam antibiotics. When CBAP acylates (binds) the active site serine of the β-lactam sensor domain of BlaR1 (BlaRS), it shifts the time scale of the active site dynamics to the slow exchange regime. Slow exchange enables direct characterization of inter-converting protein and bound ligand conformations using NMR methods. These methods include chemical shift analysis, 2-d exchange spectroscopy, off-resonance ROESY of the bound ligand, and reduced spectral density mapping. The active site architecture of BlaRS is shared by many β-lactamases of therapeutic interest, suggesting CBAP could expose functional motions in other β-lactam binding proteins. More broadly, CBAP highlights the utility of identifying chemical probes common to structurally homologous proteins to better expose functional motions of active sites.

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

    PubMed

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

    2018-02-20

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

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  19. Functional MRI mapping of category-specific sites associated with naming of famous faces, animals and man-made objects.

    PubMed

    Bai, Hong-Min; Jiang, Tao; Wang, Wei-Min; Li, Tian-Dong; Liu, Yan; Lu, Yi-Cheng

    2011-10-01

    Category-specific recognition and naming deficits have been observed in a variety of patient populations. However, the category-specific cortices for naming famous faces, animals and man-made objects remain controversial. The present study aimed to study the specific areas involved in naming pictures of these 3 categories using functional magnetic resonance imaging. Functional images were analyzed using statistical parametric mapping and the 3 different contrasts were evaluated using t statistics by comparing the naming tasks to their baselines. The contrast images were entered into a random-effects group level analysis. The results were reported in Montreal Neurological Institute coordinates, and anatomical regions were identified using an automated anatomical labeling method with XJview 8. Naming famous faces caused more activation in the bilateral head of the hippocampus and amygdala with significant left dominance. Bilateral activation of pars triangularis and pars opercularis in the naming of famous faces was also revealed. Naming animals evoked greater responses in the left supplementary motor area, while naming man-made objects evoked more in the left premotor area, left pars orbitalis and right supplementary motor area. The extent of bilateral fusiform gyri activation by naming man-made objects was much larger than that by naming of famous faces or animals. Even in the overlapping sites of activation, some differences among the categories were found for activation in the fusiform gyri. The cortices involved in the naming process vary with the naming of famous faces, animals and man-made objects. This finding suggests that different categories of pictures should be used during intra-operative language mapping to generate a broader map of language function, in order to minimize the incidence of false-negative stimulation and permanent post-operative deficits.

  20. Alaska Geothermal Sites Map and Database: Bringing together legacy and new geothermal data for research, exploration and development

    NASA Astrophysics Data System (ADS)

    Clough, J. G.; Harun, N. T.; Hughes, C. A.; Weakland, J. R.; Cameron, C. E.

    2013-12-01

    Geothermal exploration activities in Alaska from the late 1970s into the 1980s generated vast quantities of scientific data that currently is in unpublished, forgotten and obscure, as well as published formats. Alaska has 61 hot springs (hotter than 50°C) and 34 'warm to cool springs' (cooler than 50°C). Thirty-seven thermal springs are located within the Aleutian and Alaska Peninsula volcanic arc into and are related to elevated heat flows in areas of arc volcanism as well as crustal scale faults associated with accretionary tectonism. The central interior belt that extends from the Seward Peninsula to Circle Hot Springs contains 37 thermal springs that formed due to mostly extensional tectonic forces. An additional 17 thermal springs are in southeast Alaska and 4 are in the Wrangell Mountains. A new cycle of geothermal exploration is underway in Alaska and is producing a wealth of new geothermal data. The Alaska Division of Geological and Geophysical Surveys (ADGGS), funded by the National Geothermal Data System, is compiling both new and legacy geothermal data into a comprehensive database accessible on the ADGGS website. ADGGS has created a new ';Geothermal Sites of Alaska Map' and associated database that includes data on geothermal hot springs, direct use of geothermal resources, volcanic vents, aqueous geochemistry, borehole temperatures, core descriptions, rock chemistry, earthquakes in proximity to hot springs, and active faults. Geothermal hot springs includes locality, temperature, flow rate, sources and related resources. Direct use of geothermal resources contains facilities, capacity, energy use, temperature, flow rate and contact information from geothermal hot springs that are or have recently been used for recreational use, space heating, agricultural or energy use. Volcanic vents records 395 volcanic vents and fumaroles throughout the state that are Holocene or younger. It includes their age, location, elevation, geologic history, composition

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

    NASA Astrophysics Data System (ADS)

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

    1997-11-01

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

  2. The New USGS Volcano Hazards Program Web Site

    NASA Astrophysics Data System (ADS)

    Venezky, D. Y.; Graham, S. E.; Parker, T. J.; Snedigar, S. F.

    2008-12-01

    The U.S. Geological Survey's (USGS) Volcano Hazard Program (VHP) has launched a revised web site that uses a map-based interface to display hazards information for U.S. volcanoes. The web site is focused on better communication of hazards and background volcano information to our varied user groups by reorganizing content based on user needs and improving data display. The Home Page provides a synoptic view of the activity level of all volcanoes for which updates are written using a custom Google® Map. Updates are accessible by clicking on one of the map icons or clicking on the volcano of interest in the adjacent color-coded list of updates. The new navigation provides rapid access to volcanic activity information, background volcano information, images and publications, volcanic hazards, information about VHP, and the USGS volcano observatories. The Volcanic Activity section was tailored for emergency managers but provides information for all our user groups. It includes a Google® Map of the volcanoes we monitor, an Elevated Activity Page, a general status page, information about our Volcano Alert Levels and Aviation Color Codes, monitoring information, and links to monitoring data from VHP's volcano observatories: Alaska Volcano Observatory (AVO), Cascades Volcano Observatory (CVO), Long Valley Observatory (LVO), Hawaiian Volcano Observatory (HVO), and Yellowstone Volcano Observatory (YVO). The YVO web site was the first to move to the new navigation system and we are working on integrating the Long Valley Observatory web site next. We are excited to continue to implement new geospatial technologies to better display our hazards and supporting volcano information.

  3. Active edge maps for medical image registration

    NASA Astrophysics Data System (ADS)

    Kerwin, William; Yuan, Chun

    2001-07-01

    Applying edge detection prior to performing image registration yields several advantages over raw intensity- based registration. Advantages include the ability to register multicontrast or multimodality images, immunity to intensity variations, and the potential for computationally efficient algorithms. In this work, a common framework for edge-based image registration is formulated as an adaptation of snakes used in boundary detection. Called active edge maps, the new formulation finds a one-to-one transformation T(x) that maps points in a source image to corresponding locations in a target image using an energy minimization approach. The energy consists of an image component that is small when edge features are well matched in the two images, and an internal term that restricts T(x) to allowable configurations. The active edge map formulation is illustrated here with a specific example developed for affine registration of carotid artery magnetic resonance images. In this example, edges are identified using a magnitude of gradient operator, image energy is determined using a Gaussian weighted distance function, and the internal energy includes separate, adjustable components that control volume preservation and rigidity.

  4. 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.

  5. Dissecting the active site of a photoreceptor protein

    NASA Astrophysics Data System (ADS)

    Hoff, Wouter; Hara, Miwa; Ren, Jie; Moghadam, Farzaneh; Xie, Aihua; Kumauchi, Masato

    While enzymes are quite large molecules, functionally important chemical events are often limited to a small region of the protein: the active site. The physical and chemical properties of residues at such active sites are often strongly altered compared to the same groups dissolved in water. Understanding such effects is important for unraveling the mechanisms underlying protein function and for protein engineering, but has proven challenging. Here we report on our ongoing efforts on using photoactive yellow protein (PYP), a bacterial photoreceptor, as a model system for such effects. We will report on the following questions: How many residues affect active site properties? Are these residues in direct physical contact with the active site? Can functionally important residues be recognized in the crystal structure of a protein? What structural resolution is needed to understand active sites? What spectroscopic techniques are most informative? Which weak interactions dominate active site properties?

  6. Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

    PubMed

    Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

    1998-08-01

    Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

  7. Active site dynamics of ribonuclease.

    PubMed Central

    Brünger, A T; Brooks, C L; Karplus, M

    1985-01-01

    The stochastic boundary molecular dynamics method is used to study the structure, dynamics, and energetics of the solvated active site of bovine pancreatic ribonuclease A. Simulations of the native enzyme and of the enzyme complexed with the dinucleotide substrate CpA and the transition-state analog uridine vanadate are compared. Structural features and dynamical couplings for ribonuclease residues found in the simulation are consistent with experimental data. Water molecules, most of which are not observed in crystallographic studies, are shown to play an important role in the active site. Hydrogen bonding of residues with water molecules in the free enzyme is found to mimic the substrate-enzyme interactions of residues involved in binding. Networks of water stabilize the cluster of positively charged active site residues. Correlated fluctuations between the uridine vanadate complex and the distant lysine residues are mediated through water and may indicate a possible role for these residues in stabilizing the transition state. Images PMID:3866234

  8. Low dielectric response in enzyme active site

    PubMed Central

    Mertz, Edward L.; Krishtalik, Lev I.

    2000-01-01

    The kinetics of charge transfer depend crucially on the dielectric reorganization of the medium. In enzymatic reactions that involve charge transfer, atomic dielectric response of the active site and of its surroundings determines the efficiency of the protein as a catalyst. We report direct spectroscopic measurements of the reorganization energy associated with the dielectric response in the active site of α-chymotrypsin. A chromophoric inhibitor of the enzyme is used as a spectroscopic probe. We find that water strongly affects the dielectric reorganization in the active site of the enzyme in solution. The reorganization energy of the protein matrix in the vicinity of the active site is similar to that of low-polarity solvents. Surprisingly, water exhibits an anomalously high dielectric response that cannot be described in terms of the dielectric continuum theory. As a result, sequestering the active site from the aqueous environment inside low-dielectric enzyme body dramatically reduces the dielectric reorganization. This reduction is particularly important for controlling the rate of enzymatic reactions. PMID:10681440

  9. An efficient cardiac mapping strategy for radiofrequency catheter ablation with active learning.

    PubMed

    Feng, Yingjing; Guo, Ziyan; Dong, Ziyang; Zhou, Xiao-Yun; Kwok, Ka-Wai; Ernst, Sabine; Lee, Su-Lin

    2017-07-01

    A major challenge in radiofrequency catheter ablation procedures is the voltage and activation mapping of the endocardium, given a limited mapping time. By learning from expert interventional electrophysiologists (operators), while also making use of an active-learning framework, guidance on performing cardiac voltage mapping can be provided to novice operators or even directly to catheter robots. A learning from demonstration (LfD) framework, based upon previous cardiac mapping procedures performed by an expert operator, in conjunction with Gaussian process (GP) model-based active learning, was developed to efficiently perform voltage mapping over right ventricles (RV). The GP model was used to output the next best mapping point, while getting updated towards the underlying voltage data pattern as more mapping points are taken. A regularized particle filter was used to keep track of the kernel hyperparameter used by GP. The travel cost of the catheter tip was incorporated to produce time-efficient mapping sequences. The proposed strategy was validated on a simulated 2D grid mapping task, with leave-one-out experiments on 25 retrospective datasets, in an RV phantom using the Stereotaxis Niobe ® remote magnetic navigation system, and on a tele-operated catheter robot. In comparison with an existing geometry-based method, regression error was reduced and was minimized at a faster rate over retrospective procedure data. A new method of catheter mapping guidance has been proposed based on LfD and active learning. The proposed method provides real-time guidance for the procedure, as well as a live evaluation of mapping sufficiency.

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

    PubMed

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

    2017-01-01

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

  11. Repeat AUV Mapping and ROV Observations of Active Mud Volcanos on the Canadian Beaufort Sea Continental Slope

    NASA Astrophysics Data System (ADS)

    Caress, D. W.; Paull, C. K.; Dallimore, S.; Lundsten, E. M.; Anderson, K.; Gwiazda, R.; Melling, H.; Lundsten, L.; Graves, D.; Thomas, H. J.; Cote, M.

    2017-12-01

    Two active submarine mud volcano sites located at 420 and 740 m depths on the margin of the Canadian Beaufort Sea were mapped in 2013 and again in 2016 using the same survey line pattern allowing detection of change over three years. The surveys were conducted using MBARI's mapping AUVs which fields a 200 kHz or 400 kHz multibeam sonar, a 1-6 kHz chirp sub-bottom profiler, and a 110 kHz chirp sidescan from a 50 m altitude. The resulting bathymetry has 1 m lateral resolution and 0.1 m vertical precision and sidescan mosaics have 1 m lateral resolution. Vertical changes of ≥0.2 m are observable by differencing repeat surveys. These features were also visited with MBARI's miniROV, which was outfitted for these dives with a manipulator mounted temperature probe. The 420 m mud volcano is nearly circular, 1100 m across, flat-topped, and superimposed on the pre-existing smooth slope. The central plateau has low relief <3 m consisting of concentric rings and ovoid mounds that appear to reflect distinct eruptions at shifting locations. The 740 m site contains 3 mud volcanoes, most prominently a 630 m wide, 30 m high flat-topped plateau with about 4 m of relief similar to the 420 m feature plus a 5 m high cone on the southern rim. North of this plateau is a smooth-textured conically shaped feature also standing about 30 m above the floor of the subsidence structure. Sidescan mosaics reveal significant changes in backscatter patterns at both mud volcano sites between surveys. Comparison of bathymetry also reveals new flows of up to 1.8 m thickness at both sites, as well as subtle spreading of the flat plateaus rims. An active mudflow was encountered during a miniROV dive on a high backscatter target at the 740 m site. This tongue of mud was observed to be slowly flowing downslope. The ROV temperature probe inserted 2 cm into the flow measured 23°C, compared to ambient water (-0.4°C), indicating the rapid ascent of the mud from considerable subsurface depths. Bubbles

  12. 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.

  13. Mapping barriers and intervention activities to behaviour change theory for Mobilization of Vulnerable Elders in Ontario (MOVE ON), a multi-site implementation intervention in acute care hospitals.

    PubMed

    Moore, Julia E; Mascarenhas, Alekhya; Marquez, Christine; Almaawiy, Ummukulthum; Chan, Wai-Hin; D'Souza, Jennifer; Liu, Barbara; Straus, Sharon E

    2014-10-30

    As evidence-informed implementation interventions spread, they need to be tailored to address the unique needs of each setting, and this process should be well documented to facilitate replication. To facilitate the spread of the Mobilization of Vulnerable Elders in Ontario (MOVE ON) intervention, the aim of the current study is to develop a mapping guide that links identified barriers and intervention activities to behaviour change theory. Focus groups were conducted with front line health-care professionals to identify perceived barriers to implementation of an early mobilization intervention targeted to hospitalized older adults. Participating units then used or adapted intervention activities from an existing menu or developed new activities to facilitate early mobilization. A thematic analysis was performed on the focus group data, emphasizing concepts related to barriers to behaviour change. A behaviour change theory, the 'capability, opportunity, motivation-behaviour (COM-B) system', was used as a taxonomy to map the identified barriers to their root causes. We also mapped the behaviour constructs and intervention activities to overcome these. A total of 46 focus groups were conducted across 26 hospital inpatient units in Ontario, Canada, with 261 participants. The barriers were conceptualized at three levels: health-care provider (HCP), patient, and unit. Commonly mentioned barriers were time constraints and workload (HCP), patient clinical acuity and their perceived 'sick role' (patient), and lack of proper equipment and human resources (unit level). Thirty intervention activities to facilitate early mobilization of older adults were implemented across hospitals; examples of unit-developed intervention activities include the 'mobility clock' communication tool and the use of staff champions. A mapping guide was created with barriers and intervention activities matched though the lens of the COM-B system. We used a systematic approach to develop a guide

  14. A contact photo-cross-linking investigation of the active site of the 8-17 deoxyribozyme.

    PubMed

    Liu, Yong; Sen, Dipankar

    2008-09-12

    The small RNA-cleaving 8-17 deoxyribozyme (DNAzyme) has been the subject of extensive mechanistic and structural investigation, including a number of recent single-molecule studies of its global folding. Little detailed insight exists, however, into this DNAzyme's active site; for instance, the identity of specific nucleotides that are proximal to or in contact with the scissile site in the substrate. Here, we report a systematic replacement of a number of bases within the magnesium-folded DNAzyme-substrate complex with thio- and halogen-substituted base analogues, which were then photochemically activated to generate contact cross-links within the complex. Mapping of the cross-links revealed a striking pattern of DNAzyme-substrate cross-links but an absence of significant intra-DNAzyme cross-links. Notably, the two nucleotides directly flanking the scissile phosphodiester cross-linked strongly with functionally important elements within the DNAzyme, the thymine of a G.T wobble base pair, a WCGR bulge loop, and a terminal AGC loop. Mutation of the wobble base pair to a G-C pair led to a significant folding instability of the DNAzyme-substrate complex. The cross-linking patterns obtained were used to generate a model for the DNAzyme's active site that had the substrate's scissile phosphodiester sandwiched between the DNAzyme's wobble thymine and its AGC and WCGR loops.

  15. Various abiotic stresses rapidly activate Arabidopsis MAP kinases ATMPK4 and ATMPK6.

    PubMed

    Ichimura, K; Mizoguchi, T; Yoshida, R; Yuasa, T; Shinozaki, K

    2000-12-01

    Mitogen-activated protein kinase (MAP kinase, MAPK) cascades play pivotal roles in signal transduction of extracellular stimuli, such as environmental stresses and growth regulators, in various organisms. Arabidopsis thaliana MAP kinases constitute a gene family, but stimulatory signals for each MAP kinase have not been elucidated. Here we show that environmental stresses such as low temperature, low humidity, hyper-osmolarity, touch and wounding induce rapid and transient activation of the Arabidopsis MAP kinases ATMPK4 and ATMPK6. Activation of ATMPK4 and ATMPK6 was associated with tyrosine phosphorylation but not with the amounts of mRNA or protein. Kinetics during activation differ between these two MAP kinases. These results suggest that ATMPK4 and ATMPK6 are involved in distinct signal transduction pathways responding to these environmental stresses.

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

    PubMed

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

    2016-07-15

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

  17. Epicardial-endocardial breakthrough during stable atrial macroreentry: Evidence from ultra-high-resolution 3-dimensional mapping.

    PubMed

    Pathik, Bhupesh; Lee, Geoffrey; Sacher, Frédéric; Haïssaguerre, Michel; Jaïs, Pierre; Massoullié, Grégoire; Derval, Nicolas; Sanders, Prashanthan; Kistler, Peter; Kalman, Jonathan M

    2017-08-01

    Evidence for epicardial-endocardial breakthrough (EEB) is derived from mapping inferences in patients with atrial fibrillation who may also have focal activations. The purpose of this study was to investigate whether EEB could be discerned during stable right atrial (RA) macroreentry using high-density high-spatial resolution 3-dimensional mapping. Macroreentry was diagnosed using 3-dimensional mapping and entrainment. Bipolar maps were reviewed for EEB defined as (1) presence of focal endocardial activation with radial spread unaccounted for by an endocardial wavefront and (2) present with the same timing on every tachycardia cycle. The EEB site was always in proximity to a line of endocardial conduction slowing or block. Distance and conduction velocity from the line of block to the EEB site was calculated. Electrograms at EEB sites were individually analyzed for morphology and to confirm direction of activation. Entrainment was performed at EEB sites. Twenty-six patients were studied. Fourteen examples of EEB were seen: 11 at the posterior RA (4 at the superior portion of the posterior wall and 7 at the inferior section) and 1 each at the cavotricuspid isthmus postablation, RA septum, and inferolateral RA. The mean area of the EEB site was 0.6 ± 0.2 cm 2 . A mean of 79.5% ± 18.6% of unipolar electrograms at the EEB site demonstrated an rS morphology. The mean distance and conduction velocity from the line of endocardial block to the EEB site at the posterior RA was 13.6 ± 2.3 mm and 59.3 ± 12.3 cm/s, respectively. In 4 patients, entrainment demonstrated that EEB sites were within the circuit and in 1 of these patients critical to arrhythmia maintenance. Activation maps during tachycardia and coronary sinus pacing demonstrated EEB at the same anatomic site. EEB sites were demonstrated in stable atrial macroreentry supported by systematic entrainment confirmation and demonstration of the same phenomenon during pacing. Copyright © 2017 Heart Rhythm Society

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

    PubMed Central

    Jishage, Miki; Dasgupta, Dipak; Ishihama, Akira

    2001-01-01

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

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

    PubMed

    Jishage, M; Dasgupta, D; Ishihama, A

    2001-05-01

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

  20. Activation of phenylalanine hydroxylase by phenylalanine does not require binding in the active site.

    PubMed

    Roberts, Kenneth M; Khan, Crystal A; Hinck, Cynthia S; Fitzpatrick, Paul F

    2014-12-16

    Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein's regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The k(cat)/K(phe) value is down 10⁴ for the mutant enzyme, and the K(m) value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain.

  1. Activation of Phenylalanine Hydroxylase by Phenylalanine Does Not Require Binding in the Active Site

    PubMed Central

    2015-01-01

    Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. The lack of activity at low levels of phenylalanine has been attributed to the N-terminus of the protein’s regulatory domain acting as an inhibitory peptide by blocking substrate access to the active site. The location of the site at which phenylalanine binds to activate the enzyme is unknown, and both the active site in the catalytic domain and a separate site in the N-terminal regulatory domain have been proposed. Binding of catecholamines to the active-site iron was used to probe the accessibility of the active site. Removal of the regulatory domain increases the rate constants for association of several catecholamines with the wild-type enzyme by ∼2-fold. Binding of phenylalanine in the active site is effectively abolished by mutating the active-site residue Arg270 to lysine. The kcat/Kphe value is down 104 for the mutant enzyme, and the Km value for phenylalanine for the mutant enzyme is >0.5 M. Incubation of the R270K enzyme with phenylalanine also results in a 2-fold increase in the rate constants for catecholamine binding. The change in the tryptophan fluorescence emission spectrum seen in the wild-type enzyme upon activation by phenylalanine is also seen with the R270K mutant enzyme in the presence of phenylalanine. Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. This is consistent with a separate allosteric site, likely in the regulatory domain. PMID:25453233

  2. An Inquiry Activity for Genetics Using Chromosome Mapping.

    ERIC Educational Resources Information Center

    Leonard, William H.; Snodgrass, George

    1982-01-01

    Concepts to be developed, objectives, and student instructions are provided for an activity useful as an introduction to or review of Mendelian genetics and sex determination. Universal codes (read by optical scanners at supermarket checkout stands) from soup can labels are used as chromosome maps during the activity. (JN)

  3. Non-competitive inhibition by active site binders.

    PubMed

    Blat, Yuval

    2010-06-01

    Classical enzymology has been used for generations to understand the interactions of inhibitors with their enzyme targets. Enzymology tools enabled prediction of the biological impact of inhibitors as well as the development of novel, more potent, ones. Experiments designed to examine the competition between the tested inhibitor and the enzyme substrate(s) are the tool of choice to identify inhibitors that bind in the active site. Competition between an inhibitor and a substrate is considered a strong evidence for binding of the inhibitor in the active site, while the lack of competition suggests binding to an alternative site. Nevertheless, exceptions to this notion do exist. Active site-binding inhibitors can display non-competitive inhibition patterns. This unusual behavior has been observed with enzymes utilizing an exosite for substrate binding, isomechanism enzymes, enzymes with multiple substrates and/or products and two-step binding inhibitors. In many of these cases, the mechanisms underlying the lack of competition between the substrate and the inhibitor are well understood. Tools like alternative substrates, testing the enzyme reaction in the reverse direction and monitoring inhibition time dependence can be applied to enable distinction between 'badly behaving' active site binders and true exosite inhibitors.

  4. Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch*

    PubMed Central

    Harvey, Beth M.; Rana, Nadia A.; Moss, Hillary; Leonardi, Jessica; Jafar-Nejad, Hamed; Haltiwanger, Robert S.

    2016-01-01

    Glycosylation of the Notch receptor is essential for its activity and serves as an important modulator of signaling. Three major forms of O-glycosylation are predicted to occur at consensus sites within the epidermal growth factor-like repeats in the extracellular domain of the receptor: O-fucosylation, O-glucosylation, and O-GlcNAcylation. We have performed comprehensive mass spectral analyses of these three types of O-glycosylation on Drosophila Notch produced in S2 cells and identified peptides containing all 22 predicted O-fucose sites, all 18 predicted O-glucose sites, and all 18 putative O-GlcNAc sites. Using semiquantitative mass spectral methods, we have evaluated the occupancy and relative amounts of glycans at each site. The majority of the O-fucose sites were modified to high stoichiometries. Upon expression of the β3-N-acetylglucosaminyltransferase Fringe with Notch, we observed varying degrees of elongation beyond O-fucose monosaccharide, indicating that Fringe preferentially modifies certain sites more than others. Rumi modified O-glucose sites to high stoichiometries, although elongation of the O-glucose was site-specific. Although the current putative consensus sequence for O-GlcNAcylation predicts 18 O-GlcNAc sites on Notch, we only observed apparent O-GlcNAc modification at five sites. In addition, we performed mass spectral analysis on endogenous Notch purified from Drosophila embryos and found that the glycosylation states were similar to those found on Notch from S2 cells. These data provide foundational information for future studies investigating the mechanisms of how O-glycosylation regulates Notch activity. PMID:27268051

  5. Safety Oversight of Decommissioning Activities at DOE Nuclear Sites

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

    Zull, Lawrence M.; Yeniscavich, William

    2008-01-15

    The Defense Nuclear Facilities Safety Board (Board) is an independent federal agency established by Congress in 1988 to provide nuclear safety oversight of activities at U.S. Department of Energy (DOE) defense nuclear facilities. The activities under the Board's jurisdiction include the design, construction, startup, operation, and decommissioning of defense nuclear facilities at DOE sites. This paper reviews the Board's safety oversight of decommissioning activities at DOE sites, identifies the safety problems observed, and discusses Board initiatives to improve the safety of decommissioning activities at DOE sites. The decommissioning of former defense nuclear facilities has reduced the risk of radioactive materialmore » contamination and exposure to the public and site workers. In general, efforts to perform decommissioning work at DOE defense nuclear sites have been successful, and contractors performing decommissioning work have a good safety record. Decommissioning activities have recently been completed at sites identified for closure, including the Rocky Flats Environmental Technology Site, the Fernald Closure Project, and the Miamisburg Closure Project (the Mound site). The Rocky Flats and Fernald sites, which produced plutonium parts and uranium materials for defense needs (respectively), have been turned into wildlife refuges. The Mound site, which performed R and D activities on nuclear materials, has been converted into an industrial and technology park called the Mound Advanced Technology Center. The DOE Office of Legacy Management is responsible for the long term stewardship of these former EM sites. The Board has reviewed many decommissioning activities, and noted that there are valuable lessons learned that can benefit both DOE and the contractor. As part of its ongoing safety oversight responsibilities, the Board and its staff will continue to review the safety of DOE and contractor decommissioning activities at DOE defense nuclear sites.« less

  6. Enhanced dispersion of epicardial activation-recovery intervals at sites of histological inhomogeneity during regional cardiac ischaemia and reperfusion

    PubMed Central

    Gottwald, E; Gottwald, M; Dhein, S

    1998-01-01

    Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures.
Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides.
Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged.
Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis. 

 Keywords: dispersion;  epicardial activation-recovery interval;  ischaemia PMID

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

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

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2012-01-01

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

  9. Insurance Applications of Active Fault Maps Showing Epistemic Uncertainty

    NASA Astrophysics Data System (ADS)

    Woo, G.

    2005-12-01

    Insurance loss modeling for earthquakes utilizes available maps of active faulting produced by geoscientists. All such maps are subject to uncertainty, arising from lack of knowledge of fault geometry and rupture history. Field work to undertake geological fault investigations drains human and monetary resources, and this inevitably limits the resolution of fault parameters. Some areas are more accessible than others; some may be of greater social or economic importance than others; some areas may be investigated more rapidly or diligently than others; or funding restrictions may have curtailed the extent of the fault mapping program. In contrast with the aleatory uncertainty associated with the inherent variability in the dynamics of earthquake fault rupture, uncertainty associated with lack of knowledge of fault geometry and rupture history is epistemic. The extent of this epistemic uncertainty may vary substantially from one regional or national fault map to another. However aware the local cartographer may be, this uncertainty is generally not conveyed in detail to the international map user. For example, an area may be left blank for a variety of reasons, ranging from lack of sufficient investigation of a fault to lack of convincing evidence of activity. Epistemic uncertainty in fault parameters is of concern in any probabilistic assessment of seismic hazard, not least in insurance earthquake risk applications. A logic-tree framework is appropriate for incorporating epistemic uncertainty. Some insurance contracts cover specific high-value properties or transport infrastructure, and therefore are extremely sensitive to the geometry of active faulting. Alternative Risk Transfer (ART) to the capital markets may also be considered. In order for such insurance or ART contracts to be properly priced, uncertainty should be taken into account. Accordingly, an estimate is needed for the likelihood of surface rupture capable of causing severe damage. Especially where a

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

    PubMed Central

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

    2010-01-01

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

  11. 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.

  12. Bringing MapReduce Closer To Data With Active Drives

    NASA Astrophysics Data System (ADS)

    Golpayegani, N.; Prathapan, S.; Warmka, R.; Wyatt, B.; Halem, M.; Trantham, J. D.; Markey, C. A.

    2017-12-01

    Moving computation closer to the data location has been a much theorized improvement to computation for decades. The increase in processor performance, the decrease in processor size and power requirement combined with the increase in data intensive computing has created a push to move computation as close to data as possible. We will show the next logical step in this evolution in computing: moving computation directly to storage. Hypothetical systems, known as Active Drives, have been proposed as early as 1998. These Active Drives would have a general-purpose CPU on each disk allowing for computations to be performed on them without the need to transfer the data to the computer over the system bus or via a network. We will utilize Seagate's Active Drives to perform general purpose parallel computing using the MapReduce programming model directly on each drive. We will detail how the MapReduce programming model can be adapted to the Active Drive compute model to perform general purpose computing with comparable results to traditional MapReduce computations performed via Hadoop. We will show how an Active Drive based approach significantly reduces the amount of data leaving the drive when performing several common algorithms: subsetting and gridding. We will show that an Active Drive based design significantly improves data transfer speeds into and out of drives compared to Hadoop's HDFS while at the same time keeping comparable compute speeds as Hadoop.

  13. Ionizable Side Chains at Catalytic Active Sites of Enzymes

    PubMed Central

    Jimenez-Morales, David; Liang, Jie

    2012-01-01

    Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes. PMID:22484856

  14. Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps

    PubMed Central

    2016-01-01

    Abstract Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor‐preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface‐based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory‐motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory‐motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe almost completely overlaps visual maps, whereas a significant portion of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to a small region on the anterior bank of the central sulcus near the border between the face and hand representations of M‐I. Hum Brain Mapp 37:2784–2810, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061771

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

    DOE Data Explorer

    Jaffe, Todd

    2012-01-01

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

  16. Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.

    ERIC Educational Resources Information Center

    Torello, Michael, W.; Duffy, Frank H.

    1985-01-01

    Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)

  17. Discriminative structural approaches for enzyme active-site prediction.

    PubMed

    Kato, Tsuyoshi; Nagano, Nozomi

    2011-02-15

    Predicting enzyme active-sites in proteins is an important issue not only for protein sciences but also for a variety of practical applications such as drug design. Because enzyme reaction mechanisms are based on the local structures of enzyme active-sites, various template-based methods that compare local structures in proteins have been developed to date. In comparing such local sites, a simple measurement, RMSD, has been used so far. This paper introduces new machine learning algorithms that refine the similarity/deviation for comparison of local structures. The similarity/deviation is applied to two types of applications, single template analysis and multiple template analysis. In the single template analysis, a single template is used as a query to search proteins for active sites, whereas a protein structure is examined as a query to discover the possible active-sites using a set of templates in the multiple template analysis. This paper experimentally illustrates that the machine learning algorithms effectively improve the similarity/deviation measurements for both the analyses.

  18. Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps.

    PubMed

    Sood, Mariam R; Sereno, Martin I

    2016-08-01

    Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor-preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface-based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory-motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory-motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe almost completely overlaps visual maps, whereas a significant portion of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to a small region on the anterior bank of the central sulcus near the border between the face and hand representations of M-I. Hum Brain Mapp 37:2784-2810, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  19. Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

    PubMed

    Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

    2016-06-16

    Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Mapping of brain activity by automated volume analysis of immediate early genes

    PubMed Central

    Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

    2016-01-01

    Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

  1. Ionizable side chains at catalytic active sites of enzymes.

    PubMed

    Jimenez-Morales, David; Liang, Jie; Eisenberg, Bob

    2012-05-01

    Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

  2. GeoMapApp Learning Activities: Enabling the democratisation of geoscience learning

    NASA Astrophysics Data System (ADS)

    Goodwillie, A. M.; Kluge, S.

    2011-12-01

    GeoMapApp Learning Activities (http://serc.carleton.edu/geomapapp) are step-by-step guided inquiry geoscience education activities that enable students to dictate the pace of learning. They can be used in the classroom or out of class, and their guided nature means that the requirement for teacher intervention is minimised which allows students to spend increased time analysing and understanding a broad range of geoscience data, content and concepts. Based upon GeoMapApp (http://www.geomapapp.org), a free, easy-to-use map-based data exploration and visualisation tool, each activity furnishes the educator with an efficient package of downloadable documents. This includes step-by-step student instructions and answer sheet; a teacher's edition annotated worksheet containing teaching tips, additional content and suggestions for further work; quizzes for use before and after the activity to assess learning; and a multimedia tutorial. The activities can be used by anyone at any time in any place with an internet connection. In essence, GeoMapApp Learning Activities provide students with cutting-edge technology, research-quality geoscience data sets, and inquiry-based learning in a virtual lab-like environment. Examples of activities so far created are student calculation and analysis of the rate of seafloor spreading, and present-day evidence on the seafloor for huge ancient landslides around the Hawaiian islands. The activities are designed primarily for students at the community college, high school and introductory undergraduate levels, exposing students to content and concepts typically found in those settings.

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

    USGS Publications Warehouse

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

    1998-01-01

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

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

    PubMed

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

    2004-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Using low-cost drones to map malaria vector habitats.

    PubMed

    Hardy, Andy; Makame, Makame; Cross, Dónall; Majambere, Silas; Msellem, Mwinyi

    2017-01-14

    There is a growing awareness that if we are to achieve the ambitious goal of malaria elimination, we must compliment indoor-based vector control interventions (such as bednets and indoor spraying) with outdoor-based interventions such as larval source management (LSM). The effectiveness of LSM is limited by our capacity to identify and map mosquito aquatic habitats. This study provides a proof of concept for the use of a low-cost (< $1000) drone (DJI Phantom) for mapping water bodies in seven sites across Zanzibar including natural water bodies, irrigated and non-irrigated rice paddies, peri-urban and urban locations. With flying times of less than 30 min for each site, high-resolution (7 cm) georeferenced images were successfully generated for each of the seven sites, covering areas up to 30 ha. Water bodies were readily identifiable in the imagery, as well as ancillary information for planning LSM activities (access routes to water bodies by road and foot) and public health management (e.g. identification of drinking water sources, mapping individual households and the nature of their construction). The drone-based surveys carried out in this study provide a low-cost and flexible solution to mapping water bodies for operational dissemination of LSM initiatives in mosquito vector-borne disease elimination campaigns. Generated orthomosaics can also be used to provide vital information for other public health planning activities.

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

    USGS Publications Warehouse

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

    2011-01-01

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

  8. Transient Rotor Activity During Prolonged 3-Dimensional Phase Mapping in Human Persistent Atrial Fibrillation.

    PubMed

    Pathik, Bhupesh; Kalman, Jonathan M; Walters, Tomos; Kuklik, Pawel; Zhao, Jichao; Madry, Andrew; Prabhu, Sandeep; Nalliah, Chrishan; Kistler, Peter; Lee, Geoffrey

    2018-01-01

    This study sought to validate a 3-dimensional (3D) phase mapping system and determine the distribution of dominant propagation patterns in persistent atrial fibrillation (AF). Currently available systems display phase as simplified 2-dimensional maps. We developed a novel 3D phase mapping system that uses the 3D location of basket catheter electrodes and the patient's 3D left atrial surface geometry to interpolate phase and create a 3D representation of phase progression. Six-min AF recordings from the left atrium were obtained in 14 patients using the Constellation basket catheter and analyzed offline. Exported signals underwent both phase and traditional activation analysis and were then visualized using a novel 3D mapping system. Analysis involved: 1) validation of phase analysis by comparing beat-to-beat AF cycle length calculated using phase inversion with that determined from activation timing in the same 20-s segment; 2) validation of 3D phase by comparing propagation patterns observed using 3D phase with 3D activation in the same 1-min segment; and 3) determining the distribution of dominant propagation patterns in 6-min recordings using 3D phase. There was strong agreement of beat-to-beat AF cycle length between activation analysis and phase inversion (R 2  = 0.91). There was no significant difference between 3D activation and 3D phase in mean percentage of propagation patterns classified as single wavefronts (p = 0.99), focal activations (p = 0.26), disorganized activity (p = 0.76), or multiple wavefronts (p = 0.70). During prolonged 3D phase, single wavefronts were the most common propagation pattern (50.2%). A total of 34 rotors were seen in 9 of 14 patients. All rotors were transient with mean duration of 1.0 ± 0.6 s. Rotors were only observed in areas of high electrode density where the interelectrode distance was significantly shorter than nonrotor sites (7.4 [interquartile range: 6.3 to 14.6] vs. 15.3 mm [interquartile range: 10.1 to

  9. Metal active site elasticity linked to activation of homocysteine in methionine synthases

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

    Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.

    2008-04-02

    Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry uponmore » binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.« less

  10. N-acetylcysteine attenuates TNF-α-induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells

    PubMed Central

    Hashimoto, Shu; Gon, Yasuhiro; Matsumoto, Ken; Takeshita, Ikuko; Horie, Takashi

    2001-01-01

    We have previously shown that tumour necrosis factor-α (TNF-α) activates p38 mitogen-activated protein (MAP) kinase to produce interleukin-8 (IL-8) by human pulmonary vascular endothelial cells. Reactive oxygen species (ROS) including H2O2 generated by TNF-α can act as signalling intermediates for cytokine induction; therefore, scavenging ROS by anti-oxidants is important for the regulation of cytokine production. However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione (GSH) synthesis, on TNF-α-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined. To clarify these issues, we examined the effect of NAC on TNF-α-induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase-mediated IL-8 production. Human pulmonary vascular endothelial cells that had been preincubated with NAC were stimulated with TNF-α and then the activation of p38 MAP kinase and MKK3/MKK6 in the cells and IL-8 concentrations in the culture supernatants were determined. Intracellular GSH levels increased in NAC-treated cells. NAC attenuated TNF-α-induced activation of p38 MAP kinase and MKK3/MKK6. NAC attenuated p38 MAP kinase-mediated IL-8 production by TNF-α-stimulated cells. These results indicate that the cellular reduction and oxidation (redox) regulated by intracellular GSH is critical for TNF-α-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury. PMID:11156586

  11. N-acetylcysteine attenuates TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells.

    PubMed

    Hashimoto, S; Gon, Y; Matsumoto, K; Takeshita, I; Horie, T

    2001-01-01

    1. We have previously shown that tumour necrosis factor-alpha (TNF-alpha) activates p38 mitogen-activated protein (MAP) kinase to produce interleukin-8 (IL-8) by human pulmonary vascular endothelial cells. Reactive oxygen species (ROS) including H(2)O(2) generated by TNF-alpha can act as signalling intermediates for cytokine induction; therefore, scavenging ROS by anti-oxidants is important for the regulation of cytokine production. However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione (GSH) synthesis, on TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined. To clarify these issues, we examined the effect of NAC on TNF-alpha-induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase-mediated IL-8 production. 2. Human pulmonary vascular endothelial cells that had been preincubated with NAC were stimulated with TNF-alpha and then the activation of p38 MAP kinase and MKK3/MKK6 in the cells and IL-8 concentrations in the culture supernatants were determined. 3. Intracellular GSH levels increased in NAC-treated cells. 4. NAC attenuated TNF-alpha-induced activation of p38 MAP kinase and MKK3/MKK6. 5. NAC attenuated p38 MAP kinase-mediated IL-8 production by TNF-alpha-stimulated cells. 6. These results indicate that the cellular reduction and oxidation (redox) regulated by intracellular GSH is critical for TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury.

  12. Absence of rotational activity detected using 2-dimensional phase mapping in the corresponding 3-dimensional phase maps in human persistent atrial fibrillation.

