Active-site protein dynamics and solvent accessibility in native Achromobacter cycloclastes copper nitrite reductase.

PubMed

Sen, Kakali; Horrell, Sam; Kekilli, Demet; Yong, Chin W; Keal, Thomas W; Atakisi, Hakan; Moreau, David W; Thorne, Robert E; Hough, Michael A; Strange, Richard W

2017-07-01

Microbial nitrite reductases are denitrifying enzymes that are a major component of the global nitrogen cycle. Multiple structures measured from one crystal (MSOX data) of copper nitrite reductase at 240 K, together with molecular-dynamics simulations, have revealed protein dynamics at the type 2 copper site that are significant for its catalytic properties and for the entry and exit of solvent or ligands to and from the active site. Molecular-dynamics simulations were performed using different protonation states of the key catalytic residues (Asp CAT and His CAT ) involved in the nitrite-reduction mechanism of this enzyme. Taken together, the crystal structures and simulations show that the Asp CAT protonation state strongly influences the active-site solvent accessibility, while the dynamics of the active-site 'capping residue' (Ile CAT ), a determinant of ligand binding, are influenced both by temperature and by the protonation state of Asp CAT . A previously unobserved conformation of Ile CAT is seen in the elevated temperature series compared with 100 K structures. DFT calculations also show that the loss of a bound water ligand at the active site during the MSOX series is consistent with reduction of the type 2 Cu atom.

Expansion of access tunnels and active-site cavities influence activity of haloalkane dehalogenases in organic cosolvents.

PubMed

Stepankova, Veronika; Khabiri, Morteza; Brezovsky, Jan; Pavelka, Antonin; Sykora, Jan; Amaro, Mariana; Minofar, Babak; Prokop, Zbynek; Hof, Martin; Ettrich, Rudiger; Chaloupkova, Radka; Damborsky, Jiri

2013-05-10

The use of enzymes for biocatalysis can be significantly enhanced by using organic cosolvents in the reaction mixtures. Selection of the cosolvent type and concentration range for an enzymatic reaction is challenging and requires extensive empirical testing. An understanding of protein-solvent interaction could provide a theoretical framework for rationalising the selection process. Here, the behaviour of three model enzymes (haloalkane dehalogenases) was investigated in the presence of three representative organic cosolvents (acetone, formamide, and isopropanol). Steady-state kinetics assays, molecular dynamics simulations, and time-resolved fluorescence spectroscopy were used to elucidate the molecular mechanisms of enzyme-solvent interactions. Cosolvent molecules entered the enzymes' access tunnels and active sites, enlarged their volumes with no change in overall protein structure, but surprisingly did not act as competitive inhibitors. At low concentrations, the cosolvents either enhanced catalysis by lowering K(0.5) and increasing k(cat), or caused enzyme inactivation by promoting substrate inhibition and decreasing k(cat). The induced activation and inhibition of the enzymes correlated with expansion of the active-site pockets and their occupancy by cosolvent molecules. The study demonstrates that quantitative analysis of the proportions of the access tunnels and active-sites occupied by organic solvent molecules provides the valuable information for rational selection of appropriate protein-solvent pair and effective cosolvent concentration. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The dynamics of camphor in the cytochrome P450 CYP101D2

PubMed Central

Vohra, Shabana; Musgaard, Maria; Bell, Stephen G; Wong, Luet-Lok; Zhou, Weihong; Biggin, Philip C

2013-01-01

The recent crystal structures of CYP101D2, a cytochrome P450 protein from the oligotrophic bacterium Novosphingobium aromaticivorans DSM12444 revealed that both the native (substrate-free) and camphor-soaked forms have open conformations. Furthermore, two other potential camphor-binding sites were also identified from electron densities in the camphor-soaked structure, one being located in the access channel and the other in a cavity on the surface near the F-helix side of the F-G loop termed the substrate recognition site. These latter sites may be key intermediate positions on the pathway for substrate access to or product egress from the active site. Here, we show via the use of unbiased atomistic molecular dynamics simulations that despite the open conformation of the native and camphor-bound crystal structures, the underlying dynamics of CYP101D2 appear to be very similar to other CYP proteins. Simulations of the native structure demonstrated that the protein is capable of sampling many different conformational substates. At the same time, simulations with the camphor positioned at various locations within the access channel or recognition site show that movement towards the active site or towards bulk solvent can readily occur on a short timescale, thus confirming many previously reported in silico studies using steered molecular dynamics. The simulations also demonstrate how the fluctuations of an aromatic gate appear to control access to the active site. Finally, comparison of camphor-bound simulations with the native simulations suggests that the fluctuations can be of similar level and thus are more representative of the conformational selection model rather than induced fit. PMID:23832606

Two signs indicative of successful access in nuclear medicine cerebrospinal fluid diversionary shunt studies.

PubMed

Bermo, Mohammed S; Khalatbari, Hedieh; Parisi, Marguerite T

2018-05-08

Successful shunt access is the first step in a properly performed nuclear medicine cerebrospinal fluid (CSF) shunt study. To determine the significance of the radiotracer configuration at the injection site during initial nuclear medicine CSF shunt imaging and the lack of early systemic radiotracer activity as predictors of successful shunt access. With Institutional Review Board approval, three nuclear medicine physicians performed a retrospective review of all consecutive CSF shunt studies performed in children at our institution in 2015. Antecedent nuclear medicine CSF shunt studies in these patients were also assessed and included in the review. The appearance of the reservoir site immediately after radiotracer injection was classified as either figure-of-eight or round/ovoid configuration. The presence or absence of early systemic distribution of the tracer on the 5-min static images was noted and separately evaluated. A total of 98 nuclear medicine ventriculoperitoneal CSF shunt studies were evaluated. Figure-of-eight configuration was identified in 87% of studies and, when present, had 93% sensitivity, 78% specificity, 92% accuracy, 98% positive predictive value (PPV) and 54% negative predictive value (NPV) as a predictor of successful shunt access. Early systemic activity was absent in 89 of 98 studies. Lack of early systemic distribution of the radiotracer had 98% sensitivity, 78% specificity, 96% accuracy, 98% PPV and 78% NPV as a predictor of successful shunt access. Figure-of-eight configuration in conjunction with the absence of early systemic tracer activity had 99% PPV for successful shunt access. Figure-of-eight configuration at the injection site or lack of early systemic radiotracer activity had moderate specificity for successful shunt access. Specificity and PPV significantly improved when both signs were combined in assessment.

SWS: accessing SRS sites contents through Web Services.

PubMed

Romano, Paolo; Marra, Domenico

2008-03-26

Web Services and Workflow Management Systems can support creation and deployment of network systems, able to automate data analysis and retrieval processes in biomedical research. Web Services have been implemented at bioinformatics centres and workflow systems have been proposed for biological data analysis. New databanks are often developed by taking into account these technologies, but many existing databases do not allow a programmatic access. Only a fraction of available databanks can thus be queried through programmatic interfaces. SRS is a well know indexing and search engine for biomedical databanks offering public access to many databanks and analysis tools. Unfortunately, these data are not easily and efficiently accessible through Web Services. We have developed 'SRS by WS' (SWS), a tool that makes information available in SRS sites accessible through Web Services. Information on known sites is maintained in a database, srsdb. SWS consists in a suite of WS that can query both srsdb, for information on sites and databases, and SRS sites. SWS returns results in a text-only format and can be accessed through a WSDL compliant client. SWS enables interoperability between workflow systems and SRS implementations, by also managing access to alternative sites, in order to cope with network and maintenance problems, and selecting the most up-to-date among available systems. Development and implementation of Web Services, allowing to make a programmatic access to an exhaustive set of biomedical databases can significantly improve automation of in-silico analysis. SWS supports this activity by making biological databanks that are managed in public SRS sites available through a programmatic interface.

Synthetic, structural mimetics of the β-hairpin flap of HIV-1 protease inhibit enzyme function.

PubMed

Chauhan, Jay; Chen, Shen-En; Fenstermacher, Katherine J; Naser-Tavakolian, Aurash; Reingewertz, Tali; Salmo, Rosene; Lee, Christian; Williams, Emori; Raje, Mithun; Sundberg, Eric; DeStefano, Jeffrey J; Freire, Ernesto; Fletcher, Steven

2015-11-01

Small-molecule mimetics of the β-hairpin flap of HIV-1 protease (HIV-1 PR) were designed based on a 1,4-benzodiazepine scaffold as a strategy to interfere with the flap-flap protein-protein interaction, which functions as a gated mechanism to control access to the active site. Michaelis-Menten kinetics suggested our small-molecules are competitive inhibitors, which indicates the mode of inhibition is through binding the active site or sterically blocking access to the active site and preventing flap closure, as designed. More generally, a new bioactive scaffold for HIV-1PR inhibition has been discovered, with the most potent compound inhibiting the protease with a modest K(i) of 11 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Downgrade of the Savannah River Sites FB-Line

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

SADOWSKI, ED; YOURCHAK, RANDY; PRETZELLO MARJI

2005-07-05

This paper will discuss the Safeguards & Security (S&S) activities that resulted in the downgrade of the Savannah River Site's FB-Line (FBL) from a Category I Material Balance Area (MBA) in a Material Access Area (MAA) to a Category IV MBA in a Property Protection Area (PPA). The Safeguards activities included measurement of final product items, transferal of nuclear material to other Savannah River Site (SRS) facilities, discard of excess nuclear material items, and final measurements of holdup material. The Security activities included relocation and destruction of classified documents and repositories, decertification of a classified computer, access control changes, updatesmore » to planning documents, deactivation and removal of security systems, Human Reliability Program (HRP) removals, and information security training for personnel that will remain in the FBL PPA.« less

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.

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

Coupling Oxygen Consumption with Hydrocarbon Oxidation in Bacterial Multicomponent Monooxygenases.

PubMed

Wang, Weixue; Liang, Alexandria D; Lippard, Stephen J

2015-09-15

A fundamental goal in catalysis is the coupling of multiple reactions to yield a desired product. Enzymes have evolved elegant approaches to address this grand challenge. A salient example is the biological conversion of methane to methanol catalyzed by soluble methane monooxygenase (sMMO), a member of the bacterial multicomponent monooxygenase (BMM) superfamily. sMMO is a dynamic protein complex of three components: a hydroxylase, a reductase, and a regulatory protein. The active site, a carboxylate-rich non-heme diiron center, is buried inside the 251 kDa hydroxylase component. The enzyme processes four substrates: O2, protons, electrons, and methane. To couple O2 activation to methane oxidation, timely control of substrate access to the active site is critical. Recent studies of sMMO, as well as its homologues in the BMM superfamily, have begun to unravel the mechanism. The emerging and unifying picture reveals that each substrate gains access to the active site along a specific pathway through the hydroxylase. Electrons and protons are delivered via a three-amino-acid pore located adjacent to the diiron center; O2 migrates via a series of hydrophobic cavities; and hydrocarbon substrates reach the active site through a channel or linked set of cavities. The gating of these pathways mediates entry of each substrate to the diiron active site in a timed sequence and is coordinated by dynamic interactions with the other component proteins. The result is coupling of dioxygen consumption with hydrocarbon oxidation, avoiding unproductive oxidation of the reductant rather than the desired hydrocarbon. To initiate catalysis, the reductase delivers two electrons to the diiron(III) center by binding over the pore of the hydroxylase. The regulatory component then displaces the reductase, docking onto the same surface of the hydroxylase. Formation of the hydroxylase-regulatory component complex (i) induces conformational changes of pore residues that may bring protons to the active site; (ii) connects hydrophobic cavities in the hydroxylase leading from the exterior to the diiron active site, providing a pathway for O2 and methane, in the case of sMMO, to the reduced diiron center for O2 activation and substrate hydroxylation; (iii) closes the pore, as well as a channel in the case of four-component BMM enzymes, restricting proton access to the diiron center during formation of "Fe2O2" intermediates required for hydrocarbon oxidation; and (iv) inhibits undesired electron transfer to the Fe2O2 intermediates by blocking reductase binding during O2 activation. This mechanism is quite different from that adopted by cytochromes P450, a large class of heme-containing monooxygenases that catalyze reactions very similar to those catalyzed by the BMM enzymes. Understanding the timed enzyme control of substrate access has implications for designing artificial catalysts. To achieve multiple turnovers and tight coupling, synthetic models must also control substrate access, a major challenge considering that nature requires large, multimeric, dynamic protein complexes to accomplish this feat.

Interaction Between the Biotin Carboxyl Carrier Domain and the Biotin Carboxylase Domain in Pyruvate Carboxylase from Rhizobium etli†

PubMed Central

Lietzan, Adam D.; Menefee, Ann L.; Zeczycki, Tonya N.; Kumar, Sudhanshu; Attwood, Paul V.; Wallace, John C.; Cleland, W. Wallace; Maurice, Martin St.

2011-01-01

Pyruvate carboxylase (PC) catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in mammalian tissues. To effect catalysis, the tethered biotin of PC must gain access to active sites in both the biotin carboxylase domain and the carboxyl transferase domain. Previous studies have demonstrated that a mutation of threonine 882 to alanine in PC from Rhizobium etli renders the carboxyl transferase domain inactive and favors the positioning of biotin in the biotin carboxylase domain. We report the 2.4 Å resolution X-ray crystal structure of the Rhizobium etli PC T882A mutant which reveals the first high-resolution description of the domain interaction between the biotin carboxyl carrier protein domain and the biotin carboxylase domain. The overall quaternary arrangement of Rhizobium etli PC remains highly asymmetrical and is independent of the presence of allosteric activator. While biotin is observed in the biotin carboxylase domain, its access to the active site is precluded by the interaction between Arg353 and Glu248, revealing a mechanism for regulating carboxybiotin access to the BC domain active site. The binding location for the biotin carboxyl carrier protein domain demonstrates that tethered biotin cannot bind in the biotin carboxylase domain active site in the same orientation as free biotin, helping to explain the difference in catalysis observed between tethered biotin and free biotin substrates in biotin carboxylase enzymes. Electron density located in the biotin carboxylase domain active site is assigned to phosphonoacetate, offering a probable location for the putative carboxyphosphate intermediate formed during biotin carboxylation. The insights gained from the T882A Rhizobium etli PC crystal structure provide a new series of catalytic snapshots in PC and offer a revised perspective on catalysis in the biotin-dependent enzyme family. PMID:21958016

MyEnviroMapper

EPA Pesticide Factsheets

EnviroMapper for Envirofacts is a single point of access to select U.S. EPA environmental data. This Web site provides access to several EPA databases to provide you with information about environmental activities that may affect air, water, and l

Solvent Flux Method (SFM): A Case Study of Water Access to Candida antarctica Lipase B.

PubMed

Benson, Sven P; Pleiss, Jürgen

2014-11-11

The solvent flux method (SFM) was developed to comprehensively characterize the influx of solvent molecules from the solvent environment into the active site of a protein in the framework of molecular dynamics simulations. This was achieved by introducing a solvent concentration gradient as well as partially reorienting and rescaling the velocity vector of all solvent molecules contained within a spherical volume enclosing the protein, thus inducing an accelerated solvent influx toward the active site. In addition to the detection of solvent access pathway within the protein structure, it is hereby possible to identify potential amino acid positions relevant to solvent-related enzyme engineering with high statistical significance. The method is particularly aimed at improving the reverse hydrolysis reaction rates in nonaqueous media. Candida antarctica lipase B (CALB) binds to a triglyceride-water interface with its substrate entrance channel oriented toward the hydrophobic substrate interface. The lipase-triglyceride-water system served as a model system for SFM to evaluate the influx of water molecules to the active site. As a proof of principle for SFM, a previously known water access pathway in CALB was identified as the primary water channel. In addition, a secondary water channel and two pathways for water access which contribute to water leakage between the protein and the triglyceride-water interface were identified.

10 CFR 960.5-2-2 - Site ownership and control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... NUCLEAR WASTE REPOSITORY Preclosure Guidelines Preclosure Radiological Safety § 960.5-2-2 Site ownership... control of access that are required in order that surface and subsurface activities during repository...

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

Direct accessibility of mixed-metal (III/II) acid sites through the rational synthesis of porous metal carboxylates.

PubMed

Wongsakulphasatch, S; Nouar, F; Rodriguez, J; Scott, L; Le Guillouzer, C; Devic, T; Horcajada, P; Grenèche, J-M; Llewellyn, P L; Vimont, A; Clet, G; Daturi, M; Serre, C

2015-06-25

The scalable and environmentally-friendly synthesis of mixed Fe(III)/M(II) (M = Ni, Co, Mg) polycarboxylate porous MOFs based on the Secondary Building Unit approach is reported. A combination of in situ infrared spectroscopy, (57)Fe Mössbauer spectrometry and adsorption microcalorimetry confirms the direct accessibility of the iron(III) and metal(II) sites under low temperature activation conditions.

Pt-Pd Bimetal Popcorn Nanocrystals: Enhancing the Catalytic Performance by Combination Effect of Stable Multipetals Nanostructure and Highly Accessible Active Sites.

PubMed

Ma, Yanxia; Yin, Lisi; Cao, Guojian; Huang, Qingli; He, Maoshuai; Wei, Wenxian; Zhao, Hong; Zhang, Dongen; Wang, Mingyan; Yang, Tao

2018-04-01

Exploration of highly efficient electrocatalysts is significantly urgent for the extensive adoption of the fuel cells. Because of their high activity and super stability, Pt-Pd bimetal nanocrystals have been widely recognized as one class of promising electrocatalysts for oxygen reduction. This article presents the synthesis of popcorn-shaped Pt-Pd bimetal nanoparticles with a wide composition range through a facile hydrothermal strategy. The hollow-centered nanoparticles are surrounded by several petals and concave surfaces. By exploring the oxygen reduction reaction on the carbon supported Pt-Pd popcorns in perchloric acid solution, it is found that compared with the commercial Pt/C catalyst the present catalysts display superior catalytic performances in aspects of catalytic activity and stability. More importantly, the Pt-Pd popcorns display minor performance degradations through prolonged potential cycling. The enhanced performances can be mainly attributed to the unique popcorn structure of the Pt-Pd components, which allows the appearance and long existence of the high active sites with more accessibility. The present work highlights the key roles of accessible high active sites in the oxygen reduction reaction, which will ultimately guide the design of highly durable Pt-Pd catalysts. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

12 CFR 404.1 - General provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... subpart B of this part also shall be processed under this subpart A. (d) Ex-Im Bank Internet site. Ex-Im Bank maintains an Internet site at http://www.exim.gov. The site contains information on Ex-Im Bank functions, activities, programs, and transactions. Web site visitors have access to Board of Directors and...

Vascular closure devices in stroke patients receiving tissue plasminogen activator: A retrospective analysis from an academic tertiary medical center and a teaching community hospital stroke database.

PubMed

Patil, Mangaladevi S; Jayaraman, Mahesh V; Ahn, Sun H

2017-06-01

To determine the safety and effectiveness of vascular closure devices in prevention of access site complications in acute stroke patient receiving intravenous (IV) and/or intra-arterial (IA) IV tissue plasminogen activator (tPA). All patients with acute stroke onset treated with IV and/or IA tPA closed with vascular closure device and adult age (>18 years) were identified from an academic tertiary medical center and a teaching community hospital stroke database for 9 years (from March 2005 to June 2014). A total of 69 patients were included in the study. The mean age was 68.86±16.70 years and 49.2% female. All accesses were under fluoroscopic guidance into the right common femoral artery. We observed a 5.8% complication rate in patients receiving IV and/or IA tPA closed with vascular closure device. Access site complications included 3 cases of hematoma and 1 case of residual oozing. One patient required transfusion due to access site hematoma. Three patients were on aspirin and heparin and 1 was on no prior anticoagulation. Vascular closure device access site hemorrhagic complication rate in those receiving IV and/or IA tPA is low and similar to reported rates in those not receiving thrombolytic therapy. Vascular closure device use in patients receiving thrombolytic therapy is safe and effectively achieves hemostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

A 4-year prospective study of the progression of periodontal disease in a rural Chinese population.

PubMed

Pei, Xiyan; Ouyang, Xiangying; He, Lu; Cao, Caifang; Luan, Qingxian; Suda, Reiko

2015-02-01

The natural progression of periodontitis in the Chinese population is not well researched. We investigated the progression of periodontal disease over 4 years in 15-44-year-old Chinese villagers with no access to regular dental care. In 1992, 486 villagers were enrolled, and in 1996, 413 villagers were re-examined. Probing depth (PD) and clinical attachment level (CAL) were examined at six sites per tooth. Sites with ΔCAL ≥3 mm were defined as active sites. Cross-sectional and longitudinal analyses were performed using means and percentile plots. The mean CAL increased by 0.26 mm over 4 years. The incidence of periodontitis (at least one site with CAL ≥3 mm) was 8%. The incidence of periodontitis among those with no periodontal disease at baseline was 44.9%. Seventy-eight percent of the subjects had at least one active site. In the 15-24-year group, 244 of 401 active sites had gingival recession, while only 51 active sites had both gingival recession and deeper pockets. In the 25-34-year and 35-44-year groups, almost one-third of the active sites (329/1087) and more than one-third of the active sites (580/1312) respectively had a combination of gingival recession and deeper pockets. In this study, we demonstrated that in Chinese population without regular dental care, both the initiation of periodontitis and progression of previously existed periodontitis contributed to the natural progression of periodontitis and periodontal pocketing played a greater role with age increasing. This rare study reports the natural progression of periodontal disease in a group of Chinese villagers (15-44 years) with virtually no access to regular dental care. Copyright © 2014 Elsevier Ltd. All rights reserved.

High Plains Regional Ground-water Study web site

USGS Publications Warehouse

Qi, Sharon L.

2000-01-01

Now available on the Internet is a web site for the U.S. Geological Survey's (USGS) National Water-Quality Assessment (NAWQA) Program-High Plains Regional Ground-Water Study. The purpose of the web site is to provide public access to a wide variety of information on the USGS investigation of the ground-water resources within the High Plains aquifer system. Typical pages on the web site include the following: descriptions of the High Plains NAWQA, the National NAWQA Program, the study-area setting, current and past activities, significant findings, chemical and ancillary data (which can be downloaded), listing and access to publications, links to other sites about the High Plains area, and links to other web sites studying High Plains ground-water resources. The High Plains aquifer is a regional aquifer system that underlies 174,000 square miles in parts of eight States (Colorado, Kansas, Nebraska, New Mexico, Oklahoma, South Dakota, Texas, and Wyoming). Because the study area is so large, the Internet is an ideal way to provide project data and information on a near real-time basis. The web site will be a collection of living documents where project data and information are updated as it becomes available throughout the life of the project. If you have an interest in the High Plains area, you can check this site periodically to learn how the High Plains NAWQA activities are progressing over time and access new data and publications as they become available.

Chelating agent-free, vapor-assisted crystallization method to synthesize hierarchical microporous/mesoporous MIL-125 (Ti).

PubMed

McNamara, Nicholas D; Hicks, Jason C

2015-03-11

Titanium-based microporous heterogeneous catalysts are widely studied but are often limited by the accessibility of reactants to active sites. Metal-organic frameworks (MOFs), such as MIL-125 (Ti), exhibit enhanced surface areas due to their high intrinsic microporosity, but the pore diameters of most microporous MOFs are often too small to allow for the diffusion of larger reactants (>7 Å) relevant to petroleum and biomass upgrading. In this work, hierarchical microporous MIL-125 exhibiting significantly enhanced interparticle mesoporosity was synthesized using a chelating-free, vapor-assisted crystallization method. The resulting hierarchical MOF was examined as an active catalyst for the oxidation of dibenzothiophene (DBT) with tert-butyl hydroperoxide and outperformed the solely microporous analogue. This was attributed to greater access of the substrate to surface active sites, as the pores in the microporous analogues were of inadequate size to accommodate DBT. Moreover, thiophene adsorption studies suggested the mesoporous MOF contained larger amounts of unsaturated metal sites that could enhance the observed catalytic activity.

Unprecedented access of phenolic substrates to the heme active site of a catalase: substrate binding and peroxidase-like reactivity of Bacillus pumilus catalase monitored by X-ray crystallography and EPR spectroscopy.

PubMed

Loewen, Peter C; Villanueva, Jacylyn; Switala, Jacek; Donald, Lynda J; Ivancich, Anabella

2015-05-01

Heme-containing catalases and catalase-peroxidases catalyze the dismutation of hydrogen peroxide as their predominant catalytic activity, but in addition, individual enzymes support low levels of peroxidase and oxidase activities, produce superoxide, and activate isoniazid as an antitubercular drug. The recent report of a heme enzyme with catalase, peroxidase and penicillin oxidase activities in Bacillus pumilus and its categorization as an unusual catalase-peroxidase led us to investigate the enzyme for comparison with other catalase-peroxidases, catalases, and peroxidases. Characterization revealed a typical homotetrameric catalase with one pentacoordinated heme b per subunit (Tyr340 being the axial ligand), albeit in two orientations, and a very fast catalatic turnover rate (kcat  = 339,000 s(-1) ). In addition, the enzyme supported a much slower (kcat  = 20 s(-1) ) peroxidatic activity utilizing substrates as diverse as ABTS and polyphenols, but no oxidase activity. Two binding sites, one in the main access channel and the other on the protein surface, accommodating pyrogallol, catechol, resorcinol, guaiacol, hydroquinone, and 2-chlorophenol were identified in crystal structures at 1.65-1.95 Å. A third site, in the heme distal side, accommodating only pyrogallol and catechol, interacting with the heme iron and the catalytic His and Arg residues, was also identified. This site was confirmed in solution by EPR spectroscopy characterization, which also showed that the phenolic oxygen was not directly coordinated to the heme iron (no low-spin conversion of the Fe(III) high-spin EPR signal upon substrate binding). This is the first demonstration of phenolic substrates directly accessing the heme distal side of a catalase. © 2015 Wiley Periodicals, Inc.

Open-access microfluidic patch-clamp array with raised lateral cell trapping sites.

PubMed

Lau, Adrian Y; Hung, Paul J; Wu, Angela R; Lee, Luke P

2006-12-01

A novel open-access microfluidic patch-clamp array chip with lateral cell trapping sites raised above the bottom plane of the chip was developed by combining both a microscale soft-lithography and a macroscale polymer fabrication method. This paper demonstrates the capability of using such an open-access fluidic system for patch-clamp measurements. The surface of the open-access patch-clamp sites prepared by the macroscale hole patterning method of soft-state elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are characterized and correlated with the aperture dimensions. Whole cell patch-clamp measurements are carried out with CHO cells expressing Kv2.1 ion channels. Kv2.1 ion channel blocker (TEA) dosage response is characterized and the binding activity is examined. The results demonstrate that the system is capable of performing whole cell measurements and drug profiling in a more efficient manner than the traditional patch-clamp set-up.

Molecular investigation of active binding site of isoniazid (INH) and insight into resistance mechanism of S315T-MtKatG in Mycobacterium tuberculosis.

PubMed

Srivastava, Gaurava; Tripathi, Shubhandra; Kumar, Akhil; Sharma, Ashok

2017-07-01

Multi drug resistant tuberculosis is a major threat for mankind. Resistance against Isoniazid (INH), targeting MtKatG protein, is one of the most commonly occurring resistances in MDR TB strains. S315T-MtKatG mutation is widely reported for INH resistance. Despite having knowledge about the mechanism of INH, exact binding site of INH to MtKatG is still uncertain and proposed to have three presumable binding sites (site-1, site-2, and site-3). In the current study docking, molecular dynamics simulation, binding free energy estimation, principal component analysis and free energy landscape analysis were performed to get molecular level details of INH binding site on MtKatG, and to probe the effect of S315T mutation on INH binding. Molecular docking and MD analysis suggested site-1 as active binding site of INH, where the effects of S315T mutation were observed on both access tunnel as well as molecular interaction between INH and its neighboring residues. MMPBSA also supported site-1 as potential binding site with lowest binding energy of -44.201 kJ/mol. Moreover, PCA and FEL revealed that S315T mutation not only reduces the dimension of heme access tunnel but also showed that extra methyl group at 315 position altered heme cavity, enforcing heme group distantly from INH, and thus preventing INH activation. The present study not only investigated the active binding site of INH but also provides a new insight about the conformational changes in the binding site of S315T-MtKatG. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of target site accessibility on the design of effective siRNAs.

PubMed

Tafer, Hakim; Ameres, Stefan L; Obernosterer, Gregor; Gebeshuber, Christoph A; Schroeder, Renée; Martinez, Javier; Hofacker, Ivo L

2008-05-01

Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.

Everyday Inclusive Web Design: An Activity Perspective

ERIC Educational Resources Information Center

Kane, Shaun K.

2007-01-01

Introduction: Website accessibility is a problem that affects millions of people with disabilities. While most current accessibility initiatives target government or commercial sites, a growing segment of online content is being created by non-professionals. This content is often inaccessible to users with disabilities. Everyday inclusive Web…

National Facilities Study. Volume 1: Facilities Inventory

NASA Technical Reports Server (NTRS)

1994-01-01

The inventory activity was initiated to solve the critical need for a single source of site specific descriptive and parametric data on major public and privately held aeronautics and aerospace related facilities. This a challenging undertaking due to the scope of the effort and the short lead time in which to assemble the inventory and have it available to support the task group study needs. The inventory remains dynamic as sites are being added and the data is accessed and refined as the study progresses. The inventory activity also included the design and implementation of a computer database and analytical tools to simplify access to the data. This volume describes the steps which were taken to define the data requirements, select sites, and solicit and acquire data from them. A discussion of the inventory structure and analytical tools is also provided.

Mechanism of reactant and product dissociation from the anthrax edema factor: a locally enhanced sampling and steered molecular dynamics study.

PubMed

Martínez, Leandro; Malliavin, Thérèse E; Blondel, Arnaud

2011-05-01

The anthrax edema factor is a toxin overproducing damaging levels of cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi) from ATP. Here, mechanisms of dissociation of ATP and products (cAMP, PPi) from the active site are studied using locally enhanced sampling (LES) and steered molecular dynamics simulations. Various substrate conformations and ionic binding modes found in crystallographic structures are considered. LES simulations show that PPi and cAMP dissociate through different solvent accessible channels, while ATP dissociation requires significant active site exposure to solvent. The ionic content of the active site directly affects the dissociation of ATP and products. Only one ion dissociates along with ATP in the two-Mg(2+) binding site, suggesting that the other ion binds EF prior to ATP association. Dissociation of reaction products cAMP and PPi is impaired by direct electrostatic interactions between products and Mg(2+) ions. This provides an explanation for the inhibitory effect of high Mg(2+) concentrations on EF enzymatic activity. Breaking of electrostatic interactions is dependent on a competitive binding of water molecules to the ions, and thus on the solvent accessibility of the active site. Consequently, product dissociation seems to be a two-step process. First, ligands are progressively solvated while preserving the most important electrostatic interactions, in a process that is dependent on the flexibility of the active site. Second, breakage of the electrostatic bonds follows, and ligands diffuse into solvent. In agreement with this mechanism, product protonation facilitates dissociation.

Polycomb Group Repression Reduces DNA Accessibility

PubMed Central

Fitzgerald, Daniel P.; Bender, Welcome

2001-01-01

The Polycomb group proteins are responsible for long-term repression of a number of genes in Drosophila melanogaster, including the homeotic genes of the bithorax complex. The Polycomb protein is thought to alter the chromatin structure of its target genes, but there has been little direct evidence for this model. In this study, the chromatin structure of the bithorax complex was probed with three separate assays for DNA accessibility: (i) activation of polymerase II (Pol II) transcription by Gal4, (ii) transcription by the bacteriophage T7 RNA polymerase (T7RNAP), and (iii) FLP-mediated site-specific recombination. All three processes are restricted or blocked in Polycomb-repressed segments. In contrast, control test sites outside of the bithorax complex permitted Gal4, T7RNAP, and FLP activities throughout the embryo. Several P insertions in the bithorax complex were tested, providing evidence that the Polycomb-induced effect is widespread over target genes. This accessibility effect is similar to that seen for SIR silencing in Saccharomyces cerevisiae. In contrast to SIR silencing, however, episomes excised from Polycomb-repressed chromosomal sites do not show an altered superhelix density. PMID:11533246

Volcanology curricula development aided by online educational resource

USGS Publications Warehouse

Poland, Michael P.; van der Hoeven Kraft, Katrien J.; Teasdale, Rachel

2011-01-01

Volcanic activity is an excellent hook for engaging college and university students in geoscience classes. An increasing number of Internet-accessible real-time and near–real time volcano monitoring data are now available and constitute an important resource for geoscience education; however, relatively few data sets are comprehensive, and many lack background information to aid in interpretation. In response to the need for organized, accessible, and well-documented volcano education resources, the U.S. Geological Survey's Hawaiian Volcano Observatory (HVO), in collaboration with NASA and the University of Hawai`i at Manoa, established the Volcanoes Exploration Project: Pu`u `Ō`ō (VEPP). The VEPP Web site (http://vepp.wr.usgs.gov) is an educational resource that provides access, in near real time, to geodetic, seismic, and geologic data from the active Pu`u `Ō`ō eruptive vent on Kilauea volcano, Hawaii, along with background and context information. A strength of the VEPP site is the common theme of the Pu`u `Ō`ō eruption, which allows the site to be revisited multiple times to demonstrate different principles and integrate many aspects of volcanology.

Health assessment for Midwest Industrial Waste Disposal Company, Inc. (Midco II) NPL (National Priorities List) Site, 5900 Industrial Highway, Gary, Indiana, Region 5. CERCLIS No. IND980679559. Final report

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

Not Available

1989-04-12

The 7-acre Midco II Site is located at 5900 Industrial Highway, Gary, Indiana. The site is listed on the National Priorities List. Various heavy metals, inorganic, and organic compounds were found in the media on-site. The environmental media of concern at the site are ground water, surface water, and soil. Although access to the Midco II site is restricted, the contaminants detected on-site will continue to migrate and may pose health threats until remedial activities are completed. Therefore, the Midco II site poses a potential health concern until an evaluation of the site is completed and remedial activities are chosen.

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.

In Search of Functional Advantages of Knots in Proteins.

PubMed

Dabrowski-Tumanski, Pawel; Stasiak, Andrzej; Sulkowska, Joanna I

2016-01-01

We analysed the structure of deeply knotted proteins representing three unrelated families of knotted proteins. We looked at the correlation between positions of knotted cores in these proteins and such local structural characteristics as the number of intra-chain contacts, structural stability and solvent accessibility. We observed that the knotted cores and especially their borders showed strong enrichment in the number of contacts. These regions showed also increased thermal stability, whereas their solvent accessibility was decreased. Interestingly, the active sites within these knotted proteins preferentially located in the regions with increased number of contacts that also have increased thermal stability and decreased solvent accessibility. Our results suggest that knotting of polypeptide chains provides a favourable environment for the active sites observed in knotted proteins. Some knotted proteins have homologues without a knot. Interestingly, these unknotted homologues form local entanglements that retain structural characteristics of the knotted cores.

Sent packing: protein engineering generates a new crystal form of Pseudomonas aeruginosa DsbA1 with increased catalytic surface accessibility

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

McMahon, Roisin M., E-mail: r.mcmahon1@uq.edu.au; Coinçon, Mathieu; Tay, Stephanie

The crystal structure of a P. aeruginosa DsbA1 variant is more suitable for fragment-based lead discovery efforts to identify inhibitors of this antimicrobial drug target. In the reported structures the active site of the protein can simultaneously bind multiple ligands introduced in the crystallization solution or via soaking. Pseudomonas aeruginosa is an opportunistic human pathogen for which new antimicrobial drug options are urgently sought. P. aeruginosa disulfide-bond protein A1 (PaDsbA1) plays a pivotal role in catalyzing the oxidative folding of multiple virulence proteins and as such holds great promise as a drug target. As part of a fragment-based lead discoverymore » approach to PaDsbA1 inhibitor development, the identification of a crystal form of PaDsbA1 that was more suitable for fragment-soaking experiments was sought. A previously identified crystallization condition for this protein was unsuitable, as in this crystal form of PaDsbA1 the active-site surface loops are engaged in the crystal packing, occluding access to the target site. A single residue involved in crystal-packing interactions was substituted with an amino acid commonly found at this position in closely related enzymes, and this variant was successfully used to generate a new crystal form of PaDsbA1 in which the active-site surface is more accessible for soaking experiments. The PaDsbA1 variant displays identical redox character and in vitro activity to wild-type PaDsbA1 and is structurally highly similar. Two crystal structures of the PaDsbA1 variant were determined in complex with small molecules bound to the protein active site. These small molecules (MES, glycerol and ethylene glycol) were derived from the crystallization or cryoprotectant solutions and provide a proof of principle that the reported crystal form will be amenable to co-crystallization and soaking with small molecules designed to target the protein active-site surface.« less

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.

Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.

PubMed

Silverman, William R; Bannister, John P A; Papazian, Diane M

2004-11-01

In ether-a-go-go K+ channels, voltage-dependent activation is modulated by ion binding to a site located in an extracellular-facing crevice between transmembrane segments S2 and S3 in the voltage sensor. We find that acidic residues D278 in S2 and D327 in S3 are able to coordinate a variety of divalent cations, including Mg2+, Mn2+, and Ni2+, which have qualitatively similar functional effects, but different half-maximal effective concentrations. Our data indicate that ions binding to individual voltage sensors in the tetrameric channel act without cooperativity to modulate activation gating. We have taken advantage of the unique phenotype of Ni2+ in the D274A channel, which contains a mutation of a nonbinding site residue, to demonstrate that ions can access the binding site from the extracellular solution when the voltage sensor is in the resting conformation. Our results are difficult to reconcile with the x-ray structure of the KvAP K+ channel, in which the binding site residues are widely separated, and with the hydrophobic paddle model for voltage-dependent activation, in which the voltage sensor domain, including the S3-S4 loop, is near the cytoplasmic side of the membrane in the closed channel.

Internet Use and Cognitive Development: A Theoretical Framework

ERIC Educational Resources Information Center

Johnson, Genevieve

2006-01-01

The number of children and adolescents accessing the Internet as well as the amount of time online are steadily increasing. The most common online activities include playing video games, accessing web sites, and communicating via chat rooms, email, and instant messaging. A theoretical framework for understanding the effects of Internet use on…

Chemical Safety Information, Site Security and Fuels Regulatory Relief Act: Public Distribution of Off-Site Consequence Analysis Information Fact Sheet

EPA Pesticide Factsheets

Based on assessments of increased risk of terrorist/criminal activity, EPA and DOJ have issued a rule that allows public access to OCA information in ways that are designed to minimize likelihood of chemical accidents and public harm.

Embedded with Facebook: DoD Faces Risks from Social Media

DTIC Science & Technology

2011-06-01

appropriate conduct. Embedded with Social Media Today Facebook is the world’s dominant social network site . Facebook boasts over 600 million active users...billion minutes on the site each month [4]. Facebook is also the most popular social network site for DoD personnel. Using our techniques for correlating...media sites [6], directing that the Non-classified Internet Protocol Router Network (NIPRNET) be configured to allow access to social media, e-mail

78 FR 53173 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2013-0112] Agency Information Collection Activities... for employment), contractors, and consultants of NRC licensees and contractors whose activities involve access to, or control over, special nuclear material at either fixed sites or for transportation...

Status Report for Remediation Decision Support Project, Task 1, Activity 1.B – Physical and Hydraulic Properties Database and Interpretation

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

Rockhold, Mark L.

2008-09-26

The objective of Activity 1.B of the Remediation Decision Support (RDS) Project is to compile all available physical and hydraulic property data for sediments from the Hanford Site, to port these data into the Hanford Environmental Information System (HEIS), and to make the data web-accessible to anyone on the Hanford Local Area Network via the so-called Virtual Library. In past years efforts were made by RDS project staff to compile all available physical and hydraulic property data for Hanford sediments and to transfer these data into SoilVision{reg_sign}, a commercial geotechnical software package designed for storing, analyzing, and manipulating soils data.more » Although SoilVision{reg_sign} has proven to be useful, its access and use restrictions have been recognized as a limitation to the effective use of the physical and hydraulic property databases by the broader group of potential users involved in Hanford waste site issues. In order to make these data more widely available and useable, a decision was made to port them to HEIS and to make them web-accessible via a Virtual Library module. In FY08 the objectives of Activity 1.B of the RDS Project were to: (1) ensure traceability and defensibility of all physical and hydraulic property data currently residing in the SoilVision{reg_sign} database maintained by PNNL, (2) transfer the physical and hydraulic property data from the Microsoft Access database files used by SoilVision{reg_sign} into HEIS, which has most recently been maintained by Fluor-Hanford, Inc., (3) develop a Virtual Library module for accessing these data from HEIS, and (4) write a User's Manual for the Virtual Library module. The development of the Virtual Library module was to be performed by a third party under subcontract to Fluor. The intent of these activities is to make the available physical and hydraulic property data more readily accessible and useable by technical staff and operable unit managers involved in waste site assessments and remedial action decisions for Hanford. This status report describes the history of this development effort and progress to date.« less

Sport Fields as Potential Catalysts for Physical Activity in the Neighbourhood

PubMed Central

Cutumisu, Nicoleta; Spence, John C.

2012-01-01

Physical activity is associated with access to recreational facilities such as sports fields. Because it is not clear whether objectively- or subjectively-assessed access to facilities exerts a stronger influence on physical activity, we investigated the association between the objective and perceived accessibility of sport fields and the levels of self-reported physical activity among adults in Edmonton, Canada. A sample of 2879 respondents was surveyed regarding their socio-demographics, health status, self-efficacy, levels of physical activity, as well as their perceptions of built environment in relation to physical activity. Neighbourhood-level data were obtained for each respondent based on their residence. Accessibility to facilities was assessed using the enhanced Two-Step Floating Catchment Area method. Geographic Information Systems were employed. A logistic regression was performed to predict physical activity using individual- and neighbourhood-level variables. Women, older individuals, and individuals with higher educational attainment were less likely to be physically active. Also, individuals with higher self-efficacy and higher objectively-assessed access to facilities were more likely to be physically active. Interventions that integrate provision of relevant programs for various population groups and of improved recreational facilities may contribute to sport fields becoming catalysts for physical activity by generating movement both on the site and in the neighbourhood. PMID:22470293

Visualizing the kinetic power stroke that drives proton-coupled Zn(II) transport

PubMed Central

Gupta, Sayan; Chai, Jin; Cheng, Jie; D'Mello, Rhijuta; Chance, Mark R.; Fu, Dax

2014-01-01

The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of E. coli, and the transport-site of YiiP receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(II) efflux1,2. This membrane protein is a well characterized member3-7 of the protein family of cation diffusion facilitators (CDFs) that occurs at all phylogenetic levels8-10. X-ray mediated hydroxyl radical labeling of YiiP and mass spectrometric analysis showed that Zn(II) binding triggered a highly localized, all-or-none change of water accessibility to the transport-site and an adjacent hydrophobic gate. Millisecond time-resolved dynamics revealed a concerted and reciprocal pattern of accessibility changes along a transmembrane helix, suggesting a rigid-body helical reorientation linked to Zn(II) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport-site enables a stationary proton gradient to facilitate the conversion of zinc binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights into a proton-coupled active transport reaction. PMID:25043033

Health information exchange usage in emergency departments and clinics: the who, what, and why.

PubMed

Johnson, Kevin B; Unertl, Kim M; Chen, Qingxia; Lorenzi, Nancy M; Nian, Hui; Bailey, James; Frisse, Mark

2011-01-01

Health information exchange (HIE) systems are being developed across the nation. Understanding approaches taken by existing successful exchanges can help new exchange efforts determine goals and plan implementations. The goal of this study was to explore characteristics of use and users of a successful regional HIE. We used a mixed-method analysis, consisting of cross-sectional audit log data, semi-structured interviews, and direct observation in a sample of emergency departments and ambulatory safety net clinics actively using HIE. For each site, we measured overall usage trends, user logon statistics, and data types accessed by users. We also assessed reasons for use and outcomes of use. Overall, users accessed HIE for 6.8% of all encounters, with higher rates of access for repeat visits, for patients with comorbidities, for patients known to have data in the exchange, and at sites providing HIE access to both nurses and physicians. Discharge summaries and test reports were the most frequently accessed data in the exchange. Providers consistently noted retrieving additional history, preventing repeat tests, comparing new results to retrieved results, and avoiding hospitalizations as a consequence of HIE access. HIE use in emergency departments and ambulatory clinics was focused on patients where missing information was believed to be present in the exchange and was related to factors including the roles of people with access, the setting, and other site-specific issues that impacted the overall breadth of routine system use. These data should form an important foundation as other sites embark upon HIE implementation.

Spectral-analysis-based extraction of land disturbances arising from oil and gas development in diverse landscapes

NASA Astrophysics Data System (ADS)

Zhang, Ying; Lantz, Nicholas; Guindon, Bert; Jiao, Xianfen

2017-01-01

Accurate and frequent monitoring of land surface changes arising from oil and gas exploration and extraction is a key requirement for the responsible and sustainable development of these resources. Petroleum deposits typically extend over large geographic regions but much of the infrastructure required for oil and gas recovery takes the form of numerous small-scale features (e.g., well sites, access roads, etc.) scattered over the landscape. Increasing exploitation of oil and gas deposits will increase the presence of these disturbances in heavily populated regions. An object-based approach is proposed to utilize RapidEye satellite imagery to delineate well sites and related access roads in diverse complex landscapes, where land surface changes also arise from other human activities, such as forest logging and agriculture. A simplified object-based change vector approach, adaptable to operational use, is introduced to identify the disturbances on land based on red-green spectral response and spatial attributes of candidate object size and proximity to roads. Testing of the techniques has been undertaken with RapidEye multitemporal imagery in two test sites located at Alberta, Canada: one was a predominant natural forest landscape and the other landscape dominated by intensive agricultural activities. Accuracies of 84% and 73%, respectively, have been achieved for the identification of well site and access road infrastructure of the two sites based on fully automated processing. Limited manual relabeling of selected image segments can improve these accuracies to 95%.

Site-directed spin labeling reveals a conformational switch in the phosphorylation domain of smooth muscle myosin.

PubMed

Nelson, Wendy D; Blakely, Sarah E; Nesmelov, Yuri E; Thomas, David D

2005-03-15

We have used site-directed spin labeling and EPR spectroscopy to detect structural changes within the regulatory light chain (RLC) of smooth muscle myosin upon phosphorylation. Smooth muscle contraction is activated by phosphorylation of S19 on RLC, but the structural basis of this process is unknown. There is no crystal structure containing a phosphorylated RLC, and there is no crystal structure for the N-terminal region of any RLC. Therefore, we have prepared single-Cys mutations throughout RLC, exchanged each mutant onto smooth muscle heavy meromyosin, verified normal regulatory function, and used EPR to determine dynamics and solvent accessibility at each site. A survey of spin-label sites throughout the RLC revealed that only the N-terminal region (first 24 aa) shows a significant change in dynamics upon phosphorylation, with most of the first 17 residues showing an increase in rotational amplitude. Therefore, we focused on this N-terminal region. Additional structural information was obtained from the pattern of oxygen accessibility along the sequence. In the absence of phosphorylation, little or no periodicity was observed, suggesting a lack of secondary structural order in this region. However, phosphorylation induced a strong helical pattern (3.6-residue periodicity) in the first 17 residues, while increasing accessibility throughout the first 24 residues. We have identified a domain within RLC, the N-terminal phosphorylation domain, in which phosphorylation increases helical order, internal dynamics, and accessibility. These results support a model in which this disorder-to-order transition within the phosphorylation domain results in decreased head-head interactions, activating myosin in smooth muscle.

Virtual screening of selective inhibitors of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Kuranova, I. P.

2017-05-01

Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs.

Bringing the CMS distributed computing system into scalable operations

NASA Astrophysics Data System (ADS)

Belforte, S.; Fanfani, A.; Fisk, I.; Flix, J.; Hernández, J. M.; Kress, T.; Letts, J.; Magini, N.; Miccio, V.; Sciabà, A.

2010-04-01

Establishing efficient and scalable operations of the CMS distributed computing system critically relies on the proper integration, commissioning and scale testing of the data and workload management tools, the various computing workflows and the underlying computing infrastructure, located at more than 50 computing centres worldwide and interconnected by the Worldwide LHC Computing Grid. Computing challenges periodically undertaken by CMS in the past years with increasing scale and complexity have revealed the need for a sustained effort on computing integration and commissioning activities. The Processing and Data Access (PADA) Task Force was established at the beginning of 2008 within the CMS Computing Program with the mandate of validating the infrastructure for organized processing and user analysis including the sites and the workload and data management tools, validating the distributed production system by performing functionality, reliability and scale tests, helping sites to commission, configure and optimize the networking and storage through scale testing data transfers and data processing, and improving the efficiency of accessing data across the CMS computing system from global transfers to local access. This contribution reports on the tools and procedures developed by CMS for computing commissioning and scale testing as well as the improvements accomplished towards efficient, reliable and scalable computing operations. The activities include the development and operation of load generators for job submission and data transfers with the aim of stressing the experiment and Grid data management and workload management systems, site commissioning procedures and tools to monitor and improve site availability and reliability, as well as activities targeted to the commissioning of the distributed production, user analysis and monitoring systems.

Analysis of the Accuracy of Weight Loss Information Search Engine Results on the Internet

PubMed Central

Shokar, Navkiran K.; Peñaranda, Eribeth; Nguyen, Norma

2014-01-01

Objectives. We systematically identified and evaluated the quality and comprehensiveness of online information related to weight loss that users were likely to access. Methods. We evaluated the content quality, accessibility of the information, and author credentials for Web sites in 2012 that were identified from weight loss specific queries that we generated. We scored the content with respect to available evidence-based guidelines for weight loss. Results. One hundred three Web sites met our eligibility criteria (21 commercial, 52 news/media, 7 blogs, 14 medical, government, or university, and 9 unclassified sites). The mean content quality score was 3.75 (range = 0–16; SD = 2.48). Approximately 5% (4.85%) of the sites scored greater than 8 (of 12) on nutrition, physical activity, and behavior. Content quality score varied significantly by type of Web site; the medical, government, or university sites (mean = 4.82, SD = 2.27) and blogs (mean = 6.33, SD = 1.99) had the highest scores. Commercial (mean = 2.37, SD = 2.60) or news/media sites (mean = 3.52, SD = 2.31) had the lowest scores (analysis of variance P < .005). Conclusions. The weight loss information that people were likely to access online was often of substandard quality because most comprehensive and quality Web sites ranked too low in search results. PMID:25122030

Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

PubMed

Seegar, Tom C M; Killingsworth, Lauren B; Saha, Nayanendu; Meyer, Peter A; Patra, Dhabaleswar; Zimmerman, Brandon; Janes, Peter W; Rubinstein, Eric; Nikolov, Dimitar B; Skiniotis, Georgios; Kruse, Andrew C; Blacklow, Stephen C

2017-12-14

Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Counting Active Sites on Titanium Oxide-Silica Catalysts for Hydrogen Peroxide Activation through In Situ Poisoning with Phenylphosphonic Acid

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

Eaton, Todd R.; Boston, Andrew M.; Thompson, Anthony B.

2015-06-04

Quantifying specific active sites in supported catalysts improves our understanding and assists in rational design. Supported oxides can undergo significant structural changes as surface densities increase from site-isolated cations to monolayers and crystallites, which changes the number of kinetically relevant sites. Herein, TiO x domains are titrated on TiO x–SiO 2 selectively with phenylphosphonic acid (PPA). An ex situ method quantifies all fluid-accessible TiO x, whereas an in situ titration during cis-cyclooctene epoxidation provides previously unavailable values for the number of tetrahedral Ti sites on which H 2O 2 activation occurs. We use this method to determine the active sitemore » densities of 22 different catalysts with different synthesis methods, loadings, and characteristic spectra and find a single intrinsic turnover frequency for cis-cyclooctene epoxidation of (40±7) h -1. This simple method gives molecular-level insight into catalyst structure that is otherwise hidden when bulk techniques are used.« less

Habitat characteristics at marten subnivean access sites

USGS Publications Warehouse

Corn, Janelle G.; Raphael, Martin G.

1992-01-01

The occurrence of coarse woody debris (CWD) at sites of subnivean (under snow) access by martens (Martes americana) has not been quantified adequately, and must be better understood to provide suitable winter habitat management for the species. Consequently, we studied subnivean activity of martens in a subalpine forest in southern Wyoming to determine how subnivean space was accessed, and to examine microhabitat characteristics around entry sites. Martens used existing openings in snow, created primarily by logs at low snow depths and by small live spruce and fir trees at greater snow depths. Sites of marten subnivean entry had greater percent cover (P ≤ 0.01) and total volume of CWD (P ≤ 0.01), greater numbers of log layers (all P ≤ 0.02), greater volume of undecayed (P ≤ 0.05) and moderately decayed logs (P ≤ 0.02), less volume of very decayed logs (P ≤ 0.001), and fewer small root masses (P ≤ 0.001) than surrounding forest stands. Provision of sufficient CWD in winter habitat of martens may require specific effort, particularly in managed forests of the central Rocky Mountains.

The IRS and the Internet: new issues for tax-exempt organizations.

PubMed

Griffith, Gerald M

2002-01-01

Tax-exempt healthcare organizations increasingly are using the Internet to provide an inexpensive, easily accessible forum for information exchange, organization publicity, and community-relations programs. A tax-exempt organization that engages in certain activities on its Web site, however, risks losing its tax-exempt status. Such activities may include political messages and lobbying, substantial advertising and other revenue-generating programs, and inappropriate solicitation of charitable contributions. Therefore, providers should carefully monitor all information on their Web sites, including hyperlinks to other Web sites, chat-room and bulletin-board content, and advertisements, to make certain they comply with IRS rules.

Relationship between Use of Online Support Materials and Student Performance in an Introductory Finance Course

ERIC Educational Resources Information Center

Biktimirov, Ernest N.; Klassen, Kenneth J.

2008-01-01

The authors examined the relationship between student online activity, including access to specific course materials, and performance in a traditional face-to-face introductory finance course that a class Web site supported. The authors used 6 measures: (a) total hits, (b) hit consistency, (c) number of unique files that the students accessed, (d)…

A study in usability: redesigning a health sciences library's mobile site.

PubMed

Rosario, Jovy-Anne; Ascher, Marie T; Cunningham, Diana J

2012-01-01

A mobile site redesign was conducted at a medium-sized academic health sciences library with the goal of creating a site that meets the mobile information needs of its users. The redesign phases included (1) needs assessment, (2) usability testing, and (3) site design. The survey results showed that Apple devices were the most prevalent; the most desirable activities performed on a mobile site were searching for articles, accessing full-text articles and e-books, searching databases, and searching the catalog. These activities guided the development of the usability testing tasks and the redesign. All phases were completed within six months, and the total project cost was $50 for incentive purchases. Copyright © Taylor & Francis Group, LLC

Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules.

PubMed

Boron, Ignacio; Bustamante, Juan Pablo; Davidge, Kelly S; Singh, Sandip; Bowman, Lesley Ah; Tinajero-Trejo, Mariana; Carballal, Sebastián; Radi, Rafael; Poole, Robert K; Dikshit, Kanak; Estrin, Dario A; Marti, Marcelo A; Boechi, Leonardo

2015-01-01

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O 2 and • NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify • NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, • NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.

The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes.

PubMed

Jacobs, Jelle; Atkins, Mardelle; Davie, Kristofer; Imrichova, Hana; Romanelli, Lucia; Christiaens, Valerie; Hulselmans, Gert; Potier, Delphine; Wouters, Jasper; Taskiran, Ibrahim I; Paciello, Giulia; González-Blas, Carmen B; Koldere, Duygu; Aibar, Sara; Halder, Georg; Aerts, Stein

2018-06-04

Transcriptional enhancers function as docking platforms for combinations of transcription factors (TFs) to control gene expression. How enhancer sequences determine nucleosome occupancy, TF recruitment and transcriptional activation in vivo remains unclear. Using ATAC-seq across a panel of Drosophila inbred strains, we found that SNPs affecting binding sites of the TF Grainy head (Grh) causally determine the accessibility of epithelial enhancers. We show that deletion and ectopic expression of Grh cause loss and gain of DNA accessibility, respectively. However, although Grh binding is necessary for enhancer accessibility, it is insufficient to activate enhancers. Finally, we show that human Grh homologs-GRHL1, GRHL2 and GRHL3-function similarly. We conclude that Grh binding is necessary and sufficient for the opening of epithelial enhancers but not for their activation. Our data support a model positing that complex spatiotemporal expression patterns are controlled by regulatory hierarchies in which pioneer factors, such as Grh, establish tissue-specific accessible chromatin landscapes upon which other factors can act.

Endovascular Revascularization of Chronically Thrombosed Arteriovenous Fistulas and Grafts for Hemodialysis: A Retrospective Study in 15 Patients With 18 Access Sites

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

Weng Meijui; Chen, Matt Chiung-Yu, E-mail: jjychen@gmail.com; Chi Wenche

2011-04-15

The current study retrospectively evaluated whether endovascular revascularization of chronically thrombosed and long-discarded vascular access sites for hemodialysis was feasible. Technical and clinical success rates, postintervention primary and secondary patency rates, and complications were reported. During a 1-year period, we reviewed a total of 924 interventions performed for dysfunction and/or failed hemodialysis vascular access sites and permanent catheters in 881 patients. In patients whose vascular access-site problems were considered untreatable or were considered treatable with a high risk of failure and access-site abandonment, we attempted to revascularize (resurrect) the chronically occluded and long-discarded (mummy) vascular access sites. We attempted tomore » resurrect a total of 18 mummy access sites (mean age 46.6 {+-} 38.7 months; range 5-144) in 15 patients (8 women and 7 men; mean age 66.2 {+-} 11.5 years; age range 50-85) and had an overall technical success rate of 77.8%. Resurrection failure occurred in 3 fistulas and in 1 straight graft. The clinical success rate was 100% at 2 months after resurrection. In the 14 resurrected vascular access sites, 6 balloon-assisted maturation procedures were required in 5 fistulas; after access-site maturation, a total of 22 interventions were performed to maintain access-site patency. The mean go-through time for successful resurrection procedures was 146.6 {+-} 34.3 min (range 74-193). Postmaturation primary patency rates were 71.4 {+-} 12.1% at 30 days, 57.1 {+-} 13.2% at 60 days, 28.6 {+-} 13.4% at 90 days, and 19 {+-} 11.8% at 180 days. Postmaturation secondary patency rates were 100% at 30, 60, and 90 days and 81.8 {+-} 11.6% at 180 days. There were 2 major complications consisting of massive venous ruptures in 2 mummy access sites during balloon dilation; in both cases, prolonged balloon inflation failed to achieve hemostasis, but percutaneous N-butyl cyanoacrylate glue seal-off was performed successfully. Percutaneous resurrection of mummy vascular access sites for hemodialysis is technically feasible with high clinical success rates. In selected patients, resurrection of mummy access sites provides long-discarded access sites one more chance to be used for hemodialysis in an effort to preserve potential extremity sites for future access-site placement and to prevent long-term catheter indwelling.« less

How Accessible Are Public Libraries' Web Sites? A Study of Georgia Public Libraries

ERIC Educational Resources Information Center

Ingle, Emma; Green, Ravonne A.; Huprich, Julia

2009-01-01

One issue that public librarians must consider when planning Web site design is accessibility for patrons with disabilities. This article reports a study of Web site accessibility of public libraries in Georgia. The focus of the report is whether public libraries use accessible guidelines and standards in making their Web sites accessible. An…

Dive and Discover: Bringing Oceanographic Research into the Classroom and to the General Public

NASA Astrophysics Data System (ADS)

Fornari, D. J.; Fino, D.; Humphris, S. E.; Fruth, L. L.; Dean, S.

2001-12-01

We have developed the "Dive and Discover" web site for use in classrooms and for the general public to provide near real-time, daily access to oceanographic research expeditions, particularly those using deep submergence vehicles operated by Woods Hole Oceanographic Institution. The site was one of five science sites nominated for a 2001 Webby Award, was selected by Scientific American as one of the top five sites in the category of earth and environmental science, and was one of Eisenhower National Clearinghouse's "digital dozen" for science resources. The web site consists of two major components. A series of educational modules provide both general educational information about the oceans and the people that study them, as well as cruise-specific information about the natural systems being studied, the participating scientists, and the data and sample-collecting methodologies and technologies being used. The second component consists of modules that allow access to near real-time updates of the progress of the cruise, images of seafloor features and animals, samples of data being collected and used on board, and general information about life on board. In addition, a Mail Buoy provides e-mail access for students to ask questions of the scientists on board the ship during the course of the expedition. COSI Toledo have a linked Educator's Companion that gives access to COSI project management tips, background information, activities, correlations to national science education standards, assessment tools, and a vast array of resources to assist educators in using the web site. We have worked with teachers and students from all over the United States to test, evaluate, and refine the web site during five cruises in the Pacific and Indian Oceans over the last two years. These cruises focused on various problems associated with mid-ocean ridge volcanism, and the chemical, physical and biological processes associated with seafloor hydrothermal activity. Our intention is that the conceptual approach we have developed will have broad application for marine scientists to promote ocean science education and public outreach in the future.

When roads appear jaguars decline: Increased access to an Amazonian wilderness area reduces potential for jaguar conservation

PubMed Central

Celis, Gerardo; Branch, Lyn C.

2018-01-01

Roads are a main threat to biodiversity conservation in the Amazon, in part, because roads increase access for hunters. We examine how increased landscape access by hunters may lead to cascading effects that influence the prey community and abundance of the jaguar (Panthera onca), the top Amazonian terrestrial predator. Understanding such ecological effects originating from anthropogenic actions is essential for conservation and management of wildlife populations in areas undergoing infrastructure development. Our study was conducted in Yasuní Biosphere Reserve, the protected area with highest potential for jaguar conservation in Ecuador, and an area both threatened by road development and inhabited by indigenous groups dependent upon bushmeat. We surveyed prey and jaguar abundance with camera traps in four sites that differed in accessibility to hunters and used site occupancy and spatially explicit capture-recapture analyses to evaluate prey occurrence and estimate jaguar density, respectively. Higher landscape accessibility to hunters was linked with lower occurrence and biomass of game, particularly white-lipped peccary (Tayassu pecari) and collared peccary (Pecari tajacu), the primary game for hunters and prey for jaguars. Jaguar density was up to 18 times higher in the most remote site compared to the most accessible site. Our results provide a strong case for the need to: 1) consider conservation of large carnivores and other wildlife in policies about road construction in protected areas, 2) coordinate conservation initiatives with local governments so that development activities do not conflict with conservation objectives, and 3) promote development of community-based strategies for wildlife management that account for the needs of large carnivores. PMID:29298311

When roads appear jaguars decline: Increased access to an Amazonian wilderness area reduces potential for jaguar conservation.

PubMed

Espinosa, Santiago; Celis, Gerardo; Branch, Lyn C

2018-01-01

Roads are a main threat to biodiversity conservation in the Amazon, in part, because roads increase access for hunters. We examine how increased landscape access by hunters may lead to cascading effects that influence the prey community and abundance of the jaguar (Panthera onca), the top Amazonian terrestrial predator. Understanding such ecological effects originating from anthropogenic actions is essential for conservation and management of wildlife populations in areas undergoing infrastructure development. Our study was conducted in Yasuní Biosphere Reserve, the protected area with highest potential for jaguar conservation in Ecuador, and an area both threatened by road development and inhabited by indigenous groups dependent upon bushmeat. We surveyed prey and jaguar abundance with camera traps in four sites that differed in accessibility to hunters and used site occupancy and spatially explicit capture-recapture analyses to evaluate prey occurrence and estimate jaguar density, respectively. Higher landscape accessibility to hunters was linked with lower occurrence and biomass of game, particularly white-lipped peccary (Tayassu pecari) and collared peccary (Pecari tajacu), the primary game for hunters and prey for jaguars. Jaguar density was up to 18 times higher in the most remote site compared to the most accessible site. Our results provide a strong case for the need to: 1) consider conservation of large carnivores and other wildlife in policies about road construction in protected areas, 2) coordinate conservation initiatives with local governments so that development activities do not conflict with conservation objectives, and 3) promote development of community-based strategies for wildlife management that account for the needs of large carnivores.

Commissions as information organizations: Meeting the information needs of an electronic society

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

Sevel, F.

1997-11-01

This paper describes how commission-sponsored web sites can effectively meet electronic information needs. Demographics of internet users are presented and analyzed. Online activities and user access data are also described. The implications of the characteristics of internet users for commission-sponsored web sites are discussed, and guidelines for determining marketing objectives are presented.

Geographic approaches to quantifying the risk environment: a focus on syringe exchange program site access and drug-related law enforcement activities

PubMed Central

Cooper, Hannah LF; Bossak, Brian; Tempalski, Barbara; Des Jarlais, Don C.; Friedman, Samuel R.

2009-01-01

The concept of the “risk environment” – defined as the “space … [where] factors exogenous to the individual interact to increase the chances of HIV transmission” – draws together the disciplines of public health and geography. Researchers have increasingly turned to geographic methods to quantify dimensions of the risk environment that are both structural and spatial (e.g., local poverty rates). The scientific power of the intersection between public health and geography, however, has yet to be fully mined. In particular, research on the risk environment has rarely applied geographic methods to create neighbourhood-based measures of syringe exchange programs (SEPs) or of drug-related law enforcement activities, despite the fact that these interventions are widely conceptualized as structural and spatial in nature and are two of the most well-established dimensions of the risk environment. To strengthen research on the risk environment, this paper presents a way of using geographic methods to create neighbourhood-based measures of (1) access to SEP sites and (2) exposure to drug-related arrests, and then applies these methods to one setting (New York City). NYC-based results identified substantial cross-neighbourhood variation in SEP site access and in exposure to drug-related arrest rates (even within the subset of neighbourhoods nominally experiencing the same drug-related police strategy). These geographic measures – grounded as they are in conceptualizations of SEPs and drug-related law enforcement strategies – can help develop new arenas of inquiry regarding the impact of these two dimensions of the risk environment on injectors’ health, including exploring whether and how neighbourhood-level access to SEP sites and exposure to drug-related arrests shape a range of outcomes among local injectors. PMID:18963907

Effectiveness of off-line and web-based promotion of health information web sites.

PubMed

Jones, Craig E; Pinnock, Carole B

2002-01-01

The relative effectiveness of off-line and web-based promotional activities in increasing the use of health information web sites by target audiences were compared. Visitor sessions were classified according to their method of arrival at the site (referral) as external web site, search engine, or "no referrer" (i.e., visitor arriving at the site by inputting URL or using bookmarks). The number of Australian visitor sessions correlated with no referrer referrals but not web site or search-engine referrals. Results showed that the targeted consumer group is more likely to access the web site as a result of off-line promotional activities. The properties of target audiences likely to influence the effectiveness of off-line versus on-line promotional strategies include the size of the Internet using population of the target audience, their proficiency in the use of the Internet, and the increase in effectiveness of off-line promotional activities when applied to locally defined target audiences.

Volcanology Curricula Development Aided by Online Educational Resource

NASA Astrophysics Data System (ADS)

Poland, Michael P.; van der Hoeven Kraft, Katrien J.; Teasdale, Rachel

2011-03-01

Using On-Line Volcano Monitoring Data in College and University Courses: The Volcano Exploration Project: Pu`u `Ō`ō (VEPP); Hawaii Volcanoes National Park, Hawaii, 26-30 July 2010; Volcanic activity is an excellent hook for engaging college and university students in geoscience classes. An increasing number of Internet-accessible real-time and near-real time volcano monitoring data are now available and constitute an important resource for geoscience education; however, relatively few data sets are comprehensive, and many lack background information to aid in interpretation. In response to the need for organized, accessible, and well-documented volcano education resources, the U.S. Geological Survey's Hawaiian Volcano Observatory (HVO), in collaboration with NASA and the University of Hawai`i at Manoa, established the Volcanoes Exploration Project: Pu`u `Ō`ō (VEPP). The VEPP Web site (http://vepp.wr.usgs.gov) is an educational resource that provides access, in near real time, to geodetic, seismic, and geologic data from the active Pu`u `Ō`ō eruptive vent on Kilauea volcano, Hawaii, along with background and context information. A strength of the VEPP site is the common theme of the Pu`u `Ō`ō eruption, which allows the site to be revisited multiple times to demonstrate different principles and integrate many aspects of volcanology.

Volcanology curricula development aided by online educational resource

USGS Publications Warehouse

Poland, Michael P.; Van Der Hoeven, Kraft; Teasdale, R.

2011-01-01

Using On-Line Volcano Monitoring Data in College and University Courses: The Volcano Exploration Project: Pu`u `Ō`ō (VEPP); Hawaii Volcanoes National Park, Hawaii, 26–30 July 2010; Volcanic activity is an excellent hook for engaging college and university students in geoscience classes. An increasing number of Internet-accessible real-time and near–real time volcano monitoring data are now available and constitute an important resource for geoscience education; however, relatively few data sets are comprehensive, and many lack background information to aid in interpretation. In response to the need for organized, accessible, and well-documented volcano education resources, the U.S. Geological Survey's Hawaiian Volcano Observatory (HVO), in collaboration with NASA and the University of Hawai`i at Manoa, established the Volcanoes Exploration Project: Pu`u `Ō`ō (VEPP). The VEPP Web site (http://vepp.wr.usgs.gov) is an educational resource that provides access, in near real time, to geodetic, seismic, and geologic data from the active Pu`u `Ō`ō eruptive vent on Kilauea volcano, Hawaii, along with background and context information. A strength of the VEPP site is the common theme of the Pu`u `Ō`ō eruption, which allows the site to be revisited multiple times to demonstrate different principles and integrate many aspects of volcanology.

HealtheSteps™ Study Protocol: a pragmatic randomized controlled trial promoting active living and healthy lifestyles in at-risk Canadian adults delivered in primary care and community-based clinics.

PubMed

Gill, Dawn P; Blunt, Wendy; Bartol, Cassandra; Pulford, Roseanne W; De Cruz, Ashleigh; Simmavong, P Karen; Gavarkovs, Adam; Newhouse, Ian; Pearson, Erin; Ostenfeldt, Bayley; Law, Barbi; Karvinen, Kristina; Moffit, Pertice; Jones, Gareth; Watson, Cori; Zou, Guangyong; Petrella, Robert J

2017-02-07

Physical inactivity is one of the leading causes of chronic disease in Canadian adults. With less than 50% of Canadian adults reaching the recommended amount of daily physical activity, there is an urgent need for effective programs targeting this risk factor. HealtheSteps™ is a healthy lifestyle prescription program, developed from an extensive research base to address risk factors for chronic disease such as physical inactivity, sedentary behaviour and poor eating habits. HealtheSteps™ participants are provided with in-person lifestyle coaching and access to eHealth technologies delivered in community-based primary care clinics and health care organizations. To determine the effectiveness of Healthesteps™, we will conduct a 6-month pragmatic randomized controlled trial with integrated process and economic evaluations of HealtheSteps™ in 5 clinic settings in Southwestern Ontario. 110 participants will be individually randomized (1:1; stratified by site) to either the intervention (HealtheSteps™ program) or comparator (Wait-list control). There are 3 phases of the HealtheSteps™ program, lasting 6 months each. The active phase consists of bi-monthly in-person coaching with access to a full suite of eHealth technology supports. During the maintenance phase I, the in-person coaching will be removed, but participants will still have access to the full suite of eHealth technology supports. In the final stage, maintenance phase II, access to the full suite of eHealth technology supports is removed and participants only have access to publicly available resources and tools. This trial aims to determine the effectiveness of the program in increasing physical activity levels and improving other health behaviours and indicators, the acceptability of the HealtheSteps™ program, and the direct cost for each person participating in the program as well as the costs associated with delivering the program at the different community sites. These results will inform future optimization and scaling up of the program into additional community-based primary care sites. NCT02413385 (Clinicaltrials.gov). Date Registered: April 6, 2015.

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.

25 CFR 170.121 - What is a cultural access road?

Code of Federal Regulations, 2014 CFR

2014-04-01

... example: (1) Sacred and medicinal sites; (2) Gathering medicines or materials such as grasses for basket weaving; or (3) Other traditional activities, including, but not limited to, subsistence hunting, fishing...

25 CFR 170.121 - What is a cultural access road?

Code of Federal Regulations, 2011 CFR

2011-04-01

... example: (1) Sacred and medicinal sites; (2) Gathering medicines or materials such as grasses for basket weaving; or (3) Other traditional activities, including, but not limited to, subsistence hunting, fishing...

25 CFR 170.121 - What is a cultural access road?

Code of Federal Regulations, 2013 CFR

2013-04-01

... example: (1) Sacred and medicinal sites; (2) Gathering medicines or materials such as grasses for basket weaving; or (3) Other traditional activities, including, but not limited to, subsistence hunting, fishing...

25 CFR 170.121 - What is a cultural access road?

Code of Federal Regulations, 2012 CFR

2012-04-01

... example: (1) Sacred and medicinal sites; (2) Gathering medicines or materials such as grasses for basket weaving; or (3) Other traditional activities, including, but not limited to, subsistence hunting, fishing...

Automated Rocket Propulsion Test Management

NASA Technical Reports Server (NTRS)

Walters, Ian; Nelson, Cheryl; Jones, Helene

2007-01-01

The Rocket Propulsion Test-Automated Management System provides a central location for managing activities associated with Rocket Propulsion Test Management Board, National Rocket Propulsion Test Alliance, and the Senior Steering Group business management activities. A set of authorized users, both on-site and off-site with regard to Stennis Space Center (SSC), can access the system through a Web interface. Web-based forms are used for user input with generation and electronic distribution of reports easily accessible. Major functions managed by this software include meeting agenda management, meeting minutes, action requests, action items, directives, and recommendations. Additional functions include electronic review, approval, and signatures. A repository/library of documents is available for users, and all items are tracked in the system by unique identification numbers and status (open, closed, percent complete, etc.). The system also provides queries and version control for input of all items.

Interrupted breeding in a songbird migrant triggers development of nocturnal locomotor activity.

PubMed

Mukhin, Andrey; Kobylkov, Dmitry; Kishkinev, Dmitry; Grinkevich, Vitaly

2018-04-03

Long-distance avian migrants, e.g. Eurasian reed warblers (Acrocephalus scirpaceus), can precisely schedule events of their annual cycle. However, the proximate mechanisms controlling annual cycle and their interplay with environmental factors are poorly understood. We artificially interrupted breeding in reed warblers by bringing them into captivity and recording birds' locomotor activity for 5-7 days. Over this time, most of the captive birds gradually developed nocturnal locomotor activity not observed in breeding birds. When the birds were later released and radio-tracked, the individuals with highly developed caged activity performed nocturnal flights. We also found that reed warblers kept indoors without access to local cues developed a higher level of nocturnal activity compared to the birds kept outdoors with an access to the familiar environment. Also, birds translocated from a distant site (21 km) had a higher motivation to fly at night-time after release compared to the birds captured within 1 km of a study site. Our study suggests that an interrupted breeding triggers development of nocturnal locomotor activity in cages, and the level of activity is correlated with motivation to perform nocturnal flights in the wild, which can be restrained by familiar environment.

Quantifying accessible sites and reactivity on titania–silica (photo)catalysts: Refining TOF calculations

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

Eaton, Todd R.; Campos, Michael P.; Gray, Kimberly A.

2014-01-01

It can be difficult to determine the number of active atoms accessible to the fluid phase in mixed oxide catalysts, as required for obtaining true turnover frequencies (TOF). Here, we utilize the selective titration of surface Ti atoms with phenylphosphonic acid (PPA) on TiO 2–SiO 2 materials to estimate the number of reactant-accessible sites. TiO 2–SiO 2 composites were synthesized over a range of Ti loadings from grafting of titanocene dichloride (Cp 2TiCl 2) or tetraethoxy orthotitanate (TEOT) on SiO 2 and sol–gel co-hydrolysis of Si and Ti alkoxides. The materials were characterized by DRUV–vis, XRD, BET, and XANES. Despitemore » the significant morphological and electronic differences, materials prepared by Cp 2TiCl 2 and TEOT yielded a near-constant TOF of 0.14 h -1 (±0.04) across Ti loadings, for benzyl alcohol photooxidation, when normalizing rates by sites titrated by PPA. The fraction of Ti atoms titrated by PPA was strongly dependent on synthesis method and surface density. PPA titration and benzyl alcohol photooxidation may be useful measures of surface accessibility in other supported oxides.« less

Accuracy of weight loss information in Spanish search engine results on the internet.

PubMed

Cardel, Michelle I; Chavez, Sarah; Bian, Jiang; Peñaranda, Eribeth; Miller, Darci R; Huo, Tianyao; Modave, François

2016-11-01

To systematically assess the quality of online information related to weight loss that Spanish speakers in the U.S. are likely to access. This study evaluated the accessibility and quality of information for websites that were identified from weight loss queries in Spanish and compared this with previously published results in English. The content was scored with respect to five dimensions: nutrition, physical activity, behavior, pharmacotherapy, and surgical recommendations. Sixty-six websites met eligibility criteria (21 commercial, 24 news/media, 10 blogs, 0 medical/government/university, 11 unclassified sites). Of 16 possible points, mean content quality score was 3.4 (SD = 2.0). Approximately 1.5% of sites scored greater than 8 (out of 12) on nutrition, physical activity, and behavior. Unsubstantiated claims were made on 94% of the websites. Content quality scores varied significantly by type of website (P < 0.0001) with unclassified websites scoring the highest (mean = 6.3, SD = 1.4) and blogs scoring the lowest (mean = 2.2, SD = 1.2). All content quality scores were lower for Spanish websites relative to English websites. Weight loss information accessed in Spanish Web searches is suboptimal and relatively worse than weight loss information accessed in English, suggesting that U.S. Spanish speakers accessing weight loss information online may be provided with incomplete and inaccurate information. © 2016 The Obesity Society.

The Design, Synthesis, and Characterization of Open Sites on Metal Clusters

NASA Astrophysics Data System (ADS)

Nigra, Michael Mark

Coordinatively unsaturated corner and edge atoms have been hypothesized to have the highest activity of sites responsible for many catalytic reactions on a metal surface. Recent studies have validated this hypothesis in varied reaction systems. However, quantification of different types of coordinatively unsaturated sites, and elucidation of their individual catalytic rates has remained a largely unresolved challenge when understanding catalysis on metal surfaces. Yet such structure-function knowledge would be invaluable to the design of more active and selective metal-surface catalysts in the future. I investigated the catalytic contributions of undercoordinated sites such as corner and edge atoms are investigated in a model reaction system using organic ligands bound to the gold nanoparticle surface. The catalyst consisted of 4 nm gold nanoparticles on a metal oxide support, using resazurin to resorufin as a model reaction system. My results demonstrate that in this system, corner atom sites are the most undercoordinated sites, and are over an order of magnitude more active when compared to undercoordinated edge atom sites, while terrace sites remain catalytically inactive for the reduction reaction of resazurin to resorufin. Catalytic activity has been also demonstrated for calixarene-bound gold nanoparticles using the reduction of 4-nitrophenol. With the 4-nitrophenol reduction reaction, a comparative study was undertaken to compare calixarene phosphine and calixarene thiol bound 4 nm gold particles. The results of the study suggested that a leached site was responsible for catalysis and not sites on the original gold nanoparticles. Future experiments with calixarene bound gold clusters could investigate ligand effects in reactions where the active site is not a leached or aggregated gold species, possibly in oxidation reactions, where electron-rich gold is hypothesized to be a good catalyst. The results that emphasize the enhanced catalytic activity of undercoordinated sites led me to synthesize small gold clusters consisting of a high fraction of coordinatively unsaturated open sites. This was enabled through an approach that utilized bulky calix[4]arene ligands that are bound to a gold core. Since the size of the calix[4]arene ligand is commensurate with the size of the gold cluster core, the calix[4]arene ligand does not pack closely together on the gold cluster surface. This in turn results in areas of accessible gold atom sites between ligands. Additionally, these calix[4]arene ligands prevent cluster aggregation and electronically tune the gold core in a manner conceptually similar to enzymes affecting reactivity through organic side-chains acting as ligands. I quantified the number of open sites that result from this packing problem on the gold cluster surface, using fluorescence probe chemisorption experiments. The results of these chemisorption measurements support the mechanical model of accessibility whereby accessibility is not dependent on the identity of the functional group, whether it be calixarene phosphines or N-heterocyclic carbenes, bound to the gold surface, but rather to the relative radii of curvature of bound ligands and the gold cluster core. Additional materials characterization was completed with transmission electron microscopy in both bright-field imaging of zeolites, in MCM-22 and delaminated ITQ-2 and UCB-1 materials, and in dark field imaging of glucan coatings on oxide particles. These materials could prove to be interesting materials as to use as supports for the calixarene-bound metal clusters described above or for other metal clusters.

Social Networks Use, Loneliness and Academic Performance among University Students

ERIC Educational Resources Information Center

Stankovska, Gordana; Angelkovska, Slagana; Grncarovska, Svetlana Pandiloska

2016-01-01

The world is extensively changed by Social Networks Sites (SNSs) on the Internet. A large number of children and adolescents in the world have access to the internet and are exposed to the internet at a very early age. Most of them use the Social Networks Sites with the purpose of exchanging academic activities and developing a social network all…

Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes

PubMed Central

Taylor, Benjamin JM; Wu, Yee Ling; Rada, Cristina

2014-01-01

Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral infection. Improper access to the genome leads to translocations and mutations in B cells and contributes to the mutation landscape in cancer, such as kataegis. It remains unclear how deaminases access double stranded genomes and whether off-target mutations favor certain loci, although transcription and opportunistic access during DNA repair are thought to play a role. In yeast, AID and the catalytic domain of APOBEC3G preferentially mutate transcriptionally active genes within narrow regions, 110 base pairs in width, fixed at RNA polymerase initiation sites. Unlike APOBEC3G, AID shows enhanced mutational preference for small RNA genes (tRNAs, snoRNAs and snRNAs) suggesting a putative role for RNA in its recruitment. We uncover the high affinity of the deaminases for the single stranded DNA exposed by initiating RNA polymerases (a DNA configuration reproduced at stalled polymerases) without a requirement for specific cofactors. DOI: http://dx.doi.org/10.7554/eLife.03553.001 PMID:25237741

Cytochrome p450 architecture and cysteine nucleophile placement impact raloxifene-mediated mechanism-based inactivation.

PubMed

VandenBrink, Brooke M; Davis, John A; Pearson, Josh T; Foti, Robert S; Wienkers, Larry C; Rock, Dan A

2012-11-01

The propensity for cytochrome P450 (P450) enzymes to bioactivate xenobiotics is governed by the inherent chemistry of the xenobiotic itself and the active site architecture of the P450 enzyme(s). Accessible nucleophiles in the active site or egress channels of the P450 enzyme have the potential of sequestering reactive metabolites through covalent modification, thereby limiting their exposure to other proteins. Raloxifene, a drug known to undergo CYP3A-mediated reactive metabolite formation and time-dependent inhibition in vitro, was used to explore the potential for bioactivation and enzyme inactivation of additional P450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5). Every P450 tested except CYP2E1 was capable of raloxifene bioactivation, based on glutathione adduct formation. However, raloxifene-mediated time-dependent inhibition only occurred in CYP2C8 and CYP3A4. Comparable inactivation kinetics were achieved with K(I) and k(inact) values of 0.26 μM and 0.10 min(-1) and 0.81 μM and 0.20 min(-1) for CYP2C8 and CYP3A4, respectively. Proteolytic digests of CYP2C8 and CYP3A4 Supersomes revealed adducts to Cys225 and Cys239 for CYP2C8 and CYP3A4, respectively. For each P450 enzyme, proposed substrate/metabolite access channels were mapped and active site cysteines were identified, which revealed that only CYP2C8 and CYP3A4 possess accessible cysteine residues near the active site cavities, a result consistent with the observed kinetics. The combined data suggest that the extent of bioactivation across P450 enzymes does not correlate with P450 inactivation. In addition, multiple factors contribute to the ability of reactive metabolites to form apo-adducts with P450 enzymes.

Identification of protein–protein interfaces by decreased amide proton solvent accessibility

PubMed Central

Mandell, Jeffrey G.; Falick, Arnold M.; Komives, Elizabeth A.

1998-01-01

Matrix-assisted laser desorption ionization–time-of-flight mass spectrometry was used to identify peptic fragments from protein complexes that retained deuterium under hydrogen exchange conditions due to decreased solvent accessibility at the interface of the complex. Short deuteration times allowed preferential labeling of rapidly exchanging surface amides so that primarily solvent accessibility changes and not conformational changes were detected. A single mass spectrum of the peptic digest mixture was analyzed to determine the deuterium content of all proteolytic fragments of the protein. The protein–protein interface was reliably indicated by those peptides that retained more deuterons in the complex compared with control experiments in which only one protein was present. The method was used to identify the kinase inhibitor [PKI(5–24)] and ATP-binding sites in the cyclic-AMP-dependent protein kinase. Three overlapping peptides identified the ATP-binding site, three overlapping peptides identified the glycine-rich loop, and two peptides identified the PKI(5–24)-binding site. A complex of unknown structure also was analyzed, human α-thrombin bound to an 83-aa fragment of human thrombomodulin [TMEGF(4–5)]. Five peptides from thrombin showed significantly decreased solvent accessibility in the complex. Three peptides identified the anion-binding exosite I, confirming ligand competition experiments. Two peptides identified a new region of thrombin near the active site providing a potential mechanism of how thrombomodulin alters thrombin substrate specificity. PMID:9843953

Measuring Air Quality in a Construction Site Biotope Using the AQM-65 Analyser

NASA Astrophysics Data System (ADS)

Ioana-Alina, Creţan; Nicoleta, Nemeș

2017-10-01

Activities related to the execution of construction works often exert pressure on the quality of environmental factors in adjacent habitat. In various stages of realization of the works if is the opening of the building site and access roads, borrow pits and the storage, or the construction itself, all the related activities will cause harm in various degrees of vegetation on the construction site and its surroundings. Large areas are rendered non-productive and, although they should be restored for use in the same place or elsewhere, sometimes they can lose their natural habitat baseline. The paper is presenting a case study of air quality monitoring using the AQM 65 analyser for a construction site located near Timisoara locality, Timis County, Romania.

Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules

PubMed Central

Davidge, Kelly S; Singh, Sandip; Bowman, Lesley AH; Tinajero-Trejo, Mariana; Carballal, Sebastián; Radi, Rafael; Poole, Robert K; Dikshit, Kanak; Estrin, Dario A; Marti, Marcelo A; Boechi, Leonardo

2015-01-01

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O 2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site. PMID:26478812

Innovative E-portal for prevention and therapeutic programme for treatment of the obesity and overweight in health-tourism

NASA Astrophysics Data System (ADS)

Zuzda, Jolanta G.; Półjanowicz, Wiesław; Latosiewicz, Robert; Borkowski, Piotr; Bierkus, Mirosław; Moska, Owidiusz

2017-11-01

Modern technologies enable overweight and obesity people to enjoy physical activity. We have developed electronic portal containing rotational exercises useful in fight against those disorders. Easy access is provided with QR codes placed on web-site and simply accessed with electronic personal equipment (smartphones). QR codes can also be printed and hanged in different places of health tourism facilities.

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

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.

A prototype of Virtual Observatory access for planetary data in the framework of Europlanet-RI/IDIS

NASA Astrophysics Data System (ADS)

Gangloff, M.; Cecconi, B.; Bourrel, N.; Jacquey, C.; Le Sidaner, P.; Berthier, J.; André, N.; Pallier, E.; Erard, S.; Aboudarham, J.; Chanteur, G. M.; Capria, M. T.; Khodachenko, M.; Manaud, N.; Schmidt, W.; Schmitt, B.; Topf, F.; Trautan, F.; Sarkissian, A.

2011-12-01

Europlanet RI is a four-year project supported by the European Union under the Seventh Framework Programme. Launched in January 2009, it is an Integrated Infrastructure Initiative, ie. A combination of Networking Activities, Transnational Access Activities and Joint Research Activities. The Networking Activities aim at further fostering a culture of cooperation in the field of Planetary Sciences. The objective of the Transnational Access Activities is to provide transnational access to a range of laboratory and field site facilities tailored to the needs of planetary research and on-line access to the available planetary science data, information and software tools, through the IDIS e-service. The overall aim of the Joint Research Activities (JRA) is to improve the services provided by the ensemble of Transnational Access Activities. In EuroPlaNet-RI, JRA4 must prepare essential tools for IDIS (Integrated and Distributed Information Service) allowing the planetary science community to interrogate some selected data centres, access and process data and visualize the results. This is the first step towards a Planetary Virtual Observatory. The first requirement for different data centres to be able to operate together collectively is adequate standardization. In particular a common description of data and services is essential. This is why the major part of JRA4/Task2 activity is focussing on data models, associated dictionnaries, and protocols to exchange queries. A specific data model is being developed for IDIS, associated with the PDAP protocol, a standard defined by the IPDA (International Planetary Data Alliance) The scope of this prototype is to demonstrate the capabilities of the IDIS Data Model, and the PDAP protocol to search and retrieve data in the wide topical planetology context.

More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature

PubMed Central

Ladunga, Istvan

2007-01-01

Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at . PMID:17169992

Personal computer versus personal computer/mobile device combination users' preclinical laboratory e-learning activity.

PubMed

Kon, Haruka; Kobayashi, Hiroshi; Sakurai, Naoki; Watanabe, Kiyoshi; Yamaga, Yoshiro; Ono, Takahiro

2017-11-01

The aim of the present study was to clarify differences between personal computer (PC)/mobile device combination and PC-only user patterns. We analyzed access frequency and time spent on a complete denture preclinical website in order to maximize website effectiveness. Fourth-year undergraduate students (N=41) in the preclinical complete denture laboratory course were invited to participate in this survey during the final week of the course to track login data. Students accessed video demonstrations and quizzes via our e-learning site/course program, and were instructed to view online demonstrations before classes. When the course concluded, participating students filled out a questionnaire about the program, their opinions, and devices they had used to access the site. Combination user access was significantly more frequent than PC-only during supplementary learning time, indicating that students with mobile devices studied during lunch breaks and before morning classes. Most students had favorable opinions of the e-learning site, but a few combination users commented that some videos were too long and that descriptive answers were difficult on smartphones. These results imply that mobile devices' increased accessibility encouraged learning by enabling more efficient time use between classes. They also suggest that e-learning system improvements should cater to mobile device users by reducing video length and including more short-answer questions. © 2016 John Wiley & Sons Australia, Ltd.

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

Holloway, Lawrence E.; Qu, Zhihua; Mohr-Schroeder, Margaret J.

In this study, we consider collaborative power systems education through the FEEDER consortium. To increase students' access to power engineering educational content, the consortium of seven universities was formed. A framework is presented to characterize different collaborative education activities among the universities. Three of these approaches of collaborative educational activities are presented and discussed. These include 1) cross-institutional blended courses ("MS-MD''); 2) cross-institutional distance courses ("SS-MD''); and 3) single-site special experiential courses and concentrated on-site programs available to students across consortium institutions ("MS-SD''). As a result, this paper presents the advantages and disadvantages of each approach.

Use of StreamStats in the Upper French Broad River Basin, North Carolina: A Pilot Water-Resources Web Application

USGS Publications Warehouse

Wagner, Chad R.; Tighe, Kirsten C.; Terziotti, Silvia

2009-01-01

StreamStats is a Web-based Geographic Information System (GIS) application that was developed by the U.S. Geological Survey (USGS) in cooperation with Environmental Systems Research Institute, Inc. (ESRI) to provide access to an assortment of analytical tools that are useful for water-resources planning and management. StreamStats allows users to easily obtain streamflow statistics, basin characteristics, and descriptive information for USGS data-collection sites and selected ungaged sites. StreamStats also allows users to identify stream reaches upstream and downstream from user-selected sites and obtain information for locations along streams where activities occur that can affect streamflow conditions. This functionality can be accessed through a map-based interface with the user's Web browser or through individual functions requested remotely through other Web applications.

A survey of whitewater recreation impacts along five West Virginia rivers

USGS Publications Warehouse

Leung, Y.-F.; Marion, J.L.

1998-01-01

Results are reported from an assessment of whitewater river recreation impacts at river accesses and recreation sites along five West Virginia rivers: the New, Gauley, Cheat, Tygart, and Shenandoah. Procedures were developed and applied to assess resource conditions on 24 river access roads, 68 river accesses, and 151 recreation sites. The majority of river accesses and recreation sites are located on the New and Gauley rivers, which account for most of the state?s whitewater recreation use. Site conditions are variable. While some river accesses and sites are situated on resistant rocky substrates, many are poorly designed and/or located on erodible soil and sand substrates. Recreation site sizes and other areal measures of site disturbance are quite large, coincident with the large group sizes associated with commercially outfitted whitewater rafting trips. Recommendations are offered for managing river accesses and sites and whitewater visitation and the selection of indicators and standards as part of a Limits of Acceptable Change management process. Procedures and recommendations for continued visitor impact monitoring are also offered.

40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

Code of Federal Regulations, 2011 CFR

2011-07-01

... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

Code of Federal Regulations, 2013 CFR

2013-07-01

... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

Code of Federal Regulations, 2012 CFR

2012-07-01

... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

40 CFR 1400.8 - Access to off-site consequence analysis information by Federal government officials.

Code of Federal Regulations, 2014 CFR

2014-07-01

... analysis information by Federal government officials. 1400.8 Section 1400.8 Protection of Environment... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.8 Access to off-site consequence analysis information by Federal...

40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL... INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.3 Public access to paper copies of off-site consequence analysis information. (a) General. The Administrator and the...

Enabling Remote Activity: Using mobile technology for remote participation in geoscience fieldwork

NASA Astrophysics Data System (ADS)

Davies, Sarah; Collins, Trevor; Gaved, Mark; Bartlett, Jessica; Valentine, Chris; McCann, Lewis

2010-05-01

Field-based activities are regarded as essential to the development of a range of professional and personal skills within the geosciences. Students enjoy field activities, preferring these to learning with simulations (Spicer and Stratford 2001), and these improve deeper learning and understanding (Kern and Carpenter, 1984; Elkins and Elkins, 2007). However, some students find it difficult to access these field-based learning opportunities. Field sites may be remote and often require travel across uneven, challenging or potentially dangerous terrain. Mobility-impaired students are particularly limited in their opportunities to participate in field-based learning activities and, as higher education institutions have a responsibility to provide inclusive opportunities for students (UK Disability Discrimination Act 1995, UK Special Education Needs and Disability Rights Act 2001), the need for inclusive fieldwork learning is being increasingly recognised. The Enabling Remote Activity (ERA) project has been investigating how mobile communications technologies might allow field learning experiences to be brought to students who would otherwise find it difficult to participate, and also to enhance activities for all participants. It uses a rapidly deployable, battery-powered wireless network to transmit video, audio, and high resolution still images to connect participants at an accessible location with participants in the field. Crucially, the system uses a transient wireless network, allowing multiple locations to be explored during a field visit, and for plans to be changed dynamically if required. Central to the concept is the requirement for independent investigative learning: students are enabled to participate actively in the learning experience and to direct the investigations, as opposed to being simply remote viewers of the experience. Two ways of using the ERA system have been investigated: remote access and collaborative groupwork. In 2006 and 2008 remote access was used to enable mobility-impaired students to take part in and complete a field course. This involved connecting the student in an accessible vehicle located close to the field site, via a wireless network, to a geologist in the field. The geologist worked alongside the general body of students and the field tutor as each geological site was investigated. Two-way communications allowed the student to guide the geologist to provide video panoramas of the area, to select areas of interest for further study and to obtain high resolution images of specific points. The students were able to work through the field activities alongside the rest of the student group. A collaborative groupwork trial (2007) was used to connect two groups of students; one in an accessible laboratory, the other at a field site. Traditionally, students collect data in the field and analyze it on return to the laboratory; this system proposes a more rapid collection and analysis procedure, with information being transmitted between sites with field and laboratory participants having their own distinct, significant roles within the learning activity. This project recently received an award at the 2008 Handheld Learning Conference and a HEFCE sponsored Open University Teaching Award. In contrast to the use of ‘virtual fieldwork' that aims to provide simulations or a resource for a student to use, the focus of this project is on how technology can be used to support actual fieldwork activities. This approach has been trialled now over three field seasons, with students using the system to remotely participate in fieldwork activities. Interviews with tutors and students have shown that this was perceived as valuable and allowed participants to achieve the learning objectives of the course alongside their peers. The challenges of remote fieldwork concern the co-ordination of students' activities, the integration of remote and field activities and practical issues of lightweight, easy-to-use, robust technologies and the provision of a reliable communications network. References Elkins, J.T. & Elkins, N.M.L. (2007) Teaching geology in the field: significant geoscience concept gains in entirely field-based introductory geology courses. Journal of Geoscience Education, 55 (2), 126-132. Kern, E. and Carpenter, J. (2004). Enhancement of student values, interests and attitudes in Earth Science through a field-oriented approach. Journal of Geological Education, 32 (5), 299-305. Spicer, J. I. and Stratford, J. (2001) Student perceptions of a virtual field trip to replace a real field trip. Journal of Computer Assisted Learning, 17(4), 345-354.

Secure web-based access to radiology: forms and databases for fast queries

NASA Astrophysics Data System (ADS)

McColl, Roderick W.; Lane, Thomas J.

2002-05-01

Currently, Web-based access to mini-PACS or similar databases commonly utilizes either JavaScript, Java applets or ActiveX controls. Many sites do not permit applets or controls or other binary objects for fear of viruses or worms sent by malicious users. In addition, the typical CGI query mechanism requires several parameters to be sent with the http GET/POST request, which may identify the patient in some way; this in unacceptable for privacy protection. Also unacceptable are pages produced by server-side scripts which can be cached by the browser, since these may also contain sensitive information. We propose a simple mechanism for access to patient information, including images, which guarantees security of information, makes it impossible to bookmark the page, or to return to the page after some defined length of time. In addition, this mechanism is simple, therefore permitting rapid access without the need to initially download an interface such as an applet or control. In addition to image display, the design of the site allows the user to view and save movies of multi-phasic data, or to construct multi-frame datasets from entire series. These capabilities make the site attractive for research purposes such as teaching file preparation.

Preorganization of molecular binding sites in designed diiron proteins.

PubMed

Maglio, Ornella; Nastri, Flavia; Pavone, Vincenzo; Lombardi, Angela; DeGrado, William F

2003-04-01

De novo protein design provides an attractive approach to critically test the features that are required for metalloprotein structure and function. Previously we designed and crystallographically characterized an idealized dimeric model for the four-helix bundle class of diiron and dimanganese proteins [Dueferri 1 (DF1)]. Although the protein bound metal ions in the expected manner, access to its active site was blocked by large bulky hydrophobic residues. Subsequently, a substrate-access channel was introduced proximal to the metal-binding center, resulting in a protein with properties more closely resembling those of natural enzymes. Here we delineate the energetic and structural consequences associated with the introduction of these binding sites. To determine the extent to which the binding site was preorganized in the absence of metal ions, the apo structure of DF1 in solution was solved by NMR and compared with the crystal structure of the di-Zn(II) derivative. The overall fold of the apo protein was highly similar to that of the di-Zn(II) derivative, although there was a rotation of one of the helices. We also examined the thermodynamic consequences associated with building a small molecule-binding site within the protein. The protein exists in an equilibrium between folded dimers and unfolded monomers. DF1 is a highly stable protein (K(diss) = 0.001 fM), but the dissociation constant increases to 0.6 nM (deltadeltaG = 5.4 kcalmol monomer) as the active-site cavity is increased to accommodate small molecules.

Recovery Efficiency Test Project: Phase 1, Activity report

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

Overbey, W.K. Jr.; Wilkins, D.W.; Keltch, B.

1988-04-01

This report is the second volume of the Recovery Efficiency Test Phase I Report of Activities. Volume 1 covered selection, well planning, drilling, coring, logging and completion operations. This volume reports on well testing activities, reclamation activities on the drilling site and access roads, and the results of physical and mechanical properties tests on the oriented core material obtained from a horizontal section of the well. 3 refs., 21 figs., 10 tabs.

The AAS Working Group on Accessibility and Disability (WGAD): Year 1 Highlights

NASA Astrophysics Data System (ADS)

Aarnio, Alicia; Monkiewicz, Jacqueline; Murphy, Nicholas Arnold; Nordhaus, Jason; Tuttle, Sarah E.

2017-01-01

The AAS Working Group on Accessibility and Disability (WGAD) was formed in January of 2016 with the express purpose of seeking equity of opportunity and building inclusive practices for disabled astronomers at all career stages. In our first year, the WGAD has been actively developing resources and the online infrastructure for the dissemination of information and engagement with the astronomy community. Our official WGAD website has gone live, and we have used both the access: astronomy google group and blog to discuss specific issues of disability justice and to raise awareness for less-discussed barriers to access. The WGAD has developed relationships and collaboration with AAS inclusion committees (SGMA, CSMA, CSWA) so our work can recognize and address the intersections of identity astronomers occupy. In this presentation, we summarize our year one activities, focusing on our recently developed set of recommendations for journal accessibility to ensure everyone can engage with journal content and navigate the submission process. We will also discuss ongoing and future endeavors: a best practices guide for accessibility to be available via our website, and a site visit program.

Access channels to the buried active site control substrate specificity in CYP1A P450 enzymes.

PubMed

Urban, Philippe; Truan, Gilles; Pompon, Denis

2015-04-01

A cytochrome P450 active site is buried within the protein molecule and several channels connect the catalytic cavity to the protein surface. Their role in P450 catalysis is still matter of debate. The aim of this study was to understand the possible relations existing between channels and substrate specificity. Time course studies were carried out with a collection of polycyclic substrates of increasing sizes assayed with a library of wild-type and chimeric CYP1A enzymes. This resulted in a matrix of activities sufficiently large to allow statistical analysis. Multivariate statistical tools were used to decipher the correlation between observed activity shifts and sequence segment swaps. The global kinetic behavior of CYP1A enzymes toward polycyclic substrates is significantly different depending on the size of the substrate. Mutations which are close or lining the P450 channels significantly affect this discrimination, whereas mutations distant from the P450 channels do not. Size discrimination is taking place for polycyclic substrates at the entrance of the different P450 access channels. It is thus hypothesized that channels differentiate small from large substrates in CYP1A enzymes, implying that residues located at the surface of the protein may be implied in this differential recognition. Catalysis thus occurs after a two-step recognition process, one at the surface of the protein and the second within the catalytic cavity in enzymes with a buried active site. Copyright © 2014 Elsevier B.V. All rights reserved.

Self-optimizing, highly surface-active layered metal dichalcogenide catalysts for hydrogen evolution

NASA Astrophysics Data System (ADS)

Liu, Yuanyue; Wu, Jingjie; Hackenberg, Ken P.; Zhang, Jing; Wang, Y. Morris; Yang, Yingchao; Keyshar, Kunttal; Gu, Jing; Ogitsu, Tadashi; Vajtai, Robert; Lou, Jun; Ajayan, Pulickel M.; Wood, Brandon C.; Yakobson, Boris I.

2017-09-01

Low-cost, layered transition-metal dichalcogenides (MX2) based on molybdenum and tungsten have attracted substantial interest as alternative catalysts for the hydrogen evolution reaction (HER). These materials have high intrinsic per-site HER activity; however, a significant challenge is the limited density of active sites, which are concentrated at the layer edges. Here we unravel electronic factors underlying catalytic activity on MX2 surfaces, and leverage the understanding to report group-5 MX2 (H-TaS2 and H-NbS2) electrocatalysts whose performance instead mainly derives from highly active basal-plane sites, as suggested by our first-principles calculations and performance comparisons with edge-active counterparts. Beyond high catalytic activity, they are found to exhibit an unusual ability to optimize their morphology for enhanced charge transfer and accessibility of active sites as the HER proceeds, offering a practical advantage for scalable processing. The catalysts reach 10 mA cm-2 current density at an overpotential of ˜50-60 mV with a loading of 10-55 μg cm-2, surpassing other reported MX2 candidates without any performance-enhancing additives.

Intergenerational equity and environmental restoration cleanup levels.

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

Hocking, E. K.; Environmental Assessment

2001-01-01

The United States Department of Energy environmental restoration program faces difficult decisions about the levels of cleanup to be achieved at its many contaminated sites and has acknowledged the need for considering intergenerational equity in its decision making. Intergenerational equity refers to the fairness of access to resources across generations. Environmental restoration cleanup levels can have unintended and unfair consequences for future generations access to resources. The potentially higher costs associated with using low, non-risk-based cleanup levels for remediation may divert funding from other activities that could have a greater beneficial impact on future generations. Low, non-risk-based cleanup levels couldmore » also result in more damage to the nation's resources than would occur if a higher cleanup level were used. The loss or impairment of these resources could have an inequitable effect on future generations. However, intergenerational inequity could arise if sites are not completely restored and if access to and use of natural and cultural resources are unfairly limited as a result of residual contamination. In addition to concerns about creating possible intergenerational inequities related to selected cleanup levels, the tremendous uncertainties associated with sites and their restoration can lead site planners to rely on stewardship by default. An ill-conceived stewardship program can contribute to intergenerational inequity by limiting access to resources while passing on risks to future generations and not preparing them for those risks. This paper presents a basic model and process for designing stewardship programs that can achieve equity among generations.« less

77 FR 24952 - Agency Information Collection Activities; Proposed Collection; Comment Request; Regional Haze...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

....regulations.gov Web site is an ``anonymous access'' system, which means the EPA will not know your identity or... and the states will be shifting their focus to development of interim progress reports required by the...

40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

Code of Federal Regulations, 2014 CFR

2014-07-01

... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

Code of Federal Regulations, 2011 CFR

2011-07-01

... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

Code of Federal Regulations, 2010 CFR

2010-07-01

... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

Code of Federal Regulations, 2013 CFR

2013-07-01

... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

40 CFR 1400.9 - Access to off-site consequence analysis information by State and local government officials.

Code of Federal Regulations, 2012 CFR

2012-07-01

... analysis information by State and local government officials. 1400.9 Section 1400.9 Protection of... CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Access to Off-Site Consequence Analysis Information by Government Officials. § 1400.9 Access to off-site consequence analysis...

Hand Society and Matching Program Web Sites Provide Poor Access to Information Regarding Hand Surgery Fellowship.

PubMed

Hinds, Richard M; Klifto, Christopher S; Naik, Amish A; Sapienza, Anthony; Capo, John T

2016-08-01

The Internet is a common resource for applicants of hand surgery fellowships, however, the quality and accessibility of fellowship online information is unknown. The objectives of this study were to evaluate the accessibility of hand surgery fellowship Web sites and to assess the quality of information provided via program Web sites. Hand fellowship Web site accessibility was evaluated by reviewing the American Society for Surgery of the Hand (ASSH) on November 16, 2014 and the National Resident Matching Program (NRMP) fellowship directories on February 12, 2015, and performing an independent Google search on November 25, 2014. Accessible Web sites were then assessed for quality of the presented information. A total of 81 programs were identified with the ASSH directory featuring direct links to 32% of program Web sites and the NRMP directory directly linking to 0%. A Google search yielded direct links to 86% of program Web sites. The quality of presented information varied greatly among the 72 accessible Web sites. Program description (100%), fellowship application requirements (97%), program contact email address (85%), and research requirements (75%) were the most commonly presented components of fellowship information. Hand fellowship program Web sites can be accessed from the ASSH directory and, to a lesser extent, the NRMP directory. However, a Google search is the most reliable method to access online fellowship information. Of assessable programs, all featured a program description though the quality of the remaining information was variable. Hand surgery fellowship applicants may face some difficulties when attempting to gather program information online. Future efforts should focus on improving the accessibility and content quality on hand surgery fellowship program Web sites.

Elimination of a ligand gating site generates a supersensitive olfactory receptor.

PubMed

Sharma, Kanika; Ahuja, Gaurav; Hussain, Ashiq; Balfanz, Sabine; Baumann, Arnd; Korsching, Sigrun I

2016-06-21

Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors.

Elimination of a ligand gating site generates a supersensitive olfactory receptor

PubMed Central

Sharma, Kanika; Ahuja, Gaurav; Hussain, Ashiq; Balfanz, Sabine; Baumann, Arnd; Korsching, Sigrun I.

2016-01-01

Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors. PMID:27323929

Hierarchically structured graphene-carbon nanotube-cobalt hybrid electrocatalyst for seawater battery

NASA Astrophysics Data System (ADS)

Suh, Dong Hoon; Park, Sul Ki; Nakhanivej, Puritut; Kim, Youngsik; Hwang, Soo Min; Park, Ho Seok

2017-12-01

The design of cost-effective and highly active catalysts is a critical challenge. Inspired by the strong points of stability and conductivity of carbon nanotubes (CNTs), high catalytic activity of Co nanoparticles, and rapid ion diffusion and large accessible area of three-dimensional (3D) graphene, we demonstrate a novel strategy to construct a hierarchical hybrid structure consisting of Co/CoOx nanoparticles-incorporated CNT branches onto the 3D reduced graphene oxide (rGO) architecture. The surface-modified 3D rGO by steam activation process has a large surface area and abundant defect sites, which serve as active sites to uniformly grow Co/CoOx nanoparticles. Furthermore, the CNTs preserve their performance stably by encapsulating Co nanoparticles, while the uniformly decorated Co/CoOx nanoparticles exhibit superior electrocatalytic activity toward oxygen evolution/reduction reaction due to highly exposed active sites. Employing the hybrid particle electrocatalyst, the seawater battery operates stably at 0.01 mA cm-2 during 50 cycles, owing to the good electrocatalytic ability.

Human dynamics revealed through Web analytics

NASA Astrophysics Data System (ADS)

Gonçalves, Bruno; Ramasco, José J.

2008-08-01

The increasing ubiquity of Internet access and the frequency with which people interact with it raise the possibility of using the Web to better observe, understand, and monitor several aspects of human social behavior. Web sites with large numbers of frequently returning users are ideal for this task. If these sites belong to companies or universities, their usage patterns can furnish information about the working habits of entire populations. In this work, we analyze the properly anonymized logs detailing the access history to Emory University’s Web site. Emory is a medium-sized university located in Atlanta, Georgia. We find interesting structure in the activity patterns of the domain and study in a systematic way the main forces behind the dynamics of the traffic. In particular, we find that linear preferential linking, priority-based queuing, and the decay of interest for the contents of the pages are the essential ingredients to understand the way users navigate the Web.

40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Internet access to certain off-site... DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... elements in the risk management plan database available on the Internet: (a) The concentration of the...

Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors

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

Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas

Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization andmore » conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.« less

The binding sites of inhibitory monoclonal antibodies on acetylcholinesterase. Identification of a novel regulatory site at the putative "back door".