    PubMed

    Pathik, Bhupesh; Kalman, Jonathan M; Walters, Tomos; Kuklik, Pawel; Zhao, Jichao; Madry, Andrew; Sanders, Prashanthan; Kistler, Peter M; Lee, Geoffrey

    2018-02-01

    Current phase mapping systems for atrial fibrillation create 2-dimensional (2D) maps. This process may affect the accurate detection of rotors. We developed a 3-dimensional (3D) phase mapping technique that uses the 3D locations of basket electrodes to project phase onto patient-specific left atrial 3D surface anatomy. We sought to determine whether rotors detected in 2D phase maps were present at the corresponding time segments and anatomical locations in 3D phase maps. One-minute left atrial atrial fibrillation recordings were obtained in 14 patients using the basket catheter and analyzed off-line. Using the same phase values, 2D and 3D phase maps were created. Analysis involved determining the dominant propagation patterns in 2D phase maps and evaluating the presence of rotors detected in 2D phase maps in the corresponding 3D phase maps. Using 2D phase mapping, the dominant propagation pattern was single wavefront (36.6%) followed by focal activation (34.0%), disorganized activity (23.7%), rotors (3.3%), and multiple wavefronts (2.4%). Ten transient rotors were observed in 9 of 14 patients (64%). The mean rotor duration was 1.1 ± 0.7 seconds. None of the 10 rotors observed in 2D phase maps were seen at the corresponding time segments and anatomical locations in 3D phase maps; 4 of 10 corresponded with single wavefronts in 3D phase maps, 2 of 10 with 2 simultaneous wavefronts, 1 of 10 with disorganized activity, and in 3 of 10 there was no coverage by the basket catheter at the corresponding 3D anatomical location. Rotors detected in 2D phase maps were not observed in the corresponding 3D phase maps. These findings may have implications for current systems that use 2D phase mapping. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  13. Road-map to plan and structure the preliminary site investigation program for a geological repository in Japan

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

    Deguchi, Akira; Tsuchi, Hiroyuki; Kitayama, Kazumi

    2007-07-01

    Available in abstract form only. Full text of publication follows: A stepwise site selection process has been adopted for geological disposal of HLW in Japan. Literature surveys (LS), followed by preliminary investigations (PI) and, finally, detailed investigations (DI) in underground facilities will be carried out in the successive selection stages. In the PI stage, surface-based investigations such as borehole surveys and geophysical prospecting will be implemented with two main objectives. The first is to obtain information relating to legal requirements on siting, such as the occurrence of igneous or fault activity, and to confirm the extremely low likelihood of adversemore » impacts on the candidate site resulting from such phenomena. The second is to obtain the information required for the design and performance assessment of the engineered barrier system and the repository. In order to implement these preliminary investigations rigorously and efficiently within the constraints of a limited time period, budget and resources, PI planning before commencing investigations and on-site PI management during the investigation phase are very important issues. The planning and management of PI have to be performed by NUMO staff, but not all staff have sufficient experience in the range of disciplines involved. NUMO therefore decided to compile existing knowledge and experience in the planning and management of investigations in the form of manuals to be used to improve and maintain internal expertise. Experts with experience in overseas investigation programs were requested to prepare these manuals. This paper outlines the structure and scope of the upper level manual (road-map) and discusses NUMO's experience in applying it in 'dry-runs' to model sites. (authors)« less

  14. Improving accuracy of simultaneously reconstructed activity and attenuation maps using deep learning.

    PubMed

    Hwang, Donghwi; Kim, Kyeong Yun; Kang, Seung Kwan; Seo, Seongho; Paeng, Jin Chul; Lee, Dong Soo; Lee, Jae Sung

    2018-02-15

    Simultaneous reconstruction of activity and attenuation using the maximum likelihood reconstruction of activity and attenuation (MLAA) augmented by time-of-flight (TOF) information is a promising method for positron emission tomography (PET) attenuation correction. However, it still suffers from several problems, including crosstalk artifacts, slow convergence speed, and noisy attenuation maps (μ-maps). In this work, we developed deep convolutional neural networks (CNNs) to overcome these MLAA limitations, and we verified their feasibility using a clinical brain PET data set. Methods: We applied the proposed method to one of the most challenging PET cases for simultaneous image reconstruction ( 18 F-FP-CIT PET scans with highly specific binding to striatum of the brain). Three different CNN architectures (convolutional autoencoder (CAE), U-net, hybrid of CAE and U-net) were designed and trained to learn x-ray computed tomography (CT) derived μ-map (μ-CT) from the MLAA-generated activity distribution and μ-map (μ-MLAA). PET/CT data of 40 patients with suspected Parkinson's disease were employed for five-fold cross-validation. For the training of CNNs, 800,000 transverse PET slices and CTs augmented from 32 patient data sets were used. The similarity to μ-CT of the CNN-generated μ-maps (μ-CAE, μ-Unet, and μ-Hybrid) and μ-MLAA was compared using Dice similarity coefficients. In addition, we compared the activity concentration of specific (striatum) and non-specific binding regions (cerebellum and occipital cortex) and the binding ratios in the striatum in the PET activity images reconstructed using those μ-maps. Results: The CNNs generated less noisy and more uniform μ-maps than original μ-MLAA. Moreover, the air cavities and bones were better resolved in the proposed CNN outputs. In addition, the proposed deep learning approach was useful for mitigating the crosstalk problem in the MLAA reconstruction. The hybrid network of CAE and U-net yielded the

  15. Quantum mechanical design of enzyme active sites.

    PubMed

    Zhang, Xiyun; DeChancie, Jason; Gunaydin, Hakan; Chowdry, Arnab B; Clemente, Fernando R; Smith, Adam J T; Handel, T M; Houk, K N

    2008-02-01

    The design of active sites has been carried out using quantum mechanical calculations to predict the rate-determining transition state of a desired reaction in presence of the optimal arrangement of catalytic functional groups (theozyme). Eleven versatile reaction targets were chosen, including hydrolysis, dehydration, isomerization, aldol, and Diels-Alder reactions. For each of the targets, the predicted mechanism and the rate-determining transition state (TS) of the uncatalyzed reaction in water is presented. For the rate-determining TS, a catalytic site was designed using naturalistic catalytic units followed by an estimation of the rate acceleration provided by a reoptimization of the catalytic site. Finally, the geometries of the sites were compared to the X-ray structures of related natural enzymes. Recent advances in computational algorithms and power, coupled with successes in computational protein design, have provided a powerful context for undertaking such an endeavor. We propose that theozymes are excellent candidates to serve as the active site models for design processes.

  16. X-ray Reverberation Mapping in Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Kara, Erin

    2018-01-01

    Active Galactic Nuclei can produce as much or more electromagnetic and kinetic luminosities than the combined stellar luminosity of an entire galaxy. The energy output from AGN comes from the gravitational potential energy of the infalling material and the rotational energy of the black hole, both of which are released very close to the black hole. Therefore, probing the relativistic region of the inner accretion flow is essential to understanding how AGN work and effect their environments. In this talk, I will present a new technique for probing these relativistic environments: X-ray reverberation mapping. Similar to Optical reverberation mapping, where time delays of days or weeks between the continuum and Broad Line Region lines map out centiparsec scales, X-ray reverberation reveals time delays of tens of seconds, which map out microparsec scales in the accretion flow—well beyond the spatial resolution power of any instrument. This technique has been discovered in the past decade, so I will give a brief overview of how the measurements are made, and highlight some recent discoveries, which allow us to map the gas falling on to the black hole and measure the effects of strongly curved spacetime close to the event horizon.

  17. The Serra de Tramuntana World Heritage Site (Mallorca, Spain). Landslide activity valuation by means of Persistent Scatterers Interferometry

    NASA Astrophysics Data System (ADS)

    Mateos, Rosa Maria; Bianchini, Silvia; Herrera, Gerardo; Garcia, Inmaculada; Sanabria, Margarita

    2016-04-01

    The Serra de Tramuntana, which forms the backbone of the north-west of Mallorca (Spain), was declared in 2011 World Heritage Site by UNESCO under the cultural landscape category. The particular landscape of this range is the fruit of the exchange of knowledge between cultures, with small-scale works performed collectively for a productive aim, conditioned by the limitations imposed by the physical medium. The steep topography of the chain, highly related to its geological complexity, and the Mediterranean climate, influence intense slope dynamics with the consequent multiple types of slope failures: rock slides, earth landslides and rockfalls, which cause significant damage and specifically to the road network (Mateos, 2013a). The human landscape marked by agricultural terraces (dry stone constructions) has significantly contributed to the slope stability in the range for centuries. In the present work, a landslide inventory map with 918 events has been updated and the landslides state of activity was analyzed exploiting 14 ALOS PALSAR satellite SAR (Synthetic Aperture Radar) images acquired during the period 2007-2010. Landslide activity maps were elaborated through the use of PSI (Persistent Scatterers Interferometry) technique (Bianchini et al., 2013). Besides assessing the PS visibility of the study area according to the relief, land use and satellite acquisition parameters, these maps evaluate, for every monitored landslide, the average velocities along the satellite Line Of Sight (VLOS) and along the maximum local steepest slope (VSLOPE), providing an estimate of their state of activity and their potential to cause damages. Additionally, a ground motion activity map is also generated, based on active PS clusters not included within any mapped landslide phenomenon. A confidence degree evaluation is carried out to attest the reliability of measured displacements to represent landslide dynamics. Results show that 42 landslides were identified as active (VSLOPE

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

    PubMed Central

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

    2017-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

  20. Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex.

    PubMed

    Higo, Noriyuki; Kunori, Nobuo; Murata, Yumi

    2016-01-01

    In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv.

  1. Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex

    PubMed Central

    Kunori, Nobuo; Murata, Yumi

    2016-01-01

    In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv. PMID:27494282

  2. Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity.

    PubMed

    Sun, Yun; Sun, Fenghui; Li, Jianlong; Wu, Minlu; Fan, Xiang; Meng, Yanfa; Meng, Yao

    2016-10-31

    PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N -terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs.

  3. Left ventricular lead placement in the latest activated region guided by coronary venous electroanatomic mapping.

    PubMed

    Rad, Masih Mafi; Blaauw, Yuri; Dinh, Trang; Pison, Laurent; Crijns, Harry J; Prinzen, Frits W; Vernooy, Kevin

    2015-01-01

    Left ventricular (LV) lead placement in the latest activated region is an important determinant of response to cardiac resynchronization therapy (CRT). We investigated the feasibility of coronary venous electroanatomic mapping (EAM) to guide LV lead placement to the latest activated region. Twenty-five consecutive CRT candidates with left bundle-branch block underwent intra-procedural coronary venous EAM using EnSite NavX. A guidewire was used to map the coronary veins during intrinsic activation, and to test for phrenic nerve stimulation (PNS). The latest activated region, defined as the region with an electrical delay >75% of total QRS duration, was located anterolaterally in 18 (basal, n = 10; mid, n = 8) and inferolaterally in 6 (basal, n = 3; mid, n = 3). In one patient, identification of the latest activated region was impeded by limited coronary venous anatomy. In patients with >1 target vein (n = 12), the anatomically targeted inferolateral vein was rarely the vein with maximal electrical delay (n = 3). A concordant LV lead position was achieved in 18 of 25 patients. In six patients, this was hampered by PNS (n = 4), lead instability (n = 1), and coronary vein stenosis (n = 1). Coronary venous EAM can be used intraprocedurally to guide LV lead placement to the latest activated region free of PNS. This approach especially contributes to optimization of LV lead electrical delay in patients with multiple target veins. Conventional anatomical LV lead placement strategy does not target the vein with maximal electrical delay in many of these patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  4. Use of Bedrock and Geomorphic Mapping Compilations in Assessing Geologic Hazards at Recreation Sites on National Forests in NW California

    NASA Astrophysics Data System (ADS)

    de La Fuente, J. A.; Bell, A.; Elder, D.; Mowery, R.; Mikulovsky, R.; Klingel, H.; Stevens, M.

    2010-12-01

    coverage is a compilation of the best available mapping for all National Forests in California. The geomorphic coverage includes features such as active and dormant landslides, alluvial fans, headwall basins, glacial features, and valley inner gorge. Criteria will be developed which utilize elements of this data to evaluate geologic hazards in the vicinity of developed recreation sites. The second phase will be conducted later and involves site specific analyses focusing on areas identified as higher hazard in the first phase, along with verification and updating of phase 1 findings. The third phase will complete any site level geologic or hydrologic investigations, and wrap up the hazard assessment process. A summary report with hazard maps and recommendations will be prepared at the end of each phase. The overriding goal of this project is to provide sound geologic information to managers so they can use a science-based approach in recognizing and managing geologic hazards at recreation sites.

  5. Mapping the Active Vents of Stromboli Volcano with an Unmanned Aerial Vehicle

    NASA Astrophysics Data System (ADS)

    Turner, N.; Houghton, B. F.; von der Lieth, J.; Hort, M. K.; Taddeucci, J.; Kueppers, U.; Ricci, T.; Gaudin, D.

    2016-12-01

    We present a new detailed map of the active vents of Stromboli volcano obtained from UAV flights in May 2016, when the active NE and SW craters were repeatedly mapped. Due to high levels of gas emissions and frequent explosions, fine-scale measurements of vent geometry from single flights were challenging. However, the compilation of data acquired over 12 flights used with Structure from Motion software allowed us to create a 10 cm Digital Elevation Model (DEM) offering a non-obstructed view into the active craters. Such direct observations permits us to constrain parameters such as vent geometry and depth with an unprecedented precision, thus potentially reducing the uncertainty of models depending on such inputs (e.g. conduit and acoustic models). Furthermore, the low-cost and safety of UAVs allows mapping changes at small temporal and spatial resolutions, making this technique complementary to monitoring efforts at active volcanoes.

  6. Active and regulatory sites of cytosolic 5'-nucleotidase.

    PubMed

    Pesi, Rossana; Allegrini, Simone; Careddu, Maria Giovanna; Filoni, Daniela Nicole; Camici, Marcella; Tozzi, Maria Grazia

    2010-12-01

    Cytosolic 5'-nucleotidase (cN-II), which acts preferentially on 6-hydroxypurine nucleotides, is essential for the survival of several cell types. cN-II catalyses both the hydrolysis of nucleotides and transfer of their phosphate moiety to a nucleoside acceptor through formation of a covalent phospho-intermediate. Both activities are regulated by a number of phosphorylated compounds, such as diadenosine tetraphosphate (Ap₄A), ADP, ATP, 2,3-bisphosphoglycerate (BPG) and phosphate. On the basis of a partial crystal structure of cN-II, we mutated two residues located in the active site, Y55 and T56. We ascertained that the ability to catalyse the transfer of phosphate depends on the presence of a bulky residue in the active site very close to the aspartate residue that forms the covalent phospho-intermediate. The molecular model indicates two possible sites at which adenylic compounds may interact. We mutated three residues that mediate interaction in the first activation site (R144, N154, I152) and three in the second (F127, M436 and H428), and found that Ap₄A and ADP interact with the same site, but the sites for ATP and BPG remain uncertain. The structural model indicates that cN-II is a homotetrameric protein that results from interaction through a specific interface B of two identical dimers that have arisen from interaction of two identical subunits through interface A. Point mutations in the two interfaces and gel-filtration experiments indicated that the dimer is the smallest active oligomerization state. Finally, gel-filtration and light-scattering experiments demonstrated that the native enzyme exists as a tetramer, and no further oligomerization is required for enzyme activation. © 2010 The Authors Journal compilation © 2010 FEBS.

  7. Water in the Active Site of Ketosteroid Isomerase

    PubMed Central

    Hanoian, Philip; Hammes-Schiffer, Sharon

    2011-01-01

    Classical molecular dynamics simulations were utilized to investigate the structural and dynamical properties of water in the active site of ketosteroid isomerase (KSI) to provide insight into the role of these water molecules in the enzyme-catalyzed reaction. This reaction is thought to proceed via a dienolate intermediate that is stabilized by hydrogen bonding with residues Tyr16 and Asp103. A comparative study was performed for the wild-type (WT) KSI and the Y16F, Y16S, and Y16F/Y32F/Y57F (FFF) mutants. These systems were studied with three different bound ligands: equilenin, which is an intermediate analog, and the intermediate states of two steroid substrates. Several distinct water occupation sites were identified in the active site of KSI for the WT and mutant systems. Three additional sites were identified in the Y16S mutant that were not occupied in WT KSI or the other mutants studied. The number of water molecules directly hydrogen bonded to the ligand oxygen was approximately two waters in the Y16S mutant, one water in the Y16F and FFF mutants, and intermittent hydrogen bonding of one water molecule in WT KSI. The molecular dynamics trajectories of the Y16F and FFF mutants reproduced the small conformational changes of residue 16 observed in the crystal structures of these two mutants. Quantum mechanical/molecular mechanical calculations of 1H NMR chemical shifts of the protons in the active site hydrogen-bonding network suggest that the presence of water in the active site does not prevent the formation of short hydrogen bonds with far-downfield chemical shifts. The molecular dynamics simulations indicate that the active site water molecules exchange much more frequently for WT KSI and the FFF mutant than for the Y16F and Y16S mutants. This difference is most likely due to the hydrogen-bonding interaction between Tyr57 and an active site water molecule that is persistent in the Y16F and Y16S mutants but absent in the FFF mutant and significantly less

  8. Water in the active site of ketosteroid isomerase.

    PubMed

    Hanoian, Philip; Hammes-Schiffer, Sharon

    2011-08-09

    Classical molecular dynamics simulations were utilized to investigate the structural and dynamical properties of water in the active site of ketosteroid isomerase (KSI) to provide insight into the role of these water molecules in the enzyme-catalyzed reaction. This reaction is thought to proceed via a dienolate intermediate that is stabilized by hydrogen bonding with residues Tyr16 and Asp103. A comparative study was performed for the wild-type (WT) KSI and the Y16F, Y16S, and Y16F/Y32F/Y57F (FFF) mutants. These systems were studied with three different bound ligands: equilenin, which is an intermediate analog, and the intermediate states of two steroid substrates. Several distinct water occupation sites were identified in the active site of KSI for the WT and mutant systems. Three additional sites were identified in the Y16S mutant that were not occupied in WT KSI or the other mutants studied. The number of water molecules directly hydrogen bonded to the ligand oxygen was approximately two in the Y16S mutant and one in the Y16F and FFF mutants, with intermittent hydrogen bonding of one water molecule in WT KSI. The molecular dynamics trajectories of the Y16F and FFF mutants reproduced the small conformational changes of residue 16 observed in the crystal structures of these two mutants. Quantum mechanical/molecular mechanical calculations of (1)H NMR chemical shifts of the protons in the active site hydrogen-bonding network suggest that the presence of water in the active site does not prevent the formation of short hydrogen bonds with far-downfield chemical shifts. The molecular dynamics simulations indicate that the active site water molecules exchange much more frequently for WT KSI and the FFF mutant than for the Y16F and Y16S mutants. This difference is most likely due to the hydrogen-bonding interaction between Tyr57 and an active site water molecule that is persistent in the Y16F and Y16S mutants but absent in the FFF mutant and significantly less probable

  9. Active Site Characterization of Proteases Sequences from Different Species of Aspergillus.

    PubMed

    Morya, V K; Yadav, Virendra K; Yadav, Sangeeta; Yadav, Dinesh

    2016-09-01

    A total of 129 proteases sequences comprising 43 serine proteases, 36 aspartic proteases, 24 cysteine protease, 21 metalloproteases, and 05 neutral proteases from different Aspergillus species were analyzed for the catalytically active site residues using MEROPS database and various bioinformatics tools. Different proteases have predominance of variable active site residues. In case of 24 cysteine proteases of Aspergilli, the predominant active site residues observed were Gln193, Cys199, His364, Asn384 while for 43 serine proteases, the active site residues namely Asp164, His193, Asn284, Ser349 and Asp325, His357, Asn454, Ser519 were frequently observed. The analysis of 21 metalloproteases of Aspergilli revealed Glu298 and Glu388, Tyr476 as predominant active site residues. In general, Aspergilli species-specific active site residues were observed for different types of protease sequences analyzed. The phylogenetic analysis of these 129 proteases sequences revealed 14 different clans representing different types of proteases with diverse active site residues.

  10. Half-of-the-sites reactivity of outer-membrane phospholipase A against an active-site-directed inhibitor.

    PubMed

    Ubarretxena-Belandia, I; Cox, R C; Dijkman, R; Egmond, M R; Verheij, H M; Dekker, N

    1999-03-01

    The reaction of a novel active-site-directed phospholipase A1 inhibitor with the outer-membrane phospholipase A (OMPLA) was investigated. The inhibitor 1-p-nitrophenyl-octylphosphonate-2-tridecylcarbamoyl-3-et hanesulfonyl -amino-3-deoxy-sn-glycerol irreversibly inactivated OMPLA. The inhibition reaction did not require the cofactor calcium or an unprotonated active-site His142. The inhibition of the enzyme solubilized in hexadecylphosphocholine micelles was characterized by a rapid (t1/2 = 20 min) and complete loss of enzymatic activity, concurrent with the covalent modification of 50% of the active-site serines, as judged from the amount of p-nitrophenolate (PNP) released. Modification of the remaining 50% occurred at a much lower rate, indicative of half-of-the-sites reactivity against the inhibitor of this dimeric enzyme. Inhibition of monomeric OMPLA solubilized in hexadecyl-N,N-dimethyl-1-ammonio-3-propanesulfonate resulted in an equimolar monophasic release of PNP, concurrent with the loss of enzymatic activity (t1/2 = 14 min). The half-of-the-sites reactivity is discussed in view of the dimeric nature of this enzyme.

  11. Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

    PubMed

    Thune, I; Furberg, A S

    2001-06-01

    The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect

  12. Mapping Cryo-volcanic Activity from Enceladus’ South Polar Region

    NASA Astrophysics Data System (ADS)

    Tigges, Mattie; Spitale, Joseph N.

    2017-10-01

    Using Cassini images taken of Enceladus’ south polar plumes at various times and orbital locations, we are producing maps of eruptive activity at various times. The purpose of this experiment is to understand the mechanism that controls the cryo-volcanic eruptions.The current hypothesis is that Tiger Stripe activity is modulated by tidal forcing, which would predict a correlation between orbital phase and the amount and distribution of eruptive activity. The precise nature of those correlations depends on how the crust is failing and how the plumbing system is organized.We use simulated curtains of ejected material that are superimposed over Cassini images, obtained during thirteen different flybys, taken between mid-2009 and mid-2012. Each set represents a different time and location in Enceladus’ orbit about Saturn, and contains images of the plumes from various angles. Shadows cast onto the backlit ejected material by the terminator of the moon are used to determine which fractures were active at that point in the orbit.Maps of the spatial distribution of eruptive activity at various orbital phases can be used to evaluate various hypotheses about the failure modes that produce the eruptions.

  13. Active Site Metal Occupancy and Cyclic Di-GMP Phosphodiesterase Activity of Thermotoga maritima HD-GYP.

    PubMed

    Miner, Kyle D; Kurtz, Donald M

    2016-02-16

    HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.

  14. Contour Mapping

    NASA Technical Reports Server (NTRS)

    1995-01-01

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

  15. Lesson Plans: Road Maps for the Active Learning Classroom.

    PubMed

    Moore-Cox, Annie

    2017-11-01

    Lesson planning is a documentation process used extensively in education from kindergarten through 12th grade, but rarely in higher education, including undergraduate, prelicensure nursing education. Lesson plans help teachers plan what will happen during a class period from moment to moment. Trends in nursing education, such as the incorporation of active learning strategies in the classroom, make lesson plans a timely addition to the nurse educator's toolkit. This article describes the components of a lesson plan and offers an author-developed template for use in nursing education. Using the template helps nurse educators map out activities for all class participants, such as students, student pairs and teams, and faculty. The lesson plan enables faculty to plot out the many dynamic components of an active learning class period. It also serves as a road map for subsequent faculty, which is an important feature as the profession faces a wave of retirements in the coming decade. [J Nurs Educ. 2017;56(11):697-700.]. Copyright 2017, SLACK Incorporated.

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

    NASA Astrophysics Data System (ADS)

    Hren, Rok

    1998-06-01

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

  17. Diffusional correlations among multiple active sites in a single enzyme.

    PubMed

    Echeverria, Carlos; Kapral, Raymond

    2014-04-07

    Simulations of the enzymatic dynamics of a model enzyme containing multiple substrate binding sites indicate the existence of diffusional correlations in the chemical reactivity of the active sites. A coarse-grain, particle-based, mesoscopic description of the system, comprising the enzyme, the substrate, the product and solvent, is constructed to study these effects. The reactive and non-reactive dynamics is followed using a hybrid scheme that combines molecular dynamics for the enzyme, substrate and product molecules with multiparticle collision dynamics for the solvent. It is found that the reactivity of an individual active site in the multiple-active-site enzyme is reduced substantially, and this effect is analyzed and attributed to diffusive competition for the substrate among the different active sites in the enzyme.

  18. The MAP Kinase Cascade Is Activated prior to the Induction of Gliosis in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Model of Dopaminergic Neurotoxicity.

    PubMed

    Callaghan, James P; Martin, Parthena M; Mass, Marc J

    1998-05-01

    Injury to the central nervous system (CNS) provokes microglial activation and astrocytic hypertrophy at the site of damage. The signaling events that underlie these cellular responses remain unknown. Recent evidence has implicated tyrosine phosphorylation systems, in general, and the mitogen-activated protein kinase (MAP kinase) cascade, in particular, in the mediation of growth-associated events linked to neural degeneration, such as glial activation. 1 Moreover, an increase in the mRNA coding for the 14.3.3 protein, a known regulator of the MAP kinase pathway, 2 appears to be involved in methamphetamine neurotoxicity. 3 To examine the potential role of these protein kinase pathways in drug-induced damage to the CNS, we used the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to damage nerve terminals in the mouse neostriatum and elicit a glial reaction. The onset of reactive gliosis then was verified by Northern blot analysis of glial fibrillary acidic protein (GFAP) mRNA and qualified by enzyme-linked immunosorbent assay (ELISA) of GFAP (protein). A single administration of MPTP (12.5 mg/kg, subcutaneously (s.c.)) to the C57B1/6J mouse resulted in a 10-fold increase in GFAP mRNA by 1 day and a 4-fold increase in GFAP (protein) by 2 days. To determine the potential role of protein tyrosine phosphorylation and MAP kinase activation in these events, blots of striatal homogenates were probed with antibodies directed against phospho-tyr 204 and phospho-thr 202, residues corresponding to the active sites of p42/44 MAP kinase. After mice were sacrificed by focused microwave irradiation to preserve steady-state phosphorylation, proteins from striatal homogenates were resolved by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblots of these samples showed a number of phosphotyrosine-labeled bands, but there were no apparent differences between control and MPTP groups. In contrast, phospho-MAP kinase was

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

    PubMed

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

    2017-05-05

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

  20. Comparison of 3D quantitative structure-activity relationship methods: Analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis

    NASA Astrophysics Data System (ADS)

    Woolfrey, John R.; Avery, Mitchell A.; Doweyko, Arthur M.

    1998-03-01

    Two three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL), were compared with respect to the analysis of a training set of 154 artemisinin analogues. Five models were created, including a complete HASL and two trimmed versions, as well as two CoMFA models (leave-one-out standard CoMFA and the guided-region selection protocol). Similar r2 and q2 values were obtained by each method, although some striking differences existed between CoMFA contour maps and the HASL output. Each of the four predictive models exhibited a similar ability to predict the activity of a test set of 23 artemisinin analogues, although some differences were noted as to which compounds were described well by either model.

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

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

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

  2. The Lunar Mapping and Modeling Project

    NASA Technical Reports Server (NTRS)

    Nall, M.; French, R.; Noble, S.; Muery, K.

    2010-01-01

    The Lunar Mapping and Modeling Project (LMMP) is managing a suite of lunar mapping and modeling tools and data products that support lunar exploration activities, including the planning, de-sign, development, test, and operations associated with crewed and/or robotic operations on the lunar surface. Although the project was initiated primarily to serve the needs of the Constellation program, it is equally suited for supporting landing site selection and planning for a variety of robotic missions, including NASA science and/or human precursor missions and commercial missions such as those planned by the Google Lunar X-Prize participants. In addition, LMMP should prove to be a convenient and useful tool for scientific analysis and for education and public out-reach (E/PO) activities.

  3. Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site

    PubMed Central

    Sigala, Paul A.; Fafarman, Aaron T.; Schwans, Jason P.; Fried, Stephen D.; Fenn, Timothy D.; Caaveiro, Jose M. M.; Pybus, Brandon; Ringe, Dagmar; Petsko, Gregory A.; Boxer, Steven G.; Herschlag, Daniel

    2013-01-01

    Hydrogen bond networks are key elements of protein structure and function but have been challenging to study within the complex protein environment. We have carried out in-depth interrogations of the proton transfer equilibrium within a hydrogen bond network formed to bound phenols in the active site of ketosteroid isomerase. We systematically varied the proton affinity of the phenol using differing electron-withdrawing substituents and incorporated site-specific NMR and IR probes to quantitatively map the proton and charge rearrangements within the network that accompany incremental increases in phenol proton affinity. The observed ionization changes were accurately described by a simple equilibrium proton transfer model that strongly suggests the intrinsic proton affinity of one of the Tyr residues in the network, Tyr16, does not remain constant but rather systematically increases due to weakening of the phenol–Tyr16 anion hydrogen bond with increasing phenol proton affinity. Using vibrational Stark spectroscopy, we quantified the electrostatic field changes within the surrounding active site that accompany these rearrangements within the network. We were able to model these changes accurately using continuum electrostatic calculations, suggesting a high degree of conformational restriction within the protein matrix. Our study affords direct insight into the physical and energetic properties of a hydrogen bond network within a protein interior and provides an example of a highly controlled system with minimal conformational rearrangements in which the observed physical changes can be accurately modeled by theoretical calculations. PMID:23798390

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

    PubMed Central

    2016-01-01

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

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

    PubMed

    Brown, M Christian

    2016-03-01

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

  6. Homology modeling and molecular dynamics simulation of N-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design

    NASA Astrophysics Data System (ADS)

    Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian

    2009-06-01

    Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.

  7. Activation of MAP kinase kinase (MEK) and Ras by cholecystokinin in rat pancreatic acini.

    PubMed

    Duan, R D; Zheng, C F; Guan, K L; Williams, J A

    1995-06-01

    Cholecystokinin (CCK) has recently been shown to activate mitogen-activated protein (MAP) kinase in rat pancreatic acini [Duan and Williams, Am. J. Physiol. 267 (Gastrointest. Liver Physiol. 30): G401-G408, 1994]. To evaluate the mechanism of MAP kinase activation, we studied the effects of CCK on MAP kinase kinase (MEK) in rat pancreatic acini. Two forms of MEK were identified by immunoblotting, using antibodies specific to MEK1 and MEK2. MEK activity in acinar extracts and after immunoprecipitation with anti-MEK was detected using a recombinant fusion protein, glutathione S-transferase-MAP kinase, as a substrate. MEK activity rapidly increased after stimulation of acini by CCK, with significant stimulation at 1 min and a maximal effect at 5 min, followed by a slow decline to slightly above control levels after 30 min. The threshold concentration of CCK was approximately 10 pM, and the maximal effect was induced by 1 nM CCK, which increased MEK activity by 120%. In addition to CCK, bombesin and carbachol, but not secretin or vasoactive intestinal peptide, enhanced MEK activity. Phorbol ester mimicked the effect of CCK, whereas ionomycin and thapsigargin failed to activate MEK. We further studied the activation of Ras, an important component leading to activation of MEK by growth factors. Ras in acini was immunoprecipitated and identified by Western blotting. CCK and 12-O-tetradecanoylphorbol-13-acetate stimulated the incorporation of GTP into Ras, a requirement for its activation, reaching a maximum at 10 min of approximately 120% over control. In conclusion, the activation of MAP kinase by CCK can be explained by activation of MEK and may involve the activation of Ras by a protein kinase C-dependent mechanism.

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

    PubMed

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

    2017-06-16

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

  9. Mapping Inhibitory Neuronal Circuits by Laser Scanning Photostimulation

    PubMed Central

    Ikrar, Taruna; Olivas, Nicholas D.; Shi, Yulin; Xu, Xiangmin

    2011-01-01

    Inhibitory neurons are crucial to cortical function. They comprise about 20% of the entire cortical neuronal population and can be further subdivided into diverse subtypes based on their immunochemical, morphological, and physiological properties1-4. Although previous research has revealed much about intrinsic properties of individual types of inhibitory neurons, knowledge about their local circuit connections is still relatively limited3,5,6. Given that each individual neuron's function is shaped by its excitatory and inhibitory synaptic input within cortical circuits, we have been using laser scanning photostimulation (LSPS) to map local circuit connections to specific inhibitory cell types. Compared to conventional electrical stimulation or glutamate puff stimulation, LSPS has unique advantages allowing for extensive mapping and quantitative analysis of local functional inputs to individually recorded neurons3,7-9. Laser photostimulation via glutamate uncaging selectively activates neurons perisomatically, without activating axons of passage or distal dendrites, which ensures a sub-laminar mapping resolution. The sensitivity and efficiency of LSPS for mapping inputs from many stimulation sites over a large region are well suited for cortical circuit analysis. Here we introduce the technique of LSPS combined with whole-cell patch clamping for local inhibitory circuit mapping. Targeted recordings of specific inhibitory cell types are facilitated by use of transgenic mice expressing green fluorescent proteins (GFP) in limited inhibitory neuron populations in the cortex3,10, which enables consistent sampling of the targeted cell types and unambiguous identification of the cell types recorded. As for LSPS mapping, we outline the system instrumentation, describe the experimental procedure and data acquisition, and present examples of circuit mapping in mouse primary somatosensory cortex. As illustrated in our experiments, caged glutamate is activated in a spatially

  10. Automated detection of qualitative spatio-temporal features in electrocardiac activation maps.

    PubMed

    Ironi, Liliana; Tentoni, Stefania

    2007-02-01

    This paper describes a piece of work aiming at the realization of a tool for the automated interpretation of electrocardiac maps. Such maps can capture a number of electrical conduction pathologies, such as arrhytmia, that can be missed by the analysis of traditional electrocardiograms. But, their introduction into the clinical practice is still far away as their interpretation requires skills that belongs to very few experts. Then, an automated interpretation tool would bridge the gap between the established research outcome and clinical practice with a consequent great impact on health care. Qualitative spatial reasoning can play a crucial role in the identification of spatio-temporal patterns and salient features that characterize the heart electrical activity. We adopted the spatial aggregation (SA) conceptual framework and an interplay of numerical and qualitative information to extract features from epicardial maps, and to make them available for reasoning tasks. Our focus is on epicardial activation isochrone maps as they are a synthetic representation of spatio-temporal aspects of the propagation of the electrical excitation. We provide a computational SA-based methodology to extract, from 3D epicardial data gathered over time, (1) the excitation wavefront structure, and (2) the salient features that characterize wavefront propagation and visually correspond to specific geometric objects. The proposed methodology provides a robust and efficient way to identify salient pieces of information in activation time maps. The hierarchical structure of the abstracted geometric objects, crucial in capturing the prominent information, facilitates the definition of general rules necessary to infer the correlation between pathophysiological patterns and wavefront structure and propagation.

  11. 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).

  12. The identity of the active site of oxalate decarboxylase and the importance of the stability of active-site lid conformations1

    PubMed Central

    Just, Victoria J.; Burrell, Matthew R.; Bowater, Laura; McRobbie, Iain; Stevenson, Clare E. M.; Lawson, David M.; Bornemann, Stephen

    2007-01-01

    Oxalate decarboxylase (EC 4.1.1.2) catalyses the conversion of oxalate into carbon dioxide and formate. It requires manganese and, uniquely, dioxygen for catalysis. It forms a homohexamer and each subunit contains two similar, but distinct, manganese sites termed sites 1 and 2. There is kinetic evidence that only site 1 is catalytically active and that site 2 is purely structural. However, the kinetics of enzymes with mutations in site 2 are often ambiguous and all mutant kinetics have been interpreted without structural information. Nine new site-directed mutants have been generated and four mutant crystal structures have now been solved. Most mutants targeted (i) the flexibility (T165P), (ii) favoured conformation (S161A, S164A, D297A or H299A) or (iii) presence (Δ162–163 or Δ162–164) of a lid associated with site 1. The kinetics of these mutants were consistent with only site 1 being catalytically active. This was particularly striking with D297A and H299A because they disrupted hydrogen bonds between the lid and a neighbouring subunit only when in the open conformation and were distant from site 2. These observations also provided the first evidence that the flexibility and stability of lid conformations are important in catalysis. The deletion of the lid to mimic the plant oxalate oxidase led to a loss of decarboxylase activity, but only a slight elevation in the oxalate oxidase side reaction, implying other changes are required to afford a reaction specificity switch. The four mutant crystal structures (R92A, E162A, Δ162–163 and S161A) strongly support the hypothesis that site 2 is purely structural. PMID:17680775

  13. Role of active site rigidity in activity: MD simulation and fluorescence study on a lipase mutant.

    PubMed

    Kamal, Md Zahid; Mohammad, Tabrez Anwar Shamim; Krishnamoorthy, G; Rao, Nalam Madhusudhana

    2012-01-01

    Relationship between stability and activity of enzymes is maintained by underlying conformational flexibility. In thermophilic enzymes, a decrease in flexibility causes low enzyme activity while in less stable proteins such as mesophiles and psychrophiles, an increase in flexibility is associated with enhanced enzyme activity. Recently, we identified a mutant of a lipase whose stability and activity were enhanced simultaneously. In this work, we probed the conformational dynamics of the mutant and the wild type lipase, particularly flexibility of their active site using molecular dynamic simulations and time-resolved fluorescence techniques. In contrast to the earlier observations, our data show that active site of the mutant is more rigid than wild type enzyme. Further investigation suggests that this lipase needs minimal reorganization/flexibility of active site residues during its catalytic cycle. Molecular dynamic simulations suggest that catalytically competent active site geometry of the mutant is relatively more preserved than wild type lipase, which might have led to its higher enzyme activity. Our study implies that widely accepted positive correlation between conformation flexibility and enzyme activity need not be stringent and draws attention to the possibility that high enzyme activity can still be accomplished in a rigid active site and stable protein structures. This finding has a significant implication towards better understanding of involvement of dynamic motions in enzyme catalysis and enzyme engineering through mutations in active site.

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

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

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

    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 tomore » 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.« less

  15. Local activation time sampling density for atrial tachycardia contact mapping: how much is enough?

    PubMed

    Williams, Steven E; Harrison, James L; Chubb, Henry; Whitaker, John; Kiedrowicz, Radek; Rinaldi, Christopher A; Cooklin, Michael; Wright, Matthew; Niederer, Steven; O'Neill, Mark D

    2018-02-01

    Local activation time (LAT) mapping forms the cornerstone of atrial tachycardia diagnosis. Although anatomic and positional accuracy of electroanatomic mapping (EAM) systems have been validated, the effect of electrode sampling density on LAT map reconstruction is not known. Here, we study the effect of chamber geometry and activation complexity on optimal LAT sampling density using a combined in silico and in vivo approach. In vivo 21 atrial tachycardia maps were studied in three groups: (1) focal activation, (2) macro-re-entry, and (3) localized re-entry. In silico activation was simulated on a 4×4cm atrial monolayer, sampled randomly at 0.25-10 points/cm2 and used to re-interpolate LAT maps. Activation patterns were studied in the geometrically simple porcine right atrium (RA) and complex human left atrium (LA). Activation complexity was introduced into the porcine RA by incomplete inter-caval linear ablation. In all cases, optimal sampling density was defined as the highest density resulting in minimal further error reduction in the re-interpolated maps. Optimal sampling densities for LA tachycardias were 0.67 ± 0.17 points/cm2 (focal activation), 1.05 ± 0.32 points/cm2 (macro-re-entry) and 1.23 ± 0.26 points/cm2 (localized re-entry), P = 0.0031. Increasing activation complexity was associated with increased optimal sampling density both in silico (focal activation 1.09 ± 0.14 points/cm2; re-entry 1.44 ± 0.49 points/cm2; spiral-wave 1.50 ± 0.34 points/cm2, P < 0.0001) and in vivo (porcine RA pre-ablation 0.45 ± 0.13 vs. post-ablation 0.78 ± 0.17 points/cm2, P = 0.0008). Increasing chamber geometry was also associated with increased optimal sampling density (0.61 ± 0.22 points/cm2 vs. 1.0 ± 0.34 points/cm2, P = 0.0015). Optimal sampling densities can be identified to maximize diagnostic yield of LAT maps. Greater sampling density is required to correctly reveal complex activation and

  16. From retinal waves to activity-dependent retinogeniculate map development.

    PubMed

    Markowitz, Jeffrey; Cao, Yongqiang; Grossberg, Stephen

    2012-01-01

    A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

  17. 40 CFR 61.154 - Standard for active waste disposal sites.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 8 2011-07-01 2011-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

  18. 40 CFR 61.154 - Standard for active waste disposal sites.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 9 2013-07-01 2013-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

  19. 40 CFR 61.154 - Standard for active waste disposal sites.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 9 2012-07-01 2012-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

  20. 40 CFR 61.154 - Standard for active waste disposal sites.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

  1. 40 CFR 61.154 - Standard for active waste disposal sites.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 9 2014-07-01 2014-07-01 false Standard for active waste disposal... for Asbestos § 61.154 Standard for active waste disposal sites. Each owner or operator of an active... visible emissions to the outside air from any active waste disposal site where asbestos-containing waste...

  2. MBARI Mapping AUV: A High-Resolution Deep Ocean Seafloor Mapping Capability

    NASA Astrophysics Data System (ADS)

    Caress, D. W.; Kirkwood, W. J.; Thomas, H.; McEwen, R.; Henthorn, R.; McGill, P.; Thompson, D.; Sibenac, M.; Jensen, S.; Shane, F.; Hamilton, A.

    2005-05-01

    The Monterey Bay Aquarium Research Institute (MBARI) is developing an autonomous seafloor mapping capability for deep ocean science applications. The MBARI Mapping AUV is a 0.53 m (21 in) diameter, 5.1 m (16.7 ft) long, Dorado-class vehicle designed to carry four mapping sonars. The primary sensor is a 200 kHz multibeam sonar producing swath bathymetry and sidescan. In addition, the vehicle carries 100 kHz and 410 kHz chirp sidescan sonars, and a 2-16 kHz sweep chirp subbottom profiler. Navigation and attitude data are obtained from an inertial navigation system (INS) incorporating a ring laser gyro and a 300 kHz Doppler velocity log (DVL). The vehicle also includes acoustic modem, ultra-short baseline navigation, and long-baseline navigation systems. The Mapping AUV is powered by 6 kWhr of Li-polymer batteries, providing expected mission duration of 12 hours at a typical speed of 1.5 m/s. All components of the vehicle are rated to 6000 m depth, allowing MBARI to conduct high-resolution mapping of the deep-ocean seafloor. The sonar package is also be mountable on ROV Ventana, allowing surveys at altitudes less than 20 m at topographically challenging sites. The vehicle was assembled and extensively tested during 2004; this year we are commencing operations for MBARI science projects while continuing the process of testing and integrating the complete suite of sensors and systems. MBARI is beginning to use this capability to observe the changing morphology of dynamic systems such as submarine canyons and active slumps, to map deep-water benthic habitats at resolutions comparable to ROV and submersible observations, to provide basemaps for ROV dives, and to provide high resolution bathymetry and subbottom profiles as part of a variety of projects requiring knowledge of the seafloor. We will present initial results from surveys in and around Monterey Canyon, including high resolution repeat surveys of four sites along the canyon axis.