PubMed

Simon, S; Le Goff, A; Frobert, Y; Grassi, J; Massoulié, J

1999-09-24

We investigated the target sites of three inhibitory monoclonal antibodies on Electrophorus acetylcholinesterase (AChE). Previous studies showed that Elec-403 and Elec-410 are directed to overlapping but distinct epitopes in the peripheral site, at the entrance of the catalytic gorge, whereas Elec-408 binds to a different region. Using Electrophorus/rat AChE chimeras, we identified surface residues that differed between sensitive and insensitive AChEs: the replacement of a single Electrophorus residue by its rat homolog was able to abolish binding and inhibition, for each antibody. Reciprocally, binding and inhibition by Elec-403 and by Elec-410 could be conferred to rat AChE by the reverse mutation. Elec-410 appears to bind to one side of the active gorge, whereas Elec-403 covers its opening, explaining why the AChE-Elec-410 complex reacts faster than the AChE-Elec-403 or AChE-fasciculin complexes with two active site inhibitors, m-(N,N, N-trimethyltammonio)trifluoro-acetophenone and echothiophate. Elec-408 binds to the region of the putative "back door," distant from the peripheral site, and does not interfere with the access of inhibitors to the active site. The binding of an antibody to this novel regulatory site may inhibit the enzyme by blocking the back door or by inducing a conformational distortion within the active site.

Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors.

PubMed

Wang, Shouming; Beck, Richard; Burd, Andrew; Blench, Toby; Marlin, Frederic; Ayele, Tenagne; Buxton, Stuart; Dagostin, Claudio; Malic, Maja; Joshi, Rina; Barry, John; Sajad, Mohammed; Cheung, Chiming; Shaikh, Shaheda; Chahwala, Suresh; Chander, Chaman; Baumgartner, Christine; Holthoff, Hans-Peter; Murray, Elizabeth; Blackney, Michael; Giddings, Amanda

2010-02-25

On the basis of our understanding on the binding interactions of the benzothiophene template within the FIXa active site by X-ray crystallography and molecular modeling studies, we developed our SAR strategy by targeting the 4-position of the template to access the S1 beta and S2-S4 sites. A number of highly selective and potent factor Xa (FXa) and FIXa inhibitors were identified by simple switch of functional groups with conformational changes toward the S2-S4 sites.

Fermilab Security Site Access Request Database

Science.gov Websites

Fermilab Security Site Access Request Database Use of the online version of the Fermilab Security Site Access Request Database requires that you login into the ESH&Q Web Site. Note: Only Fermilab generated from the ESH&Q Section's Oracle database on May 27, 2018 05:48 AM. If you have a question

Integrating NASA Dryden Research Endeavors into the Teaching-Learning of Mathematics in the K-12 Classroom via the WWW

NASA Technical Reports Server (NTRS)

Ward, Robin A.

2002-01-01

The primary goal of this project was to continue populating the currently existing web site developed in 1998 in conjunction with the NASA Dryden Flight Research Center and California Polytechnic State University, with more mathematics lesson plans and activities that K-12 teachers, students, home-schoolers, and parents could access. All of the activities, while demonstrating some mathematical topic, also showcase the research endeavors of the NASA Dryden Flight Research Center. The website is located at: http://daniel.calpoly.edu/dfrc/Robin. The secondary goal of this project was to share the web-based activities with educators at various conferences and workshops. To address the primary goal of this project, over the past year, several new activities were posted on the web site and some of the existing activities were enhanced to contain more video clips, photos, and materials for teachers. To address the project's secondary goal, the web-based activities were showcased at several conferences and workshops. Additionally, in order to measure and assess the outreach impact of the web site, a link to the web site hitbox.com was established in April 2001, which allowed for the collection of traffic statistics against the web site (such as the domains of visitors, the frequency of visitors to this web site, etc.) Provided is a description of some of the newly created activities posted on the web site during the project period of 2001-2002, followed by a description of the conferences and workshops at which some of the web-based activities were showcased. Next is a brief summary of the web site's traffic statistics demonstrating its worldwide educational impact, followed by a listing of some of the awards and accolades the web site has received.

Active Agents of Health Promotion? The School's Role in Supporting the HPV Vaccination Programme

ERIC Educational Resources Information Center

Spratt, Jennifer; Shucksmith, Janet; Philip, Kate; McNaughton, Rebekah

2013-01-01

By providing a place in which children can be accessed, the school has long been a site for population-level health initiatives. Recent policy shifts towards health-promoting schools have however re-cast the school from passive host to active collaborator in public health. This paper examines secondary school teachers' views of their roles as…

Access site complications and puncture site pain following transradial coronary procedures: a correlational study.

PubMed

Cheng, Ka Yan; Chair, Sek Ying; Choi, Kai Chow

2013-10-01

Transradial coronary angiography (CA) and percutaneous coronary intervention (PCI) are gaining worldwide popularity due to the low incidence of major vascular complications and early mobilization of patients post procedures. Although post transradial access site complications are generally considered as minor in nature, they are not being routinely recorded in clinical settings. To evaluate the incidence of access site complications and level of puncture site pain experienced by patients undergoing transradial coronary procedures and to examine factors associated with access site complications occurrence and puncture site pain severity. A cross-sectional correlational study of 85 Chinese speaking adult patients scheduled for elective transradial CA and or PCI. Ecchymosis, bleeding, hematoma and radial artery occlusion (RAO) were assessed through observation, palpation and plethysmographic signal of pulse oximetry after coronary procedures. Puncture site pain was assessed with a 100mm Visual Analogue Scale. Factors that were related to access site complications and puncture site pain were obtained from medical records. Ecchymosis was the most commonly reported transradial access site complication in this study. Paired t-test showed that the level of puncture site pain at 24 h was significantly (p<0.001) lower than that at 3 h after the procedure. Stepwise multivariable regression showed that female gender and shorter sheath time were found to be significantly associated with bleeding during gradual deflation of compression device. Only longer sheath time was significantly associated with RAO. Female gender and larger volume of compression air were associated with the presence of ecchymosis and puncture site pain at 3 h after procedure, respectively. The study findings suggest that common access site complications post transradial coronary procedures among Chinese population are relatively minor in nature. Individual puncture site pain assessment during the period of hemostasis is important. Nurses should pay more attention to factors such as female gender, sheath time and volume of compression that are more likely to be associated with transradial access site complications and puncture site pain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glyphosate resistance in Ambrosia trifida: Part 1. Novel rapid cell death response to glyphosate.

PubMed

Van Horn, Christopher R; Moretti, Marcelo L; Robertson, Renae R; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Schulz, Burkhard; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Hall, J Christopher; McLean, Michael D; Lawton, Mark B; Sammons, R Douglas; Wang, Dafu; Westra, Philip; Gaines, Todd A

2018-05-01

Glyphosate-resistant (GR) Ambrosia trifida is now present in the midwestern United States and in southwestern Ontario, Canada. Two distinct GR phenotypes are known, including a rapid response (GR RR) phenotype, which exhibits cell death within hours after treatment, and a non-rapid response (GR NRR) phenotype. The mechanisms of resistance in both GR RR and GR NRR remain unknown. Here, we present a description of the RR phenotype and an investigation of target-site mechanisms on multiple A. trifida accessions. Glyphosate resistance was confirmed in several accessions, and whole-plant levels of resistance ranged from 2.3- to 7.5-fold compared with glyphosate-susceptible (GS) accessions. The two GR phenotypes displayed similar levels of resistance, despite having dramatically different phenotypic responses to glyphosate. Glyphosate resistance was not associated with mutations in EPSPS sequence, increased EPSPS copy number, EPSPS quantity, or EPSPS activity. These encompassing results suggest that resistance to glyphosate in these GR RR A. trifida accessions is not conferred by a target-site resistance mechanism. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Evolution of herbicide resistance mechanisms in grass weeds.

PubMed

Matzrafi, Maor; Gadri, Yaron; Frenkel, Eyal; Rubin, Baruch; Peleg, Zvi

2014-12-01

Herbicide resistant weeds are becoming increasingly common, threatening global food security. Here, we present BrIFAR: a new model system for the functional study of mechanisms of herbicide resistance in grass weeds. We have developed a large collection of Brachypodium accessions, the BrI collection, representing a wide range of habitats. Wide screening of the responses of the accessions to four major herbicide groups (PSII, ACCase, ALS/AHAS and EPSPS inhibitors) identified 28 herbicide-resistance candidate accessions. Target-site resistance to PSII inhibitors was found in accessions collected from habitats with a known history of herbicide applications. An amino acid substitution in the psbA gene (serine264 to glycine) conferred resistance and also significantly affected the flowering and shoot dry weight of the resistant accession, as compared to the sensitive accession. Non-target site resistance to ACCase inhibitors was found in accessions collected from habitats with a history of herbicide application and from a nature reserve. In-vitro enzyme activity tests and responses following pre-treatment with malathion (a cytochrome-P450 inhibitor) indicated sensitivity at the enzyme level, and give strong support to diclofop-methyl and pinoxaden enhanced detoxification as NTS resistance mechanism. BrIFAR can promote better understanding of the evolution of mechanisms of herbicide resistance and aid the implementation of integrative management approaches for sustainable agriculture. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Is excessive online usage a function of medium or activity? An empirical pilot study

PubMed Central

Griffiths, Mark D.; Szabo, Attila

2014-01-01

Aims: The purpose of the study was to seek a better insight into whether the online medium or the online activity was more important in relation to excessive online use. It is not clear whether those people who spend excessive amounts of time on the Internet are engaged in general Internet or whether excessive Internet use is linked to specific activities. Methods: Perceived changes in Internet use habits as function of hypothetical accessibility of favorite sites were investigated in young adults. University students (n = 130, mean age = 20.6 years) who had (on average) spent over 20 hours a week on the Internet for at least nine years completed a survey. The most favored online activities and expected quality of life without Internet access were also investigated. Results: Findings revealed that social networking was by far the most popular online activity, and that lack of access to their preferred online activities would drop by 65% (as measured by perceived Internet usage). Approximately one in six participants (16%) claimed they would not even switch on the computer if access to their favorite online activities were unavailable. In relation to a hypothetical question about the quality of life without Internet access, the responses were normally distributed (rather than skewed). Conclusions: These results show that time spent with Internet activity is not random and/or generalized, but appears more focused. Attraction or addiction on Internet to one or more specific behavior(s) may be a better way forward in the quest for better understanding excessive human behavior in the online environment. PMID:25215216

The structure of amylosucrase from Deinococcus radiodurans has an unusual open active-site topology.

PubMed

Skov, Lars K; Pizzut-Serin, Sandra; Remaud-Simeon, Magali; Ernst, Heidi A; Gajhede, Michael; Mirza, Osman

2013-09-01

Amylosucrases (ASes) catalyze the formation of an α-1,4-glucosidic linkage by transferring a glucosyl unit from sucrose onto an acceptor α-1,4-glucan. To date, several ligand-bound crystal structures of wild-type and mutant ASes from Neisseria polysaccharea and Deinococcus geothermalis have been solved. These structures all display a very similar overall conformation with a deep pocket leading to the site for transglucosylation, subsite -1. This has led to speculation on how sucrose enters the active site during glucan elongation. In contrast to previous studies, the AS structure from D. radiodurans presented here has a completely empty -1 subsite. This structure is strikingly different from other AS structures, as an active-site-lining loop comprising residues Leu214-Asn225 is found in a previously unobserved conformation. In addition, a large loop harbouring the conserved active-site residues Asp133 and Tyr136 is disordered. The result of the changed loop conformations is that the active-site topology is radically changed, leaving subsite -1 exposed and partially dismantled. This structure provides novel insights into the dynamics of ASes and comprises the first structural support for an elongation mechanism that involves considerable conformational changes to modulate accessibility to the sucrose-binding site and thereby allows successive cycles of glucosyl-moiety transfer to a growing glucan chain.

Social Media Use and Access to Digital Technology in US Young Adults in 2016.

PubMed

Villanti, Andrea C; Johnson, Amanda L; Ilakkuvan, Vinu; Jacobs, Megan A; Graham, Amanda L; Rath, Jessica M

2017-06-07

In 2015, 90% of US young adults with Internet access used social media. Digital and social media are highly prevalent modalities through which young adults explore identity formation, and by extension, learn and transmit norms about health and risk behaviors during this developmental life stage. The purpose of this study was to provide updated estimates of social media use from 2014 to 2016 and correlates of social media use and access to digital technology in data collected from a national sample of US young adults in 2016. Young adult participants aged 18-24 years in Wave 7 (October 2014, N=1259) and Wave 9 (February 2016, N=989) of the Truth Initiative Young Adult Cohort Study were asked about use frequency for 11 social media sites and access to digital devices, in addition to sociodemographic characteristics. Regular use was defined as using a given social media site at least weekly. Weighted analyses estimated the prevalence of use of each social media site, overlap between regular use of specific sites, and correlates of using a greater number of social media sites regularly. Bivariate analyses identified sociodemographic correlates of access to specific digital devices. In 2014, 89.42% (weighted n, 1126/1298) of young adults reported regular use of at least one social media site. This increased to 97.5% (weighted n, 965/989) of young adults in 2016. Among regular users of social media sites in 2016, the top five sites were Tumblr (85.5%), Vine (84.7%), Snapchat (81.7%), Instagram (80.7%), and LinkedIn (78.9%). Respondents reported regularly using an average of 7.6 social media sites, with 85% using 6 or more sites regularly. Overall, 87% of young adults reported access or use of a smartphone with Internet access, 74% a desktop or laptop computer with Internet access, 41% a tablet with Internet access, 29% a smart TV or video game console with Internet access, 11% a cell phone without Internet access, and 3% none of these. Access to all digital devices with Internet was lower in those reporting a lower subjective financial situation; there were also significant differences in access to specific digital devices with Internet by race, ethnicity, and education. The high mean number of social media sites used regularly and the substantial overlap in use of multiple social media sites reflect the rapidly changing social media environment. Mobile devices are a primary channel for social media, and our study highlights disparities in access to digital technologies with Internet access among US young adults by race/ethnicity, education, and subjective financial status. Findings from this study may guide the development and implementation of future health interventions for young adults delivered via the Internet or social media sites. ©Andrea C Villanti, Amanda L Johnson, Vinu Ilakkuvan, Megan A Jacobs, Amanda L Graham, Jessica M Rath. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 07.06.2017.

Social Media Use and Access to Digital Technology in US Young Adults in 2016

PubMed Central

Johnson, Amanda L; Ilakkuvan, Vinu; Jacobs, Megan A; Graham, Amanda L; Rath, Jessica M

2017-01-01

Background In 2015, 90% of US young adults with Internet access used social media. Digital and social media are highly prevalent modalities through which young adults explore identity formation, and by extension, learn and transmit norms about health and risk behaviors during this developmental life stage. Objective The purpose of this study was to provide updated estimates of social media use from 2014 to 2016 and correlates of social media use and access to digital technology in data collected from a national sample of US young adults in 2016. Methods Young adult participants aged 18-24 years in Wave 7 (October 2014, N=1259) and Wave 9 (February 2016, N=989) of the Truth Initiative Young Adult Cohort Study were asked about use frequency for 11 social media sites and access to digital devices, in addition to sociodemographic characteristics. Regular use was defined as using a given social media site at least weekly. Weighted analyses estimated the prevalence of use of each social media site, overlap between regular use of specific sites, and correlates of using a greater number of social media sites regularly. Bivariate analyses identified sociodemographic correlates of access to specific digital devices. Results In 2014, 89.42% (weighted n, 1126/1298) of young adults reported regular use of at least one social media site. This increased to 97.5% (weighted n, 965/989) of young adults in 2016. Among regular users of social media sites in 2016, the top five sites were Tumblr (85.5%), Vine (84.7%), Snapchat (81.7%), Instagram (80.7%), and LinkedIn (78.9%). Respondents reported regularly using an average of 7.6 social media sites, with 85% using 6 or more sites regularly. Overall, 87% of young adults reported access or use of a smartphone with Internet access, 74% a desktop or laptop computer with Internet access, 41% a tablet with Internet access, 29% a smart TV or video game console with Internet access, 11% a cell phone without Internet access, and 3% none of these. Access to all digital devices with Internet was lower in those reporting a lower subjective financial situation; there were also significant differences in access to specific digital devices with Internet by race, ethnicity, and education. Conclusions The high mean number of social media sites used regularly and the substantial overlap in use of multiple social media sites reflect the rapidly changing social media environment. Mobile devices are a primary channel for social media, and our study highlights disparities in access to digital technologies with Internet access among US young adults by race/ethnicity, education, and subjective financial status. Findings from this study may guide the development and implementation of future health interventions for young adults delivered via the Internet or social media sites. PMID:28592394

Civic Engagement through Digital Citizenship: Engaging Youth in Active, Participatory Citizenship through Digital Media. The Progress of Education Reform. Volume 13, Number 1

ERIC Educational Resources Information Center

Baumann, Paul

2012-01-01

Participatory digital media--broadly defined as media such as the Internet, social network sites and cell phones that allow users to interact--are ubiquitous among today's youth. Among teens ages 12-17, 95% have access to the Internet; 70% go online daily; 80% use social networking sites such as Facebook and Twitter; and 77% have cell phones. Many…

Active-site copper reduction promotes substrate binding of fungal lytic polysaccharide monooxygenase and reduces stability.

PubMed

Kracher, Daniel; Andlar, Martina; Furtmüller, Paul G; Ludwig, Roland

2018-02-02

Lytic polysaccharide monooxygenases (LPMOs) are a class of copper-containing enzymes that oxidatively degrade insoluble plant polysaccharides and soluble oligosaccharides. Upon reductive activation, they cleave the substrate and promote biomass degradation by hydrolytic enzymes. In this study, we employed LPMO9C from Neurospora crassa , which is active toward cellulose and soluble β-glucans, to study the enzyme-substrate interaction and thermal stability. Binding studies showed that the reduction of the mononuclear active-site copper by ascorbic acid increased the affinity and the maximum binding capacity of LPMO for cellulose. The reduced redox state of the active-site copper and not the subsequent formation of the activated oxygen species increased the affinity toward cellulose. The lower affinity of oxidized LPMO could support its desorption after catalysis and allow hydrolases to access the cleavage site. It also suggests that the copper reduction is not necessarily performed in the substrate-bound state of LPMO. Differential scanning fluorimetry showed a stabilizing effect of the substrates cellulose and xyloglucan on the apparent transition midpoint temperature of the reduced, catalytically active enzyme. Oxidative auto-inactivation and destabilization were observed in the absence of a suitable substrate. Our data reveal the determinants of LPMO stability under turnover and non-turnover conditions and indicate that the reduction of the active-site copper initiates substrate binding. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Transcription factor target site search and gene regulation in a background of unspecific binding sites.

PubMed

Hettich, J; Gebhardt, J C M

2018-06-02

Response time and transcription level are vital parameters of gene regulation. They depend on how fast transcription factors (TFs) find and how efficient they occupy their specific target sites. It is well known that target site search is accelerated by TF binding to and sliding along unspecific DNA and that unspecific associations alter the occupation frequency of a gene. However, whether target site search time and occupation frequency can be optimized simultaneously is mostly unclear. We developed a transparent and intuitively accessible state-based formalism to calculate search times to target sites on and occupation frequencies of promoters of arbitrary state structure. Our formalism is based on dissociation rate constants experimentally accessible in live cell experiments. To demonstrate our approach, we consider promoters activated by a single TF, by two coactivators or in the presence of a competitive inhibitor. We find that target site search time and promoter occupancy differentially vary with the unspecific dissociation rate constant. Both parameters can be harmonized by adjusting the specific dissociation rate constant of the TF. However, while measured DNA residence times of various eukaryotic TFs correspond to a fast search time, the occupation frequencies of target sites are generally low. Cells might tolerate low target site occupancies as they enable timely gene regulation in response to a changing environment. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Secure Web-Site Access with Tickets and Message-Dependent Digests

USGS Publications Warehouse

Donato, David I.

2008-01-01

Although there are various methods for restricting access to documents stored on a World Wide Web (WWW) site (a Web site), none of the widely used methods is completely suitable for restricting access to Web applications hosted on an otherwise publicly accessible Web site. A new technique, however, provides a mix of features well suited for restricting Web-site or Web-application access to authorized users, including the following: secure user authentication, tamper-resistant sessions, simple access to user state variables by server-side applications, and clean session terminations. This technique, called message-dependent digests with tickets, or MDDT, maintains secure user sessions by passing single-use nonces (tickets) and message-dependent digests of user credentials back and forth between client and server. Appendix 2 provides a working implementation of MDDT with PHP server-side code and JavaScript client-side code.

Identification and conservation of apple genetic diversity

USDA-ARS?s Scientific Manuscript database

The USDA-ARS National Plant Germplasm System (NPGS) maintains a vast collection of plant genetic resources that includes over 570,000 accessions representing nearly 15,000 species. This collection is dispersed amongst 17 active sites throughout the United States. The NPGS base collection at the Nati...

76 FR 40925 - Commercial Wind Lease Issuance and Site Characterization Activities on the Atlantic Outer...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-12

.... The purpose of this notice is to inform the public of the availability of the draft EA for review and... Impact Statement (EIS) would need to be prepared. The draft EA can be accessed online at: http://www...

Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

DOE PAGES

van Driel, Tim B.; Kjær, Kasper S.; Hartsock, Robert W.; ...

2016-11-28

The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir 2(dimen) 4] 2+, where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute–solvent pair distribution function, enabling themore » solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.« less

The Origin of Word-related Motor Activity

PubMed Central

Papeo, Liuba; Lingnau, Angelika; Agosta, Sara; Pascual-Leone, Alvaro; Battelli, Lorella; Caramazza, Alfonso

2015-01-01

Conceptual processing of verbs consistently recruits the left posterior middle temporal gyrus (lpMTG). The left precentral motor cortex also responds to verbs, with higher activity for action than nonaction verbs. The early timing of this effect has suggested that motor features of words' meaning are accessed directly, bypassing access to conceptual representations in lpMTG. An alternative hypothesis is that the retrieval of conceptual representations in lpMTG is necessary to drive more specific, motor-related representations in the precentral gyrus. To test these hypotheses, we first showed that repetitive transcranial magnetic stimulation (rTMS) applied to the verb-preferring lpMTG site selectively impoverished the semantic processing of verbs. In a second experiment, rTMS perturbation of lpMTG, relative to no stimulation (no-rTMS), eliminated the action–nonaction verb distinction in motor activity, as indexed by motor-evoked potentials induced in peripheral muscles with single-pulse TMS over the left primary motor cortex. rTMS pertubation of an occipital control site, relative to no-rTMS, did not affect the action–nonaction verb distinction in motor activity, but the verb contrast did not differ reliably from the lpMTG effect. The results show that lpMTG carries core semantic information necessary to drive the activation of specific (motor) features in the precentral gyrus. PMID:24421174

Noninvasive optical evaluation of low frequency oscillations in prefrontal cortex hemodynamics during verbal working memory

NASA Astrophysics Data System (ADS)

Li, Ting; Zhao, Yue; Li, Kai; Sun, Yunlong

2014-03-01

The low frequency oscillation (LFO) around 0.1 Hz has been observed recently in cerebral hemodynamic signals during rest/sleep, enhanced breathing, and head- up-tilting, showing that cerebral autoregulation can be accessed by LFOs. However, many brain function researches require direct measurement of LFOs during specified brain function activities. This pilot study explored using near-infrared spectroscopy/imaging (NIRS) to noninvasively and simultaneously detect LFOs of prefrontal cerebral hemodynamics (i.e., oxygenated/deoxygenated/total hemoglobin concentration: △[oxy-Hb]/ △[deoxy-Hb]/ △[tot-Hb]) during N-back visual verbal working memory task. The LFOs were extracted from the measured variables using power spectral analysis. We found the brain activation sites struck clear LFOs while other sites did not. The LFO of △[deoxy-Hb] acted as a negative pike and ranged in (0.05, 0.1) Hz, while LFOs of △[oxy-Hb] and △[tot-Hb] acted as a positive pike and ranged in (0.1, 0.15) Hz. The amplitude difference and frequency lag between △[deoxy-Hb] and △[oxy-Hb]/ △[tot-Hb] produced a more focused and sensitive activation map compare to hemodynamic amplitude-quantified activation maps. This study observed LFOs in brain activities and showed strong potential of LFOs in accessing brain functions.

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

Roberts, Barry L; Lord, David; Lord, Anna C. Snider

This report summarizes the work performed in the prioritization of cavern access wells for remediation and monitoring at the Bayou Choctaw Strategic Petroleum Reserve site. The grading included consideration of all 15 wells at the Bayou Choctaw site, with each active well receiving a separate grade for remediation and monitoring. Numerous factors affecting well integrity were incorporated into the grading including casing survey results, cavern pressure history, results from geomechanical simulations, and site geologic factors. The factors and grading framework used here are the same as those used in developing similar well remediation and monitoring priorities at the Big Hill,more » Bryan Mound, and West Hackberry Strategic Petroleum Reserve Sites.« less

Substrate tunnels in enzymes: structure-function relationships and computational methodology.

PubMed

Kingsley, Laura J; Lill, Markus A

2015-04-01

In enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein, and, in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years because of implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with buried active sites and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. © 2015 Wiley Periodicals, Inc.

Cleanups In My Community (CIMC) - RCRA and Base Realignment and Closure (BRAC) Federal Facilities, National Layer

EPA Pesticide Factsheets

This data layer provides access to Resource Conservation and Recovery Act (RCRA) Base Realignment and Closure (BRAC) sites as part of the CIMC web service. The Resource Conservation and Recovery Act, among other things, helps ensure that wastes are managed in an environmentally sound manner so as to protect human health and the environment from the potential hazards of waste disposal.In particular RCRA tightly regulates all hazardous waste from cradle to grave. In general, all generators, transporters, treaters, storers, and disposers of hazardous waste are required to provide information about their activities to state environmental agencies. These agencies, in turn pass on the information to regional and national EPA offices. Accidents or other activities at facilities that treat, store or dispose of hazardous wastes have sometimes led to the release of hazardous waste or hazardous constituents into soil, ground water, surface water, or air. When that happens, the RCRA Corrective Action program is one program that may be used to accomplish the necessary cleanup.This data layer shows those RCRA sites that are located at BRAC Federal Facilities. Additional RCRA sites and other BRAC sites (those that are not RCRA sites) are included in other data layers as part of this web service.Note: RCRA facilities which are not undergoing corrective action are not considered ??Cleanups?? in Cleanups in My Community. The complete set of RCRA facilities can be accessed via

Integrating expert knowledge in a GIS to optimize siting decisions for small-scale healthy food retail interventions.

PubMed

Sadler, Richard Casey

2016-06-16

The availability of healthy foods in a neighborhood remains a key determinant of diet and diet-related disease in disadvantaged communities. Innovative solutions to the 'food desert' problem include the deployment of mobile markets and healthy corner store initiatives. Such initiatives, however, do not always capitalize on the principles guiding retail development and the possibilities of GIS-based data. Simultaneously, community partners are not always engaged effectively in the planning for such interventions, which limits acceptability and suitability of such work. This paper highlights the results of a participatory mapping exercise to optimize the siting of a planned healthy food retail intervention in Flint, Michigan. Potential sites are chosen by engaging experts in a three-stage mapping process that includes the analytic hierarchy process and point allocation of five key variables (including food access, socioeconomic distress, population density, access to transit, and proximity to neighborhood centers), as well as direct mapping of suitable sites. Results suggest a discrete set of areas-primarily in the northwestern quadrant of the city-where small-scale healthy food retail interventions might be most strategically located. Areas with the most consistent overlap between directly mapped sites and very high levels of suitability align well with neighborhoods which are distant from existing grocery stores. As a community-based strategy, this increases the opportunity for effectively improving neighborhood access to healthy foods by optimizing the potential sites for healthy food interventions. Community partners have already been active in using these results in project planning for just such an intervention.

X-ray Crystallographic Analysis of [alpha]-Ketoheterocycle Inhibitors Bound to a Humanized Variant of Fatty Acid Amide Hydrolase

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

Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine

2010-11-03

Three cocrystal X-ray structures of the {alpha}-ketoheterocycle inhibitors 3-5 bound to a humanized variant of fatty acid amide hydrolase (FAAH) are disclosed and comparatively discussed alongside those of 1 (OL-135) and its isomer 2. These five X-ray structures systematically probe each of the three active site regions key to substrate or inhibitor binding: (1) the conformationally mobile acyl chain-binding pocket and membrane access channel responsible for fatty acid amide substrate and inhibitor acyl chain binding, (2) the atypical active site catalytic residues and surrounding oxyanion hole that covalently binds the core of the {alpha}-ketoheterocycle inhibitors captured as deprotonated hemiketals mimickingmore » the tetrahedral intermediate of the enzyme-catalyzed reaction, and (3) the cytosolic port and its uniquely important imbedded ordered water molecules and a newly identified anion binding site. The detailed analysis of their key active site interactions and their implications on the interpretation of the available structure-activity relationships are discussed providing important insights for future design.« less

Provider perceptions of knowledge exchange and communication in a multisite family health team

PubMed Central

Slater, Morgan; Nicholas, Emily; Leung, Fok-Han; Lofters, Aisha

2016-01-01

Abstract Objective To describe providers’ self-reported knowledge and use of family health team (FHT) services and to explore attitudes and perspectives about communication issues among health care professionals active within a large multisite FHT. Design Electronic questionnaire. Setting A multisite FHT in Toronto, Ont. Participants Health care professionals active within the FHT (N = 90). Main outcome measures The survey captured demographic characteristics, including the respondents’ roles and experience; knowledge about services available within the FHT; use of services; and perceived communication issues within the FHT. Results Forty-six health care professionals participated (51% response rate). While respondents were highly aware of the clinical resources and services offered at their own site of practice (95% agreed or strongly agreed), only 54% were aware of services offered at other sites within the FHT. Internal referrals for certain specialty services were high (ie, methadone management, obstetric care, intrauterine device insertion, and psychiatry), but less than 50% of other referrals (ie, sports medicine, joint injections, or tropical medicine) were to physicians within the FHT, despite physicians within the FHT offering services in these areas of expertise. Only 60% of respondents believed that patients had equal access to all of the services within the FHT, and 42% agreed or strongly agreed that patients were unlikely to travel between sites to access services. Roughly one-quarter of respondents believed that physicians were unlikely to refer patients to another site within the FHT to receive health care services. Most respondents agreed that the geographic distribution of the sites negatively affected communication within the FHT (68% agreed or strongly agreed). Conclusion Geographic dispersion of team members in a multisite FHT had a negative effect on provider knowledge of available services, perceived patient access to services, and communication within the team. As most FHTs are spread across multiple locations, finding ways to improve communication among team members will be key to maximizing the effectiveness of the patient care provided by these team-based models.

Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain

PubMed Central

Djordjevic, Snezana; Goudreau, Paul N.; Xu, Qingping; Stock, Ann M.; West, Ann H.

1998-01-01

We report the x-ray crystal structure of the methylesterase CheB, a phosphorylation-activated response regulator involved in reversible modification of bacterial chemotaxis receptors. Methylesterase CheB and methyltransferase CheR modulate signaling output of the chemotaxis receptors by controlling the level of receptor methylation. The structure of CheB, which consists of an N-terminal regulatory domain and a C-terminal catalytic domain joined by a linker, was solved by molecular replacement methods using independent search models for the two domains. In unphosphorylated CheB, the N-terminal domain packs against the active site of the C-terminal domain and thus inhibits methylesterase activity by directly restricting access to the active site. We propose that phosphorylation of CheB induces a conformational change in the regulatory domain that disrupts the domain interface, resulting in a repositioning of the domains and allowing access to the active site. Structural similarity between the two companion receptor modification enzymes, CheB and CheR, suggests an evolutionary and/or functional relationship. Specifically, the phosphorylated N-terminal domain of CheB may facilitate interaction with the receptors, similar to the postulated role of the N-terminal domain of CheR. Examination of surfaces in the N-terminal regulatory domain of CheB suggests that despite a common fold throughout the response regulator family, surfaces used for protein–protein interactions differ significantly. Comparison between CheB and other response regulators indicates that analogous surfaces are used for different functions and conversely, similar functions are mediated by different molecular surfaces. PMID:9465023

End User Evaluations

NASA Astrophysics Data System (ADS)

Jay, Caroline; Lunn, Darren; Michailidou, Eleni

As new technologies emerge, and Web sites become increasingly sophisticated, ensuring they remain accessible to disabled and small-screen users is a major challenge. While guidelines and automated evaluation tools are useful for informing some aspects of Web site design, numerous studies have demonstrated that they provide no guarantee that the site is genuinely accessible. The only reliable way to evaluate the accessibility of a site is to study the intended users interacting with it. This chapter outlines the processes that can be used throughout the design life cycle to ensure Web accessibility, describing their strengths and weaknesses, and discussing the practical and ethical considerations that they entail. The chapter also considers an important emerging trend in user evaluations: combining data from studies of “standard” Web use with data describing existing accessibility issues, to drive accessibility solutions forward.

The RCSB Protein Data Bank: new resources for research and education

PubMed Central

Rose, Peter W.; Bi, Chunxiao; Bluhm, Wolfgang F.; Christie, Cole H.; Dimitropoulos, Dimitris; Dutta, Shuchismita; Green, Rachel K.; Goodsell, David S.; Prlić, Andreas; Quesada, Martha; Quinn, Gregory B.; Ramos, Alexander G.; Westbrook, John D.; Young, Jasmine; Zardecki, Christine; Berman, Helen M.; Bourne, Philip E.

2013-01-01

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) develops tools and resources that provide a structural view of biology for research and education. The RCSB PDB web site (http://www.rcsb.org) uses the curated 3D macromolecular data contained in the PDB archive to offer unique methods to access, report and visualize data. Recent activities have focused on improving methods for simple and complex searches of PDB data, creating specialized access to chemical component data and providing domain-based structural alignments. New educational resources are offered at the PDB-101 educational view of the main web site such as Author Profiles that display a researcher’s PDB entries in a timeline. To promote different kinds of access to the RCSB PDB, Web Services have been expanded, and an RCSB PDB Mobile application for the iPhone/iPad has been released. These improvements enable new opportunities for analyzing and understanding structure data. PMID:23193259

77 FR 67656 - Agency Information Collection Activities: Proposed Collection: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

... of information technology to minimize the information collection burden. Information Collection... to improve access to primary care, which is supported by clinicians who remain in their sites well... of learning how to bolster retention. Survey data will be gathered anonymously and presented in...

User Centric Policy Management

ERIC Educational Resources Information Center

Cheek, Gorrell P.

2013-01-01

Internet use, in general, and online social networking sites, in particular, are experiencing tremendous growth with hundreds of millions of active users. As a result, there is a tremendous amount of privacy information and content online. Protecting this information is a challenge. Access control policy composition is complex, laborious and…

48 CFR 8.402 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... System.) Ordering activities may access GSA Advantage! through the GSA Federal Supply Service Home Page (http://www.gsa.gov/fss) or the GSA Federal Supply Schedule Home Page at http://www.gsa.gov/schedules..., review the following Web site: http://www.gsa.gov/schedules. Additionally, for on-line training courses...

EVA 2 activity on Flight Day 5 to service the Hubble Space Telescope

NASA Image and Video Library

1997-02-15

S82-E-5407 (15 Feb. 1997) --- Astronauts Gregory J. Harbaugh (left) and Joseph R. Tanner on Remote Manipulator System (RMS) during accessing Fine Guidance Sensor (FGS) in the F site. This view was taken with an Electronic Still Camera (ESC).

NASA's EOSDIS: options for data providers

NASA Astrophysics Data System (ADS)

Khalsa, Siri J.; Ujhazy, John E.

1995-12-01

EOSDIS, the data and information system being developed by NASA to support interdisciplinary earth science research into the 21st century, will do more than manage and distribute data from EOS-era satellites. It will also promote the exchange of data, tools, and research results across disciplinary, agency, and national boundaries. This paper describes the options that data providers will have for interacting with the EOSDIS Core System (ECS), the infrastructure of EOSDIS. The options include: using the ECS advertising service to announce the availability of data at the provider's site; submitting a candidate data set to one of the Distributed Active Archive Centers (DAACs); establishing a data server that will make the data accessible via ECS and establishing Local Information Manager (LIM) which would make the data available for multi-site searches. One additional option is through custom gateway interfaces which would provide access to existing data archives. The gateway, data server, and LIM options require the implementation of ECS code at the provider site to insure proper protocols. The advertisement and ingest options require no part of ECS design to reside at the provider site.

Structure and Dynamic Properties of a Glucocorticoid Receptor-Induced Chromatin Transition

PubMed Central

Fletcher, Terace M.; Ryu, Byung-Woo; Baumann, Christopher T.; Warren, Barbour S.; Fragoso, Gilberto; John, Sam; Hager, Gordon L.

2000-01-01

Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633–3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a “hit-and-run” mechanism for GR action in living cells (J. G. McNally, W. G. Müller, D. Walker, and G. L. Hager, Science 287:1262–1264, 2000). PMID:10938123

Molecular dynamics simulation of the last step of a catalytic cycle: product release from the active site of the enzyme chorismate mutase from Mycobacterium tuberculosis.

PubMed

Choutko, Alexandra; van Gunsteren, Wilfred F

2012-11-01

The protein chorismate mutase MtCM from Mycobacterium tuberculosis catalyzes one of the few pericyclic reactions known in biology: the transformation of chorismate to prephenate. Chorismate mutases have been widely studied experimentally and computationally to elucidate the transition state of the enzyme catalyzed reaction and the origin of the high catalytic rate. However, studies about substrate entry and product exit to and from the highly occluded active site of the enzyme have to our knowledge not been performed on this enzyme. Crystallographic data suggest a possible substrate entry gate, that involves a slight opening of the enzyme for the substrate to access the active site. Using multiple molecular dynamics simulations, we investigate the natural dynamic process of the product exiting from the binding pocket of MtCM. We identify a dominant exit pathway, which is in agreement with the gate proposed from the available crystallographic data. Helices H2 and H4 move apart from each other which enables the product to exit from the active site. Interestingly, in almost all exit trajectories, two residues arginine 72 and arginine 134, which participate in the burying of the active site, are accompanying the product on its exit journey from the catalytic site. Copyright © 2012 The Protein Society.

School Web Sites: Are They Accessible to All?

ERIC Educational Resources Information Center

Wells, Julie A.; Barron, Ann E.

2006-01-01

In 2002, the National Center for Educational Statistics reported that 99% of public schools had Internet access and 86% of those schools had a web site or web page (Kleiner & Lewis, 2003). This study examined accessibility issues on elementary school homepages. Using a random sample of elementary school web sites, the researchers documented…

40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... consequence analysis data elements. 1400.5 Section 1400.5 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... consequence analysis data elements. 1400.5 Section 1400.5 Protection of Environment ENVIRONMENTAL PROTECTION...

40 CFR 1400.5 - Internet access to certain off-site consequence analysis data elements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.5 Internet access to certain off... consequence analysis data elements. 1400.5 Section 1400.5 Protection of Environment ENVIRONMENTAL PROTECTION...

A facile reflux procedure to increase active surface sites form highly active and durable supported palladium@platinum bimetallic nanodendrites

NASA Astrophysics Data System (ADS)

Wang, Qin; Li, Yingjun; Liu, Baocang; Xu, Guangran; Zhang, Geng; Zhao, Qi; Zhang, Jun

2015-11-01

A series of well-dispersed bimetallic Pd@Pt nanodendrites uniformly supported on XC-72 carbon black are fabricated by using different capping agents. These capping agents are essential for the branched morphology control. However, the surfactant adsorbed on the nanodendrites surface blocks the access of reactant molecules to the active surface sites, and the catalytic activities of these bimetallic nanodendrites are significantly restricted. Herein, a facile reflux procedure to effectively remove the capping agent molecules without significantly affecting their sizes is reported for activating supported nanocatalysts. More significantly, the structure and morphology of the nanodendrites can also be retained, enhancing the numbers of active surface sites, catalytic activity and stability toward methanol and ethanol electro-oxidation reactions. The as-obtained hot water reflux-treated Pd@Pt/C catalyst manifests superior catalytic activity and stability both in terms of surface and mass specific activities, as compared to the untreated catalysts and the commercial Pt/C and Pd/C catalysts. We anticipate that this effective and facile removal method has more general applicability to highly active nanocatalysts prepared with various surfactants, and should lead to improvements in environmental protection and energy production.

Structure Effects of 2D Materials on α-Nickel Hydroxide for Oxygen Evolution Reaction.

PubMed

Luan, Chenglong; Liu, Guangli; Liu, Yujie; Yu, Lei; Wang, Yao; Xiao, Yun; Qiao, Hongyan; Dai, Xiaoping; Zhang, Xin

2018-04-24

To engineer low-cost, high-efficiency, and stable oxygen evolution reaction (OER) catalysts, structure effects should be primarily understood. Focusing on this, we systematically investigated the relationship between structures of materials and their OER performances by taking four 2D α-Ni(OH) 2 as model materials, including layer-stacked bud-like Ni(OH) 2 -NB, flower-like Ni(OH) 2 -NF, and petal-like Ni(OH) 2 -NP as well as the ultralarge sheet-like Ni(OH) 2 -NS. For the first three (layer-stacking) catalysts, with the decrease of stacked layers, their accessible surface areas, abilities to adsorb OH - , diffusion properties, and the intrinsic activities of active sites increase, which accounts for their steadily enhanced activity. As expected, Ni(OH) 2 -NP shows the lowest overpotential (260 mV at 10 mA cm -2 ) and Tafel slope (78.6 mV dec -1 ) with a robust stability over 10 h among the samples, which also outperforms the benchmark IrO 2 (360 mV and 115.8 mV dec -1 ) catalyst. Interestingly, Ni(OH) 2 -NS relative to Ni(OH) 2 -NP exhibits even faster substance diffusion due to the sheet-like structure, but shows inferior OER activity, which is mainly because the Ni(OH) 2 -NP with a smaller size possesses more active boundary sites (higher reactivity of active sites) than Ni(OH) 2 -NS, considering the adsorption properties and accessible surface areas of the two samples are quite similar. By comparing the different structures and their OER behaviors of four α-Ni(OH) 2 samples, our work may shed some light on the structure effect of 2D materials and accelerate the development of efficient OER catalysts.

LASIC: Light Activated Site-Specific Conjugation of Native IgGs.

PubMed

Hui, James Z; Tamsen, Shereen; Song, Yang; Tsourkas, Andrew

2015-08-19

Numerous biological applications, from diagnostic assays to immunotherapies, rely on the use of antibody-conjugates. The efficacy of these conjugates can be significantly influenced by the site at which Immunoglobulin G (IgG) is modified. Current methods that provide control over the conjugation site, however, suffer from a number of shortfalls and often require large investments of time and cost. We have developed a novel adapter protein that, when activated by long wavelength UV light, can covalently and site-specifically label the Fc region of nearly any native, full-length IgG, including all human IgG subclasses. Labeling occurs with unprecedented efficiency and speed (>90% after 30 min), with no effect on IgG affinity. The adapter domain can be bacterially expressed and customized to contain a variety of moieties (e.g., biotin, azide, fluorophores), making reliable and efficient conjugation of antibodies widely accessible to researchers at large.

Novel Use of a Pneumatic Compression Device for Haemostasis of Haemodialysis Fistula Access Catheterisation Sites

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

O’Reilly, Michael K., E-mail: moreilly1@mater.ie; Ryan, David; Sugrue, Gavin

PurposeTransradial pneumatic compression devices can be used to achieve haemostasis following radial artery puncture. This article describes a novel technique for acquiring haemostasis of arterio-venous haemodialysis fistula access sites without the need for suture placement using one such compression device.Materials and MethodsA retrospective review of fistulograms with or without angioplasty/thrombectomy in a single institution was performed. 20 procedures performed on 12 patients who underwent percutaneous intervention of failing or thrombosed arterio-venous fistulas (AVF) had 27 puncture sites. Haemostasis was achieved using a pneumatic compression device at all access sites. Procedure details including size of access sheath, heparin administration and complicationsmore » were recorded.ResultsTwo diagnostic fistulograms, 14 fistulograms and angioplasties and four thrombectomies were performed via access sheaths with an average size (±SD) of 6 Fr (±1.12). IV unfractionated heparin was administered in 11 of 20 procedures. Haemostasis was achieved in 26 of 27 access sites following 15–20 min of compression using the pneumatic compression device. One case experienced limited bleeding from an inflow access site that was successfully treated with reinflation of the device for a further 5 min. No other complication was recorded.ConclusionsHaemostasis of arterio-venous haemodialysis fistula access sites can be safely and effectively achieved using a pneumatic compression device. This is a technically simple, safe and sutureless technique for acquiring haemostasis after AVF intervention.« less

A multi-institutional approach to delivering shared curricula for developing a next-generation energy workforce

DOE PAGES

Holloway, Lawrence E.; Qu, Zhihua; Mohr-Schroeder, Margaret J.; ...

2017-02-06

In this study, we consider collaborative power systems education through the FEEDER consortium. To increase students' access to power engineering educational content, the consortium of seven universities was formed. A framework is presented to characterize different collaborative education activities among the universities. Three of these approaches of collaborative educational activities are presented and discussed. These include 1) cross-institutional blended courses ("MS-MD''); 2) cross-institutional distance courses ("SS-MD''); and 3) single-site special experiential courses and concentrated on-site programs available to students across consortium institutions ("MS-SD''). As a result, this paper presents the advantages and disadvantages of each approach.

Aldosterone alters the chromatin structure of the murine endothelin-1 gene.

PubMed

Welch, Amanda K; Jeanette Lynch, I; Gumz, Michelle L; Cain, Brian D; Wingo, Charles S

2016-08-15

Aldosterone increases sodium reabsorption in the renal collecting duct and systemic blood pressure. Paradoxically, aldosterone also induces transcription of the endothelin-1 (Edn1) gene to increase protein (ET-1) levels, which inhibits sodium reabsorption. Here we investigated changes in the chromatin structure of the Edn1 gene of collecting duct cell lines in response to aldosterone treatment. The Edn1 gene has a CpG island that encompasses the transcription start site and four sites in the 5' regulatory region previously linked to transcriptional regulation. The chromatin structure of the Edn1 gene was investigated using a quantitative PCR-based DNaseI hypersensitivity assay in murine hepatocyte (AML12), renal cortical collecting duct (mpkCCDC14), outer medullary collecting duct1 (OMCD1), and inner medullary collecting duct-3 (IMCD-3) cell lines. The CpG island was uniformly accessible. One calcium-responsive NFAT element remained at low chromatin accessibility in all cell lines under all conditions tested. However, the second calcium responsive NFAT element located at -1563bp upstream became markedly more accessible in IMCD-3 cells exposed to aldosterone. Importantly, one established aldosterone hormone response element HRE at -671bp relative to the transcription start site was highly accessible, and another HRE (-551bp) became more accessible in aldosterone-treated IMCD-3 and OMCD1 cells. The evidence supports a model in which aldosterone activation of the mineralocorticoid receptor (MR) results in the MR-hormone complex binding at HRE at -671bp to open chromatin structure around other regulatory elements in the Edn1 gene. Published by Elsevier Inc.

MED31/437: A Web-based Diabetes Management System: DiabNet

PubMed Central

Zhao, N; Roudsari, A; Carson, E

1999-01-01

Introduction A web-based system (DiabNet) was developed to provide instant access to the Electronic Diabetes Records (EDR) for end-users, and real-time information for healthcare professionals to facilitate their decision-making. It integrates portable glucometer, handheld computer, mobile phone and Internet access as a combined telecommunication and mobile computing solution for diabetes management. Methods: Active Server Pages (ASP) embedded with advanced ActiveX controls and VBScript were developed to allow remote data upload, retrieval and interpretation. Some advisory and Internet-based learning features, together with a video teleconferencing component make DiabNet web site an informative platform for Web-consultation. Results The evaluation of the system is being implemented among several UK Internet diabetes discussion groups and the Diabetes Day Centre at the Guy's & St. Thomas' Hospital. Many positive feedback are received from the web site demonstrating DiabNet is an advanced web-based diabetes management system which can help patients to keep closer control of self-monitoring blood glucose remotely, and is an integrated diabetes information resource that offers telemedicine knowledge in diabetes management. Discussion In summary, DiabNet introduces an innovative online diabetes management concept, such as online appointment and consultation, to enable users to access diabetes management information without time and location limitation and security concerns.

The significance of low substrate concentration measurements for mechanistic interpretation in cholinesterases.

PubMed

Stojan, Jure

2013-03-25

Cholinesterases do not follow the Michaelis-Menten kinetics. In the past, many reaction schemes were suggested to explain their complex interactions during the substrate turnover. Covalent catalysis was recognized very early and therefore, double intermediate traditional reaction scheme for the hydrolysis of good substrates at low concentrations was postulated. However, at intermediate and high substrate concentrations homotropic pseudocooperative effects take place in all cholinesterases, due to the nature of their buried active center. In this study, the significance and usefulness of experimental data obtained at low substrate concentrations, where only one substrate molecule accesses the active site at a time, are to be specified for the overall mechanistic evaluations. Indeed, different interpretations are expected when data are processed with equations derived from different reaction schemes. Consequently, the scheme with two substrate binding sites which comprises the structurally evidenced fully occupied active site as ultimate cause for substantially decreased cholinesterase activity at extremely high substrate concentrations is considered here. A special emphasis is put on butyrylcholinesterase, the enzyme with the largest active site among cholinesterases, where the pseudocooperative effects appear at much higher concentrations than in acetylcholinesterases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Access NASA Satellite Global Precipitation Data Visualization on YouTube

NASA Technical Reports Server (NTRS)

Liu, Z.; Su, J.; Acker, J.; Huffman, G.; Vollmer, B.; Wei, J.; Meyer, D.

2017-01-01

Since the satellite era began, NASA has collected a large volume of Earth science observations for research and applications around the world. The collected and archived satellite data at 12 NASA data centers can also be used for STEM education and activities such as disaster events, climate change, etc. However, accessing satellite data can be a daunting task for non-professional users such as teachers and students because of unfamiliarity of terminology, disciplines, data formats, data structures, computing resources, processing software, programming languages, etc. Over the years, many efforts including tools, training classes, and tutorials have been developed to improve satellite data access for users, but barriers still exist for non-professionals. In this presentation, we will present our latest activity that uses a very popular online video sharing Web site, YouTube (https://www.youtube.com/), for accessing visualizations of our global precipitation datasets at the NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC). With YouTube, users can access and visualize a large volume of satellite data without the necessity to learn new software or download data. The dataset in this activity is a one-month animation for the GPM (Global Precipitation Measurement) Integrated Multi-satellite Retrievals for GPM (IMERG). IMERG provides precipitation on a near-global (60 deg. N-S) coverage at half-hourly time interval, providing more details on precipitation processes and development compared to the 3-hourly TRMM (Tropical Rainfall Measuring Mission) Multisatellite Precipitation Analysis (TMPA, 3B42) product. When the retro-processing of IMERG during the TRMM era is finished in 2018, the entire video will contain more than 330,000 files and will last 3.6 hours. Future plans include development of flyover videos for orbital data for an entire satellite mission or project. All videos, including the one-month animation, will be uploaded and available at the GES DISC site on YouTube (https://www.youtube.com/user/NASAGESDISC).

Challenges in Obtaining Property Access: The FUSRAP Maywood Site Experience - 13433

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

Kollar, William

2013-07-01

The Formerly Utilized Sites Remedial Action Program (FUSRAP) is the US government program started in 1974 to identify, investigate and clean up or control sites that became contaminated as a result of the nation's early atomic programs. Many of these sites are not owned by the federal government and therefore require owner permission to enter. The experience in pursuing such access at the FUSRAP Maywood Superfund Site (the Maywood Site or the Site) in Bergen County, New Jersey, is extensive. Since the US Army Corps of Engineers (the Corps) assumed responsibility for the Maywood Site from the US Department ofmore » Energy in 1997, at least 186 separate property access agreements (known in FUSRAP as a Real Estate Right-of- Entry or ROE) have been executed between the Corps and approximately 55 different land owners and tenant occupants at the Maywood Site (agreement renewals with the same owners over time account for the difference). Maywood's experience during the Corps' tenure, reflected here in three case studies of representative property access efforts, offers some lessons and best practices that may apply to other remedial programs. While the Site Community Relations Manager (the author of this paper) managed the property access task, multi-disciplinary support from across the project was also critical to success in this endeavor. (authors)« less

The Pathfinder Microrover

NASA Technical Reports Server (NTRS)

Matijevic, J. R.; Bickler, D. B.; Braun, D. F.; Eisen, H. J.; Matthies, L. H.; Mishkin, A. H.; Stone, H. W.; van Nieuwstadt, L. M.; Wen, L. C.; Wilcox, B. H.;

Project PARTnership: Instructional Kit. A Model Program for Encouraging Self-Determination through Access to the Arts.

ERIC Educational Resources Information Center

Harris, Carolyn DeMeyer, Ed.; McKinney, David D., Ed.

This instructional kit outlines procedures for implementing Project PARTnership, a program for teaching students with disabilities greater self-determination skills through specifically designed arts experiences. An introductory section describes key project activities, including establishing a site steering committee comprised of teachers,…

Managing Construction Operations Visually: 3-D Techniques for Complex Topography and Restricted Visibility

ERIC Educational Resources Information Center

Rodriguez, Walter; Opdenbosh, Augusto; Santamaria, Juan Carlos

2006-01-01

Visual information is vital in planning and managing construction operations, particularly, where there is complex terrain topography and salvage operations with limited accessibility and visibility. From visually-assessing site operations and preventing equipment collisions to simulating material handling activities to supervising remotes sites…

77 FR 50495 - Agency Information Collection Activities; Proposed Collection; Comment Request; Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-21

... www.regulations.gov Web site is an ``anonymous access'' system, which means EPA will not know your... public docket that are available electronically. Once in the system, select ``search,'' then key in the... homes under Home Performance with ENERGY STAR and ENERGY STAR's HVAC Quality Installation program...

75 FR 34449 - Agency Information Collection Activities: Extension Without Change of Existing Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

... to EEOC, comments may be submitted to EEOC electronically on the Federal eRulemaking Portal: http://www.regulations.gov . After accessing this web site, follow its instructions for submitting comments. All comments received will be posted without change to http://www.regulations.gov , including any...

Atomic resolution crystal structure of VcLMWPTP-1 from Vibrio cholerae O395: Insights into a novel mode of dimerization in the low molecular weight protein tyrosine phosphatase family

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

Nath, Seema; Banerjee, Ramanuj; Sen, Udayaditya, E-mail: udayaditya.sen@saha.ac.in

Highlights: • VcLMWPTP-1 forms dimer in solution. • The dimer is catalytically active unlike other reported dimeric LMWPTPs. • The formation of extended dimeric surface excludes the active site pocket. • The surface bears closer resemblance to eukaryotic LMWPTPs. - Abstract: Low molecular weight protein tyrosine phosphatase (LMWPTP) is a group of phosphotyrosine phosphatase ubiquitously found in a wide range of organisms ranging from bacteria to mammals. Dimerization in the LMWPTP family has been reported earlier which follows a common mechanism involving active site residues leading to an enzymatically inactive species. Here we report a novel form of dimerization inmore » a LMWPTP from Vibrio cholera 0395 (VcLMWPTP-1). Studies in solution reveal the existence of the dimer in solution while kinetic study depicts the active form of the enzyme. This indicates that the mode of dimerization in VcLMWPTP-1 is different from others where active site residues are not involved in the process. A high resolution (1.45 Å) crystal structure of VcLMWPTP-1 confirms a different mode of dimerization where the active site is catalytically accessible as evident by a tightly bound substrate mimicking ligand, MOPS at the active site pocket. Although being a member of a prokaryotic protein family, VcLMWPTP-1 structure resembles very closely to LMWPTP from a eukaryote, Entamoeba histolytica. It also delineates the diverse surface properties around the active site of the enzyme.« less

Leveraging Technology and Social Media for Information Sharing

DTIC Science & Technology

2009-04-01

praised as a "gift to humanity the benefits of social networking sites such as Facebook and MySpace in forging friendships and understanding.2” The...is relatively easy to sign-up to and access. It should be noted that many DoD installations and agencies restrict access to social networking sites for...to sign-up to and access. As with facebook, many DoD installations and agencies restrict access to social networking sites . Users of Twitter are

Nevada National Security Site Environmental Report 2011 Attachment A: Site Description

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

Cathy Wills, ed.

2012-09-12

This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2011. Included are subsections that summarize the site's geological, hydrological, climatological, and ecological setting and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site's environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current site operations, and assess the impacts of site operationsmore » on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

Exploring the Active Site of the Tungsten, Iron-Sulfur Enzyme Acetylene Hydratase▿ †

PubMed Central

tenBrink, Felix; Schink, Bernhard; Kroneck, Peter M. H.

2011-01-01

The soluble tungsten, iron-sulfur enzyme acetylene hydratase (AH) from mesophilic Pelobacter acetylenicus is a member of the dimethyl sulfoxide (DMSO) reductase family. It stands out from its class as it catalyzes a nonredox reaction, the addition of H2O to acetylene (H—C☰C—H) to form acetaldehyde (CH3CHO). Caught in its active W(IV) state, the high-resolution three-dimensional structure of AH offers an excellent starting point to tackle its unique chemistry and to identify catalytic amino acid residues within the active site cavity: Asp13 close to W(IV) coordinated to two molybdopterin-guanosine-dinucleotide ligands, Lys48 which couples the [4Fe-4S] cluster to the W site, and Ile142 as part of a hydrophobic ring at the end of the substrate access channel designed to accommodate the substrate acetylene. A protocol was developed to express AH in Escherichia coli and to produce active-site variants which were characterized with regard to activity and occupancy of the tungsten and iron-sulfur centers. By this means, fusion of the N-terminal chaperone binding site of the E. coli nitrate reductase NarG to the AH gene improved the yield and activity of AH and its variants significantly. Results from site-directed mutagenesis of three key residues, Asp13, Lys48, and Ile142, document their important role in catalysis of this unusual tungsten enzyme. PMID:21193613

Gardening in the desert: a spatial optimization approach to locating gardens in rapidly expanding urban environments.

PubMed

Mack, Elizabeth A; Tong, Daoqin; Credit, Kevin

2017-10-16

Food access is a global issue, and for this reason, a wealth of studies are dedicated to understanding the location of food deserts and the benefits of urban gardens. However, few studies have linked these two strands of research together to analyze whether urban gardening activity may be a step forward in addressing issues of access for food desert residents. The Phoenix, Arizona metropolitan area is used as a case to demonstrate the utility of spatial optimization models for siting urban gardens near food deserts and on vacant land. The locations of urban gardens are derived from a list obtained from the Maricopa County Cooperative Extension office at the University of Arizona which were geo located and aggregated to Census tracts. Census tracts were then assigned to one of three categories: tracts that contain a garden, tracts that are immediately adjacent to a tract with a garden, and all other non-garden/non-adjacent census tracts. Analysis of variance is first used to ascertain whether there are statistical differences in the demographic, socio-economic, and land use profiles of these three categories of tracts. A maximal covering spatial optimization model is then used to identify potential locations for future gardening activities. A constraint of these models is that gardens be located on vacant land, which is a growing problem in rapidly urbanizing environments worldwide. The spatial analysis of garden locations reveals that they are centrally located in tracts with good food access. Thus, the current distribution of gardens does not provide an alternative food source to occupants of food deserts. The maximal covering spatial optimization model reveals that gardens could be sited in alternative locations to better serve food desert residents. In fact, 53 gardens may be located to cover 96.4% of all food deserts. This is an improvement over the current distribution of gardens where 68 active garden sites provide coverage to a scant 8.4% of food desert residents. People in rapidly urbanizing environments around the globe suffer from poor food access. Rapid rates of urbanization also present an unused vacant land problem in cities around the globe. This paper highlights how spatial optimization models can be used to improve healthy food access for food desert residents, which is a critical first step in ameliorating the health problems associated with lack of healthy food access including heart disease and obesity.

8 CFR 214.12 - Preliminary enrollment of schools in the Student and Exchange Visitor Information System (SEVIS).

Code of Federal Regulations, 2011 CFR

2011-01-01

... eligible schools to apply for preliminary enrollment through the Internet is as follows: (1) Eligible institutions must access the Internet site, http://www.ins.usdoj.gov/sevis. Upon accessing the site, the... access the Internet site and will electronically enter the school's information for its Form I-17. (c...

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.

"Change yourself and the whole world will become kinder": Russian activists for reproductive health and the limits of claims making for women.

PubMed

Rivkin-Fish, Michele

2004-09-01

This article views reproductive health activism as a fruitful site for analyzing the cultural logics through which legitimate claims for women's needs become expressed and circumscribed. It begins from the observation that in the United States and Britain, reproductive health has been a key arena for feminist political claims and struggles for women's rights, bodily integrity, access to health care, and demands for authority in relations with experts. These concerns and struggles have not, however, emerged in all postsocialist contexts, and new activism in Russia reveals strikingly different agendas. Innovative groups of health providers seeking to increase women's access to birth control methods and safe sex, home birth opportunities, and improved health services work outside of feminist perspectives and reject political paths for change. By examining the ideological inspirations, cultural logics, and political-economic constraints shaping the outreach work of Russian health practitioners, the article explains how and why health activism became a site for personal "spiritual" revival and the strengthening of nuclear families. It also explores how conditions following the collapse of socialism have further legitimized activists' rejection of political agendas for change.

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

Clayton, C.; Gueretta, J.; Tack, J.

The Manhattan Engineer District (MED) and U.S. Atomic Energy Commission (AEC) contracted for support work through private and academic parties through the early 1960's. The work often involved radioactive materials. Residual radioactive contamination was left at some of more than 600 potentially contaminated (candidate) sites, and worker health and safety concerns remain from the site operations and subsequent remediation activities. The U.S. Department of Energy (DOE) initiated a program to identify and protect records of MED/AEC activities and of remediation work conducted under the Formerly Utilized Sites Remedial Action Program (FUSRAP) to aid in resolving questions about site conditions, liability,more » and worker health and safety and to ensure ongoing protectiveness of human health and the environment. This paper discusses DOE activities undertaken to locate records collections, confirm retention schedules and access requirements, and document information about the collections for use by future stewards. In conclusion: DOE-LM recognizes that records and information management is a critical component of effective LTS and M. Records are needed to answer questions about site conditions and demonstrate to the public in the future that the sites are safe. DOE-LM is working to satisfy present needs and anticipate future uses for FUSRAP records, and compile a collection of site and program information from which future stewards can readily locate and retrieve needed information. (authors)« less

Hydrophobic Shielding Drives Catalysis of Hydride Transfer in a Family of F420H2-Dependent Enzymes.

PubMed

Mohamed, A Elaaf; Condic-Jurkic, Karmen; Ahmed, F Hafna; Yuan, Peng; O'Mara, Megan L; Jackson, Colin J; Coote, Michelle L

2016-12-13

A family of flavin/deazaflavin-dependent oxidoreductases (FDORs) from mycobacteria has been recently characterized and found to play a variety of catalytic roles, including the activation of prodrugs such as the candidate anti-tuberculosis drug pretomanid (PA-824). However, our understanding of the catalytic mechanism used by these enzymes is relatively limited. To address this, we have used a combination of quantum mechanics and molecular dynamics calculations to study the catalytic mechanism of the activation of pretomanid by the deazaflavin-dependent nitroreductase (Ddn) from Mycobacterium tuberculosis. The preferred pathway involves an initial hydride transfer step from the deprotonated cofactor (i.e., F 420 H - ), with subsequent protonation, before a series of spontaneous intramolecular reactions to form the final reactive nitrogen species. The most likely proton source is a hydroxonium ion within the solvent accessible active site. Intriguingly, catalysis of the rate-determining hydride transfer step is aided by three tyrosine residues that form a hydrophobic barrier around the active site that, upon reaction, is then disrupted to allow increased water accessibility to facilitate the subsequent proton transfer step. The catalytic mechanism we propose is consistent with previous experimental observations of the Ddn enzyme and will inform the design of improved prodrugs in the future.

Eisenhower National Historic Site visitor transportation and access study

DOT National Transportation Integrated Search

2017-11-01

This study evaluates the current shuttle system and Eisenhower National Historic Site, which is currently the sole access to the site. Visitation at Eisenhower has been declining since the site opened, and the study looks at the impacts of this trend...

Effectiveness of a Web-Supplemented Astronomy Survey Course

NASA Astrophysics Data System (ADS)

Hufnagel, B.

1997-12-01

An astronomy survey course for \\ 200 non-science majors, offered in spring 1997 at Michigan State University, was supplemented with an internet site. Web access was voluntary, with the exception of about 10% of the homework problems. In addition, all of the answers to homeworks, in-class activities, and tests were available only on the website. The website included web versions of all the usual hard-copy handouts, as well as lecture notes, links to other astronomy URLs, and a frequently-asked question (FAQ) site taken from student email to the professors. MSU students can access the Web through \\ 30 PC labs on and off campus, and through private PCs in the dorms where most of the MSU students live. A mid-semester open-ended feedback form (for class credit) was administered in-class to the students, with 151 respondents. Their responses to the question ``About how frequently do you access the course website?'' will be correlated to their grade at that point in the course, their gender, and their purpose for accessing the website. These results will be interesting to astronomy teachers who would like to offer additional resources and more lines of communication to their students at low cost and without abandoning traditional methods.

Matriptase shedding is closely coupled with matriptase zymogen activation and requires de novo proteolytic cleavage likely involving its own activity

PubMed Central

Barndt, Robert; Gu, Yayun; Chen, Chien-Yu; Tseng, I-Chu; Su, Sheng-Fang; Wang, Jehng-Kang; Johnson, Michael D.

2017-01-01

The type 2 transmembrane serine protease matriptase is involved in many pathophysiological processes probably via its enzymatic activity, which depends on the dynamic relationship between zymogen activation and protease inhibition. Matriptase shedding can prolong the life of enzymatically active matriptase and increase accessibility to substrates. We show here that matriptase shedding occurs via a de novo proteolytic cleavage at sites located between the SEA domain and the CUB domain. Point or combined mutations at the four positively charged amino acid residues in the region following the SEA domain allowed Arg-186 to be identified as the primary cleavage site responsible for matriptase shedding. Kinetic studies further demonstrate that matriptase shedding is temporally coupled with matriptase zymogen activation. The onset of matriptase shedding lags one minute behind matriptase zymogen activation. Studies with active site triad Ser-805 point mutated matriptase, which no longer undergoes zymogen activation or shedding, further suggests that matriptase shedding depends on matriptase zymogen activation, and that matriptase proteolytic activity may be involved in its own shedding. Our studies uncover an autonomous mechanism coupling matriptase zymogen activation, proteolytic activity, and shedding such that a proportion of newly generated active matriptase escapes HAI-1-mediated rapid inhibition by shedding into the extracellular milieu. PMID:28829816

Condensation of chromatin in transcriptional regions of an inactivated plant transgene: evidence for an active role of transcription in gene silencing.

PubMed

van Blokland, R; ten Lohuis, M; Meyer, P

1997-12-01

The chromatin structures of two epigenetic alleles of a transgene were investigated by measuring the local accessibility of transgene chromatin to endonucleases. The two epialleles represented the active, hypomethylated state of a transgene in line 17-I of Petunia hybrida, and a transcriptionally inactive, hypermethylated derivative of the same transgene in line 17-IV. In nuclear preparations the inactive epiallele was significantly less sensitive to DNasel digestion and nuclease S7 digestion than the transcriptionally active epiallele, whereas no significant differences in accessibility were observed between naked DNA samples of the two epialleles. Our data suggest that a condensed chromatin structure is specifically imposed on transcribed regions of the construct in line 17-IV. In contrast, in both epialleles the plasmid region of the transgene, which is not transcriptionally active in plants, retains the same accessibility to endonucleases as the chromosomal integration site. These data suggest that transcriptional inactivation is linked to the process of transcription, and imply that control of transgene expression via the use of inducible or tissue-specific promoters might prevent transgene silencing and conserve the active state of transgenes during sexual propagation.

An Ecological Approach to Exploring Rural Food Access and Active Living for Families With Preschoolers.

PubMed

Buro, Brandy; Gold, Abby; Contreras, Dawn; Keim, Ann L; Mobley, Amy R; Oscarson, Renee; Peters, Paula; Procter, Sandy; Smathers, Carol

2015-01-01

To identify factors using the Ecological Model of Childhood Overweight related to accessing nutritious foods and physical activity opportunities from the perspectives of rural parents of preschoolers. A mixed-methods study using a quantitative survey (Active Where?) and qualitative interviews. Analyzed interview themes provided context to the survey results. The setting was Head Start centers, county human service offices, and Women, Infants, and Children Program sites in rural counties in the Midwest. Rural parents (n = 377) of preschoolers took part in the survey in 7 Midwestern states; 15 similar participants were interviewed from 1 of the states. Transcribed interviews were coded. Frequencies and chi-square tests were computed; significance was set at P < .05. The Active Where? survey and interviews revealed that close proximity to recreation spaces and traffic safety issues influenced physical activity. For food access, close proximity to full service grocery stores did not influence access to healthy foods because respondents traveled to urban communities to purchase healthy foods. Public transportation solutions and enhanced neighborhood safety are potential community-wide obesity prevention strategies in rural communities. However, interventions should be tailored to the community's stage of readiness. Strong social networks should be considered an asset for community change in these regions. Copyright © 2015 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Ty1-copia elements reveal diverse insertion sites linked to polymorphisms among flax (Linum usitatissimum L.) accessions.

PubMed

Galindo-González, Leonardo; Mhiri, Corinne; Grandbastien, Marie-Angèle; Deyholos, Michael K

2016-12-07

Initial characterization of the flax genome showed that Ty1-copia retrotransposons are abundant, with several members being recently inserted, and in close association with genes. Recent insertions indicate a potential for ongoing transpositional activity that can create genomic diversity among accessions, cultivars or varieties. The polymorphisms generated constitute a good source of molecular markers that may be associated with phenotype if the insertions alter gene activity. Flax, where accessions are bred mainly for seed nutritional properties or for fibers, constitutes a good model for studying the relationship of transpositional activity with diversification and breeding. In this study, we estimated copy number and used a type of transposon display known as Sequence-Specific Amplification Polymorphisms (SSAPs), to characterize six families of Ty1-copia elements across 14 flax accessions. Polymorphic insertion sites were sequenced to find insertions that could potentially alter gene expression, and a preliminary test was performed with selected genes bearing transposable element (TE) insertions. Quantification of six families of Ty1-copia elements indicated different abundances among TE families and between flax accessions, which suggested diverse transpositional histories. SSAPs showed a high level of polymorphism in most of the evaluated retrotransposon families, with a trend towards higher levels of polymorphism in low-copy number families. Ty1-copia insertion polymorphisms among cultivars allowed a general distinction between oil and fiber types, and between spring and winter types, demonstrating their utility in diversity studies. Characterization of polymorphic insertions revealed an overwhelming association with genes, with insertions disrupting exons, introns or within 1 kb of coding regions. A preliminary test on the potential transcriptional disruption by TEs of four selected genes evaluated in three different tissues, showed one case of significant impact of the insertion on gene expression. We demonstrated that specific Ty1-copia families have been active since breeding commenced in flax. The retrotransposon-derived polymorphism can be used to separate flax types, and the close association of many insertions with genes defines a good source of potential mutations that could be associated with phenotypic changes, resulting in diversification processes.

Not Just a Walk in the Park: Methodological Improvements for Determining Environmental Justice Implications of Park Access in New York City for the Promotion of Physical Activity

PubMed Central

Miyake, Keith K.; Maroko, Andrew R.; Grady, Kristen L.; Maantay, Juliana A.; Arno, Peter S.

2011-01-01

The purpose of this study is to test the hypothesis that access to parks in New York City is not equitable across racial and ethnic categories. It builds on previous research that has linked access to parks and open space with increased physical activity, which in turn may reduce the risk for adverse health outcomes related to obesity. Systematic patterns of uneven access to parks might help to explain disparities in these health outcomes across sociodemographic populations that are not fully explained by individual-level risk factors and health behaviors, and therefore access to parks becomes an environmental justice issue. This study is designed to shed light on the “unpatterned inequities” of park distributions identified in previous studies of New York City park access. It uses a combination of network analysis and a cadastral-based expert dasymetric system (CEDS) to estimate the racial/ethnic composition of populations within a reasonable walking distance of 400m from parks. The distance to the closest park, number of parks within walking distance, amount of accessible park space, and number of physical activity sites are then evaluated across racial/ethnic categories, and are compared to the citywide populations using odds ratios. The odds ratios revealed patterns that at first glance appear to contradict the notion of distributional inequities. However, discussion of the results points to the need for reassessing what is meant by “access” to more thoroughly consider the aspects of parks that are most likely to contribute to physical activity and positive health outcomes. PMID:21874148

UTSA-74: A MOF-74 Isomer with Two Accessible Binding Sites per Metal Center for Highly Selective Gas Separation.

PubMed

Luo, Feng; Yan, Changsheng; Dang, Lilong; Krishna, Rajamani; Zhou, Wei; Wu, Hui; Dong, Xinglong; Han, Yu; Hu, Tong-Liang; O'Keeffe, Michael; Wang, Lingling; Luo, Mingbiao; Lin, Rui-Biao; Chen, Banglin

2016-05-04

A new metal-organic framework Zn2(H2O)(dobdc)·0.5(H2O) (UTSA-74, H4dobdc = 2,5-dioxido-1,4-benzenedicarboxylic acid), Zn-MOF-74/CPO-27-Zn isomer, has been synthesized and structurally characterized. It has a novel four coordinated fgl topology with one-dimensional channels of about 8.0 Å. Unlike metal sites in the well-established MOF-74 with a rod-packing structure in which each of them is in a five coordinate square pyramidal coordination geometry, there are two different Zn(2+) sites within the binuclear secondary building units in UTSA-74 in which one of them (Zn1) is in a tetrahedral while another (Zn2) in an octahedral coordination geometry. After activation, the two axial water molecules on Zn2 sites can be removed, generating UTSA-74a with two accessible gas binding sites per Zn2 ion. Accordingly, UTSA-74a takes up a moderately high and comparable amount of acetylene (145 cm(3)/cm(3)) to Zn-MOF-74. Interestingly, the accessible Zn(2+) sites in UTSA-74a are bridged by carbon dioxide molecules instead of being terminally bound in Zn-MOF-74, so UTSA-74a adsorbs a much smaller amount of carbon dioxide (90 cm(3)/cm(3)) than Zn-MOF-74 (146 cm(3)/cm(3)) at room temperature and 1 bar, leading to a superior MOF material for highly selective C2H2/CO2 separation. X-ray crystal structures, gas sorption isotherms, molecular modeling, and simulated and experimental breakthroughs comprehensively support this result.

How to Write Easy-to-Read Health Materials: MedlinePlus

MedlinePlus

... practices. An accessible Web site helps people with reading and learning disabilities. For more information on Web accessibility, see the WebAIM (Web Accessibility in Mind) site from the Center for Persons with Disabilities ...

Beyond Section 508: The Spectrum of Legal Requirements for Accessible e-Government Web Sites in the United States

ERIC Educational Resources Information Center

Jaeger, Paul T.

2004-01-01

In the United States, a number of federal laws establish requirements that electronic government (e-government) information and services be accessible to individuals with disabilities. These laws affect e-government Web sites at the federal, state, and local levels. To this point, research about the accessibility of e-government Web sites has…

Information-Seeking on the Internet.

PubMed

Singaravelu, Vinod; Stewart, Anne; Adams, Joanna; Simkin, Sue; Hawton, Keith

2015-01-01

The Internet is used by young people at risk of self-harm to communicate, find information, and obtain support. We aimed to identify and analyze websites potentially accessed by these young people. Six search terms, relating to self-harm/suicide and depression, were input into four search engines. Websites were analyzed for access, content/purpose, and tone. In all, 314 websites were included in the analysis. Most could be accessed without restriction. Sites accessed by self-harm/suicide search terms were mostly positive or preventive in tone, whereas sites accessed by the term ways to kill yourself tended to have a negative tone. Information about self-harm methods was common with specific advice on how to self-harm in 15.8% of sites, encouragement of self-harm in 7.0%, and evocative images of self-harm/suicide in 20.7%. Advice on how to get help was given in 56.1% of sites. Websites relating to suicide or self-harm are easily accessed. Many sites are potentially helpful. However, a significant proportion of sites are potentially harmful through normalizing or encouraging self-harm. Enquiry regarding Internet use should be routinely included while assessing young people at risk.

Participatory role of zinc in structural and functional characterization of bioremediase: a unique thermostable microbial silica leaching protein.

PubMed

Chowdhury, Trinath; Sarkar, Manas; Chaudhuri, Biswadeep; Chattopadhyay, Brajadulal; Halder, Umesh Chandra

2015-07-01

A unique protein, bioremediase (UniProt Knowledgebase Accession No.: P86277), isolated from a hot spring bacterium BKH1 (GenBank Accession No.: FJ177512), has shown to exhibit silica leaching activity when incorporated to prepare bio-concrete material. Matrix-assisted laser desorption ionization mass spectrometry analysis suggests that bioremediase is 78% homologous to bovine carbonic anhydrase II though it does not exhibit carbonic anhydrase-like activity. Bioinformatics study is performed for understanding the various physical and chemical parameters of the protein which predicts the involvement of zinc encircled by three histidine residues (His94, His96 and His119) at the active site of the protein. Isothermal titration calorimetric-based thermodynamic study on diethyl pyrocarbonate-modified protein recognizes the presence of Zn(2+) in the enzyme moiety. Exothermic to endothermic transition as observed during titration of the protein with Zn(2+) discloses that there are at least two binding sites for zinc within the protein moiety. Addition of Zn(2+) regains the activity of EDTA chelated bioremediase confirming the presence of extra binding site of Zn(2+) in the protein moiety. Revival of folding pattern of completely unfolded urea-treated protein by Zn(2+) explains the participatory role of zinc in structural stability of the protein. Restoration of the λ max in intrinsic fluorescence emission study of the urea-treated protein by Zn(2+) similarly confirms the involvement of Zn in the refolding of the protein. The utility of bioremediase for silica nanoparticles preparation is observed by field emission scanning electron microscopy.

Breast reconstruction post mastectomy- Let's Google it. Accessibility, readability and quality of online information.

PubMed

Lynch, Noel P; Lang, Bronagh; Angelov, Sophia; McGarrigle, Sarah A; Boyle, Terence J; Al-Azawi, Dhafir; Connolly, Elizabeth M

2017-04-01

This study evaluated the readability, accessibility and quality of information pertaining to breast reconstruction post mastectomy on the Internet in the English language. Using the Google © search engine the keywords "Breast reconstruction post mastectomy" were searched for. We analyzed the top 75 sites. The Flesch Reading Ease Score and Gunning Fog Index were calculated to assess readability. Web site quality was assessed objectively using the University of Michigan Consumer Health Web site Evaluation Checklist. Accessibility was determined using an automated accessibility tool. In addition, the country of origin, type of organisation producing the site and presence of Health on the Net (HoN) Certification status was recorded. The Web sites were difficult to read and comprehend. The mean Flesch Reading Ease scores were 55.5. The mean Gunning Fog Index scores was 8.6. The mean Michigan score was 34.8 indicating weak quality of websites. Websites with HoN certification ranked higher in the search results (p = 0.007). Website quality was influenced by organisation type (p < 0.0001) with academic/healthcare, not for profit and government sites having higher Michigan scores. 20% of sites met the minimum accessibility criteria. Internet information on breast reconstruction post mastectomy and procedures is poorly written and we suggest that Webpages providing information must be made more readable and accessible. We suggest that health professionals should recommend Web sites that are easy to read and contain high-quality surgical information. Medical information on the Internet should be readable, accessible, reliable and of a consistent quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost effective Internet access and video conferencing for a community cancer network.

PubMed Central

London, J. W.; Morton, D. E.; Marinucci, D.; Catalano, R.; Comis, R. L.

1995-01-01

Utilizing the ubiquitous personal computer as a platform, and Integrated Services Digital Network (ISDN) communications, cost effective medical information access and consultation can be provided for physicians at geographically remote sites. Two modes of access are provided: information retrieval via the Internet, and medical consultation video conferencing. Internet access provides general medical information such as current treatment options, literature citations, and active clinical trials. During video consultations, radiographic and pathology images, and medical text reports (e.g., history and physical, pathology, radiology, clinical laboratory reports), may be viewed and simultaneously annotated by either video conference participant. Both information access modes have been employed by physicians at community hospitals which are members of the Jefferson Cancer Network, and oncologists at Thomas Jefferson University Hospital. This project has demonstrated the potential cost effectiveness and benefits of this technology. Images Figure 1 Figure 2 Figure 3 PMID:8563397

Structure of granzyme C reveals an unusual mechanism of protease autoinhibition

PubMed Central

Kaiserman, Dion; Buckle, Ashley M.; Van Damme, Petra; Irving, James A.; Law, Ruby H. P.; Matthews, Antony Y.; Bashtannyk-Puhalovich, Tanya; Langendorf, Chris; Thompson, Philip; Vandekerckhove, Joël; Gevaert, Kris; Whisstock, James C.; Bird, Phillip I.

2009-01-01

Proteases act in important homeostatic pathways and are tightly regulated. Here, we report an unusual structural mechanism of regulation observed by the 2.5-Å X-ray crystal structure of the serine protease, granzyme C. Although the active-site triad residues adopt canonical conformations, the oxyanion hole is improperly formed, and access to the primary specificity (S1) pocket is blocked through a reversible rearrangement involving Phe-191. Specifically, a register shift in the 190-strand preceding the active-site serine leads to Phe-191 filling the S1 pocket. Mutation of a unique Glu–Glu motif at positions 192–193 unlocks the enzyme, which displays chymase activity, and proteomic analysis confirms that activity of the wild-type protease can be released through interactions with an appropriate substrate. The 2.5-Å structure of the unlocked enzyme reveals unprecedented flexibility in the 190-strand preceding the active-site serine that results in Phe-191 vacating the S1 pocket. Overall, these observations describe a broadly applicable mechanism of protease regulation that cannot be predicted by template-based modeling or bioinformatic approaches alone. PMID:19299505

Substrate-Induced Facilitated Dissociation of the Competitive Inhibitor from the Active Site of O-Acetyl Serine Sulfhydrylase Reveals a Competitive-Allostery Mechanism.

PubMed

Singh, Appu Kumar; Ekka, Mary Krishna; Kaushik, Abhishek; Pandya, Vaibhav; Singh, Ravi P; Banerjee, Shrijita; Mittal, Monica; Singh, Vijay; Kumaran, S

2017-09-19

By classical competitive antagonism, a substrate and competitive inhibitor must bind mutually exclusively to the active site. The competitive inhibition of O-acetyl serine sulfhydrylase (OASS) by the C-terminus of serine acetyltransferase (SAT) presents a paradox, because the C-terminus of SAT binds to the active site of OASS with an affinity that is 4-6 log-fold (10 4 -10 6 ) greater than that of the substrate. Therefore, we employed multiple approaches to understand how the substrate gains access to the OASS active site under physiological conditions. Single-molecule and ensemble approaches showed that the active site-bound high-affinity competitive inhibitor is actively dissociated by the substrate, which is not consistent with classical views of competitive antagonism. We employed fast-flow kinetic approaches to demonstrate that substrate-mediated dissociation of full length SAT-OASS (cysteine regulatory complex) follows a noncanonical "facilitated dissociation" mechanism. To understand the mechanism by which the substrate induces inhibitor dissociation, we resolved the crystal structures of enzyme·inhibitor·substrate ternary complexes. Crystal structures reveal a competitive allosteric binding mechanism in which the substrate intrudes into the inhibitor-bound active site and disengages the inhibitor before occupying the site vacated by the inhibitor. In summary, here we reveal a new type of competitive allosteric binding mechanism by which one of the competitive antagonists facilitates the dissociation of the other. Together, our results indicate that "competitive allostery" is the general feature of noncanonical "facilitated/accelerated dissociation" mechanisms. Further understanding of the mechanistic framework of "competitive allosteric" mechanism may allow us to design a new family of "competitive allosteric drugs/small molecules" that will have improved selectivity and specificity as compared to their competitive and allosteric counterparts.

The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence

PubMed Central

Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S.

2018-01-01

Species’ distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised recreation in areas occupied by grizzly bears. PMID:29389939

The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence.

PubMed

Ladle, Andrew; Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S

2018-01-01

Species' distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised recreation in areas occupied by grizzly bears.

Structural Insights into the Protease-like Antigen Plasmodium falciparum SERA5 and Its Noncanonical Active-Site Serine

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

Hodder, Anthony N.; Malby, Robyn L.; Clarke, Oliver B.

The sera genes of the malaria-causing parasite Plasmodium encode a family of unique proteins that are maximally expressed at the time of egress of parasites from infected red blood cells. These multi-domain proteins are unique, containing a central papain-like cysteine-protease fragment enclosed between the disulfide-linked N- and C-terminal domains. However, the central fragment of several members of this family, including serine repeat antigen 5 (SERA5), contains a serine (S596) in place of the active-site cysteine. Here we report the crystal structure of the central protease-like domain of Plasmodium falciparum SERA5, revealing a number of anomalies in addition to the putativemore » nucleophilic serine: (1) the structure of the putative active site is not conducive to binding substrate in the canonical cysteine-protease manner; (2) the side chain of D594 restricts access of substrate to the putative active site; and (3) the S{sub 2} specificity pocket is occupied by the side chain of Y735, reducing this site to a small depression on the protein surface. Attempts to determine the structure in complex with known inhibitors were not successful. Thus, despite having revealed its structure, the function of the catalytic domain of SERA5 remains an enigma.« less

22 CFR 502.6 - Terms of use for accessing program materials available on agency Web sites.

Code of Federal Regulations, 2014 CFR

2014-04-01

... available on agency Web sites. 502.6 Section 502.6 Foreign Relations BROADCASTING BOARD OF GOVERNORS... program materials available on agency Web sites. (a) By accessing Agency Web sites, Requestors agree to all the Terms of Use available on those Web sites. (b) All Requestors are advised that Agency program...

Chemical tailoring of teicoplanin with site-selective reactions.

PubMed

Pathak, Tejas P; Miller, Scott J

2013-06-05

Semisynthesis of natural product derivatives combines the power of fermentation with orthogonal chemical reactions. Yet, chemical modification of complex structures represents an unmet challenge, as poor selectivity often undermines efficiency. The complex antibiotic teicoplanin eradicates bacterial infections. However, as resistance emerges, the demand for improved analogues grows. We have discovered chemical reactions that achieve site-selective alteration of teicoplanin. Utilizing peptide-based additives that alter reaction selectivities, certain bromo-teicoplanins are accessible. These new compounds are also scaffolds for selective cross-coupling reactions, enabling further molecular diversification. These studies enable two-step access to glycopeptide analogues not available through either biosynthesis or rapid total chemical synthesis alone. The new compounds exhibit a spectrum of activities, revealing that selective chemical alteration of teicoplanin may lead to analogues with attenuated or enhanced antibacterial properties, in particular against vancomycin- and teicoplanin-resistant strains.

Access to Space Interactive Design Web Site

NASA Technical Reports Server (NTRS)

Leon, John; Cutlip, William; Hametz, Mark

2000-01-01

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

Probing Conformational Changes and Interfacial Recognition Site of Lipases With Surfactants and Inhibitors.

PubMed

Mateos-Diaz, E; Amara, S; Roussel, A; Longhi, S; Cambillau, C; Carrière, F

2017-01-01

Structural studies on lipases by X-ray crystallography have revealed conformational changes occurring in the presence of surfactants/inhibitors and the pivotal role played by a molecular "lid" of variable size and structure depending on the enzyme. Besides controlling the access to the enzyme active site, the lid is involved in lipase activation, formation of the interfacial recognition site (IRS), and substrate docking within the active site. The combined use of surfactants and inhibitors has been critical for a better understanding of lipase structure-function relationships. An overview of crystal structures of lipases in complex with surfactants and inhibitors reveals common structural features and shows how surfactants monomers interact with the lid in its open conformation. The location of surfactants, inhibitors, and hydrophobic residues exposed upon lid opening provides insights into the IRS of lipases. The mechanism by which surfactants promote the lid opening can be further investigated in solution by site-directed spin labeling of lipase coupled to electron paramagnetic resonance spectroscopy. These experimental approaches are illustrated here by results obtained with mammalian digestive lipases, fungal lipases, and cutinases. © 2017 Elsevier Inc. All rights reserved.

Archaeological data recovery at drill pad U19au, Nye County, Nevada

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

Henton, G.H.; Pippin, L.C.

1991-01-01

Construction activities accompanying underground nuclear tests result in the disturbance of the surface terrain at the Nevada Test Site. In compliance with Federal legislation (National Historic Preservation Act of 1966 (PL 89-665) and National Environmental Policy Act of 1969 (PL 91-190)), the US Department of Energy (DOE), Field Office, Nevada, has long required that cultural resources studies must precede all land-disturbing activities on the Nevada Test Site. In accordance with 36 CFR Part 800, these studies consist of archaeological surveys conducted prior to the land-disturbing activities. The intent of these surveys is to identify and evaluate all cultural resources thatmore » might be adversely affected by the proposed construction activity. This report presents the final analysis of the data recovered from archaeological investigations conducted at the U19au drill site and access road. This report includes descriptions of the archaeological sites as recorded during the original survey, the research design used to guide the investigations, the method and techniques used to collect and analyze the data, and the results and interpretations of the analysis. 200 refs., 112 figs., 53 tabs.« less

Dihydrofolate reductase: A potential drug target in trypanosomes and leishmania

NASA Astrophysics Data System (ADS)

Zuccotto, Fabio; Martin, Andrew C. R.; Laskowski, Roman A.; Thornton, Janet M.; Gilbert, Ian H.

1998-05-01

Dihydrofolate reductase has successfully been used as a drug target in the area of anti-cancer, anti-bacterial and anti-malarial chemotherapy. Little has been done to evaluate it as a drug target for treatment of the trypanosomiases and leishmaniasis. A crystal structure of Leishmania major dihydrofolate reductase has been published. In this paper, we describe the modelling of Trypanosoma cruzi and Trypanosoma brucei dihydrofolate reductases based on this crystal structure. These structures and models have been used in the comparison of protozoan, bacterial and human enzymes in order to highlight the different features that can be used in the design of selective anti-protozoan agents. Comparison has been made between residues present in the active site, the accessibility of these residues, charge distribution in the active site, and the shape and size of the active sites. Whilst there is a high degree of similarity between protozoan, human and bacterial dihydrofolate reductase active sites, there are differences that provide potential for selective drug design. In particular, we have identified a set of residues which may be important for selective drug design and identified a larger binding pocket in the protozoan than the human and bacterial enzymes.

78 FR 57150 - Agency Information Collection Activities; Proposed Collection; Request for Comments on Three...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-17

... (Identify Docket ID No. EPA-HQ- OW-2008-0719 in the subject line). Mail: Water Docket, Environmental... or email. The www.regulations.gov Web site is an ``anonymous access'' system, which means EPA will.../epahome/dockets.htm . FOR FURTHER INFORMATION CONTACT: Sandra Rivera, State and Regional Branch, Water...

77 FR 29320 - Proposed Information Collection; Election Administration in Urban and Rural Areas; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... duties and activities to promote the effective administration of Federal elections. DATES: Written....gov with Urban/Rural study as the subject line. Written comments on the proposed information... survey: (1) Access the EAC Web site at www.eac.gov ; (2) write to the EAC (including your address and...

75 FR 81643 - Hydropower Resource Assessment at Existing Reclamation Facilities-Draft Report

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

[email protected] . The Draft Report is also accessible from the following Web site: http://www.usbr.gov/power... or about 48.4 billion pounds of coal. Reclamation is the second largest producer of hydroelectric power in the United States, and is actively engaged in looking for opportunities to encourage...

76 FR 5800 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

....regulations.gov Web site is an ``anonymous access'' system, which means EPA will not know your identity or... renew an existing approved Information Collection Request (ICR) 2258.02-- Implementation of the 1997 and...-566-1741 Mail: Attention Docket ID No. EPA-HQ-OAR-2007-0265, U.S. Environmental Protection Agency, EPA...

78 FR 67395 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Registration...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

..., contain fillable- fileable, and E-signature capabilities, and the FARA eFile system in operation since March 1, 2011, permits registrants to file their registration forms electronically to the FARA Registration Unit, 24 hours a day, seven days a week. FARA eFile is accessed via the FARA public Web site...

Activation of Latent Dihydroorotase from Aquifex aeolicus by Pressure*

PubMed Central

Hervé, Guy; Evans, Hedeel Guy; Fernado, Roshini; Patel, Chandni; Hachem, Fatme; Evans, David R.

2017-01-01

Elevated hydrostatic pressure was used to probe conformational changes of Aquifex aeolicus dihydroorotase (DHO), which catalyzes the third step in de novo pyrimidine biosynthesis. The isolated protein, a 45-kDa monomer, lacks catalytic activity but becomes active upon formation of a dodecameric complex with aspartate transcarbamoylase (ATC). X-ray crystallographic studies of the isolated DHO and of the complex showed that association induces several major conformational changes in the DHO structure. In the isolated DHO, a flexible loop occludes the active site blocking the access of substrates. The loop is mostly disordered but is tethered to the active site region by several electrostatic and hydrogen bonds. This loop becomes ordered and is displaced from the active site upon formation of DHO-ATC complex. The application of pressure to the complex causes its time-dependent dissociation and the loss of both DHO and ATC activities. Pressure induced irreversible dissociation of the obligate ATC trimer, and as a consequence the DHO is also inactivated. However, moderate hydrostatic pressure applied to the isolated DHO subunit mimics the complex formation and reversibly activates the isolated subunit in the absence of ATC, suggesting that the loop has been displaced from the active site. This effect of pressure is explained by the negative volume change associated with the disruption of ionic interactions and exposure of ionized amino acids to the solvent (electrostriction). The interpretation that the loop is relocated by pressure was validated by site-directed mutagenesis and by inhibition by small peptides that mimic the loop residues. PMID:27746403

Charge neutralization in the active site of the catalytic trimer of aspartate transcarbamoylase promotes diverse structural changes.

PubMed

Endrizzi, James A; Beernink, Peter T

2017-11-01

A classical model for allosteric regulation of enzyme activity posits an equilibrium between inactive and active conformations. An alternative view is that allosteric activation is achieved by increasing the potential for conformational changes that are essential for catalysis. In the present study, substitution of a basic residue in the active site of the catalytic (C) trimer of aspartate transcarbamoylase with a non-polar residue results in large interdomain hinge changes in the three chains of the trimer. One conformation is more open than the chains in both the wild-type C trimer and the catalytic chains in the holoenzyme, the second is closed similar to the bisubstrate-analog bound conformation and the third hinge angle is intermediate to the other two. The active-site 240s loop conformation is very different between the most open and closed chains, and is disordered in the third chain, as in the holoenzyme. We hypothesize that binding of anionic substrates may promote similar structural changes. Further, the ability of the three catalytic chains in the trimer to access the open and closed active-site conformations simultaneously suggests a cyclic catalytic mechanism, in which at least one of the chains is in an open conformation suitable for substrate binding whereas another chain is closed for catalytic turnover. Based on the many conformations observed for the chains in the isolated catalytic trimer to date, we propose that allosteric activation of the holoenzyme occurs by release of quaternary constraint into an ensemble of active-site conformations. © 2017 The Protein Society.

Identification of S-glutathionylation sites in species-specific proteins by incorporating five sequence-derived features into the general pseudo-amino acid composition.

PubMed

Zhao, Xiaowei; Ning, Qiao; Ai, Meiyue; Chai, Haiting; Yang, Guifu

2016-06-07

As a selective and reversible protein post-translational modification, S-glutathionylation generates mixed disulfides between glutathione (GSH) and cysteine residues, and plays an important role in regulating protein activity, stability, and redox regulation. To fully understand S-glutathionylation mechanisms, identification of substrates and specific S-Glutathionylated sites is crucial. Experimental identification of S-glutathionylated sites is labor-intensive and time consuming, so establishing an effective computational method is much desirable due to their convenient and fast speed. Therefore, in this study, a new bioinformatics tool named SSGlu (Species-Specific identification of Protein S-glutathionylation Sites) was developed to identify species-specific protein S-glutathionylated sites, utilizing support vector machines that combine multiple sequence-derived features with a two-step feature selection. By 5-fold cross validation, the performance of SSGlu was measured with an AUC of 0.8105 and 0.8041 for Homo sapiens and Mus musculus, respectively. Additionally, SSGlu was compared with the existing methods, and the higher MCC and AUC of SSGlu demonstrated that SSGlu was very promising to predict S-glutathionylated sites. Furthermore, a site-specific analysis showed that S-glutathionylation intimately correlated with the features derived from its surrounding sites. The conclusions derived from this study might help to understand more of the S-glutathionylation mechanism and guide the related experimental validation. For public access, SSGlu is freely accessible at http://59.73.198.144:8080/SSGlu/. Copyright © 2016 Elsevier Ltd. All rights reserved.

Internet-accessible, near-real-time volcano monitoring data for geoscience education: the Volcanoes Exploration Project—Pu`u `O`o

NASA Astrophysics Data System (ADS)

Poland, M. P.; Teasdale, R.; Kraft, K.

2010-12-01

Internet-accessible real- and near-real-time Earth science datasets are an important resource for geoscience education, but relatively few comprehensive datasets are available, and background information to aid interpretation is often lacking. In response to this need, the U.S. Geological Survey’s (USGS) Hawaiian Volcano Observatory, in collaboration with the National Aeronautics and Space Administration and the University of Hawai‘i, Mānoa, established the Volcanoes Exploration Project: Pu‘u ‘O‘o (VEPP). The VEPP Web site provides access, in near-real time, to geodetic, seismic, and geologic data from the Pu‘u ‘O‘o eruptive vent on Kilauea Volcano, Hawai‘i. On the VEPP Web site, a time series query tool provides a means of interacting with continuous geophysical data. In addition, results from episodic kinematic GPS campaigns and lava flow field maps are posted as data are collected, and archived Webcam images from Pu‘u ‘O‘o crater are available as a tool for examining visual changes in volcanic activity over time. A variety of background information on volcano surveillance and the history of the 1983-present Pu‘u ‘O‘o-Kupaianaha eruption puts the available monitoring data in context. The primary goal of the VEPP Web site is to take advantage of high visibility monitoring data that are seldom suitably well-organized to constitute an established educational resource. In doing so, the VEPP project provides a geoscience education resource that demonstrates the dynamic nature of volcanoes and promotes excitement about the process of scientific discovery through hands-on learning. To support use of the VEPP Web site, a week-long workshop was held at Kilauea Volcano in July 2010, which included 25 participants from the United States and Canada. The participants represented a diverse cross-section of higher learning, from community colleges to research universities, and included faculty who teach both large introductory non-major classes and seminar-style upper division and graduate-level classes. Overall workshop goals were for participants to learn how to interpret each of the VEPP data types, become proficient in the use of the VEPP Web site, provide feedback on site content, and create teaching modules that integrate the site into college and university geoscience curriculum. By the end of the workshop, over 20 new teaching modules were developed and the VEPP Web site was modified based on participant feedback. Teaching activities are available via the VEPP Workshop section of the Science Education Resource Center (SERC) Web site (http://www.nagt.org/nagt/vepp/index.html).

The feasibility of implementing cognitive remediation for work in community based psychiatric rehabilitation programs.

PubMed

McGurk, Susan R; Mueser, Kim T; Watkins, Melanie A; Dalton, Carline M; Deutsch, Heather

2017-03-01

Adding cognitive remediation to vocational rehabilitation services improves cognitive and work functioning in people with serious mental illness, but despite interest, the uptake of cognitive programs into community services has been slow. This study evaluated the feasibility of implementing an empirically supported cognitive remediation program in routine rehabilitation services at 2 sites. The Thinking Skills for Work (TSW) program was adapted for implementation at 2 sites of a large psychiatric rehabilitation agency providing prevocational services, but not community-based vocational services, which were provided off-site. Agency staff were trained to deliver TSW to clients with work or educational goals. Cognitive assessments were conducted at baseline and posttreatment, with work and school activity tracked for 2 years. Eighty-three participants enrolled in TSW, of whom 79.5% completed at least 6 of the 24 computer cognitive exercise sessions (M = 16.7) over an average of 18 weeks. Participants improved significantly from baseline to posttreatment in verbal learning and memory, speed of processing, and overall cognitive functioning. Over the follow-up, 25.3% of participants worked and 47.0% were involved in work or school activity. Higher work rates were observed at the site where participants had easier access to vocational services. The results support the feasibility of implementing the TSW program by frontline staff in agencies providing psychiatric rehabilitation, and suggest that ease of access to vocational services may influence work outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Activity screening of environmental metagenomic libraries reveals novel carboxylesterase families

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

Popovic, Ana; Hai, Tran; Tchigvintsev, Anatoly

Metagenomics has made accessible an enormous reserve of global biochemical diversity. In order to tap into this vast resource of novel enzymes, we have screened over one million clones from metagenome DNA libraries derived from sixteen different environments for carboxylesterase activity and identified 714 positive hits. Here, we validated the esterase activity of 80 selected genes, which belong to 17 different protein families including unknown and cyclase-like proteins. Three metagenomic enzymes exhibited lipase activity, and seven proteins showed polyester depolymerization activity against polylactic acid and polycaprolactone. Detailed biochemical characterization of four new enzymes revealed their substrate preference, whereas their catalyticmore » residues were identified using site-directed mutagenesis. The crystal structure of the metal-ion dependent esterase MGS0169 from the amidohydrolase superfamily revealed a novel active site with a bound unknown ligand. Thus, activity-centered metagenomics has revealed diverse enzymes and novel families of microbial carboxylesterases, whose activity could not have been predicted using bioinformatics tools.« less

Activity screening of environmental metagenomic libraries reveals novel carboxylesterase families

DOE PAGES

Popovic, Ana; Hai, Tran; Tchigvintsev, Anatoly; ...

2017-03-08

Metagenomics has made accessible an enormous reserve of global biochemical diversity. In order to tap into this vast resource of novel enzymes, we have screened over one million clones from metagenome DNA libraries derived from sixteen different environments for carboxylesterase activity and identified 714 positive hits. Here, we validated the esterase activity of 80 selected genes, which belong to 17 different protein families including unknown and cyclase-like proteins. Three metagenomic enzymes exhibited lipase activity, and seven proteins showed polyester depolymerization activity against polylactic acid and polycaprolactone. Detailed biochemical characterization of four new enzymes revealed their substrate preference, whereas their catalyticmore » residues were identified using site-directed mutagenesis. The crystal structure of the metal-ion dependent esterase MGS0169 from the amidohydrolase superfamily revealed a novel active site with a bound unknown ligand. Thus, activity-centered metagenomics has revealed diverse enzymes and novel families of microbial carboxylesterases, whose activity could not have been predicted using bioinformatics tools.« less

Recent Developments on the Turbulence Modeling Resource Website (Invited)

NASA Technical Reports Server (NTRS)

Rumssey, Christopher L.

2015-01-01

The NASA Langley Turbulence Model Resource (TMR) website has been active for over five years. Its main goal of providing a one-stop, easily accessible internet site for up-to-date information on Reynolds-averaged Navier-Stokes turbulence models remains unchanged. In particular, the site strives to provide an easy way for users to verify their own implementations of widely-used turbulence models, and to compare the results from different models for a variety of simple unit problems covering a range of flow physics. Some new features have been recently added to the website. This paper documents the site's features, including recent developments, future plans, and open questions.

Speciation and Attenuation of Arsenic and Selenium at Coal Combustion By-Product Management Facilities

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

K. Ladwig; B. Hensel; D. Wallschlager

2005-10-18

Following completion of contracting activities, sites were identified for the field leachate characterization study. Sampling and Analyses Plans (SAPs) and Site Access Agreements (SAAs) were developed for each site. A total of ten sites were sampled during this reporting period. Among the trace constituents, boron, silicon, and strontium were present in highest concentrations, with median values above 1 mg/L (1,000 {micro}g/L). Work on the first of three sites for the detailed arsenic and selenium adsorption studies began in 2002, prior to completion of the final DOE award. Kd values ranged from 100 to 12,000 L/kg for arsenic (V), 15 tomore » 160 L.kg for As(III), and 5 to 25 L/kg for Se(VI).« less

Modulation of Cardiac Ryanodine Receptor Channels by Alkaline Earth Cations

PubMed Central

Diaz-Sylvester, Paula L.; Porta, Maura; Copello, Julio A.

2011-01-01

Cardiac ryanodine receptor (RyR2) function is modulated by Ca2+ and Mg2+. To better characterize Ca2+ and Mg2+ binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M2+: Mg2+, Ca2+, Sr2+, Ba2+) were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M2+ binding to high affinity activating sites at the cytosolic channel surface, specific for Ca2+ or Sr2+. This activation was interfered by Mg2+ and Ba2+ acting at low affinity M2+-unspecific binding sites. When testing the effects of luminal M2+ as current carriers, all M2+ increased maximal RyR2 open probability (compared to Cs+), suggesting the existence of low affinity activating M2+-unspecific sites at the luminal surface. Responses to M2+ vary from channel to channel (heterogeneity). However, with luminal Ba2+or Mg2+, RyR2 were less sensitive to cytosolic Ca2+ and caffeine-mediated activation, openings were shorter and voltage-dependence was more marked (compared to RyR2 with luminal Ca2+or Sr2+). Kinetics of RyR2 with mixtures of luminal Ba2+/Ca2+ and additive action of luminal plus cytosolic Ba2+ or Mg2+ suggest luminal M2+ differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca2+/Sr2+-specific sites, which stabilize high Po mode (less voltage-dependent) and increase RyR2 sensitivity to cytosolic Ca2+ activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M2+ binding sites (specific for Ca2+ and unspecific for Ca2+/Mg2+) that dynamically modulate channel activity and gating status, depending on SR voltage. PMID:22039534

Atmospheric Radiation Measurement Program Climate Research Facility Operations Quarterly Report. October 1 - December 31, 2009.

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

D. L. Sisterson

2010-01-12

Individual raw data streams from instrumentation at the Atmospheric Radiation Measurement (ARM) Program Climate Research Facility (ACRF) fixed and mobile sites are collected and sent to the Data Management Facility (DMF) at Pacific Northwest National Laboratory (PNNL) for processing in near real-time. Raw and processed data are then sent approximately daily to the ACRF Archive, where they are made available to users. For each instrument, we calculate the ratio of the actual number of data records received daily at the Archive to the expected number of data records. The results are tabulated by (1) individual data stream, site, and monthmore » for the current year and (2) site and fiscal year (FY) dating back to 1998. The U.S. Department of Energy (DOE) requires national user facilities to report time-based operating data. The requirements concern the actual hours of operation (ACTUAL); the estimated maximum operation or uptime goal (OPSMAX), which accounts for planned downtime; and the VARIANCE [1 - (ACTUAL/OPSMAX)], which accounts for unplanned downtime. The OPSMAX time for the first quarter of FY 2010 for the North Slope Alaska (NSA) locale is 1,987.20 hours (0.90 x 2,208); for the Southern Great Plains (SGP) site is 2,097.60 hours (0.95 x 2,208); and for the Tropical Western Pacific (TWP) locale is 1,876.8 hours (0.85 x 2,208). The ARM Mobile Facility (AMF) deployment in Graciosa Island, the Azores, Portugal, continues; its OPSMAX time this quarter is 2,097.60 hours (0.95 x 2,208). The differences in OPSMAX performance reflect the complexity of local logistics and the frequency of extreme weather events. It is impractical to measure OPSMAX for each instrument or data stream. Data availability reported here refers to the average of the individual, continuous data streams that have been received by the Archive. Data not at the Archive are the result of downtime (scheduled or unplanned) of the individual instruments. Therefore, data availability is directly related to individual instrument uptime. Thus, the average percentage of data in the Archive represents the average percentage of the time (24 hours per day, 92 days for this quarter) the instruments were operating this quarter. The Site Access Request System is a web-based database used to track visitors to the fixed and mobile sites, all of which have facilities that can be visited. The NSA locale has the Barrow and Atqasuk sites. The SGP locale has historically had a central facility, 23 extended facilities, 4 boundary facilities, and 3 intermediate facilities. Beginning this quarter, the SGP began a transition to a smaller footprint (150 km x 150 km) by rearranging the original and new instrumentation made available through the American Recovery and Reinvestment Act (ARRA). The central facility and 4 extended facilities will remain, but there will be up to 16 surface new characterization facilities, 4 radar facilities, and 3 profiler facilities sited in the smaller domain. This new configuration will provide observations at scales more appropriate to current and future climate models. The TWP locale has the Manus, Nauru, and Darwin sites. These sites will also have expanded measurement capabilities with the addition of new instrumentation made available through ARRA funds. It is anticipated that the new instrumentation at all the fixed sites will be in place within the next 12 months. The AMF continues its 20-month deployment in Graciosa Island, Azores, Portugal, that started May 1, 2009. The AMF will also have additional observational capabilities within the next 12 months. Users can participate in field experiments at the sites and mobile facility, or they can participate remotely. Therefore, a variety of mechanisms are provided to users to access site information. Users who have immediate (real-time) needs for data access can request a research account on the local site data systems. This access is particularly useful to users for quick decisions in executing time-dependent activities associated with field campaigns at the fixed sites and mobile facility locations. The eight computers for the research accounts are located at the Barrow and Atqasuk sites; the SGP central facility; the TWP Manus, Nauru, and Darwin sites; the AMF; and the DMF at PNNL. However, users are warned that the data provided at the time of collection have not been fully screened for quality and therefore are not considered to be official ACRF data. Hence, these accounts are considered to be part of the facility activities associated with field campaign activities, and users are tracked. In addition, users who visit sites can connect their computer or instrument to an ACRF site data system network, which requires an on-site device account. Remote (off-site) users can also have remote access to any ACRF instrument or computer system at any ACRF site, which requires an off-site device account. These accounts are also managed and tracked.« less

The Effectiveness of Commercial Internet Web Sites: A User's Perspective.

ERIC Educational Resources Information Center

Bell, Hudson; Tang, Nelson K. H.

1998-01-01

A user survey of 60 company Web sites (electronic commerce, entertainment and leisure, financial and banking services, information services, retailing and travel, and tourism) determined that 30% had facilities for conducting online transactions and only 7% charged for site access. Overall, Web sites were rated high in ease of access, content, and…

Risk based requirements for long term stewardship: A proof-of-principle analysis of an analytic method tested on selected Hanford locations

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

Jarvis, T.T.; Andrews, W.B.; Buck, J.W.