  3. Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP)

    PubMed Central

    Wang, Jigang; Zhang, Chong-Jing; Zhang, Jianbin; He, Yingke; Lee, Yew Mun; Chen, Songbi; Lim, Teck Kwang; Ng, Shukie; Shen, Han-Ming; Lin, Qingsong

    2015-01-01

    Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) activity-based protein profiling (ABPP) and iTRAQ™ quantitative proteomics for identification of target proteins and (ii) acid-cleavable linker-based ABPP for identification of peptides with specific binding sites. It is known that reaction of aspirin with its target proteins leads to acetylation. We thus applied the above technique using aspirin-based probes in human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides with exact acetylation sites. By correlating these two sets of data, 523 proteins were identified as targets of aspirin. We used various biological assays to validate the effects of aspirin on inhibition of protein synthesis and induction of autophagy which were elicited from the pathway analysis of Aspirin target profile. This technique is widely applicable for target identification in the field of drug discovery and biology, especially for the covalent drugs. PMID:25600173

  4. Comprehensive identification of novel proteins and N-glycosylation sites in royal jelly

    PubMed Central

    2014-01-01

    Background Royal jelly (RJ) is a proteinaceous secretion produced from the hypopharyngeal and mandibular glands of nurse bees. It plays vital roles in honeybee biology and in the improvement of human health. However, some proteins remain unknown in RJ, and mapping N-glycosylation modification sites on RJ proteins demands further investigation. We used two different liquid chromatography-tandem mass spectrometry techniques, complementary N-glycopeptide enrichment strategies, and bioinformatic approaches to gain a better understanding of novel and glycosylated proteins in RJ. Results A total of 25 N-glycosylated proteins, carrying 53 N-glycosylation sites, were identified in RJ proteins, of which 42 N-linked glycosylation sites were mapped as novel on RJ proteins. Most of the glycosylated proteins were related to metabolic activities and health improvement. The 13 newly identified proteins were also mainly associated with metabolic processes and health improvement activities. Conclusion Our in-depth, large-scale mapping of novel glycosylation sites represents a crucial step toward systematically revealing the functionality of N-glycosylated RJ proteins, and is potentially useful for producing a protein with desirable pharmacokinetic and biological activity using a genetic engineering approach. The newly-identified proteins significantly extend the proteome coverage of RJ. These findings contribute vital and new knowledge to our understanding of the innate biochemical nature of RJ at both the proteome and glycoproteome levels. PMID:24529077

  5. Controlling the Active Sites of Sulfur-Doped Carbon Nanotube-Graphene Nanolobes for Highly Efficient Oxygen Evolution and Reduction Catalysis

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

    El-Sawy, Abdelhamid M.; Mosa, Islam M.; Su, Dong

    Controlling active sites of metal-free catalysts is an important strategy to enhance activity of the oxygen evolution reaction (OER). We made many attempts have been made to develop metal-free catalysts, but the lack of understanding of active-sites at the atomic-level has slowed the design of highly active and stable metal-free catalysts. We also developed a sequential two-step strategy to dope sulfur into carbon nanotube–graphene nanolobes. This bidoping strategy introduces stable sulfur–carbon active-sites. Fluorescence emission of the sulfur K-edge by X-ray absorption near edge spectroscopy (XANES) and scanning transmission electron microscopy electron energy loss spectroscopy (STEM-EELS) mapping and spectra confirm thatmore » increasing the incorporation of heterocyclic sulfur into the carbon ring of CNTs not only enhances OER activity with an overpotential of 350 mV at a current density of 10 mA cm -2, but also retains 100% of stability after 75 h. Furthermore, the bidoped sulfur carbon nanotube–graphene nanolobes behave like the state-of-the-art catalysts for OER but outperform those systems in terms of turnover frequency (TOF) which is two orders of magnitude greater than (20% Ir/C) at 400 mV overpotential with very high mass activity 1000 mA cm -2 at 570 mV. Moreover, the sulfur bidoping strategy shows high catalytic activity for the oxygen reduction reaction (ORR). Stable bifunctional (ORR and OER) catalysts are low cost, and light-weight bidoped sulfur carbon nanotubes are potential candidates for next-generation metal-free regenerative fuel cells.« less

  6. Controlling the Active Sites of Sulfur-Doped Carbon Nanotube-Graphene Nanolobes for Highly Efficient Oxygen Evolution and Reduction Catalysis

    DOE PAGES

    El-Sawy, Abdelhamid M.; Mosa, Islam M.; Su, Dong; ...

    2015-12-03

    Controlling active sites of metal-free catalysts is an important strategy to enhance activity of the oxygen evolution reaction (OER). We made many attempts have been made to develop metal-free catalysts, but the lack of understanding of active-sites at the atomic-level has slowed the design of highly active and stable metal-free catalysts. We also developed a sequential two-step strategy to dope sulfur into carbon nanotube–graphene nanolobes. This bidoping strategy introduces stable sulfur–carbon active-sites. Fluorescence emission of the sulfur K-edge by X-ray absorption near edge spectroscopy (XANES) and scanning transmission electron microscopy electron energy loss spectroscopy (STEM-EELS) mapping and spectra confirm thatmore » increasing the incorporation of heterocyclic sulfur into the carbon ring of CNTs not only enhances OER activity with an overpotential of 350 mV at a current density of 10 mA cm -2, but also retains 100% of stability after 75 h. Furthermore, the bidoped sulfur carbon nanotube–graphene nanolobes behave like the state-of-the-art catalysts for OER but outperform those systems in terms of turnover frequency (TOF) which is two orders of magnitude greater than (20% Ir/C) at 400 mV overpotential with very high mass activity 1000 mA cm -2 at 570 mV. Moreover, the sulfur bidoping strategy shows high catalytic activity for the oxygen reduction reaction (ORR). Stable bifunctional (ORR and OER) catalysts are low cost, and light-weight bidoped sulfur carbon nanotubes are potential candidates for next-generation metal-free regenerative fuel cells.« less

  7. Somatic activating mutations in MAP2K1 cause melorheostosis.

    PubMed

    Kang, Heeseog; Jha, Smita; Deng, Zuoming; Fratzl-Zelman, Nadja; Cabral, Wayne A; Ivovic, Aleksandra; Meylan, Françoise; Hanson, Eric P; Lange, Eileen; Katz, James; Roschger, Paul; Klaushofer, Klaus; Cowen, Edward W; Siegel, Richard M; Marini, Joan C; Bhattacharyya, Timothy

    2018-04-11

    Melorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we identify somatic mosaic MAP2K1 mutations in affected, but not unaffected, bone of eight unrelated patients with melorheostosis. The activating mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2 activation, and increased cell proliferation. However, these MAP2K1 mutations inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro, underlying the markedly increased osteoid detected in affected bone histology. Mosaicism is also detected in the skin overlying bone lesions in four of five patients tested. Our data show that the MAP2K1 oncogene is important in human bone formation and implicate MEK1 inhibition as a potential treatment avenue for melorheostosis.

  8. Comparing Two Forms of Concept Map Critique Activities to Facilitate Knowledge Integration Processes in Evolution Education

    ERIC Educational Resources Information Center

    Schwendimann, Beat A.; Linn, Marcia C.

    2016-01-01

    Concept map activities often lack a subsequent revision step that facilitates knowledge integration. This study compares two collaborative critique activities using a Knowledge Integration Map (KIM), a form of concept map. Four classes of high school biology students (n?=?81) using an online inquiry-based learning unit on evolution were assigned…

  9. Geology Report: Area 3 Radioactive Waste Management Site DOE/Nevada Test Site, Nye County, Nevada

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

    NSTec Environmental Management

    2006-07-01

    Surficial geologic studies near the Area 3 Radioactive Waste Management Site (RWMS) were conducted as part of a site characterization program. Studies included evaluation of the potential for future volcanism and Area 3 fault activity that could impact waste disposal operations at the Area 3 RWMS. Future volcanic activity could lead to disruption of the Area 3 RWMS. Local and regional studies of volcanic risk indicate that major changes in regional volcanic activity within the next 1,000 years are not likely. Mapped basalts of Paiute Ridge, Nye Canyon, and nearby Scarp Canyon are Miocene in age. There is a lackmore » of evidence for post-Miocene volcanism in the subsurface of Yucca Flat, and the hazard of basaltic volcanism at the Area 3 RWMS, within the 1,000-year regulatory period, is very low and not a forseeable future event. Studies included a literature review and data analysis to evaluate unclassified published and unpublished information regarding the Area 3 and East Branch Area 3 faults mapped in Area 3 and southern Area 7. Two trenches were excavated along the Area 3 fault to search for evidence of near-surface movement prior to nuclear testing. Allostratigraphic units and fractures were mapped in Trenches ST02 and ST03. The Area 3 fault is a plane of weakness that has undergone strain resulting from stress imposed by natural events and underground nuclear testing. No major vertical displacement on the Area 3 fault since the Early Holocene, and probably since the Middle Pleistocene, can be demonstrated. The lack of major displacement within this time frame and minimal vertical extent of minor fractures suggest that waste disposal operations at the Area 3 RWMS will not be impacted substantially by the Area 3 fault, within the regulatory compliance period. A geomorphic surface map of Yucca Flat utilizes the recent geomorphology and soil characterization work done in adjacent northern Frenchman Flat. The approach taken was to adopt the map unit boundaries

  10. National Park Service Vegetation Mapping Inventory Program: Appalachian National Scenic Trail vegetation mapping project

    USGS Publications Warehouse

    Hop, Kevin D.; Strassman, Andrew C.; Hall, Mark; Menard, Shannon; Largay, Ery; Sattler, Stephanie; Hoy, Erin E.; Ruhser, Janis; Hlavacek, Enrika; Dieck, Jennifer

    2017-01-01

    The National Park Service (NPS) Vegetation Mapping Inventory (VMI) Program classifies, describes, and maps existing vegetation of national park units for the NPS Natural Resource Inventory and Monitoring (I&M) Program. The NPS VMI Program is managed by the NPS I&M Division and provides baseline vegetation information to the NPS Natural Resource I&M Program. The U.S. Geological Survey Upper Midwest Environmental Sciences Center, NatureServe, NPS Northeast Temperate Network, and NPS Appalachian National Scenic Trail (APPA) have completed vegetation classification and mapping of APPA for the NPS VMI Program.Mappers, ecologists, and botanists collaborated to affirm vegetation types within the U.S. National Vegetation Classification (USNVC) of APPA and to determine how best to map the vegetation types by using aerial imagery. Analyses of data from 1,618 vegetation plots were used to describe USNVC associations of APPA. Data from 289 verification sites were collected to test the field key to vegetation associations and the application of vegetation associations to a sample set of map polygons. Data from 269 validation sites were collected to assess vegetation mapping prior to submitting the vegetation map for accuracy assessment (AA). Data from 3,265 AA sites were collected, of which 3,204 were used to test accuracy of the vegetation map layer. The collective of these datasets affirmed 280 USNVC associations for the APPA vegetation mapping project.To map the vegetation and land cover of APPA, 169 map classes were developed. The 169 map classes consist of 150 that represent natural (including ruderal) vegetation types in the USNVC, 11 that represent cultural (agricultural and developed) vegetation types in the USNVC, 5 that represent natural landscapes with catastrophic disturbance or some other modification to natural vegetation preventing accurate classification in the USNVC, and 3 that represent nonvegetated water (non-USNVC). Features were interpreted from viewing 4

  11. The GAAIN Entity Mapper: An Active-Learning System for Medical Data Mapping.

    PubMed

    Ashish, Naveen; Dewan, Peehoo; Toga, Arthur W

    2015-01-01

    This work is focused on mapping biomedical datasets to a common representation, as an integral part of data harmonization for integrated biomedical data access and sharing. We present GEM, an intelligent software assistant for automated data mapping across different datasets or from a dataset to a common data model. The GEM system automates data mapping by providing precise suggestions for data element mappings. It leverages the detailed metadata about elements in associated dataset documentation such as data dictionaries that are typically available with biomedical datasets. It employs unsupervised text mining techniques to determine similarity between data elements and also employs machine-learning classifiers to identify element matches. It further provides an active-learning capability where the process of training the GEM system is optimized. Our experimental evaluations show that the GEM system provides highly accurate data mappings (over 90% accuracy) for real datasets of thousands of data elements each, in the Alzheimer's disease research domain. Further, the effort in training the system for new datasets is also optimized. We are currently employing the GEM system to map Alzheimer's disease datasets from around the globe into a common representation, as part of a global Alzheimer's disease integrated data sharing and analysis network called GAAIN. GEM achieves significantly higher data mapping accuracy for biomedical datasets compared to other state-of-the-art tools for database schema matching that have similar functionality. With the use of active-learning capabilities, the user effort in training the system is minimal.

  12. 10 CFR 63.16 - Review of site characterization activities. 2

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

  13. 10 CFR 63.16 - Review of site characterization activities. 2

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

  14. 10 CFR 63.16 - Review of site characterization activities. 2

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

  15. 10 CFR 63.16 - Review of site characterization activities. 2

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

  16. 10 CFR 63.16 - Review of site characterization activities. 2

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... which such activities are carried out and to observe excavations, borings, and in situ tests, as they... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Licenses Preapplication Review § 63.16 Review of site characterization activities. 2 2 In addition to the review of site characterization activities...

  17. Three-dimensional mapping of equiprobable hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site

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

    Shirley, C.; Pohlmann, K.; Andricevic, R.

    1996-09-01

    Geological and geophysical data are used with the sequential indicator simulation algorithm of Gomez-Hernandez and Srivastava to produce multiple, equiprobable, three-dimensional maps of informal hydrostratigraphic units at the Frenchman Flat Corrective Action Unit, Nevada Test Site. The upper 50 percent of the Tertiary volcanic lithostratigraphic column comprises the study volume. Semivariograms are modeled from indicator-transformed geophysical tool signals. Each equiprobable study volume is subdivided into discrete classes using the ISIM3D implementation of the sequential indicator simulation algorithm. Hydraulic conductivity is assigned within each class using the sequential Gaussian simulation method of Deutsch and Journel. The resulting maps show the contiguitymore » of high and low hydraulic conductivity regions.« less

  18. A System and Method for Online High-Resolution Mapping of Gastric Slow-Wave Activity

    PubMed Central

    Bull, Simon H.; O’Grady, Gregory; Du, Peng

    2015-01-01

    High-resolution (HR) mapping employs multielectrode arrays to achieve spatially detailed analyses of propagating bioelectrical events. A major current limitation is that spatial analyses must currently be performed “off-line” (after experiments), compromising timely recording feedback and restricting experimental interventions. These problems motivated development of a system and method for “online” HR mapping. HR gastric recordings were acquired and streamed to a novel software client. Algorithms were devised to filter data, identify slow-wave events, eliminate corrupt channels, and cluster activation events. A graphical user interface animated data and plotted electrograms and maps. Results were compared against off-line methods. The online system analyzed 256-channel serosal recordings with no unexpected system terminations with a mean delay 18 s. Activation time marking sensitivity was 0.92; positive predictive value was 0.93. Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and colliding wave fronts were reliably identified. Compared to traditional analysis methods, online mapping had comparable results with equivalent coverage of 90% of electrodes, average RMS errors of less than 1 s, and CC of activation maps of 0.99. Accurate slow-wave mapping was achieved in near real-time, enabling monitoring of recording quality and experimental interventions targeted to dysrhythmic onset. This work also advances the translation of HR mapping toward real-time clinical application. PMID:24860024

  19. A system and method for online high-resolution mapping of gastric slow-wave activity.

    PubMed

    Bull, Simon H; O'Grady, Gregory; Du, Peng; Cheng, Leo K

    2014-11-01

    High-resolution (HR) mapping employs multielectrode arrays to achieve spatially detailed analyses of propagating bioelectrical events. A major current limitation is that spatial analyses must currently be performed "off-line" (after experiments), compromising timely recording feedback and restricting experimental interventions. These problems motivated development of a system and method for "online" HR mapping. HR gastric recordings were acquired and streamed to a novel software client. Algorithms were devised to filter data, identify slow-wave events, eliminate corrupt channels, and cluster activation events. A graphical user interface animated data and plotted electrograms and maps. Results were compared against off-line methods. The online system analyzed 256-channel serosal recordings with no unexpected system terminations with a mean delay 18 s. Activation time marking sensitivity was 0.92; positive predictive value was 0.93. Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and colliding wave fronts were reliably identified. Compared to traditional analysis methods, online mapping had comparable results with equivalent coverage of 90% of electrodes, average RMS errors of less than 1 s, and CC of activation maps of 0.99. Accurate slow-wave mapping was achieved in near real-time, enabling monitoring of recording quality and experimental interventions targeted to dysrhythmic onset. This work also advances the translation of HR mapping toward real-time clinical application.

  20. Remote Sensing Mars Landing Sites: An Out-of-School Time Planetary Science Education Activity for Middle School Students

    NASA Astrophysics Data System (ADS)

    Anderson, R. B.; Gaither, T. A.; Edgar, L. A.; Milazzo, M. P.; Vaughan, R. G.; Rubino-Hare, L.; Clark, J.; Ryan, S.

    2017-12-01

    As part of the Planetary Learning that Advances the Nexus of Engineering, Technology, and Science (PLANETS) project, we have developed an out-of-school time unit for middle school students focused on planetary remote sensing. The activity is divided into two exercises, with the goal of choosing a scientifically interesting and safe landing site for a future Mars mission. Students are introduced to NASA data from several actual and proposed landing sites and must use what they learn about remote sensing to choose a site that satisfies scientific and engineering criteria. The activity also includes background information for educators, including a summary of how landing on Mars helps answer major scientific questions, brief overviews of the data sets that the students will use, summaries of the site geology, and a list of relevant vocabulary. The first exercise introduces students to the concept of reflectance spectroscopy and how it can be used to identify the "fingerprints" of different minerals on the surface of Mars. Students are provided with simplified maps of mineral spectra at the four sites, based on Compact Reconnaissance Imaging Spectrometer (CRISM) observations, as well as a reference sheet with the spectra of common minerals on Mars. They can use this information to determine which sites have hydrated minerals, mafic minerals, or both. The second exercise adds data from the Mars Orbital Laser Altimeter (MOLA), and high resolution visible data from the Context Camera (CTX) on the Mars Reconnaissance Orbiter. Students learn about laser altimetry and how to interpret topographic contours to assess whether a landing site is too rough. The CTX data allow students to study the sites at higher resolution, with annotations that indicate key landforms of interest. These data, along with the spectroscopy data, allow students to rank the sites based on science and engineering criteria. This activity was developed as a collaboration between subject matter experts at

  1. Long-term comparison of Kuparuk Watershed active layer maps, northern Alaska, USA

    NASA Astrophysics Data System (ADS)

    Nyland, K. E.; Queen, C.; Nelson, F. E.; Shiklomanov, N. I.; Streletskiy, D. A.; Klene, A. E.

    2017-12-01

    The active layer, or the uppermost soil horizon that thaws seasonally, is among the most dynamic components of the permafrost system. Evaluation of the thickness and spatial variation of the active layer is critical to many components of Arctic research, including climatology, ecology, environmental monitoring, and engineering. In this study we mapped active-layer thickness (ALT) across the 22,278 sq. km Kuparuk River basin on Alaska's North Slope throughout the summer of 2016. The Kuparuk River extends from the Brooks Range through the Arctic Foothills and across the Arctic Coastal Plain physiographic provinces, and drains into the Beaufort Sea. Methodology followed procedures used to produce an ALT map of the basin in 1995 accounting for the effects of topography, vegetation, topoclimate, and soils, using the same spatial sampling scheme for direct ALT and temperature measurement at representative locations and relating these parameters to vegetation-soil associations. A simple semi-empirical engineering solution was used to estimate thaw rates for the different associations. An improved lapse-rate formulation and a higher-resolution DEM were used to relate temperature to elevation. Three ALT maps were generated for the 2016 summer, combining measured thaw depth, temperature records, the 25 m ArcticDEM, high resolution remote sensed data, empirical laps rates, and a topoclimatic index through the thaw solution. These maps were used to track the spatial progression of thaw through the 2016 summer season and estimate a total volume of thawed soil. Maps produced in this study were compared to the 1995 map to track areas of significant geographic changes in patterns of ALT and total volume of thawed soil.

  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. Decoding natural images from evoked brain activities using encoding models with invertible mapping.

    PubMed

    Li, Chao; Xu, Junhai; Liu, Baolin

    2018-05-21

    Recent studies have built encoding models in the early visual cortex, and reliable mappings have been made between the low-level visual features of stimuli and brain activities. However, these mappings are irreversible, so that the features cannot be directly decoded. To solve this problem, we designed a sparse framework-based encoding model that predicted brain activities from a complete feature representation. Moreover, according to the distribution and activation rules of neurons in the primary visual cortex (V1), three key transformations were introduced into the basic feature to improve the model performance. In this setting, the mapping was simple enough that it could be inverted using a closed-form formula. Using this mapping, we designed a hybrid identification method based on the support vector machine (SVM), and tested it on a published functional magnetic resonance imaging (fMRI) dataset. The experiments confirmed the rationality of our encoding model, and the identification accuracies for 2 subjects increased from 92% and 72% to 98% and 92% with the chance level only 0.8%. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Maps | Geospatial Data Science | NREL

    Science.gov Websites

    Maps Maps NREL develops an array of maps to support renewable energy development and generation resource in the United States by county Geothermal Maps of geothermal power plants, resources for enhanced geothermal systems, and hydrothermal sites in the United States Hydrogen Maps of hydrogen production

  5. Characterization of Foci and Breakthrough Sites During Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: Studies Using High-Density (510-512 Electrodes) Biatrial Epicardial Mapping.

    PubMed

    Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Markowitz, Alan; Waldo, Albert L

    2017-03-17

    We previously demonstrated that persistent and long-standing persistent atrial fibrillation is maintained by activation emanating from foci and breakthrough sites of different cycle lengths (CLs). The purpose of this study was to characterize the behavior of focal and nonrandom breakthrough activation identified during high-density mapping of atrial fibrillation in these patients. During open heart surgery, we recorded activation from both atria simultaneously using 510 to 512 epicardial electrodes along with ECG lead II in 12 patients with persistent and long-standing persistent atrial fibrillation. For each patient, analysis of 32 consecutive seconds of activation from identified focal (sustained and/or intermittent) and nonrandom breakthrough sites was performed. Multiple foci (sustained and/or intermittent) of different CLs were present in both atria in 11 of 12 patients; 8 foci were sustained, and 22 were intermittent. Temporal CL behavior of sustained foci varied over time (≤20 ms of the mean CL). For intermittent foci, no activation periods were due to a spontaneous pause (18 of 22) or activation of the focus by another wave front (11 of 22). All patients had breakthrough activation. Seven patients had 12 nonrandom breakthrough sites. Periods of no breakthrough activation were caused by a spontaneous pause (6 of 12 patients) or activation from another wave front (4 of 12) or were uncertain (5 of 12). Focal and nonrandom breakthrough activation sometimes produced repetitive "wannabe" (incomplete) reentry in 6 of 12 patients. During persistent and long-standing persistent atrial fibrillation, sustained foci manifested variable CLs. Spontaneous pauses or activation from other wave fronts explained the intermittency of foci and nonrandom breakthrough. Focal and nonrandom breakthrough activation occasionally produced wannabe reentry. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  6. Language Mapping in Multilingual Patients: Electrocorticography and Cortical Stimulation During Naming

    PubMed Central

    Cervenka, Mackenzie C.; Boatman-Reich, Dana F.; Ward, Julianna; Franaszczuk, Piotr J.; Crone, Nathan E.

    2011-01-01

    Multilingual patients pose a unique challenge when planning epilepsy surgery near language cortex because the cortical representations of each language may be distinct. These distinctions may not be evident with routine electrocortical stimulation mapping (ESM). Electrocorticography (ECoG) has recently been used to detect task-related spectral perturbations associated with functional brain activation. We hypothesized that using broadband high gamma augmentation (HGA, 60–150 Hz) as an index of cortical activation, ECoG would complement ESM in discriminating the cortical representations of first (L1) and second (L2) languages. We studied four adult patients for whom English was a second language, in whom subdural electrodes (a total of 358) were implanted to guide epilepsy surgery. Patients underwent ECoG recordings and ESM while performing the same visual object naming task in L1 and L2. In three of four patients, ECoG found sites activated during naming in one language but not the other. These language-specific sites were not identified using ESM. In addition, ECoG HGA was observed at more sites during L2 versus L1 naming in two patients, suggesting that L2 processing required additional cortical resources compared to L1 processing in these individuals. Post-operative language deficits were identified in three patients (one in L2 only). These deficits were predicted by ECoG spectral mapping but not by ESM. These results suggest that pre-surgical mapping should include evaluation of all utilized languages to avoid post-operative functional deficits. Finally, this study suggests that ECoG spectral mapping may potentially complement the results of ESM of language. PMID:21373361

  7. The GAAIN Entity Mapper: An Active-Learning System for Medical Data Mapping

    PubMed Central

    Ashish, Naveen; Dewan, Peehoo; Toga, Arthur W.

    2016-01-01

    This work is focused on mapping biomedical datasets to a common representation, as an integral part of data harmonization for integrated biomedical data access and sharing. We present GEM, an intelligent software assistant for automated data mapping across different datasets or from a dataset to a common data model. The GEM system automates data mapping by providing precise suggestions for data element mappings. It leverages the detailed metadata about elements in associated dataset documentation such as data dictionaries that are typically available with biomedical datasets. It employs unsupervised text mining techniques to determine similarity between data elements and also employs machine-learning classifiers to identify element matches. It further provides an active-learning capability where the process of training the GEM system is optimized. Our experimental evaluations show that the GEM system provides highly accurate data mappings (over 90% accuracy) for real datasets of thousands of data elements each, in the Alzheimer's disease research domain. Further, the effort in training the system for new datasets is also optimized. We are currently employing the GEM system to map Alzheimer's disease datasets from around the globe into a common representation, as part of a global Alzheimer's disease integrated data sharing and analysis network called GAAIN1. GEM achieves significantly higher data mapping accuracy for biomedical datasets compared to other state-of-the-art tools for database schema matching that have similar functionality. With the use of active-learning capabilities, the user effort in training the system is minimal. PMID:26793094

  8. 2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation.

    PubMed

    Lee, Yi-Nan; Yeh, Hung-I; Tian, Tin-Yi; Lu, Wen-Wei; Ko, Yu-Shien; Tsai, Cheng-Ho

    2002-09-30

    We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation.

  9. Remote magnetic navigation for mapping and ablating right ventricular outflow tract tachycardia.

    PubMed

    Thornton, Andrew S; Jordaens, Luc J

    2006-06-01

    Navigation, mapping, and ablation in the right ventricular outflow tract (RVOT) can be difficult. Catheter navigation using external magnetic fields may allow more accurate mapping and ablation. The purpose of this study was to assess the feasibility of RVOT tachycardia ablation using remote magnetic navigation. Mapping and ablation were performed in eight patients with outflow tract ventricular arrhythmias. Tachycardia mapping was undertaken with a 64-polar basket catheter, followed by remote activation and pace-mapping using a magnetically enabled catheter. The area of interest was localized on the basket catheter in seven patients in whom an RVOT arrhythmia was identified. Remote navigation of the magnetic catheter to this area was followed by pace-mapping. Ablation was performed at the site of perfect pace-mapping, with earliest activation if possible. Acute success was achieved in all patients (median four applications). Median procedural time was 144 minutes, with 13.4 minutes of patient fluoroscopy time and 3.8 minutes of physician fluoroscopy time. No complications occurred. One recurrence occurred during follow-up (mean 366 days). RVOT tachycardias can be mapped and ablated using remote magnetic navigation, initially guided by a basket catheter. Precise activation and pace-mapping are possible. Remote magnetic navigation permitted low fluoroscopy exposure for the physician. Long-term results are promising.

  10. Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles.

    PubMed

    Chiappini, Ciro; Campagnolo, Paola; Almeida, Carina S; Abbassi-Ghadi, Nima; Chow, Lesley W; Hanna, George B; Stevens, Molly M

    2015-09-16

    Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor human esophageal mucosa. Assembling a peptide-based Cathepsin B cleavable sensor over a large array of nano-needles allows the discrimination of cancer cells from healthy ones in mixed culture. The same sensor applied to tissue can map Cathepsin B activity with high resolution across the tumor margin area of esophageal adenocarcinoma. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Insights into earthquake hazard map performance from shaking history simulations

    NASA Astrophysics Data System (ADS)

    Stein, S.; Vanneste, K.; Camelbeeck, T.; Vleminckx, B.

    2017-12-01

    Why recent large earthquakes caused shaking stronger than predicted by earthquake hazard maps is under debate. This issue has two parts. Verification involves how well maps implement probabilistic seismic hazard analysis (PSHA) ("have we built the map right?"). Validation asks how well maps forecast shaking ("have we built the right map?"). We explore how well a map can ideally perform by simulating an area's shaking history and comparing "observed" shaking to that predicted by a map generated for the same parameters. The simulations yield shaking distributions whose mean is consistent with the map, but individual shaking histories show large scatter. Infrequent large earthquakes cause shaking much stronger than mapped, as observed. Hence, PSHA seems internally consistent and can be regarded as verified. Validation is harder because an earthquake history can yield shaking higher or lower than that predicted while being consistent with the hazard map. The scatter decreases for longer observation times because the largest earthquakes and resulting shaking are increasingly likely to have occurred. For the same reason, scatter is much less for the more active plate boundary than for a continental interior. For a continental interior, where the mapped hazard is low, even an M4 event produces exceedances at some sites. Larger earthquakes produce exceedances at more sites. Thus many exceedances result from small earthquakes, but infrequent large ones may cause very large exceedances. However, for a plate boundary, an M6 event produces exceedance at only a few sites, and an M7 produces them in a larger, but still relatively small, portion of the study area. As reality gives only one history, and a real map involves assumptions about more complicated source geometries and occurrence rates, which are unlikely to be exactly correct and thus will contribute additional scatter, it is hard to assess whether misfit between actual shaking and a map — notably higher-than-mapped

  12. De novo active sites for resurrected Precambrian enzymes

    NASA Astrophysics Data System (ADS)

    Risso, Valeria A.; Martinez-Rodriguez, Sergio; Candel, Adela M.; Krüger, Dennis M.; Pantoja-Uceda, David; Ortega-Muñoz, Mariano; Santoyo-Gonzalez, Francisco; Gaucher, Eric A.; Kamerlin, Shina C. L.; Bruix, Marta; Gavira, Jose A.; Sanchez-Ruiz, Jose M.

    2017-07-01

    Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties. We provide experimental and computational evidence that conformational flexibility can assist the emergence and subsequent evolution of new active sites by improving substrate and transition-state binding, through the sampling of many potentially productive conformations. Our results suggest a mechanism for the emergence of primordial enzymes and highlight the potential of ancestral reconstruction as a tool for protein engineering.

  13. Mapping of mosquito breeding sites in malaria endemic areas in Pos Lenjang, Kuala Lipis, Pahang, Malaysia.

    PubMed

    Ahmad, Rohani; Ali, Wan N W M; Nor, Zurainee M; Ismail, Zamree; Hadi, Azahari A; Ibrahim, Mohd N; Lim, Lee H

    2011-12-13

    The application of the Geographic Information Systems (GIS) to the study of vector transmitted diseases considerably improves the management of the information obtained from the field survey and facilitates the study of the distribution patterns of the vector species. As part of a study to assess remote sensing data as a tool for vector mapping, geographical features like rivers, small streams, forest, roads and residential area were digitized from the satellite images and overlaid with entomological data. Map of larval breeding habitats distribution and map of malaria transmission risk area were developed using a combination of field data, satellite image analysis and GIS technique. All digital data in the GIS were displayed in the WGS 1984 coordinate system. Six occasions of larval surveillance were also conducted to determine the species of mosquitoes, their characteristics and the abundance of habitats. Larval survey studies showed that anopheline and culicine larvae were collected and mapped from 79 and 67 breeding sites respectively. Breeding habitats were located at 100-400 m from human settlement. Map of villages with 400 m buffer zone visualizes that more than 80% of Anopheles maculatus s.s. immature habitats were found within the buffer zone. This study amplifies the need for a broadening of the GIS approach which is emphasized with the aim of rejuvenating the dynamic aspect of entomological studies in Malaysia. In fact, the use of such basic GIS platforms promote a more rational basis for strategic planning and management in the control of endemic diseases at the national level.

  14. Mapping of mosquito breeding sites in malaria endemic areas in Pos Lenjang, Kuala Lipis, Pahang, Malaysia

    PubMed Central

    2011-01-01

    Background The application of the Geographic Information Systems (GIS) to the study of vector transmitted diseases considerably improves the management of the information obtained from the field survey and facilitates the study of the distribution patterns of the vector species. Methods As part of a study to assess remote sensing data as a tool for vector mapping, geographical features like rivers, small streams, forest, roads and residential area were digitized from the satellite images and overlaid with entomological data. Map of larval breeding habitats distribution and map of malaria transmission risk area were developed using a combination of field data, satellite image analysis and GIS technique. All digital data in the GIS were displayed in the WGS 1984 coordinate system. Six occasions of larval surveillance were also conducted to determine the species of mosquitoes, their characteristics and the abundance of habitats. Results Larval survey studies showed that anopheline and culicine larvae were collected and mapped from 79 and 67 breeding sites respectively. Breeding habitats were located at 100-400 m from human settlement. Map of villages with 400 m buffer zone visualizes that more than 80% of Anopheles maculatus s.s. immature habitats were found within the buffer zone. Conclusions This study amplifies the need for a broadening of the GIS approach which is emphasized with the aim of rejuvenating the dynamic aspect of entomological studies in Malaysia. In fact, the use of such basic GIS platforms promote a more rational basis for strategic planning and management in the control of endemic diseases at the national level. PMID:22166101

  15. Molecular dynamics explorations of active site structure in designed and evolved enzymes.

    PubMed

    Osuna, Sílvia; Jiménez-Osés, Gonzalo; Noey, Elizabeth L; Houk, K N

    2015-04-21

    This Account describes the use of molecular dynamics (MD) simulations to reveal how mutations alter the structure and organization of enzyme active sites. As proposed by Pauling about 70 years ago and elaborated by many others since then, biocatalysis is efficient when functional groups in the active site of an enzyme are in optimal positions for transition state stabilization. Changes in mechanism and covalent interactions are often critical parts of enzyme catalysis. We describe our explorations of the dynamical preorganization of active sites using MD, studying the fluctuations between active and inactive conformations normally concealed to static crystallography. MD shows how the various arrangements of active site residues influence the free energy of the transition state and relates the populations of the catalytic conformational ensemble to the enzyme activity. This Account is organized around three case studies from our laboratory. We first describe the importance of dynamics in evaluating a series of computationally designed and experimentally evolved enzymes for the Kemp elimination, a popular subject in the enzyme design field. We find that the dynamics of the active site is influenced not only by the original sequence design and subsequent mutations but also by the nature of the ligand present in the active site. In the second example, we show how microsecond MD has been used to uncover the role of remote mutations in the active site dynamics and catalysis of a transesterase, LovD. This enzyme was evolved by Tang at UCLA and Codexis, Inc., and is a useful commercial catalyst for the production of the drug simvastatin. X-ray analysis of inactive and active mutants did not reveal differences in the active sites, but relatively long time scale MD in solution showed that the active site of the wild-type enzyme preorganizes only upon binding of the acyl carrier protein (ACP) that delivers the natural acyl group to the active site. In the absence of bound ACP

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  17. Relocating the Active-Site Lysine in Rhodopsin: 2. Evolutionary Intermediates.

    PubMed

    Devine, Erin L; Theobald, Douglas L; Oprian, Daniel D

    2016-08-30

    The visual pigment rhodopsin is a G protein-coupled receptor that covalently binds its retinal chromophore via a Schiff base linkage to an active-site Lys residue in the seventh transmembrane helix. Although this residue is strictly conserved among all type II retinylidene proteins, we found previously that the active-site Lys in bovine rhodopsin (Lys296) can be moved to three other locations (G90K, T94K, S186K) while retaining the ability to form a pigment with retinal and to activate transducin in a light-dependent manner [ Devine et al. ( 2013 ) Proc. Natl. Acad. Sci. USA 110 , 13351 - 13355 ]. Because the active-site Lys is not functionally constrained to be in helix seven, it is possible that it could relocate within the protein, most likely via an evolutionary intermediate with two active-site Lys. Therefore, in this study we characterized potential evolutionary intermediates with two Lys in the active site. Four mutant rhodopsins were prepared in which the original Lys296 was left untouched and a second Lys residue was substituted for G90K, T94K, S186K, or F293K. All four constructs covalently bind 11-cis-retinal, form a pigment, and activate transducin in a light-dependent manner. These results demonstrate that rhodopsin can tolerate a second Lys in the retinal binding pocket and suggest that an evolutionary intermediate with two Lys could allow migration of the Schiff base Lys to a position other than the observed, highly conserved location in the seventh TM helix. From sequence-based searches, we identified two groups of natural opsins, insect UV cones and neuropsins, that contain Lys residues at two positions in their active sites and also have intriguing spectral similarities to the mutant rhodopsins studied here.

  18. A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation.

    PubMed

    Dikic, I; Tokiwa, G; Lev, S; Courtneidge, S A; Schlessinger, J

    1996-10-10

    The mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. Transient overexpression of a dominant interfering mutant of Pyk2 or the protein tyrosine kinase Csk reduces LPA- or bradykinin-induced activation of MAP kinase. LPA- or bradykinin-induced MAP kinase activation was also inhibited by overexpression of dominant interfering mutants of Grb2 and Sos. We propose that Pyk2 acts with Src to link Gi- and Gq-coupled receptors with Grb2 and Sos to activate the MAP kinase signalling pathway in PC12 cells.

  19. The U.S. Geological Survey mapping and cartographic database activities, 2006-2010

    USGS Publications Warehouse

    Craun, Kari J.; Donnelly, John P.; Allord, Gregory J.

    2011-01-01

    The U.S. Geological Survey (USGS) began systematic topographic mapping of the United States in the 1880s, beginning with scales of 1:250,000 and 1:125,000 in support of geological mapping. Responding to the need for higher resolution and more detail, the 1:62,500-scale, 15-minute, topographic map series was begun in the beginning of the 20th century. Finally, in the 1950s the USGS adopted the 1:24,000-scale, 7.5-minute topographic map series to portray even more detail, completing the coverage of the conterminous 48 states of the United States with this series in 1992. In 2001, the USGS developed the vision and concept of The National Map, a topographic database for the 21st century and the source for a new generation of topographic maps (http://nationalmap.gov/). In 2008, the initial production of those maps began with a 1:24,000-scale digital product. In a separate, but related project, the USGS began scanning the existing inventory of historical topographic maps at all scales to accompany the new topographic maps. The USGS also had developed a digital database of The National Atlas of the United States. The digital version of Atlas is now Web-available and supports a mapping engine for small scale maps of the United States and North America. These three efforts define topographic mapping activities of the USGS during the last few years and are discussed below.

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

    PubMed

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

    2007-01-01

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

  1. Allosteric site-mediated active site inhibition of PBP2a using Quercetin 3-O-rutinoside and its combination.

    PubMed

    Rani, Nidhi; Vijayakumar, Saravanan; P T V, Lakshmi; Arunachalam, Annamalai

    2016-08-01

    Recent crystallographic study revealed the involvement of allosteric site in active site inhibition of penicillin binding protein (PBP2a), where one molecule of Ceftaroline (Cef) binds to the allosteric site of PBP2a and paved way for the other molecule (Cef) to bind at the active site. Though Cef has the potency to inhibit the PBP2a, its adverse side effects are of major concern. Previous studies have reported the antibacterial property of Quercetin derivatives, a group of natural compounds. Hence, the present study aims to evaluate the effect of Quercetin 3-o-rutinoside (Rut) in allosteric site-mediated active site inhibition of PBP2a. The molecular docking studies between allosteric site and ligands (Rut, Que, and Cef) revealed a better binding efficiency (G-score) of Rut (-7.790318) and Cef (-6.194946) with respect to Que (-5.079284). Molecular dynamic (MD) simulation studies showed significant changes at the active site in the presence of ligands (Rut and Cef) at allosteric site. Four different combinations of Rut and Cef were docked and their G-scores ranged between -6.320 and -8.623. MD studies revealed the stability of the key residue (Ser403) with Rut being at both sites, compared to other complexes. Morphological analysis through electron microscopy confirmed that combination of Rut and Cefixime was able to disturb the bacterial cell membrane in a similar fashion to that of Rut and Cefixime alone. The results of this study indicate that the affinity of Rut at both sites were equally good, with further validations Rut could be considered as an alternative for inhibiting MRSA growth.

  2. Construction of a high density SNP linkage map of kelp (Saccharina japonica) by sequencing Taq I site associated DNA and mapping of a sex determining locus.

    PubMed

    Zhang, Ning; Zhang, Linan; Tao, Ye; Guo, Li; Sun, Juan; Li, Xia; Zhao, Nan; Peng, Jie; Li, Xiaojie; Zeng, Liang; Chen, Jinsa; Yang, Guanpin

    2015-03-15

    Kelp (Saccharina japonica) has been intensively cultured in China for almost a century. Its genetic improvement is comparable with that of rice. However, the development of its molecular tools is extremely limited, thus its genes, genetics and genomics. Kelp performs an alternative life cycle during which sporophyte generation alternates with gametophyte generation. The gametophytes of kelp can be cloned and crossed. Due to these characteristics, kelp may serve as a reference for the biological and genetic studies of Volvox, mosses and ferns. We constructed a high density single nucleotide polymorphism (SNP) linkage map for kelp by restriction site associated DNA (RAD) sequencing. In total, 4,994 SNP-containing physical (tag-defined) RAD loci were mapped on 31 linkage groups. The map expanded a total genetic distance of 1,782.75 cM, covering 98.66% of the expected (1,806.94 cM). The length of RAD tags (85 bp) was extended to 400-500 bp with Miseq method, offering us an easiness of developing SNP chips and shifting SNP genotyping to a high throughput track. The number of linkage groups was in accordance with the documented with cytological methods. In addition, we identified a set of microsatellites (99 in total) from the extended RAD tags. A gametophyte sex determining locus was mapped on linkage group 2 in a window about 9.0 cM in width, which was 2.66 cM up to marker_40567 and 6.42 cM down to marker_23595. A high density SNP linkage map was constructed for kelp, an intensively cultured brown alga in China. The RAD tags were also extended so that a SNP chip could be developed. In addition, a set of microsatellites were identified among mapped loci, and a gametophyte sex determining locus was mapped. This map will facilitate the genetic studies of kelp including for example the evaluation of germplasm and the decipherment of the genetic bases of economic traits.