1998-03-01

Since 1989, the Department of Energy`s (DOE) Environmental Management (EM) Program has managed the environmental legacy of US nuclear weapons production, research and testing at 137 facilities in 31 states and one US territory. The EM program has conducted several studies on the public risks posed by contaminated sites at these facilities. In Risks and the Risk Debate [DOE, 1995a], the Department analyzed the risks at sites before, during, and after remediation work by the EM program. The results indicated that aside from a few urgent risks, most hazards present little inherent risk because physical and active site management controlsmore » limit both the releases of site contaminants, and public access to these hazards. Without these controls, these sites would pose greater risks to the public. Past risk reports, however, provided little information about post-cleanup risk, primarily because of uncertainty about future site uses and site characteristics at the end of planned cleanup activities. This is of concern because in many cases current cleanup technologies, and remedies, will last a shorter period of time than the waste itself and the resulting contamination will remain hazardous.« less

Carnegie Science Academy Web Site

NASA Astrophysics Data System (ADS)

Kotwicki, John; Atzinger, Joe; Turso, Denise

1997-11-01

The Carnegie Science Academy is a professional society "For Teens...By Teens" at the Carnegie Science Center in Pittsburgh. The CSA Web Site [ http://csa.clpgh.org ] is designed for teens who have an interest in science and technology. This online or virtual science academy provides resources for teens in high school science classes. The Web site also allows students around the world to participate and communicate with other students, discuss current events in science, share opinions, find answers to questions, or make online friends. Visitors can enjoy the main components of the site or sign up for a free membership which allows access to our chat room for monthly meeting, online newsletter, members forum, and much more. Main components to the site include a spot for cool links and downloads, available for any visitor to download or view. Online exhibits are created by students to examine and publish an area of study and also allow teachers to easily post classroom activities as exhibits by submitting pictures and text. Random Access, the interactive part of the academy, allows users to share ideas and opinions. Planet CSA focuses on current events in science and the academy. In the future the CSA Web site will become a major resource for teens and science teachers providing materials that will allow students to further enhance their interest and experiences in science.

Tool independence for the Web Accessibility Quantitative Metric.

PubMed

Vigo, Markel; Brajnik, Giorgio; Arrue, Myriam; Abascal, Julio

2009-07-01

The Web Accessibility Quantitative Metric (WAQM) aims at accurately measuring the accessibility of web pages. One of the main features of WAQM among others is that it is evaluation tool independent for ranking and accessibility monitoring scenarios. This article proposes a method to attain evaluation tool independence for all foreseeable scenarios. After demonstrating that homepages have a more similar error profile than any other web page in a given web site, 15 homepages were measured with 10,000 different values of WAQM parameters using EvalAccess and LIFT, two automatic evaluation tools for accessibility. A similar procedure was followed with random pages and with several test files obtaining several tuples that minimise the difference between both tools. One thousand four hundred forty-nine web pages from 15 web sites were measured with these tuples and those values that minimised the difference between the tools were selected. Once the WAQM was tuned, the accessibility of 15 web sites was measured with two metrics for web sites, concluding that even if similar values can be produced, obtaining the same scores is undesirable since evaluation tools behave in a different way.

Site Planning and Layout.

ERIC Educational Resources Information Center

Moore, Gary T.

1998-01-01

Examines five issues related to child care facility design: (1) siting the building, outdoor play, and service areas; (2) creating favorable microclimates; (3) developmentally appropriate play yards; (4) pedestrian access and site circulation; and (5) vehicular access and parking away from pedestrians and play. (KB)

Insights into Substrate Specificity and Metal Activation of Mammalian Tetrahedral Aspartyl Aminopeptidase*

PubMed Central

Chen, Yuanyuan; Farquhar, Erik R.; Chance, Mark R.; Palczewski, Krzysztof; Kiser, Philip D.

2012-01-01

Aminopeptidases are key enzymes involved in the regulation of signaling peptide activity. Here, we present a detailed biochemical and structural analysis of an evolutionary highly conserved aspartyl aminopeptidase called DNPEP. We show that this peptidase can cleave multiple physiologically relevant substrates, including angiotensins, and thus may play a key role in regulating neuron function. Using a combination of x-ray crystallography, x-ray absorption spectroscopy, and single particle electron microscopy analysis, we provide the first detailed structural analysis of DNPEP. We show that this enzyme possesses a binuclear zinc-active site in which one of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity of the protein. The plasticity of this metal-binding site suggests a mechanism for regulation of DNPEP activity. We also demonstrate that DNPEP assembles into a functionally relevant tetrahedral complex that restricts access of peptide substrates to the active site. These structural data allow rationalization of the enzyme's preference for short peptide substrates with N-terminal acidic residues. This study provides a structural basis for understanding the physiology and bioinorganic chemistry of DNPEP and other M18 family aminopeptidases. PMID:22356908

40 CFR 1400.6 - Enhanced local access.

Code of Federal Regulations, 2011 CFR

2011-07-01

...); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.6 Enhanced local access. (a) OCA data elements. Consistent with 42 U.S.C...) OCA information. (1) LEPCs and related local government agencies are authorized and encouraged to...

40 CFR 1400.6 - Enhanced local access.

Code of Federal Regulations, 2012 CFR

2012-07-01

...); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.6 Enhanced local access. (a) OCA data elements. Consistent with 42 U.S.C...) OCA information. (1) LEPCs and related local government agencies are authorized and encouraged to...

40 CFR 1400.6 - Enhanced local access.

Code of Federal Regulations, 2013 CFR

2013-07-01

...); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.6 Enhanced local access. (a) OCA data elements. Consistent with 42 U.S.C...) OCA information. (1) LEPCs and related local government agencies are authorized and encouraged to...

40 CFR 1400.6 - Enhanced local access.

Code of Federal Regulations, 2014 CFR

2014-07-01

...); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Public Access § 1400.6 Enhanced local access. (a) OCA data elements. Consistent with 42 U.S.C...) OCA information. (1) LEPCs and related local government agencies are authorized and encouraged to...

Robotic single-access splenectomy using the Da Vinci Single-Site® platform: a case report.

PubMed

Corcione, Francesco; Bracale, Umberto; Pirozzi, Felice; Cuccurullo, Diego; Angelini, Pier Luigi

2014-03-01

Single-access laparoscopic splenectomy can offer patients some advantages. It has many difficulties, such as instrument clashing, lack of triangulation, odd angles and lack of space. The Da Vinci Single-Site® robotic surgery platform could decrease these difficulties. We present a case of single-access robotic splenectomy using this device. A 37 year-old female with idiopathic thrombocytopenic purpura was operated on with a single-site approach, using the Da Vinci Single-Site robotic surgery device. The procedure was successfully completed in 140 min. No intraoperative and postoperative complications occurred. The patient was discharged from hospital on day 3. Single-access robotic splenectomy seems to be feasible and safe using the new robotic single-access platform, which seems to overcome certain limits of previous robotic or conventional single-access laparoscopy. We think that additional studies should also be performed to explore the real cost-effectiveness of the platform. Copyright © 2013 John Wiley & Sons, Ltd.

Catalytic surface radical in dye-decolorizing peroxidase: a computational, spectroscopic and site-directed mutagenesis study

PubMed Central

Linde, Dolores; Pogni, Rebecca; Cañellas, Marina; Lucas, Fátima; Guallar, Victor; Baratto, Maria Camilla; Sinicropi, Adalgisa; Sáez-Jiménez, Verónica; Coscolín, Cristina; Romero, Antonio; Medrano, Francisco Javier; Ruiz-Dueñas, Francisco J.; Martínez, Angel T.

2014-01-01

Dye-decolorizing peroxidase (DyP) of Auricularia auricula-judae has been expressed in Escherichia coli as a representative of a new DyP family, and subjected to mutagenic, spectroscopic, crystallographic and computational studies. The crystal structure of DyP shows a buried haem cofactor, and surface tryptophan and tyrosine residues potentially involved in long-range electron transfer from bulky dyes. Simulations using PELE (Protein Energy Landscape Exploration) software provided several binding-energy optima for the anthraquinone-type RB19 (Reactive Blue 19) near the above aromatic residues and the haem access-channel. Subsequent QM/MM (quantum mechanics/molecular mechanics) calculations showed a higher tendency of Trp-377 than other exposed haem-neighbouring residues to harbour a catalytic protein radical, and identified the electron-transfer pathway. The existence of such a radical in H2O2-activated DyP was shown by low-temperature EPR, being identified as a mixed tryptophanyl/tyrosyl radical in multifrequency experiments. The signal was dominated by the Trp-377 neutral radical contribution, which disappeared in the W377S variant, and included a tyrosyl contribution assigned to Tyr-337 after analysing the W377S spectra. Kinetics of substrate oxidation by DyP suggests the existence of high- and low-turnover sites. The high-turnover site for oxidation of RB19 (kcat> 200 s−1) and other DyP substrates was assigned to Trp-377 since it was absent from the W377S variant. The low-turnover site/s (RB19 kcat ~20 s−1) could correspond to the haem access-channel, since activity was decreased when the haem channel was occluded by the G169L mutation. If a tyrosine residue is also involved, it will be different from Tyr-337 since all activities are largely unaffected in the Y337S variant. PMID:25495127

Land-use legacies and present fire regimes interact to mediate herbivory by altering the neighboring plant community

DOE PAGES

Hahn, Philip G.; Orrock, John L.

2014-10-03

Past and present human activities, such as historic agriculture and fire suppression, are widespread and can create depauperate plant communities. Although many studies show that herbivory on focal plants depends on the density of herbivores or the composition of the surrounding plant community, it is unclear whether anthropogenic changes to plant communities alter herbivory. We tested the hypothesis that human activities that alter the plant community lead to subsequent changes in herbivory. At 20 sites distributed across 80 300 hectares, we conducted a field experiment that manipulated insect herbivore access (full exclosures and pseudo-exclosures) to four focal plant species inmore » longleaf pine woodlands with diff erent land-use histories (post-agricultural sites or non-agricultural sites) and degrees of fi re frequency (frequent and infrequent). Plant cover, particularly herbaceous cover, was lower in post-agricultural and fi re suppressed woodlands. Density of the dominant insect herbivore at our site (grasshoppers) was positively related to plant cover. Herbivore access reduced biomass of the palatable forb Solidago odora in frequently burned post-agricultural sites and in infrequently burned non-agricultural woodlands and increased mortality of another forb (Pityopsis graminifolia ), but did not aff ect two other less palatable species ( Schizachyrium scoparium and Tephrosia virginiana ). Herbivory on S. odora exhibited a hump-shaped response to plant cover, with low herbivory at low and high levels of plant cover. Herbivore density had a weak negative effect on herbivory. These findings suggest that changes in plant cover related to past and present human activities can modify damage rates on focal S. odora plants by altering grasshopper foraging behavior rather than by altering local grasshopper density. The resulting changes in herbivory may have the potential to limit natural recovery or restoration eff orts by reducing the establishment or performance of palatable plant species.« less

Land-use legacies and present fire regimes interact to mediate herbivory by altering the neighboring plant community

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

Hahn, Philip G.; Orrock, John L.

Past and present human activities, such as historic agriculture and fire suppression, are widespread and can create depauperate plant communities. Although many studies show that herbivory on focal plants depends on the density of herbivores or the composition of the surrounding plant community, it is unclear whether anthropogenic changes to plant communities alter herbivory. We tested the hypothesis that human activities that alter the plant community lead to subsequent changes in herbivory. At 20 sites distributed across 80 300 hectares, we conducted a field experiment that manipulated insect herbivore access (full exclosures and pseudo-exclosures) to four focal plant species inmore » longleaf pine woodlands with diff erent land-use histories (post-agricultural sites or non-agricultural sites) and degrees of fi re frequency (frequent and infrequent). Plant cover, particularly herbaceous cover, was lower in post-agricultural and fi re suppressed woodlands. Density of the dominant insect herbivore at our site (grasshoppers) was positively related to plant cover. Herbivore access reduced biomass of the palatable forb Solidago odora in frequently burned post-agricultural sites and in infrequently burned non-agricultural woodlands and increased mortality of another forb (Pityopsis graminifolia ), but did not aff ect two other less palatable species ( Schizachyrium scoparium and Tephrosia virginiana ). Herbivory on S. odora exhibited a hump-shaped response to plant cover, with low herbivory at low and high levels of plant cover. Herbivore density had a weak negative effect on herbivory. These findings suggest that changes in plant cover related to past and present human activities can modify damage rates on focal S. odora plants by altering grasshopper foraging behavior rather than by altering local grasshopper density. The resulting changes in herbivory may have the potential to limit natural recovery or restoration eff orts by reducing the establishment or performance of palatable plant species.« less

Catalytic surface radical in dye-decolorizing peroxidase: a computational, spectroscopic and site-directed mutagenesis study.

PubMed

Linde, Dolores; Pogni, Rebecca; Cañellas, Marina; Lucas, Fátima; Guallar, Victor; Baratto, Maria Camilla; Sinicropi, Adalgisa; Sáez-Jiménez, Verónica; Coscolín, Cristina; Romero, Antonio; Medrano, Francisco Javier; Ruiz-Dueñas, Francisco J; Martínez, Angel T

2015-03-01

Dye-decolorizing peroxidase (DyP) of Auricularia auricula-judae has been expressed in Escherichia coli as a representative of a new DyP family, and subjected to mutagenic, spectroscopic, crystallographic and computational studies. The crystal structure of DyP shows a buried haem cofactor, and surface tryptophan and tyrosine residues potentially involved in long-range electron transfer from bulky dyes. Simulations using PELE (Protein Energy Landscape Exploration) software provided several binding-energy optima for the anthraquinone-type RB19 (Reactive Blue 19) near the above aromatic residues and the haem access-channel. Subsequent QM/MM (quantum mechanics/molecular mechanics) calculations showed a higher tendency of Trp-377 than other exposed haem-neighbouring residues to harbour a catalytic protein radical, and identified the electron-transfer pathway. The existence of such a radical in H₂O₂-activated DyP was shown by low-temperature EPR, being identified as a mixed tryptophanyl/tyrosyl radical in multifrequency experiments. The signal was dominated by the Trp-377 neutral radical contribution, which disappeared in the W377S variant, and included a tyrosyl contribution assigned to Tyr-337 after analysing the W377S spectra. Kinetics of substrate oxidation by DyP suggests the existence of high- and low-turnover sites. The high-turnover site for oxidation of RB19 (k(cat) > 200 s⁻¹) and other DyP substrates was assigned to Trp-377 since it was absent from the W377S variant. The low-turnover site/s (RB19 k(cat) ~20 s⁻¹) could correspond to the haem access-channel, since activity was decreased when the haem channel was occluded by the G169L mutation. If a tyrosine residue is also involved, it will be different from Tyr-337 since all activities are largely unaffected in the Y337S variant.

Diversification and intensification of agricultural adaptation from global to local scales.

PubMed

Chen, Minjie; Wichmann, Bruno; Luckert, Marty; Winowiecki, Leigh; Förch, Wiebke; Läderach, Peter

2018-01-01

Smallholder farming systems are vulnerable to a number of challenges, including continued population growth, urbanization, income disparities, land degradation, decreasing farm size and productivity, all of which are compounded by uncertainty of climatic patterns. Understanding determinants of smallholder farming practices is critical for designing and implementing successful interventions, including climate change adaptation programs. We examine two dimensions wherein smallholder farmers may adapt agricultural practices; through intensification (i.e., adopt more practices) or diversification (i.e. adopt different practices). We use data on 5314 randomly sampled households located in 38 sites in 15 countries across four regions (East and West Africa, South Asia, and Central America). We estimate empirical models designed to assess determinants of both intensification and diversification of adaptation activities at global scales. Aspects of adaptive capacity that are found to increase intensification of adaptation globally include variables associated with access to information and human capital, financial considerations, assets, household infrastructure and experience. In contrast, there are few global drivers of adaptive diversification, with a notable exception being access to weather information, which also increases adaptive intensification. Investigating reasons for adaptation indicate that conditions present in underdeveloped markets provide the primary impetus for adaptation, even in the context of climate change. We also compare determinants across spatial scales, which reveals a variety of local avenues through which policy interventions can relax economic constraints and boost agricultural adaptation for both intensification and diversification. For example, access to weather information does not affect intensification adaptation in Africa, but is significant at several sites in Bangladesh and India. Moreover, this information leads to diversification of adaptive activities on some sites in South Asia and Central America, but increases specialization in West and East Africa.

Diversification and intensification of agricultural adaptation from global to local scales

PubMed Central

Chen, Minjie; Wichmann, Bruno; Luckert, Marty; Winowiecki, Leigh; Förch, Wiebke

2018-01-01

Smallholder farming systems are vulnerable to a number of challenges, including continued population growth, urbanization, income disparities, land degradation, decreasing farm size and productivity, all of which are compounded by uncertainty of climatic patterns. Understanding determinants of smallholder farming practices is critical for designing and implementing successful interventions, including climate change adaptation programs. We examine two dimensions wherein smallholder farmers may adapt agricultural practices; through intensification (i.e., adopt more practices) or diversification (i.e. adopt different practices). We use data on 5314 randomly sampled households located in 38 sites in 15 countries across four regions (East and West Africa, South Asia, and Central America). We estimate empirical models designed to assess determinants of both intensification and diversification of adaptation activities at global scales. Aspects of adaptive capacity that are found to increase intensification of adaptation globally include variables associated with access to information and human capital, financial considerations, assets, household infrastructure and experience. In contrast, there are few global drivers of adaptive diversification, with a notable exception being access to weather information, which also increases adaptive intensification. Investigating reasons for adaptation indicate that conditions present in underdeveloped markets provide the primary impetus for adaptation, even in the context of climate change. We also compare determinants across spatial scales, which reveals a variety of local avenues through which policy interventions can relax economic constraints and boost agricultural adaptation for both intensification and diversification. For example, access to weather information does not affect intensification adaptation in Africa, but is significant at several sites in Bangladesh and India. Moreover, this information leads to diversification of adaptive activities on some sites in South Asia and Central America, but increases specialization in West and East Africa. PMID:29727457

EarthInquiry: Using On-Line Data to Help Students Explore Fundamental Concepts in Geoscience

NASA Astrophysics Data System (ADS)

Alfano, M.; Keane, C. M.; Ridky, R. W.

2002-12-01

Using local case studies to learn about earth processes increases the relevance of science instruction. Students are encouraged to think about how geological processes affect their lives and experiences. Today, with many global data sets available on-line, instructors have unprecedented opportunities to bring local data into the classroom. However, while the resources are available, using on-line data presents a particular set of challenges. Access and entry to web sites frequently change and data format can be unpredictable. Often, instructors are faced with non-functional web sites on the day, or week, that they plan to assign a given activity. The American Geological Institute, with the participation of numerous geoscience professors, has developed EarthInquiry, a series of activities that utilize the abundant real-time and archived geoscience data available on-line. These modules are developed primarily for introductory college students. EarthInquiry modules follow a structured format, beginning with familiar examples at the global and national level to introduce students to the on-line data and the EarthInquiry web site. The web site offers detailed and up-to-date instructions on how to access the data, cached copies of sample data that can be used to complete each activity in the event of a network outage, and an assessment activity that helps students determine how well they have achieved an understanding of key concepts. The EarthInquiry booklet contains a series of engaging questions that allow students to solve problems in a scientific manner. As students gain content understanding and confidence in the requisite analysis, they examine the presented material at a more local level. In one activity, students explore the recurrence interval of a local stream. In other activities, they investigate the mineral resources and earthquake histories of their state. All modules are developed with the intent of building an appropriate cognitive foundation, while complimenting the topics typically discussed in an introductory physical or environmental geology course. The project is a collaboration of the American Geological Institute and W.H. Freeman and Company Publishers.

Active site specificity profiling datasets of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, 12, 13 and 14.

PubMed

Eckhard, Ulrich; Huesgen, Pitter F; Schilling, Oliver; Bellac, Caroline L; Butler, Georgina S; Cox, Jennifer H; Dufour, Antoine; Goebeler, Verena; Kappelhoff, Reinhild; Auf dem Keller, Ulrich; Klein, Theo; Lange, Philipp F; Marino, Giada; Morrison, Charlotte J; Prudova, Anna; Rodriguez, David; Starr, Amanda E; Wang, Yili; Overall, Christopher M

2016-06-01

The data described provide a comprehensive resource for the family-wide active site specificity portrayal of the human matrix metalloproteinase family. We used the high-throughput proteomic technique PICS (Proteomic Identification of protease Cleavage Sites) to comprehensively assay 9 different MMPs. We identified more than 4300 peptide cleavage sites, spanning both the prime and non-prime sides of the scissile peptide bond allowing detailed subsite cooperativity analysis. The proteomic cleavage data were expanded by kinetic analysis using a set of 6 quenched-fluorescent peptide substrates designed using these results. These datasets represent one of the largest specificity profiling efforts with subsequent structural follow up for any protease family and put the spotlight on the specificity similarities and differences of the MMP family. A detailed analysis of this data may be found in Eckhard et al. (2015) [1]. The raw mass spectrometry data and the corresponding metadata have been deposited in PRIDE/ProteomeXchange with the accession number PXD002265.

Adding Value to the Health Care System: Identifying Value-Added Systems Roles for Medical Students.

PubMed

Gonzalo, Jed D; Graaf, Deanna; Johannes, Bobbie; Blatt, Barbara; Wolpaw, Daniel R

To catalyze learning in Health Systems Science and add value to health systems, education programs are seeking to incorporate students into systems roles, which are not well described. The authors sought to identify authentic roles for students within a range of clinical sites and explore site leaders' perceptions of the value of students performing these roles. From 2013 to 2015, site visits and interviews with leadership from an array of clinical sites (n = 30) were conducted. Thematic analysis was used to identify tasks and benefits of integrating students into interprofessional care teams. Types of systems roles included direct patient benefit activities, including monitoring patient progress with care plans and facilitating access to resources, and clinic benefit activities, including facilitating coordination and improving clinical processes. Perceived benefits included improved value of the clinical mission and enhanced student education. These results elucidate a framework for student roles that enhance learning and add value to health systems.

The Internet as a communication tool for orthopedic spine fellowships in the United States.

PubMed

Silvestre, Jason; Guzman, Javier Z; Skovrlj, Branko; Overley, Samuel C; Cho, Samuel K; Qureshi, Sheeraz A; Hecht, Andrew C

2015-04-01

Orthopedic residents seeking additional training in spine surgery commonly use the Internet to manage their fellowship applications. Although studies have assessed the accessibility and content of Web sites in other medical specialties, none have looked at orthopedic spine fellowship Web sites (SFWs). The purpose of this study was to evaluate the accessibility of information from commonly used databases and assess the content of SFWs. This was a Web site accessibility and content evaluation study. A comprehensive list of available orthopedic spine fellowship programs was compiled by accessing program lists from the SF Match, North American Spine Society, Fellowship and Residency Electronic Interactive Database (FREIDA), and Orthopaedicsone.com (Ortho1). These databases were assessed for accessibility of information including viable links to SFWs and responsive program contacts. A Google search was used to identify SFWs not readily available on these national databases. SFWs were evaluated based on online education and recruitment content. Evaluators found 45 SFWs of 63 active programs (71%). Available SFWs were often not readily accessible from national program lists, and no program afforded a direct link to their SFW from SF Match. Approximately half of all programs responded via e-mail. Although many programs described surgical experience (91%) and research requirements (87%) during the fellowship, less than half mentioned didactic instruction (46%), journal clubs (41%), and national meetings or courses attended (28%). Evaluators found an average 45% of fellow recruitment content. Comparison of SFWs by program characteristics revealed three significant differences. Programs with greater than one fellowship position had greater online education content than programs with a single fellow (p=.022). Spine fellowships affiliated with an orthopedic residency program maintained greater education (p=.006) and recruitment (p=.046) content on their SFWs. Most orthopedic spine surgery programs underuse the Internet for fellow education and recruitment. The inaccessibility of information and paucity of content on SFWs allow for future opportunity to optimize these resources. Copyright © 2015 Elsevier Inc. All rights reserved.

An analysis of the accessibility of video lottery terminals: the case of Montréal.

PubMed

Robitaille, Eric; Herjean, Patrick

2008-01-18

Researchers and public health officials in Canada, the United States and Australia have for some time noted broader geographic accessibility to gambling establishments, above all in socioeconomically underprivileged communities. This increase in availability could lead to more and more gambling problems. This article focuses, in an ecological perspective, in particular on a spatial analysis of the geographic accessibility of sites possessing a VLT permit in the Montréal area, i.e. Montréal Island, the South Shore and Laval, from the standpoint of the development of an indicator of the vulnerability (socioeconomic components and demographic components) to gambling of populations at the level of certain neighbourhood units (dissemination areas). With the recent development of geographic information systems (GIS), it is now possible to ascertain accessibility to services much more accurately, for example by taking into account the configuration of the road network. The findings of our analysis reveal widespread geographic accessibility to sites possessing a VLT permit in the downtown area and in pericentral districts. In some neighbourhood units, a site possessing a VLT permit may be within a three-minute walk. In the region studied overall, average walking time to a VLT site is nine minutes. Access to this type of service on foot is usually limited in the outskirts. However, a number of groups of sites possessing VLT permits are found along certain axial highways. According to local spatial self-correlation analyses, the findings suggest a significant link between walking accessibility to sites possessing VLT permits and the vulnerability of the communities. In a number of neighbourhood units with ready access to VLT's the populations display high vulnerability. These findings reveal that accessibility to sites possessing a VLT permit is often linked to the vulnerability (socioeconomic and demographic components) of communities. Reliance in our analyses on neighbourhood units with fairly small areas enabled us to emphasize the rectilinear dimension of the spatial distribution of sites possessing VLT permits. This is a significant link that public health officials must consider when elaborating programs to combat pathological gambling.

Structural evidence for a copper-bound carbonate intermediate in the peroxidase and dismutase activities of superoxide dismutase.

PubMed

Strange, Richard W; Hough, Michael A; Antonyuk, Svetlana V; Hasnain, S Samar

2012-01-01

Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our understanding of oxidative damage. Its primary function is catalysing the dismutation of superoxide to O(2) and H(2)O(2). SOD also reacts with H(2)O(2), leading to the formation of a strong copper-bound oxidant species that can either inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate (or CO(2)) and H(2)O(2), this peroxidase activity is enhanced and produces the carbonate radical. This freely diffusible reactive oxygen species is proposed as the agent for oxidation of large substrates that are too bulky to enter the active site. Here, we provide direct structural evidence, from a 2.15 Å resolution crystal structure, of (bi)carbonate captured at the active site of reduced SOD, consistent with the view that a bound carbonate intermediate could be formed, producing a diffusible carbonate radical upon reoxidation of copper. The bound carbonate blocks direct access of substrates to Cu(I), suggesting that an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled electron transfer mechanism involving the bound carbonate rather than the solvent. Carbonate is captured in a different site when SOD is oxidised, being located in the active site channel adjacent to the catalytically important Arg143. This is the probable route of diffusion from the active site following reoxidation of the copper. In this position, the carbonate is poised for re-entry into the active site and binding to the reduced copper.

Structural Evidence for a Copper-Bound Carbonate Intermediate in the Peroxidase and Dismutase Activities of Superoxide Dismutase

PubMed Central

Strange, Richard W.; Hough, Michael A.; Antonyuk, Svetlana V.; Hasnain, S. Samar

2012-01-01

Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our understanding of oxidative damage. Its primary function is catalysing the dismutation of superoxide to O2 and H2O2. SOD also reacts with H2O2, leading to the formation of a strong copper-bound oxidant species that can either inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate (or CO2) and H2O2, this peroxidase activity is enhanced and produces the carbonate radical. This freely diffusible reactive oxygen species is proposed as the agent for oxidation of large substrates that are too bulky to enter the active site. Here, we provide direct structural evidence, from a 2.15 Å resolution crystal structure, of (bi)carbonate captured at the active site of reduced SOD, consistent with the view that a bound carbonate intermediate could be formed, producing a diffusible carbonate radical upon reoxidation of copper. The bound carbonate blocks direct access of substrates to Cu(I), suggesting that an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled electron transfer mechanism involving the bound carbonate rather than the solvent. Carbonate is captured in a different site when SOD is oxidised, being located in the active site channel adjacent to the catalytically important Arg143. This is the probable route of diffusion from the active site following reoxidation of the copper. In this position, the carbonate is poised for re-entry into the active site and binding to the reduced copper. PMID:22984565

Different forms of effective connectivity in primate frontotemporal pathways.

PubMed

Petkov, Christopher I; Kikuchi, Yukiko; Milne, Alice E; Mishkin, Mortimer; Rauschecker, Josef P; Logothetis, Nikos K

2015-01-23

It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.

Iron carbide encapsulated by porous carbon nitride as bifunctional electrocatalysts for oxygen reduction and evolution reactions

NASA Astrophysics Data System (ADS)

Wei, Liangqin; Sun, Hongdi; Yang, Tiantian; Deng, Shenzhen; Wu, Mingbo; Li, Zhongtao

2018-05-01

Herein, the study reports a facile and scale-up able strategy to synthesize metal organic frameworks (MOFs) Fe-7,7,8,8-Tetracyanoquinodimethane (Fe-TCNQ) as precursors to develop non-precious metal bifunctional electrocatalysts through a one-step hydrothermal route. Then, Fe3C/carbon nitride (Fe3C@CNx) core-shell structure composites are readily available through pyrolyzing Fe-TCNQ at reasonable temperature, during which hierarchical porous structures with multimodal porosity formed. Nitrogen doped porosity carbon layers can facilitate mass access to active sites and accelerate reaction. Consequently, the optimized catalyst exhibits superior oxygen reduction reaction (ORR) electrocatalytic activity and better catalytic activity for oxygen evolution reaction (OER) in alkaline medium than that of Pt/C, which can be attributed to the synergistic effect of strong coupling between Fe3C and nitrogen doped carbon shells, active sites Fe-NX, optimal level of nitrogen doping, and appropriate multimodal porosity.

Different forms of effective connectivity in primate frontotemporal pathways

PubMed Central

Petkov, Christopher I.; Kikuchi, Yukiko; Milne, Alice E.; Mishkin, Mortimer; Rauschecker, Josef P.; Logothetis, Nikos K.

2015-01-01

It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex. PMID:25613079

Content and Accessibility of Shoulder and Elbow Fellowship Web Sites in the United States.

PubMed

Young, Bradley L; Oladeji, Lasun O; Cichos, Kyle; Ponce, Brent

2016-01-01

Increasing numbers of training physicians are using the Internet to gather information about graduate medical education programs. The content and accessibility of web sites that provide this information have been demonstrated to influence applicants' decisions. Assessments of orthopedic fellowship web sites including sports medicine, pediatrics, hand and spine have found varying degrees of accessibility and material. The purpose of this study was to evaluate the accessibility and content of the American Shoulder and Elbow Surgeons (ASES) fellowship web sites (SEFWs). A complete list of ASES programs was obtained from a database on the ASES web site. The accessibility of each SEFWs was assessed by the existence of a functioning link found in the database and through Google®. Then, the following content areas of each SEFWs were evaluated: fellow education, faculty/previous fellow information, and recruitment. At the time of the study, 17 of the 28 (60.7%) ASES programs had web sites accessible through Google®, and only five (17.9%) had functioning links in the ASES database. Nine programs lacked a web site. Concerning web site content, the majority of SEFWs contained information regarding research opportunities, research requirements, case descriptions, meetings and conferences, teaching responsibilities, attending faculty, the application process, and a program description. Fewer than half of the SEFWs provided information regarding rotation schedules, current fellows, previous fellows, on-call expectations, journal clubs, medical school of current fellows, residency of current fellows, employment of previous fellows, current research, and previous research. A large portion of ASES fellowship programs lacked functioning web sites, and even fewer provided functioning links through the ASES database. Valuable information for potential applicants was largely inadequate across present SEFWs.

High acidity unilamellar zeolite MCM-56 and its pillared and delaminated derivatives.

PubMed

Gil, Barbara; Makowski, Wacław; Marszalek, Bartosz; Roth, Wieslaw J; Kubu, Martin; Čejka, Jiři; Olejniczak, Zbigniew

2014-07-21

The unilamellar form of zeolite MWW, MCM-56, which is obtained by direct hydrothermal synthesis has been studied with regard to acidity and porosity in its original and post-synthesis modified pillared and delaminated forms. The acidity measured by FTIR was found to be only slightly lower than the highly active 3-D MWW forms, MCM-22 and MCM-49. Pivalonitrile adsorption, which is a measure of spatial openness, showed 50% accessibility vs. <30% for MCM-22/49. It highlights the potential of MCM-56 as a layered material with increased access to acid sites because it does not entail laborious post-synthesis modification. Swelling, pillaring and delamination of MCM-56 are facile but result in a reduction in the number of Brønsted acid sites (BAS) while increasing accessibility to pivalonitrile. The delamination procedure involving sonication and acidification of the highly basic mother liquor produces the most visible increase in surface area and access to all BAS. The accompanying doubling of the solid yield and the decrease in absolute number of BAS suggest significant precipitation of dissolved silica generated during swelling and sonication in high pH medium. The viability of separating surfactant covered layers upon sonication with the consequence of exposing hydrophobic hydrocarbon tails to aqueous environment is addressed.

The structural basis of secondary active transport mechanisms.

PubMed

Forrest, Lucy R; Krämer, Reinhard; Ziegler, Christine

2011-02-01

Secondary active transporters couple the free energy of the electrochemical potential of one solute to the transmembrane movement of another. As a basic mechanistic explanation for their transport function the model of alternating access was put forward more than 40 years ago, and has been supported by numerous kinetic, biochemical and biophysical studies. According to this model, the transporter exposes its substrate binding site(s) to one side of the membrane or the other during transport catalysis, requiring a substantial conformational change of the carrier protein. In the light of recent structural data for a number of secondary transport proteins, we analyze the model of alternating access in more detail, and correlate it with specific structural and chemical properties of the transporters, such as their assignment to different functional states in the catalytic cycle of the respective transporter, the definition of substrate binding sites, the type of movement of the central part of the carrier harboring the substrate binding site, as well as the impact of symmetry on fold-specific conformational changes. Besides mediating the transmembrane movement of solutes, the mechanism of secondary carriers inherently involves a mechanistic coupling of substrate flux to the electrochemical potential of co-substrate ions or solutes. Mainly because of limitations in resolution of available transporter structures, this important aspect of secondary transport cannot yet be substantiated by structural data to the same extent as the conformational change aspect. We summarize the concepts of coupling in secondary transport and discuss them in the context of the available evidence for ion binding to specific sites and the impact of the ions on the conformational state of the carrier protein, which together lead to mechanistic models for coupling. Copyright © 2010 Elsevier B.V. All rights reserved.

Changes in RNA polymerase II progression influence somatic hypermutation of Ig-related genes by AID

PubMed Central

Kodgire, Prashant; Mukkawar, Priyanka; Ratnam, Sarayu; Martin, Terence E.

2013-01-01

Somatic hypermutation (SHM) of Ig genes is initiated by the activation-induced cytidine deaminase (AID), and requires target gene transcription. We previously proposed that AID may associate with the RNA polymerase II (Pol). Here, to determine aspects of the transcription process required for SHM, we knocked-in a transcription terminator into an Ig gene variable region in DT40 chicken B cell line. We found that the human β-globin terminator was an efficient inhibitor of downstream transcription in these cells. The terminator reduced mutations downstream of the poly(A) signal, suggesting that the process of transcription is essential for efficient SHM and that AID has better access to its target when Pol is in the elongating rather than terminating mode. Mutations upstream of the poly(A) site were almost doubled in the active terminator clones compared with an inactivated terminator, and this region showed more single-stranded DNA, indicating that Pol pausing assists SHM. Moreover, the nontranscribed DNA strand was the preferred SHM target upstream of the active terminator. Pol pausing during poly(A) site recognition may facilitate persistence of negative supercoils, exposing the coding single strand and possibly allowing the nascent RNA intermittent reannealing with the template strand, for prolonged access of AID. PMID:23752228

75 FR 25853 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

....gov , to submit or view public comments, access the index listing of the contents of the docket, and...:8080/glas/login.htm . The Web-site will contain a user-friendly data entry interface for recipients to... series of screens containing pull-down menus and text boxes, where users can enter project specific...

A Highly Active Magnetically Recoverable Nano Ferrite-Glutathione-Copper (Nano-FGT-Cu) Catalyst for Huisgen 1, 3-Dipolar Cycloadditions

EPA Science Inventory

A homogeneous catalyst, where the catalyst is in the same phase as the reactants, is generally accepted by chemists.1 One attractive property is that all catalytic sites are accessible because the catalyst is generally a soluble metal complex where it is possible to tune the chem...

Internet-Based Economic Education: The Case of EconEdLink

ERIC Educational Resources Information Center

VanFossen, Phillip J.; Herman-Ellison, Lisa C.

2006-01-01

The National Council on Economic Education's (NCEE) EconEdLink site provides lessons and classroom learning activities based on economics topics in the news, as well as access to real-time economic data. EconEdLink's content is designed to help integrate economic concepts across the curriculum as outlined in the Voluntary National Content…

Time-lapse photography to monitor riparian meadow use

Treesearch

John W. Kinney; Warren P. Clary

1998-01-01

Riparian zones are key areas of most western landscapes. The kinds and amounts of natural and human activity occurring on these sites are often in dispute as many riparian areas in the mountain West are remote or have limited seasonal access. Impacts by wild ungulates, domestic livestock, or recreationists can result in relatively similar damages to streamside...

Measuring Law Library Catalog Web Site Usability: A Web Analytic Approach

ERIC Educational Resources Information Center

Fang, Wei; Crawford, Marjorie E.

2008-01-01

Although there is a proliferation of information available on the Web, and law professors, students, and other users have a variety of channels to locate information and complete their research activities, the law library catalog still remains an important source for offering users access to information that has been evaluated and cataloged by…

Using PlacesOnline in Instructional Activities

ERIC Educational Resources Information Center

Longan, Michael W.; Owusu, Francis; Roseman, Curtis C.

2008-01-01

PlacesOnLine.org is a Web portal that provides easy access to high quality Web sites that focus on places from around the world. It is intended for use by a wide range of people, including professional geographers, teachers and students at all levels, and the general public. This article explores the potential uses of PlacesOnLine as an…

Young Canadians in a Wired World: How Canadian Kids Are Using the Internet.

ERIC Educational Resources Information Center

Taylor, Anne

2001-01-01

Canadian surveys of approximately 1,000 parents and 5,600 students aged 9-17 revealed student behaviors related to surfing the Web and engaging in online communication; differences in parent and student perceptions of students' Internet activities and the extent of parental supervision; and students' access to pornographic and violent Web sites.…

78 FR 67396 - Agency Information Collection Activities: Proposed collection; comments requested: Supplemental...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

...- fileable, and E-signature capabilities, and the FARA eFile system in operation since March 1 2011, permits registrants to file their registration forms electronically to the FARA Registration Unit, 24 hours a day, seven days a week. FARA eFile is accessed via the FARA public Web site located at http://www.fara.gov...

A Theoretical Framework for Organizing the Effect of the Internet on Cognitive Development

ERIC Educational Resources Information Center

Johnson, Genevieve Marie

2006-01-01

The number of children and adolescents accessing the Internet as well as the amount of time online are steadily increasing. The most common online activities include playing video games, navigating web sites, and communicating via chat rooms, email, and instant messaging. A theoretical framework for understanding the effects of Internet use on…

The Juggling Act: A Phenomenological Study of Gifted and Talented Girls' Experiences with Facebook

ERIC Educational Resources Information Center

Price, Eunice; Wardman, Janna; Bruce, Toni; Millward, Pam

2016-01-01

Facebook is a frequently accessed social networking site with more than one billion active users worldwide. Although there are numerous studies on its impact on teenagers, none have investigated its impact on gifted and talented girls. This study's aim was to understand the social media experiences of talented female student leaders. A qualitative…

YouTube Video Project: A "Cool" Way to Learn Communication Ethics

ERIC Educational Resources Information Center

Lehman, Carol M.; DuFrene, Debbie D.; Lehman, Mark W.

2010-01-01

The millennial generation embraces new technologies as a natural way of accessing and exchanging information, staying connected, and having fun. YouTube, a video-sharing site that allows users to upload, view, and share video clips, is among the latest "cool" technologies for enjoying quick laughs, employing a wide variety of corporate activities,…

Getting in through the Front Door: The First Hurdle of Researching in Companies

ERIC Educational Resources Information Center

Smith, Erica

2012-01-01

This paper examines what is arguably the most important issue in qualitative research--access to willing participants--specifically in the context of companies. This is of considerable importance in vocational education and training (VET) as workplaces are the site of much VET activity. While research textbooks discuss many issues in research, few…

CIRIR Programs: Drilling and Research Opportunities at the Rochechouart Impact Structure

NASA Technical Reports Server (NTRS)

Lambert, P.; Alwmark, C.; Baratoux, D.; Brack, A.; Bruneton, P.; Buchner, E.; Claeys, P.; Dence, M.; French, B.; Hoerz, F

2017-01-01

Owing to its size, accessibility and erosional level, the Rochechouart impact structure, dated at 203 +/- 2 Ma (recalc.), is a unique reser-voir of knowledge within the population of the rare terrestrial analogous to large impacts craters observed on planetary surfaces. The site gives direct access to fundamental mechanisms both in impact-related geology (origin and evolution of planets) and biology (habitability of planets, emergence and evolution of life). For the last decade P. Lambert has been installing Rochechouart as International Natural Laboratory for studying impact processes and collateral effects on planetary surfaces. For this purpose the Center for International Research on Impacts and on Rochechouart (CIRIR) was installed on site in 2016 with twofold objectives and activities. First ones are scientific and dedicated to the scientific community. The second are cultural and educational and are dedi-cated to the public sensu lato. We present here the CIRIR, its scientific programs and the related reseach opportunities.

Modulation of HIV Protease Flexibility by the T80N Mutation

PubMed Central

Zhou, Hao; Li, Shangyang; Badger, John; Nalivaika, Ellen; Cai, Yufeng; Foulkes-Murzycki, Jennifer; Schiffer, Celia; Makowski, Lee

2015-01-01

The flexibility of HIV protease plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80 which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle scattering (WAXS) data was measured for a series of HIV protease variants. Starting with a calculated WAXS pattern from a rigid atomic model, the modulations in the intensity distribution caused by structural fluctuations in the protein were predicted by simple analytic methods and compared to the experimental data. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. The effects of this single point mutation extend throughout the protein, so as to alter the mobility of amino acids in the enzymatic core. These results support the contentions that significant protein flexibility extends throughout HIV protease and is critical to catalytic function. PMID:25488402

Structure and substrate recruitment of the human spindle checkpoint kinase Bub1.

PubMed

Kang, Jungseog; Yang, Maojun; Li, Bing; Qi, Wei; Zhang, Chao; Shokat, Kevan M; Tomchick, Diana R; Machius, Mischa; Yu, Hongtao

2008-11-07

In mitosis, the spindle checkpoint detects a single unattached kinetochore, inhibits the anaphase-promoting complex or cyclosome (APC/C), and prevents premature sister chromatid separation. The checkpoint kinase Bub1 contributes to checkpoint sensitivity through phosphorylating the APC/C activator, Cdc20, and inhibiting APC/C catalytically. We report here the crystal structure of the kinase domain of Bub1, revealing the requirement of an N-terminal extension for its kinase activity. Though the activation segment of Bub1 is ordered and has structural features indicative of active kinases, the C-terminal portion of this segment sterically restricts substrate access to the active site. Bub1 uses docking motifs, so-called KEN boxes, outside its kinase domain to recruit Cdc20, one of two known KEN box receptors. The KEN boxes of Bub1 are required for the spindle checkpoint in human cells. Therefore, its unusual active-site conformation and mode of substrate recruitment suggest that Bub1 has an exquisitely tuned specificity for Cdc20.

Total Access: Making College Web Sites Accessible to Students with Disabilities

ERIC Educational Resources Information Center

Bruyere, Susanne

2008-01-01

Colleges increasingly rely on the Web to attract, inform, and interact with students. This makes Web site accessibility and usability critical concerns, particularly for public community colleges, which educate sizable numbers of students with disabilities. As committed providers of postsecondary education to students with disabilities and thus a…

Accessing Digital Libraries: A Study of ARL Members' Digital Projects

ERIC Educational Resources Information Center

Kahl, Chad M.; Williams, Sarah C.

2006-01-01

To ensure efficient access to and integrated searching capabilities for their institution's new digital library projects, the authors studied Web sites of the Association of Research Libraries' (ARL) 111 academic, English-language libraries. Data were gathered on 1117 digital projects, noting library Web site and project access, metadata, and…

Potential impact of public access defibrillators on survival after out of hospital cardiopulmonary arrest: retrospective cohort study

PubMed Central

Pell, Jill P; Sirel, Jane M; Marsden, Andrew K; Ford, Ian; Walker, Nicola L; Cobbe, Stuart M

2002-01-01

Objective To estimate the potential impact of public access defibrillators on overall survival after out of hospital cardiac arrest. Design Retrospective cohort study using data from an electronic register. A statistical model was used to estimate the effect on survival of placing public access defibrillators at suitable or possibly suitable sites. Setting Scottish Ambulance Service. Subjects Records of all out of hospital cardiac arrests due to heart disease in Scotland in 1991-8. Main outcome measures Observed and predicted survival to discharge from hospital. Results Of 15 189 arrests, 12 004 (79.0%) occurred in sites not suitable for the location of public access defibrillators, 453 (3.0%) in sites where they may be suitable, and 2732 (18.0%) in suitable sites. Defibrillation was given in 67.9% of arrests that occurred in possibly suitable sites for locating defibrillators and in 72.9% of arrests that occurred in suitable sites. Compared with an actual overall survival of 744 (5.0%), the predicted survival with public access defibrillators ranged from 942 (6.3%) to 959 (6.5%), depending on the assumptions made regarding defibrillator coverage. Conclusions The predicted increase in survival from targeted provision of public access defibrillators is less than the increase achievable through expansion of first responder defibrillation to non-ambulance personnel, such as police or firefighters, or of bystander cardiopulmonary resuscitation. Additional resources for wide scale coverage of public access defibrillators are probably not justified by the marginal improvement in survival. What is already known on this topicThree quarters of all deaths from acute coronary events occur before the patient reaches a hospitalDefibrillation is an independent predictor of survival from out of hospital cardiac arrestThe probability of a rhythm being amenable to defibrillation declines with timeInterest in providing public access defibrillators to reduce the time to defibrillation has been growing, but their potential impact on overall survival is unknownWhat this study addsMost arrests occur in sites unsuitable for locating public access defibrillatorsArrests that occur in sites suitable for locating defibrillators already have the best profile in terms of ambulance response time, use of defibrillation, and survival of the patientPublic access defibrillators are less likely to increase survival than expansion of first responder defibrillation or bystander cardiopulmonary resuscitation PMID:12217989

Empowering radiologic education on the Internet: a new virtual website technology for hosting interactive educational content on the World Wide Web.

PubMed

Frank, M S; Dreyer, K

2001-06-01

We describe a virtual web site hosting technology that enables educators in radiology to emblazon and make available for delivery on the world wide web their own interactive educational content, free from dependencies on in-house resources and policies. This suite of technologies includes a graphically oriented software application, designed for the computer novice, to facilitate the input, storage, and management of domain expertise within a database system. The database stores this expertise as choreographed and interlinked multimedia entities including text, imagery, interactive questions, and audio. Case-based presentations or thematic lectures can be authored locally, previewed locally within a web browser, then uploaded at will as packaged knowledge objects to an educator's (or department's) personal web site housed within a virtual server architecture. This architecture can host an unlimited number of unique educational web sites for individuals or departments in need of such service. Each virtual site's content is stored within that site's protected back-end database connected to Internet Information Server (Microsoft Corp, Redmond WA) using a suite of Active Server Page (ASP) modules that incorporate Microsoft's Active Data Objects (ADO) technology. Each person's or department's electronic teaching material appears as an independent web site with different levels of access--controlled by a username-password strategy--for teachers and students. There is essentially no static hypertext markup language (HTML). Rather, all pages displayed for a given site are rendered dynamically from case-based or thematic content that is fetched from that virtual site's database. The dynamically rendered HTML is displayed within a web browser in a Socratic fashion that can assess the recipient's current fund of knowledge while providing instantaneous user-specific feedback. Each site is emblazoned with the logo and identification of the participating institution. Individuals with teacher-level access can use a web browser to upload new content as well as manage content already stored on their virtual site. Each virtual site stores, collates, and scores participants' responses to the interactive questions posed on line. This virtual web site strategy empowers the educator with an end-to-end solution for creating interactive educational content and hosting that content within the educator's personalized and protected educational site on the world wide web, thus providing a valuable outlet that can magnify the impact of his or her talents and contributions.

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, a noncatalytic arrangement of the catalytic triad is dominant. Unnatural truncated substrates are inactive because of the lack of protein-protein interactions provided by the ACP. Directed evolution is able to gradually restore the catalytic organization of the active site by motion of the protein backbone that alters the active site geometry. In the third case, we demonstrate the key role of MD in combination with crystallography to identify the origins of substrate-dependent stereoselectivities in a number of Codexis-engineered ketoreductases, one of which is used commercially for the production of the antibiotic sulopenem. Here, mutations alter the shape of the active site as well as the accessibility of water to different regions of it. Each of these examples reveals something different about how mutations can influence enzyme activity and shows that directed evolution, like natural evolution, can increase catalytic activity in a variety of remarkable and often subtle ways.

Surface and adsorptive properties of Moringa oleifera bark for removal of V(V) from aqueous solutions.

PubMed

Mnisi, Robert Londi; Ndibewu, Peter Papoh

2017-11-04

The bark of Moringa oleifera, a cheap and readily available natural biopolymeric resource material, found to significantly reduce coliform load and turbidity in contaminated water is investigated in this paper. Its surface and adsorptive properties are investigated to explore its adsorptive potential in removing V(V) from aqueous solutions. Surface properties were investigated using FTIR, HRSEM/EDS, IC, and BET-N 2 adsorption techniques. Adsorptive properties were investigated by optimizing adsorption parameters such as pH, temperature, initial metal concentration, and adsorbent dosage, using V(V) as an adsorbate. The adsorption-desorption isotherms are typical of type II with a H3 hysteresis loop and is characteristic of a largely macroporous material. Bottle ink pores are observed, which can provide good accessibility of the active sites, even though the internal BET surface area is typically low (1.79 g/m 2 ). Solution pH significantly influences the adsorptive potential of the material. The low surface area negatively impacts on the adsorption capacity, but is compensated for by the exchangeable anions (Cl - , F - , PO 4 3- , NO 3 - , and SO 4 2- ) and cations (Ca 2+ , K + , Mg 2+ , and Al 3+ ) at the surface and the accessibility of the active sites. Adsorption isotherm modeling show that the surface is largely heterogeneous with complex multiple sites and adsorption is not limited to monolayer.

EarthLabs: A National Model for Earth Science Lab Courses

NASA Astrophysics Data System (ADS)

McDaris, J. R.; Dahlman, L.; Barstow, D.

2008-12-01

As a response to the need for more rigorous, inquiry-based high school Earth science courses, a coalition of scientists, educators, and five states have created EarthLabs, a set of pilot modules that can serve as a national model for lab-based science courses. The content of EarthLabs chapters focuses on Earth system science and environmental literacy and conforms to the National Science Education Standards as well as the states' curriculum frameworks. The effort is funded by NOAA's Environmental Literacy program. The pilot modules present activities on Corals, Drought, Fisheries, and Hurricanes. The Fisheries and Hurricanes units were reviewed and field-tested by educators in Texas and Arizona. The feedback from this evaluation led to revisions of these units and guided development of the Corals and Drought chapters. Each module consists of activities that use online data sets, satellite imagery, web-based readings, and hands-on laboratory experiments. The project comprises two separate websites, one for the instructor and one for students. The instructor's site contains the pedagogical underpinnings for each lab including teaching materials, assessment strategies, and the alignment of activities with state and national science standards. The student site provides access to all materials that students need to complete the activities or, in the case of the hands-on labs, where they access additional information to help extend their learning. There are also formative and summative questions embedded in the student webpages to help scaffold learning through the activities.

Warrior Transition Leader: Medical Rehabilitation Handbook

DTIC Science & Technology

2011-01-01

serve. rE f E r E n c E S 1. http://www.army.mil/warriorcarenews/. Accessed January 24, 2011. 2. Warrior Transition Command Web site. http...www.wtc.army.mil/about_us/ ctp.html. Accessed January 24, 2011. 3. Leipold JD. Warrior Transition Command stands up at Pentagon. US Army Web site. Army...January 24, 2011. 4. Warrior Transition Command Web site. http://wtc.armylive.dodlive.mil/ about-wtu/. Accessed January 24, 2011. 5. Leipold JD

Frequency and prognostic significance of access site and non-access site bleeding and impact of choice of antithrombin therapy in patients undergoing primary percutaneous coronary intervention. The EUROMAX trial.

PubMed

Kilic, Sinem; Van't Hof, Arnoud W J; Ten Berg, Jurrien; Lopez, Ana Ayesta; Zeymer, Uwe; Hamon, Martial; Soulat, Louis; Bernstein, Debra; Deliargyris, Efthymios N; Steg, Phillippe Gabriel

2016-05-15

The overall impact of post percutaneous coronary intervention (PCI) bleeding on long term prognosis after acute coronary syndromes (ACS) has been established, but it may differ between access and non-access related bleeding events. The impact of antithrombin choice on bleeding may also differ according to the origin of the bleed. We sought to determine the origin of bleeding relative to the access site, its prognostic significance and the respective impact of antithrombin therapy in the EUROMAX trial. We performed a blinded review of the case records of all TIMI major or minor bleeds in the EUROMAX trial and assigned them in one of 2 categories: access site bleeds (ASB), or rest of bleeds (ROB). Incidence of bleeding for each category was assessed according to randomization to antithrombotic treatment. A total of 231 out of 2198 patients suffered a TIMI major/minor bleed (10.5%) and ASB accounted for 48.5%, while ROB for 51.5% of the bleeds. Thirty day mortality was 2.5% (50/1967) for patients without a bleed, 2.7% (3/112, p=0.76 vs. no bleed) for patients with ASB, and 10.9% (13/119, p<0.0001 vs. no bleed) for ROB patients. The use of bivalirudin reduced both ASB and ROB with relative risk reductions of 34% and 46% respectively. In contemporary primary PCI, bleeding originates with equal frequency either at or away from the access site. Access site bleeds were not associated with an excess in 30day mortality, but the rest of the bleeds were. Bivalirudin is associated with a lower risk of bleeding irrespective of origin. ClinicalTrials.gov identifier NCT01087723. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluating existing access opportunities for disabled persons at remote shoreline recreation sites

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

Bley, M.R.; Kearns, M.T.

1995-12-31

Draft guidelines for providing outdoor recreation access opportunities for disabled persons have been recommended by the Recreation Access Advisory Committee and in the Universal Access to Outdoor Recreation: A Design Guide. The Federal Energy Regulatory Commission requires applicants for new hydropower licenses to consider access opportunities for disabled persons at existing hydropower projects. A process for evaluating existing access opportunities for disabled persons at remote shoreline recreation sites at hydropower projects is described. The process includes five steps: (1) preparing a preliminary map of existing recreation sites; (2) data collection in the field; (3) evaluating compliance of existing facilities; (4)more » feasibility of enhancing existing facilities; and (5) designing enhancements. The process will be refined when final standards and processes are approved by the appropriate agencies and organizations.« less

Discovery of Selective Inhibitors of Imidazoleglycerol-Phosphate Dehydratase from Mycobacterium tuberculosis by Virtual Screening

NASA Astrophysics Data System (ADS)

Podshivalov, D.; Mandzhieva, Yu. B.; Sidorov-Biryukov, D. D.; Timofeev, V. I.; Kuranova, I. P.

2018-01-01

Bacterial imidazoleglycerol-phosphate dehydratase from Mycobacterium tuberculosis (HisB- Mt) is a convenient target for the discovery of selective inhibitors as potential antituberculosis drugs. The virtual screening was performed to find compounds suitable for the design of selective inhibitors of HisB- Mt. The positions of four ligands, which were selected based on the docking scoring function and docked to the activesite region of the enzyme, were refined by molecular dynamics simulation. The nearest environment of the ligands was determined. These compounds selectively bind to functionally essential active-site residues, thus blocking access of substrates to the active site of the enzyme, and can be used as lead compounds for the design of selective inhibitors of HisB- M.

The Lawrence Berkeley Laboratory geothermal program in northern Nevada

NASA Technical Reports Server (NTRS)

Mirk, K. F.; Wollenberg, H. A.

1974-01-01

The Lawrence Berkeley Laboratory's geothermal program began with consideration of regions where fluids in the temperature range of 150 to 230 C may be economically accessible. Three valleys, located in an area of high regional heat flow in north central Nevada, were selected for geological, geophysical, and geochemical field studies. The objective of these ongoing field activities is to select a site for a 10-MW demonstration plant. Field activities (which started in September 1973) are described. A parallel effort has been directed toward the conceptual design of a 10-MW isobutane binary plant which is planned for construction at the selected site. Design details of the plant are described. Project schedule with milestones is shown together with a cost summary of the project.

Site-selective and stereoselective functionalization of non-activated tertiary C-H bonds

NASA Astrophysics Data System (ADS)

Liao, Kuangbiao; Pickel, Thomas C.; Boyarskikh, Vyacheslav; Bacsa, John; Musaev, Djamaladdin G.; Davies, Huw M. L.

2017-11-01

The synthesis of complex organic compounds usually relies on controlling the reactions of the functional groups. In recent years, it has become possible to carry out reactions directly on the C-H bonds, previously considered to be unreactive. One of the major challenges is to control the site-selectivity because most organic compounds have many similar C-H bonds. The most well developed procedures so far rely on the use of substrate control, in which the substrate has one inherently more reactive C-H bond or contains a directing group or the reaction is conducted intramolecularly so that a specific C-H bond is favoured. A more versatile but more challenging approach is to use catalysts to control which site in the substrate is functionalized. p450 enzymes exhibit C-H oxidation site-selectivity, in which the enzyme scaffold causes a specific C-H bond to be functionalized by placing it close to the iron-oxo haem complex. Several studies have aimed to emulate this enzymatic site-selectivity with designed transition-metal catalysts but it is difficult to achieve exceptionally high levels of site-selectivity. Recently, we reported a dirhodium catalyst for the site-selective functionalization of the most accessible non-activated (that is, not next to a functional group) secondary C-H bonds by means of rhodium-carbene-induced C-H insertion. Here we describe another dirhodium catalyst that has a very different reactivity profile. Instead of the secondary C-H bond, the new catalyst is capable of precise site-selectivity at the most accessible tertiary C-H bonds. Using this catalyst, we modify several natural products, including steroids and a vitamin E derivative, indicating the applicability of this method of synthesis to the late-stage functionalization of complex molecules. These studies show it is possible to achieve site-selectivity at different positions within a substrate simply by selecting the appropriate catalyst. We hope that this work will inspire the design of even more sophisticated catalysts, such that catalyst-controlled C-H functionalization becomes a broadly applied strategy for the synthesis of complex molecules.

Traffic-based feedback on the web.

PubMed

Aizen, Jonathan; Huttenlocher, Daniel; Kleinberg, Jon; Novak, Antal

2004-04-06

Usage data at a high-traffic web site can expose information about external events and surges in popularity that may not be accessible solely from analyses of content and link structure. We consider sites that are organized around a set of items available for purchase or download, consider, for example, an e-commerce site or collection of online research papers, and we study a simple indicator of collective user interest in an item, the batting average, defined as the fraction of visits to an item's description that result in an acquisition of that item. We develop a stochastic model for identifying points in time at which an item's batting average experiences significant change. In experiments with usage data from the Internet Archive, we find that such changes often occur in an abrupt, discrete fashion, and that these changes can be closely aligned with events such as the highlighting of an item on the site or the appearance of a link from an active external referrer. In this way, analyzing the dynamics of item popularity at an active web site can help characterize the impact of a range of events taking place both on and off the site.

Traffic-based feedback on the web

PubMed Central

Aizen, Jonathan; Huttenlocher, Daniel; Kleinberg, Jon; Novak, Antal

2004-01-01

Usage data at a high-traffic web site can expose information about external events and surges in popularity that may not be accessible solely from analyses of content and link structure. We consider sites that are organized around a set of items available for purchase or download, consider, for example, an e-commerce site or collection of online research papers, and we study a simple indicator of collective user interest in an item, the batting average, defined as the fraction of visits to an item's description that result in an acquisition of that item. We develop a stochastic model for identifying points in time at which an item's batting average experiences significant change. In experiments with usage data from the Internet Archive, we find that such changes often occur in an abrupt, discrete fashion, and that these changes can be closely aligned with events such as the highlighting of an item on the site or the appearance of a link from an active external referrer. In this way, analyzing the dynamics of item popularity at an active web site can help characterize the impact of a range of events taking place both on and off the site. PMID:14709676

Perception of Human-Derived Risk Influences Choice at Top of the Food Chain

PubMed Central

Cristescu, Bogdan; Stenhouse, Gordon B.; Boyce, Mark S.

2013-01-01

On human-used landscapes, animal behavior is a trade-off between maximizing fitness and minimizing human-derived risk. Understanding risk perception in wildlife can allow mitigation of anthropogenic risk, with benefits to long-term animal fitness. Areas where animals choose to rest should minimize risk from predators, which for large carnivores typically equate to humans. We hypothesize that high human activity leads to selection for habitat security, whereas low activity enables trading security for forage. We investigated selection of resting (bedding) sites by GPS radiocollared adult grizzly bears (n = 10) in a low density population on a multiple-use landscape in Canada. We compared security and foods at resting and random locations while accounting for land use, season, and time of day. On reclaimed mines with low human access, bears selected high horizontal cover far from trails, but did not avoid open (herbaceous) areas, resting primarily at night. In protected areas bears also bedded at night, in areas with berry shrubs and Hedysarum spp., with horizontal cover selected in the summer, during high human access. On public lands with substantial human recreation, bears bedded at day, selected resting sites with high horizontal cover in the summer and habitat edges, with bedding associated with herbaceous foods. These spatial and temporal patterns of selection suggest that bears perceive human-related risk differentially in relation to human activity level, season and time of day, and employ a security-food trade-off strategy. Although grizzly bears are presently not hunted in Alberta, their perceived risks associated with humans influence resting-site selection. PMID:24367549

Facilitating access: what information do Texas postsecondary institutions provide on accommodations and services for students who are deaf or hard of hearing?

PubMed

Cawthon, Stephanie W; Nichols, Sarah K; Collier, Mike

2009-01-01

Students who are deaf or hard of hearing often require accommodations in order to participate in essential functions of college life. Although federal law mandates access to campus activities, real access for these students varies by site. The present study investigated the level of access of students who are deaf or hard of hearing at Texas postsecondary institutions. These schools' online accommodations policies were reviewed in fall 2006. A systematic review of published policies was used to summarize accommodations and services available for instruction, assessment, and campus life. About half of the 157 schools provided information online. Examples of classroom accommodations included note takers during class lectures and extra time for tests. Nonacademicservices included referrals to community resources and course registration assistance. Results are discussed in the context of information that prospective students may need to make informed choices regarding postsecondary education.

Nursing students' perception of a Web-based intervention to support learning.

PubMed

Koch, Jane; Andrew, Sharon; Salamonson, Yenna; Everett, Bronwyn; Davidson, Patricia M

2010-08-01

Tailoring information to the needs of the learner is an important strategy in contemporary education settings. Web-based learning support, informed by multimedia theory, comprising interactive quizzes, glossaries with audio, short narrated Power Point(R) presentations, animations and digitised video clips were introduced in a first year Bachelor of Nursing biological sciences subject at a university in metropolitan Sydney. All students enrolled in this unit were invited to obtain access to the site and the number of hits to the site was recorded using the student tracking facility available on WebCT, an online course delivery tool adopted widely by many educational institutions and used in this study. Eighty-five percent of students enrolled in the subject accessed the learning support site. Students' perception of the value of a learning support site was assessed using a web-based survey. The survey was completed by 123 participants, representing a response rate of 22%. Three themes emerged from the qualitative data concerning nursing students' perception of the web-based activities: 'enhances my learning', 'study at my own pace', and 'about the activities: what I really liked/disliked'. Web-based interventions, supplementing a traditionally presented nursing science course were perceived by students to be beneficial in both learning and language development. Although students value interactive, multimedia learning they were not ready to completely abandon traditional modes of learning including face-to-face lectures. The findings of this study contribute to an understanding of how web-based resources can be best used to support students' learning in bioscience. Copyright 2009 Elsevier Ltd. All rights reserved.

5 CFR 2606.201 - Requests for access.

Code of Federal Regulations, 2011 CFR

2011-01-01

... on OGE's Web site at http://www.usoge.gov, or upon request from OGE's Office of General Counsel and... Office of Federal Register at the GPO Access Web site (http://www.access.gpo.gov/su_docs/aces/PrivacyAct... individual's full name (including her maiden name, if pertinent), dates of employment, social security number...

6 CFR 5.21 - Requests for access to records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... accessed electronically at the Government Printing Office's World Wide Web site (which can be found at http... Printing Office's World Wide Web site (which can be found at http://www.access.gpo.gov/su_docs). (c... requested records, you may also, at your option, include your social security number. (e) Verification of...

28 CFR 16.41 - Requests for access to records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Government Printing Office's World Wide Web site (which can be found at http://www.access.gpo.gov... accessed electronically at the Government Printing Office's World Wide Web site (which can be found at http... requested records, you may also, at your option, include your social security number. (e) Verification of...

6 CFR 5.21 - Requests for access to records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... accessed electronically at the Government Printing Office's World Wide Web site (which can be found at http... Printing Office's World Wide Web site (which can be found at http://www.access.gpo.gov/su_docs). (c... requested records, you may also, at your option, include your social security number. (e) Verification of...

28 CFR 16.41 - Requests for access to records.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Government Printing Office's World Wide Web site (which can be found at http://www.access.gpo.gov... accessed electronically at the Government Printing Office's World Wide Web site (which can be found at http... requested records, you may also, at your option, include your social security number. (e) Verification of...

Tools to Ease Your Internet Adventures: Part I.

ERIC Educational Resources Information Center

Descy, Don E.

1993-01-01

This first of a two-part series highlights three tools that improve accessibility to Internet resources: (1) Alex, a database that accesses files in FTP (file transfer protocol) sites; (2) Archie, software that searches for file names with a user's search term; and (3) Gopher, a menu-driven program to access Internet sites. (LRW)

Real-time Data Access From Remote Observatories

NASA Astrophysics Data System (ADS)

Detrick, D. L.; Lutz, L. F.; Etter, J. E.; Rosenberg, T. J.; Weatherwax, A. T.

2006-12-01

Real-time access to solar-terrestrial data is becoming increasingly important, not only because it is now possible to acquire and access data rapidly via the internet, but also because of the need for timely publication of real-time data for analysis and modeling efforts. Currently, engineering-scaled summary data are available routinely on a daily basis from many observatories, but only when the observatories have continuous, or at least daily network access. Increasingly, the upgrading of remote data acquisition hardware makes it possible to provide data in real-time, and it is becoming normal to expect timely access to data products. The NSF- supported PENGUIn/AGO constellation of autonomous Antarctic research observatories has provided real-time data since December, 2002, when Iridium satellite modems were installed at three sites. The Iridium telecommunications links are maintained continuously, transferring data between the remote observatories and a U.S.-based data acquisition site. The time-limiting factor with this scenario is now the delay in completing a data record before transmission, which can be as short as minutes depending on the sampling rate. The single-channel data throughput of the current systems is 20-MB/day (megabytes per day), but planned installations will be capable of operating with multiple modem channels. The data records are currently posted immediately to a web site accessible by anonymous FTP client software, for use by the instruments' principal investigators, and survey plots of selected signals are published daily. The web publication facilities are being upgraded, in order to allow other interested researchers rapid access to engineering-scaled data products, in several common formats, as well as providing interactive plotting capabilities. The web site will provide access to data from other collaborating observatories (including South Pole and McMurdo Stations), as well as ancillary data accessible from public sites (e.g., Kp, AE, Dst). The site will be accessible via common HTML interface protocols, enabling access to the data products by browsers or other compatible application software. We describe details of the hardware and software components of the Iridium telecommunications linkage, as well as details of the current and planned web publication capabilities.

Highly dispersed buckybowls as model carbocatalysts for C–H bond activation

DOE PAGES

Soykal, I. Ilgaz; Wang, Hui; Park, Jewook; ...

2015-03-19

Buckybowl fractions dispersed on mesoporous silica constitute an ideal model for studying the catalysis of graphitic forms of carbon since the dispersed carbon nanostructures contain a high ratio of edge defects and curvature induced by non-six-membered rings. Dispersion of the active centers on an easily accessible high surface area material allowed for high density of surface active sites associated with oxygenated structures. This report illustrates a facile method of creating model polycyclic aromatic nano-structures that are not only active for alkane C-H bond activation and oxidative dehydrogenation but also can be practical catalysts to be eventually used in industry.

First confirmation and characterization of target and non-target site resistance to glyphosate in Palmer amaranth (Amaranthus palmeri) from Mexico.

PubMed

Dominguez-Valenzuela, Jose Alfredo; Gherekhloo, Javid; Fernández-Moreno, Pablo Tomás; Cruz-Hipolito, Hugo Enrique; Alcántara-de la Cruz, Ricardo; Sánchez-González, Eduardo; De Prado, Rafael

2017-06-01

Following the introduction of glyphosate-resistant (GR)-cotton crops in Mexico, farmers have relied upon glyphosate as being the only herbicide for in-season weed control. Continuous use of glyphosate within the same year and over multiple successive years has resulted in the selection of glyphosate resistance in Palmer amaranth (Amarantus palmeri). Dose-response assays confirmed resistance in seven different accessions. The resistance ratio based on GR 50 values (50% growth reduction) varied between 12 and 83. At 1000 μM glyphosate, shikimic acid accumulation in the S-accession was 30- to 2-fold higher at compared to R-accessions. At 96 h after treatment, 35-44% and 61% of applied 14 C-glyphosate was taken up by leaves of plants from R- and S-accessions, respectively. At this time, a significantly higher proportion of the glyphosate absorbed remained in the treated leaf of R-plants (55-69%) compared to S-plants (36%). Glyphosate metabolism was low and did not differ between resistant and susceptible plants. Glyphosate was differentially metabolized to AMPA and glyoxylate in plants of R- and S-accessions, although it was low in both accessions (<10%). There were differences in 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme activity by 50% (I 50 ) between R- and S-accessions. However, no significant differences were found in the basal EPSPS activity (μmol inorganic phosphate μg -1 total soluble protein min -1 ) between R- and S-accessions. A point mutation Pro-106-Ser was evidenced in three accessions. The results confirmed the resistance of Palmer amaranth accessions to glyphosate collected from GR-cotton crops from Mexico. This is the first study demonstrating glyphosate-resistance in Palmer amaranth from Mexico. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

NFFA-Europe: enhancing European competitiveness in nanoscience research and innovation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Carsughi, Flavio; Fonseca, Luis

2017-06-01

NFFA-EUROPE is an European open access resource for experimental and theoretical nanoscience and sets out a platform to carry out comprehensive projects for multidisciplinary research at the nanoscale extending from synthesis to nanocharacterization to theory and numerical simulation. Advanced infrastructures specialized on growth, nano-lithography, nano-characterization, theory and simulation and fine-analysis with Synchrotron, FEL and Neutron radiation sources are integrated in a multi-site combination to develop frontier research on methods for reproducible nanoscience research and to enable European and international researchers from diverse disciplines to carry out advanced proposals impacting science and innovation. NFFA-EUROPE will enable coordinated access to infrastructures on different aspects of nanoscience research that is not currently available at single specialized ones and without duplicating their specific scopes. Approved user projects will have access to the best suited instruments and support competences for performing the research, including access to analytical large scale facilities, theory and simulation and high-performance computing facilities. Access is offered free of charge to European users and users will receive a financial contribution for their travel, accommodation and subsistence costs. The users access will include several "installations" and will be coordinated through a single entry point portal that will activate an advanced user-infrastructure dialogue to build up a personalized access programme with an increasing return on science and innovation production. The own research activity of NFFA-EUROPE will address key bottlenecks of nanoscience research: nanostructure traceability, protocol reproducibility, in-operando nano-manipulation and analysis, open data.

Quality and accuracy of publicly accessible cancer-related physical activity information on the Internet: a cross-sectional assessment.

PubMed

Buote, R D; Malone, S D; Bélanger, L J; McGowan, E L

2016-09-01

In this study, we assessed the quality of publicly available cancer-related physical activity (PA) information appearing on reputable sites from Canada and other English-speaking countries. A cross-sectional Internet search was conducted on select countries (Canada, USA, Australia, New Zealand, UK) using Google to generate top 50 results per country for the keywords "'physical activity' AND 'cancer'". Top results were assessed for quality of PA information based on a coding frame. Additional searches were performed for Canadian-based sites to produce an exhaustive list. Results found that many sites offered cancer-related PA information (94.5%), but rarely defined PA (25.2%). Top 50 results from each country did not differ on any indicator examined. The exhaustive list of Canadian sites found that many sites gave information about PA for survivorship (78.3%) and prevention (70.0%), but rarely defined (6.7%) or referenced PA guidelines (28.3%). Cancer-related PA information is plentiful on the Internet but the quality needs improvement. Sites should do more than mention PA; they should provide definitions, examples and guidelines. With improvements, these websites would enable healthcare providers to effectively educate their patients about PA, and serve as a valuable resource to the general public who may be seeking cancer-related PA information. © 2016 John Wiley & Sons Ltd.

Final report on decommissioning of wells, boreholes, and tiltmeter sites, Gulf Coast Interior Salt Domes of Louisiana

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

Not Available

1989-07-01

In the late 1970s, test holes were drilled in northern Louisiana in the vicinity of Vacherie and Rayburn`s Salt Domes as part of the Department of Energy`s (DOE) National Waste Terminal Storage (NWTS) (rename the Civilian Radioactive Waste Management (CRWM)) program. The purpose of the program was to evaluate the suitability of salt domes for long term storage or disposal of high-level nuclear waste. The Institute for Environmental Studies at Louisiana State University (IES/LSU) and Law Engineering Testing Company (LETCo) of Marietta, Georgia performed the initial field studies. In 1982, DOE awarded a contract to the Earth Technology Corporation (TETC)more » of Long Beach, California to continue the Gulf Coast Salt Dome studies. In 1986, DOE deferred salt domes from further consideration as repository sites. This report describes test well plugging and site abandonment activities performed by SWEC in accordance with Activity Plan (AP) 1--3, Well Plugging and Site Restoration of Work Sites in Louisiana. The objective of the work outlined in this AP was to return test sites to as near original condition as possible by plugging boreholes, removing equipment, regrading, and seeding. Appendices to this report contain forms required by State of Louisiana, used by SWEC to document decommissioning activities, and pertinent documentation related to lease/access agreements.« less

Human prorenin structure sheds light on a novel mechanism of its autoinhibition and on its non-proteolytic activation by the (pro)renin receptor.

PubMed

Morales, Renaud; Watier, Yves; Böcskei, Zsolt

2012-08-03

Antibodies and prorenin mutants have long been used to structurally characterize prorenin, the inactive proenzyme form of renin. They were designed on the basis of homology models built using other aspartyl protease proenzyme structures since no structure was available for prorenin. Here, we present the first X-ray structure of a prorenin. The current structure of prorenin reveals that, in this zymogene, the active site of renin is blocked by the N-terminal residues of the mature version of the renin molecule, which are, in turn, covered by an Ω-shaped prosegment. This prevents access of substrates to the active site. The departure of the prosegment on activation induces an important global conformational change in the mature renin molecule with respect to prorenin: similar to other related enzymes such as pepsin or gastricsin, the segment that constitutes the N-terminal β-strand in renin is displaced from the renin active site by about 180° straight into the position that corresponds to the N-terminal β-strand of the prorenin prosegment. This way, the renin active site will become completely exposed and capable of carrying out its catalytic functions. A unique inactivation mechanism is also revealed, which does not make use of a lysine against the catalytic aspartates, probably in order to facilitate pH-independent activation [e.g., by the (pro)renin receptor]. Copyright © 2012 Elsevier Ltd. All rights reserved.

DMSP SSJ4 Data Restoration, Classification, and On-Line Data Access

NASA Technical Reports Server (NTRS)

Wing, Simon; Bredekamp, Joseph H. (Technical Monitor)

2000-01-01

Compress and clean raw data file for permanent storage We have identified various error conditions/types and developed algorithms to get rid of these errors/noises, including the more complicated noise in the newer data sets. (status = 100% complete). Internet access of compacted raw data. It is now possible to access the raw data via our web site, http://www.jhuapl.edu/Aurora/index.html. The software to read and plot the compacted raw data is also available from the same web site. The users can now download the raw data, read, plot, or manipulate the data as they wish on their own computer. The users are able to access the cleaned data sets. Internet access of the color spectrograms. This task has also been completed. It is now possible to access the spectrograms from the web site mentioned above. Improve the particle precipitation region classification. The algorithm for doing this task has been developed and implemented. As a result, the accuracies improved. Now the web site routinely distributes the results of applying the new algorithm to the cleaned data set. Mark the classification region on the spectrograms. The software to mark the classification region in the spectrograms has been completed. This is also available from our web site.

Association of Commercial Rice Varieties with Weedy Rice Accessions (Oryza sativa complex) in Pulau Pinang's Rice Granary Area.

PubMed

Hussain, Zainudin; Man, Azmi; Othman, Ahmad Sofiman

2011-12-01

Weedy rice (WR) is the most significant weed in direct-seeded fields. It has morphological characteristics similar to those of cultivated rice varieties. WR is more difficult to control than other weeds. We collected WR accessions from four sites within the Pulau Pinang rice growing areas. Thirty six different accessions were collected from each site: B, the northern site; P, the central site; A, the southern site; and N, the southwestern site. Wild rice (Oryza rufipogon), which grows in the sampled areas, was also collected together with four varieties (MR84, MR185, MR211 and MR219) that have been widely planted in these areas for a long period of time. The objective of this study was to compare the morphological characteristics of the WR accessions and cultivated rice. Twenty characteristics were observed for the comparison of WR accessions and rice cultivars. Morpho-matrix analyses allowed the specimens to be grouped to two main groups (A and B), based on a 95% dissimilarity matrix. Group A was subdivided into 7 subgroups consisting of a few WR accessions, wild rice and MR211 (control), and group B was subdivided to 10 subgroups consisting of other WR accessions and the 3 other control varieties. Dendrogram analysis indicated that the morphological traits used in this study were able to differentiate among the WR accessions and the cultivars, except for rice cultivar MR211 and WRA8, which grouped together in subgroup A2. STRUCTURE program analysis indicated that all individuals were distinguishable and were divided into 18 clusters. These results suggest that some genes of the WR accessions have been influenced by commercial varieties. The information gained from this study will be useful to develop rice weed management protocols and good agricultural practices to control WR in the future.

Web-based volcano monitoring data from the Pu‘u ‘O‘o eruptive vent (Kilauea Volcano, Hawai‘i) as a tool for geoscience education

NASA Astrophysics Data System (ADS)

Poland, M. P.; Townson, R.; Loren, A.; Brooks, B. A.; Foster, J. H.

2009-12-01

A significant challenge in college and university geoscience courses is conveying the dynamic nature of the Earth to students. The Internet, however, offers an opportunity to engage classes by making accessible the best examples of current geologic activity, regardless of location. In volcanology, Kilauea, Hawai‘i, is well known as one of the most active volcanoes in the world, and the Web site for the U.S. Geological Survey’s Hawaiian Volcano Observatory offers a daily update of volcanic activity that is followed by people around the globe. The Pu‘u ‘O‘o eruptive vent, on Kilauea‘s east rift zone, has been the focus of near continuous eruption since 1983, experiencing cycles of growth and collapse, high lava fountains, lava lakes, and other phenomena over the course of its existence. To track volcanic activity, various types of monitoring instruments have been installed on and around Pu‘u ‘O‘o, including (as of August 2009) two webcams, one short-period seismometer, one broadband seismometer, seven continuous GPS stations, and two continuous borehole tiltmeters. Monitoring data from Pu‘u ‘O‘o will be made available via the Internet as part of a collaborative research and education project between the Hawaiian Volcano Observatory, National Aeronautics and Space Administration, and University of Hawai‘i at Mānoa. The educational Web site is intended for use in college and university courses, from introductory science classes to graduate-level seminars. Scheduled to come on line by fall 2009, the Web site will provide tools to explore current monitoring results from the eruptive vent. Geophysical data, such as GPS, seismic, and tilt measurements, will be accessible via a time-series query tool, and the complete archive of webcam imagery will be available for examination of visual changes in volcanic activity over time. The Web site will also include background information and references concerning the 1983-present eruption, descriptions of monitoring tools, and resources for instructors. The goal of this project is to demonstrate the dynamic nature of the Earth, promote excitement about the process of scientific discovery, and inspire the next generation of Earth scientists. To encourage use of the Web site, a workshop will be held in mid-2010 to develop curricula for various levels of college and university courses.

Engineering Nucleotide Specificity of Succinyl-CoA Synthetase in Blastocystis: The Emerging Role of Gatekeeper Residues.

PubMed

Vashisht, Kapil; Verma, Sonia; Gupta, Sunita; Lynn, Andrew M; Dixit, Rajnikant; Mishra, Neelima; Valecha, Neena; Hamblin, Karleigh A; Maytum, Robin; Pandey, Kailash C; van der Giezen, Mark

2017-01-24

Charged, solvent-exposed residues at the entrance to the substrate binding site (gatekeeper residues) produce electrostatic dipole interactions with approaching substrates, and control their access by a novel mechanism called "electrostatic gatekeeper effect". This proof-of-concept study demonstrates that the nucleotide specificity can be engineered by altering the electrostatic properties of the gatekeeper residues outside the binding site. Using Blastocystis succinyl-CoA synthetase (SCS, EC 6.2.1.5), we demonstrated that the gatekeeper mutant (ED) resulted in ATP-specific SCS to show high GTP specificity. Moreover, nucleotide binding site mutant (LF) had no effect on GTP specificity and remained ATP-specific. However, via combination of the gatekeeper mutant with the nucleotide binding site mutant (ED+LF), a complete reversal of nucleotide specificity was obtained with GTP, but no detectable activity was obtained with ATP. This striking result of the combined mutant (ED+LF) was due to two changes; negatively charged gatekeeper residues (ED) favored GTP access, and nucleotide binding site residues (LF) altered ATP binding, which was consistent with the hypothesis of the "electrostatic gatekeeper effect". These results were further supported by molecular modeling and simulation studies. Hence, it is imperative to extend the strategy of the gatekeeper effect in a different range of crucial enzymes (synthetases, kinases, and transferases) to engineer substrate specificity for various industrial applications and substrate-based drug design.

Crystal Structure and Functional Analysis of Homocitrate Synthase, an Essential Enzyme in Lysine Biosynthesis

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

Bulfer, Stacie L.; Scott, Erin M.; Couture, Jean-François

2010-01-12

Homocitrate synthase (HCS) catalyzes the first and committed step in lysine biosynthesis in many fungi and certain Archaea and is a potential target for antifungal drugs. Here we report the crystal structure of the HCS apoenzyme from Schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-OG). The structures reveal that HCS forms an intertwined homodimer stabilized by domain-swapping between the N- and C-terminal domains of each monomer. The N-terminal catalytic domain is composed of a TIM barrel fold in which 2-OG binds via hydrogen bonds and coordination to the active site divalent metalmore » ion, whereas the C-terminal domain is composed of mixed {alpha}/{beta} topology. In the structures of the HCS apoenzyme and one of the 2-OG binary complexes, a lid motif from the C-terminal domain occludes the entrance to the active site of the neighboring monomer, whereas in the second 2-OG complex the lid is disordered, suggesting that it regulates substrate access to the active site through its apparent flexibility. Mutations of the active site residues involved in 2-OG binding or implicated in acid-base catalysis impair or abolish activity in vitro and in vivo. Together, these results yield new insights into the structure and catalytic mechanism of HCSs and furnish a platform for developing HCS-selective inhibitors.« less

Pore-expanded SBA-15 sulfonic acid silicas for biodiesel synthesis.

PubMed

Dacquin, J P; Lee, A F; Pirez, C; Wilson, K

2012-01-07

Here we present the first application of pore-expanded SBA-15 in heterogeneous catalysis. Pore expansion over the range 6-14 nm confers a striking activity enhancement towards fatty acid methyl ester (FAME) synthesis from triglycerides (TAG), and free fatty acid (FFA), attributed to improved mass transport and acid site accessibility. This journal is © The Royal Society of Chemistry 2012

An operational data access infrastructure for accessing integrated environmental and socio-economic data from the Dutch Wadden Sea

NASA Astrophysics Data System (ADS)

De Bruin, T.

2012-12-01

The Wadden Sea, an UNESCO World Heritage Site along the Northern coasts of The Netherlands, Germany and Denmark, is a very valuable, yet also highly vulnerable tidal flats area. Knowledge is key to the sustainable management of the Wadden Sea. This knowledge should be reliable, founded on promptly accessible information and sufficiently broad to integrate both ecological and economic analyses. The knowledge is gained from extensive monotoring of both ecological and socio-economic parameters. Even though many organisations, research institutes, government agencies and NGOs carry out monitoring, there is no central overview of monitoring activities, nor easy access to the resulting data. The 'Wadden Sea Long-Term Ecosystem Research' (WaLTER) project (2011-2015) aims to set-up an integrated monitoring plan for the main environmental and management issues relevant to the Wadden Sea, such as sea-level rise, fisheries management, recreation and industry activities. The WaLTER data access infrastructure will be a distributed system of data providers, with a centralized data access portal. It is based on and makes use of the existing data access infrastructure of the Netherlands National Oceanographic Data Committee (NL-NODC), which has been operational since early 2009. The NL-NODC system is identical to and in fact developed by the European SeaDataNet project, furthering standardisation on a pan-European scale. The presentation will focus on the use of a distributed data access infrastructure to address the needs of different user groups such as policy makers, scientists and the general public.

Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

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

Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina

Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

DOE PAGES

Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina; ...

2017-05-02

Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

Nevada National Security Site Environmental Report 2012 Attachment A: Site Description

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

Wills, Cathy A

This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2012 (National Security Technologies, LLC [NSTec], 2013). Included are subsections that summarize the site’s geological, hydrological, climatological, and ecological setting and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site’s environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current site operations, andmore » assess the impacts of site operations on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

Nevada National Security Site Environmental Report 2013 Attachment A: Site Description

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

Wills, C.

This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2012 (National Security Technologies, LLC [NSTec], 2013). Included are subsections that summarize the site’s geological, hydrological, climatological, and ecological setting and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site’s environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current site operations, andmore » assess the impacts of site operations on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

Accessibility for persons with mobility impairments within an informal trading site: A case study on the markets of Warwick, South Africa

PubMed Central

Koch, Helga Elke; Anderson, Jassmine; Ghela, Prashika; Govender, Perusha; Hoosen, Nausheena; Khan, Halima

2014-01-01

Background There are a number of informal trading sites across cities in sub-Saharan Africa, of which the markets of Warwick is one example. Since the informal economy is an important contributor to a city’s economy as well as a source of employment, it is important for these sites to be accessible for all persons. Whilst the South African government has put structures in place to identify and remove environmental barriers in order to meet the individual needs of persons with mobility impairments and improve their quality of life, persons with mobility impairments still face barriers and restricting environments that prevent them from participating in society and its social and economic activities. Objectives This case study aimed at exploring accessibility within the markets of Warwick for persons with mobility impairments by an ergonomic assessment, augmented by voices of participants within the market. Method A qualitative, instrumental, single case study design was utilised with purposive sampling of the markets of Warwick as the study setting. Multiple sources of data were gathered, such as semi-structured interviews, direct observations of an environmental survey supported by photographs, and the authors’ review of relevant documents. Transcriptions were analysed using NVivo 10 software programme with inductive coding. Results Whilst policies have been in place since 1996 to adjust infrastructure, the markets of Warwick still remain inaccessible to persons with mobility impairments and do not meet the standardised infrastructural design. Conclusion The findings of this study may offer a significant understanding of the complexity of accessibility within an informal trading site and create an awareness of the limitations this has for persons with mobility impairments. Additionally, these findings may assist in effecting a positive change in terms of the infrastructure of the Markets and in continuous advocating for the rights of persons with all disabilities. PMID:28730002

Naval Oceanography Portal

Science.gov Websites

accessible and usable, working in accordance with the Web Content Accessibility Guidelines (WCAG v1.0). If navigation device enabling you to get around this web site using your keyboard. Available access keys This develop a web site that is clear and simple for everybody to use. Validation We have used XHTML 1.0 and

Global Access to Library of Congress' Digital Resources: National Digital Library and Internet Resources.

ERIC Educational Resources Information Center

Chen, Ching-chih

1996-01-01

Summarizes how the Library of Congress' digital library collections can be accessed globally via the Internet and World Wide Web. Outlines the resources found in each of the various access points: gopher, online catalog, library and legislative Web sites, legal and copyright databases, and FTP (file transfer protocol) sites. (LAM)

41 CFR 60-1.43 - Access to records and site of employment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Access to records and site of employment. 60-1.43 Section 60-1.43 Public Contracts and Property Management Other Provisions..., DEPARTMENT OF LABOR 1-OBLIGATIONS OF CONTRACTORS AND SUBCONTRACTORS Ancillary Matters § 60-1.43 Access to...

41 CFR 60-1.43 - Access to records and site of employment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Access to records and site of employment. 60-1.43 Section 60-1.43 Public Contracts and Property Management Other Provisions..., DEPARTMENT OF LABOR 1-OBLIGATIONS OF CONTRACTORS AND SUBCONTRACTORS Ancillary Matters § 60-1.43 Access to...

Methodology for Localized and Accessible Image Formation and Elucidation

ERIC Educational Resources Information Center

Patil, Sandeep R.; Katiyar, Manish

2009-01-01

Accessibility is one of the key checkpoints in all software products, applications, and Web sites. Accessibility with digital images has always been a major challenge for the industry. Images form an integral part of certain type of documents and most Web 2.0-compliant Web sites. Individuals challenged with blindness and many dyslexics only make…

Application of threshold concepts to ecological management problems: occupancy of Golden Eagles in Denali National Park, Alaska: Chapter 5

USGS Publications Warehouse

Eaton, Mitchell J.; Martin, Julien; Nichols, James D.; McIntyre, Carol; McCluskie, Maggie C.; Schmutz, Joel A.; Lubow, Bruce L.; Runge, Michael C.; Edited by Guntenspergen, Glenn R.

2014-01-01

In this chapter, we demonstrate the application of the various classes of thresholds, detailed in earlier chapters and elsewhere, via an actual but simplified natural resource management case study. We intend our example to provide the reader with the ability to recognize and apply the theoretical concepts of utility, ecological and decision thresholds to management problems through a formalized decision-analytic process. Our case study concerns the management of human recreational activities in Alaska’s Denali National Park, USA, and the possible impacts of such activities on nesting Golden Eagles, Aquila chrysaetos. Managers desire to allow visitors the greatest amount of access to park lands, provided that eagle nesting-site occupancy is maintained at a level determined to be acceptable by the managers themselves. As these two management objectives are potentially at odds, we treat minimum desired occupancy level as a utility threshold which, then, serves to guide the selection of annual management alternatives in the decision process. As human disturbance is not the only factor influencing eagle occupancy, we model nesting-site dynamics as a function of both disturbance and prey availability. We incorporate uncertainty in these dynamics by considering several hypotheses, including a hypothesis that site occupancy is affected only at a threshold level of prey abundance (i.e., an ecological threshold effect). By considering competing management objectives and accounting for two forms of thresholds in the decision process, we are able to determine the optimal number of annual nesting-site restrictions that will produce the greatest long-term benefits for both eagles and humans. Setting a utility threshold of 75 occupied sites, out of a total of 90 potential nesting sites, the optimization specified a decision threshold at approximately 80 occupied sites. At the point that current occupancy falls below 80 sites, the recommended decision is to begin restricting access to humans; above this level, it is recommended that all eagle territories be opened to human recreation. We evaluated the sensitivity of the decision threshold to uncertainty in system dynamics and to management objectives (i.e., to the utility threshold).

An adaptive-management framework for optimal control of hiking near golden eagle nests in Denali National Park

USGS Publications Warehouse

Martin, Julien; Fackler, Paul L.; Nichols, James D.; Runge, Michael C.; McIntyre, Carol L.; Lubow, Bruce L.; McCluskie, Maggie C.; Schmutz, Joel A.

2011-01-01

Unintended effects of recreational activities in protected areas are of growing concern. We used an adaptive-management framework to develop guidelines for optimally managing hiking activities to maintain desired levels of territory occupancy and reproductive success of Golden Eagles (Aquila chrysaetos) in Denali National Park (Alaska, U.S.A.). The management decision was to restrict human access (hikers) to particular nesting territories to reduce disturbance. The management objective was to minimize restrictions on hikers while maintaining reproductive performance of eagles above some specified level. We based our decision analysis on predictive models of site occupancy of eagles developed using a combination of expert opinion and data collected from 93 eagle territories over 20 years. The best predictive model showed that restricting human access to eagle territories had little effect on occupancy dynamics. However, when considering important sources of uncertainty in the models, including environmental stochasticity, imperfect detection of hares on which eagles prey, and model uncertainty, restricting access of territories to hikers improved eagle reproduction substantially. An adaptive management framework such as ours may help reduce uncertainty of the effects of hiking activities on Golden Eagles

IITA Cooperative Agreement Projects for Classroom Usability

NASA Technical Reports Server (NTRS)

Grabowski, Barbara

1997-01-01

Based on this review, the following conclusions are drawn regarding the 'school readiness' of the sites. All six of the sites had great appeal to the reviewers and therefore we can conclude that each has tremendous potential for use in the classroom. None, however, were given a completely 'school-ready' assessment. With recommended revisions, each site will be a valuable asset to the classroom teacher. For each as well, teachers particularly had problems with access or finding them, but once there, felt they all had some relevance. Many of the weaknesses noted related to lack of guidance for teachers with links to their curriculum or provision of activities. Other weaknesses related to the lack of educational purpose, however, this may be addressed in the development of strong teacher resources and guides linked to the sites. For those sites with a weak or without a teacher's guide, adding this component would be worth the expenditure of time and money needed.

Inspection Report on "Employment Verification at Savannah River Site"

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

None

2009-11-01

We conducted a review at the Savannah River Site to determine if Site subcontractors verified the employment status of all employees in accordance with Federal requirements and, if unauthorized individuals accessed the site. During our field work, we reviewed 600 I-9 Forms from 21 subcontractors to verify whether Site subcontractors were using the I-9 Forms; and if the forms were accurate and complete. We also conducted a judgmental sample of individuals who accessed the Site during a six-month period to determine if there were any documentation anomalies.

Remote Exosites of the Catalytic Domain of Matrix Metalloproteinase-12 Enhance Elastin Degradation┼

PubMed Central

Fulcher, Yan G.; Van Doren, Steven R.

2011-01-01

How does matrix metalloproteinase-12 (MMP-12 or metalloelastase) degrade elastin with high specific activity? NMR suggested soluble elastin to cover surfaces of MMP-12 far from its active site. Two of these surfaces have been found, by mutagenesis guided by the BINDSIght approach, to affect degradation and affinity for elastin substrates but not a small peptide substrate. Main exosite 1 has been extended out to Asp124 that binds calcium. Novel exosite 2 comprises residues from the II–III loop and β-strand I near the back of the catalytic domain. The high exposure of these distal exosites may make them accessible to elastin made more flexible by partial hydrolysis. Importantly, combination of a lesion at each of exosites 1 and 2 and active site decreased catalytic competence towards soluble elastin by 13- to 18-fold to the level of MMP-3, homologue and poor elastase. Double mutant cycle analysis of conservative mutations of Met156 (exosite 2) and either Asp124 (exosite 1) or Ile180 (active site) had additive effects. Compared to polar substitutions observed in other MMPs, Met156 enhanced affinity and Ile180 kcat for soluble elastin. Both residues detracted from the higher folding stability with polar mutations. This resembles the trend in enzymes of an inverse relationship between folding stability and activity. Restoring Asp124 from combination mutants enhanced kcat for soluble elastin. In elastin degradation, exosites 1 and 2 contributed independently of each other and Ile180 at the active site, but with partial coupling to Ala182 near the active site. The concept of weak, separated interactions coalescing somewhat independently can be extended to this proteolytic digestion of a protein from fibrils. PMID:21967233

Nevada National Security Site Environmental Report Summary 2016

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

Wills, Cathy

This document is a summary of the full 2016 Nevada National Security Site Environmental Report (NNSSER) prepared by the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/ NFO). This summary provides an abbreviated and more readable version of the full NNSSER. NNSA/NFO prepares the NNSSER to provide the public an understanding of the environmental monitoring and compliance activities that are conducted on the Nevada National Security Site (NNSS) to protect the public and the environment from radiation hazards and from potential nonradiological impacts. It is a comprehensive report of environmental activities performed at the NNSS andmore » offsite facilities over the previous calendar year. The NNSS is currently the nation’s unique site for ongoing national security–related missions and high-risk operations. The NNSS is located about 65 miles northwest of Las Vegas. The approximately 1,360-square-mile site is one of the largest restricted access areas in the United States. It is surrounded by federal installations with strictly controlled access as well as by lands that are open to public entry. In 2016, National Security Technologies, LLC (NSTec), was the NNSS Management and Operations Contractor accountable for ensuring work was performed in compliance with environmental regulations. NNSS activities in 2016 continued to be diverse, with the primary goal to ensure that the existing U.S. stockpile of nuclear weapons remains safe and reliable. Other activities included weapons of mass destruction first responder training; the controlled release of hazardous material at the Nonproliferation Test and Evaluation Complex (NPTEC); remediation of legacy contamination sites; characterization of waste destined for the Waste Isolation Pilot Plant in Carlsbad, New Mexico, or the Idaho National Laboratory in Idaho Falls, Idaho; disposal of low-level and mixed low-level radioactive waste; and environmental research. Facilities and centers that support the National Security/Defense mission include the U1a Facility, Big Explosives Experimental Facility (BEEF), Device Assembly Facility (DAF), National Criticality Experiments Research Center (NCERC) located in the DAF, Joint Actinide Shock Physics Experimental Research (JASPER) Facility, Dense Plasma Focus (DPF) Facility located in the Los Alamos Technical Facility (LATF), and the Radiological/ Nuclear Countermeasures Test and Evaluation Complex (RNCTEC). Facilities that support the Environmental Management mission include the Area 5 Radioactive Waste Management Complex (RWMC) and the Area 3 Radioactive Waste Management Site (RWMS), which has been in cold standby since 2006.« less

Transradial access for visceral endovascular interventions in morbidly obese patients: safety and feasibility.

PubMed

Biederman, Derek M; Marinelli, Brett; O'Connor, Paul J; Titano, Joseph J; Patel, Rahul S; Kim, Edward; Tabori, Nora E; Nowakowski, Francis S; Lookstein, Robert A; Fischman, Aaron M

2016-05-07

Transradial access (TRA) has been shown to lower morbidity and bleeding complications compared to transfemoral access in percutaneous coronary interventions. Morbid obesity, commonly defined as a body mass index (BMI) ≥40 kg/m2, has been shown to be a risk factor for access site complications irrespective of access site. This study evaluates the safety and feasibility of performing visceral endovascular interventions in morbidly obese patients via TRA. Procedural details, technical success, and 30-day major and minor access site, bleeding, and neurological adverse events were prospectively recorded in a database of 1057 procedures performed via the radial artery. From this database we identified 22 visceral interventions performed with TRA in 17 morbidly obese patients (age: 53 ± 11 years, female: 71%) with a median BMI of 42.7 kg/m2. Interventions included radio-embolization (n = 7, 31.8%), chemo-embolization (n = 6, 27.3%), uterine fibroid embolization (n = 4, 18.2%), renal embolization (n = 2, 9.1%), hepatic embolization (n = 1, 4.5%), lumbar artery embolization (n = 1, 4.5%), and renal angioplasty (n = 1, 4.5%). The technical success was 100%. There were no major or minor adverse access site, bleeding, or neurological complications at 30 days. This study suggests visceral endovascular interventions performed in morbidly obese patients are safe and feasible.

A multi-level intervention in subsidized housing sites to increase fruit and vegetable access and intake: Rationale, design and methods of the 'Live Well, Viva Bien' cluster randomized trial.

PubMed

Gans, Kim M; Gorham, Gemma; Risica, Patricia M; Dulin-Keita, Akilah; Dionne, Laura; Gao, Tina; Peters, Sarah; Principato, Ludovica

2016-06-28

Adequate fruit and vegetable (F&V) intake is important for disease prevention. Yet, most Americans, especially low-income and racial/ethnic minorities, do not eat adequate amounts. These disparities are partly attributable to food environments in low-income neighborhoods where residents often have limited access to affordable, healthful food and easy access to inexpensive, unhealthful foods. Increasing access to affordable healthful food in underserved neighborhoods through mobile markets is a promising, year-round strategy for improving dietary behaviors and reducing F&V intake disparities. However, to date, there have been no randomized controlled trials studying their effectiveness. The objective of the 'Live Well, Viva Bien' (LWVB) cluster randomized controlled trial is to evaluate the efficacy of a multicomponent mobile market intervention at increasing F&V intake among residents of subsidized housing complexes. One housing complex served as a pilot site for the intervention group and the remaining 14 demographically-matched sites were randomized into either the intervention or control group. The intervention group received bimonthly, discount, mobile, fresh F&V markets in conjunction with a nutrition education intervention (two F&V campaigns, newsletters, DVDs and cooking demonstrations) for 12 months. The control group received physical activity and stress reduction interventions. Outcome measures include F&V intake (measured by two validated F&V screeners at baseline, six-month and twelve-months) along with potential psychosocial mediating variables. Extensive quantitative and qualitative process evaluation was also conducted throughout the study. Modifying neighborhood food environments in ways that increase access to affordable, healthful food is a promising strategy for improving dietary behaviors among low-income, racial and ethnic minority groups at increased risk for obesity and other food-related chronic diseases. Discount, mobile F&V markets address all the major barriers to eating more F&V (high cost, poor quality, limited access and limited time to shop and cook) and provide a year-round solution to limited access to healthful food in low-income neighborhoods. LWVB is the first randomized controlled trial evaluating the effectiveness of mobile markets at increasing F&V intake. If proven efficacious at increasing F&V consumption, LWVB could be disseminated widely to neighborhoods that have low access to fresh F&V. Clinicatrials.gov registration number: NCT02669472 First Received: January 19, 2016.

Usability and Accessibility of eBay by Screen Reader

NASA Astrophysics Data System (ADS)

Buzzi, Maria Claudia; Buzzi, Marina; Leporini, Barbara; Akhter, Fahim

The evolution of Information and Communication Technology and the rapid growth of the Internet have fuelled a great diffusion of eCommerce websites. Usually these sites have complex layouts crowded with active elements, and thus are difficult to navigate via screen reader. Interactive environments should be properly designed and delivered to everyone, including the blind, who usually use screen readers to interact with their computers. In this paper we investigate the interaction of blind users with eBay, a popular eCommerce website, and discuss how using the W3C Accessible Rich Internet Applications (WAI-ARIA) suite could improve the user experience when navigating via screen reader.

Addressing Open Water Data Challenges in the Bureau of Reclamation

NASA Astrophysics Data System (ADS)

Brekke, L. D.; Danner, A.; Nagode, J.; Rocha, J.; Poulton, S.; Anderson, A.

2017-12-01

The Bureau of Reclamation is largest wholesaler of water in the United States. Located in the 17 western states, Reclamation serves water to 31 million people, provides irrigated water to 20 percent of Western farmers, and is the second largest producer of hydroelectric power in the United States. Through these activities, Reclamation generates large amounts of water and water-related data, describing reservoirs and river system conditions, hydropower, environmental compliance activities, infrastructure assets, and other aspects of Reclamation's mission activities. Reclamation aims to make water and water-related data sets more easily found, accessed, and used in decision-making activities in order to benefit the public, private sector, and research communities. Historically, there has not been an integrated, bureau-wide system to store data in machine-readable formats; nor a system to permit centralized browsing, open access, and web-services. Reclamation began addressing these limitations by developing the Reclamation Water Information System (RWIS), released in Spring 2017 (https://water.usbr.gov/). A bureau-wide team contributed to RWIS development, including water data stewards, database administrators, and information technology (IT) specialists. The first RWIS release publishes reservoir time series data from Reclamation's five regions and includes a map interface for sites identification, a query interface for data discovery and access, and web-services for automated retrieval. As RWIS enhancement continues, the development team is developing a companion system - the Reclamation Information Sharing Environment (RISE) - to provide access to the other data subjects and types (geospatial, documents). While RWIS and RISE are promising starts, Reclamation continues to face challenges in addressing open water data goals: making data consolidation and open publishing a value-added activity for programs that publish data locally, going beyond providing open access to also providing decision-support, and scaling up IT solutions for future success - where Reclamation programs increasingly elect to more and more data through RWIS/RISE, thereby creating a big data challenge. This presentation will highlight activities status, lessons learned, and future directions.

Commissioning of a CERN Production and Analysis Facility Based on xrootd

NASA Astrophysics Data System (ADS)

Campana, Simone; van der Ster, Daniel C.; Di Girolamo, Alessandro; Peters, Andreas J.; Duellmann, Dirk; Coelho Dos Santos, Miguel; Iven, Jan; Bell, Tim

2011-12-01

The CERN facility hosts the Tier-0 of the four LHC experiments, but as part of WLCG it also offers a platform for production activities and user analysis. The CERN CASTOR storage technology has been extensively tested and utilized for LHC data recording and exporting to external sites according to experiments computing model. On the other hand, to accommodate Grid data processing activities and, more importantly, chaotic user analysis, it was realized that additional functionality was needed including a different throttling mechanism for file access. This paper will describe the xroot-based CERN production and analysis facility for the ATLAS experiment and in particular the experiment use case and data access scenario, the xrootd redirector setup on top of the CASTOR storage system, the commissioning of the system and real life experience for data processing and data analysis.

Web-Based Geographic Information System Tool for Accessing Hanford Site Environmental Data

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

Triplett, Mark B.; Seiple, Timothy E.; Watson, David J.

Data volume, complexity, and access issues pose severe challenges for analysts, regulators and stakeholders attempting to efficiently use legacy data to support decision making at the U.S. Department of Energy’s (DOE) Hanford Site. DOE has partnered with the Pacific Northwest National Laboratory (PNNL) on the PHOENIX (PNNL-Hanford Online Environmental Information System) project, which seeks to address data access, transparency, and integration challenges at Hanford to provide effective decision support. PHOENIX is a family of spatially-enabled web applications providing quick access to decades of valuable scientific data and insight through intuitive query, visualization, and analysis tools. PHOENIX realizes broad, public accessibilitymore » by relying only on ubiquitous web-browsers, eliminating the need for specialized software. It accommodates a wide range of users with intuitive user interfaces that require little or no training to quickly obtain and visualize data. Currently, PHOENIX is actively hosting three applications focused on groundwater monitoring, groundwater clean-up performance reporting, and in-tank monitoring. PHOENIX-based applications are being used to streamline investigative and analytical processes at Hanford, saving time and money. But more importantly, by integrating previously isolated datasets and developing relevant visualization and analysis tools, PHOENIX applications are enabling DOE to discover new correlations hidden in legacy data, allowing them to more effectively address complex issues at Hanford.« less

Competitive Inhibition Mechanism of Acetylcholinesterase without Catalytic Active Site Interaction: Study on Functionalized C60 Nanoparticles via in Vitro and in Silico Assays.

PubMed

Liu, Yanyan; Yan, Bing; Winkler, David A; Fu, Jianjie; Zhang, Aiqian

2017-06-07

Acetylcholinesterase (AChE) activity regulation by chemical agents or, potentially, nanomaterials is important for both toxicology and pharmacology. Competitive inhibition via direct catalytic active sites (CAS) binding or noncompetitive inhibition through interference with substrate and product entering and exiting has been recognized previously as an AChE-inhibition mechanism for bespoke nanomaterials. The competitive inhibition by peripheral anionic site (PAS) interaction without CAS binding remains unexplored. Here, we proposed and verified the occurrence of a presumed competitive inhibition of AChE without CAS binding for hydrophobically functionalized C 60 nanoparticles (NPs) by employing both experimental and computational methods. The kinetic inhibition analysis distinguished six competitive inhibitors, probably targeting the PAS, from the pristine and hydrophilically modified C 60 NPs. A simple quantitative nanostructure-activity relationship (QNAR) model relating the pocket accessible length of substituent to inhibition capacity was then established to reveal how the geometry of the surface group decides the NP difference in AChE inhibition. Molecular docking identified the PAS as the potential binding site interacting with the NPs via a T-shaped plug-in mode. Specifically, the fullerene core covered the enzyme gorge as a lid through π-π stacking with Tyr72 and Trp286 in the PAS, while the hydrophobic ligands on the fullerene surface inserted into the AChE active site to provide further stability for the complexes. The modeling predicted that inhibition would be severely compromised by Tyr72 and Trp286 deletions, and the subsequent site-directed mutagenesis experiments proved this prediction. Our results demonstrate AChE competitive inhibition of NPs without CAS participation to gain further understanding of both the neurotoxicity and the curative effect of NPs.

Destruction of chemical warfare agents using metal-organic frameworks

NASA Astrophysics Data System (ADS)

Mondloch, Joseph E.; Katz, Michael J.; Isley, William C., III; Ghosh, Pritha; Liao, Peilin; Bury, Wojciech; Wagner, George W.; Hall, Morgan G.; Decoste, Jared B.; Peterson, Gregory W.; Snurr, Randall Q.; Cramer, Christopher J.; Hupp, Joseph T.; Farha, Omar K.

2015-05-01

Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic ZrIV ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Destruction of chemical warfare agents using metal-organic frameworks.

PubMed

Mondloch, Joseph E; Katz, Michael J; Isley, William C; Ghosh, Pritha; Liao, Peilin; Bury, Wojciech; Wagner, George W; Hall, Morgan G; DeCoste, Jared B; Peterson, Gregory W; Snurr, Randall Q; Cramer, Christopher J; Hupp, Joseph T; Farha, Omar K

2015-05-01

Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic Zr(IV) ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Accessibility Trends among Academic Library and Library School Web Sites in the USA and Canada

ERIC Educational Resources Information Center

Schmetzke, Axel; Comeaux, David

2009-01-01

This paper focuses on the accessibility of North American library and library school Web sites for all users, including those with disabilities. Web accessibility data collected in 2006 are compared to those of 2000 and 2002. The findings of this follow-up study continue to give cause for concern: Despite improvements since 2002, library and…

Simple Enough--Even for Web Virgins: Lisa Mitten's Access to Native American Web Sites. Web Site Review Essay.