  3. Plasticity of orientation preference maps in the visual cortex of adult cats.

    PubMed

    Godde, Ben; Leonhardt, Ralph; Cords, Sven M; Dinse, Hubert R

    2002-04-30

    In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.

  4. Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes.

    PubMed

    Zastrow, Melissa L; Pecoraro, Vincent L

    2013-04-17

    While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.

  5. Effects of spatial variation of skull and cerebrospinal fluid layers on optical mapping of brain activities

    NASA Astrophysics Data System (ADS)

    Wang, Shuping; Shibahara, Nanae; Kuramashi, Daishi; Okawa, Shinpei; Kakuta, Naoto; Okada, Eiji; Maki, Atsushi; Yamada, Yukio

    2010-07-01

    In order to investigate the effects of anatomical variation in human heads on the optical mapping of brain activity, we perform simulations of optical mapping by solving the photon diffusion equation for layered-models simulating human heads using the finite element method (FEM). Particularly, the effects of the spatial variations in the thicknesses of the skull and cerebrospinal fluid (CSF) layers on mapping images are investigated. Mapping images of single active regions in the gray matter layer are affected by the spatial variations in the skull and CSF layer thicknesses, although the effects are smaller than those of the positions of the active region relative to the data points. The increase in the skull thickness decreases the sensitivity of the images to active regions, while the increase in the CSF layer thickness increases the sensitivity in general. The images of multiple active regions are also influenced by their positions relative to the data points and by their depths from the skin surface.

  6. Active Sites Environmental Monitoring Program: Mid-FY 1991 report

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

    Ashwood, T.L.; Wickliff, D.S.; Morrissey, C.M.

    1991-10-01

    This report summarizes the activities of the Active Sites Environmental Monitoring Program (ASEMP) from October 1990 through March 1991. The ASEMP was established in 1989 by Solid Waste Operations and the Environmental Sciences Division to provide early detection and performance monitoring at active low-level radioactive waste (LLW) disposal sites in Solid Waste Storage Area (SWSA) 6 and transuranic (TRU) waste storage sites in SWSA 5 as required by chapters II and III of US Department of Energy Order 5820.2A. Monitoring results continue to demonstrate the no LLW is being leached from the storage vaults on the tumulus pads. Loading ofmore » vaults on Tumulus II began during this reporting period and 115 vaults had been loaded by the end of March 1991.« less

  7. Theoretical considerations for mapping activation in human cardiac fibrillation

    NASA Astrophysics Data System (ADS)

    Rappel, Wouter-Jan; Narayan, Sanjiv M.

    2013-06-01

    Defining mechanisms for cardiac fibrillation is challenging because, in contrast to other arrhythmias, fibrillation exhibits complex non-repeatability in spatiotemporal activation but paradoxically exhibits conserved spatial gradients in rate, dominant frequency, and electrical propagation. Unlike animal models, in which fibrillation can be mapped at high spatial and temporal resolution using optical dyes or arrays of contact electrodes, mapping of cardiac fibrillation in patients is constrained practically to lower resolutions or smaller fields-of-view. In many animal models, atrial fibrillation is maintained by localized electrical rotors and focal sources. However, until recently, few studies had revealed localized sources in human fibrillation, so that the impact of mapping constraints on the ability to identify rotors or focal sources in humans was not described. Here, we determine the minimum spatial and temporal resolutions theoretically required to detect rigidly rotating spiral waves and focal sources, then extend these requirements for spiral waves in computer simulations. Finally, we apply our results to clinical data acquired during human atrial fibrillation using a novel technique termed focal impulse and rotor mapping (FIRM). Our results provide theoretical justification and clinical demonstration that FIRM meets the spatio-temporal resolution requirements to reliably identify rotors and focal sources for human atrial fibrillation.

  8. AAPG-CSD geologic provinces code map

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

    Meyer, R.F.; Wallace, L.G.; Wagner, F.J. Jr.

    1991-10-01

    This article provides the history of a revised geologic map which was drawn based on both surface geology and petroleum occurrence. The map includes offshore maps for California and the Gulf Coast of Texas and Louisiana. For onshore sites it provides geologic province boundaries which were drawn along county boundaries to approximate their position relative to oil and gas production. The offshore sites are drawn based on the universal transverse Mercator system.

  9. Ablation of post-surgical intra-atrial reentrant tachycardia. Predilection target sites and mapping approach.

    PubMed

    Anné, W; van Rensburg, H; Adams, J; Ector, H; Van de Werf, F; Heidbüchel, H

    2002-10-01

    Atrial arrhythmias are a frequent complication of atrial surgery. The location of these tachycardias is very diverse due to the individual difference in the original anatomy, surgical corrections, and effects of atrial fibrosis. Nevertheless some recurrent patterns are emerging. Forty-five patients underwent 51 ablation procedures between September 1995 and March 2001 using conventional mapping and temperature-controlled ablation. A duadecapolar catheter was swept from anterior to posterior in the right (and/or left) atrium, allowing for rapid mapping followed by entrainment confirmation. Twenty-eight patients had corrected congenital heart disease, 17 surgery for acquired heart disease. One hundred and sixteen arrhythmias were found, 86 circuits were targeted, 81 with success (94%). Despite the heterogeneous anatomy, the same targets were often encountered: the posterior isthmus between the inferior vena cava and the tricuspid ring (62%), the gap between the inferior vena cava and the atriotomy scar (49%), and the region around the atriopulmonary connection in Fontans (two out of four patients). After a mean follow-up of 24 months, 13 patients had a recurrent arrhythmia (29%) after their last procedure. There was a significant association between the number of circuits found during the initial procedure and the likelihood of recurrent arrhythmias. Knowledge of anatomical predilection sites and mapping the right (and/or left) atrium with a 'sweeping Halo technique' allow for effective ablation of most post-surgical atrial tachycardias. Severely damaged atria with multiple arrhythmias may require 'preventive' ablation of all recognizable channels.

  10. PNAS Plus: Mapping patterns of long-term settlement in Northern Mesopotamia at a large scale

    NASA Astrophysics Data System (ADS)

    Menze, Bjoern H.; Ur, Jason A.

    2012-04-01

    The landscapes of the Near East show both the first settlements and the longest trajectories of settlement systems. Mounding is a characteristic property of these settlement sites, resulting from millennia of continuing settlement activity at distinguished places. So far, however, this defining feature of ancient settlements has not received much attention, or even been the subject of systematic evaluation. We propose a remote sensing approach for comprehensively mapping the pattern of human settlement at large scale and establish the largest archaeological record for a landscape in Mesopotamia, mapping about 14,000 settlement sites-spanning eight millennia-at 15-m resolution in a 23,000-km2 area in northeastern Syria. To map both low- and high-mounded places-the latter of which are often referred to as "tells"-we develop a strategy for detecting anthrosols in time series of multispectral satellite images and measure the volume of settlement sites in a digital elevation model. Using this volume as a proxy to continued occupation, we find a dependency of the long-term attractiveness of a site on local water availability, but also a strong relation to the relevance within a basin-wide exchange network that we can infer from our record and third millennium B.C. intersite routes visible on the ground until recent times. We believe it is possible to establish a nearly comprehensive map of human settlements in the fluvial plains of northern Mesopotamia and beyond, and site volume may be a key quantity to uncover long-term trends in human settlement activity from such a record.

  11. NREL: International Activities - Afghanistan Resource Maps

    Science.gov Websites

    facilities, load centers, terrain conditions, and land use. The high-resolution (1-km) annual wind power maps . The high-resolution (10-km) annual and seasonal solar resource maps were developed using weather -km Resolution Annual Maps (Direct) Low-Res (JPG 104 KB) | High-Res (ZIP 330 KB) 40-km Resolution

  12. Active Free Surface Density Maps

    NASA Astrophysics Data System (ADS)

    Çelen, S.

    2016-10-01

    Percolation problems were occupied to many physical problems after their establishment in 1957 by Broadbent and Hammersley. They can be used to solve complex systems such as bone remodeling. Volume fraction method was adopted to set some algorithms in the literature. However, different rate of osteoporosis could be observed for different microstructures which have the same mass density, mechanical stimuli, hormonal stimuli and nutrition. Thus it was emphasized that the bone might have identical porosity with different specific surfaces. Active free surface density of bone refers the used total area for its effective free surface. The purpose of this manuscript is to consolidate a mathematical approach which can be called as “active free surface density maps” for different surface patterns and derive their formulations. Active free surface density ratios were calculated for different Archimedean lattice models according to Helmholtz free energy and they were compared with their site and bond percolation thresholds from the background studies to derive their potential probability for bone remodeling.

  13. 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.

  14. Using Web Maps to Analyze the Construction of Global Scale Cognitive Maps

    ERIC Educational Resources Information Center

    Pingel, Thomas J.

    2018-01-01

    Game-based Web sites and applications are changing the ways in which students learn the world map. In this study, a Web map-based digital learning tool was used as a study aid for a university-level geography course in order to examine the way in which global scale cognitive maps are constructed. A network analysis revealed that clicks were…

  15. Concealed Accessory Pathways with a Single Ventricular and Two Discrete Atrial Insertion Sites.

    PubMed

    Kipp, Ryan T; Abu Sham'a, Raed; Hiroyuki, Ito; Han, Frederick T; Refaat, Marwan; Hsu, Jonathan C; Field, Michael E; Kopp, Douglas E; Marcus, Gregory M; Scheinman, Melvin M; Hoffmayer, Kurt S

    2017-03-01

    Atrioventricular reciprocating tachycardia (AVRT) utilizing a concealed accessory pathway is common. It is well appreciated that some patients may have multiple accessory pathways with separate atrial and ventricular insertion sites. We present three cases of AVRT utilizing concealed pathways with evidence that each utilizing a single ventricular insertion and two discrete atrial insertion sites. In case one, two discrete atrial insertion sites were mapped in two separate procedures, and only during the second ablation was the Kent potential identified. Ablation of the Kent potential at this site remote from the two atrial insertion sites resulted in the termination of the retrograde conduction in both pathways. Case two presented with supraventricular tachycardia (SVT) with alternating eccentric atrial activation patterns without alteration in the tachycardia cycle length. The two distinct atrial insertion sites during orthodromic AVRT and ventricular pacing were targeted and each of the two atrial insertion sites were successfully mapped and ablated. In case three, retrograde decremental conduction utilizing both atrial insertion sites was identified prior to ablation. After mapping and ablation of the first discrete atrial insertion site, tachycardia persisted utilizing the second atrial insertion site. Only after ablation of the second atrial insertion site was SVT noninducible, and VA conduction was no longer present. Concealed retrograde accessory pathways with discrete atrial insertion sites may have a common ventricular insertion site. Identification and ablation of the ventricular insertion site or the separate discrete atrial insertion sites result in successful treatment. © 2017 Wiley Periodicals, Inc.

  16. The Lunar Mapping and Modeling Project

    NASA Technical Reports Server (NTRS)

    Noble, Sarah K.; French, R. A.; Nall, M. E.; Muery, K. G.

    2009-01-01

    The Lunar Mapping and Modeling Project (LMMP) has been created to manage the development of a suite of lunar mapping and modeling products that support the Constellation Program (CxP) and other lunar exploration activities, including the planning, design, development, test and operations associated with lunar sortie missions, crewed and robotic operations on the surface, and the establishment of a lunar outpost. The information provided through LMMP will assist CxP in: planning tasks in the areas of landing site evaluation and selection, design and placement of landers and other stationary assets, design of rovers and other mobile assets, developing terrain-relative navigation (TRN) capabilities, and assessment and planning of science traverses.

  17. Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution

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

    Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.

    1994-09-01

    Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less

  18. Mapping site index and volume increment from forest inventory, Landsat, and ecological variables in Tahoe National Forest, California, USA

    USGS Publications Warehouse

    Huang, Shengli; Ramirez, Carlos; Conway, Scott; Kennedy, Kama; Kohler, Tanya; Liu, Jinxun

    2016-01-01

    High-resolution site index (SI) and mean annual increment (MAI) maps are desired for local forest management. We integrated field inventory, Landsat, and ecological variables to produce 30 m SI and MAI maps for the Tahoe National Forest (TNF) where different tree species coexist. We converted species-specific SI using adjustment factors. Then, the SI map was produced by (i) intensifying plots to expand the training sets to more climatic, topographic, soil, and forest reflective classes, (ii) using results from a stepwise regression to enable a weighted imputation that minimized the effects of outlier plots within classes, and (iii) local interpolation and strata median filling to assign values to pixels without direct imputations. The SI (reference age is 50 years) map had an R2 of 0.7637, a root-mean-square error (RMSE) of 3.60, and a mean absolute error (MAE) of 3.07 m. The MAI map was similarly produced with an R2 of 0.6882, an RMSE of 1.73, and a MAE of 1.20 m3·ha−1·year−1. Spatial patterns and trends of SI and MAI were analyzed to be related to elevation, aspect, slope, soil productivity, and forest type. The 30 m SI and MAI maps can be used to support decisions on fire, plantation, biodiversity, and carbon.

  19. The active site of hen egg-white lysozyme: flexibility and chemical bonding

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

    Held, Jeanette, E-mail: jeanette.netzel@uni-bayreuth.de; Smaalen, Sander van

    Chemical bonding at the active site of lysozyme is analyzed on the basis of a multipole model employing transferable multipole parameters from a database. Large B factors at low temperatures reflect frozen-in disorder, but therefore prevent a meaningful free refinement of multipole parameters. Chemical bonding at the active site of hen egg-white lysozyme (HEWL) is analyzed on the basis of Bader’s quantum theory of atoms in molecules [QTAIM; Bader (1994 ▶), Atoms in Molecules: A Quantum Theory. Oxford University Press] applied to electron-density maps derived from a multipole model. The observation is made that the atomic displacement parameters (ADPs) ofmore » HEWL at a temperature of 100 K are larger than ADPs in crystals of small biological molecules at 298 K. This feature shows that the ADPs in the cold crystals of HEWL reflect frozen-in disorder rather than thermal vibrations of the atoms. Directly generalizing the results of multipole studies on small-molecule crystals, the important consequence for electron-density analysis of protein crystals is that multipole parameters cannot be independently varied in a meaningful way in structure refinements. Instead, a multipole model for HEWL has been developed by refinement of atomic coordinates and ADPs against the X-ray diffraction data of Wang and coworkers [Wang et al. (2007), Acta Cryst. D63, 1254–1268], while multipole parameters were fixed to the values for transferable multipole parameters from the ELMAM2 database [Domagala et al. (2012), Acta Cryst. A68, 337–351] . Static and dynamic electron densities based on this multipole model are presented. Analysis of their topological properties according to the QTAIM shows that the covalent bonds possess similar properties to the covalent bonds of small molecules. Hydrogen bonds of intermediate strength are identified for the Glu35 and Asp52 residues, which are considered to be essential parts of the active site of HEWL. Furthermore, a series of weak C

  20. Mapping auroral activity with Twitter

    NASA Astrophysics Data System (ADS)

    Case, N. A.; MacDonald, E. A.; Heavner, M.; Tapia, A. H.; Lalone, N.

    2015-05-01

    Twitter is a popular, publicly accessible, social media service that has proven useful in mapping large-scale events in real time. In this study, for the first time, the use of Twitter as a measure of auroral activity is investigated. Peaks in the number of aurora-related tweets are found to frequently coincide with geomagnetic disturbances (detection rate of 91%). Additionally, the number of daily aurora-related tweets is found to strongly correlate with several auroral strength proxies (ravg≈0.7). An examination is made of the bias for location and time of day within Twitter data, and a first-order correction of these effects is presented. Overall, the results suggest that Twitter can provide both specific details about an individual aurora and accurate real-time indication of when, and even from where, an aurora is visible.

  1. Astrobiology Road Mapping (AstRoMap) - A project within FP7 of the European Commission: First results

    NASA Astrophysics Data System (ADS)

    Gomez-Gomez, Felipe; Capria, Maria Teresa; Palomba, Ernesto; Walter, Nicolas; Rettberg, Petra; Muller, Christian; Horneck, Gerda

    elaborated during the workshops, an astrobiology roadmap will be constructed tailored to the European needs and competences. 4. Education and public outreach. Parallel to the workshop and consultation activities, AstRoMap will provide a comprehensive education and outreach programme and disseminate the progress of AstRoMap through its web site (http://www.astromap.eu).

  2. Quantification and site-specification of the support practice factor when mapping soil erosion risk associated with olive plantations in the Mediterranean island of Crete.

    PubMed

    Karydas, Christos G; Sekuloska, Tijana; Silleos, Georgios N

    2009-02-01

    Due to inappropriate agricultural management practices, soil erosion is becoming one of the most dangerous forms of soil degradation in many olive farming areas in the Mediterranean region, leading to significant decrease of soil fertility and yield. In order to prevent further soil degradation, proper measures are necessary to be locally implemented. In this perspective, an increase in the spatial accuracy of remote sensing datasets and advanced image analysis are significant tools necessary and efficient for mapping soil erosion risk on a fine scale. In this study, the Revised Universal Soil Loss Equation (RUSLE) was implemented in the spatial domain using GIS, while a very high resolution satellite image, namely a QuickBird image, was used for deriving cover management (C) and support practice (P) factors, in order to map the risk of soil erosion in Kolymvari, a typical olive farming area in the island of Crete, Greece. The results comprised a risk map of soil erosion when P factor was taken uniform (conventional approach) and a risk map when P factor was quantified site-specifically using object-oriented image analysis. The results showed that the QuickBird image was necessary in order to achieve site-specificity of the P factor and therefore to support fine scale mapping of soil erosion risk in an olive cultivation area, such as the one of Kolymvari in Crete. Increasing the accuracy of the QB image classification will further improve the resulted soil erosion mapping.

  3. All the catalytic active sites of MoS 2 for hydrogen evolution

    DOE PAGES

    Li, Guoqing; Zhang, Du; Qiao, Qiao; ...

    2016-11-29

    MoS 2 presents a promising low-cost catalyst for the hydrogen evolution reaction (HER), but the understanding about its active sites has remained limited. Here we present an unambiguous study of the catalytic activities of all possible reaction sites of MoS 2, including edge sites, sulfur vacancies, and grain boundaries. We demonstrate that, in addition to the well-known catalytically active edge sites, sulfur vacancies provide another major active site for the HER, while the catalytic activity of grain boundaries is much weaker. Here, the intrinsic turnover frequencies (Tafel slopes) of the edge sites, sulfur vacancies, and grain boundaries are estimated tomore » be 7.5 s –1 (65–75 mV/dec), 3.2 s –1 (65–85 mV/dec), and 0.1 s –1 (120–160 mV/dec), respectively. We also demonstrate that the catalytic activity of sulfur vacancies strongly depends on the density of the vacancies and the local crystalline structure in proximity to the vacancies. Unlike edge sites, whose catalytic activity linearly depends on the length, sulfur vacancies show optimal catalytic activities when the vacancy density is in the range of 7–10%, and the number of sulfur vacancies in high crystalline quality MoS 2 is higher than that in low crystalline quality MoS 2, which may be related with the proximity of different local crystalline structures to the vacancies.« less

  4. Machine-Learning Methods Enable Exhaustive Searches for Active Bimetallic Facets and Reveal Active Site Motifs for CO 2 Reduction

    DOE PAGES

    Ulissi, Zachary W.; Tang, Michael T.; Xiao, Jianping; ...

    2017-07-27

    Bimetallic catalysts are promising for the most difficult thermal and electrochemical reactions, but modeling the many diverse active sites on polycrystalline samples is an open challenge. Here, we present a general framework for addressing this complexity in a systematic and predictive fashion. Active sites for every stable low-index facet of a bimetallic crystal are enumerated and cataloged, yielding hundreds of possible active sites. The activity of these sites is explored in parallel using a neural-network-based surrogate model to share information between the many density functional theory (DFT) relaxations, resulting in activity estimates with an order of magnitude fewer explicit DFTmore » calculations. Sites with interesting activity were found and provide targets for follow-up calculations. This process was applied to the electrochemical reduction of CO 2 on nickel gallium bimetallics and indicated that most facets had similar activity to Ni surfaces, but a few exposed Ni sites with a very favorable on-top CO configuration. This motif emerged naturally from the predictive modeling and represents a class of intermetallic CO 2 reduction catalysts. These sites rationalize recent experimental reports of nickel gallium activity and why previous materials screens missed this exciting material. Most importantly these methods suggest that bimetallic catalysts will be discovered by studying facet reactivity and diversity of active sites more systematically.« less

  5. Machine-Learning Methods Enable Exhaustive Searches for Active Bimetallic Facets and Reveal Active Site Motifs for CO 2 Reduction

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

    Ulissi, Zachary W.; Tang, Michael T.; Xiao, Jianping

    Bimetallic catalysts are promising for the most difficult thermal and electrochemical reactions, but modeling the many diverse active sites on polycrystalline samples is an open challenge. Here, we present a general framework for addressing this complexity in a systematic and predictive fashion. Active sites for every stable low-index facet of a bimetallic crystal are enumerated and cataloged, yielding hundreds of possible active sites. The activity of these sites is explored in parallel using a neural-network-based surrogate model to share information between the many density functional theory (DFT) relaxations, resulting in activity estimates with an order of magnitude fewer explicit DFTmore » calculations. Sites with interesting activity were found and provide targets for follow-up calculations. This process was applied to the electrochemical reduction of CO 2 on nickel gallium bimetallics and indicated that most facets had similar activity to Ni surfaces, but a few exposed Ni sites with a very favorable on-top CO configuration. This motif emerged naturally from the predictive modeling and represents a class of intermetallic CO 2 reduction catalysts. These sites rationalize recent experimental reports of nickel gallium activity and why previous materials screens missed this exciting material. Most importantly these methods suggest that bimetallic catalysts will be discovered by studying facet reactivity and diversity of active sites more systematically.« less

  6. Mutation at a strictly conserved, active site tyrosine in the copper amine oxidase leads to uncontrolled oxygenase activity.

    PubMed

    Chen, Zhi-Wei; Datta, Saumen; Dubois, Jennifer L; Klinman, Judith P; Mathews, F Scott

    2010-08-31

    The copper amine oxidases carry out two copper-dependent processes: production of their own redox-active cofactor (2,4,5-trihydroxyphenylalanine quinone, TPQ) and the subsequent oxidative deamination of substrate amines. Because the same active site pocket must facilitate both reactions, individual active site residues may serve multiple roles. We have examined the roles of a strictly conserved active site tyrosine Y305 in the copper amine oxidase from Hansenula polymorpha kinetically, spetroscopically (Dubois and Klinman (2006) Biochemistry 45, 3178), and, in the present work, structurally. While the Y305A enzyme is almost identical to the wild type, a novel, highly oxygenated species replaces TPQ in the Y305F active sites. This new structure not only provides the first direct detection of peroxy intermediates in cofactor biogenesis but also indicates the critical control of oxidation chemistry that can be conferred by a single active site residue.

  7. Mapping bathymetry in an active surf zone with the WorldView2 multispectral satellite

    NASA Astrophysics Data System (ADS)

    Trimble, S. M.; Houser, C.; Brander, R.; Chirico, P.

    2015-12-01

    Rip currents are strong, narrow seaward flows of water that originate in the surf zones of many global beaches. They are related to hundreds of international drownings each year, but exact numbers are difficult to calculate due to logistical difficulties in obtaining accurate incident reports. Annual average rip current fatalities are estimated to be ~100, 53 and 21 in the United States (US), Costa Rica, and Australia respectively. Current warning systems (e.g. National Weather Service) do not account for fine resolution nearshore bathymetry because it is difficult to capture. The method shown here could provide frequent, high resolution maps of nearshore bathymetry at a scale required for improved rip prediction and warning. This study demonstrates a method for mapping bathymetry in the surf zone (20m deep and less), specifically within rip channels, because rips form at topographically low spots in the bathymetry as a result of feedback amongst waves, substrate, and antecedent bathymetry. The methods employ the Digital Globe WorldView2 (WV2) multispectral satellite and field measurements of depth to generate maps of the changing bathymetry at two embayed, rip-prone beaches: Playa Cocles, Puerto Viejo de Talamanca, Costa Rica, and Bondi Beach, Sydney, Australia. WV2 has a 1.1 day pass-over rate with 1.84m ground pixel resolution of 8 bands, including 'yellow' (585-625 nm) and 'coastal blue' (400-450 nm). The data is used to classify bottom type and to map depth to the return in multiple bands. The methodology is tested at each site for algorithm consistency between dates, and again for applicability between sites.

  8. Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm.

    PubMed

    Atienza, Felipe; Almendral, Jesús; Jalife, José; Zlochiver, Sharon; Ploutz-Snyder, Robert; Torrecilla, Esteban G; Arenal, Angel; Kalifa, Jérôme; Fernández-Avilés, Francisco; Berenfeld, Omer

    2009-01-01

    Spectral analysis identifies localized sites of high-frequency activity during atrial fibrillation (AF). This study sought to determine the effectiveness of using real-time dominant frequency (DF) mapping for radiofrequency ablation of maximal DF (DFmax) sites and elimination of left-to-right frequency gradients in the long-term maintenance of sinus rhythm (SR) in AF patients. DF mapping was performed in 50 patients during ongoing AF (32 paroxysmal, 18 persistent), acquiring a mean of 117 +/- 38 points. Ablation was performed targeting DFmax sites, followed by circumferential pulmonary vein isolation. Ablation significantly reduced DFs (Hz) in the LA (7.9 +/- 1.4 vs. 5.7 +/- 1.3, P <.001), coronary sinus (CS) (5.7 +/- 1.1 vs. 5.3 +/- 1.2, P = .006), and RA (6.3 +/- 1.4 vs. 5.4 +/- 1.3, P <.001) abolishing baseline left-to-right atrial DF gradient (1.7 +/- 1.7 vs. 0.2 +/- 0.9; P <.001). Only a significant reduction in DFs in all chambers with a loss of the left-to-right atrial gradient after ablation was associated with a higher probability of long-term SR maintenance in both paroxysmal and persistent AF patients. After a mean follow-up of 9.3 +/- 5.4 months, 88% of paroxysmal and 56% of persistent AF patients were free of AF (P = .02). Ablation of DFmax sites was associated with a higher probability of remaining both free of arrhythmias (78% vs. 20%; P = .001) and free of AF (88% vs. 30%; P <.001). Radiofrequency ablation leading to elimination of LA-to-RA frequency gradients predicts long-term SR maintenance in AF patients.

  9. Near-Atomic Three-Dimensional Mapping for Site-Specific Chemistry of 'Superbugs'.

    PubMed

    Adineh, Vahid R; Marceau, Ross K W; Velkov, Tony; Li, Jian; Fu, Jing

    2016-11-09

    Emergence of multidrug resistant Gram-negative bacteria has caused a global health crisis and last-line class of antibiotics such as polymyxins are increasingly used. The chemical composition at the cell surface plays a key role in antibiotic resistance. Unlike imaging the cellular ultrastructure with well-developed electron microscopy, the acquisition of a high-resolution chemical map of the bacterial surface still remains a technological challenge. In this study, we developed an atom probe tomography (APT) analysis approach to acquire mass spectra in the pulsed-voltage mode and reconstructed the 3D chemical distribution of atoms and molecules in the subcellular domain at the near-atomic scale. Using focused ion beam (FIB) milling together with micromanipulation, site-specific samples were retrieved from a single cell of Acinetobacter baumannii prepared as needle-shaped tips with end radii less than 60 nm, followed by a nanoscale coating of silver in the order of 10 nm. The significantly elevated conductivity provided by the metallic coating enabled successful and routine field evaporation of the biological material, with all the benefits of pulsed-voltage APT. In parallel with conventional cryo-TEM imaging, our novel approach was applied to investigate polymyxin-susceptible and -resistant strains of A. baumannii after treatment of polymyxin B. Acquired atom probe mass spectra from the cell envelope revealed characteristic fragments of phosphocholine from the polymyxin-susceptible strain, but limited signals from this molecule were detected in the polymyxin-resistant strain. This study promises unprecedented capacity for 3D nanoscale imaging and chemical mapping of bacterial cells at the ultimate 3D spatial resolution using APT.

  10. Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

    PubMed Central

    Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

    2014-01-01

    Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. PMID:24920327

  11. Chapter 12: Daily Patterns of Marbled Murrelet Activity at Inland Sites

    Treesearch

    Nancy L. Naslund; Brian P. O’Donnell

    1995-01-01

    Patterns in the daily activity of Marbled Murrelets (Brachyramphus marmoratus) at inland sites has been studied throughout their range from California to Alaska. Murrelets are most active at inland sites around dawn, and to a lesser degree, at dusk. Throughout their range, peak levels of activity (detections) occur in the hour around dawn, but...

  12. An Active Site Water Network in the Plasminogen Activator Pla from Yersinia pestis

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

    Eren, Elif; Murphy, Megan; Goguen, Jon

    2010-08-13

    The plasminogen activator Pla from Yersinia pestis is an outer membrane protease (omptin) that is important for the virulence of plague. Here, we present the high-resolution crystal structure of wild-type, enzymatically active Pla at 1.9 {angstrom}. The structure shows a water molecule located between active site residues D84 and H208, which likely corresponds to the nucleophilic water. A number of other water molecules are present in the active site, linking residues important for enzymatic activity. The R211 sidechain in loop L4 is close to the nucleophilic water and possibly involved in the stabilization of the oxyanion intermediate. Subtle conformational changesmore » of H208 result from the binding of lipopolysaccharide to the outside of the barrel, explaining the unusual dependence of omptins on lipopolysaccharide for activity. The Pla structure suggests a model for the interaction with plasminogen substrate and provides a more detailed understanding of the catalytic mechanism of omptin proteases.« less

  13. 76 FR 77208 - Affirmation of Vertical Datum for Surveying and Mapping Activities for the Islands of St. Croix...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-12

    ... Datum for Surveying and Mapping Activities for the Islands of St. Croix, St. John, and St. Thomas... datum for surveying and mapping activities for the islands of St. Croix, St. John, and St. Thomas of the... by other Federal surveying and mapping agencies on St. Croix, St. John, and St. Thomas, with the...

  14. Application of Satellite SAR Imagery in Mapping the Active Layer of Arctic Permafrost

    NASA Technical Reports Server (NTRS)

    Li, Shu-Sun; Romanovsky, V.; Lovick, Joe; Wang, Z.; Peterson, Rorik

    2003-01-01

    A method of mapping the active layer of Arctic permafrost using a combination of conventional synthetic aperture radar (SAR) backscatter and more sophisticated interferometric SAR (INSAR) techniques is proposed. The proposed research is based on the sensitivity of radar backscatter to the freeze and thaw status of the surface soil, and the sensitivity of INSAR techniques to centimeter- to sub-centimeter-level surface differential deformation. The former capability of SAR is investigated for deriving the timing and duration of the thaw period for surface soil of the active layer over permafrost. The latter is investigated for the feasibility of quantitative measurement of frost heaving and thaw settlement of the active layer during the freezing and thawing processes. The resulting knowledge contributes to remote sensing mapping of the active layer dynamics and Arctic land surface hydrology.

  15. MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2

    PubMed Central

    Coady, Michael J.; El Tarazi, Abdulah; Santer, René; Bissonnette, Pierre; Sasseville, Louis J.; Calado, Joaquim; Lussier, Yoann; Dumayne, Christopher; Bichet, Daniel G.

    2017-01-01

    The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na+-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17–SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na+/H+ exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. PMID:27288013

  16. Mapping the active site helix-to-strand conversion of CxxxxC peroxiredoxin Q enzymes.

    PubMed

    Perkins, Arden; Gretes, Michael C; Nelson, Kimberly J; Poole, Leslie B; Karplus, P Andrew

    2012-09-25

    Peroxiredoxins (Prx) make up a family of enzymes that reduce peroxides using a peroxidatic cysteine residue; among these, members of the PrxQ subfamily are proposed to be the most ancestral-like yet are among the least characterized. In many PrxQ enzymes, a second "resolving" cysteine is located five residues downstream from the peroxidatic Cys, and these residues form a disulfide during the catalytic cycle. Here, we describe three hyperthermophilic PrxQ crystal structures originally determined by the RIKEN structural genomics group. We reprocessed the diffraction data and conducted further refinement to yield models with R(free) values lowered by 2.3-7.2% and resolution extended by 0.2-0.3 Å, making one, at 1.4 Å, one of the best resolved peroxiredoxins to date. Comparisons of two matched thiol and disulfide forms reveal that the active site conformational change required for disulfide formation involves a transition of ~20 residues from a pair of α-helices to a β-hairpin and 3(10)-helix. Each conformation has ~10 residues with a high level of disorder providing slack that allows the dramatic shift, and the two conformations are anchored to the protein core by distinct nonpolar side chains that fill three hydrophobic pockets. Sequence conservation patterns confirm the importance of these and a few additional residues for function. From a broader perspective, this study raises the provocative question of how to make use of the valuable information in the Protein Data Bank generated by structural genomics projects but not described in the literature, perhaps remaining unrecognized and certainly underutilized.

  17. Geophysical investigation, Salmon Site, Lamar County, Mississippi

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

    NONE

    Geophysical surveys were conducted in 1992 and 1993 on 21 sites at the Salmon Site (SS) located in Lamar County, Mississippi. The studies are part of the Remedial Investigation/Feasibility Study (RI/FS) being conducted by IT Corporation for the U.S. Department of Energy (DOE). During the 1960s, two nuclear devices and two chemical tests were detonated 826 meters (in) (2710 feet [ft]) below the ground surface in the salt dome underlying the SS. These tests were part of the Vela Uniform Program conducted to improve the United States capability to detect, identify, and locate underground nuclear detonations. The RI/FS is beingmore » conducted to determine if any contamination is migrating from the underground shot cavity in the salt dome and if there is any residual contamination in the near surface mud and debris disposal pits used during the testing activities. The objective of the surface geophysical surveys was to locate buried debris, disposal pits, and abandoned mud pits that may be present at the site. This information will then be used to identify the locations for test pits, cone penetrometer tests, and drill hole/monitor well installation. The disposal pits were used during the operation of the test site in the 1960s. Vertical magnetic gradient (magnetic gradient), electromagnetic (EM) conductivity, and ground-penetrating radar (GPR) surveys were used to accomplish these objectives. A description of the equipment used and a theoretical discussion of the geophysical methods are presented Appendix A. Because of the large number of figures relative to the number of pages of text, the geophysical grid-location maps, the contour maps of the magnetic-gradient data, the contour maps of the EM conductivity data, and the GPR traverse location maps are located in Appendix B, Tabs I through 22. In addition, selected GPR records are located in Appendix C.« less

  18. Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters.

    PubMed

    Cremer, Marion; Schmid, Volker J; Kraus, Felix; Markaki, Yolanda; Hellmann, Ines; Maiser, Andreas; Leonhardt, Heinrich; John, Sam; Stamatoyannopoulos, John; Cremer, Thomas

    2017-08-07

    The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an 'open' local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC-INC) form two spatially co-aligned and functionally interacting networks. Using 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[-] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[-]) are enriched toward the compacted interior of CDCs (INC). Our results add further evidence in support of the ANC-INC network model. The different 3D topographies of DHS[+] and DHS[-] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an 'open,' active and 'closed

  19. Anisotropic Covalency Contributions to Superexchange Pathways in Type One Copper Active Sites

    PubMed Central

    2015-01-01

    Type one (T1) Cu sites deliver electrons to catalytic Cu active sites: the mononuclear type two (T2) Cu site in nitrite reductases (NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs). The T1 Cu and the remote catalytic sites are connected via a Cys-His intramolecular electron-transfer (ET) bridge, which contains two potential ET pathways: P1 through the protein backbone and P2 through the H-bond between the Cys and the His. The high covalency of the T1 Cu–S(Cys) bond is shown here to activate the T1 Cu site for hole superexchange via occupied valence orbitals of the bridge. This covalency-activated electronic coupling (HDA) facilitates long-range ET through both pathways. These pathways can be selectively activated depending on the geometric and electronic structure of the T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys) bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type) T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs to NiRs, the second-sphere environment changes the conformation of the Cys-His pathway, which selectively activates HDA for superexchange by blue π sites for efficient turnover in catalysis. These studies show that a given protein bridge, here Cys-His, provides different superexchange pathways and electronic couplings depending on the anisotropic covalencies of the donor and acceptor metal sites. PMID:25310460

  20. Functional evolution of PLP-dependent enzymes based on active-site structural similarities.

    PubMed

    Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

    2014-10-01

    Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. © 2014 Wiley Periodicals, Inc.

  1. Site-conditions map for Portugal based on VS measurements: methodology and final model

    NASA Astrophysics Data System (ADS)

    Vilanova, Susana; Narciso, João; Carvalho, João; Lopes, Isabel; Quinta Ferreira, Mario; Moura, Rui; Borges, José; Nemser, Eliza; Pinto, carlos

    2017-04-01

    In this paper we present a statistically significant site-condition model for Portugal based on shear-wave velocity (VS) data and surface geology. We also evaluate the performance of commonly used Vs30 proxies based on exogenous data and analyze the implications of using those proxies for calculating site amplification in seismic hazard assessment. The dataset contains 161 Vs profiles acquired in Portugal in the context of research projects, technical reports, academic thesis and academic papers. The methodologies involved in characterizing the Vs structure at the sites in the database include seismic refraction, multichannel analysis of seismic waves and refraction microtremor. Invasive measurements were performed in selected locations in order to compare the Vs profiles obtained from both invasive and non-invasive techniques. In general there was good agreement in the subsurface structure of Vs30 obtained from the different methodologies. The database flat-file includes information on Vs30, surface geology at 1:50.000 and 1:500.000 scales, elevation and topographic slope and based on SRTM30 topographic dataset. The procedure used to develop the site-conditions map is based on a three-step process that includes defining a preliminary set of geological units based on the literature, performing statistical tests to assess whether or not the differences in the distributions of Vs30 are statistically significant, and merging of the geological units accordingly. The dataset was, to some extent, affected by clustering and/or preferential sampling and therefore a declustering algorithm was applied. The final model includes three geological units: 1) Igneous, metamorphic and old (Paleogene and Mesozoic) sedimentary rocks; 2) Neogene and Pleistocene formations, and 3) Holocene formations. The evaluation of proxies indicates that although geological analogues and topographic slope are in general unbiased, the latter shows significant bias for particular geological units and

  2. Isolation of Notl sites from chromosome 22q11

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

    Ten Hoeve, J.; Groffen, J.; Heisterkamp, N.

    1993-12-01

    Chromosome 22q11 contains a large number of interesting loci, including genes associated with cancer and developmental defects. The region is also the site of the lambda immunoglobulin variable and constants regions and the BCR, [gamma]-glutamyl transpeptidase, and GGT-like activity multigene families. Because of the complexities associated with mapping highly related gene families, the authors have examined the utility of mapping large areas of DNA using a defined approach. A total of 21 complete NotI sites from band q11 were cloned and ordered into six noncontiguous clusters of sites using a combination of somatic cell hybrid panels, NotI jumping and linkingmore » libraries, and fluorescence in situ hybridization. The largest cluster spanned an estimated 2 Mb of NotI fragments, the smallest 115 kb. Approximately 3.5 Mb of band q11 could be examined for rearrangements in NotI restriction enzyme fragments. A number of conserved sequences, two genes, and a minimum of two families of related sequences were identified adjacent to NotI sites. 51 refs., 5 figs., 4 tabs.« less

  3. Map showing recently active breaks along the San Andreas Fault between Pt. Delgada and Bolinas Bay, California

    USGS Publications Warehouse

    Brown, Robert D.; Wolfe, Edward W.

    1970-01-01

    This strip map is one of a series of maps showing recently active fault breaks along the San Andreas and other active faults in California. It is designed to inform persons who are concerned with land use near the fault of the location of those fault breaks that have moved recently. The lines on the map are lines of rupture and creep that can be identified by field evidence and that clearly affect the present surface of the land. Map users should keep in mind that these lines are intended primarily as guides to help locate the fault; the mapped lines are not necessarily shown with the precision demanded by some engineering or land utilization needs.

  4. Road Map for Development of Crystal-Tolerant High Level Waste Glasses

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

    Matyas, Josef; Vienna, John D.; Peeler, David

    This road map guides the research and development for formulation and processing of crystal-tolerant glasses, identifying near- and long-term activities that need to be completed over the period from 2014 to 2019. The primary objective is to maximize waste loading for Hanford waste glasses without jeopardizing melter operation by crystal accumulation in the melter or melter discharge riser. The potential applicability to the Savannah River Site (SRS) Defense Waste Processing Facility (DWPF) is also addressed in this road map.

  5. CPC - Monitoring & Data: Regional Climate Maps

    Science.gov Websites

    Weather Service NWS logo - Click to go to the NWS home page Climate Prediction Center Site Map News Information CPC Web Team HOME > Monitoring and Data > Global Climate Data & Maps > Global Regional Climate Maps Regional Climate Maps Banner The Monthly regional analyses products are usually

  6. Mapping the fine structure of cortical activity with different micro-ECoG electrode array geometries

    NASA Astrophysics Data System (ADS)

    Wang, Xi; Gkogkidis, C. Alexis; Iljina, Olga; Fiederer, Lukas D. J.; Henle, Christian; Mader, Irina; Kaminsky, Jan; Stieglitz, Thomas; Gierthmuehlen, Mortimer; Ball, Tonio

    2017-10-01

    Objective. Innovations in micro-electrocorticography (µECoG) electrode array manufacturing now allow for intricate designs with smaller contact diameters and/or pitch (i.e. inter-contact distance) down to the sub-mm range. The aims of the present study were: (i) to investigate whether frequency ranges up to 400 Hz can be reproducibly observed in µECoG recordings and (ii) to examine how differences in topographical substructure between these frequency bands and electrode array geometries can be quantified. We also investigated, for the first time, the influence of blood vessels on signal properties and assessed the influence of cortical vasculature on topographic mapping. Approach. The present study employed two µECoG electrode arrays with different contact diameters and inter-contact distances, which were used to characterize neural activity from the somatosensory cortex of minipigs in a broad frequency range up to 400 Hz. The analysed neural data were recorded in acute experiments under anaesthesia during peripheral electrical stimulation. Main results. We observed that µECoG recordings reliably revealed multi-focal cortical somatosensory response patterns, in which response peaks were often less than 1 cm apart and would thus not have been resolvable with conventional ECoG. The response patterns differed by stimulation site and intensity, they were distinct for different frequency bands, and the results of functional mapping proved independent of cortical vascular. Our analysis of different frequency bands exhibited differences in the number of activation peaks in topographical substructures. Notably, signal strength and signal-to-noise ratios differed between the two electrode arrays, possibly due to their different sensitivity for variations in spatial patterns and signal strengths. Significance. Our findings that the geometry of µECoG electrode arrays can strongly influence their recording performance can help to make informed decisions that maybe

  7. Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

    PubMed

    Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

    2018-01-01

    Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

  8. High-resolution mapping of the triangle of Koch: Spatial heterogeneity of fast pathway atrionodal connections.

    PubMed

    Chua, Kelvin; Upadhyay, Gaurav A; Lee, Elliot; Aziz, Zaid; Beaser, Andrew D; Ozcan, Cevher; Broman, Michael; Nayak, Hemal M; Tung, Roderick

    2018-03-01

    Dedicated mapping studies of the triangle of Koch to characterize retrograde fast pathway activation have not been previously performed using high-resolution, 3-dimensional, multielectrode mapping technology. To delineate the activation pattern and spatial distribution of the retrograde fast pathway within the triangle of Koch during typical atrioventricular nodal reentrant tachycardia (AVNRT) and right ventricular pacing in a consecutive series of patients using the Rhythmia mapping system (Boston Scientific, Natick, MA). A total of 18 patients with symptomatic typical AVNRT referred for ablation underwent ultra high-density mapping of atrial activation with minielectrode basket configuration during tachycardia. The earliest atrial activation was mapped using automated annotation, with manual overreading by 2 independent observers. The triangle of Koch was classified into 3 anatomic regions: anteroseptal (His), midseptal, and posteroseptal (coronary sinus roof). Thirteen patients underwent mapping of atrial activation during ventricular pacing. A median of 422 mapping points (interquartile range 258-896 points) was acquired within the triangle of Koch during tachycardia. The most common site of earliest atrial activation within the triangle of Koch was anterior in 67% of patients (n = 12). Midseptal early atrial activation was seen in 17% (n = 3), and posteroseptal activation was observed in 11% (n = 2). One patient exhibited broad simultaneous activation of the entire triangle of Koch. Slow pathway potentials were not identified. With high-resolution multielectrode mapping, atrial activation during typical AVNRT exhibited anatomic variability and spatially heterogeneous activation within the triangle of Koch. These findings highlight the limitations of an anatomically based classification of atrioventricular nodal retrograde pathways. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. Global Mapping of Transcription Factor Binding Sites by Sequencing Chromatin Surrogates: a Perspective on Experimental Design, Data Analysis, and Open Problems.

    PubMed

    Wei, Yingying; Wu, George; Ji, Hongkai

    2013-05-01

    Mapping genome-wide binding sites of all transcription factors (TFs) in all biological contexts is a critical step toward understanding gene regulation. The state-of-the-art technologies for mapping transcription factor binding sites (TFBSs) couple chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip). These technologies have limitations: they are low-throughput with respect to surveying many TFs. Recent advances in genome-wide chromatin profiling, including development of technologies such as DNase-seq, FAIRE-seq and ChIP-seq for histone modifications, make it possible to predict in vivo TFBSs by analyzing chromatin features at computationally determined DNA motif sites. This promising new approach may allow researchers to monitor the genome-wide binding sites of many TFs simultaneously. In this article, we discuss various experimental design and data analysis issues that arise when applying this approach. Through a systematic analysis of the data from the Encyclopedia Of DNA Elements (ENCODE) project, we compare the predictive power of individual and combinations of chromatin marks using supervised and unsupervised learning methods, and evaluate the value of integrating information from public ChIP and gene expression data. We also highlight the challenges and opportunities for developing novel analytical methods, such as resolving the one-motif-multiple-TF ambiguity and distinguishing functional and non-functional TF binding targets from the predicted binding sites. The online version of this article (doi:10.1007/s12561-012-9066-5) contains supplementary material, which is available to authorized users.

  10. 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

  11. Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites.

    PubMed

    Ribeiro, António J M; Holliday, Gemma L; Furnham, Nicholas; Tyzack, Jonathan D; Ferris, Katherine; Thornton, Janet M

    2018-01-04

    M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites and reaction mechanisms that can be accessed at www.ebi.ac.uk/thornton-srv/m-csa. Our objectives with M-CSA are to provide an open data resource for the community to browse known enzyme reaction mechanisms and catalytic sites, and to use the dataset to understand enzyme function and evolution. M-CSA results from the merging of two existing databases, MACiE (Mechanism, Annotation and Classification in Enzymes), a database of enzyme mechanisms, and CSA (Catalytic Site Atlas), a database of catalytic sites of enzymes. We are releasing M-CSA as a new website and underlying database architecture. At the moment, M-CSA contains 961 entries, 423 of these with detailed mechanism information, and 538 with information on the catalytic site residues only. In total, these cover 81% (195/241) of third level EC numbers with a PDB structure, and 30% (840/2793) of fourth level EC numbers with a PDB structure, out of 6028 in total. By searching for close homologues, we are able to extend M-CSA coverage of PDB and UniProtKB to 51 993 structures and to over five million sequences, respectively, of which about 40% and 30% have a conserved active site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Map and Compass Skills for the Secondary School (Understanding Topographic Maps, Developing Compass Skills, and Orienteering). Instructional Activities Series IA/S-18.

    ERIC Educational Resources Information Center

    Larkin, Robert P.

    This activity is one of a series of 17 teacher-developed instructional activities for geography at the secondary-grade level described in SO 009 140. The activity investigates the development of compass skills, map skills, and orienteering. It employs the educational-games approach. Given specific exercises and instructions, students become…

  13. Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

    PubMed Central

    Nicolau, Carolina Alves; Prorock, Alyson; Bao, Yongde; Neves-Ferreira, Ana Gisele da Costa; Fox, Jay William

    2018-01-01

    Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents. PMID:29415440

  14. Spm1, a stress-activated MAP kinase that regulates morphogenesis in S.pombe.

    PubMed Central

    Zaitsevskaya-Carter, T; Cooper, J A

    1997-01-01

    A gene encoding a novel MAP kinase family member, Spm1, was isolated from the fission yeast Schizosaccharomyces pombe. Overproduction of Spm1 inhibits proliferation. Disruption of the spm1+ gene interferes with cell separation and morphogenesis. Under conditions of nutrient limitation, hypertonic stress or elevated temperature, spm1 delta cells grow as short branched filaments in which the cell walls and septa are thickened, suggesting defects in polarized growth and cell wall remodeling. At high osmolarity, spm1 delta cells fail to form colonies. The Spm1 protein is tyrosine phosphorylated and activated in response to osmotic and heat stress, consistent with a role for Spm1 in adaptation to these conditions. Two other S.pombe MAP kinases are known, Spk1, required for sexual differentiation and sporulation, and Spc1/Sty1/Phh1, which is activated in hypertonic conditions. However, the distinctive features of the spm1 delta mutant phenotype and direct biochemical assays suggest that Spm1 does not lie on other known MAP kinase pathways. Our results demonstrate the existence of a new MAP kinase pathway that regulates cell wall remodeling and cytokinesis in response to environmental stresses. PMID:9135147

  15. Fragile Sites of 'Valencia' Sweet Orange (Citrus sinensis) Chromosomes Are Related with Active 45s rDNA.

    PubMed

    Lan, Hong; Chen, Chun-Li; Miao, Yin; Yu, Chang-Xiu; Guo, Wen-Wu; Xu, Qiang; Deng, Xiu-Xin

    2016-01-01

    Citrus sinensis chromosomes present a morphological differentiation of bands after staining by the fluorochromes CMA and DAPI, but there is still little information on its chromosomal characteristics. In this study, the chromosomes in 'Valencia' C. sinensis were analyzed by fluorescence in situ hybridization (FISH) using telomere DNA and the 45S rDNA gene as probes combining CMA/DAPI staining, which showed that there were two fragile sites in sweet orange chromosomes co-localizing at distended 45S rDNA regions, one proximally locating on B-type chromosome and the other subterminally locating on D-type chromosome. While the chromosomal CMA banding and 45S rDNA FISH mapping in the doubled haploid line of 'Valencia' C. sinensis indicated six 45S rDNA regions, four were identified as fragile sites as doubled comparing its parental line, which confirmed the cytological heterozygosity and chromosomal heteromorphisms in sweet orange. Furthermore, Ag-NOR identified two distended 45S rDNA regions to be active nucleolar organizing regions (NORs) in diploid 'Valencia' C. sinensis. The occurrence of quadrivalent in meiosis of pollen mother cells (PMCs) in 'Valencia' sweet orange further confirmed it was a chromosomal reciprocal translocation line. We speculated this chromosome translocation was probably related to fragile sites. Our data provide insights into the chromosomal characteristics of the fragile sites in 'Valencia' sweet orange and are expected to facilitate the further investigation of the possible functions of fragile sites.

  16. Active Site Gate Dynamics Modulate the Catalytic Activity of the Ubiquitination Enzyme E2-25K.

    PubMed

    Rout, Manoj K; Lee, Brian L; Lin, Aiyang; Xiao, Wei; Spyracopoulos, Leo

    2018-05-03

    The ubiquitin proteasome system (UPS) signals for degradation of proteins through attachment of K48-linked polyubiquitin chains, or alterations in protein-protein recognition through attachment of K63-linked chains. Target proteins are ubiquitinated in three sequential chemical steps by a three-component enzyme system. Ubiquitination, or E2 enzymes, catalyze the central step by facilitating reaction of a target protein lysine with the C-terminus of Ub that is attached to the active site cysteine of the E2 through a thioester bond. E2 reactivity is modulated by dynamics of an active site gate, whose central residue packs against the active site cysteine in a closed conformation. Interestingly, for the E2 Ubc13, which specifically catalyzes K63-linked ubiquitination, the central gate residue adopts an open conformation. We set out to determine if active site gate dynamics play a role in catalysis for E2-25K, which adopts the canonical, closed gate conformation, and which selectively synthesizes K48-linked ubiquitin chains. Gate dynamics were characterized using mutagenesis of key residues, combined with enzyme kinetics measurements, and main chain NMR relaxation. The experimental data were interpreted with all atom MD simulations. The data indicate that active site gate opening and closing rates for E2-25K are precisely balanced.

  17. 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

  18. MAPS of Cancer

    NASA Technical Reports Server (NTRS)

    Gray, Lincoln

    1998-01-01

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

  19. Role of a cysteine residue in the active site of ERK and the MAPKK family

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

    Ohori, Makoto; Kinoshita, Takayoshi; Yoshimura, Seiji

    2007-02-16

    Kinases of mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated protein kinase (ERK), represent likely targets for pharmacological intervention in proliferative diseases. Here, we report that FR148083 inhibits ERK2 enzyme activity and TGF{beta}-induced AP-1-dependent luciferase expression with respective IC{sub 50} values of 0.08 and 0.05 {mu}M. FR265083 (1'-2' dihydro form) and FR263574 (1'-2' and 7'-8' tetrahydro form) exhibited 5.5-fold less and no activity, respectively, indicating that both the {alpha},{beta}-unsaturated ketone and the conformation of the lactone ring contribute to this inhibitory activity. The X-ray crystal structure of the ERK2/FR148083 complex revealed that the compound binds to the ATP binding sitemore » of ERK2, involving a covalent bond to S{gamma} of ERK2 Cys166, hydrogen bonds with the backbone NH of Met108, N{zeta} of Lys114, backbone C=O of Ser153, N{delta}2 of Asn154, and hydrophobic interactions with the side chains of Ile31, Val39, Ala52, and Leu156. The covalent bond motif in the ERK2/FR148083 complex assures that the inhibitor has high activity for ERK2 and no activity for other MAPKs such as JNK1 and p38MAPK{alpha}/{beta}/{gamma}/{delta} which have leucine residues at the site corresponding to Cys166 in ERK2. On the other hand, MEK1 and MKK7, kinases of the MAPKK family which also can be inhibited by FR148083, contain a cysteine residue corresponding to Cys166 of ERK2. The covalent binding to the common cysteine residue in the ATP-binding site is therefore likely to play a crucial role in the inhibitory activity for these MAP kinases. These findings on the molecular recognition mechanisms of FR148083 for kinases with Cys166 should provide a novel strategy for the pharmacological intervention of MAPK cascades.« less

  20. SABER: A computational method for identifying active sites for new reactions

    PubMed Central

    Nosrati, Geoffrey R; Houk, K N

    2012-01-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644–1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were l-Ala d/l-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

  1. SABER: a computational method for identifying active sites for new reactions.

    PubMed

    Nosrati, Geoffrey R; Houk, K N

    2012-05-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

  2. Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

    PubMed Central

    Andrusiak, Matthew G.; Jin, Yishi

    2016-01-01

    Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

  3. Geoelectric hazard maps for the continental United States

    NASA Astrophysics Data System (ADS)

    Love, Jeffrey J.; Pulkkinen, Antti; Bedrosian, Paul A.; Jonas, Seth; Kelbert, Anna; Rigler, E. Joshua; Finn, Carol A.; Balch, Christopher C.; Rutledge, Robert; Waggel, Richard M.; Sabata, Andrew T.; Kozyra, Janet U.; Black, Carrie E.

    2016-09-01

    In support of a multiagency project for assessing induction hazards, we present maps of extreme-value geoelectric amplitudes over about half of the continental United States. These maps are constructed using a parameterization of induction: estimates of Earth surface impedance, obtained at discrete geographic sites from magnetotelluric survey data, are convolved with latitude-dependent statistical maps of extreme-value geomagnetic activity, obtained from decades of magnetic observatory data. Geoelectric amplitudes are estimated for geomagnetic waveforms having 240 s sinusoidal period and amplitudes over 10 min that exceed a once-per-century threshold. As a result of the combination of geographic differences in geomagnetic activity and Earth surface impedance, once-per-century geoelectric amplitudes span more than 2 orders of magnitude and are an intricate function of location. For north-south induction, once-per-century geoelectric amplitudes across large parts of the United States have a median value of 0.26 V/km; for east-west geomagnetic variation the median value is 0.23 V/km. At some locations, once-per-century geoelectric amplitudes exceed 3 V/km.

  4. Geoelectric Hazard Maps for the Continental United States

    NASA Technical Reports Server (NTRS)

    Love, Jeffrey J.; Pulkkinen, Antti; Bedrosian, Paul A.; Jonas, Seth; Kelbert, Anna; Rigler, Joshua E.; Finn, Carol A.; Balch, Christopher C.; Rutledge, Robert; Waggle, Richard M.

    2016-01-01

    In support of a multiagency project for assessing induction hazards, we present maps of extreme-value geoelectric amplitudes over about half of the continental United States. These maps are constructed using a parameterization of induction: estimates of Earth surface impedance, obtained at discrete geographic sites from magnetotelluric survey data, are convolved with latitude-dependent statistical maps of extreme-value geomagnetic activity, obtained from decades of magnetic observatory data. Geoelectric amplitudes are estimated for geomagnetic waveforms having 240 s sinusoidal period and amplitudes over 10 min that exceed a once-per-century threshold. As a result of the combination of geographic differences in geomagnetic activity and Earth surface impedance, once-per-century geoelectric amplitudes span more than 2 orders of magnitude and are an intricate function of location. For north-south induction, once-per-century geoelectric amplitudes across large parts of the United States have a median value of 0.26 Vkm; for east-west geomagnetic variation the median value is 0.23 Vkm. At some locations,once-per-century geoelectric amplitudes exceed 3 Vkm.

  5. Geoelectric hazard maps for the continental United States

    USGS Publications Warehouse

    Love, Jeffrey J.; Pulkkinen, Antti; Bedrosian, Paul A.; Jonas, Seth; Kelbert, Anna; Rigler, Erin (Josh); Finn, Carol; Balch, Christopher; Rutledge, Robert; Waggel, Richard; Sabata, Andrew; Kozyra, Janet; Black, Carrie

    2016-01-01

    In support of a multiagency project for assessing induction hazards, we present maps of extreme-value geoelectric amplitudes over about half of the continental United States. These maps are constructed using a parameterization of induction: estimates of Earth surface impedance, obtained at discrete geographic sites from magnetotelluric survey data, are convolved with latitude-dependent statistical maps of extreme-value geomagnetic activity, obtained from decades of magnetic observatory data. Geoelectric amplitudes are estimated for geomagnetic waveforms having 240 s sinusoidal period and amplitudes over 10 min that exceed a once-per-century threshold. As a result of the combination of geographic differences in geomagnetic activity and Earth surface impedance, once-per-century geoelectric amplitudes span more than 2 orders of magnitude and are an intricate function of location. For north-south induction, once-per-century geoelectric amplitudes across large parts of the United States have a median value of 0.26 V/km; for east-west geomagnetic variation the median value is 0.23 V/km. At some locations, once-per-century geoelectric amplitudes exceed 3 V/km.

  6. 'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

    PubMed

    Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

    2014-04-09

    The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

  7. Enhanced enzyme kinetic stability by increasing rigidity within the active site.

    PubMed

    Xie, Yuan; An, Jiao; Yang, Guangyu; Wu, Geng; Zhang, Yong; Cui, Li; Feng, Yan

    2014-03-14

    Enzyme stability is an important issue for protein engineers. Understanding how rigidity in the active site affects protein kinetic stability will provide new insight into enzyme stabilization. In this study, we demonstrated enhanced kinetic stability of Candida antarctica lipase B (CalB) by mutating the structurally flexible residues within the active site. Six residues within 10 Å of the catalytic Ser(105) residue with a high B factor were selected for iterative saturation mutagenesis. After screening 2200 colonies, we obtained the D223G/L278M mutant, which exhibited a 13-fold increase in half-life at 48 °C and a 12 °C higher T50(15), the temperature at which enzyme activity is reduced to 50% after a 15-min heat treatment. Further characterization showed that global unfolding resistance against both thermal and chemical denaturation also improved. Analysis of the crystal structures of wild-type CalB and the D223G/L278M mutant revealed that the latter formed an extra main chain hydrogen bond network with seven structurally coupled residues within the flexible α10 helix that are primarily involved in forming the active site. Further investigation of the relative B factor profile and molecular dynamics simulation confirmed that the enhanced rigidity decreased fluctuation of the active site residues at high temperature. These results indicate that enhancing the rigidity of the flexible segment within the active site may provide an efficient method for improving enzyme kinetic stability.

  8. GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms.

    PubMed

    Moraes, João P A; Pappa, Gisele L; Pires, Douglas E V; Izidoro, Sandro C

    2017-07-03

    Enzyme active sites are important and conserved functional regions of proteins whose identification can be an invaluable step toward protein function prediction. Most of the existing methods for this task are based on active site similarity and present limitations including performing only exact matches on template residues, template size restraints, despite not being capable of finding inter-domain active sites. To fill this gap, we proposed GASS-WEB, a user-friendly web server that uses GASS (Genetic Active Site Search), a method based on an evolutionary algorithm to search for similar active sites in proteins. GASS-WEB can be used under two different scenarios: (i) given a protein of interest, to match a set of specific active site templates; or (ii) given an active site template, looking for it in a database of protein structures. The method has shown to be very effective on a range of experiments and was able to correctly identify >90% of the catalogued active sites from the Catalytic Site Atlas. It also managed to achieve a Matthew correlation coefficient of 0.63 using the Critical Assessment of protein Structure Prediction (CASP 10) dataset. In our analysis, GASS was ranking fourth among 18 methods. GASS-WEB is freely available at http://gass.unifei.edu.br/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Identification and mapping of natural vegetation on a coastal site using a Worldview-2 satellite image.

    PubMed

    Rapinel, Sébastien; Clément, Bernard; Magnanon, Sylvie; Sellin, Vanessa; Hubert-Moy, Laurence

    2014-11-01

    Identification and mapping of natural vegetation are major issues for biodiversity management and conservation. Remotely sensed data with very high spatial resolution are currently used to study vegetation, but most satellite sensors are limited to four spectral bands, which is insufficient to identify some natural vegetation formations. The study objectives are to discriminate natural vegetation and identify natural vegetation formations using a Worldview-2 satellite image. The classification of the Worldview-2 image and ancillary thematic data was performed using a hybrid pixel-based and object-oriented approach. A hierarchical scheme using three levels was implemented, from land cover at a field scale to vegetation formation. This method was applied on a 48 km² site located on the French Atlantic coast which includes a classified NATURA 2000 dune and marsh system. The classification accuracy was very high, the Kappa index varying between 0.90 and 0.74 at land cover and vegetation formation levels respectively. These results show that Wordlview-2 images are suitable to identify natural vegetation. Vegetation maps derived from Worldview-2 images are more detailed than existing ones. They provide a useful medium for environmental management of vulnerable areas. The approach used to map natural vegetation is reproducible for a wider application by environmental managers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. PEER Site Map

    Science.gov Websites

    * PEER's Industry Partners * PEER's Educational Affiliates * History of PEER * Technology Transfer * Annual * PEER's Educational Affiliates * Student Design Competition * Student Leadership Council * Classes and Other Educational Activities Frequently Asked Questions Links - Important Earthquake Engineering

  11. The active site of O-GlcNAc transferase imposes constraints on substrate sequence

    PubMed Central

    Rafie, Karim; Blair, David E.; Borodkin, Vladimir S.; Albarbarawi, Osama; van Aalten, Daan M. F.

    2016-01-01

    O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoa. Although this enzyme modifies hundreds of proteins with O-GlcNAc, it is not understood how OGT achieves substrate specificity. In this study, we describe the application of a high-throughput OGT assay on a library of peptides. The sites of O-GlcNAc modification were mapped by ETD-mass spectrometry, and found to correlate with previously detected O-GlcNAc sites. Crystal structures of four acceptor peptides in complex with human OGT suggest that a combination of size and conformational restriction defines sequence specificity in the −3 to +2 subsites. This work reveals that while the N-terminal TPR repeats of hOGT may play a role in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a significant contribution to O-GlcNAc site specificity. PMID:26237509

  12. Mapping brain activity with flexible graphene micro-transistors

    NASA Astrophysics Data System (ADS)

    Blaschke, Benno M.; Tort-Colet, Núria; Guimerà-Brunet, Anton; Weinert, Julia; Rousseau, Lionel; Heimann, Axel; Drieschner, Simon; Kempski, Oliver; Villa, Rosa; Sanchez-Vives, Maria V.; Garrido, Jose A.

    2017-06-01

    Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants.

  13. Map showing seismicity and sandblows in the vicinity of New Madrid, Missouri

    USGS Publications Warehouse

    Rhea, B. Susan; Tarr, Arthur C.; Wheeler, Russell L.

    1994-01-01

    This is one of a series of five seismotectic maps of the seismically active New Madrid, Missouri, area (table 1; Wheeler and others, 1992). The map area centers near the sites of three great earthquakes that struck during the winter of 1811-12 (Fuller, 1912; Nuttli, 1973). These earthquakes and continuing subsequent seismicity rank the New Madrid area with Cherlevoix, Quebec, as the two most seismically active areas in North America east of the Rocky Mountains. The threat posed by New Madrid seismicity to the central United States makes the area the focus of many investigations (for examples, Heyl and McKeown, 1978; McKeown and Pakiser, 1982; Algemissen and Hopper, 1984; Hamilton and Johnston, 1990; Applied Technology Council, 1991; Johnston and others, 1992). The map area includes the most intense seismic activity in the New Madrid region. A seismotectic map shows some of the geologic and geophysical information needed to assess seismic hazard (Hadley and Devine, 1974; Pavoni, 1985). A previous seismotectonic map of the central Mississippi River valley (Heyl and McKeown, 1978) has had wide use for planning field surveys, as a base map for plotting data collected during single investigations, and for compiling a range of information. Since 1978 numcrous researchers have greatly advanced our knowledge of the geology and geophysics of the central Mississippi Valley. The New Madrid seismotectonic map folio updates approximately the south-central sixth of the central Mississippi Valley seismotectonic map of Heyl and McKeown (1978).

  14. Facebook, Twitter Activities Sites, Location and Students' Interest in Learning

    ERIC Educational Resources Information Center

    Igbo, J. N.; Ezenwaji, Ifeyinwa; Ajuziogu, Christiana U.

    2018-01-01

    This study was carried out to ascertain the influence of social networking sites activities (twitter and Facebook) on secondary school students' interest in learning It also considered the impact of these social networking sites activities on location of the students. Two research questions and two null hypotheses guided the study. Mean and…

  15. New Map Symbol System for Disaster Management

    NASA Astrophysics Data System (ADS)

    Marinova, Silvia T.

    2018-05-01

    In the last 10 years Bulgaria was frequently affected by natural and man-made disasters that caused considerable losses. According to the Bulgarian Disaster Management Act (2006) disaster management should be planned at local, regional and national level. Disaster protection is based on plans that include maps such as hazard maps, maps for protection, maps for evacuation planning, etc. Decision-making and cooperation between two or more neighboring municipalities or regions in crisis situation are still rendered difficult because the maps included in the plans differ in scale, colors, map symbols and cartographic design. To improve decision-making process in case of emergency and to reduce the number of human loss and property damages disaster management plans at local and regional level should be supported by detailed thematic maps created in accordance with uniform contents, map symbol system and design. The paper proposes a new symbol system for disaster management that includes a four level hierarchical classification of objects and phenomena according to their type and origin. All objects and phenomena of this classification are divided into five categories: disasters; infrastructure; protection services and infrastructure for protection; affected people and affected infrastructure; operational sites and activities. The symbols of these categories are shown with different background colors and shapes so that they are identifiable. All the symbols have simple but associative design. The new symbol system is used in the design of a series of maps for disaster management at local and regional level.

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

    NASA Astrophysics Data System (ADS)

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

    2017-12-01

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

  17. HEALTHY BOUTS OF ACTIVITY: INTEGRATING GPS AND ACCELEROMETRY FOR MAP-PROMPTED BOUT RECALLS

    PubMed Central

    Brown, Barbara B.; Wilson, Laura; Tribby, Calvin P.; Werner, Carol M.; Wolf, Jean; Miller, Harvey J.; Smith, Ken R.

    2015-01-01

    Objective Obtaining the “when, where, and why” of healthy bouts of moderate-to-vigorous physical activity (MVPA) provides insights into natural physical activity Design In Salt Lake City, Utah, adults wore accelerometer and GPS loggers for a week in a cross-sectional study to establish baseline travel and activity patterns near a planned Complete Street intervention involving a new rail line, new sidewalks, and a bike path. Results At the end of the week research assistants met with the 918 participants who had at least three 10-hour days of good accelerometer readings. Accelerometer and GPS data were uploaded and integrated within a custom application, and participants were provided with maps and time information for past MVPA bouts of ≥ 3 minutes to help them recall bout details. Participants said that ‘getting someplace” was, on average, a more important motivation for their bouts than leisure or exercise. A series of recall tests showed that participants recalled most bouts they were asked about, regardless of duration of the bout, suggesting that participant perceptions of their shorter lifestyle bouts can be studied with this methodology. Visual prompting with a map depicting where each bout took place yielded more accurate recall than prompting with time cues alone. Conclusion These techniques provide a novel way to understand participant memories of the context and subjective assessments associated with healthy bouts of physical activity. Prompts with time-stamped maps that illustrate places of moderate-to-vigorous physical activity offer an effective method to improve understanding of activity and its supportive socio-physical contexts. PMID:24815545

  18. Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1

    PubMed Central

    2016-01-01

    Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70–81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1’s lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1’s lactonase activity is minimal, whereas the kcat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1’s active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar “gating loop” or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates. PMID:28026940

  19. Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.

    PubMed

    Blaha-Nelson, David; Krüger, Dennis M; Szeler, Klaudia; Ben-David, Moshe; Kamerlin, Shina Caroline Lynn

    2017-01-25

    Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k cat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1's active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar "gating loop" or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates.

  20. Characterization of the active site properties of CYP4F12.

    PubMed

    Eksterowicz, John; Rock, Dan A; Rock, Brooke M; Wienkers, Larry C; Foti, Robert S

    2014-10-01

    Cytochrome P450 4F12 is a drug-metabolizing enzyme that is primarily expressed in the liver, kidney, colon, small intestine, and heart. The properties of CYP4F12 that may impart an increased catalytic selectivity (decreased promiscuity) were explored through in vitro metabolite elucidation, kinetic isotope effect experiments, and computational modeling of the CYP4F12 active site. By using astemizole as a probe substrate for CYP4F12 and CYP3A4, it was observed that although CYP4F12 favored astemizole O-demethylation as the primary route of metabolism, CYP3A4 was capable of metabolizing astemizole at multiple sites on the molecule. Deuteration of astemizole at the site of O-demethylation resulted in an isotope effect of 7.1 as well as an 8.3-fold decrease in the rate of clearance for astemizole by CYP4F12. Conversely, although an isotope effect of 3.8 was observed for the formation of the O-desmethyl metabolite when deuterated astemizole was metabolized by CYP3A4, there was no decrease in the clearance of astemizole. Development of a homology model of CYP4F12 based on the crystal structure of cytochrome P450 BM3 predicted an active site volume for CYP4F12 that was approximately 76% of the active site volume of CYP3A4. As predicted, multiple favorable binding orientations were available for astemizole docked into the active site of CYP3A4, but only a single binding orientation with the site of O-demethylation oriented toward the heme was identified for CYP4F12. Overall, it appears that although CYP4F12 may be capable of binding similar ligands to other cytochrome P450 enzymes such as CYP3A4, the ability to achieve catalytically favorable orientations may be inherently more difficult because of the increased steric constraints of the CYP4F12 active site. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Mapping Atlantic coastal marshlands, Maryland, Georgia, using ERTS-1 imagery

    NASA Technical Reports Server (NTRS)

    Anderson, R. R.; Carter, V. L.; Mcginness, J. W., Jr.

    1973-01-01

    Eastern coastal marshes are the most extensive and productive in the United States. A relatively low cost, moderately accurate method is needed to map these areas for management and protection. Groundbased and low-altitude aircraft methods for mapping are time-consuming and quite expensive. The launch of NASA's Earth Resources Technology Satellite has provided an opportunity to test the feasibility of mapping wetlands using small scale imagery. The test sites selected were in Chesapeake Bay, Maryland, and Ossabaw Island, Georgia. Results of the investigation indicate that the following may be ascertained from ERTS imagery, enlarged to 1:250,000: (1) upper wetland boundary; (2) drainage pattern in the wetland; (3) plant communities; (4) ditching activities associated with agriculture; and (5) lagooning for water-side home development. Conclusions are that ERTS will be an excellent tool for many types of coastal wetland mapping.

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

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  3. Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans.

    PubMed

    Andrusiak, Matthew G; Jin, Yishi

    2016-04-08

    Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundwormCaenorhabditis eleganswas developed as a system to study genes required for development and nervous system function. The powerful genetics ofC. elegansin combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components inC. elegans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Deletion of loop fragment adjacent to active site diminishes the stability and activity of exo-inulinase.

    PubMed

    Arjomand, Maryam Rezaei; Habibi-Rezaei, Mehran; Ahmadian, Gholamreza; Hassanzadeh, Malihe; Karkhane, Ali Asghar; Asadifar, Mandana; Amanlou, Massoud

    2016-11-01

    Inulinases are classified as hydrolases and widely used in the food and medical industries. Here, we report the deletion of a six-membered adjacent active site loop fragment ( 74 YGSDVT 79 sequence) from third Ω-loop of the exo-inulinase containing aspartate residue from Aspergillus niger to study its structural and functional importance. Site-directed mutagenesis was used to create the mutant of the exo-inulinase (Δ6SL). To investigate the stability of the region spanning this loop, MD simulations were performed 80ns for 20-85 residues. Molecular docking was performed to compare the interactions in the active sites of enzymes with fructose as a ligand. Accordingly, the functional thermostability of the exo-inulinase was significantly decreased upon loop fragment deletion. Evaluation of the kinetics parameters (V max , K m , k cat and, k cat /K m ) and activation energy (E a ) of the catalysis of enzymes indicated the importance of the deleted sequence on the catalytic performance of the enzyme. In conclusion, six-membered adjacent active site loop fragment not only plays a crucial role in the stability of the enzyme, but also it involves in the enzyme catalysis through lowering the activation energy of the catalysis and effective improving the catalytic performance. Copyright © 2016. Published by Elsevier B.V.

  5. 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

  6. National Park Service Vegetation Mapping Inventory Program: Natchez Trace Parkway vegetation mapping project report

    USGS Publications Warehouse

    Hop, Kevin D.; Strassman, Andrew C.; Nordman, Carl; Pyne, Milo; White, Rickie; Jakusz, Joseph; Hoy, Erin E.; Dieck, Jennifer

    2016-01-01

    The National Park Service (NPS) Vegetation Mapping Inventory (VMI) Program is an effort to classify, describe, and map existing vegetation of national park units for the NPS Natural Resource Inventory and Monitoring (I&M) Program. The NPS VMI Program is managed by the NPS I&M Division and provides baseline vegetation information to the NPS Natural Resource I&M Program. The U.S. Geological Survey Upper Midwest Environmental Sciences Center, NatureServe, NPS Gulf Coast Network, and NPS Natchez Trace Parkway (NATR; also referred to as Parkway) have completed vegetation classification and mapping of NATR for the NPS VMI Program.Mappers, ecologists, and botanists collaborated to affirm vegetation types within the U.S. National Vegetation Classification (USNVC) of NATR and to determine how best to map them by using aerial imagery. Analyses of data from 589 vegetation plots had been used to describe an initial 99 USNVC associations in the Parkway; this classification work was completed prior to beginning this NATR vegetation mapping project. Data were collected during this project from another eight quick plots to support new vegetation types not previously identified at the Parkway. Data from 120 verification sites were collected to test the field key to vegetation associations and the application of vegetation associations to a sample set of map polygons. Furthermore, data from 900 accuracy assessment (AA) sites were collected (of which 894 were used to test accuracy of the vegetation map layer). The collective of all these datasets resulted in affirming 122 USNVC associations at NATR.To map the vegetation and open water of NATR, 63 map classes were developed. including the following: 54 map classes represent natural (including ruderal) vegetation types in the USNVC, 5 map classes represent cultural (agricultural and developed) vegetation types in the USNVC, 3 map classes represent nonvegetation open-water bodies (non-USNVC), and 1 map class represents landscapes that

  7. The Crystal Structure of a Quercetin 2,3-Dioxygenase from Bacillus subtilis Suggests Modulation of Enzyme Activity by a Change in the Metal Ion at the Active Site(s)

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

    Gopal, B.; Madan, Lalima L.; Betz, Stephen F.

    2010-11-10

    Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with up to 14% of its genes in the form of doublets, thus making it an attractive system for studying the effects of gene duplication. There are four bicupins in B. subtilis encoded by the genes yvrK, yoaN, yxaG, and ywfC. The gene products of yvrK and yoaN function as oxalate decarboxylases with a manganese ion at the active site(s),more » whereas YwfC is a bacitracin synthetase. Here we present the crystal structure of YxaG, a novel iron-containing quercetin 2,3-dioxygenase with one active site in each cupin domain. Yxag is a dimer, both in solution and in the crystal. The crystal structure shows that the coordination geometry of the Fe ion is different in the two active sites of YxaG. Replacement of the iron at the active site with other metal ions suggests modulation of enzymatic activity in accordance with the Irving-Williams observation on the stability of metal ion complexes. This observation, along with a comparison with the crystal structure of YvrK determined recently, has allowed for a detailed structure-function analysis of the active site, providing clues to the diversification of function in the bicupin family of proteins.« less

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

    Treesearch

    Robert S. Bristow; Steven Riberdy

    2002-01-01

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

  9. Online Discovery and Mapping of Great Lakes Climate Change Education and Scientific Research Activities: Building an Online Collaborative Learning Community of Scientists and Educators

    NASA Astrophysics Data System (ADS)

    Tuddenham, P.; Bishop, K.; Walters, H.; Carley, S.

    2011-12-01

    The Great Lakes Climate Change Science and Education Systemic Network (GLCCSESN) project is an NSF-funded CCEP program awarded to Eastern Michigan University in 2010. The College of Exploration is one of the project partners and has conducted a series of online surveys, workshop and focus group to identify a wide range of organizations, individuals, resources and needs related to climate change education and research activities in and about the Great Lakes Region and to provide information about climate change science to the education community. One of the first steps taken to build this community was to build a web site that features a dynamic online map of individuals and organizations concerned about climate change as well as interested in resources and activities specific to the Great Lakes. Individuals and organizations have been, and are still, invited to put themselves on the map at http://greatlakesclimate.org This map of the Great Lakes region provides both a visual representation of activities and resources as well as a database of climate change activities. This map will grow over time as more people and organizations put themselves on the map. The use of online technologies has helped broaden the participation and representation in the GLCCSESN from all states/provinces in the Great Lakes region, encouraging diverse audiences and stakeholders, including scientists, educators, and journalists, etc.to engage with the project. In the fall of 2011 a combined online professional development workshop and focus group is planned. Educators and scientists working on climate change studies and issues related to the Great Lakes will be sharing their work and expertise in an online workshop and focus group. Following the professional development activity a focus group will be conducted online using a model developed as part of a NSF funded COSEE project. The focus group purpose is to review current educational resources and to identify gaps and needs for further

  10. Comparison of RS/GIS analysis with classic mapping approaches for siting low-yield boreholes for hand pumps in crystalline terrains. An application to rural communities of the Caimbambo province, Angola

    NASA Astrophysics Data System (ADS)

    Martín-Loeches, Miguel; Reyes-López, Jaime; Ramírez-Hernández, Jorge; Temiño-Vela, Javier; Martínez-Santos, Pedro

    2018-02-01

    In poverty-stricken regions of Sub-Saharan Africa, groundwater for supply is often obtained by means of hand pumps, which means that low-yield boreholes are acceptable. However, boreholes are often sited without sufficient hydrogeological information due to budget constraints, which leads to high failure rates. Cost-effective techniques for borehole siting need to be developed in order to maximize the success rate. In regions underlain by granite, weathered formations are usually targeted for drilling, as these are generally presented as a better cost-benefit ratio than the fractured basement. Within this context, this research focuses on a granite region of Angola. A comparison of two mapping techniques for borehole siting-groundwater prospect is presented. A classic hydrogeomorphological map was developed first based on aerial photographs, field mapping and a geophysical survey. This map represents a considerable time investment and was developed by qualified technicians. The second map (RS/GIS) is considerably simpler and more cost-effective. It was developed by the integration in a GIS platform of six maps of equal importance-slope, drainage density, vegetation vigor, presence of clay in the soil, lineaments and rock outcrops-prepared from Landsat 8 imagery and a Digital Elevation Model (DEM). Similar results were obtained in both cases. By means of a supervised classification of Landsat images, RS/GIS analysis allows for the identification of granitic outcrops, house clusters and sandy alluvial valleys. This in turn allows for the delineation of low-interest or contamination-prone areas, thus contributing additional qualitative information. The position of a well that is going to be powered by a handpump is chosen also upon social and local matters as the distance to the stakeholders, information that are not difficult to integrate in the GIS. Although the second map needs some field inputs (i.e. surveys to determine the thickness of the weathered pack

  11. Special-Status Plant Species Surveys and Vegetation Mapping at Lawrence Livermore National Laboratory

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

    Preston, R E

    This report presents the results of Jones & Stokes special-status plant surveys and vegetation mapping for the University of California, Lawrence Livermore National Laboratory (LLNL). Special-status plant surveys were conducted at Site 300 in April to May 1997 and in March to April 2002. Eight special-status plants were identified at Site 300: large-flowered fiddleneck, big tarplant, diamond-petaled poppy, round-leaved filaree, gypsum-loving larkspur, California androsace, stinkbells, and hogwallow starfish. Maps identifying the locations of these species, a discussion of the occurrence of these species at Site 300, and a checklist of the flora of Site 300 are presented. A reconnaissance surveymore » of the LLNL Livermore Site was conducted in June 2002. This survey concluded that no special-status plants occur at the Livermore Site. Vegetation mapping was conducted in 2001 at Site 300 to update a previous vegetation study done in 1986. The purpose of the vegetation mapping was to update and to delineate more precisely the boundaries between vegetation types and to map vegetation types that previously were not mapped. The vegetation map is presented with a discussion of the vegetation classification used.« less

  12. NREL: International Activities - Pakistan Resource Maps

    Science.gov Websites

    . The high-resolution (1-km) annual wind power maps were developed using a numerical modeling approach along with NREL's empirical validation methodology. The high-resolution (10-km) annual and seasonal KB) | High-Res (ZIP 281 KB) 40-km Resolution Annual Maps (Direct) Low-Res (JPG 156 KB) | High-Res

  13. 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.

  14. Nautical Charts: Another Dimension in Developing Map Skills. Instructional Activities Series IA/S-11.

    ERIC Educational Resources Information Center

    McCallum, W. F.; Botly, D. H.

    These activities are part of a series of 17 teacher-developed instructional activities for geography at the secondary-grade level described in SO 009 140. In the activities students develop map skills by learning about and using nautical charts. The first activity involves students in using parallel rulers and a compass rose to find their…

  15. Seismic hazard maps of Mexico, the Caribbean, and Central and South America

    USGS Publications Warehouse

    Tanner, J.G.; Shedlock, K.M.