ERIC Educational Resources Information Center

Belgarde, Mary Jiron

1998-01-01

A mixed-blood Mohawk urban Indian and university librarian, Lisa Mitten provides access to Web sites with solid information about American Indians. Links are provided to 10 categories--Native nations, Native organizations, Indian education, Native media, powwows and festivals, Indian music, Native arts, Native businesses, and Indian-oriented home…

Evaluation of the content and accessibility of web sites for accredited orthopaedic sports medicine fellowships.

PubMed

Mulcahey, Mary K; Gosselin, Michelle M; Fadale, Paul D

2013-06-19

The Internet is a common source of information for orthopaedic residents applying for sports medicine fellowships, with the web sites of the American Orthopaedic Society for Sports Medicine (AOSSM) and the San Francisco Match serving as central databases. We sought to evaluate the web sites for accredited orthopaedic sports medicine fellowships with regard to content and accessibility. We reviewed the existing web sites of the ninety-five accredited orthopaedic sports medicine fellowships included in the AOSSM and San Francisco Match databases from February to March 2012. A Google search was performed to determine the overall accessibility of program web sites and to supplement information obtained from the AOSSM and San Francisco Match web sites. The study sample consisted of the eighty-seven programs whose web sites connected to information about the fellowship. Each web site was evaluated for its informational value. Of the ninety-five programs, fifty-one (54%) had links listed in the AOSSM database. Three (3%) of all accredited programs had web sites that were linked directly to information about the fellowship. Eighty-eight (93%) had links listed in the San Francisco Match database; however, only five (5%) had links that connected directly to information about the fellowship. Of the eighty-seven programs analyzed in our study, all eighty-seven web sites (100%) provided a description of the program and seventy-six web sites (87%) included information about the application process. Twenty-one web sites (24%) included a list of current fellows. Fifty-six web sites (64%) described the didactic instruction, seventy (80%) described team coverage responsibilities, forty-seven (54%) included a description of cases routinely performed by fellows, forty-one (47%) described the role of the fellow in seeing patients in the office, eleven (13%) included call responsibilities, and seventeen (20%) described a rotation schedule. Two Google searches identified direct links for 67% to 71% of all accredited programs. Most accredited orthopaedic sports medicine fellowships lack easily accessible or complete web sites in the AOSSM or San Francisco Match databases. Improvement in the accessibility and quality of information on orthopaedic sports medicine fellowship web sites would facilitate the ability of applicants to obtain useful information.

Loop Electrostatics Asymmetry Modulates the Preexisting Conformational Equilibrium in Thrombin.

PubMed

Pozzi, Nicola; Zerbetto, Mirco; Acquasaliente, Laura; Tescari, Simone; Frezzato, Diego; Polimeno, Antonino; Gohara, David W; Di Cera, Enrico; De Filippis, Vincenzo

2016-07-19

Thrombin exists as an ensemble of active (E) and inactive (E*) conformations that differ in their accessibility to the active site. Here we show that redistribution of the E*-E equilibrium can be achieved by perturbing the electrostatic properties of the enzyme. Removal of the negative charge of the catalytic Asp102 or Asp189 in the primary specificity site destabilizes the E form and causes a shift in the 215-217 segment that compromises substrate entrance. Solution studies and existing structures of D102N document stabilization of the E* form. A new high-resolution structure of D189A also reveals the mutant in the collapsed E* form. These findings establish a new paradigm for the control of the E*-E equilibrium in the trypsin fold.

Distribution and Features of the Six Classes of Peroxiredoxins

PubMed Central

Poole, Leslie B.; Nelson, Kimberly J.

2016-01-01

Peroxiredoxins are cysteine-dependent peroxide reductases that group into 6 different, structurally discernable classes. In 2011, our research team reported the application of a bioinformatic approach called active site profiling to extract active site-proximal sequence segments from the 29 distinct, structurally-characterized peroxiredoxins available at the time. These extracted sequences were then used to create unique profiles for the six groups which were subsequently used to search GenBank(nr), allowing identification of ∼3500 peroxiredoxin sequences and their respective subgroups. Summarized in this minireview are the features and phylogenetic distributions of each of these peroxiredoxin subgroups; an example is also provided illustrating the use of the web accessible, searchable database known as PREX to identify subfamily-specific peroxiredoxin sequences for the organism Vitis vinifera (grape). PMID:26810075

Patients undergoing PCI from the femoral route by default radial operators are at high risk of vascular access-site complications.

PubMed

Rafie, Ihsan M; Uddin, Muez M; Ossei-Gerning, Nicholas; Anderson, Richard A; Kinnaird, Timothy D

2014-02-01

Radial artery (RA) access for PCI has a lower incidence of vascular access-site (VAS) complications than the femoral artery (FA) approach. However, even for default radial operators certain patients are intervened upon from the FA. We examined the demographics and incidence of VAS complications when default radial operators resort to the FA for PCI. The demographics and VAS complications were compared by access site retrospectively for all PCI cases performed by default radial operators (n=1,392). A modified ACUITY trial definition of major VAS complication was used. FA puncture occurred in 25.2% (351/1,392) of cases. Patients were more likely to be female, older and weigh less than patients undergoing PCI from the RA. The FA procedure was likely to be more complex with larger sheaths, more left main stem, graft and multivessel intervention, and there was a greater proportion of emergency cases. Despite increased case complexity, glycoprotein inhibitors were used less frequently in femoral cases (26.5% vs. 36.8%, p<0.001). A VAS complication occurred in 12.5% (44/351) of cases. The risk factors for access-site bleeding are disproportionately high in the population requiring FA puncture by default radial operators, and as a result such patients have a high rate of vascular access-site complications.

Overview of the 2015 Algodones Sand Dunes field campaign to support sensor intercalibration

NASA Astrophysics Data System (ADS)

McCorkel, Joel; Bachmann, Charles M.; Coburn, Craig; Gerace, Aaron; Leigh, Larry; Czapla-Myers, Jeff; Helder, Dennis; Cook, Bruce

2018-01-01

Several sites from around the world are being used operationally and are suitable for vicarious calibration of space-borne imaging platforms. However, due to the proximity of these sites (e.g., Libya 4), a rigorous characterization of the landscape is not feasible, limiting their utility for sensor intercalibration efforts. Due to its accessibility and similarities to Libya 4, the Algodones Sand Dunes System in California, USA, was identified as a potentially attractive intercalibration site for space-borne, reflective instruments such as Landsat. In March 2015, a 4-day field campaign was conducted to develop an initial characterization of Algodones with a primary goal of assessing its intercalibration potential. Five organizations from the US and Canada collaborated to collect both active and passive airborne image data, spatial and temporal measurements of spectral bidirectional reflectance distribution function, and in-situ sand samples from several locations across the Algodones system. The collection activities conducted to support the campaign goal is summarized, including a summary of all instrumentation used, the data collected, and the experiments performed in an effort to characterize the Algodones site.

A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial.

PubMed

Rao, Sunil V; Hess, Connie N; Barham, Britt; Aberle, Laura H; Anstrom, Kevin J; Patel, Tejan B; Jorgensen, Jesse P; Mazzaferri, Ernest L; Jolly, Sanjit S; Jacobs, Alice; Newby, L Kristin; Gibson, C Michael; Kong, David F; Mehran, Roxana; Waksman, Ron; Gilchrist, Ian C; McCourt, Brian J; Messenger, John C; Peterson, Eric D; Harrington, Robert A; Krucoff, Mitchell W

2014-08-01

This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Ensembl Web Site: Mechanics of a Genome Browser

PubMed Central

Stalker, James; Gibbins, Brian; Meidl, Patrick; Smith, James; Spooner, William; Hotz, Hans-Rudolf; Cox, Antony V.

2004-01-01

The Ensembl Web site (http://www.ensembl.org/) is the principal user interface to the data of the Ensembl project, and currently serves >500,000 pages (∼2.5 million hits) per week, providing access to >80 GB (gigabyte) of data to users in more than 80 countries. Built atop an open-source platform comprising Apache/mod_perl and the MySQL relational database management system, it is modular, extensible, and freely available. It is being actively reused and extended in several different projects, and has been downloaded and installed in companies and academic institutions worldwide. Here, we describe some of the technical features of the site, with particular reference to its dynamic configuration that enables it to handle disparate data from multiple species. PMID:15123591

Structural and biochemical insights into 7β-hydroxysteroid dehydrogenase stereoselectivity.

PubMed

Savino, Simone; Ferrandi, Erica Elisa; Forneris, Federico; Rovida, Stefano; Riva, Sergio; Monti, Daniela; Mattevi, Andrea

2016-06-01

Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo- and regio-selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β-hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active-site accessibility, the bases of the specificity for NADP(+) , and the general architecture of the steroid binding site. Comparison with 7α-hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C-terminal extension reshapes the substrate site of the β-selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859-865. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Ensembl Web site: mechanics of a genome browser.

PubMed

Stalker, James; Gibbins, Brian; Meidl, Patrick; Smith, James; Spooner, William; Hotz, Hans-Rudolf; Cox, Antony V

2004-05-01

The Ensembl Web site (http://www.ensembl.org/) is the principal user interface to the data of the Ensembl project, and currently serves >500,000 pages (approximately 2.5 million hits) per week, providing access to >80 GB (gigabyte) of data to users in more than 80 countries. Built atop an open-source platform comprising Apache/mod_perl and the MySQL relational database management system, it is modular, extensible, and freely available. It is being actively reused and extended in several different projects, and has been downloaded and installed in companies and academic institutions worldwide. Here, we describe some of the technical features of the site, with particular reference to its dynamic configuration that enables it to handle disparate data from multiple species.

Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A

PubMed Central

Kaminishi, Tatsuya; Schedlbauer, Andreas; Fabbretti, Attilio; Brandi, Letizia; Ochoa-Lizarralde, Borja; He, Cheng-Guang; Milón, Pohl; Connell, Sean R.; Gualerzi, Claudio O.; Fucini, Paola

2015-01-01

Hygromycin A (HygA) binds to the large ribosomal subunit and inhibits its peptidyl transferase (PT) activity. The presented structural and biochemical data indicate that HygA does not interfere with the initial binding of aminoacyl-tRNA to the A site, but prevents its subsequent adjustment such that it fails to act as a substrate in the PT reaction. Structurally we demonstrate that HygA binds within the peptidyl transferase center (PTC) and induces a unique conformation. Specifically in its ribosomal binding site HygA would overlap and clash with aminoacyl-A76 ribose moiety and, therefore, its primary mode of action involves sterically restricting access of the incoming aminoacyl-tRNA to the PTC. PMID:26464437

ReOpt[trademark] V2.0 user guide

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

White, M K; Bryant, J L

1992-10-01

Cleaning up the large number of contaminated waste sites at Department of Energy (DOE) facilities in the US presents a large and complex problem. Each waste site poses a singular set of circumstances (different contaminants, environmental concerns, and regulations) that affect selection of an appropriate response. Pacific Northwest Laboratory (PNL) developed ReOpt to provide information about the remedial action technologies that are currently available. It is an easy-to-use personal computer program and database that contains data about these remedial technologies and auxiliary data about contaminants and regulations. ReOpt will enable engineers and planners involved in environmental restoration efforts to quicklymore » identify potentially applicable environmental restoration technologies and access corresponding information required to select cleanup activities for DOE sites.« less

Point mutations abolishing the mannose-binding capability of boar spermadhesin AQN-1.

PubMed

Ekhlasi-Hundrieser, Mahnaz; Calvete, Juan J; Von Rad, Bettina; Hettel, Christiane; Nimtz, Manfred; Töpfer-Petersen, Edda

2008-05-01

The mannose-binding capability of recombinant wild-type boar spermadhesin AQN-1 and of its site-directed mutants in the highly-conserved region around of the single glycosylation site (asparagine 50) of some spermadhesins, where the carbohydrate binding site has been proposed to be located, was checked using a solid-phase assay and a biotinylated mannose ligand. Substitution of glycine 54 by amino acids bearing an unipolar side chain did not cause significant decrease in the mannose-binding activity. However, amino acids with uncharged polar side chains or having a charged polar side chain abolished the binding of biotinylated mannose to the corresponding AQN-1 mutants. The results suggest that the higher surface accessibility of amino acids possessing polar side chains compared to those bearing nonpolar groups may sterically interfere with monosaccharide binding. The location of the mannose-binding site in AQN-1 appears to be topologically conserved in other heparin-binding boar spermadhesins, i.e., AQN-3 and AWN, but departs from the location of the mannose-6-phosphate-recognition site of PSP-II. This indicates that different spermadhesin molecules have evolved non-equivalent carbohydrate-binding capabilities, which may underlie their distinct patterns of biological activities.

Extrapulmonary sites of radiogallium accumulation in sarcoidosis

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

Sulavik, S.B.; Palestro, C.J.; Spencer, R.P.

1990-12-01

In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the panda sign in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic andmore » nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.« less

Internet-Based Laboratory Activities Designed for Studying the Sun with Satellites

NASA Astrophysics Data System (ADS)

Slater, T. F.

1998-12-01

Yohkoh Public Outreach Project (YPOP) is a collaborative industry, university, and K-16 project bringing fascinating and dynamic images of the Sun to the public in real-time. Partners have developed an extensive public access and educational WWW site containing more than 100 pages of vibrant images with current information that focuses on movies of the X-ray output of our Sun taken by the Yohkoh Satellite. More than 5 Gb of images and movies are available on the WWW site from the Yohkoh satellite, a joint project of the Institute for Space and Astronautical Sciences (ISAS) and NASA. Using a movie theater motif, the site was created by teams working at Lockheed Martin Advanced Technology Center, Palo Alto, CA in the Solar and Astrophysics Research Group, the Montana State University Solar Physics Research Group, and the Montana State University Conceptual Astronomy and Physics Education Research Group with funding from the NASA Learning Technology Project (LTP) program (NASA LTP SK30G4410R). The Yohkoh Movie Theater Internet Site is found at URL: http://www.lmsal.com/YPOP/ and mirrored at URL: http://solar.physics.montana.edu/YPOP/. In addition to being able to request automated movies for any dates in a 5 Gb on-line database, the user can view automatically updated daily images and movies of our Sun over the last 72 hours. Master science teachers working with the NASA funded Yohkoh Public Outreach Project have developed nine technology-based on-line lessons for K-16 classrooms. These interdisciplinary science, mathematics, and technology lessons integrate Internet resources, real-time images of the Sun, and extensive NASA image databases. Instructors are able to freely access each of the classroom-ready activities. The activities require students to use scientific inquiry skills and manage electronic information to solve problems consistent with the emphasis of the NRC National Science Education Standards.

Patient Factors But Not the Use of Novel Anticoagulants or Warfarin Are Associated With Internal Jugular Vein Access-Site Hematoma After Right Heart Catheterization.

PubMed

Dasa, Osama; Shafiq, Qaiser; Ruzieh, Mohammed; Alhazmi, Luai; Al-Dabbas, Maen; Ammari, Zaid; Khouri, Samer; Moukarbel, George

2017-12-01

Right heart catheterization (RHC) is routinely performed to assess hemodynamics. Generally, anticoagulants are held prior to the procedure. At our center, anticoagulants are continued and ultrasound guidance is always used for internal jugular vein access. A micropuncture access kit is used to place a 5 or 6 Fr sheath using the modified Seldinger technique. Manual compression is applied for 10-15 min and the patient is observed for at least 2 hours after the procedure. In a retrospective analysis, we investigated the risk of bleeding complications associated with RHC via the internal jugular vein in patients with and without full anticoagulation. Our catheterization laboratory database was searched for adult patients who underwent RHC by a single operator between January 2012 and December 2015. A total of 571 patients were included in the analysis. Baseline characteristics, labs, relevant invasive hemodynamics, co-morbid conditions, and incidence of access-site hematoma are presented. Multivariable binary logistic regression was performed using IBM SPSS v. 23.0 software. Statistically significant associations with access-site hematoma were observed with body mass index (P=.02; 95% confidence interval [CI], 1.0-1.1), right atrial pressure (P=.03; 95% CI, 0.7-0.9), and dialysis dependence (P<.01; 95% CI, 0.1-0.6). There was no association of access-site hematoma with the use of anticoagulants (P>.99). The incidence of internal jugular vein access-site hematoma is small when using careful access techniques for RHC even with the continued use of novel oral anticoagulants and warfarin. Patient characteristics and co-morbid conditions are related to bleeding complications.

Data access systems in the real world: How distributed environmental and socio-economic data from the Dutch Wadden Sea are being integrated and made accessible through one portal, using the SeaDataNet infrastructure as a basis

NASA Astrophysics Data System (ADS)

De Bruin, T.; Thijsse, P.

2013-12-01

The Wadden Sea, an UNESCO World Heritage Site along the Northern coasts of The Netherlands, Germany and Denmark, is a very valuable, yet also highly vulnerable tidal flats area. It is noted for its ecological diversity and value, being a stopover for large numbers of migrating birds. The Wadden Sea is also used intensively for economic activities by inhabitants of the surrounding coasts and islands, as well as by the many tourists visiting the area every year. A whole series of monitoring programmes of both ecological and socio-economic parameters is carried out by a range of governmental bodies and institutes, to study the natural processes occuring in the Wadden Sea ecosystems as well as the influence of human activities on those ecosystems. Yet, the monitoring programmes are scattered and it is difficult to get an overview of those monitoring activities or to get access to the data resulting from those monitoring programmes. The Wadden Sea Long Term Ecosystem Research (WaLTER) project aims to: 1. Provide access through one data portal to a base set of consistent, standardized, long-term data on changes in the Wadden Sea ecological and socio-economic systems, in order to model and understand interrelationships with human use, climate variation and possible other drivers. 2. Provide a research infrastructure, open access to commonly shared databases, educational facilities and one or more field sites in which experimental, innovative and process-driven research can be carried out. This presentation will, after a short introduction of the WaLTER-project (2011-2015), focus on the distributed data access infrastructure which is being developed and used for WaLTER. This is based on and makes use of the existing data access infrastructure of the Netherlands National Oceanographic Data Committee (NL-NODC), which has been operational since early 2009. The NL-NODC system is identical to and in fact developed by the European SeaDataNet project, furthering standardisation on a pan-European scale. The WaLTER data portal will provide a centralized overview of all relevant Wadden Sea data, both from environmental as well as socio-economic disciplines and it will provide access to a system of distributed data sources. Much emphasis is given to address the different needs of various groups of users, such as policy makers, scientists and the general public. Benefits and pitfalls (and ways to circumvent the latter) of using this infrastructure with data from widely different disciplines will be addressed.

Noctis Landing: A Proposed Landing Site/Exploration Zone for Human Missions to the Surface of Mars

NASA Technical Reports Server (NTRS)

Lee, Pascal; Acedillo, Shannen; Braham, Stephen; Brown, Adrian; Elphic, Richard; Fong, Terry; Glass, Brian; Hoftun, Christopher; Johansen, Brage W.; Lorber, Kira;

Building a Prototype of LHC Analysis Oriented Computing Centers

NASA Astrophysics Data System (ADS)

Bagliesi, G.; Boccali, T.; Della Ricca, G.; Donvito, G.; Paganoni, M.

2012-12-01

A Consortium between four LHC Computing Centers (Bari, Milano, Pisa and Trieste) has been formed in 2010 to prototype Analysis-oriented facilities for CMS data analysis, profiting from a grant from the Italian Ministry of Research. The Consortium aims to realize an ad-hoc infrastructure to ease the analysis activities on the huge data set collected at the LHC Collider. While “Tier2” Computing Centres, specialized in organized processing tasks like Monte Carlo simulation, are nowadays a well established concept, with years of running experience, site specialized towards end user chaotic analysis activities do not yet have a defacto standard implementation. In our effort, we focus on all the aspects that can make the analysis tasks easier for a physics user not expert in computing. On the storage side, we are experimenting on storage techniques allowing for remote data access and on storage optimization on the typical analysis access patterns. On the networking side, we are studying the differences between flat and tiered LAN architecture, also using virtual partitioning of the same physical networking for the different use patterns. Finally, on the user side, we are developing tools and instruments to allow for an exhaustive monitoring of their processes at the site, and for an efficient support system in case of problems. We will report about the results of the test executed on different subsystem and give a description of the layout of the infrastructure in place at the site participating to the consortium.

77 FR 55470 - Agency Information Collection Activities; Proposed Collection; Comment Request; Reporting and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

....regulations.gov Web site is an ``anonymous access'' system, which means EPA will not know your identity or... , or in person at the Air and Radiation Docket in the EPA Docket Center (EPA/DC), EPA West, Room 3334...: This ICR will expire on 02/28/2013. An agency may not conduct or sponsor, and a person is not required...

Achieving Accountability in Cyberspace: Revolution or Evolution?

DTIC Science & Technology

2014-01-01

hours, the malware propagates throughout both networks and begins to beacon to a site known for its state - sponsored cyberspace espionage activities...installation in the United States , communications personnel in a tenant unit, whose primary unclassified operating network is neither owned nor...protect its unclas- sified proprietary network. A known nation- state actor gains access to the company’s network and begins to exfil- trate megabytes

Astronomical activities with disabled people

NASA Astrophysics Data System (ADS)

Ortiz-Gil, Amelia; Blay, Pere; Gallego Calvente, A. Teresa; Gómez, Miquel; Guirado, José Carlos; Lanzara, Mariana; Martínez Núñez, Silvia

2011-06-01

As we celebrate the International Year of Astronomy, we have been working on four different projects with the goal of making astronomy more accessible to people with special needs. These projects are 1) an astronomy book and web site for blind people, 2) an open source software for people with motor disabilities, 3) a planetarium program for the visually impaired and 4) educational material for intellectually disabled people.

Recycling/Disposal Alternatives for Depleted Uranium Wastes

DTIC Science & Technology

1981-01-01

could pass before new sites are available. Recent experi- ence with attempts to dispose of wastes generated by cleanup of the Three Mile Island...commercial sector. Nonordnance uses include counterweights, Lallast, shielding , and special appli- cations machinery. Although the purity requirements...Refer- ence 11). Since the activity of the tailings is higher than allow- able for unrestricted access, large earth -dam retention systems, known as

Role of the Conserved Valine 236 in Access of Ligands to the Active Site of Thermus thermophilus ba3 Cytochrome Oxidase.

PubMed

Funatogawa, Chie; Li, Yang; Chen, Ying; McDonald, William; Szundi, Istvan; Fee, James A; Stout, C David; Einarsdóttir, Ólöf

2017-01-10

Knowledge of the role of conserved residues in the ligand channel of heme-copper oxidases is critical for understanding how the protein scaffold modulates the function of these enzymes. In this study, we investigated the role of the conserved valine 236 in the ligand channel of ba 3 cytochrome c oxidase from Thermus thermophilus by mutating the residue to a more polar (V236T), smaller (V236A), or larger (V236I, V236N, V236L, V236M, and V236F) residue. The crystal structures of the mutants were determined, and the effects of the mutations on the rates of CO, O 2 , and NO binding were investigated. O 2 reduction and NO binding were unaffected in V236T, while the oxidation of heme b during O-O bond cleavage was not detected in V236A. The V236A results are attributed to a decrease in the rate of electron transfer between heme b and heme a 3 during O-O bond cleavage in V236A, followed by faster re-reduction of heme b by Cu A . This interpretation is supported by classical molecular dynamics simulations of diffusion of O 2 to the active site in V236A that indicated a larger distance between the two hemes compared to that in the wild type and increased contact of heme a 3 with water and weakened interactions with residues R444 and R445. As the size of the mutant side chain increased and protruded more into the ligand cavity, the rates of ligand binding decreased correspondingly. These results demonstrate the importance of V236 in facilitating access of ligands to the active site in T. thermophilus ba 3 .

Hanford Site near-facility environmental monitoring annual report, calendar year 1997

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

Perkins, C.J.

1998-07-28

Near-facility environmental monitoring provides a means to measure the impacts of operations, waste management, and remediation activities on the environment adjacent to facilities and ensure compliance with local, state, and federal environmental regulations. Specifically, near-facility environmental monitoring monitors new and existing sites, processes, and facilities for potential impacts and releases; fugitive emissions and diffuse sources associated with contaminated areas, facilities (both active and those undergoing surveillance and maintenance), and environmental restoration activities. External radiation, ambient air particulates, ground and surface water, soil, sediment, and biota (plants and animals) are sampled or monitored. Parameters include, as appropriate, radionuclides; radiation fields; chemicalmore » or physical constituents, such as nitrates; pH; and water temperature. All ambient air results were below the US Department of Energy (DOE) Derived Concentration Guides (DCGs). Groundwater concentrations at the two wells at the 107-N Facility were below both the DOE DCG and US Environmental Protection Agency Interim Drinking Water Standards for gamma emitting radionuclides. Soil and vegetation results were generally within historic ranges and mostly below the Accessible Soil Concentration limits (included in HNF-PRO-454, Inactive Waste Sites) with the exception of one soil sampling location at 1 00 N Area. External radiation fields continued an overall downward trend. Surface water disposal unit samples (water, sediment, and aquatic vegetation) showed radionuclide concentrations below their respective DCG and Accessible Soil Concentration limits. The 100 N Area Columbia river shoreline springs results were below DCGs with the exception of one Sr concentration. More than 4,600 ha (11,300 acres) of radiologically controlled areas were surveyed in 1997, approximately the same as in 1996.« less

Electrochemical generation of sulfur vacancies in the basal plane of MoS2 for hydrogen evolution

PubMed Central

Tsai, Charlie; Li, Hong; Park, Sangwook; Park, Joonsuk; Han, Hyun Soo; Nørskov, Jens K.; Zheng, Xiaolin; Abild-Pedersen, Frank

2017-01-01

Recently, sulfur (S)-vacancies created on the basal plane of 2H-molybdenum disulfide (MoS2) using argon plasma exposure exhibited higher intrinsic activity for the electrochemical hydrogen evolution reaction than the edge sites and metallic 1T-phase of MoS2 catalysts. However, a more industrially viable alternative to the argon plasma desulfurization process is needed. In this work, we introduce a scalable route towards generating S-vacancies on the MoS2 basal plane using electrochemical desulfurization. Even though sulfur atoms on the basal plane are known to be stable and inert, we find that they can be electrochemically reduced under accessible applied potentials. This can be done on various 2H-MoS2 nanostructures. By changing the applied desulfurization potential, the extent of desulfurization and the resulting activity can be varied. The resulting active sites are stable under extended desulfurization durations and show consistent HER activity. PMID:28429782

Electrochemical generation of sulfur vacancies in the basal plane of MoS2 for hydrogen evolution

DOE PAGES

Tsai, Charlie; Li, Hong; Park, Sangwook; ...

2017-04-21

Recently, sulfur (S)-vacancies created on the basal plane of 2H-molybdenum disulfide (MoS 2) using argon plasma exposure exhibited higher intrinsic activity for the electrochemical hydrogen evolution reaction than the edge sites and metallic 1T-phase of MoS 2 catalysts. But, a more industrially viable alternative to the argon plasma desulfurization process is needed. In this work, we introduce a scalable route towards generating S-vacancies on the MoS 2 basal plane using electrochemical desulfurization. We found that they can be electrochemically reduced under accessible applied potentials, even though sulfur atoms on the basal plane are known to be stable and inert. Thismore » can be done on various 2H-MoS 2 nanostructures. Furthermore, by changing the applied desulfurization potential, the extent of desulfurization and the resulting activity can be varied. The resulting active sites are stable under extended desulfurization durations and show consistent HER activity.« less

Crystal structure of Bacillus anthracis transpeptidase enzyme CapD.

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

Wu, R.; Richter, S.; Zhang, R.

2009-09-04

Bacillus anthracis elaborates a poly-{gamma}-d-glutamic acid capsule that protects bacilli from phagocytic killing during infection. The enzyme CapD generates amide bonds with peptidoglycan cross-bridges to anchor capsular material within the cell wall envelope of B. anthracis. The capsular biosynthetic pathway is essential for virulence during anthrax infections and can be targeted for anti-infective inhibition with small molecules. Here, we present the crystal structures of the {gamma}-glutamyltranspeptidase CapD with and without {alpha}-l-Glu-l-Glu dipeptide, a non-hydrolyzable analog of poly-{gamma}-d-glutamic acid, in the active site. Purified CapD displays transpeptidation activity in vitro, and its structure reveals an active site broadly accessible for poly-{gamma}-glutamatemore » binding and processing. Using structural and biochemical information, we derive a mechanistic model for CapD catalysis whereby Pro{sup 427}, Gly{sup 428}, and Gly{sup 429} activate the catalytic residue of the enzyme, Thr{sup 352}, and stabilize an oxyanion hole via main chain amide hydrogen bonds.« less

A unique H2A histone variant occupies the transcriptional start site of active genes.

PubMed

Soboleva, Tatiana A; Nekrasov, Maxim; Pahwa, Anuj; Williams, Rohan; Huttley, Gavin A; Tremethick, David J

2011-12-04

Transcriptional activation is controlled by chromatin, which needs to be unfolded and remodeled to ensure access to the transcription start site (TSS). However, the mechanisms that yield such an 'open' chromatin structure, and how these processes are coordinately regulated during differentiation, are poorly understood. We identify the mouse (Mus musculus) H2A histone variant H2A.Lap1 as a previously undescribed component of the TSS of active genes expressed during specific stages of spermatogenesis. This unique chromatin landscape also includes a second histone variant, H2A.Z. In the later stages of round spermatid development, H2A.Lap1 dynamically loads onto the inactive X chromosome, enabling the transcriptional activation of previously repressed genes. Mechanistically, we show that H2A.Lap1 imparts unique unfolding properties to chromatin. We therefore propose that H2A.Lap1 coordinately regulates gene expression by directly opening the chromatin structure of the TSS at genes regulated during spermatogenesis.

Simple-Cubic Carbon Frameworks with Atomically Dispersed Iron Dopants toward High-Efficiency Oxygen Reduction.

PubMed

Wang, Biwei; Wang, Xinxia; Zou, Jinxiang; Yan, Yancui; Xie, Songhai; Hu, Guangzhi; Li, Yanguang; Dong, Angang

2017-03-08

Iron and nitrogen codoped carbons (Fe-N-C) have attracted increasingly greater attention as electrocatalysts for oxygen reduction reaction (ORR). Although challenging, the synthesis of Fe-N-C catalysts with highly dispersed and fully exposed active sites is of critical importance for improving the ORR activity. Here, we report a new type of graphitic Fe-N-C catalysts featuring numerous Fe single atoms anchored on a three-dimensional simple-cubic carbon framework. The Fe-N-C catalyst, derived from self-assembled Fe 3 O 4 nanocube superlattices, was prepared by in situ ligand carbonization followed by acid etching and ammonia activation. Benefiting from its homogeneously dispersed and fully accessible active sites, highly graphitic nature, and enhanced mass transport, our Fe-N-C catalyst outperformed Pt/C and many previously reported Fe-N-C catalysts for ORR. Furthermore, when used for constructing the cathode for zinc-air batteries, our Fe-N-C catalyst exhibited current and power densities comparable to those of the state-of-the-art Pt/C catalyst.

Spectroscopic and metal-binding properties of DF3: an artificial protein able to accommodate different metal ions

PubMed Central

Torres Martin de Rosales, Rafael; Faiella, Marina; Farquhar, Erik; Que, Lawrence; Andreozzi, Concetta; Pavone, Vincenzo; Maglio, Ornella; Nastri, Flavia

2010-01-01

The design, synthesis, and metal-binding properties of DF3, a new de novo designed di-iron protein model are described (“DF” represents due ferri, Italian for “two iron,” “di-iron”). DF3 is the latest member of the DF family of synthetic proteins. They consist of helix–loop–helix hairpins, designed to dimerize and form an antiparallel four-helix bundle that encompasses a metal-binding site similar to those of non-heme carboxylate-bridged di-iron proteins. Unlike previous DF proteins, DF3 is highly soluble in water (up to 3 mM) and forms stable complexes with several metal ions (Zn, Co, and Mn), with the desired secondary structure and the expected stoichiometry of two ions per protein. UV–vis studies of Co(II) and Fe(III) complexes confirm a metal-binding environment similar to previous di-Co(II)- and di-Fe(III)-DF proteins, including the presence of a µ-oxo-di-Fe(III) unit. Interestingly, UV–vis, EPR, and resonance Raman studies suggest the interaction of a tyro-sine adjacent to the di-Fe(III) center. The design of DF3 was aimed at increasing the accessibility of small molecules to the active site of the four-helix bundle. Indeed, binding of azide to the di-Fe(III) site demonstrates a more accessible metal site compared with previous DFs. In fact, fitting of the binding curve to the Hill equation allows us to quantify a 150% accessibility enhancement, with respect to DF2. All these results represent a significant step towards the development of a functional synthetic DF metalloprotein. PMID:20225070

Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells

PubMed Central

Camp, J. Gray; Weiser, Matthew; Cocchiaro, Jordan L.; Kingsley, David M.; Furey, Terrence S.; Sheikh, Shehzad Z.; Rawls, John F.

2017-01-01

The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs) in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS) found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development and physiology. PMID:28850571

How far will they go? Assessing the travel distance of current and former drug users to access harm reduction services.

PubMed

Allen, Sean; Ruiz, Monica; O'Rourke, Allison

2015-03-01

Prior research has explored spatial access to syringe exchange programs (SEPs) among people who inject drugs (PWID), but little is known about service utilization by former PWID who continue to access services (e.g., HIV screenings and referrals for social services) at harm reduction providers. The purpose of this research is to examine differences in access to SEPs between current and former PWID seeking services at a mobile SEP in Washington, DC. A geometric point distance estimation technique was applied to data collected as part of a PWID population estimation study that took place in Washington, DC, in March and April 2014. We calculated the walking distance from the centroid point of home residence zip code to the mobile exchange site where PWID presented for services. An independent samples t-test was used to examine differences in walking distance measures between current and former PWID. Differences in mean walking distance were statistically significant with current and former PWID having mean walking distances of 2.75 and 1.80 miles, respectively. The results of this study suggest that former PWID who are engaging with SEPs primarily for non-needle exchange services (e.g., medical or social services) may have decreased access to SEPs than their counterparts who are active injectors. This research provides support for expanding SEP operations such that both active and former PWID have increased access to harm reduction providers and associated health and social services. Increasing service accessibility may help resolve unmet needs among current and former PWID.

Nevada National Security Site Environmental Report 2016, Attachment A: Site Description

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

Wills, Cathy

This attachment expands on the general description of the Nevada National Security Site (NNSS) presented in the Introduction to the Nevada National Security Site Environmental Report 2016 (prepared by National Security Technologies, LLC [NSTec], 2017). Included are subsections that summarize the site’s geological, hydrological, climatological, and ecological settings and the cultural resources of the NNSS. The subsections are meant to aid the reader in understanding the complex physical and biological environment of the NNSS. An adequate knowledge of the site’s environment is necessary to assess the environmental impacts of new projects, design and implement environmental monitoring activities for current sitemore » operations, and assess the impacts of site operations on the public residing in the vicinity of the NNSS. The NNSS environment contributes to several key features of the site that afford protection to the inhabitants of adjacent areas from potential exposure to radioactivity or other contaminants resulting from NNSS operations. These key features include the general remote location of the NNSS, restricted access, extended wind transport times, the great depths to slow-moving groundwater, little or no surface water, and low population density. This attachment complements the annual summary of monitoring program activities and dose assessments presented in the main body of this report.« less

Internet Usage by Low-Literacy Adults Seeking Health Information: An Observational Analysis

PubMed Central

Birru, Mehret S; Monaco, Valerie M; Charles, Lonelyss; Drew, Hadiya; Njie, Valerie; Bierria, Timothy; Detlefsen, Ellen

2004-01-01

Background Adults with low literacy may encounter informational obstacles on the Internet when searching for health information, in part because most health Web sites require at least a high-school reading proficiency for optimal access. Objective The purpose of this study was to 1) determine how low-literacy adults independently access and evaluate health information on the Internet, 2) identify challenges and areas of proficiency in the Internet-searching skills of low-literacy adults. Methods Subjects (n=8) were enrolled in a reading assistance program at Bidwell Training Center in Pittsburgh, PA, and read at a 3rd to 8th grade level. Subjects conducted self-directed Internet searches for designated health topics while utilizing a think-aloud protocol. Subjects' keystrokes and comments were recorded using Camtasia Studio screen-capture software. The search terms used to find health information, the amount of time spent on each Web site, the number of Web sites accessed, the reading level of Web sites accessed, and the responses of subjects to questionnaires were assessed. Results Subjects collectively answered 8 out of 24 questions correctly. Seven out of 8 subjects selected "sponsored sites"-paid Web advertisements-over search engine-generated links when answering health questions. On average, subjects accessed health Web sites written at or above a 10th grade reading level. Standard methodologies used for measuring health literacy and for promoting subjects to verbalize responses to Web-site form and content had limited utility in this population. Conclusion This study demonstrates that Web health information requires a reading level that prohibits optimal access by some low-literacy adults. These results highlight the low-literacy adult population as a potential audience for Web health information, and indicate some areas of difficulty that these individuals face when using the Internet and health Web sites to find information on specific health topics. PMID:15471751

Site characterization progress report: Yucca Mountain, Nevada. Number 15, April 1--September 30, 1996

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

NONE

1997-04-01

During the second half of fiscal year 1996, activities at the Yucca Mountain Site Characterization Project (Project) supported the objectives of the revised Program Plan released this period by the Office of Civilian Radioactive Waste Management of the US Department of Energy (Department). Outlined in the revised plan is a focused, integrated program of site characterization, design, engineering, environmental, and performance assessment activities that will achieve key Program and statutory objectives. The plan will result in the development of a license application for repository construction at Yucca Mountain, if the site is found suitable. Activities this period focused on twomore » of the three near-term objectives of the revised plan: updating in 1997 the regulatory framework for determining the suitability of the site for the proposed repository concept and providing information for a 1998 viability assessment of continuing toward the licensing of a repository. The Project has also developed a new design approach that uses the advanced conceptual design published during the last reporting period as a base for developing a design that will support the viability assessment. The initial construction phase of the Thermal Testing Facility was completed and the first phase of the in situ heater tests began on schedule. In addition, phase-one construction was completed for the first of two alcoves that will provide access to the Ghost Dance fault.« less

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

PubMed Central

Fedrigo, Olivier; Babbitt, Courtney C.; Wortham, Matthew; Tewari, Alok K.; London, Darin; Song, Lingyun; Lee, Bum-Kyu; Iyer, Vishwanath R.; Parker, Stephen C. J.; Margulies, Elliott H.; Wray, Gregory A.; Furey, Terrence S.; Crawford, Gregory E.

2012-01-01

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species. PMID:22761590

The role of conserved surface hydrophobic residues in the carbapenemase activity of the class D β-lactamases.

PubMed

Toth, Marta; Smith, Clyde A; Antunes, Nuno T; Stewart, Nichole K; Maltz, Lauren; Vakulenko, Sergei B

2017-08-01

Carbapenem-hydrolyzing class D β-lactamases (CHDLs) produce resistance to the last-resort carbapenem antibiotics and render these drugs ineffective for the treatment of life-threatening infections. Here, it is shown that among the clinically important CHDLs, OXA-143 produces the highest levels of resistance to carbapenems and has the highest catalytic efficiency against these substrates. Structural data demonstrate that acylated carbapenems entirely fill the active site of CHDLs, leaving no space for water molecules, including the deacylating water. Since the entrance to the active site is obstructed by the acylated antibiotic, the deacylating water molecule must take a different route for entry. It is shown that in OXA-143 the movement of a conserved hydrophobic valine residue on the surface opens a channel to the active site of the enzyme, which would not only allow the exchange of water molecules between the active site and the milieu, but would also create extra space for a water molecule to position itself in the vicinity of the scissile bond of the acyl-enzyme intermediate to perform deacylation. Structural analysis of the OXA-23 carbapenemase shows that in this enzyme movement of the conserved leucine residue, juxtaposed to the valine on the molecular surface, creates a similar channel to the active site. These data strongly suggest that all CHDLs may employ a mechanism whereupon the movement of highly conserved valine or leucine residues would allow a water molecule to access the active site to promote deacylation. It is further demonstrated that the 6α-hydroxyethyl group of the bound carbapenem plays an important role in the stabilization of this channel. The recognition of a universal deacylation mechanism for CHDLs suggests a direction for the future development of inhibitors and novel antibiotics for these enzymes of utmost clinical importance.

Soil and surface temperatures at the Viking landing sites

NASA Technical Reports Server (NTRS)

Kieffer, H. H.

1976-01-01

The annual temperature range for the Martian surface at the Viking lander sites is computed on the basis of thermal parameters derived from observations made with the infrared thermal mappers. The Viking lander 1 (VL1) site has small annual variations in temperature, whereas the Viking lander 2 (VL2) site has large annual changes. With the Viking lander images used to estimate the rock component of the thermal emission, the daily temperature behavior of the soil alone is computed over the range of depths accessible to the lander; when the VL1 and VL2 sites were sampled, the daily temperature ranges at the top of the soil were 183 to 263 K and 183 to 268 K, respectively. The diurnal variation decreases with depth with an exponential scale of about 5 centimeters. The maximum temperature of the soil sampled from beneath rocks at the VL2 site is calculated to be 230 K. These temperature calculations should provide a reference for study of the active chemistry reported for the Martian soil.

Soil and surface temperatures at the viking landing sites.

PubMed

Kieffer, H H

1976-12-11

The annual temperature range for the martian surface at the Viking lander sites is computed on the basis of thermal parameters derived from observations made with the infrared thermal mappers. The Viking lander 1 (VL1) site has small annual variations in temperature, whereas the Viking lander 2 (VL2) site has large annual changes. With the Viking lander images used to estimate the rock component of the thermal emission, the daily temperature behavior of the soil alone is computed over the range of depths accessible to the lander; when the VL1 and VL2 sites were sampled, the daily temperature ranges at the top of the soil were 183 to 263 K and 183 to 268 K, respectively. The diurnal variation decreases with depth with an exponential scale of about 5 centimeters. The maximum temperature of the soil sampled from beneath rocks at the VL2 site is calculated to be 230 K. These temperature calculations should provide a reference for study of the active chemistry reported for the martian soil.

An Investigation into Web Content Accessibility Guideline Conformance for an Aging Population

ERIC Educational Resources Information Center

Curran, Kevin; Robinson, David

2007-01-01

Poor web site design can cause difficulties for specific groups of users. By applying the Web Content Accessibility Guidelines to a web site, the amount of possible users who can successfully view the content of that site will increase, especially for those who are in the disabled and older adult categories of online users. Older adults are coming…

Landing site rationality scaling for subsurface sampling on Mars—Case study for ExoMars Rover-like missions

NASA Astrophysics Data System (ADS)

Kereszturi, Akos

2012-11-01

Subsurface sampling will be important in the robotic exploration of Mars in the future, and this activity requires a somewhat different approach in landing site selection than earlier, surface analysis focused missions. In this work theoretical argumentation for the selection of ideal sites is summarized, including various parameters that were defined as examples for the earlier four candidate landing sites of Mars Science Laboratory. The aim here was to compare interesting sites; the decision on the final site does not affect this work. Analyzing the theoretical background, to identify ideal locations for subsurface analysis, several factors could be identified by remote sensing, including the dust and dune coverage, the cap layer distribution as well as the location of probable important outcrops. Beyond the fact that image based information on the rock hardness on Mars is lacking, more work would be also useful to put the interesting sites into global context and to understand the role of secondary cratering in age estimation. More laboratory work would be also necessary to improve our knowledge on the extraction and preservation of organic materials under different conditions. Beyond the theoretical argumentation mentioned above, the size and accessibility of possible important shallow subsurface materials were analyzed at the four earlier candidate landing sites of Mars Science Laboratory. At the sample terrains, interesting but inaccessible, interesting and sideward accessible, and interesting and from above accessible outcrops were identified. Surveying these outcrop types at the sample terrains, the currently available datasets showed only 3-9% of exposed strata over the entire analyzed area is present at Eberswalde and Holden crater, and individual outcrops have an average diameter between 100 and 400 m there. For Gale crater and Mawrth Valles region, these parameters were 46-35% of exposed strata, with an average outcrop diameter of ˜300 m. In the case of the first two sites smaller and elongated outcrops were present in larger number, while in the second group average sizes of outcrops were around 3000 m in diameter. The analysis suggests that for future missions aimed at subsurface sampling, different exploration strategies would be ideal at different terrains, and the target terrain's characteristics should be taken into account during the planning phase of the mission.

Seasonal variations in harvest index and bacoside A contents amongst accessions of Bacopa monnieri (L.) Wettst. collected from wild populations.

PubMed

Bansal, Mahima; Reddy, M Sudhakara; Kumar, Anil

2016-07-01

Bacoside A, a major active principle of Bacopa monnieri known for its cognitive effects is a mixture of saponins like bacoside A3, bacopaside II, isomer of bacopasaponin C and bacopasaponin C. Seasonal changes in biomass and bacoside A levels in fourteen accessions of B. monnieri were evaluated after maintaining these at a common site at Thapar University campus, Patiala (30°19'36.12″N and 76°24'1.08″E) for 1 year. Harvestable biomass and total bacoside A contents varied significantly between the accessions and also in a particular accession during different seasons of the year. The maximum dry weight of plant (biomass 1.64 g) and bacoside A levels (6.82 mg/plant) were recorded in accession BM1. Harvestable biomass was highest during summer in accessions BM1 and BM7 (FW 4.2 g/plant), whereas bacoside A levels were also highest during summer and in accession BM1 (6.82 mg/plant). The lowest bacoside A level (0.06 mg/plant) was recorded in accession BM14 during winter. Principal component analysis showed that samples of summer were positively correlated with both the components suggesting an appropriate time for the harvest.

Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

PubMed

Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

2017-09-07

How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

Engineering the Band Gap States of the Rutile TiO2 (110) Surface by Modulating the Active Heteroatom.

PubMed

Yu, Yaoguang; Yang, Xu; Zhao, Yanling; Zhang, Xiangbin; An, Liang; Huang, Miaoyan; Chen, Gang; Zhang, Ruiqin

2018-04-19

Introducing band gap states to TiO 2 photocatalysts is an efficient strategy for expanding the range of accessible energy available in the solar spectrum. However, few approaches are able to introduce band gap states and improve photocatalytic performance simultaneously. Introducing band gap states by creating surface disorder can incapacitate reactivity where unambiguous adsorption sites are a prerequisite. An alternative method for introduction of band gap states is demonstrated in which selected heteroatoms are implanted at preferred surface sites. Theoretical prediction and experimental verification reveal that the implanted heteroatoms not only introduce band gap states without creating surface disorder, but also function as active sites for the Cr VI reduction reaction. This promising approach may be applicable to the surfaces of other solar harvesting materials where engineered band gap states could be used to tune photophysical and -catalytic properties. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Terbinafine: novel formulations that potentiate antifungal activities.

PubMed

Ma, Y; Chen, X; Guan, S

2015-03-01

Terbinafine, an orally and topically active antifungal agent, has been available for the treatment of dermatophytic infections and onychomycosis for more than a decade. In addition, oral administration has been shown to be associated with drug-drug interactions, hepatotoxicity, low concentration at the infected sites, gastrointestinal and systemic side effects and other adverse effects. Since topical drug delivery can provide higher patient compliance, allow immediate access to the infected site and reduce unwanted systemic drug exposure, an improved topical drug delivery approach with high permeability, sustained release and prolonged retainment could overcome the limitations and side effects caused by oral administration. Conventional topical formulations cannot keep the drug in the targeted sites for a long duration of time and hence a novel drug delivery that can avoid the side effects while still providing sustained efficacy in treatment should be developed. This brief review of novel formulations based on polymers and nanostructure carriers provides insight into the efficacy and topical delivery of terbinafine. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Substrate Tunnels in Enzymes: Structure-Function Relationships and Computational Methodology

PubMed Central

Kingsley, Laura J.; Lill, Markus A.

2015-01-01

In enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein and in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years due to implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with tunnels and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. PMID:25663659

Environmental Assessment and Final Finding of No Significant Impact for Lantirn Village & Camera I Site Upgrades Fort Wainwright Yukon Training Area Fort Wainwright, Alaska

DTIC Science & Technology

2009-08-01

improved road access and overhead power. The site contains a WISS shelter, five (5) 40’ connex containers, UMTE pedestal, shelter, and a weather ...monitoring station (Figure 3- 1 ). 3.1.8.3 Camera I site consists of a roughly l acre site with semi-improved road access and overhead power. The site...characteristics such as microclimate , soil temperature, and moisture regimes. which in turn influence the type of vegetation that will be found there

Non-visual Web Browsing: Beyond Web Accessibility

PubMed Central

Ramakrishnan, I.V.; Ashok, Vikas

2017-01-01

People with vision impairments typically use screen readers to browse the Web. To facilitate non-visual browsing, web sites must be made accessible to screen readers, i.e., all the visible elements in the web site must be readable by the screen reader. But even if web sites are accessible, screen-reader users may not find them easy to use and/or easy to navigate. For example, they may not be able to locate the desired information without having to listen to a lot of irrelevant contents. These issues go beyond web accessibility and directly impact web usability. Several techniques have been reported in the accessibility literature for making the Web usable for screen reading. This paper is a review of these techniques. Interestingly, the review reveals that understanding the semantics of the web content is the overarching theme that drives these techniques for improving web usability. PMID:29202137

Non-visual Web Browsing: Beyond Web Accessibility.

PubMed

Ramakrishnan, I V; Ashok, Vikas; Billah, Syed Masum

2017-07-01

People with vision impairments typically use screen readers to browse the Web. To facilitate non-visual browsing, web sites must be made accessible to screen readers, i.e., all the visible elements in the web site must be readable by the screen reader. But even if web sites are accessible, screen-reader users may not find them easy to use and/or easy to navigate. For example, they may not be able to locate the desired information without having to listen to a lot of irrelevant contents. These issues go beyond web accessibility and directly impact web usability. Several techniques have been reported in the accessibility literature for making the Web usable for screen reading. This paper is a review of these techniques. Interestingly, the review reveals that understanding the semantics of the web content is the overarching theme that drives these techniques for improving web usability.

Monomerization alters the dynamics of the lid region in Campylobacter jejuni CstII: an MD simulation study.

PubMed

Prabhakar, Pradeep Kumar; Srivastava, Alka; Rao, K Krishnamurthy; Balaji, Petety V

2016-01-01

CstII, a bifunctional (α2,3/8) sialyltransferase from Campylobacter jejuni, is a homotetramer. It has been reported that mutation of the interface residues Phe121 (F121D) or Tyr125 (Y125Q) leads to monomerization and partial loss of enzyme activity, without any change in the secondary or tertiary structures. MD simulations of both tetramer and monomer, with and without bound donor substrate, were performed for the two mutants and WT to understand the reasons for partial loss of activity due to monomerization since the active site is located within each monomer. RMSF values were found to correlate with the crystallographic B-factor values indicating that the simulations are able to capture the flexibility of the molecule effectively. There were no gross changes in either the secondary or tertiary structure of the proteins during MD simulations. However, interface is destabilized by the mutations, and more importantly the flexibility of the lid region (Gly152-Lys190) is affected. The lid region accesses three major conformations named as open, intermediate, and closed conformations. In both Y121Q and F121D mutants, the closed conformation is accessed predominantly. In this conformation, the catalytic base His188 is also displaced. Normal mode analysis also revealed differences in the lid movement in tetramer and monomer. This provides a possible explanation for the partial loss of enzyme activity in both interface mutants. The lid region controls the traffic of substrates and products in and out of the active site, and the dynamics of this region is regulated by tetramerization. Thus, this study provides valuable insights into the role of loop dynamics in enzyme activity of CstII.

Protecting intellectual property associated with Canadian academic clinical trials--approaches and impact.

PubMed

Ross, Sue; Magee, Laura; Walker, Mark; Wood, Stephen

2012-12-27

Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation. The 'open access' approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism. The 'restricted access' approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who 'needs to know' about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial. It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results.

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia.

PubMed

Titano, J J; Biederman, D M; Marinelli, B S; Patel, R S; Kim, E; Tabori, N E; Nowakowski, F S; Lookstein, R A; Fischman, A M

2016-05-01

Transradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions. Patients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications. From July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6% with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9%) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1%) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups. Transradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

Molecular dynamics simulations of glycosyltransferase LgtC.

PubMed

Snajdrová, Lenka; Kulhánek, Petr; Imberty, Anne; Koca, Jaroslav

2004-04-02

Molecular dynamics simulations have been performed on fully solvated alpha-(1-->4)-galactosyltransferase LgtC from Neisseria meningitidis with and without the donor substrate UDP-Gal and in the presence of the manganese ion. The analysis of the trajectories revealed a limited movement in the loop X (residues 75-80) and a larger conformational change in the loop Y (residues 246-251) in the simulation, when UDP-Gal was not present. In this case, the loops X and Y open by almost 10A, exposing the active site to the solvent. The 'hinge region' responsible for the opening is composed of residues 246-247. We have also analyzed the behavior of the manganese ion in the simulations. The coordination number is 6 when UDP-Gal is present and it increases to 7 when it is absent. In the latter case, three water molecules become coordinated to the ion. In both cases, the coordination is very stable implying that the manganese ion is tightly bound in the active site of the enzyme even if UDP-Gal is not present. Further analysis of the structural water molecules location confirmed that the mobility of water molecules in the active site and the accessibility of this site for solvent are higher in the absence of the substrate.

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.

Single or Multiple Access Channels to the CYP450s Active Site? An Answer from Free Energy Simulations of the Human Aromatase Enzyme.

PubMed

Magistrato, Alessandra; Sgrignani, Jacopo; Krause, Rolf; Cavalli, Andrea

2017-05-04

Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism, and their overexpression in tumors is associated with drug resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several grueling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450. This has profound implications for enzymatic efficiency and drug efficacy/toxicity. Here, by applying free energy methods, for a cumulative simulation time of 20 μs, we provide detailed atomistic characterization and free energy profiles of the entry/exit routes preferentially followed by a substrate (androstenedione) and a last-generation inhibitor (letrozole) to/from the catalytic site of CYP19A1 (the human aromatase (HA) enzyme), a key clinical target against breast cancer, studied here as prototypical CYP450. Despite the remarkably different size/shape/hydrophobicity of the ligands, two channels appear accessible to their entrance, while only one exit route appears to be preferential. Our study shows that the preferential paths may be conserved among different CYP450s. Moreover, our results highlight that, at least in the case of HA, ligand channeling is associated with large enzyme structural rearrangements. A wise choice of the computational method and very long simulations are, thus, required to obtain fully converged quantitative free energy profiles, which might be used to design novel biocatalysts or next-generation cytochrome inhibitors with an in silico tuned K m .

Documenting pharmacist interventions on an intranet.

PubMed

Simonian, Armen I

2003-01-15

The process of developing and implementing an intranet Web site for clinical intervention documentation is described. An inpatient pharmacy department initiated an organizationwide effort to improve documentation of interventions by pharmacists at its seven hospitals to achieve real-time capture of meaningful benchmarking data. Standardization of intervention types would allow the health system to contrast and compare medication use, process improvement, and patient care initiatives among its hospitals. After completing a needs assessment and reviewing current methodologies, a computerized tracking tool was developed in-house and integrated with the organization's intranet. Representatives from all hospitals agreed on content and functionality requirements for the Web site. The site was completed and activated in February 2002. Before this Web site was established, the most documented intervention types were Renal Adjustment and Clarify Dose, with a daily average of four and three, respectively. After site activation, daily averages for Renal Adjustment remained unchanged, but Clarify Dose is now documented nine times per day. Drug Information and i.v.-to-p.o. intervention types, which previously averaged less than one intervention per day, are now documented an average of four times daily. Approximately 91% of staff pharmacists are using this site. Future plans for this site include enhanced accessibility to the site with wireless personal digital assistants. The design and implementation of an intranet Web site to document pharmacists' interventions doubled the rate of intervention documentation and standardized the intervention types among hospitals in the health system.