    2004-01-01

    The growth of megacities in seismically active regions around the world often includes the construction of seismically unsafe buildings and infrastructures due to an insufficient knowledge of existing seismic hazard and/or economic constraints. Minimization of the loss of life, property damage, and social and economic disruption due to earthquakes depends on reliable estimates of seismic hazard. We have produced a suite of seismic hazard estimates for Mexico, the Caribbean, and Central and South America. One of the preliminary maps in this suite served as the basis for the Caribbean and Central and South America portion of the Global Seismic Hazard Map (GSHM) published in 1999, which depicted peak ground acceleration (pga) with a 10% chance of exceedance in 50 years for rock sites. Herein we present maps depicting pga and 0.2 and 1.0 s spectral accelerations (SA) with 50%, 10%, and 2% chances of exceedance in 50 years for rock sites. The seismicity catalog used in the generation of these maps adds 3 more years of data to those used to calculate the GSH Map. Different attenuation functions (consistent with those used to calculate the U.S. and Canadian maps) were used as well. These nine maps are designed to assist in global risk mitigation by providing a general seismic hazard framework and serving as a resource for any national or regional agency to help focus further detailed studies required for regional/local needs. The largest seismic hazard values in Mexico, the Caribbean, and Central and South America generally occur in areas that have been, or are likely to be, the sites of the largest plate boundary earthquakes. High hazard values occur in areas where shallow-to-intermediate seismicity occurs frequently. ?? 2004 Elsevier B.V. All rights reserved.

  16. Fragile Sites of ‘Valencia’ Sweet Orange (Citrus sinensis) Chromosomes Are Related with Active 45s rDNA

    PubMed Central

    Lan, Hong; Chen, Chun-Li; Miao, Yin; Yu, Chang-Xiu; Guo, Wen-Wu; Xu, Qiang; Deng, Xiu-Xin

    2016-01-01

    Citrus sinensis chromosomes present a morphological differentiation of bands after staining by the fluorochromes CMA and DAPI, but there is still little information on its chromosomal characteristics. In this study, the chromosomes in ‘Valencia’ C. sinensis were analyzed by fluorescence in situ hybridization (FISH) using telomere DNA and the 45S rDNA gene as probes combining CMA/DAPI staining, which showed that there were two fragile sites in sweet orange chromosomes co-localizing at distended 45S rDNA regions, one proximally locating on B-type chromosome and the other subterminally locating on D-type chromosome. While the chromosomal CMA banding and 45S rDNA FISH mapping in the doubled haploid line of ‘Valencia’ C. sinensis indicated six 45S rDNA regions, four were identified as fragile sites as doubled comparing its parental line, which confirmed the cytological heterozygosity and chromosomal heteromorphisms in sweet orange. Furthermore, Ag-NOR identified two distended 45S rDNA regions to be active nucleolar organizing regions (NORs) in diploid ‘Valencia’ C. sinensis. The occurrence of quadrivalent in meiosis of pollen mother cells (PMCs) in ‘Valencia’ sweet orange further confirmed it was a chromosomal reciprocal translocation line. We speculated this chromosome translocation was probably related to fragile sites. Our data provide insights into the chromosomal characteristics of the fragile sites in ‘Valencia’ sweet orange and are expected to facilitate the further investigation of the possible functions of fragile sites. PMID:26977938

  17. Hydraulic model and flood-inundation maps developed for the Pee Dee National Wildlife Refuge, North Carolina

    USGS Publications Warehouse

    Smith, Douglas G.; Wagner, Chad R.

    2016-04-08

    A series of digital flood-inundation maps were developed on the basis of the water-surface profiles produced by the model. The inundation maps, which can be accessed through the USGS Flood Inundation Mapping Program Web site at http://water.usgs.gov/osw/flood_inundation, depict estimates of the areal extent and depth of flooding corresponding to selected water levels at the USGS streamgage Pee Dee River at Pee Dee Refuge near Ansonville, N.C. These maps, when combined with real-time water-level information from USGS streamgages, provide managers with critical information to help plan flood-response activities and resource protection efforts.

  18. Across-site patterns of modulation detection: Relation to speech recognitiona)

    PubMed Central

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

    2012-01-01

    The aim of this study was to identify across-site patterns of modulation detection thresholds (MDTs) in subjects with cochlear implants and to determine if removal of sites with the poorest MDTs from speech processor programs would result in improved speech recognition. Five hundred millisecond trains of symmetric-biphasic pulses were modulated sinusoidally at 10 Hz and presented at a rate of 900 pps using monopolar stimulation. Subjects were asked to discriminate a modulated pulse train from an unmodulated pulse train for all electrodes in quiet and in the presence of an interleaved unmodulated masker presented on the adjacent site. Across-site patterns of masked MDTs were then used to construct two 10-channel MAPs such that one MAP consisted of sites with the best masked MDTs and the other MAP consisted of sites with the worst masked MDTs. Subjects’ speech recognition skills were compared when they used these two different MAPs. Results showed that MDTs were variable across sites and were elevated in the presence of a masker by various amounts across sites. Better speech recognition was observed when the processor MAP consisted of sites with best masked MDTs, suggesting that temporal modulation sensitivity has important contributions to speech recognition with a cochlear implant. PMID:22559376

  19. Looking for an old map

    USGS Publications Warehouse

    ,

    1996-01-01

    Many people want maps that show an area of the United States as it existed many years ago. These are called historical maps, and there are two types. The most common type consists of special maps prepared by commercial firms to show such historical features as battle-fields, military routes, or the paths taken by famous travelers. Typically, these maps are for sale to tourists at the sites of historical events. The other type is the truly old map--one compiled by a surveyor or cartographer many years ago. Lewis and Clark, for example, made maps of their journeys into the Northwest Territories in 1803-6, and originals of some of these maps still exist.

  20. 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

  1. Engineered bi-histidine metal chelation sites map the structure of the mechanical unfolding transition state of an elastomeric protein domain GB1.

    PubMed

    Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin

    2012-08-22

    Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The φ(M2+)(U)-value is defined as ΔΔG(‡-N)/ΔΔG(U-N), which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG(‡-N)) relative to its thermodynamic stability (ΔG(U-N)) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify φ(M2+)(U)-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1's mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs

  2. A hybrid QM/MM simulation study of intramolecular proton transfer in the pyridoxal 5'-phosphate in the active site of transaminase: influence of active site interaction on proton transfer.

    PubMed

    Dutta Banik, Sindrila; Chandra, Amalendu

    2014-09-25

    Pyridoxal 5'-phosphate (PLP) Schiff base, a versatile cofactor, exhibits a tautomeric equilibrium that involves an intramolecular proton transfer between the N-protonated zwitterionic ketoenamine tautomer and the O-protonated covalent enolimine tautomer. It has been postulated that for the catalytic activity, the PLP has to be in the zwitterionic ketoenamine tautomeric form. However, the exact position of the tautomeric equilibrium of Schiff base in the active site of PLP-dependent enzyme is not known yet. In the present work, we investigated the tautomeric equilibrium for the external aldimine state of PLP aspartate (PLP-Asp) Schiff base in the active site of aspartate aminotransferase (AspAT) using combined quantum mechanical and molecular mechanical simulations. The main focus of the present study is to analyze the factors that control the tautomeric equilibrium in the active sites of various PLP-dependent enzymes. The results show that the ketoenamine tautomer is more preferred than the enolimine tautomer both in the gas and aqueous phases as well as in the active site of AspAT. Current simulations show that the active site of AspAT is more suitable for the ketoenamine tautomer compared to the enolimine tautomer. Interestingly, the Tyr225 acts as a proton donor to the phenolic oxygen in the ketoenamine tautomer, while in the covalent enolimine tautomer, it acts as a proton acceptor to the phenolic oxygen. Finally, the metadynamics study confirms this result. The calculated free energy barrier is about 7.5 kcal/mol. A comparative analysis of the microenvironment created by the active site residues of three different PLP-dependent enzymes (aspartate aminotransferase, Dopa decarboxylase, and Ala-racemase) has been carried out to understand the controlling factor(s) of the tautomeric equilibrium. The analysis shows that the intermolecular hydrogen bonding between active site residues and the phenolic oxygen of PLP shifts the tautomeric equilibrium toward the N

  3. Six Landing Sites on Mars

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The landing site chosen for NASA's Phoenix Mars Lander, at about 68 degrees north latitude, is much farther north than the sites where previous spacecraft have landed on Mars.

    Color coding on this map indicates relative elevations based on data from the Mars Orbiter Laser Altimeter on NASA's Mars Global Surveyor. Red is higher elevation; blue is lower elevation. In longitude, the map extends from 70 degrees (north) to minus 70 degrees (south).

  4. Mapping epitopes and antigenicity by site-directed masking

    NASA Astrophysics Data System (ADS)

    Paus, Didrik; Winter, Greg

    2006-06-01

    Here we describe a method for mapping the binding of antibodies to the surface of a folded antigen. We first created a panel of mutant antigens (-lactamase) in which single surface-exposed residues were mutated to cysteine. We then chemically tethered the cysteine residues to a solid phase, thereby masking a surface patch centered on each cysteine residue and blocking the binding of antibodies to this region of the surface. By these means we mapped the epitopes of several mAbs directed to -lactamase. Furthermore, by depleting samples of polyclonal antisera to the masked antigens and measuring the binding of each depleted sample of antisera to unmasked antigen, we mapped the antigenicity of 23 different epitopes. After immunization of mice and rabbits with -lactamase in Freund's adjuvant, we found that the antisera reacted with both native and denatured antigen and that the antibody response was mainly directed to an exposed and flexible loop region of the native antigen. By contrast, after immunization in PBS, we found that the antisera reacted only weakly with denatured antigen and that the antibody response was more evenly distributed over the antigenic surface. We suggest that denatured antigen (created during emulsification in Freund's adjuvant) elicits antibodies that bind mainly to the flexible regions of the native protein and that this explains the correlation between antigenicity and backbone flexibility. Denaturation of antigen during vaccination or natural infections would therefore be expected to focus the antibody response to the flexible loops. backbone flexibility | Freund's adjuvant | conformational epitope | antisera

  5. Creative Concept Mapping.

    ERIC Educational Resources Information Center

    Brown, David S.

    2002-01-01

    Recommends the use of concept mapping in science teaching and proposes that it be presented as a creative activity. Includes a sample lesson plan of a potato stamp concept mapping activity for astronomy. (DDR)

  6. Identification of active atrial fibrillation sources and their discrimination from passive rotors using electrographical flow mapping.

    PubMed

    Bellmann, Barbara; Lin, Tina; Ruppersberg, Peter; Zettwitz, Marit; Guttmann, Selma; Tscholl, Verena; Nagel, Patrick; Roser, Mattias; Landmesser, Ulf; Rillig, Andreas

    2018-05-09

    The optimal ablation approach for the treatment of persistent atrial fibrillation (AF) is still under debate; however, the identification and elimination of AF sources is thought to play a key role. Currently available technologies for the identification of AF sources are not able to differentiate between active rotors or focal impulse (FI) and passive circular turbulences as generated by the interaction of a wave front with a functional obstacle such as fibrotic tissue. This study introduces electrographic flow (EGF) mapping as a novel technology for the identification and characterization of AF sources in humans. Twenty-five patients with AF (persistent: n = 24, long-standing persistent: n = 1; mean age 70.0 ± 8.3 years, male: n = 17) were included in this prospective study. Focal impulse and Rotor-Mapping (FIRM) was performed in addition to pulmonary vein isolation using radiofrequency in conjunction with a 3D-mapping-system. One-minute epochs were exported from the EP-recording-system and re-analyzed using EGF mapping after the procedure. 44 potential AF sources (43 rotors and one FI) were identified with FIRM and 39 of these rotors were targeted for ablation. EGF mapping verified 40 of these patterns and identified 24/40 (60%) as active sources while 16/40 (40%) were classified as passive circular turbulences. Four rotors were not identified by EGF mapping. EGF is the first method to identify active AF sources during AF ablation procedures in humans and discriminate them from passive rotational phenomena, which occur if the excitation wavefront passes conduction bariers. EGF mapping may allow improved guidance of AF ablation procedures.

  7. Community Update on Site Activities, July 19, 2013

    EPA Pesticide Factsheets

    In an effort to engage and inform community members interested in the New Bedford Harbor Superfund Site cleanup, EPA will be issuing periodic topic-based fact sheets that will provide background information and updates about ongoing activities.

  8. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

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

    Crichlow, G.; Lubetsky, J; Leng, L

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic datamore » indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.« less

  9. Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.

    PubMed

    Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas; Rosen, Michael K

    2017-09-26

    The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

  10. Monocopper active site for partial methane oxidation in Cu-exchanged 8MR zeolites

    DOE PAGES

    Kulkarni, Ambarish R.; Zhao, Zhi -Jian; Siahrostami, Samira; ...

    2016-08-17

    Direct conversion of methane to methanol using oxygen is experiencing renewed interest owing to the availability of new natural gas resources. Copper-exchanged zeolites such as mordenite and ZSM-5 have shown encouraging results, and di- and tri-copper species have been suggested as active sites. Recently, small eight-membered ring (8MR) zeolites including SSZ-13, -16, and -39 have been shown to be active for methane oxidation, but the active sites and reaction mechanisms in these 8MR zeolites are not known. In this work, we use density functional theory (DFT) calculations to systematically evaluate monocopper species as active sites for the partial methane oxidationmore » reaction in Cu-exchanged SSZ-13. On the basis of kinetic and thermodynamic arguments, we suggest that [Cu IIOH] + species in the 8MR are responsible for the experimentally observed activity. Furthermore, our results successfully explain the available spectroscopic data and experimental observations including (i) the necessity of water for methanol extraction and (ii) the effect of Si/Al ratio on the catalyst activity. Monocopper species have not yet been suggested as an active site for the partial methane oxidation reaction, and our results suggest that [Cu IIOH] + active site may provide complementary routes for methane activation in zeolites in addition to the known [Cu–O–Cu] 2+ and Cu 3O 3 motifs.« less

  11. Frequency Count Attribute Oriented Induction of Corporate Network Data for Mapping Business Activity

    NASA Astrophysics Data System (ADS)

    Tanutama, Lukas

    2014-03-01

    Companies increasingly rely on Internet for effective and efficient business communication. As Information Technology infrastructure backbone for business activities, corporate network connects the company to Internet and enables its activities globally. It carries data packets generated by the activities of the users performing their business tasks. Traditionally, infrastructure operations mainly maintain data carrying capacity and network devices performance. It would be advantageous if a company knows what activities are running in its network. The research provides a simple method of mapping the business activity reflected by the network data. To map corporate users' activities, a slightly modified Attribute Oriented Induction (AOI) approach to mine the network data was applied. The frequency of each protocol invoked were counted to show what the user intended to do. The collected data was samples taken within a certain sampling period. Samples were taken due to the enormous data packets generated. Protocols of interest are only Internet related while intranet protocols are ignored. It can be concluded that the method could provide the management a general overview of the usage of its infrastructure and lead to efficient, effective and secure ICT infrastructure.

  12. Electrocorticographic Frequency Alteration Mapping of Speech Cortex during an Awake Craniotomy: Case Report

    PubMed Central

    Breshears, J.; Sharma, M.; Anderson, N.R.; Rashid, S.; Leuthardt, E.C.

    2010-01-01

    Objective Traditional electrocortical stimulation (ECS) mapping is limited by the lengthy serial investigation (one location at a time) and the risk of afterdischarges in localizing eloquent cortex. Electrocorticographic frequency alteration mapping (EFAM) allows the parallel investigation of many cortical sites in much less time and with no risk of afterdischarges because of its passive nature. We examined its use with ECS in the context of language mapping during an awake craniotomy for a tumor resection. Clinical Presentation The patient was a 61-year-old right-handed Caucasian male who presented with headache and mild aphasia. Imaging demonstrated a 3-cm cystic mass in the posterior temporal-parietal lobe. The patient underwent an awake craniotomy for the mapping of his speech cortex and resection of the mass. Intervention Using a 32-contact electrode array, electrocorticographic signals were recorded from the exposed cortex as the patient participated in a 3-min screening task involving active (patient naming visually presented words) and rest (patient silent) conditions. A spectral comparison of the 2 conditions revealed specific cortical locations associated with activation during speech. The patient was then widely mapped using ECS. Three of 4 sites identified by ECS were also identified passively and in parallel by EFAM, 2 with statistical significance and the third by qualitative inspection. Conclusion EFAM was technically achieved in an awake craniotomy patient and had good concordance with ECS mapping. Because it poses no risk of afterdischarges and offers substantial time savings, EFAM holds promise for future development as an adjunct intraoperative mapping tool. Additionally, the cortical signals obtained by this modality can be utilized for localization in the presence of a tumor adjacent to the eloquent regions. PMID:19940544

  13. Mapping the Active Site Helix-to-Strand Conversion of CxxxxC Peroxiredoxin Q Enzymes †

    PubMed Central

    Perkins, Arden; Gretes, Michael C.; Nelson, Kimberly J.; Poole, Leslie B.; Karplus, P. Andrew

    2012-01-01

    Peroxiredoxins (Prx) are a family of enzymes which reduce peroxides using a peroxidatic cysteine residue; among these, the PrxQ subfamily members are proposed to be the most ancestral-like yet are among the least characterized. In many PrxQ enzymes, a second “resolving” cysteine is located six residues downstream from the peroxidatic Cys, and these residues form a disulfide during the catalytic cycle. Here, we describe three hyperthermophilic PrxQ crystal structures originally solved by the RIKEN structural genomics group. We reprocessed the diffraction data and carried out further refinement to yield models with Rfree lowered by 2.3–7.2% and resolution extended by 0.2–0.3 Å, making one, at 1.4 Å, the best resolved peroxiredoxin to date. Comparisons of two matched thiol and disulfide forms reveal that the active site conformational change required for disulfide formation involves a transition of about 20 residues from a pair of α-helices to a β-hairpin and 310-helix. Each conformation has about 10 residues with high disorder providing slack that enables the dramatic shift, and the two conformations are anchored to the protein core by distinct non-polar side chains that fill three hydrophobic pockets. Sequence conservation patterns confirm the importance of these and a few additional residues for function. From a broader perspective, this study raises the provocative question of how to make use of the valuable information in the protein data bank generated by structural genomics projects but not described in the literature, perhaps remaining unrecognized and certainly underutilized. PMID:22928725

  14. The Xanthomonas euvesicatoria type III effector XopAU is an active protein kinase that manipulates plant MAP kinase signaling.

    PubMed

    Teper, Doron; Girija, Anil Madhusoodana; Bosis, Eran; Popov, Georgy; Savidor, Alon; Sessa, Guido

    2018-01-01

    The Gram-negative bacterium Xanthomonas euvesicatoria (Xe) is the causal agent of bacterial spot disease of pepper and tomato. Xe delivers effector proteins into host cells through the type III secretion system to promote disease. Here, we show that the Xe effector XopAU, which is conserved in numerous Xanthomonas species, is a catalytically active protein kinase and contributes to the development of disease symptoms in pepper plants. Agrobacterium-mediated expression of XopAU in host and non-host plants activated typical defense responses, including MAP kinase phosphorylation, accumulation of pathogenesis-related (PR) proteins and elicitation of cell death, that were dependent on the kinase activity of the effector. XopAU-mediated cell death was not dependent on early signaling components of effector-triggered immunity and was also observed when the effector was delivered into pepper leaves by Xanthomonas campestris pv. campestris, but not by Xe. Protein-protein interaction studies in yeast and in planta revealed that XopAU physically interacts with components of plant immunity-associated MAP kinase cascades. Remarkably, XopAU directly phosphorylated MKK2 in vitro and enhanced its phosphorylation at multiple sites in planta. Consistent with the notion that MKK2 is a target of XopAU, silencing of the MKK2 homolog or overexpression of the catalytically inactive mutant MKK2K99R in N. benthamiana plants reduced XopAU-mediated cell death and MAPK phosphorylation. Furthermore, yeast co-expressing XopAU and MKK2 displayed reduced growth and this phenotype was dependent on the kinase activity of both proteins. Together, our results support the conclusion that XopAU contributes to Xe disease symptoms in pepper plants and manipulates host MAPK signaling through phosphorylation and activation of MKK2.

  15. Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

    PubMed Central

    2015-01-01

    We developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. A 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. PMID:25075558

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

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

    Slate, J.L.; Berry, M.E.; Rowley, P.D.

    2000-03-08

    This digital geologic map of the Nevada Test Site (NTS) and vicinity, as well as its accompanying digital geophysical maps, are compiled at 1:100,000 scale. The map area covers two 30 {times} 60-minute quadrangles-the Pahute Mesa quadrangle to the north and the Beatty quadrangle to the south-plus a strip of 7 1/2-minute quadrangles on the east side. In addition to the NTS, the map area includes the rest of the southwest Nevada volcanic field, part of the Walker Lane, most of the Amargosa Desert, part of the Funeral and Grapevine Mountains, some of Death Valley, and the northern Spring Mountains.more » This geologic map improves on previous geologic mapping of the same area by providing new and updated Quaternary and bedrock geology, new geophysical interpretations of faults beneath the basins, and improved GIS coverages. This publication also includes a new isostatic gravity map and a new aeromagnetic map. The primary purpose of the three maps is to provide an updated geologic framework to aid interpretation of ground-water flow through and off the NTS. The NTS is centrally located within the area of the Death Valley regional ground-water flow system of southwestern Nevada and adjacent California. During the last 40 years, DOE and its predecessor agencies have conducted about 900 nuclear tests on the NTS, of which 100 were atmospheric tests and the rest were underground tests. More than 200 of the tests were detonated at or beneath the water table, which commonly is about 500 to 600 m below the surface. Because contaminants introduced by these test may move into water supplies off the NTS, rates and directions of ground-water flow must be determined. Knowledge about the ground water also is needed to properly appraise potential future effects of the possible nuclear waste repository at Yucca Mountain, adjacent to the NTS.« less

  17. SfiI genomic cleavage map of Escherichia coli K-12 strain MG1655.

    PubMed Central

    Perkins, J D; Heath, J D; Sharma, B R; Weinstock, G M

    1992-01-01

    An SfiI restriction map of Escherichia coli K-12 strain MG1655 is presented. The map contains thirty-one cleavage sites separating fragments ranging in size from 407 kb to 3.7 kb. Several techniques were used in the construction of this map, including CHEF pulsed field gel electrophoresis; physical analysis of a set of twenty-six auxotrophic transposon insertions; correlation with the restriction map of Kohara and coworkers using the commercially available E. coli Gene Mapping Membranes; analysis of publicly available sequence information; and correlation of the above data with the combined genetic and physical map developed by Rudd, et al. The combination of these techniques has yielded a map in which all but one site can be localized within a range of +/- 2 kb, and over half the sites can be localized precisely by sequence data. Two sites present in the EcoSeq5 sequence database are not cleaved in MG1655 and four sites are noted to be sensitive to methylation by the dcm methylase. This map, combined with the NotI physical map of MG1655, can aid in the rapid, precise mapping of several different types of genetic alterations, including transposon mediated mutations and other insertions, inversions, deletions and duplications. Images PMID:1312707

  18. What Motivates Young Adults to Talk About Physical Activity on Social Network Sites?

    PubMed

    Zhang, Ni; Campo, Shelly; Yang, Jingzhen; Eckler, Petya; Snetselaar, Linda; Janz, Kathleen; Leary, Emily

    2017-06-22

    Electronic word-of-mouth on social network sites has been used successfully in marketing. In social marketing, electronic word-of-mouth about products as health behaviors has the potential to be more effective and reach more young adults than health education through traditional mass media. However, little is known about what motivates people to actively initiate electronic word-of-mouth about health behaviors on their personal pages or profiles on social network sites, thus potentially reaching all their contacts on those sites. This study filled the gap by applying a marketing theoretical model to explore the factors associated with electronic word-of-mouth on social network sites about leisure-time physical activity. A Web survey link was sent to undergraduate students at one of the Midwestern universities and 439 of them completed the survey. The average age of the 439 participants was 19 years (SD=1 year, range: 18-24). Results suggested that emotional engagement with leisure-time physical activity (ie, affective involvement in leisure-time physical activity) predicted providing relevant opinions or information on social network sites. Social network site users who perceived stronger ties with all their contacts were more likely to provide and seek leisure-time physical activity opinions and information. People who provided leisure-time physical activity opinions and information were more likely to seek opinions and information, and people who forwarded information about leisure-time physical activity were more likely to chat about it. This study shed light on the application of the electronic word-of-mouth theoretical framework in promoting health behaviors. The findings can also guide the development of future social marketing interventions using social network sites to promote leisure-time physical activity. ©Ni Zhang, Shelly Campo, Jingzhen Yang, Petya Eckler, Linda Snetselaar, Kathleen Janz, Emily Leary. Originally published in the Journal of Medical

  19. What Motivates Young Adults to Talk About Physical Activity on Social Network Sites?

    PubMed Central

    Campo, Shelly; Yang, Jingzhen; Eckler, Petya; Snetselaar, Linda; Janz, Kathleen; Leary, Emily

    2017-01-01

    Background Electronic word-of-mouth on social network sites has been used successfully in marketing. In social marketing, electronic word-of-mouth about products as health behaviors has the potential to be more effective and reach more young adults than health education through traditional mass media. However, little is known about what motivates people to actively initiate electronic word-of-mouth about health behaviors on their personal pages or profiles on social network sites, thus potentially reaching all their contacts on those sites. Objective This study filled the gap by applying a marketing theoretical model to explore the factors associated with electronic word-of-mouth on social network sites about leisure-time physical activity. Methods A Web survey link was sent to undergraduate students at one of the Midwestern universities and 439 of them completed the survey. Results The average age of the 439 participants was 19 years (SD=1 year, range: 18-24). Results suggested that emotional engagement with leisure-time physical activity (ie, affective involvement in leisure-time physical activity) predicted providing relevant opinions or information on social network sites. Social network site users who perceived stronger ties with all their contacts were more likely to provide and seek leisure-time physical activity opinions and information. People who provided leisure-time physical activity opinions and information were more likely to seek opinions and information, and people who forwarded information about leisure-time physical activity were more likely to chat about it. Conclusions This study shed light on the application of the electronic word-of-mouth theoretical framework in promoting health behaviors. The findings can also guide the development of future social marketing interventions using social network sites to promote leisure-time physical activity. PMID:28642215

  20. Glossary of Common Site Terms

    MedlinePlus

    ... Maps Downloading Content for Analysis About Site What's New ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking to This Site Terms and ...

  1. Corrosion Research And Web Site Activities

    NASA Technical Reports Server (NTRS)

    Heidersbach, Robert H.

    2001-01-01

    This report covers corrosion-related activities at the NASA Kennedy Space Center during the summer of 2000. The NASA Kennedy Space Center's corrosion web site, corrosion.ksc.nasa.gov, was updated with new information based on feedback over the past two years. The methodology for a two-year atmospheric exposure testing program to study the effectiveness of commercial chemicals sold for rinsing aircraft and other equipment was developed and some preliminary laboratory chemical analyses are presented.

  2. Corrosion Research and Web Site Activities

    NASA Technical Reports Server (NTRS)

    Heidersbach, Robert H.

    2002-01-01

    This report covers corrosion-related activities at the NASA Kennedy Space Center during the summer of 2000. The NASA Kennedy Space Center's corrosion web site, corrosion.ksc.nasa.gov, was updated with new information based on feedback over the past two years. The methodology for a two-year atmospheric exposure testing program to study the effectiveness of commercial chemicals sold for rinsing aircraft and other equipment was developed and some preliminary laboratory chemical analyses are presented.

  3. Channeling by Proximity: The Catalytic Advantages of Active Site Colocalization Using Brownian Dynamics.

    PubMed

    Bauler, Patricia; Huber, Gary; Leyh, Thomas; McCammon, J Andrew

    2010-05-06

    Nature often colocalizes successive steps in a metabolic pathway. Such organization is predicted to increase the effective concentration of pathway intermediates near their recipient active sites and to enhance catalytic efficiency. Here, the pathway of a two-step reaction is modeled using a simple spherical approximation for the enzymes and substrate particles. Brownian dynamics are used to simulate the trajectory of a substrate particle as it diffuses between the active site zones of two different enzyme spheres. The results approximate distances for the most effective reaction pathways, indicating that the most effective reaction pathway is one in which the active sites are closely aligned. However, when the active sites are too close, the ability of the substrate to react with the first enzyme was hindered, suggesting that even the most efficient orientations can be improved for a system that is allowed to rotate or change orientation to optimize the likelihood of reaction at both sites.

  4. Spatial patterns of high Aedes aegypti oviposition activity in northwestern Argentina.

    PubMed

    Estallo, Elizabet Lilia; Más, Guillermo; Vergara-Cid, Carolina; Lanfri, Mario Alberto; Ludueña-Almeida, Francisco; Scavuzzo, Carlos Marcelo; Introini, María Virginia; Zaidenberg, Mario; Almirón, Walter Ricardo

    2013-01-01

    In Argentina, dengue has affected mainly the Northern provinces, including Salta. The objective of this study was to analyze the spatial patterns of high Aedes aegypti oviposition activity in San Ramón de la Nueva Orán, northwestern Argentina. The location of clusters as hot spot areas should help control programs to identify priority areas and allocate their resources more effectively. Oviposition activity was detected in Orán City (Salta province) using ovitraps, weekly replaced (October 2005-2007). Spatial autocorrelation was measured with Moran's Index and depicted through cluster maps to identify hot spots. Total egg numbers were spatially interpolated and a classified map with Ae. aegypti high oviposition activity areas was performed. Potential breeding and resting (PBR) sites were geo-referenced. A logistic regression analysis of interpolated egg numbers and PBR location was performed to generate a predictive mapping of mosquito oviposition activity. Both cluster maps and predictive map were consistent, identifying in central and southern areas of the city high Ae. aegypti oviposition activity. A logistic regression model was successfully developed to predict Ae. aegypti oviposition activity based on distance to PBR sites, with tire dumps having the strongest association with mosquito oviposition activity. A predictive map reflecting probability of oviposition activity was produced. The predictive map delimitated an area of maximum probability of Ae. aegypti oviposition activity in the south of Orán city where tire dumps predominate. The overall fit of the model was acceptable (ROC=0.77), obtaining 99% of sensitivity and 75.29% of specificity. Distance to tire dumps is inversely associated with high mosquito activity, allowing us to identify hot spots. These methodologies are useful for prevention, surveillance, and control of tropical vector borne diseases and might assist National Health Ministry to focus resources more effectively.

  5. Spatial Patterns of High Aedes aegypti Oviposition Activity in Northwestern Argentina

    PubMed Central

    Estallo, Elizabet Lilia; Más, Guillermo; Vergara-Cid, Carolina; Lanfri, Mario Alberto; Ludueña-Almeida, Francisco; Scavuzzo, Carlos Marcelo; Introini, María Virginia; Zaidenberg, Mario; Almirón, Walter Ricardo

    2013-01-01

    Background In Argentina, dengue has affected mainly the Northern provinces, including Salta. The objective of this study was to analyze the spatial patterns of high Aedes aegypti oviposition activity in San Ramón de la Nueva Orán, northwestern Argentina. The location of clusters as hot spot areas should help control programs to identify priority areas and allocate their resources more effectively. Methodology Oviposition activity was detected in Orán City (Salta province) using ovitraps, weekly replaced (October 2005–2007). Spatial autocorrelation was measured with Moran’s Index and depicted through cluster maps to identify hot spots. Total egg numbers were spatially interpolated and a classified map with Ae. aegypti high oviposition activity areas was performed. Potential breeding and resting (PBR) sites were geo-referenced. A logistic regression analysis of interpolated egg numbers and PBR location was performed to generate a predictive mapping of mosquito oviposition activity. Principal Findings Both cluster maps and predictive map were consistent, identifying in central and southern areas of the city high Ae. aegypti oviposition activity. A logistic regression model was successfully developed to predict Ae. aegypti oviposition activity based on distance to PBR sites, with tire dumps having the strongest association with mosquito oviposition activity. A predictive map reflecting probability of oviposition activity was produced. The predictive map delimitated an area of maximum probability of Ae. aegypti oviposition activity in the south of Orán city where tire dumps predominate. The overall fit of the model was acceptable (ROC = 0.77), obtaining 99% of sensitivity and 75.29% of specificity. Conclusions Distance to tire dumps is inversely associated with high mosquito activity, allowing us to identify hot spots. These methodologies are useful for prevention, surveillance, and control of tropical vector borne diseases and might assist National Health

  6. Restriction site polymorphism-based candidate gene mapping for seedling drought tolerance in cowpea [Vigna unguiculata (L.) Walp.].

    PubMed

    Muchero, Wellington; Ehlers, Jeffrey D; Roberts, Philip A

    2010-02-01

    Quantitative trait loci (QTL) studies provide insight into the complexity of drought tolerance mechanisms. Molecular markers used in these studies also allow for marker-assisted selection (MAS) in breeding programs, enabling transfer of genetic factors between breeding lines without complete knowledge of their exact nature. However, potential for recombination between markers and target genes limit the utility of MAS-based strategies. Candidate gene mapping offers an alternative solution to identify trait determinants underlying QTL of interest. Here, we used restriction site polymorphisms to investigate co-location of candidate genes with QTL for seedling drought stress-induced premature senescence identified previously in cowpea. Genomic DNA isolated from 113 F(2:8) RILs of drought-tolerant IT93K503-1 and drought susceptible CB46 genotypes was digested with combinations of EcoR1 and HpaII, Mse1, or Msp1 restriction enzymes and amplified with primers designed from 13 drought-responsive cDNAs. JoinMap 3.0 and MapQTL 4.0 software were used to incorporate polymorphic markers onto the AFLP map and to analyze their association with the drought response QTL. Seven markers co-located with peaks of previously identified QTL. Isolation, sequencing, and blast analysis of these markers confirmed their significant homology with drought or other abiotic stress-induced expressed sequence tags (EST) from cowpea and other plant systems. Further, homology with coding sequences for a multidrug resistance protein 3 and a photosystem I assembly protein ycf3 was revealed in two of these candidates. These results provide a platform for the identification and characterization of genetic trait determinants underlying seedling drought tolerance in cowpea.

  7. Interactive Geophysical Mapping on the Web

    NASA Astrophysics Data System (ADS)

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

    2002-12-01

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

  8. Knowledge Activation versus Sentence Mapping When Representing Fictional Characters' Emotional States.

    ERIC Educational Resources Information Center

    Gernsbacher, Morton Ann; Robertson, Rachel R. W.

    1992-01-01

    In a study of knowledge activation and sentence mapping, subjects read stories that described concrete actions, and then the content of the stories was manipulated (i.e. stories were written that implied different emotional states). It is suggested that the more emotionally evoking situations one encounters the more memory traces are stored and…

  9. Investigation on Hot Workability of Homogenized Al-Zn-Mg-Cu Alloy Based on Activation Energy and Processing Map

    NASA Astrophysics Data System (ADS)

    Peng, Xiaoyan; Su, Wusen; Xiao, Dan; Xu, Guofu

    2018-06-01

    Hot deformation behaviors of the homogenized Al-Zn-Mg-Cu alloy were studied by uniaxial compression tests carried out at 623-743 K and strain rates of 0.01-10 s-1. The constitutive equation was developed for the activation energy, and thus the activation energy map was constructed. During the hot deformation, the dominated softening mechanisms were the dynamic recovery and dynamic recrystallization, which were most likely to be driven with increasing temperature and decreasing activation energy. Based on the superposition of the activation energy map and the processing map, together with the microstructure characteristics, the optimized hot workability of the alloy was proposed at the domain (670-743 K and 0.01-0.16 s-1), where the peak efficiency was 0.39 and the activation energy range was 196-260 kJ mol-1.

  10. Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

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

    Anderson, Courtney M.; Hu, Jianxin; Thomas, Reuben

    2017-03-28

    Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by themore » SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.« less

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

    PubMed

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

    2009-09-02

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

  12. Geologic resource evaluation of Pu‘ukoholā Heiau National Historic Site, Hawai‘i, part II: Benthic habitat mapping

    USGS Publications Warehouse

    Cochran, Susan A.; Gibbs, Ann E.; Logan, Joshua B.

    2006-01-01

    In cooperation with the U.S. National Park Service (NPS), the U.S. Geological Survey (USGS) has mapped the underwater environment in and adjacent to three parks along the Kona coast on the island of Hawai‘i. This report is the second of two produced for the NPS on the geologic resource evaluation of Pu‘ukoholā Heiau National Historic Site (PUHE) and presents benthic habitat mapping of the waters of Kawaihae Bay offshore of PUHE. See Part I (Richmond and others, 2006) for an overview of the regional geology, local volcanics, and a detailed description of coastal landforms in the park. PUHE boundaries do not officially extend into the marine environment; however, impacts downslope of any activity in the park are of concern to management. The area of Kawaihae Bay mapped for this report extends from the north edge of the U.S. Coast Guard Reservation north of Kawaihae Harbor approximately 3.5 km south to the north edge of the Mauna Kea Golf Course and Beach Resort at Waikoloa and from the shoreline to depths of approximately 40 m (130 ft), where the fore reef drops off to the sandy shelf. The waters of smaller Pelekane Bay directly offshore of the park, while not formally under NPS jurisdiction, are managed by the park under an agreement with the State. This embayment is described in greater detail because of its special resource status. PUHE lies within the Kawaihae watershed, which contributes ~75 percent of the drainage in the northern portion of the study area; the Waikoloa/Waiulaula watershed contributes ~25 percent in the southern portion of the study area. Drainages from these watersheds into the study area include Makahuna, Makeāhua, Pohaukole, Kukui, and Waikoloa/Waiulaula Gulches. The Waikoloa/Waiulaula Gulch is the only perennial stream with a year-round water flow. Only during periods of extreme rainfall will water flow in the Makeāhua and Pohaukole gulches, merge together in the park, and empty directly into Pelekane Bay. In the late 1950s the reef

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

    USDA-ARS?s Scientific Manuscript database

    JournalMap is a scientific literature search engine that empowers you to find relevant research based on location and biophysical variables as well as traditional keyword searches. All publications are geotagged based on reported location information and plotted on a world map showing where the rese...

  14. Maturation of the [Ni-4Fe-4S] active site of carbon monoxide dehydrogenases.

    PubMed

    Merrouch, Mériem; Benvenuti, Martino; Lorenzi, Marco; Léger, Christophe; Fourmond, Vincent; Dementin, Sébastien

    2018-02-14

    Nickel-containing enzymes are diverse in terms of function and active site structure. In many cases, the biosynthesis of the active site depends on accessory proteins which transport and insert the Ni ion. We review and discuss the literature related to the maturation of carbon monoxide dehydrogenases (CODH) which bear a nickel-containing active site consisting of a [Ni-4Fe-4S] center called the C-cluster. The maturation of this center has been much less studied than that of other nickel-containing enzymes such as urease and NiFe hydrogenase. Several proteins present in certain CODH operons, including the nickel-binding proteins CooT and CooJ, still have unclear functions. We question the conception that the maturation of all CODH depends on the accessory protein CooC described as essential for nickel insertion into the active site. The available literature reveals biological variations in CODH active site biosynthesis.

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

    PubMed Central

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

    2018-01-01

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

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

    USDA-ARS?s Scientific Manuscript database

    A prescription map is a set of instructions that controls a variable rate irrigation (VRI) system. These maps, which may be based on prior yield, soil texture, topography, or soil electrical conductivity data, are often manually applied at the beginning of an irrigation season and remain static. The...

  17. Prediction of active sites of enzymes by maximum relevance minimum redundancy (mRMR) feature selection.

    PubMed

    Gao, Yu-Fei; Li, Bi-Qing; Cai, Yu-Dong; Feng, Kai-Yan; Li, Zhan-Dong; Jiang, Yang

    2013-01-27

    Identification of catalytic residues plays a key role in understanding how enzymes work. Although numerous computational methods have been developed to predict catalytic residues and active sites, the prediction accuracy remains relatively low with high false positives. In this work, we developed a novel predictor based on the Random Forest algorithm (RF) aided by the maximum relevance minimum redundancy (mRMR) method and incremental feature selection (IFS). We incorporated features of physicochemical/biochemical properties, sequence conservation, residual disorder, secondary structure and solvent accessibility to predict active sites of enzymes and achieved an overall accuracy of 0.885687 and MCC of 0.689226 on an independent test dataset. Feature analysis showed that every category of the features except disorder contributed to the identification of active sites. It was also shown via the site-specific feature analysis that the features derived from the active site itself contributed most to the active site determination. Our prediction method may become a useful tool for identifying the active sites and the key features identified by the paper may provide valuable insights into the mechanism of catalysis.

  18. Genome-wide mapping and analysis of active promoters in mouse embryonic stem cells and adult organs

    PubMed Central

    Barrera, Leah O.; Li, Zirong; Smith, Andrew D.; Arden, Karen C.; Cavenee, Webster K.; Zhang, Michael Q.; Green, Roland D.; Ren, Bing

    2008-01-01

    By integrating genome-wide maps of RNA polymerase II (Polr2a) binding with gene expression data and H3ac and H3K4me3 profiles, we characterized promoters with enriched activity in mouse embryonic stem cells (mES) as well as adult brain, heart, kidney, and liver. We identified ∼24,000 promoters across these samples, including 16,976 annotated mRNA 5′ ends and 5153 additional sites validating cap-analysis of gene expression (CAGE) 5′ end data. We showed that promoters with CpG islands are typically non-tissue specific, with the majority associated with Polr2a and the active chromatin modifications in nearly all the tissues examined. By contrast, the promoters without CpG islands are generally associated with Polr2a and the active chromatin marks in a tissue-dependent way. We defined 4396 tissue-specific promoters by adapting a quantitative index of tissue-specificity based on Polr2a occupancy. While there is a general correspondence between Polr2a occupancy and active chromatin modifications at the tissue-specific promoters, a subset of them appear to be persistently marked by active chromatin modifications in the absence of detectable Polr2a binding, highlighting the complexity of the functional relationship between chromatin modification and gene expression. Our results provide a resource for exploring promoter Polr2a binding and epigenetic states across pluripotent and differentiated cell types in mammals. PMID:18042645

  19. Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI

    PubMed Central

    Fox, Michael D.; Qian, Tianyi; Madsen, Joseph R.; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-cong; Groppe, David M.; Mehta, Ashesh D.; Hong, Bo; Liu, Hesheng

    2016-01-01

    Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20 years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach is demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. PMID:26408860

  20. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts

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

    Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

    The activation of molecular O 2as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O 2activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O 2dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O 2dissociationmore » is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O 2dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction.« less

  1. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts

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

    Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

    2016-01-01

    The activation of molecular O 2as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O 2activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O 2dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O 2dissociationmore » is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O 2dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction.« less

  2. Brownfields Road Map

    EPA Pesticide Factsheets

    The Brownfields Road Map publication and companion website provide a general outline of how to assess and clean up a brownfields site and introduce stakeholders to a range of technology options and available resources.

  3. Brownian aggregation rate of colloid particles with several active sites

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

    Nekrasov, Vyacheslav M.; Yurkin, Maxim A.; Chernyshev, Andrei V., E-mail: chern@ns.kinetics.nsc.ru

    2014-08-14

    We theoretically analyze the aggregation kinetics of colloid particles with several active sites. Such particles (so-called “patchy particles”) are well known as chemically anisotropic reactants, but the corresponding rate constant of their aggregation has not yet been established in a convenient analytical form. Using kinematic approximation for the diffusion problem, we derived an analytical formula for the diffusion-controlled reaction rate constant between two colloid particles (or clusters) with several small active sites under the following assumptions: the relative translational motion is Brownian diffusion, and the isotropic stochastic reorientation of each particle is Markovian and arbitrarily correlated. This formula was shownmore » to produce accurate results in comparison with more sophisticated approaches. Also, to account for the case of a low number of active sites per particle we used Monte Carlo stochastic algorithm based on Gillespie method. Simulations showed that such discrete model is required when this number is less than 10. Finally, we applied the developed approach to the simulation of immunoagglutination, assuming that the formed clusters have fractal structure.« less

  4. Selective Enrichment and Direct Analysis of Protein S-Palmitoylation Sites.

    PubMed

    Thinon, Emmanuelle; Fernandez, Joseph P; Molina, Henrik; Hang, Howard C

    2018-05-04

    S-Fatty-acylation is the covalent attachment of long chain fatty acids, predominately palmitate (C16:0, S-palmitoylation), to cysteine (Cys) residues via a thioester linkage on proteins. This post-translational and reversible lipid modification regulates protein function and localization in eukaryotes and is important in mammalian physiology and human diseases. While chemical labeling methods have improved the detection and enrichment of S-fatty-acylated proteins, mapping sites of modification and characterizing the endogenously attached fatty acids are still challenging. Here, we describe the integration and optimization of fatty acid chemical reporter labeling with hydroxylamine-mediated enrichment of S-fatty-acylated proteins and direct tagging of modified Cys residues to selectively map lipid modification sites. This afforded improved enrichment and direct identification of many protein S-fatty-acylation sites compared to previously described methods. Notably, we directly identified the S-fatty-acylation sites of IFITM3, an important interferon-stimulated inhibitor of virus entry, and we further demonstrated that the highly conserved Cys residues are primarily modified by palmitic acid. The methods described here should facilitate the direct analysis of protein S-fatty-acylation sites and their endogenously attached fatty acids in diverse cell types and activation states important for mammalian physiology and diseases.

  5. Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

    PubMed

    Hoque, Md Anarul; Zhang, Yong; Chen, Liuqing; Yang, Guangyu; Khatun, Mst Afroza; Chen, Haifeng; Hao, Liu; Feng, Yan

    2017-05-19

    The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used to investigate StLois's potential for changing enzyme function. By inserting six residues into active site loop 7, the best variant ML7-B6 demonstrated a 16-fold further increase in catalytic efficiency toward ethyl-paraoxon compared with its initial template, that is a 609-fold higher, >10 7 fold substrate specificity shift relative to that of wild-type lactonase. The remodeled variants displayed 760-fold greater organophosphate hydrolysis activity toward the organophosphates parathion, diazinon, and chlorpyrifos. Structure and docking computations support the source of notably inverted enzyme specificity. Considering the fundamental importance of active site loops, the strategy has potential for the rapid generation of novel enzyme functions by loop remodeling.

  6. Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality.

    PubMed

    Zhou, Quansheng; Kapoor, Mili; Guo, Min; Belani, Rajesh; Xu, Xiaoling; Kiosses, William B; Hanan, Melanie; Park, Chulho; Armour, Eva; Do, Minh-Ha; Nangle, Leslie A; Schimmel, Paul; Yang, Xiang-Lei

    2010-01-01

    Protein multifunctionality is an emerging explanation for the complexity of higher organisms. In this regard, aminoacyl tRNA synthetases catalyze amino acid activation for protein synthesis, but some also act in pathways for inflammation, angiogenesis and apoptosis. It is unclear how these multiple functions evolved and how they relate to the active site. Here structural modeling analysis, mutagenesis and cell-based functional studies show that the potent angiostatic, natural fragment of human tryptophanyl-tRNA synthetase (TrpRS) associates via tryptophan side chains that protrude from its cognate cellular receptor vascular endothelial cadherin (VE-cadherin). VE-cadherin's tryptophan side chains fit into the tryptophan-specific active site of the synthetase. Thus, specific side chains of the receptor mimic amino acid substrates and expand the functionality of the active site of the synthetase. We propose that orthogonal use of the same active site may be a general way to develop multifunctionality of human tRNA synthetases and other proteins.

  7. CH4 emission estimates from an active landfill site inferred from a combined approach of CFD modelling and in situ FTIR measurements

    NASA Astrophysics Data System (ADS)

    Sonderfeld, Hannah; Boesch, Hartmut; Jeanjean, Antoine P. R.; Riddick, Stuart N.; Allen, Grant; Ars, Sebastien; Davies, Stewart; Harris, Neil; Humpage, Neil; Leigh, Roland; Pitt, Joseph

    2017-04-01

    Globally, the waste sector contributes to nearly a fifth of anthropogenic methane (CH4) emitted to the atmosphere and is the second largest source of methane in the UK. In recent years great improvements to reduce those emissions have been achieved by installation of methane recovery systems at landfill sites and subsequently methane emissions reported in national emission inventories have been reduced. Nevertheless, methane emissions of landfills remain uncertain and quantification of emission fluxes is essential to verify reported emission inventories and to monitor changes in emissions. We are presenting data from the deployment of an in situ FTIR (Fourier Transform Infrared Spectrometer, Ecotech) for continuous and simultaneous sampling of CO2, CH4, N2O and CO with high time resolution of the order of minutes. During a two week field campaign at an operational landfill site in Eastern England in August 2014, measurements were taken within a radius of 320 m of the uncovered and active area of the landfill, which was still filled with new incoming waste. We have applied a computation fluid dynamics (CFD) model, constrained with local wind measurements and a detailed topographic map of the landfill site, to the in situ concentration data to calculate CH4 fluxes of the active site. A mean daytime flux of 0.83 mg m-2 s-1 (53.26 kg h-1) was calculated for the area of the active site. An additional source area was identified and incorporated into the CFD model, which resulted in higher total methane emissions of 75.97 kg h-1 for the combined emission areas. Our method of combining a CFD model to in situ data, in medium proximity of the source area, allows to distinguish between different emission areas and thereby provide more detailed information compared to bulk emission approaches.

  8. In silico analysis of Pycnoporus cinnabarinus laccase active site with toxic industrial dyes.

    PubMed

    Prasad, Nirmal K; Vindal, Vaibhav; Narayana, Siva Lakshmi; Ramakrishna, V; Kunal, Swaraj Priyaranjan; Srinivas, M

    2012-05-01

    Laccases belong to multicopper oxidases, a widespread class of enzymes implicated in many oxidative functions in various industrial oxidative processes like production of fine chemicals to bioremediation of contaminated soil and water. In order to understand the mechanisms of substrate binding and interaction between substrates and Pycnoporus cinnabarinus laccase, a homology model was generated. The resulted model was further validated and used for docking studies with toxic industrial dyes- acid blue 74, reactive black 5 and reactive blue 19. Interactions of chemical mediators with the laccase was also examined. The docking analysis showed that the active site always cannot accommodate the dye molecules, due to constricted nature of the active site pocket and steric hindrance of the residues whereas mediators are relatively small and can easily be accommodated into the active site pocket, which, thereafter leads to the productive binding. The binding properties of these compounds along with identification of critical active site residues can be used for further site-directed mutagenesis experiments in order to identify their role in activity and substrate specificity, ultimately leading to improved mutants for degradation of these toxic compounds.

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

    NASA Astrophysics Data System (ADS)

    Guangwei, Z.

    2013-07-01

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

  10. Rapid and minimum invasive functional brain mapping by real-time visualization of high gamma activity during awake craniotomy.

    PubMed

    Ogawa, Hiroshi; Kamada, Kyousuke; Kapeller, Christoph; Hiroshima, Satoru; Prueckl, Robert; Guger, Christoph

    2014-11-01

    Electrocortical stimulation (ECS) is the gold standard for functional brain mapping during an awake craniotomy. The critical issue is to set aside enough time to identify eloquent cortices by ECS. High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram is assumed to reflect localized cortical processing. In this report, we used real-time HGA mapping and functional neuronavigation integrated with functional magnetic resonance imaging (fMRI) for rapid and reliable identification of motor and language functions. Four patients with intra-axial tumors in their dominant hemisphere underwent preoperative fMRI and lesion resection with an awake craniotomy. All patients showed significant fMRI activation evoked by motor and language tasks. During the craniotomy, we recorded electrocorticogram activity by placing subdural grids directly on the exposed brain surface. Each patient performed motor and language tasks and demonstrated real-time HGA dynamics in hand motor areas and parts of the inferior frontal gyrus. Sensitivity and specificity of HGA mapping were 100% compared with ECS mapping in the frontal lobe, which suggested HGA mapping precisely indicated eloquent cortices. We found different HGA dynamics of language tasks in frontal and temporal regions. Specificities of the motor and language-fMRI did not reach 85%. The results of HGA mapping was mostly consistent with those of ECS mapping, although fMRI tended to overestimate functional areas. This novel technique enables rapid and accurate identification of motor and frontal language areas. Furthermore, real-time HGA mapping sheds light on underlying physiological mechanisms related to human brain functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Mapping of RNA accessible sites by extension of random oligonucleotide libraries with reverse transcriptase.

    PubMed Central

    Allawi, H T; Dong, F; Ip, H S; Neri, B P; Lyamichev, V I

    2001-01-01

    A rapid and simple method for determining accessible sites in RNA that is independent of the length of target RNA and does not require RNA labeling is described. In this method, target RNA is allowed to hybridize with sequence-randomized libraries of DNA oligonucleotides linked to a common tag sequence at their 5'-end. Annealed oligonucleotides are extended with reverse transcriptase and the extended products are then amplified by using PCR with a primer corresponding to the tag sequence and a second primer specific to the target RNA sequence. We used the combination of both the lengths of the RT-PCR products and the location of the binding site of the RNA-specific primer to determine which regions of the RNA molecules were RNA extendible sites, that is, sites available for oligonucleotide binding and extension. We then employed this reverse transcription with the random oligonucleotide libraries (RT-ROL) method to determine the accessible sites on four mRNA targets, human activated ras (ha-ras), human intercellular adhesion molecule-1 (ICAM-1), rabbit beta-globin, and human interferon-gamma (IFN-gamma). Our results were concordant with those of other researchers who had used RNase H cleavage or hybridization with arrays of oligonucleotides to identify accessible sites on some of these targets. Further, we found good correlation between sites when we compared the location of extendible sites identified by RT-ROL with hybridization sites of effective antisense oligonucleotides on ICAM-1 mRNA in antisense inhibition studies. Finally, we discuss the relationship between RNA extendible sites and RNA accessibility. PMID:11233988

  12. Thermodynamic compensation upon binding to exosite 1 and the active site of thrombin

    PubMed Central

    Treuheit, Nicholas A.; Beach, Muneera A.; Komives, Elizabeth A.

    2011-01-01

    Several lines of experimental evidence including amide exchange and NMR suggest that ligands binding to thrombin cause reduced backbone dynamics. Binding of the covalent inhibitor dPhe-Pro-Arg chloromethylketone to the active site serine, as well as non-covalent binding of a fragment of the regulatory protein, thrombomodulin, to exosite 1 on the back side of the thrombin molecule both cause reduced dynamics. However, the reduced dynamics do not appear to be accompanied by significant conformational changes. In addition, binding of ligands to the active site does not change the affinity of thrombomodulin fragments binding to exosite 1, however, the thermodynamic coupling between exosite 1 and the active site has not been fully explored. We present isothermal titration calorimetry experiments that probe changes in enthalpy and entropy upon formation of binary ligand complexes. The approach relies on stringent thrombin preparation methods and on the use of dansyl-L-arginine-(3-methyl-1,5-pantanediyl) amide and a DNA aptamer as ligands with ideal thermodynamic signatures for binding to the active site and to exosite 1. Using this approach, the binding thermodynamic signatures of each ligand alone as well as the binding signatures of each ligand when the other binding site was occupied were measured. Different exosite 1 ligands with widely varied thermodynamic signatures cause the same reduction in ΔH and a concomitantly lower entropy cost upon DAPA binding at the active site. The results suggest a general phenomenon of enthalpy-entropy compensation consistent with reduction of dynamics/increased folding of thrombin upon ligand binding to either the active site or to exosite 1. PMID:21526769

  13. Thermodynamic compensation upon binding to exosite 1 and the active site of thrombin.

    PubMed

    Treuheit, Nicholas A; Beach, Muneera A; Komives, Elizabeth A

    2011-05-31

    Several lines of experimental evidence including amide exchange and NMR suggest that ligands binding to thrombin cause reduced backbone dynamics. Binding of the covalent inhibitor dPhe-Pro-Arg chloromethyl ketone to the active site serine, as well as noncovalent binding of a fragment of the regulatory protein, thrombomodulin, to exosite 1 on the back side of the thrombin molecule both cause reduced dynamics. However, the reduced dynamics do not appear to be accompanied by significant conformational changes. In addition, binding of ligands to the active site does not change the affinity of thrombomodulin fragments binding to exosite 1; however, the thermodynamic coupling between exosite 1 and the active site has not been fully explored. We present isothermal titration calorimetry experiments that probe changes in enthalpy and entropy upon formation of binary ligand complexes. The approach relies on stringent thrombin preparation methods and on the use of dansyl-l-arginine-(3-methyl-1,5-pantanediyl)amide and a DNA aptamer as ligands with ideal thermodynamic signatures for binding to the active site and to exosite 1. Using this approach, the binding thermodynamic signatures of each ligand alone as well as the binding signatures of each ligand when the other binding site was occupied were measured. Different exosite 1 ligands with widely varied thermodynamic signatures cause a similar reduction in ΔH and a concomitantly lower entropy cost upon DAPA binding at the active site. The results suggest a general phenomenon of enthalpy-entropy compensation consistent with reduction of dynamics/increased folding of thrombin upon ligand binding to either the active site or exosite 1.

  14. MOLA-Based Landing Site Characterization

    NASA Technical Reports Server (NTRS)

    Duxbury, T. C.; Ivanov, A. B.

    2001-01-01

    The Mars Global Surveyor (MGS) Mars Orbiter Laser Altimeter (MOLA) data provide the basis for site characterization and selection never before possible. The basic MOLA information includes absolute radii, elevation and 1 micrometer albedo with derived datasets including digital image models (DIM's illuminated elevation data), slopes maps and slope statistics and small scale surface roughness maps and statistics. These quantities are useful in downsizing potential sites from descent engineering constraints and landing/roving hazard and mobility assessments. Slope baselines at the few hundred meter level and surface roughness at the 10 meter level are possible. Additionally, the MOLA-derived Mars surface offers the possibility to precisely register and map project other instrument datasets (images, ultraviolet, infrared, radar, etc.) taken at different resolution, viewing and lighting geometry, building multiple layers of an information cube for site characterization and selection. Examples of direct MOLA data, data derived from MOLA and other instruments data registered to MOLA arc given for the Hematite area.

  15. Active-Site Hydration and Water Diffusion in Cytochrome P450cam: A Highly Dynamic Process

    PubMed Central

    Miao, Yinglong; Baudry, Jerome

    2011-01-01

    Long-timescale molecular dynamics simulations (300 ns) are performed on both the apo- (i.e., camphor-free) and camphor-bound cytochrome P450cam (CYP101). Water diffusion into and out of the protein active site is observed without biased sampling methods. During the course of the molecular dynamics simulation, an average of 6.4 water molecules is observed in the camphor-binding site of the apo form, compared to zero water molecules in the binding site of the substrate-bound form, in agreement with the number of water molecules observed in crystal structures of the same species. However, as many as 12 water molecules can be present at a given time in the camphor-binding region of the active site in the case of apo-P450cam, revealing a highly dynamic process for hydration of the protein active site, with water molecules exchanging rapidly with the bulk solvent. Water molecules are also found to exchange locations frequently inside the active site, preferentially clustering in regions surrounding the water molecules observed in the crystal structure. Potential-of-mean-force calculations identify thermodynamically favored trans-protein pathways for the diffusion of water molecules between the protein active site and the bulk solvent. Binding of camphor in the active site modifies the free-energy landscape of P450cam channels toward favoring the diffusion of water molecules out of the protein active site. PMID:21943431

  16. Topographic mapping

    USGS Publications Warehouse

    ,

    2008-01-01

    The U.S. Geological Survey (USGS) produced its first topographic map in 1879, the same year it was established. Today, more than 100 years and millions of map copies later, topographic mapping is still a central activity for the USGS. The topographic map remains an indispensable tool for government, science, industry, and leisure. Much has changed since early topographers traveled the unsettled West and carefully plotted the first USGS maps by hand. Advances in survey techniques, instrumentation, and design and printing technologies, as well as the use of aerial photography and satellite data, have dramatically improved mapping coverage, accuracy, and efficiency. Yet cartography, the art and science of mapping, may never before have undergone change more profound than today.

  17. Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

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

    Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak

    Here, we developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16more » and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. Lastly, a 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.« less

  18. Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)

    DOE PAGES

    Tan, Li; Nomanbhoy, Tyzoon; Gurbani, Deepak; ...

    2014-07-17

    Here, we developed a pharmacophore model for type II inhibitors that was used to guide the construction of a library of kinase inhibitors. Kinome-wide selectivity profiling of the library resulted in the identification of a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines that exhibited potent inhibitory activity against two mitogen-activated protein kinases (MAPKs), TAK1 (MAP3K7) and MAP4K2, as well as pharmacologically well interrogated kinases such as p38α (MAPK14) and ABL. Further investigation of the structure–activity relationship (SAR) resulted in the identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16more » and 17. Some of these inhibitors possess good pharmacokinetic properties that will enable their use in pharmacological studies in vivo. Lastly, a 2.4 Å cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors.« less

  19. Active Site Mutations Change the Cleavage Specificity of Neprilysin

    PubMed Central

    Sexton, Travis; Hitchcook, Lisa J.; Rodgers, David W.; Bradley, Luke H.; Hersh, Louis B.

    2012-01-01

    Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid β1–40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß1–40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential. PMID:22384224

  20. Carbinolamine Formation and Dehydration in a DNA Repair Enzyme Active Site

    PubMed Central

    Dodson, M. L.; Walker, Ross C.; Lloyd, R. Stephen

    2012-01-01

    In order to suggest detailed mechanistic hypotheses for the formation and dehydration of a key carbinolamine intermediate in the T4 pyrimidine dimer glycosylase (T4PDG) reaction, we have investigated these reactions using steered molecular dynamics with a coupled quantum mechanics–molecular mechanics potential (QM/MM). We carried out simulations of DNA abasic site carbinolamine formation with and without a water molecule restrained to remain within the active site quantum region. We recovered potentials of mean force (PMF) from thirty replicate reaction trajectories using Jarzynski averaging. We demonstrated feasible pathways involving water, as well as those independent of water participation. The water–independent enzyme–catalyzed reaction had a bias–corrected Jarzynski–average barrier height of approximately for the carbinolamine formation reaction and ) for the reverse reaction at this level of representation. When the proton transfer was facilitated with an intrinsic quantum water, the barrier height was approximately in the forward (formation) reaction and for the reverse. In addition, two modes of unsteered (free dynamics) carbinolamine dehydration were observed: in one, the quantum water participated as an intermediate proton transfer species, and in the other, the active site protonated glutamate hydrogen was directly transferred to the carbinolamine oxygen. Water–independent unforced proton transfer from the protonated active site glutamate carboxyl to the unprotonated N–terminal amine was also observed. In summary, complex proton transfer events, some involving water intermediates, were studied in QM/MM simulations of T4PDG bound to a DNA abasic site. Imine carbinolamine formation was characterized using steered QM/MM molecular dynamics. Dehydration of the carbinolamine intermediate to form the final imine product was observed in free, unsteered, QM/MM dynamics simulations, as was unforced acid-base transfer between the active site

  1. Immobilization of alkaline phosphatase on solid surface through self-assembled monolayer and by active-site protection.

    PubMed

    Gao, En-Feng; Kang, Kyung Lhi; Kim, Jeong Hee

    2014-06-01

    Retaining biological activity of a protein after immobilization is an important issue and many studies reported to enhance the activity of proteins after immobilization. We recently developed a new immobilization method of enzyme using active-site protection and minimization of the cross-links between enzyme and surface with a DNA polymerase as a model system. In this study, we extended the new method to an enzyme with a small mono-substrate using alkaline phosphatase (AP) as another model system. A condition to apply the new method is that masking agents, in this case its own substrate needs to stay at the active-site of the enzyme to be immobilized in order to protect the active-site during the harsh immobilization process. This could be achieved by removal of essential divalent ion, Zn2+ that is required for full enzyme activity of AP from the masking solution while active-site of AP was protected with p-nitrophenyl phosphate (pNPP). Approximately 40% of the solution-phase activity was acquired with active-site protected immobilized AP. In addition to protection active-site of AP, the number of immobilization links was kinetically controlled. When the mole fraction of the activated carboxyl group of the linker molecule in self-assembled monolayer (SAM) of 12-mercaptododecanoic acid and 6-mercapto-1-ethanol was varied, 10% of 12-mercaptododecanoic acid gave the maximum enzyme activity. Approximately 51% increase in enzyme activity of the active-site protected AP was observed compared to that of the unprotected group. It was shown that the concept of active-site protection and kinetic control of the number of covalent immobilization bonds can be extended to enzymes with small mono-substrates. It opens the possibility of further extension of the new methods of active-site protection and kinetic control of immobilization bond to important enzymes used in research and industrial fields.

  2. High Resolution Mapping of an Alleged Chemical Weapons Dump Site in the Santa Cruz Basin, offshore California

    NASA Astrophysics Data System (ADS)

    Brewer, P. G.; Peltzer, E. T.; Walz, P. M.; Caress, D. W.; Thomas, H. J.

    2013-12-01

    Nautical charts record seven locations off the coast of California labeled as 'Chemical Munitions Dumping Area, Disused' that together cover some 12,000 km2 of sea floor. However only one such chemical munitions site is officially documented and no record exists of any chemical munitions disposed of at other locations, thus creating confusion. We have executed a one day AUV mapping survey of a corner of one such site in the Santa Cruz Basin, south of Port Hueneme, to examine and investigate the debris field. The region is covered with soft sediment and the overlying water is very low in oxygen at ~10 μmol/kg. The processed 110 kHz sidescan data revealed some 754 targets in 25.6 km2 for an average of 29 targets per km2. This was followed by two ROV dives to investigate the targets identified. We found but one false positives among the over 40 targets visited, and found items ranging from two distinct lines of unmarked or labeled and now empty barrels, two target drones, and much miscellaneous debris including 4-packs of cat food cans and a large ships mast over 30m in length. There was zero evidence of chemical weapons materiel as expected given the lack of official records. Almost all of the targets were covered in dense and colorful assemblages of invertebrates: sponges, anemones, and crabs. Where barrels were sufficiently open for full visual inspection, the interior sea floor appeared to have become fully anoxic and was covered in white and yellow bacterial mat. The area chosen for our survey (centered at 33.76 deg N 119.56 deg W) was across the north western boundary of the marked site, and represents only ~ 10% percent of the designated area. Our expectation, that human nature would drive the disposal activities to the nearest corner of the chosen area rather than the center of the field appears to have been confirmed. Objects were found both within and outside of the boundary of the dump site. We have not surveyed the full marked area but there appears to be

  3. Integrating Radar Image Data with Google Maps

    NASA Technical Reports Server (NTRS)

    Chapman, Bruce D.; Gibas, Sarah

    2010-01-01

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

  4. LiDAR-Derived Flood-Inundation Maps for Real-Time Flood-Mapping Applications, Tar River Basin, North Carolina

    USGS Publications Warehouse

    Bales, Jerad D.; Wagner, Chad R.; Tighe, Kirsten C.; Terziotti, Silvia

    2007-01-01

    Flood-inundation maps were created for selected streamgage sites in the North Carolina Tar River basin. Light detection and ranging (LiDAR) data with a vertical accuracy of about 20 centimeters, provided by the Floodplain Mapping Information System of the North Carolina Floodplain Mapping Program, were processed to produce topographic data for the inundation maps. Bare-earth mass point LiDAR data were reprocessed into a digital elevation model with regularly spaced 1.5-meter by 1.5-meter cells. A tool was developed as part of this project to connect flow paths, or streams, that were inappropriately disconnected in the digital elevation model by such features as a bridge or road crossing. The Hydraulic Engineering Center-River Analysis System (HEC-RAS) model, developed by the U.S. Army Corps of Engineers, was used for hydraulic modeling at each of the study sites. Eleven individual hydraulic models were developed for the Tar River basin sites. Seven models were developed for reaches with a single gage, and four models were developed for reaches of the Tar River main stem that receive flow from major gaged tributaries, or reaches in which multiple gages were near one another. Combined, the Tar River hydraulic models included 272 kilometers of streams in the basin, including about 162 kilometers on the Tar River main stem. The hydraulic models were calibrated to the most current stage-discharge relations at 11 long-term streamgages where rating curves were available. Medium- to high-flow discharge measurements were made at some of the sites without rating curves, and high-water marks from Hurricanes Fran and Floyd were available for high-stage calibration. Simulated rating curves matched measured curves over the full range of flows. Differences between measured and simulated water levels for a specified flow were no more than 0.44 meter and typically were less. The calibrated models were used to generate a set of water-surface profiles for each of the 11 modeled

  5. Global Transcriptional Start Site Mapping Using Differential RNA Sequencing Reveals Novel Antisense RNAs in Escherichia coli

    PubMed Central

    Thomason, Maureen K.; Bischler, Thorsten; Eisenbart, Sara K.; Förstner, Konrad U.; Zhang, Aixia; Herbig, Alexander; Nieselt, Kay

    2014-01-01

    While the model organism Escherichia coli has been the subject of intense study for decades, the full complement of its RNAs is only now being examined. Here we describe a survey of the E. coli transcriptome carried out using a differential RNA sequencing (dRNA-seq) approach, which can distinguish between primary and processed transcripts, and an automated prediction algorithm for transcriptional start sites (TSS). With the criterion of expression under at least one of three growth conditions examined, we predicted 14,868 TSS candidates, including 5,574 internal to annotated genes (iTSS) and 5,495 TSS corresponding to potential antisense RNAs (asRNAs). We examined expression of 14 candidate asRNAs by Northern analysis using RNA from wild-type E. coli and from strains defective for RNases III and E, two RNases reported to be involved in asRNA processing. Interestingly, nine asRNAs detected as distinct bands by Northern analysis were differentially affected by the rnc and rne mutations. We also compared our asRNA candidates with previously published asRNA annotations from RNA-seq data and discuss the challenges associated with these cross-comparisons. Our global transcriptional start site map represents a valuable resource for identification of transcription start sites, promoters, and novel transcripts in E. coli and is easily accessible, together with the cDNA coverage plots, in an online genome browser. PMID:25266388

  6. 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.

  7. 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.

  8. Entrainment and high-density three-dimensional mapping in right atrial macroreentry provide critical complementary information: Entrainment may unmask "visual reentry" as passive.

    PubMed

    Pathik, Bhupesh; Lee, Geoffrey; Nalliah, Chrishan; Joseph, Stephen; Morton, Joseph B; Sparks, Paul B; Sanders, Prashanthan; Kistler, Peter M; Kalman, Jonathan M

    2017-10-01

    With the recent advent of high-density (HD) 3-dimensional (3D) mapping, the utility of entrainment is uncertain. However, the limitations of visual representation and interpretation of these high-resolution 3D maps are unclear. The purpose of this study was to determine the strengths and limitations of both HD 3D mapping and entrainment mapping during mapping of right atrial macroreentry. Fifteen patients were studied. The number and type of circuits accounting for ≥90% of the tachycardia cycle length using HD 3D mapping were verified using systematic entrainment mapping. Entrainment sites with an unexpectedly long postpacing interval despite proximity to the active circuit were evaluated. Based on HD 3D mapping, 27 circuits were observed: 12 peritricuspid, 2 upper loop reentry, 10 lower loop reentry, and 3 lateral wall circuits. With entrainment, 17 of the 27 circuits were active: all 12 peritricuspid and 2 upper loop reentry. However, lower loop reentry was confirmed in only 3 of 10, and none of the 3 lateral wall circuits were present. Mean percentage of tachycardia cycle length covered by active circuits was 98% ± 1% vs 97% ± 2% for passive circuits (P = .09). None of the 345 entrainment runs terminated tachycardia or changed tachycardia mechanism. In 8 of 15 patients, 13 examples of unexpectedly long postpacing interval were observed at entrainment sites located distal to localized zones of slow conduction seen on HD 3D mapping. Using HD 3D mapping, "visual reentry" may be due to passive circuitous propagation rather than a critical reentrant circuit. HD 3D mapping provides new insights into regional conduction and helps explain unusual entrainment phenomena. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. Ultrafast Light-Driven Substrate Expulsion from the Active Site of a Photoswitchable Catalyst.

    PubMed

    Pescher, Manuel D; van Wilderen, Luuk J G W; Grützner, Susanne; Slavov, Chavdar; Wachtveitl, Josef; Hecht, Stefan; Bredenbeck, Jens

    2017-09-25

    The photoswitchable piperidine general base catalyst is a prototype structure for light control of catalysis. Its azobenzene moiety moves sterically shielding groups to either protect or expose the active site, thereby changing the basicity and hydrogen-bonding affinity of the compound. The reversible switching dynamics of the catalyst is probed in the infrared spectral range by monitoring hydrogen bond (HB) formation between its active site and methanol (MeOH) as HB donor. Steady-state infrared (IR) and ultrafast IR and UV/Vis spectroscopies are used to uncover ultrafast expulsion of MeOH from the active site within a few picoseconds. Thus, the force generated by the azobenzene moiety even in the final phase of its isomerization is sufficient to break a strong HB within 3 ps and to shut down access to the active site. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed Central

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

    2001-01-01

    Contact sites in interaction between light-activated rhodopsin and transducin (T) have been investigated by using a chemically preactivated crosslinking reagent, N-succinimidyl 3-(2-pyridyldithio)propionate. The 3 propionyl-N-succinimidyl group in the reagent was attached by a disulfide exchange reaction to rhodopsin mutants containing single reactive cysteine groups in the cytoplasmic loops. Complex formation between the derivatized rhodopsin mutants and T was carried out by illumination at λ > 495 nm. Subsequent increase in pH (from 6 to 7.5 or higher) of the complex resulted in crosslinking of rhodopsin to the Tα subunit. Crosslinking to Tα was demonstrated for the rhodopsin mutants K141C, S240C, and K248C, and the crosslinked sites in Tα were identified for the rhodopsin mutant S240C. The peptides carrying the crosslinking moiety were isolated from the trypsin-digested peptide mixture, and their identification was carried out by matrix-assisted laser desorption ionization–time of flight mass spectrometry. The main site of crosslinking is within the peptide sequence, Leu-19–Arg-28 at the N-terminal region of Tα. The total results show that both the N and the C termini of Tα are in close vicinity to the third cytoplasmic loop of rhodopsin in the complex between rhodopsin and T. PMID:11320238

  11. Dynamic Perturbation of the Active Site Determines Reversible Thermal Inactivation in Glycoside Hydrolase Family 12.

    PubMed

    Jiang, Xukai; Li, Wen; Chen, Guanjun; Wang, Lushan

    2017-02-27

    The temperature dependence of enzyme catalysis is highly debated. Specifically, how high temperatures induce enzyme inactivation has broad implications for both fundamental and applied science. Here, we explored the mechanism of the reversible thermal inactivation in glycoside hydrolase family 12 (GH12) using comparative molecular dynamics simulations. First, we investigated the distribution of structural flexibility over the enzyme and found that the active site was the general thermal-sensitive region in GH12 cellulases. The dynamic perturbation of the active site before enzyme denaturation was explored through principal-component analysis, which indicated that variations in the collective motion and conformational ensemble of the active site may precisely correspond to enzyme transition from its active form to the inactive form. Furthermore, the degree of dynamic perturbation of the active site was found to be negatively correlated with the melting temperatures of GH12 enzymes, further proving the importance of the dynamic stability of the active site. Additionally, analysis of the residue-interaction network revealed that the active site in thermophilic enzyme was capable of forming additional contacts with other amino acids than those observed in the mesophilic enzyme. These interactions are likely the key mechanisms underlying the differences in rigidity of the active site. These findings provide further biophysical insights into the reversible thermal inactivation of enzymes and potential applications in future protein engineering.

  12. Genome Wide Association Mapping of Grain Arsenic, Copper, Molybdenum and Zinc in Rice (Oryza sativa L.) Grown at Four International Field Sites

    PubMed Central

    Norton, Gareth J.; Douglas, Alex; Lahner, Brett; Yakubova, Elena; Guerinot, Mary Lou; Pinson, Shannon R. M.; Tarpley, Lee; Eizenga, Georgia C.; McGrath, Steve P.; Zhao, Fang-Jie; Islam, M. Rafiqul; Islam, Shofiqul; Duan, Guilan; Zhu, Yongguan; Salt, David E.; Meharg, Andrew A.; Price, Adam H.

    2014-01-01

    The mineral concentrations in cereals are important for human health, especially for individuals who consume a cereal subsistence diet. A number of elements, such as zinc, are required within the diet, while some elements are toxic to humans, for example arsenic. In this study we carry out genome-wide association (GWA) mapping of grain concentrations of arsenic, copper, molybdenum and zinc in brown rice using an established rice diversity panel of ∼300 accessions and 36.9 k single nucleotide polymorphisms (SNPs). The study was performed across five environments: one field site in Bangladesh, one in China and two in the US, with one of the US sites repeated over two years. GWA mapping on the whole dataset and on separate subpopulations of rice revealed a large number of loci significantly associated with variation in grain arsenic, copper, molybdenum and zinc. Seventeen of these loci were detected in data obtained from grain cultivated in more than one field location, and six co-localise with previously identified quantitative trait loci. Additionally, a number of candidate genes for the uptake or transport of these elements were located near significantly associated SNPs (within 200 kb, the estimated global linkage disequilibrium previously employed in this rice panel). This analysis highlights a number of genomic regions and candidate genes for further analysis as well as the challenges faced when mapping environmentally-variable traits in a highly genetically structured diversity panel. PMID:24586963

  13. Generative Topographic Mapping (GTM): Universal Tool for Data Visualization, Structure-Activity Modeling and Dataset Comparison.

    PubMed

    Kireeva, N; Baskin, I I; Gaspar, H A; Horvath, D; Marcou, G; Varnek, A

    2012-04-01

    Here, the utility of Generative Topographic Maps (GTM) for data visualization, structure-activity modeling and database comparison is evaluated, on hand of subsets of the Database of Useful Decoys (DUD). Unlike other popular dimensionality reduction approaches like Principal Component Analysis, Sammon Mapping or Self-Organizing Maps, the great advantage of GTMs is providing data probability distribution functions (PDF), both in the high-dimensional space defined by molecular descriptors and in 2D latent space. PDFs for the molecules of different activity classes were successfully used to build classification models in the framework of the Bayesian approach. Because PDFs are represented by a mixture of Gaussian functions, the Bhattacharyya kernel has been proposed as a measure of the overlap of datasets, which leads to an elegant method of global comparison of chemical libraries. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Non-active site mutation (Q123A) in New Delhi metallo-β-lactamase (NDM-1) enhanced its enzyme activity.

    PubMed

    Ali, Abid; Azam, Mohd W; Khan, Asad U

    2018-06-01

    New Delhi metallo β-lactamase-1 is one of the carbapenemases, causing hydrolysis of almost all β-lactamase antibiotics. Seventeen different NDM variants have been reported so far, they varied in their sequences either by single or multiple amino acid substitutions. Hence, it is important to understand its structural and functional relation. In the earlier studies role of active site residues has been studied but non-active site residues has not studied in detail. Therefore, we have initiated to further comprehend its structure and function relation by mutating some of its non-active site residues. A laboratory mutant of NDM-1 was generated by PCR-based site-directed mutagenesis, replacing Q to A at 123 position. The MICs of imipenem and meropenem for NDM-1 Q123A were found increased by 2 fold as compare to wild type and so the hydrolytic activity was enhanced (Kcat/Km) as compared to NDM-1 wild type. GOLD fitness scores were also found in favour of kinetics data. Secondary structure for α-helical content was determined by Far-UV circular dichroism (CD), which showed significant conformational changes. We conclude a noteworthy role of non-active-site amino acid residues in the catalytic activity of NDM-1. This study also provides an insight of emergence of new variants through natural evolution. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Mapping the Topography of Europa: The Galileo-Clipper Story

    NASA Astrophysics Data System (ADS)

    Schenk, Paul M.

    2014-11-01

    The renewed effort to return to Europa for global mapping and landing site selection raises the question: What do we know about Europa topography and how do we know it? The question relates to geologic questions of feature formation, to the issue of ice shell thickness, mechanical strength, and internal activity, and to landing hazards. Our topographic data base for Europa is sparse indeed (no global map is possible), but we are not without hope. Two prime methods have been employed in our mapping program are stereo image and shape-from-shading (PC) slope analyses. On Europa, we are fortunate that many PC-DEM areas are also controlled by stereo-DEMs, mitigating the long-wavelength uncertainties in the PC data. Due to the Galileo antenna malfunction, mapping is limited to no more than 20% of the surface, far less than for any of the inner planets. Thirty-seven individual mapping sites have been identified, scattered across the globe, and all have now been mapped. Excellent stereo mapping is possible at all Sun angles, if resolution is below ~350 m. PC mapping is possible at Sun angles greater than ~60 degrees, if emission angles are less than ~40 degrees. The only extended contiguous areas of topographic mapping larger than 150 km across are the two narrow REGMAP mapping mosaics extending pole-to-pole along longitudes 85 and 240 W. These are PC-only and subject to long-wavelength uncertainties and errors, especially in the north/south where oblique imaging produces layover. Key findings include the mean slopes of individual terrain types (Schenk, 2009), topography across chaos (Schenk and Pappalardo, 2004), topography of craters and inferences for ice shell thickness (Schenk, 2002; Schenk and Turtle, 2009), among others. A key discovery, despite the limited data, is that Europan terrains rarely have topographic amplitude greater than 250 meters, but that regionally Europa has imprinted on it topographic amplitudes of +/- 1 km, in the form of raised plateaus and

  16. Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

    PubMed

    Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

    2016-08-01

    Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Heterogeneous Electrocatalyst with Molecular Cobalt Ions Serving as the Center of Active Sites.

    PubMed

    Wang, Jiong; Ge, Xiaoming; Liu, Zhaolin; Thia, Larissa; Yan, Ya; Xiao, Wei; Wang, Xin

    2017-02-08

    Molecular Co 2+ ions were grafted onto doped graphene in a coordination environment, resulting in the formation of molecularly well-defined, highly active electrocatalytic sites at a heterogeneous interface for the oxygen evolution reaction (OER). The S dopants of graphene are suggested to be one of the binding sites and to be responsible for improving the intrinsic activity of the Co sites. The turnover frequency of such Co sites is greater than that of many Co-based nanostructures and IrO 2 catalysts. Through a series of carefully designed experiments, the pathway for the evolution of the Co cation-based molecular catalyst for the OER was further demonstrated on such a single Co-ion site for the first time. The Co 2+ ions were successively oxidized to Co 3+ and Co 4+ states prior to the OER. The sequential oxidation was coupled with the transfer of different numbers of protons/hydroxides and generated an active Co 4+ ═O fragment. A side-on hydroperoxo ligand of the Co 4+ site is proposed as a key intermediate for the formation of dioxygen.

  18. US Topo: topographic maps for the nation

    USGS Publications Warehouse

    Carswell, William J.

    2013-01-01

    US Topo is the next generation of topographic maps from the U.S. Geological Survey (USGS). Arranged in the familiar 7.5-minute quadrangle format, digital US Topo maps are designed to look and feel (and perform) like the traditional paper topographic maps for which the USGS is so well known. In contrast to paper-based maps, US Topo maps provide modern technical advantages that support faster, wider public distribution and enable basic, on-screen geographic analysis for all users. The US Topo quadrangle map has been redesigned so that map elements are visually distinguishable with the imagery turned on and off, while keeping the file size as small as possible. The US Topo map redesign includes improvements to various display factors, including symbol definitions (color, line thickness, line symbology, area fills), layer order, and annotation fonts. New features for 2013 include the following: a raster shaded relief layer, military boundaries, cemeteries and post offices, and a US Topo cartographic symbols legend as an attachment. US Topo quadrangle maps are available free on the Web. Each map quadrangle is constructed in GeoPDF® format using key layers of geographic data (orthoimagery, roads, geographic names, topographic contours, and hydrographic features) from The National Map databases. US Topo quadrangle maps can be printed from personal computers or plotters as complete, full-sized, maps or in customized sections, in a user-desired specific format. Paper copies of the maps can also be purchased from the USGS Store. Download links and a users guide are featured on the US Topo Web site. US Topo users can turn geographic data layers on and off as needed; they can zoom in and out to highlight specific features or see a broader area. File size for each digital 7.5-minute quadrangle, about 30 megabytes. Associated electronic tools for geographic analysis are available free for download. The US Topo provides the Nation with a topographic product that users can

  19. Metalloproteinase-dependent transforming growth factor-alpha release mediates neurotensin-stimulated MAP kinase activation in human colonic epithelial cells.

    PubMed

    Zhao, Dezheng; Zhan, Yanai; Koon, Hon Wai; Zeng, Huiyan; Keates, Sarah; Moyer, Mary P; Pothoulakis, Charalabos

    2004-10-15

    Expression of the neuropeptide neurotensin (NT) and its high affinity receptor (NTR1) is increased during the course of Clostridium difficile toxin A-induced acute colitis, and NTR1 antagonism attenuates the severity of toxin A-induced inflammation. We recently demonstrated in non-transformed human colonic epithelial NCM460 cells that NT treatment caused activation of a Ras-mediated MAP kinase pathway that significantly contributes to NT-induced interleukin-8 (IL-8) secretion. Here we used NCM460 cells, which normally express low levels of NTR1, and NCM460 cells stably transfected with NTR1 to identify the upstream signaling molecules involved in NT-NTR1-mediated MAP kinase activation. We found that inhibition of the epidermal growth factor receptor (EGFR) by either an EGFR neutralizing antibody or by its specific inhibitor AG1478 (0.2 microm) blocked NT-induced MAP kinase activation. Moreover, NT stimulated tyrosine phosphorylation of the EGFR, and pretreatment with a broad spectrum metalloproteinase inhibitor batimastat reduced NT-induced MAP kinase activation. Using neutralizing antibodies against the EGFR ligands EGF, heparin-binding-EGF, transforming growth factor-alpha (TGFalpha), or amphiregulin we have shown that only the anti-TGFalpha antibody significantly decreases NT-induced phosphorylation of EGFR and MAP kinases. Furthermore, inhibition of the EGF receptor by AG1478 significantly reduced NT-induced IL-8 promoter activity and IL-8 secretion. This is the first report demonstrating that NT binding to NTR1 transactivates the EGFR and that this response is linked to NT-mediated proinflammatory signaling. Our findings indicate that matrix metalloproteinase-mediated release of TGFalpha and subsequent EGFR transactivation triggers a NT-mediated MAP kinase pathway that leads to IL-8 gene expression in human colonic epithelial cells.

  20. Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor.

    PubMed

    Spatzal, Thomas; Perez, Kathryn A; Howard, James B; Rees, Douglas C

    2015-12-16

    Dinitrogen reduction in the biological nitrogen cycle is catalyzed by nitrogenase, a two-component metalloenzyme. Understanding of the transformation of the inert resting state of the active site FeMo-cofactor into an activated state capable of reducing dinitrogen remains elusive. Here we report the catalysis dependent, site-selective incorporation of selenium into the FeMo-cofactor from selenocyanate as a newly identified substrate and inhibitor. The 1.60 Å resolution structure reveals selenium occupying the S2B site of FeMo-cofactor in the Azotobacter vinelandii MoFe-protein, a position that was recently identified as the CO-binding site. The Se2B-labeled enzyme retains substrate reduction activity and marks the starting point for a crystallographic pulse-chase experiment of the active site during turnover. Through a series of crystal structures obtained at resolutions of 1.32-1.66 Å, including the CO-inhibited form of Av1-Se2B, the exchangeability of all three belt-sulfur sites is demonstrated, providing direct insights into unforeseen rearrangements of the metal center during catalysis.

  1. Implications of NGA for NEHRP site coefficients

    USGS Publications Warehouse

    Borcherdt, Roger D.

    2012-01-01

    Three proposals are provided to update tables 11.4-1 and 11.4-2 of Minimum Design Loads for Buildings and Other Structures (7-10), by the American Society of Civil Engineers (2010) (ASCE/SEI 7-10), with site coefficients implied directly by NGA (Next Generation Attenuation) ground motion prediction equations (GMPEs). Proposals include a recommendation to use straight-line interpolation to infer site coefficients at intermediate values of ̅vs (average shear velocity). Site coefficients are recommended to ensure consistency with ASCE/SEI 7-10 MCER (Maximum Considered Earthquake) seismic-design maps and simplified site-specific design spectra procedures requiring site classes with associated tabulated site coefficients and a reference site class with unity site coefficients. Recommended site coefficients are confirmed by independent observations of average site amplification coefficients inferred with respect to an average ground condition consistent with that used for the MCER maps. The NGA coefficients recommended for consideration are implied directly by the NGA GMPEs and do not require introduction of additional models.

  2. Conceptualizing physical activity parenting practices using expert informed concept mapping analysis.

    PubMed

    Mâsse, Louise C; O'Connor, Teresia M; Tu, Andrew W; Hughes, Sheryl O; Beauchamp, Mark R; Baranowski, Tom

    2017-06-14

    Parents are widely recognized as playing a central role in the development of child behaviors such as physical activity. As there is little agreement as to the dimensions of physical activity-related parenting practices that should be measured or how they should be operationalized, this study engaged experts to develop an integrated conceptual framework for assessing parenting practices that influence multiple aspects of 5 to 12 year old children's participation in physical activity. The ultimate goal of this study is to inform the development of an item bank (repository of calibrated items) aimed at measuring physical activity parenting practices. Twenty four experts from 6 countries (Australia, Canada, England, Scotland, the Netherlands, & United States (US)) sorted 77 physical activity parenting practice concepts identified from our previously published synthesis of the literature (74 measures) and survey of Canadian and US parents. Concept Mapping software was used to conduct the multi-dimensional scaling (MDS) analysis and a cluster analysis of the MDS solution of the Expert's sorting which was qualitatively reviewed and commented on by the Experts. The conceptual framework includes 12 constructs which are presented using three main domains of parenting practices (neglect/control, autonomy support, and structure). The neglect/control domain includes two constructs: permissive and pressuring parenting practices. The autonomy supportive domain includes four constructs: encouragement, guided choice, involvement in child physical activities, and praises/rewards for their child's physical activity. Finally, the structure domain includes six constructs: co-participation, expectations, facilitation, modeling, monitoring, and restricting physical activity for safety or academic concerns. The concept mapping analysis provided a useful process to engage experts in re-conceptualizing physical activity parenting practices and identified key constructs to include in

  3. Measurement of sitting balance using the Manchester Active Position Seat (MAPS): a feasibility study.

    PubMed

    Powell, E S; Pyburn, R E; Hill, E; Smith, K S; Ribbands, M S; Mickelborough, J; Pomeroy, V M

    2002-09-01

    Evaluation of the effectiveness of therapy to improve sitting balance has been hampered by the limited number of sensitive objective clinical measures. We developed the Manchester Active Position Seat (MAPS) to provide a portable system to track change in the position of centre of force over time. (1) To investigate whether there is correspondence between the measurement of position change by a forceplate and by MAPS. (2) To explore whether and how MAPS measures changes in position when seated healthy adults change posture. A feasibility study. (1) An adult subject sat on MAPS placed on top of a forceplate. The x and y coordinates of the centre of pressure recorded from the forceplate and centre of force from MAPS during movement were compared graphically. (2) Four adults sat on MAPS using a standardized starting position and moving into six sets of six standardized target postures in a predetermined randomized order. The absolute shift in centre of force from the starting position was calculated. (1) The pattern of change of position over time was similar for the forceplate and for MAPS although there was a measurement difference, which increased with distance from the centre. (2) The direction of change of position corresponded to the direction of movement to the target postures but the amount of change varied between subjects. MAPS shows promise as an objective clinical measure of sitting balance, but peripheral accuracy of measurement needs to be improved.

  4. Application of the High Resolution Melting analysis for genetic mapping of Sequence Tagged Site markers in narrow-leafed lupin (Lupinus angustifolius L.).

    PubMed

    Kamel, Katarzyna A; Kroc, Magdalena; Święcicki, Wojciech

    2015-01-01

    Sequence tagged site (STS) markers are valuable tools for genetic and physical mapping that can be successfully used in comparative analyses among related species. Current challenges for molecular markers genotyping in plants include the lack of fast, sensitive and inexpensive methods suitable for sequence variant detection. In contrast, high resolution melting (HRM) is a simple and high-throughput assay, which has been widely applied in sequence polymorphism identification as well as in the studies of genetic variability and genotyping. The present study is the first attempt to use the HRM analysis to genotype STS markers in narrow-leafed lupin (Lupinus angustifolius L.). The sensitivity and utility of this method was confirmed by the sequence polymorphism detection based on melting curve profiles in the parental genotypes and progeny of the narrow-leafed lupin mapping population. Application of different approaches, including amplicon size and a simulated heterozygote analysis, has allowed for successful genetic mapping of 16 new STS markers in the narrow-leafed lupin genome.

  5. The Zamama-Thor region of Io: Insights from a synthesis of mapping, topography, and Galileo spacecraft data

    USGS Publications Warehouse

    Williams, D.A.; Keszthelyi, L.P.; Schenk, P.M.; Milazzo, M.P.; Lopes, R.M.C.; Rathbun, J.A.; Greeley, R.

    2005-01-01

    We have studied data from the Galileo spacecraft's three remote sensing instruments (Solid-State Imager (SSI), Near-Infrared Mapping Spectrometer (NIMS), and Photopolarimeter-Radiometer (PPR)) covering the Zamama - Thor region of Io's antijovian hemisphere, and produced a geomorphological map of this region. This is the third of three regional maps we are producing from the Galileo spacecraft data. Our goal is to assess the variety of volcanic and tectonic materials and their interrelationships on Io using planetary mapping techniques, supplemented with all available Galileo remote sensing data. Based on the Galileo data analysis and our mapping, we have determined that the most recent geologic activity in the Zamama - Thor region has been dominated by two sites of large-scale volcanic surface changes. The Zamama Eruptive Center is a site of both explosive and effusive eruptions, which emanate from two relatively steep edifices (Zamama Tholi A and B) that appear to be built by both silicate and sulfur volcanism. A ???100-km long flow field formed sometime after the 1979 Voyager flybys, which appears to be a site of promethean-style compound flows, flow-front SO2 plumes, and adjacent sulfur flows. Larger, possibly stealthy, plumes have on at least one occasion during the Galileo mission tapped a source that probably includes S and/or Cl to produce a red pyroclastic deposit from the same vent from which silicate lavas were erupted. The Thor Eruptive Center, which may have been active prior to Voyager, became active again during the Galileo mission between May and August 2001. A pillanian-style eruption at Thor included the tallest plume observed to date on Io (at least 500 km high) and new dark lava flows. The plume produced a central dark pyroclastic deposit (probably silicate-rich) and an outlying white diffuse ring that is SO2-rich. Mapping shows that several of th000e new dark lava flows around the plume vent have reoccupied sites of earlier flows. Unlike most of

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  7. A Watered-Down Topographic Map. Submarine Ring of Fire--Grades 6-8. Topographic and Bathymetric Maps.

    ERIC Educational Resources Information Center

    National Oceanic and Atmospheric Administration (DOC), Rockville, MD.

    This activity is designed to teach about topographic maps and bathymetric charts. Students are expected to create a topographic map from a model landform, interpret a simple topographic map, and explain the difference between topographic and bathymetric maps. The activity provides learning objectives, a list of needed materials, key vocabulary…

  8. Discovering a "True" Map of the World--Learning Activities.

    ERIC Educational Resources Information Center

    Hantula, James

    "True" maps of the world, as seen from the perspective of the time in which they were produced, remain an ethnocentric visual language in modern times. Students can gain insight into such "true" maps by studying maps produced in the great traditions of the West and East. Teachers can determine a map's appropriateness by identifying its title,…

  9. MAP18 regulates the direction of pollen tube growth in Arabidopsis by modulating F-actin organization.

    PubMed

    Zhu, Lei; Zhang, Yan; Kang, Erfang; Xu, Qiangyi; Wang, Miaoying; Rui, Yue; Liu, Baoquan; Yuan, Ming; Fu, Ying

    2013-03-01

    For fertilization to occur in plants, the pollen tube must be guided to enter the ovule via the micropyle. Previous reports have implicated actin filaments, actin binding proteins, and the tip-focused calcium gradient as key contributors to polar growth of pollen tubes; however, the regulation of directional pollen tube growth is largely unknown. We reported previously that Arabidopsis thaliana MICROTUBULE-ASSOCIATED PROTEIN18 (MAP18) contributes to directional cell growth and cortical microtubule organization. The preferential expression of MAP18 in pollen and in pollen tubes suggests that MAP18 also may function in pollen tube growth. In this study, we demonstrate that MAP18 functions in pollen tubes by influencing actin organization, rather than microtubule assembly. In vitro biochemical results indicate that MAP18 exhibits Ca(2+)-dependent filamentous (F)-actin-severing activity. Abnormal expression of MAP18 in map18 and MAP18 OX plants was associated with disorganization of the actin cytoskeleton in the tube apex, resulting in aberrant pollen tube growth patterns and morphologies, inaccurate micropyle targeting, and fewer fertilization events. Experiments with MAP18 mutants created by site-directed mutagenesis suggest that F-actin-severing activity is essential to the effects of MAP18 on pollen tube growth direction. Our study demonstrates that in Arabidopsis, MAP18 guides the direction of pollen tube growth by modulating actin filaments.

  10. Methylation of an alpha-foetoprotein gene intragenic site modulates gene activity.

    PubMed Central

    Opdecamp, K; Rivière, M; Molné, M; Szpirer, J; Szpirer, C

    1992-01-01

    By comparing the methylation pattern of Mspl/Hpall sites in the 5' region of the mouse alpha-foetoprotein (AFP) gene of different cells (hepatoma cells, foetal and adult liver, fibroblasts), we found a correlation between gene expression and unmethylation of a site located in the first intron of the gene. Other sites did not show this correlation. In transfection experiments of unmethylated and methylated AFP-CAT chimeric constructions, we then showed that methylation of the intronic site negatively modulates expression of CAT activity. We also found that a DNA segment centered on this site binds nuclear proteins; however methylation did not affect protein binding. Images PMID:1371343

  11. Where to Go Next? Identifying Target Areas in the North Atlantic for Future Seafloor Mapping Initiatives

    NASA Astrophysics Data System (ADS)

    Woelfl, A. C.; Jencks, J.; Johnston, G.; Varner, J. D.; Devey, C. W.

    2017-12-01

    Human activities are rapidly expanding into the oceans, yet detailed bathymetric maps do not exist for most of the seafloor that would permit governments to formulate sensible usage rules. Changing this situation will require an enormous international mapping effort. To ensure that this effort is directed towards the regions most in need of mapping, we need to know which areas have already been mapped and which areas are potentially most interesting. Despite various mapping efforts in recent years, large parts of the Atlantic still lack detailed bathymetric information. To successfully plan for future mapping efforts to fill these gaps, knowledge of current data coverage is imperative to avoid duplication of effort. While certain datasets are publically available online (e.g. NOAA's NCEI, EMODnet, IHO-DCDB, LDEO's GMRT), many are not. However, with the limited information we do have at hand, the question remains, where should we map next? And what criteria should we take into account? In 2016, a study was taken on as part of the efforts of the International Atlantic Seabed Mapping Working Group (ASMIWG). The ASMIWG, established by the Tri-Partite Galway Statement Implementation Committee, was tasked to develop a cohesive seabed mapping strategy for the Atlantic Ocean. The aim of our study was to develop a reproducible process for identifying and evaluating potential target areas within the North Atlantic that represent suitable sites for future bathymetric surveys. The sites were selected by applying a GIS-based suitability analysis that included specific user group-based parameters of the marine environment. Furthermore, information regarding current data coverage were gathered to take into account in the selection process. The results reveal the suitability of sites within the North Atlantic based on the selected criteria. Three potential target sites should be seen as flexible suggestions for future mapping initiatives rather than a rigid, defined set of areas

  12. Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: implications for principles underlying odor mapping

    PubMed Central

    Sanganahalli, Basavaraju G.; Rebello, Michelle R.; Herman, Peter; Papademetris, Xenophon; Shepherd, Gordon M.; Verhagen, Justus V.; Hyder, Fahmeed

    2015-01-01

    Functional imaging signals arise from distinct metabolic and hemodynamic events at the neuropil, but how these processes are influenced by pre- and post-synaptic activities need to be understood for quantitative interpretation of stimulus-evoked mapping data. The olfactory bulb (OB) glomeruli, spherical neuropil regions with well-defined neuronal circuitry, can provide insights into this issue. Optical calcium-sensitive fluorescent dye imaging (OICa2+) reflects dynamics of pre-synaptic input to glomeruli, whereas high-resolution functional magnetic resonance imaging (fMRI) using deoxyhemoglobin contrast reveals neuropil function within the glomerular layer where both pre- and post-synaptic activities contribute. We imaged odor-specific activity patterns of the dorsal OB in the same anesthetized rats with fMRI and OICa2+ and then co-registered the respective maps to compare patterns in the same space. Maps by each modality were very reproducible as trial-to-trial patterns for a given odor, overlapping by ~80%. Maps evoked by ethyl butyrate and methyl valerate for a given modality overlapped by ~80%, suggesting activation of similar dorsal glomerular networks by these odors. Comparison of maps generated by both methods for a given odor showed ~70% overlap, indicating similar odor-specific maps by each method. These results suggest that odor-specific glomerular patterns by high-resolution fMRI primarily tracks pre-synaptic input to the OB. Thus combining OICa2+ and fMRI lays the framework for studies of OB processing over a range of spatiotemporal scales, where OICa2+ can feature the fast dynamics of dorsal glomerular clusters and fMRI can map the entire glomerular sheet in the OB. PMID:26631819

  13. Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

    PubMed

    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.

  14. 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

  15. Estimating the social value of geologic map information: A regulatory application

    USGS Publications Warehouse

    Bernknopf, R.L.; Brookshire, D.S.; McKee, M.; Soller, D.R.

    1997-01-01

    People frequently regard the landscape as part of a static system. The mountains and rivers that cross the landscape, and the bedrock that supports the surface, change little during the course of a lifetime. Society can alter the geologic history of an area and, in so doing, affect the occurrence and impact of environmental hazards. For example, changes in land use can induce changes in erosion, sedimentation, and ground-water supply. As the environmental system is changed by both natural processes and human activities, the system's capacity to respond to additional stresses also changes. Information such as geologic maps describes the physical world and is critical for identifying solutions to land use and environmental issues. In this paper, a method is developed for estimating the economic value of applying geologic map information to siting a waste disposal facility. An improvement in geologic map information is shown to have a net positive value to society. Such maps enable planners to make superior land management decisions.

  16. Taking potential probability function maps to the local scale and matching them with land use maps

    NASA Astrophysics Data System (ADS)

    Garg, Saryu; Sinha, Vinayak; Sinha, Baerbel

    2013-04-01

    resolution. By making use of high temporal resolution data, our model can produce maps for different times of the day, thus accounting for temporal changes and activity profiles of different sources. The main advantage of our approach compared to geostationary numerical methods that interpolate measured concentration values of multiple measurement sites to produce maps (gridding) is that the maps produced are more accurate in terms of spatial identification of sources. The model was applied to isoprene and meteorological data recorded during clean post-monsoon season (1 October- 7 October, 2012) between 11 am and 4 pm at a receptor site in the North-West Indo-Gangetic Plains (IISER Mohali, 30.665° N, 76.729°E, 300 m asl), near the foothills of the Himalayan range. Considering the lifetime of isoprene, the model was run only 2 hours backward in time. The map shows highest residence time weighted concentration of isoprene (up to 3.5 ppbv) over agricultural land with high number of trees (>180 trees/gridsquare); moderate concentrations for agricultural lands with low tree density (1.5-2.5 ppbv for 250 μg/m3 for traffic hotspots in Chandigarh City are observed. Based on the validation against the land use maps, the model appears to do an excellent job in source apportionment and identifying emission hotspots. Acknowledgement: We thank the IISER Mohali Atmospheric Chemistry Facility for data and the Ministry of Human Resource Development (MHRD), India and IISER Mohali for funding the facility. Chinmoy Sarkar is acknowledged for technical support, Saryu Garg thanks the Max Planck-DST India Partner Group on Tropospheric OH reactivity and VOCs for funding the research.

  17. Employing a portable X-Ray fluorescence (P-XRF) analyser and GIS to identify and map heavy metal pollution in soils of a traditional bonfire site

    NASA Astrophysics Data System (ADS)

    Dao, Ligang; Zhang, Chaosheng; Morrison, Liam

    2010-05-01

    Soils in the vicinity of bonfires are recipients of metal contaminants from burning of metal-containing materials. In order to better understand the impacts of bonfires on soils, a total of 218 surface soil samples were collected from a traditional bonfire site in Galway City, Ireland. Concentrations of Cu, Pb and Zn were determined using a portable X-ray Fluorescence (P-XRF) analyser. Strong variations were observed for these metals, and several samples contained elevated Zn concentrations which exceeded the intervention threshold of the Dutch criteria (720 mg kg-1). Spatial clusters and spatial outliers were detected using the local Moran's I index and were mapped using GIS. Two clear high value spatial clusters could be observed on the upper left side and centre part of the study area for Cu, Pb and Zn. Results of variogram analyses showed high nugget-sill-ratios for Cu, Pb and Zn, indicating strong spatial variation over short distances which could be resulted from anthropogenic activities. The spatial interpolation method of ordinary kriging was applied to produce the spatial interpolation maps for Cu, Pb and Zn, and the areas with elevated concentrations were in line with historical locations of the bonfires. The hazard maps showed small parts of the study area with Zn concentrations exceeding the Dutch intervention values. In order to prevent further contamination from bonfires, it is advised that tyres and other metal-containing wastes should not be burnt. The results in this study provide useful information for management of bonfires.

  18. Adventures with Maps.

    ERIC Educational Resources Information Center

    Hofferber, Michael

    1989-01-01

    Orienteering--the game of following a map to find predetermined locations--can spark interest and develop skills in map making and map reading. This article gives background on orienteering; describes indoor and outdoor orienteering activities; offers suggestions for incorporating orienteering into science, math, and language arts; and provides a…

  19. Molecular imprint of enzyme active site by camel nanobodies: rapid and efficient approach to produce abzymes with alliinase activity.

    PubMed

    Li, Jiang-Wei; Xia, Lijie; Su, Youhong; Liu, Hongchun; Xia, Xueqing; Lu, Qinxia; Yang, Chunjin; Reheman, Kalbinur

    2012-04-20

    Screening of inhibitory Ab1 antibodies is a critical step for producing catalytic antibodies in the anti-idiotypic approach. However, the incompatible surface of the active site of the enzyme and the antigen-binding site of heterotetrameric conventional antibodies become the limiting step. Because camelid-derived nanobodies possess the potential to preferentially bind to the active site of enzymes due to their small size and long CDR3, we have developed a novel approach to produce antibodies with alliinase activities by exploiting the molecular mimicry of camel nanobodies. By screening the camelid-derived variable region of the heavy chain cDNA phage display library with alliinase, we obtained an inhibitory nanobody VHHA4 that recognizes the active site. Further screening with VHHA4 from the same variable domain of the heavy chain of a heavy-chain antibody library led to a higher incidence of anti-idiotypic Ab2 abzymes with alliinase activities. One of the abzymes, VHHC10, showed the highest activity that can be inhibited by Ab1 VHHA4 and alliinase competitive inhibitor penicillamine and significantly suppressed the B16 tumor cell growth in the presence of alliin in vitro. The results highlight the feasibility of producing abzymes via anti-idiotypic nanobody approach.

  20. Functional mapping of the neural circuitry of rat maternal motivation: effects of site-specific transient neural inactivation

    PubMed Central

    Pereira, Mariana; Morrell, Joan I.

    2011-01-01

    The present review focuses on recent studies from our laboratory examining the neural circuitry subserving rat maternal motivation across postpartum. We employed a site-specific neural inactivation method by infusion of bupivacaine to map the maternal motivation circuitry using two complementary behavioral approaches: unconditioned maternal responsiveness and choice of pup- over cocaine-conditioned incentives in a concurrent pup/cocaine choice conditioned place preference task. Our findings revealed that during the early postpartum period, distinct brain structures, including the medial preoptic area, ventral tegmental area and medial prefrontal cortex infralimbic and anterior cingulate subregions, contribute a pup-specific bias to the motivational circuitry. As the postpartum period progresses and the pups grow older, our findings further revealed that maternal responsiveness becomes progressively less dependent on medial preoptic area and medial prefrontal cortex infralimbic activity, and more distributed in the maternal circuitry, such that additional network components, including the medial prefrontal cortex prelimbic subregion, are recruited with maternal experience, and contribute to the expression of late postpartum maternal behavior. Collectively, our findings provide strong evidence that the remarkable ability of postpartum females to successfully care for their developing infants is subserved by a distributed neural network that carries out efficient and dynamic processing of complex, constantly changing incoming environmental and pup-related stimuli, ultimately allowing the progression of appropriate expression and waning of maternal responsiveness across the postpartum period. PMID:21815954

  1. Quantitative susceptibility mapping of human brain at 3T: a multisite reproducibility study.

    PubMed

    Lin, P-Y; Chao, T-C; Wu, M-L

    2015-03-01

    Quantitative susceptibility mapping of the human brain has demonstrated strong potential in examining iron deposition, which may help in investigating possible brain pathology. This study assesses the reproducibility of quantitative susceptibility mapping across different imaging sites. In this study, the susceptibility values of 5 regions of interest in the human brain were measured on 9 healthy subjects following calibration by using phantom experiments. Each of the subjects was imaged 5 times on 1 scanner with the same procedure repeated on 3 different 3T systems so that both within-site and cross-site quantitative susceptibility mapping precision levels could be assessed. Two quantitative susceptibility mapping algorithms, similar in principle, one by using iterative regularization (iterative quantitative susceptibility mapping) and the other with analytic optimal solutions (deterministic quantitative susceptibility mapping), were implemented, and their performances were compared. Results show that while deterministic quantitative susceptibility mapping had nearly 700 times faster computation speed, residual streaking artifacts seem to be more prominent compared with iterative quantitative susceptibility mapping. With quantitative susceptibility mapping, the putamen, globus pallidus, and caudate nucleus showed smaller imprecision on the order of 0.005 ppm, whereas the red nucleus and substantia nigra, closer to the skull base, had a somewhat larger imprecision of approximately 0.01 ppm. Cross-site errors were not significantly larger than within-site errors. Possible sources of estimation errors are discussed. The reproducibility of quantitative susceptibility mapping in the human brain in vivo is regionally dependent, and the precision levels achieved with quantitative susceptibility mapping should allow longitudinal and multisite studies such as aging-related changes in brain tissue magnetic susceptibility. © 2015 by American Journal of Neuroradiology.

  2. Synthesis of a molecularly defined single-active site heterogeneous catalyst for selective oxidation of N-heterocycles.

    PubMed

    Zhang, Yujing; Pang, Shaofeng; Wei, Zhihong; Jiao, Haijun; Dai, Xingchao; Wang, Hongli; Shi, Feng

    2018-04-13

    Generally, a homogeneous catalyst exhibits good activity and defined active sites but it is difficult to recycle. Meanwhile, a heterogeneous catalyst can easily be reused but its active site is difficult to reveal. It is interesting to bridge the gap between homogeneous and heterogeneous catalysis via controllable construction of a heterogeneous catalyst containing defined active sites. Here, we report that a molecularly defined, single-active site heterogeneous catalyst has been designed and prepared via the oxidative polymerization of maleimide derivatives. These polymaleimide derivatives can be active catalysts for the selective oxidation of heterocyclic compounds to quinoline and indole via the recycling of -C=O and -C-OH groups, which was confirmed by tracing the reaction with GC-MS using maleimide as the catalyst and by FT-IR analysis with polymaleimide as the catalyst. These results might promote the development of heterogeneous catalysts with molecularly defined single active sites exhibiting a comparable activity to homogeneous catalysts.

  3. Electromechanical Wave Imaging (EWI) validation in all four cardiac chambers with 3D electroanatomic mapping in canines in vivo

    PubMed Central

    Costet, Alexandre; Wan, Elaine; Bunting, Ethan; Grondin, Julien; Garan, Hasan; Konofagou, Elisa

    2016-01-01

    Characterization and mapping of arrhythmias is currently performed through invasive insertion and manipulation of cardiac catheters. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique, which tracks the electromechanical activation that immediately follows electrical activation. Electrical and electromechanical activations were previously found to be linearly correlated in the left ventricle, but the relationship has not yet been investigated in the three other chambers of the heart. The objective of this study was to investigate the relationship between electrical and electromechanical activations and validate EWI in all four chambers of the heart with conventional 3D electroanatomical mapping. Six (n = 6) normal adult canines were used in this study. The electrical activation sequence was mapped in all four chambers of the heart, both endocardially and epicardially using the St Jude's EnSite 3D mapping system (St. Jude Medical, Secaucus, NJ). EWI acquisitions were performed in all four chambers during normal sinus rhythm, and during pacing in the left ventricle. Isochrones of the electromechanical activation were generated from standard echocardiographic imaging views. Electrical and electromechanical activation maps were co-registered and compared, and electrical and electromechanical activation times were plotted against each other and linear regression was performed for each pair of activation maps. Electromechanical and electrical activations were found to be directly correlated with slopes of the correlation ranging from 0.77 to 1.83, electromechanical delays between 9 and 58 ms and R2 values from 0.71 to 0.92. The linear correlation between electrical and electromechanical activations and the agreement between the activation maps indicate that the electromechanical activation follows the pattern of propagation of the electrical activation. This suggests that EWI may be used as a novel non-invasive method to accurately

  4. Electromechanical wave imaging (EWI) validation in all four cardiac chambers with 3D electroanatomic mapping in canines in vivo.

    PubMed

    Costet, Alexandre; Wan, Elaine; Bunting, Ethan; Grondin, Julien; Garan, Hasan; Konofagou, Elisa

    2016-11-21

    Characterization and mapping of arrhythmias is currently performed through invasive insertion and manipulation of cardiac catheters. Electromechanical wave imaging (EWI) is a non-invasive ultrasound-based imaging technique, which tracks the electromechanical activation that immediately follows electrical activation. Electrical and electromechanical activations were previously found to be linearly correlated in the left ventricle, but the relationship has not yet been investigated in the three other chambers of the heart. The objective of this study was to investigate the relationship between electrical and electromechanical activations and validate EWI in all four chambers of the heart with conventional 3D electroanatomical mapping. Six (n  =  6) normal adult canines were used in this study. The electrical activation sequence was mapped in all four chambers of the heart, both endocardially and epicardially using the St Jude's EnSite 3D mapping system (St. Jude Medical, Secaucus, NJ). EWI acquisitions were performed in all four chambers during normal sinus rhythm, and during pacing in the left ventricle. Isochrones of the electromechanical activation were generated from standard echocardiographic imaging views. Electrical and electromechanical activation maps were co-registered and compared, and electrical and electromechanical activation times were plotted against each other and linear regression was performed for each pair of activation maps. Electromechanical and electrical activations were found to be directly correlated with slopes of the correlation ranging from 0.77 to 1.83, electromechanical delays between 9 and 58 ms and R 2 values from 0.71 to 0.92. The linear correlation between electrical and electromechanical activations and the agreement between the activation maps indicate that the electromechanical activation follows the pattern of propagation of the electrical activation. This suggests that EWI may be used as a novel non-invasive method to

  5. Biological role of site-specific O-glycosylation in cell adhesion activity and phosphorylation of osteopontin.

    PubMed

    Oyama, Midori; Kariya, Yoshinobu; Kariya, Yukiko; Matsumoto, Kana; Kanno, Mayumi; Yamaguchi, Yoshiki; Hashimoto, Yasuhiro

    2018-05-09

    Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr 134 /Thr 138 /Thr 143 /Thr 147 /Thr 152 ) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr 134 /Thr 138 or Thr 143 /Thr 147 /Thr 152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay using function-blocking antibodies against αvβ3 and β1 integrins, as well as αvβ3 integrin-overexpressing A549 cells, revealed that site-specific O-glycosylation affected the association of OPN with the two integrins. Phosphorylation analyses using phos-tag and LC-MS/MS indicated that phosphorylation levels and sites were influenced by the O-glycosylation status, although the number of O-glycosylation sites was not correlated with the phosphorylation level in OPN. Furthermore, a correlation analysis between phosphorylation level and cell adhesion activity in OPN mutants with the site-specific O-glycosylation showed that they were not always correlated. These results provide conclusive evidence of a novel regulatory mechanism of cell adhesion activity and phosphorylation of OPN by site-specific O-glycosylation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  6. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. 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.

  8. Ultrafast infrared spectroscopy reveals water-mediated coherent dynamics in an enzyme active site.

    PubMed

    Adamczyk, Katrin; Simpson, Niall; Greetham, Gregory M; Gumiero, Andrea; Walsh, Martin A; Towrie, Michael; Parker, Anthony W; Hunt, Neil T

    2015-01-01

    Understanding the impact of fast dynamics upon the chemical processes occurring within the active sites of proteins and enzymes is a key challenge that continues to attract significant interest, though direct experimental insight in the solution phase remains sparse. Similar gaps in our knowledge exist in understanding the role played by water, either as a solvent or as a structural/dynamic component of the active site. In order to investigate further the potential biological roles of water, we have employed ultrafast multidimensional infrared spectroscopy experiments that directly probe the structural and vibrational dynamics of NO bound to the ferric haem of the catalase enzyme from Corynebacterium glutamicum in both H 2 O and D 2 O. Despite catalases having what is believed to be a solvent-inaccessible active site, an isotopic dependence of the spectral diffusion and vibrational lifetime parameters of the NO stretching vibration are observed, indicating that water molecules interact directly with the haem ligand. Furthermore, IR pump-probe data feature oscillations originating from the preparation of a coherent superposition of low-frequency vibrational modes in the active site of catalase that are coupled to the haem ligand stretching vibration. Comparisons with an exemplar of the closely-related peroxidase enzyme family shows that they too exhibit solvent-dependent active-site dynamics, supporting the presence of interactions between the haem ligand and water molecules in the active sites of both catalases and peroxidases that may be linked to proton transfer events leading to the formation of the ferryl intermediate Compound I. In addition, a strong, water-mediated, hydrogen bonding structure is suggested to occur in catalase that is not replicated in peroxidase; an observation that may shed light on the origins of the different functions of the two enzymes.

  9. Unmasking tandem site interaction in human acetylcholinesterase. Substrate activation with a cationic acetanilide substrate.

    PubMed

    Johnson, Joseph L; Cusack, Bernadette; Davies, Matthew P; Fauq, Abdul; Rosenberry, Terrone L

    2003-05-13

    Acetylcholinesterase (AChE) contains a narrow and deep active site gorge with two sites of ligand binding, an acylation site (or A-site) at the base of the gorge, and a peripheral site (or P-site) near the gorge entrance. The P-site contributes to catalytic efficiency by transiently binding substrates on their way to the acylation site, where a short-lived acyl enzyme intermediate is produced. A conformational interaction between the A- and P-sites has recently been found to modulate ligand affinities. We now demonstrate that this interaction is of functional importance by showing that the acetylation rate constant of a substrate bound to the A-site is increased by a factor a when a second molecule of substrate binds to the P-site. This demonstration became feasible through the introduction of a new acetanilide substrate analogue of acetylcholine, 3-(acetamido)-N,N,N-trimethylanilinium (ATMA), for which a = 4. This substrate has a low acetylation rate constant and equilibrates with the catalytic site, allowing a tractable algebraic solution to the rate equation for substrate hydrolysis. ATMA affinities for the A- and P-sites deduced from the kinetic analysis were confirmed by fluorescence titration with thioflavin T as a reporter ligand. Values of a >1 give rise to a hydrolysis profile called substrate activation, and the AChE site-specific mutant W86F, and to a lesser extent wild-type human AChE itself, showed substrate activation with acetylthiocholine as the substrate. Substrate activation was incorporated into a previous catalytic scheme for AChE in which a bound P-site ligand can also block product dissociation from the A-site, and two additional features of the AChE catalytic pathway were revealed. First, the ability of a bound P-site ligand to increase the substrate acetylation rate constant varied with the structure of the ligand: thioflavin T accelerated ATMA acetylation by a factor a(2) of 1.3, while propidium failed to accelerate. Second, catalytic rate

  10. 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

  11. Problem-Solving Test: Restriction Endonuclease Mapping

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2011-01-01

    The term "restriction endonuclease mapping" covers a number of related techniques used to identify specific restriction enzyme recognition sites on small DNA molecules. A method for restriction endonuclease mapping of a 1,000-basepair (bp)-long DNA molecule is described in the fictitious experiment of this test. The most important fact needed to…

  12. Engineering streptokinase for generation of active site-labeled plasminogen analogs*

    PubMed Central

    Laha, Malabika; Panizzi, Peter; Nahrendorf, Matthias; Bock, Paul E.

    2011-01-01

    We previously demonstrated that streptokinase (SK) can be used to generate active site-labeled fluorescent analogs of plasminogen (Pg) by virtue of its non-proteolytic activation of the zymogen. The method is versatile and allows for stoichiometric and active site-specific incorporation of any one of many molecular probes. The limitation of the labeling approach is that it is both time-consuming and low yield. Here we demonstrate an improved method for the preparation of labeled Pg analogs by the use of an engineered SK mutant fusion protein with both COOH- and NH2-terminal His6-tags. The NH2-terminal tag is followed by a tobacco etch virus proteinase cleavage site to ensure that the SK Ile1 residue, essential for conformational activation of Pg, is preserved. The SK COOH-terminal Lys414 residue and residues Arg253-Leu260 in the SK β-domain were deleted to prevent cleavage by plasmin (Pm), and to disable Pg substrate binding to the SK·Pg*/Pm catalytic complexes, respectively. Near-elimination of Pm generation with the SKΔ(R253-L260)ΔK414-His6 mutant increased the yield of labeled Pg 2.6-fold and reduced the time required >2-fold. The versatility of the labeling method was extended to the application of Pg labeled with a near-infrared probe to quantitate Pg receptors on immune cells by flow cytometry. PMID:21570944

  13. Use of ocean color scanner data in water quality mapping

    NASA Technical Reports Server (NTRS)

    Khorram, S.

    1981-01-01

    Remotely sensed data, in combination with in situ data, are used in assessing water quality parameters within the San Francisco Bay-Delta. The parameters include suspended solids, chlorophyll, and turbidity. Regression models are developed between each of the water quality parameter measurements and the Ocean Color Scanner (OCS) data. The models are then extended to the entire study area for mapping water quality parameters. The results include a series of color-coded maps, each pertaining to one of the water quality parameters, and the statistical analysis of the OCS data and regression models. It is found that concurrently collected OCS data and surface truth measurements are highly useful in mapping the selected water quality parameters and locating areas having relatively high biological activity. In addition, it is found to be virtually impossible, at least within this test site, to locate such areas on U-2 color and color-infrared photography.

  14. Chromosome segregation drives division site selection in Streptococcus pneumoniae.

    PubMed

    van Raaphorst, Renske; Kjos, Morten; Veening, Jan-Willem

    2017-07-18

    Accurate spatial and temporal positioning of the tubulin-like protein FtsZ is key for proper bacterial cell division. Streptococcus pneumoniae (pneumococcus) is an oval-shaped, symmetrically dividing opportunistic human pathogen lacking the canonical systems for division site control (nucleoid occlusion and the Min-system). Recently, the early division protein MapZ was identified and implicated in pneumococcal division site selection. We show that MapZ is important for proper division plane selection; thus, the question remains as to what drives pneumococcal division site selection. By mapping the cell cycle in detail, we show that directly after replication both chromosomal origin regions localize to the future cell division sites, before FtsZ. Interestingly, Z-ring formation occurs coincidently with initiation of DNA replication. Perturbing the longitudinal chromosomal organization by mutating the condensin SMC, by CRISPR/Cas9-mediated chromosome cutting, or by poisoning DNA decatenation resulted in mistiming of MapZ and FtsZ positioning and subsequent cell elongation. Together, we demonstrate an intimate relationship between DNA replication, chromosome segregation, and division site selection in the pneumococcus, providing a simple way to ensure equally sized daughter cells.

  15. Nanotools for Neuroscience and Brain Activity Mapping

    PubMed Central

    Alivisatos, A. Paul; Andrews, Anne M.; Boyden, Edward S.; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Fraser, Scott E.; Lippincott-Schwartz, Jennifer; Looger, Loren L.; Masmanidis, Sotiris; McEuen, Paul L.; Nurmikko, Arto V.; Park, Hongkun; Peterka, Darcy S.; Reid, Clay; Roukes, Michael L.; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J.; Shepard, Kenneth L.; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S.; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei

    2013-01-01

    Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function. PMID:23514423

  16. Transcription Factor Map Alignment of Promoter Regions

    PubMed Central

    Blanco, Enrique; Messeguer, Xavier; Smith, Temple F; Guigó, Roderic

    2006-01-01

    We address the problem of comparing and characterizing the promoter regions of genes with similar expression patterns. This remains a challenging problem in sequence analysis, because often the promoter regions of co-expressed genes do not show discernible sequence conservation. In our approach, thus, we have not directly compared the nucleotide sequence of promoters. Instead, we have obtained predictions of transcription factor binding sites, annotated the predicted sites with the labels of the corresponding binding factors, and aligned the resulting sequences of labels—to which we refer here as transcription factor maps (TF-maps). To obtain the global pairwise alignment of two TF-maps, we have adapted an algorithm initially developed to align restriction enzyme maps. We have optimized the parameters of the algorithm in a small, but well-curated, collection of human–mouse orthologous gene pairs. Results in this dataset, as well as in an independent much larger dataset from the CISRED database, indicate that TF-map alignments are able to uncover conserved regulatory elements, which cannot be detected by the typical sequence alignments. PMID:16733547

  17. Longleaf pine site zones

    Treesearch

    Phillip J. Craul; John S. Kush; William D. Boyer

    2005-01-01

    The authors delineate six major climatic areas of the longleaf pine (Pinus palustris Mill.) region. They subdivide these areas into 21 site zones, each of which is deemed homogenous with respect to climate, physiography, and soils. The site zones are mapped and their climate, physiography, and soils described. The authors recommend that plantings of...

  18. PRAK, a novel protein kinase regulated by the p38 MAP kinase.

    PubMed Central

    New, L; Jiang, Y; Zhao, M; Liu, K; Zhu, W; Flood, L J; Kato, Y; Parry, G C; Han, J

    1998-01-01

    We have identified and cloned a novel serine/ threonine kinase, p38-regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with 20-30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human tissues and cell lines examined. In HeLa cells, PRAK was activated in response to cellular stress and proinflammatory cytokines. PRAK activity was regulated by p38alpha and p38beta both in vitro and in vivo and Thr182 was shown to be the regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase assay demonstrated that PRAK is a major stress-activated kinase that can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in vivo. PMID:9628874

  19. 7 CFR 12.31 - On-site wetland identification criteria.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...

  20. 7 CFR 12.31 - On-site wetland identification criteria.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...