StreamStats in North Carolina: a water-resources Web application

USGS Publications Warehouse

Weaver, J. Curtis; Terziotti, Silvia; Kolb, Katharine R.; Wagner, Chad R.

2012-01-01

A statewide StreamStats application for North Carolina was developed in cooperation with the North Carolina Department of Transportation following completion of a pilot application for the upper French Broad River basin in western North Carolina (Wagner and others, 2009). StreamStats for North Carolina, available at http://water.usgs.gov/osw/streamstats/north_carolina.html, is a Web-based Geographic Information System (GIS) application developed by the U.S. Geological Survey (USGS) in consultation with Environmental Systems Research Institute, Inc. (Esri) to provide access to an assortment of analytical tools that are useful for water-resources planning and management (Ries and others, 2008). The StreamStats application provides an accurate and consistent process that allows users to easily obtain streamflow statistics, basin characteristics, and descriptive information for USGS data-collection sites and user-selected ungaged sites. In the North Carolina application, users can compute 47 basin characteristics and peak-flow frequency statistics (Weaver and others, 2009; Robbins and Pope, 1996) for a delineated drainage basin. Selected streamflow statistics and basin characteristics for data-collection sites have been compiled from published reports and also are immediately accessible by querying individual sites from the web interface. Examples of basin characteristics that can be computed in StreamStats include drainage area, stream slope, mean annual precipitation, and percentage of forested area (Ries and others, 2008). Examples of streamflow statistics that were previously available only through published documents include peak-flow frequency, flow-duration, and precipitation data. These data are valuable for making decisions related to bridge design, floodplain delineation, water-supply permitting, and sustainable stream quality and ecology. The StreamStats application also allows users to identify stream reaches upstream and downstream from user-selected sites and obtain information for locations along streams where activities occur that may affect streamflow conditions. This functionality can be accessed through a map-based interface with the user’s Web browser, or individual functions can be requested remotely through Web services (Ries and others, 2008).

Combined Use of Bivalirudin and Radial Access in Acute Coronary Syndromes Is Not Superior to the Use of Either One Separately: Meta-Analysis of Randomized Controlled Trials.

PubMed

Mina, George S; Gobrial, George F; Modi, Kalgi; Dominic, Paari

2016-08-08

The aim of this meta-analysis was to study the relation between access site and bivalirudin use on outcomes in patients with acute coronary syndrome (ACS). Bivalirudin and radial access use are 2 strategies that are increasingly used to lower major bleeding in patients with ACS undergoing invasive approaches. The interaction between these 2 strategies and the benefit of using them in combination are unclear. This analysis included randomized controlled trials that compared bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with ACS and reported outcomes stratified by arterial access site. Meta-analyses of outcome data were performed on the basis of access site and anticoagulation regimen. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from event rates using random-effects models. Eight trials with a total of 27,491 patients were included. Bivalirudin reduced major bleeding risk in patients with femoral access (OR: 0.51; 95% CI: 0.46 to 0.6; p < 0.001) but not in patients with radial access (OR: 0.75; 95% CI: 0.45 to 1.26; p = 0.28). Moreover, radial access reduced major bleeding risk in patients treated with heparin (OR: 0.57; 95% CI: 0.43 to 0.77; p < 0.001) but not in patients treated with bivalirudin (OR: 0.96; 95% CI: 0.65 to 1.41; p = 0.83). There were no differences in major adverse cardiovascular events or all-cause mortality between bivalirudin and heparin, regardless of access site. Bivalirudin reduces bleeding risk only with femoral access, and radial access reduces bleeding risk only with heparin anticoagulation. Therefore, there is no additional benefit to the combined use of bivalirudin and radial access strategies in patients with ACS. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cleanups In My Community (CIMC) - Federal Facility RCRA Sites, National Layer

EPA Pesticide Factsheets

Federal facilities are properties owned by the federal government. This data layer provides access to Federal facilities that are Resource Conservation and Recovery Act (RCRA) sites as part of the CIMC web service. The Resource Conservation and Recovery Act, among other things, helps ensure that wastes are managed in an environmentally sound manner so as to protect human health and the environment from the potential hazards of waste disposal.In particular, RCRA tightly regulates all hazardous waste from cradle to grave. In general, all generators, transporters, treaters, storers, and disposers of hazardous waste are required to provide information about their activities to state environmental agencies. These agencies, in turn pass on the information to regional and national EPA offices. Accidents or other activities at facilities that treat, store or dispose of hazardous wastes have sometimes led to the release of hazardous waste or hazardous constituents into soil, ground water, surface water, or air. When that happens, the RCRA Corrective Action program is one program that may be used to accomplish the necessary cleanup.In Cleanups in My Community, you can map or list RCRA Corrective Action sites that are currently undergoing corrective action, sites for which a remedy has been selected, sites for which construction has been completed, and sites where the corrective action cleanup is complete. This data layer shows those RCRA sites that are located at Federa

Former UST Site Reused as Greenspace and Access to Ancient Ceremonial Nikwasi Mound in North Carolina

EPA Pesticide Factsheets

Read about a former underground storage tank site fronting on the Little Tennessee River in Franklin, NC that is now reused as an attractive greenspace with parking and Main Street access to the Nikwasi Mound.

N-Glycosylation Improves the Pepsin Resistance of Histidine Acid Phosphatase Phytases by Enhancing Their Stability at Acidic pHs and Reducing Pepsin's Accessibility to Its Cleavage Sites

PubMed Central

Niu, Canfang; Luo, Huiying; Shi, Pengjun; Huang, Huoqing; Wang, Yaru; Yang, Peilong

2015-01-01

N-Glycosylation can modulate enzyme structure and function. In this study, we identified two pepsin-resistant histidine acid phosphatase (HAP) phytases from Yersinia kristensenii (YkAPPA) and Yersinia rohdei (YrAPPA), each having an N-glycosylation motif, and one pepsin-sensitive HAP phytase from Yersinia enterocolitica (YeAPPA) that lacked an N-glycosylation site. Site-directed mutagenesis was employed to construct mutants by altering the N-glycosylation status of each enzyme, and the mutant and wild-type enzymes were expressed in Pichia pastoris for biochemical characterization. Compared with those of the N-glycosylation site deletion mutants and N-deglycosylated enzymes, all N-glycosylated counterparts exhibited enhanced pepsin resistance. Introduction of the N-glycosylation site into YeAPPA as YkAPPA and YrAPPA conferred pepsin resistance, shifted the pH optimum (0.5 and 1.5 pH units downward, respectively) and improved stability at acidic pH (83.2 and 98.8% residual activities at pH 2.0 for 1 h). Replacing the pepsin cleavage sites L197 and L396 in the immediate vicinity of the N-glycosylation motifs of YkAPPA and YrAPPA with V promoted their resistance to pepsin digestion when produced in Escherichia coli but had no effect on the pepsin resistance of N-glycosylated enzymes produced in P. pastoris. Thus, N-glycosylation may improve pepsin resistance by enhancing the stability at acidic pH and reducing pepsin's accessibility to peptic cleavage sites. This study provides a strategy, namely, the manipulation of N-glycosylation, for improvement of phytase properties for use in animal feed. PMID:26637601

78 FR 67881 - Nondiscrimination on the Basis of Disability in Air Travel: Accessibility of Web Sites and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... corresponding accessible pages on a mobile Web site by one year after the final rule's effective date; and (3... Mobile Web site conformant with any of the following standards: WCAG 1.0, WCAG 2.0 at Level A, existing Section 508 standards, or Mobile Web Best Practices (MWBP) 1.0 (if applicable). Two of the options they...

Comparative chromosomal localization of 45S and 5S rDNAs and implications for genome evolution in Cucumis.

PubMed

Zhang, Zhen-Tao; Yang, Shu-Qiong; Li, Zi-Ang; Zhang, Yun-Xia; Wang, Yun-Zhu; Cheng, Chun-Yan; Li, Ji; Chen, Jin-Feng; Lou, Qun-Feng

2016-07-01

Ribosomal DNAs are useful cytogenetic markers for chromosome analysis. Studies investigating site numbers and distributions of rDNAs have provided important information for elucidating genome organization and chromosomal relationships of many species by fluorescence in situ hybridization. But relevant studies are scarce for species of the genus Cucumis, especially in wild species. In the present study, FISH was conducted to investigate the organization of 45S and 5S rDNA among 20 Cucumis accessions, including cultivars and wild accessions. Our results showed that the number of 45S rDNA sites varied from one to five pairs in different accessions, and most of these sites are located at the terminal regions of chromosomes. Interestingly, up to five pairs of 45S rDNA sites were observed in C. sativus var. sativus, the species which has the lowest chromosome number, i.e., 2n = 14. Only one pair of 5S rDNA sites was detected in all accessions, except for C. heptadactylus, C. sp, and C. spp that had two pairs of 5S rDNA sites. The distributions of 5S rDNA sites showed more variation than 45S rDNA sites. The phylogenetic analysis in this study showed that 45S and 5S rDNA have contrasting evolutionary patterns. We find that 5S rDNA has a polyploidization-related tendency towards the terminal location from an interstitial location but maintains a conserved site number, whereas the 45S rDNA showed a trend of increasing site number but a relatively conserved location.

Creating Patient and Family Education Web Sites

PubMed Central

YADRICH, DONNA MACAN; FITZGERALD, SHARON A.; WERKOWITCH, MARILYN; SMITH, CAROL E.

2013-01-01

This article gives details about the methods and processes used to ensure that usability and accessibility were achieved during development of the Home Parenteral Nutrition Family Caregivers Web site, an evidence-based health education Web site for the family members and caregivers of chronically ill patients. This article addresses comprehensive definitions of usability and accessibility and illustrates Web site development according to Section 508 standards and the national Health and Human Services’ Research-Based Web Design and Usability Guidelines requirements. PMID:22024970

Access NASA Satellite Global Precipitation Data Visualization on YouTube

NASA Astrophysics Data System (ADS)

Liu, Z.; Su, J.; Acker, J. G.; Huffman, G. J.; Vollmer, B.; Wei, J.; Meyer, D. J.

2017-12-01

Since the satellite era began, NASA has collected a large volume of Earth science observations for research and applications around the world. Satellite data at 12 NASA data centers can also be used for STEM activities such as disaster events, climate change, etc. However, accessing satellite data can be a daunting task for non-professional users such as teachers and students because of unfamiliarity of terminology, disciplines, data formats, data structures, computing resources, processing software, programing languages, etc. Over the years, many efforts have been developed to improve satellite data access, but barriers still exist for non-professionals. In this presentation, we will present our latest activity that uses the popular online video sharing web site, YouTube, to access visualization of global precipitation datasets at the NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC). With YouTube, users can access and visualize a large volume of satellite data without necessity to learn new software or download data. The dataset in this activity is the 3-hourly TRMM (Tropical Rainfall Measuring Mission) Multi-satellite Precipitation Analysis (TMPA). The video consists of over 50,000 data files collected since 1998 onwards, covering a zone between 50°N-S. The YouTube video will last 36 minutes for the entire dataset record (over 19 years). Since the time stamp is on each frame of the video, users can begin at any time by dragging the time progress bar. This precipitation animation will allow viewing precipitation events and processes (e.g., hurricanes, fronts, atmospheric rivers, etc.) on a global scale. The next plan is to develop a similar animation for the GPM (Global Precipitation Measurement) Integrated Multi-satellitE Retrievals for GPM (IMERG). The IMERG provides precipitation on a near-global (60°N-S) coverage at half-hourly time interval, showing more details on precipitation processes and development, compared to the 3-hourly TMPA product. The entire video will contain more than 330,000 files and will last 3.6 hours. Future plans include development of fly-over videos for orbital data for an entire satellite mission or project. All videos will be uploaded and available at the GES DISC site on YouTube (https://www.youtube.com/user/NASAGESDISC).

Access site-related complications after transradial catheterization can be reduced with smaller sheath size and statins.

PubMed

Honda, Tsuyoshi; Fujimoto, Kazuteru; Miyao, Yuji; Koga, Hidenobu; Hirata, Yoshihiro

2012-09-01

The aim of this study was to investigate the risk factors for access site-related complications after transradial coronary angiography (CAG) or percutaneous coronary intervention (PCI). Transradial PCI has been shown to reduce access site-related bleeding complications compared with procedures performed through a femoral approach. Although previous studies focused on risk factors for access site-related complications after a transfemoral approach or transfemoral and transradial approaches, it is uncertain which factors affect vascular complications after transradial catheterization. We enrolled 500 consecutive patients who underwent transradial CAG or PCI. We determined the incidence and risk factors for access site-related complications such as radial artery occlusion and bleeding complications. Age, sheath size, the dose of heparin and the frequency of PCI (vs. CAG) were significantly greater in patients with than without bleeding complications. However, body mass index (BMI) was significantly lower in patients with than without bleeding complications. Sheath size was significantly higher and the frequency of statin use was significantly lower in patients with than without radial artery occlusion. Multiple logistic analysis revealed that sheath size [odds ratio (OR) 5.5; P < 0.05] and BMI (OR 0.86; P < 0.01) were risk factors for bleeding complications; and sheath size (OR 5.2; P < 0.05) and the lack of statin pretreatment (OR 0.50; P < 0.05) were risk factors for occlusive complications. In conclusion, these findings indicate that down-sizing of the devices used in transradial procedures might attenuate access site-related complications after transradial CAG or PCI. Statin pretreatment might also be a strategy that could prevent radial artery occlusion after transradial procedures.

Pentalum SpiDAR Deployment at SWiFT FY17.

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

Westergaard, Carsten; Pol, Suhas; Pereira, Tassia

2016-12-01

The Texas Tech University ( TTU ) research group is actively studying the wake development of wind turbines, as part of developing innovative wake control strategies to improve the performance of wind farms. Recently, the team received a set of five new gro und lidars to perform field measurements at the Sandia National Laboratories SWiFT site. This document describes tests details including configurations, timeframe, hardware, and the required collaboration from the Sandia team. This test plan will facili tate the coordination between both TTU and the Sandia team in terms of site accessibility, staff training, and data sharing to meetmore » the specific objectives of the tests.« less

Accessibility of summer meals and the food insecurity of low-income households with children.

PubMed

Miller, Daniel P

2016-08-01

Almost no previous research has examined the impact of the US Department of Agriculture's (USDA) Summer Food Service Program and related Seamless Summer Option, which provide meals and snacks to low-income children over the summer. The present study investigated whether geographic accessibility of summer meals programme sites (a proxy for programme participation) was associated with food insecurity for low-income households. The study used data from the California Health Interview Survey (CHIS) and administrative data on summer meals sites in California. Geocoding was used to calculate driving time between CHIS households and nearby summer meals sites. Geographic accessibility was measured using a gravity model, which accounted for the spatially distributed supply of and demand for summer meals. Food insecurity and very low food security were measured using a standard six-item measure from the USDA. Low-income families with children (n 5394). A representative surveillance study of non-institutionalized households in California. Geographic accessibility was not associated with food insecurity. However, geographic accessibility was associated with a significantly lower probability of very low food security in the full sample and among households with younger children and those living in less urban areas. The USDA's summer meals programme may be effective at reducing the most severe form of food insecurity for low-income households with children. Expanding the number of summer meals sites, the number of meals served at sites and sites' hours of operation may be effective strategies to promote nutritional health over the summer months.

Reconnaissance Strategy for Seep Chemosynthetic Communities in the Gulf of Mexico

NASA Astrophysics Data System (ADS)

MacDonald, I. R.; Roberts, H. H.; Fisher, C. R.; Bernard, B. B.; Joye, S.; Carney, R.; Hunt, J.; Shedd, W.

2007-05-01

The Continental Slope of the Gulf of Mexico hosts diverse chemosynthetic communities at oil and gas seeps. Exploration is needed to extend knowledge of the Gulf of Mexico chemosynthetic ecosystem in the zones anticipated to receive energy exploration and production activities over the coming decades. A nested survey approach can be used to identify representative sampling sites within this vast offshore area. Potential sites where chemosynthetic community could occur are selected on the basis geophysical, geochemical, and satellite remote-sensing indicators. Photo-reconnaissance using cost-effective camera systems is then used to confirm the presences or absence of chemosynthetic communities at high-probability sites. Follow-up sampling can then proceed with submersibles or ROVs to acquire tissue and or geochemical samples. However, because access is limited, submersible dives may not be possible at all sites. Two examples of this approach have recently been applied in the northern and southern Gulf of Mexico, respectively. We compared community characterizations obtained from the initial reconnaissance with more detailed characterizations forthcoming from submersible sampling. Our results show that major differences in community type and geochemical substrata are evident from preliminary reconnaissance, while details of animal densities and species compositions require targeted sampling with submersibles. However, given the limited access to submersibles, cost-effective surveys with deep-sea camera systems would greatly expand understanding of the zoogeography of chemosynthetic fauna in the Gulf of Mexico and Caribbean Sea.

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

PubMed Central

Tien, Jason; Peters, Christian J; Wong, Xiu Ming; Cheng, Tong; Jan, Yuh Nung; Jan, Lily Yeh; Yang, Huanghe

2014-01-01

TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sensors of this channel are still lacking. By aligning distantly related calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of all conserved acidic residues thought to be exposed to the cytoplasm, we identify four acidic amino acids as putative calcium-binding residues. Alterations of the charge, polarity, and size of amino acid side chains at these sites alter the ability of different divalent cations to activate the channel. Furthermore, TMEM16A mutant channels containing double cysteine substitutions at these residues are sensitive to the redox potential of the internal solution, providing evidence for their physical proximity and solvent accessibility. DOI: http://dx.doi.org/10.7554/eLife.02772.001 PMID:24980701

Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes.

PubMed

Benedetti, Angelo; Fulceri, Rosella; Allan, Bernard B; Houston, Pamela; Sukhodub, Andrey L; Marcolongo, Paola; Ethell, Brian; Burchell, Brian; Burchell, Ann

2002-10-15

Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane.

Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes.

PubMed Central

Benedetti, Angelo; Fulceri, Rosella; Allan, Bernard B; Houston, Pamela; Sukhodub, Andrey L; Marcolongo, Paola; Ethell, Brian; Burchell, Brian; Burchell, Ann

2002-01-01

Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane. PMID:12097138

Structure of Thermobifida fusca DyP-type peroxidase and activity towards Kraft lignin and lignin model compounds.

PubMed

Rahmanpour, Rahman; Rea, Dean; Jamshidi, Shirin; Fülöp, Vilmos; Bugg, Timothy D H

2016-03-15

A Dyp-type peroxidase enzyme from thermophilic cellulose degrader Thermobifida fusca (TfuDyP) was investigated for catalytic ability towards lignin oxidation. TfuDyP was characterised kinetically against a range of phenolic substrates, and a compound I reaction intermediate was observed via pre-steady state kinetic analysis at λmax 404 nm. TfuDyP showed reactivity towards Kraft lignin, and was found to oxidise a β-aryl ether lignin model compound, forming an oxidised dimer. A crystal structure of TfuDyP was determined, to 1.8 Å resolution, which was found to contain a diatomic oxygen ligand bound to the heme centre, positioned close to active site residues Asp-203 and Arg-315. The structure contains two channels providing access to the heme cofactor for organic substrates and hydrogen peroxide. Site-directed mutant D203A showed no activity towards phenolic substrates, but reduced activity towards ABTS, while mutant R315Q showed no activity towards phenolic substrates, nor ABTS. Copyright © 2016 Elsevier Inc. All rights reserved.

High spatial resolution satellite observations for validation of MODIS land products: IKONOS observations acquired under the NASA scientific data purchase.

Treesearch

Jeffrey T. Morisette; Jaime E. Nickeson; Paul Davis; Yujie Wang; Yuhong Tian; Curtis E. Woodcock; Nikolay Shabanov; Matthew Hansen; Warren B. Cohen; Doug R. Oetter; Robert E. Kennedy

2003-01-01

Phase 1I of the Scientific Data Purchase (SDP) has provided NASA investigators access to data from four different satellite and airborne data sources. The Moderate Resolution Imaging Spectrometer (MODIS) land discipline team (MODLAND) sought to utilize these data in support of land product validation activities with a lbcus on tile EOS Land Validation Core Sites. These...

Rapid access to diverse, trifluoromethyl-substituted alkenes using complementary strategies† †Electronic supplementary information (ESI) available. CCDC 1811877, 1817386–1817390. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc05420c

PubMed Central

Phelan, James P.; Wiles, Rebecca J.; Lang, Simon B.; Kelly, Christopher B.

2018-01-01

Two synergistic approaches to the facile assembly of complex α-trifluoromethyl alkenes are described. Using α-trifluoromethyl-β-silyl alcohols as masked trifluoromethyl alkenes, cross-coupling or related functionalization processes at distal electrophilic sites can be executed without inducing Peterson elimination. Subsequent Lewis acidic activation affords functionalized α-trifluoromethyl alkenes. Likewise, the development of a novel α-trifluoromethylvinyl trifluoroborate reagent complements this approach and allows a one-step cross-coupling of (hetero)aryl halides to access a broad array of complex α-trifluoromethyl alkenes. PMID:29732105

The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites

PubMed Central

Neufeldt, Christopher J.; Joyce, Michael A.; Van Buuren, Nicholas; Levin, Aviad; Kirkegaard, Karla; Gale Jr., Michael; Tyrrell, D. Lorne J.; Wozniak, Richard W.

2016-01-01

Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication. PMID:26863439

A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes.

PubMed

Singh, Satendra; Singh, Atul Kumar; Wadhwa, Gulshan; Singh, Dev Bukhsh; Dwivedi, Seema; Gautam, Budhayash; Ramteke, Pramod W

2016-06-01

Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing.

STEREO/Waves Education and Public Outreach

NASA Astrophysics Data System (ADS)

MacDowall, R. J.; Bougeret, J.; Bale, S. D.; Goetz, K.; Kaiser, M. L.

2005-05-01

We present the education and public outreach plan and activities of the STEREO Waves (aka SWAVES) investigation. SWAVES measures radio emissions from the solar corona, interplanetary medium, and terrestrial magnetosphere, as well as in situ waves in the solar wind. In addition to the web site components that display stereo/multi-spacecraft data in a graphical form and explain the science and instruments, we will focus on the following three areas of EPO: class-room demonstrations using models of the STEREO spacecraft with battery powered radio receivers (and speakers) to illustrate spacecraft radio direction finding, teacher developed and tested class-room activities using SWAVES solar radio observations to motivate geometry and trigonometry, and sound-based delivery of characteristic radio and plasma wave events from the SWAVES web site for accessibility and esthetic reasons. Examples of each element will be demonstrated.

The open science grid

NASA Astrophysics Data System (ADS)

Pordes, Ruth; OSG Consortium; Petravick, Don; Kramer, Bill; Olson, Doug; Livny, Miron; Roy, Alain; Avery, Paul; Blackburn, Kent; Wenaus, Torre; Würthwein, Frank; Foster, Ian; Gardner, Rob; Wilde, Mike; Blatecky, Alan; McGee, John; Quick, Rob

2007-07-01

The Open Science Grid (OSG) provides a distributed facility where the Consortium members provide guaranteed and opportunistic access to shared computing and storage resources. OSG provides support for and evolution of the infrastructure through activities that cover operations, security, software, troubleshooting, addition of new capabilities, and support for existing and engagement with new communities. The OSG SciDAC-2 project provides specific activities to manage and evolve the distributed infrastructure and support it's use. The innovative aspects of the project are the maintenance and performance of a collaborative (shared & common) petascale national facility over tens of autonomous computing sites, for many hundreds of users, transferring terabytes of data a day, executing tens of thousands of jobs a day, and providing robust and usable resources for scientific groups of all types and sizes. More information can be found at the OSG web site: www.opensciencegrid.org.

Activation of olefins via asymmetric Bronsted acid catalysis

DOE PAGES

Tsuji, Nobuya; Kennemur, Jennifer L.; Buyck, Thomas; ...

2018-03-30

The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Bronsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Bronsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Bronsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. In conclusion, the methodologymore » gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (–)-Boivinianin A.« less

Activation of olefins via asymmetric Bronsted acid catalysis

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

Tsuji, Nobuya; Kennemur, Jennifer L.; Buyck, Thomas

The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Bronsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Bronsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Bronsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. In conclusion, the methodologymore » gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (–)-Boivinianin A.« less

U.S. EPAs Geospatial Data Access Project

EPA Pesticide Factsheets

To improve public health and the environment, the United States Environmental Protection Agency (EPA) collects information about facilities, sites, or places subject to environmental regulation or of environmental interest. Through the Geospatial Data Download Service, the public is now able to download the EPA Geodata Shapefile, Feature Class or extensible markup language (XML) file containing facility and site information from EPA's national program systems. The files are Internet accessible from the Envirofacts Web site (https://www3.epa.gov/enviro/). The data may be used with geospatial mapping applications. (Note: The files omit facilities without latitude/longitude coordinates.) The EPA Geospatial Data contains the name, location (latitude/longitude), and EPA program information about specific facilities and sites. In addition, the files contain a Uniform Resource Locator (URL), which allows mapping applications to present an option to users to access additional EPA data resources on a specific facility or site.

Accessing wound-care information on the Internet: the implications for patients.

PubMed

Bovill, E S; Hormbrey, E; Gillespie, P H; Banwell, P E

2001-02-01

The Internet and the World Wide Web have revolutionised communication and provide a unique forum for the exchange of information. It has been proposed that the Internet has given the public more access to medical information resources and improved patient education. This study assessed the impact of the Internet on the availability of information on wound care management. The search phrases 'wound care', 'wound healing' and 'wounds' were analysed using a powerful Metacrawler search engine (www.go2net.com). Web site access was classified according to the target audience (wound-care specialists, other health professionals, patients) and the author (societies, institutions or commercial companies). The largest proportion of web sites were commercially based (32%). Of the total number, 23% specifically targeted patients, mostly by advertising. Only 20% were aimed at wound specialists. Extensive surfing was required to obtain wound-care information, and objective information sites were under-represented. Regulated, easily accessible, objective information sites on wound-healing topics are needed for improved patient education and to balance the existing commercial bias.

Impact of Zeolite Aging in Hot Liquid Water on Activity for Acid-Catalyzed Dehydration of Alcohols.

PubMed

Vjunov, Aleksei; Derewinski, Miroslaw A; Fulton, John L; Camaioni, Donald M; Lercher, Johannes A

2015-08-19

The location and stability of Brønsted acid sites catalytically active in zeolites during aqueous phase dehydration of alcohols were studied on the example of cyclohexanol. The catalytically active hydronium ions originate from Brønsted acid sites (BAS) of the zeolite that are formed by framework tetrahedral Si atom substitution by Al. Al K-edge extended X-ray absorption fine structure (EXAFS) and (27)Al magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopies in combination with density functional theory (DFT) calculations are used to determine the distribution of tetrahedral Al sites (Al T-sites) both qualitatively and quantitatively for both parent and HBEA catalysts aged in water prior to catalytic testing. The aging procedure leads to partial degradation of the zeolite framework evidenced from the decrease of material crystallinity (XRD) as well as sorption capacity (BET). With the exception of one commercial zeolite sample, which had the highest concentration of framework silanol-defects, there is no evidence of Al coordination modification after aging in water. The catalyst weight-normalized dehydration rate correlated best with the sum of strong and weak Brønsted acidic protons both able to generate the hydrated hydronium ions. All hydronium ions were equally active for the acid-catalyzed reactions in water. Zeolite aging in hot water prior to catalysis decreased the weight normalized dehydration reaction rate compared to that of the parent HBEA, which is attributed to the reduced concentration of accessible Brønsted acid sites. Sites are hypothesized to be blocked due to reprecipitation of silica dissolved during framework hydrolysis in the aging procedure.

Catalytic efficiency and thermostability improvement of Suc2 invertase through rational site-directed mutagenesis.

PubMed

Mohandesi, Nooshin; Haghbeen, Kamahldin; Ranaei, Omid; Arab, Seyed Shahriar; Hassani, Sorour

2017-01-01

Engineering of invertases has come to attention because of increasing demand for possible applications of invertases in various industrial processes. Due to the known physicochemical properties, invertases from micro-organisms such as Saccharomyces cerevisiae carrying SUC2 gene are considered as primary models. To improve thermostability and catalytic efficiency of SUC2 invertase (SInv), six influential residues with Relative Solvent Accessibility<5% were selected through multiple-sequence alignments, molecular modelling, structural and computational analyses. Consequently, SInv and 5 mutants including three mutants with single point substitution [Mut1=P152V, Mut2=S85V and Mut3=K153F)], one mutant with two points [Mut4=S305V-N463V] and one mutant with three points [Mut5=S85V-K153F-T271V] were developed via site-directed mutagenesis and produced using Pichia pastoris as the host. Physicochemical studies on these enzymes indicated that the selected amino acids which were located in the active site region mainly influenced catalytic efficiency. The best improvement belonged to Mut1 (54% increase in K cat /K m ) and Mut3 exhibited the worst effect (90% increase in K m ). These results suggest that Pro152 and Lys153 play key role in preparation of the right substrate lodging in the active site of SInv. The best thermostability improvement (16%) was observed for Mut4 in which two hydrophilic residues located on the loops, far from the active site, were replaced by Valines. These results suggest that tactful simultaneous substitution of influential hydrophilic residues in both active site region and peripheral loops with hydrophobic amino acids could result in more thermostable invertases with enhanced catalytic efficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxygen activation in flavoprotein oxidases: the importance of being positive.

PubMed

Gadda, Giovanni

2012-04-03

The oxidation of flavin hydroquinones by O(2) in solution is slow, with second-order rate constants of ~250 M(-1) s(-1). This is due to the obligatory, single-electron transfer that initiates the reaction being thermodynamically unfavored and poorly catalyzed. Notwithstanding considerations of O(2) accessibility to the reaction site, its desolvation and geometry and other factors that can also contribute to further rate acceleration, flavoprotein oxidases must activate O(2) for reaction with flavin hydroquinones to be able to achieve the 100-1000-fold rate enhancements typically observed. Protein positive charges have been identified in glucose oxidase, monomeric sarcosine oxidase, N-methyltryptophan oxidase and fructosamine oxidase that electrostatically stabilize the transition state for the initial single electron transfer that generates the O(2)(-•)/flavin semiquinone radical pair. In choline oxidase despite the presence of three histidines in the active site, the trimethylammonium group of the reaction product provides such an electrostatic stabilization. A nonpolar site proximal to the flavin C(4a) atom in choline oxidase has also been identified, which contributes to the geometry and desolvation of the O(2) reaction site. The relevance of O(2) activation by product charges to other flavoprotein oxidases, such as for example those catalyzing amine oxidations, is discussed in this review. A nonpolar site close to the flavin C(4a) atom and a positive charge is identified through structural analysis in several flavoprotein oxidases. Mutagenesis has disclosed nonpolar sites in O(2)-reducing enzymes that utilize copper/TPQ or iron. It is predicted that classes of O(2)-reducing enzymes utilizing other cofactors also contain a similar catalytic motif.

Impact of arterial access site on outcomes after primary percutaneous coronary intervention: prespecified subgroup analysis from the EUROMAX trial.

PubMed

Hamon, Martial; Coste, Pierre; Van't Hof, Arnoud; Ten Berg, Jurrien; Clemmensen, Peter; Tabone, Xavier; Benamer, Hakim; Kristensen, Steen D; Cavallini, Claudio; Marzocchi, Antonio; Hamm, Christian; Kanic, Vojko; Bernstein, Debra; Anthopoulos, Prodromos; Deliargyris, Efthymios N; Steg, Philippe Gabriel

2015-06-01

In European Ambulance Acute Coronary Syndrome Angiography (EUROMAX), bivalirudin improved 30-day clinical outcomes with reduced major bleeding compared with heparins plus optional glycoprotein IIb/IIIa inhibitors. We assessed whether choice of access site (radial or femoral) had an impact on 30-day outcomes and whether it interacted with the benefit of bivalirudin. In EUROMAX, choice of arterial access was left to operator discretion. Overall, 47% of patients underwent radial and 53% femoral access. Baseline risk was higher in the femoral access group. Unadjusted proportions for the primary outcome (death or noncoronary artery bypass graft protocol major bleeding at 30 days) were lower with radial access, however, without differences in major or major plus minor bleeding proportions. After multivariable adjustment, ischemic outcomes were no longer different between access site groups, except for a lower risk of stroke in radial patients. Bivalirudin was associated with lower proportions of the primary outcome in both the radial (odds ratio, 0.58; 95% CI, 0.33-1.03; P=0.058) and the femoral groups (odds ratio, 0.59; 95% CI, 0.37-0.93; P=0.022; interaction P=0.97). Bleeding was significantly lower in the bivalirudin group both in the radial- and femoral-treated patients but no significant difference was observed in ischemic outcomes. In multivariable analysis, bivalirudin emerged as the only independent predictor of reduced major bleeding (odds ratio, 0.45; 95% CI, 0.27-0.74; P=0.002). In this prespecified analysis from EUROMAX, radial access was preferred in lower risk patients and did not improve clinical outcomes. Bivalirudin was associated with less bleeding irrespective of access site. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01087723. © 2015 American Heart Association, Inc.

Factors affecting fuel break effectiveness in the control of large fires on the Los Padres National Forest, California

USGS Publications Warehouse

Syphard, Alexandra D.; Keeley, Jon E.; Brennan, Teresa J.

2011-01-01

As wildfires have increased in frequency and extent, so have the number of homes developed in the wildland-urban interface. In California, the predominant approach to mitigating fire risk is construction of fuel breaks, but there has been little empirical study of their role in controlling large fires.We constructed a spatial database of fuel breaks on the Los Padres National Forest in southern California to better understand characteristics of fuel breaks that affect the behaviour of large fires and to map where fires and fuel breaks most commonly intersect. We evaluated whether fires stopped or crossed over fuel breaks over a 28-year period and compared the outcomes with physical characteristics of the sites, weather and firefighting activities during the fire event. Many fuel breaks never intersected fires, but others intersected several, primarily in historically fire-prone areas. Fires stopped at fuel breaks 46% of the time, almost invariably owing to fire suppression activities. Firefighter access to treatments, smaller fires and longer fuel breaks were significant direct influences, and younger vegetation and fuel break maintenance indirectly improved the outcome by facilitating firefighter access. This study illustrates the importance of strategic location of fuel breaks because they have been most effective where they provided access for firefighting activities.

Temporal changes in radial access use, associates and outcomes in patients undergoing PCI using rotational atherectomy between 2007 and 2014: results from the British Cardiovascular Intervention Society national database.

PubMed

Kinnaird, Tim; Cockburn, James; Gallagher, Sean; Choudhury, Anirban; Sirker, Alex; Ludman, Peter; de Belder, Mark; Copt, Samuel; Mamas, Mamas; de Belder, Adam

2018-04-01

Access site choice for cases requiring rotational atherectomy (PCI-ROTA) is poorly defined. Using the British Cardiovascular Intervention Society PCI database, temporal changes and contemporary associates/outcomes of access site choice for PCI-ROTA were studied. Data were analysed from 11,444 PCI-ROTA procedures performed in England and Wales between 2007 and 2014. Multivariate logistic regression was used to identify predictors of access site choice and its association with outcomes. For PCI-ROTA, radial access increased from 19.6% in 2007 to 58.6% in 2014. Adoption of radial access was slower in females, those with prior CABG, and in patients with chronic occlusive (CTO) or left main disease. In 2013/14, the strongest predictors of femoral artery use were age (OR 1.02, [1.005-1.036], P = .008), CTO intervention (OR 1.95, [1.209-3.314], P = .006), and history of previous CABG (OR 1.68, [1.124-2.515], P = .010). Radial access was associated with reductions in overall length of stay, and increased rates of same-day discharge. Procedural success rates were similar although femoral access use was associated with increased access site complications (2.4 vs. 0.1%, P < .001). After adjustment for baseline differences, arterial complications (OR 15.6, P < .001), transfusion (OR 12.5, P = .023) and major bleeding OR 6.0, P < .001) remained more common with FA use. Adjusted mortality and MACE rates were similar in both groups. In contemporary practice, radial access for PCI-ROTA results in similar procedural success when compared to femoral access but is associated with shorter length of stay, and lower rates of vascular complication, major bleeding and transfusion. Copyright © 2018 Elsevier Inc. All rights reserved.

Accessibility of Nitroxide Side Chains: Absolute Heisenberg Exchange Rates from Power Saturation EPR

PubMed Central

Altenbach, Christian; Froncisz, Wojciech; Hemker, Roy; Mchaourab, Hassane; Hubbell, Wayne L.

2005-01-01

In site-directed spin labeling, the relative solvent accessibility of spin-labeled side chains is taken to be proportional to the Heisenberg exchange rate (Wex) of the nitroxide with a paramagnetic reagent in solution. In turn, relative values of Wex are determined by continuous wave power saturation methods and expressed as a proportional and dimensionless parameter Π. In the experiments presented here, NiEDDA is characterized as a paramagnetic reagent for solvent accessibility studies, and it is shown that absolute values of Wex can be determined from Π, and that the proportionality constant relating them is independent of the paramagnetic reagent and mobility of the nitroxide. Based on absolute exchange rates, an accessibility factor is defined (0 < ρ < 1) that serves as a quantitative measure of side-chain solvent accessibility. The accessibility factors for a nitroxide side chain at 14 different sites in T4 lysozyme are shown to correlate with a structure-based accessibility parameter derived from the crystal structure of the protein. These results provide a useful means for relating crystallographic and site-directed spin labeling data, and hence comparing crystal and solution structures. PMID:15994891

Transcolonic Perirectal NOTES Access (PNA): A feasibility study with survival in swine model.

PubMed

Oliveira, André L A; Zorron, Ricardo; Oliveira, Flavio M M DE; Santos, Marcelo B Dos; Scheffer, Jussara P; Rios, Marcelo; Antunes, Fernanda

2017-05-01

Transrectal access still has some unsolved issues such as spatial orientation, infection, access and site closure. This study presents a simple technique to perform transcolonic access with survival in a swine model series. A new technique for NOTES perirectal access to perform retroperitoneoscopy, peritoneoscopy, liver and lymphnode biopsies was performed in 6 pigs, using Totally NOTES technique. The specimens were extracted transanally. The flexible endoscope was inserted through a posterior transmural incision and the retrorectal space. Cultures of bacteria were documented for the retroperitoneal space and intra abdominal cavity after 14 days. Rectal site was closed using non-absorbable sutures. There was no bowel cleansing, nor preoperative fasting. The procedures were performed in 6 pigs through transcolonic natural orifice access using available endoscopic flexible instruments. All animals survived 14 days without complications, and cultures were negative. Histopathologic examination of the rectal closure site showed adequate healing of suture line and no micro abscesses. The results of feasibility and safety of experimental Transcolonic NOTES potentially brings new frontiers and future wider applications for minimally invasive surgery. The treatment of colorectal, abdominal and retroperitoneal diseases through a flexible Perirectal NOTES Access (PNA) is a promising new approach.

Mars-Learning AN Open Access Educational Database

NASA Astrophysics Data System (ADS)

Kolankowski, S. M.; Fox, P. A.

2016-12-01

Schools across America have begun focusing more and more on science and technology, giving their students greater opportunities to learn about planetary science and engineering. With the development of rovers and advanced scientific instrumentation, we are learning about Mars' geologic history on a daily basis. These discoveries are crucial to our understanding of Earth and our solar system. By bringing these findings into the classroom, students can learn key concepts about Earth and Planetary sciences while focusing on a relevant current event. However, with an influx of readily accessible information, it is difficult for educators and students to find accurate and relevant material. Mars-Learning seeks to unify these discoveries and resources. This site will provide links to educational resources, software, and blogs with a focus on Mars. Activities will be grouped by grade for the middle and high school levels. Programs and software will be labeled, open access, free, or paid to ensure users have the proper tools to get the information they need. For new educators or those new to the subject, relevant blogs and pre-made lesson plans will be available so instructors can ensure their success. The expectation of Mars-Learning is to provide stress-free access to learning materials that falls within a wide range of curriculum. By providing a thorough and encompassing site, Mars-Learning hopes to further our understanding of the Red Planet and equip students with the knowledge and passion to continue this research.

Getting To Know the "Invisible Web."

ERIC Educational Resources Information Center

Smith, C. Brian

2001-01-01

Discusses the portions of the World Wide Web that cannot be accessed via directories or search engines, explains why they can't be accessed, and offers suggestions for reference librarians to find these sites. Lists helpful resources and gives examples of invisible Web sites which are often databases. (LRW)

Right Filter for the Wrong Addresses: Regulating Net Access.

ERIC Educational Resources Information Center

Simpson, Carol

1996-01-01

Guides librarians in evaluating "filtering" software which schools may purchase for restricting access to potentially inappropriate Internet sites. This article discusses the workings of filtering programs and practical and ethical questions such as: how sites are restricted, who decides, and whether transactions are monitored.…

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia

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

Titano, J. J., E-mail: joseph.titano@mountsinai.org; Biederman, D. M., E-mail: derek.biederman@mountsinai.org; Marinelli, B. S., E-mail: brett.marinelli@exchange.mssm.edu

PurposeTransradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions.Methods and MaterialsPatients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications.ResultsFrom July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µLmore » (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6 % with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9 %) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1 %) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups.ConclusionsTransradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.« less

Defining Long Term Goals and Setting Priorities for Education and Outreach, 2003 to 2013 - Panel Report

NASA Astrophysics Data System (ADS)

Grier, J. A.; Atkinson, D. H.; Barlow, N.; Griffin, I.; Hoffman, J.; Kelly-Serrato, B.; Kesthelyi, L.; Klein, M.; Klug, S.; Kolvoord, B.; Lanagan, P.; Lebofsky, L. A.; Lindstrom, M.; Lopes, R.; Lowes, L.; Manifold, J.; Mastrapa, R.; Milazzo, M.; Miner, E.; Morris, P.; Runyon, C.; Sohus, A.; Urquhart, M.; Warasila, R. L.; Withers, P.; Wood, Chuck

2001-11-01

Education and Public Outreach (E/PO) activities are an integral part of NASA's mandated mission and detailed in its Strategic Plan. The Office of Space Science Solar System Exploration (OSS SSE) E/PO program has made great strides in defining priorities and achieving its goals in the last five years. The Education and Public Outreach panel for NASA's Decadal Survey has generated a list of key issues to be addressed for the years 2003-2013 to assist the OSS SSE in future prioritization and planning. Key issues under discussion include: improving the involvement of planetary science professionals in E/PO activities; combating scientific elitism; examining the association between E/PO programs and public relations; re-examining funding E/PO activities from an audience perspective as opposed to a mission-centered perspective; improving access to resources for scientists, educators, students and partner organizations; promoting communication between educational programs at NASA; and reaching traditionally underrepresented groups, women, minorities and the disabled with science education programs. The panel is developing a list of specific recommendations to be implemented to improve OSS SSE E/PO activities in the next decade. These recommendations deal with topics such as: the production of evaluated resource web sites for scientists and educators; the development of a policy of long-term funding for the maintenance of web sites and other tools after they are created; methods for reaching those who do not have computer access through television and public programs; and the development of a reward system to recognize and encourage scientist involvement in E/PO activities. Such key issues and recommendations will be presented, along with materials from current programs and initiatives for E/PO in the OSS SSE.

Analysis of the Binding Moiety Mediating the Interaction between Monocarboxylate Transporters and Carbonic Anhydrase II*

PubMed Central

Noor, Sina Ibne; Dietz, Steffen; Heidtmann, Hella; Boone, Christopher D.; McKenna, Robert; Deitmer, Joachim W.; Becker, Holger M.

2015-01-01

Proton-coupled monocarboxylate transporters (MCTs) mediate the exchange of high energy metabolites like lactate between different cells and tissues. We have reported previously that carbonic anhydrase II augments transport activity of MCT1 and MCT4 by a noncatalytic mechanism, while leaving transport activity of MCT2 unaltered. In the present study, we combined electrophysiological measurements in Xenopus oocytes and pulldown experiments to analyze the direct interaction between carbonic anhydrase II (CAII) and MCT1, MCT2, and MCT4, respectively. Transport activity of MCT2-WT, which lacks a putative CAII-binding site, is not augmented by CAII. However, introduction of a CAII-binding site into the C terminus of MCT2 resulted in CAII-mediated facilitation of MCT2 transport activity. Interestingly, introduction of three glutamic acid residues alone was not sufficient to establish a direct interaction between MCT2 and CAII, but the cluster had to be arranged in a fashion that allowed access to the binding moiety in CAII. We further demonstrate that functional interaction between MCT4 and CAII requires direct binding of the enzyme to the acidic cluster 431EEE in the C terminus of MCT4 in a similar fashion as previously shown for binding of CAII to the cluster 489EEE in the C terminus of MCT1. In CAII, binding to MCT1 and MCT4 is mediated by a histidine residue at position 64. Taken together, our results suggest that facilitation of MCT transport activity by CAII requires direct binding between histidine 64 in CAII and a cluster of glutamic acid residues in the C terminus of the transporter that has to be positioned in surroundings that allow access to CAII. PMID:25561737

Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes

PubMed Central

Jack, Benjamin R.; Meyer, Austin G.; Echave, Julian; Wilke, Claus O.

2016-01-01

Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes. PMID:27138088

Apocalmodulin and Ca2+ calmodulin bind to the same region on the skeletal muscle Ca2+ release channel

NASA Technical Reports Server (NTRS)

Moore, C. P.; Rodney, G.; Zhang, J. Z.; Santacruz-Toloza, L.; Strasburg, G.; Hamilton, S. L.

1999-01-01

The skeletal muscle Ca2+ release channel (RYR1) is regulated by calmodulin in both its Ca2+-free (apocalmodulin) and Ca2+-bound (Ca2+ calmodulin) states. Apocalmodulin is an activator of the channel, and Ca2+ calmodulin is an inhibitor of the channel. Both apocalmodulin and Ca2+ calmodulin binding sites on RYR1 are destroyed by a mild tryptic digestion of the sarcoplasmic reticulum membranes, but calmodulin (either form), bound to RYR1 prior to tryptic digestion, protects both the apocalmodulin and Ca2+ calmodulin sites from tryptic destruction. The protected sites are after arginines 3630 and 3637 on RYR1. These studies suggest that both Ca2+ calmodulin and apocalmodulin bind to the same or overlapping regions on RYR1 and block access of trypsin to sites at amino acids 3630 and 3637. This sequence is part of a predicted Ca2+ CaM binding site of amino acids 3614-3642 [Takeshima, H., et al. (1989) Nature 339, 439-445].

Kidney Biopsy Adequacy: A Metric-based Study.

PubMed

Ferrer, German; Andeen, Nicole K; Lockridge, Joseph; Norman, Douglas; Foster, Bryan R; Houghton, Donald C; Troxell, Megan L

2018-06-05

There are differences in renal biopsy yield related to on-site evaluation, tissue division, and operator, among others. To understand these variations, we collected adequacy-associated data (%cortex, glomeruli, arteries, length) from consecutive native and allograft kidney biopsies over a 22-month period. In total, 1332 biopsies (native: 873, allograft: 459) were included, 617 obtained by nephrologists, 663 by radiologists, and 559 with access to on-site division. Proceduralists with access to on-site evaluation had significantly lower inadequacy rates and better division of tissue for light microscopy (LM), immunofluorescence, and electron microscopy than those without access to on-site evaluation. Radiologists in our region were significantly less likely to have access to on-site evaluation than nephrologists. On multivariate analysis for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to on-site division were both significant predictors of obtaining greater calculated amount of cortex for LM. Despite the trend for radiologists to obtain more tissue in general, biopsies from nephrologists contained a greater percentage of cortex and were more likely to be considered adequate for LM (native kidney inadequacy rate for LM: 1.11% vs. 5.41%, P=0.0086). Biopsies in which inadequate or marginal cortical tissue was submitted for LM had only minor decreases in the amount of cortex submitted for immunofluorescence and electron microscopy, revealing an opportunity for improved specimen triaging when limited tissue is obtained. In conclusion, both on-site evaluation/division and proceduralist significantly affect quantitative kidney biopsy metrics, which in turn affects the pathologist's ability to render an accurate diagnosis with appropriate prognostic information for the patient and treating nephrologist.

Molecular basis for TPR domain-mediated regulation of protein phosphatase 5.

PubMed

Yang, Jing; Roe, S Mark; Cliff, Matthew J; Williams, Mark A; Ladbury, John E; Cohen, Patricia T W; Barford, David

2005-01-12

Protein phosphatase 5 (Ppp5) is a serine/threonine protein phosphatase comprising a regulatory tetratricopeptide repeat (TPR) domain N-terminal to its phosphatase domain. Ppp5 functions in signalling pathways that control cellular responses to stress, glucocorticoids and DNA damage. Its phosphatase activity is suppressed by an autoinhibited conformation maintained by the TPR domain and a C-terminal subdomain. By interacting with the TPR domain, heat shock protein 90 (Hsp90) and fatty acids including arachidonic acid stimulate phosphatase activity. Here, we describe the structure of the autoinhibited state of Ppp5, revealing mechanisms of TPR-mediated phosphatase inhibition and Hsp90- and arachidonic acid-induced stimulation of phosphatase activity. The TPR domain engages with the catalytic channel of the phosphatase domain, restricting access to the catalytic site. This autoinhibited conformation of Ppp5 is stabilised by the C-terminal alphaJ helix that contacts a region of the Hsp90-binding groove on the TPR domain. Hsp90 activates Ppp5 by disrupting TPR-phosphatase domain interactions, permitting substrate access to the constitutively active phosphatase domain, whereas arachidonic acid prompts an alternate conformation of the TPR domain, destabilising the TPR-phosphatase domain interface.

Characterization of molecular interactions between Zika virus protease and peptides derived from the C-terminus of NS2B.

PubMed

Li, Yan; Loh, Ying Ru; Hung, Alvin W; Kang, CongBao

2018-06-21

Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad and NS2B cofactor region is important for protease folding and activity. A protease construct-eZiPro without the transmembrane domains of NS2B was designed. Structural study on eZiPro reveals that the Thr-Gly-Lys-Arg (TGKR) sequence at the C-terminus of NS2B binds to the active site after cleavage. The bZiPro construct only contains NS2B cofactor region and the N-terminus of NS3 without any artificial linker or protease cleavage site, giving rise to an empty pocket accessible to substrate and inhibitor binding. Herein, we demonstrate that the TGKR sequence of NS2B in eZiPro is dynamic. Peptides from NS2B with various lengths exhibit different binding affinities to bZiPro. TGKR binding to the active site in eZiPro does not affect protease binding to small-molecule compounds. Our results suggest that eZiPro will also be useful for evaluating small-molecule protease inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

Constitutive expression of human gastric lipase in Pichia pastoris and site-directed mutagenesis of key lid-stabilizing residues.

PubMed

Sams, Laura; Amara, Sawsan; Chakroun, Almahdi; Coudre, Sébastien; Paume, Julie; Giallo, Jacqueline; Carrière, Frédéric

2017-10-01

The cDNA encoding human gastric lipase (HGL) was integrated into the genome of Pichia pastoris using the pGAPZα A transfer vector. The HGL signal peptide was replaced by the yeast α-factor to achieve an efficient secretion. Active rHGL was produced by the transformed yeast but its levels and stability were dependent on the pH. The highest activity was obtained upon buffering the culture medium at pH5, a condition that allowed preserving enzyme activity over time. A large fraction (72±2%) of secreted rHGL remained however bound to the yeast cells, and was released by washing the cell pellet with an acid glycine-HCl buffer (pH2.2). This procedure allowed establishing a first step of purification that was completed by size exclusion chromatography. N-terminal sequencing and MALDI-ToF mass spectrometry revealed that rHGL was produced in its mature form, with a global mass of 50,837±32Da corresponding to a N-glycosylated form of HGL polypeptide (43,193Da). rHGL activity was characterized as a function of pH, various substrates and in the presence of bile salts and pepsin, and was found similar to native HGL, except for slight changes in pH optima. We then studied by site-directed mutagenesis the role of three key residues (K4, E225, R229) involved in salt bridges stabilizing the lid domain that controls the access to the active site and is part of the interfacial recognition site. Their substitution has an impact on the pH-dependent activity of rHGL and its relative activities on medium and long chain triglycerides. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural architecture of prothrombin in solution revealed by single molecule spectroscopy

DOE PAGES

Pozzi, Nicola; Bystranowska, Dominika; Zuo, Xiaobing; ...

2016-07-19

The coagulation factor prothrombin has a complex spatial organization of its modular assembly that comprises the N-terminal Gla domain, kringle-1, kringle-2, and the C-terminal protease domain connected by three intervening linkers. Here we use single molecule Förster resonance energy transfer to access the conformational landscape of prothrombin in solution and uncover structural features of functional significance that extend recent x-ray crystallographic analysis. Prothrombin exists in equilibrium between two alternative conformations, open and closed. The closed conformation predominates (70%) and features an unanticipated intramolecular collapse of Tyr 93 in kringle-1 onto Trp 547 in the protease domain that obliterates access tomore » the active site and protects the zymogen from autoproteolytic conversion to thrombin. The open conformation (30%) is more susceptible to chymotrypsin digestion and autoactivation, and features a shape consistent with recent x-ray crystal structures. Small angle x-ray scattering measurements of prothrombin wild type stabilized 70% in the closed conformation and of the mutant Y93A stabilized 80% in the open conformation directly document two envelopes that differ 50 Å in length. These findings reveal important new details on the conformational plasticity of prothrombin in solution and the drastic structural difference between its alternative conformations. Prothrombin uses the intramolecular collapse of kringle-1 onto the active site in the closed form to prevent autoactivation. As a result, the open-closed equilibrium also defines a new structural framework for the mechanism of activation of prothrombin by prothrombinase.« less

Well-integrity survey (Phase II) of abandoned homestead water wells in the High Plains aquifer, former Pantex Ordance Plant and Texas Tech Research Farm near Amarillo, Texas, 1995

USGS Publications Warehouse

Rivers, Glenn A.

1995-01-01

The existence of abandoned homestead sites was confirmed by remains of foundations and (or) wells at 13 of 18 locations. The existence of abandoned homestead sites was indicated by broken glass and pottery and miscellaneous debris at 3 of the 18 locations. No evidence of past homestead existence was found at 2 of the 18 locations. Eight water wells were found at seven of the abandoned homestead sites. Three of the eight wells are accessible to steel tape measurement—two are accessible to more than 297 feet below land surface and one is accessible to 277.8 feet below land surface. Of the five wells not accessible to steel tape measurement, three are closed at the surface and two are blocked by debris at 12 and 3 feet below land surface, respectively. Water levels were not detected in any well that was accessible by steel tape.

Telecommunications Network Plan

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

NONE

1989-05-01

The Office of Civilian Radioactive Waste Management (OCRWM) must, among other things, be equipped to readily produce, file, store, access, retrieve, and transfer a wide variety of technical and institutional data and information. The data and information regularly produced by members of the OCRWM Program supports, and will continue to support, a wide range of program activities. Some of the more important of these information communication-related activities include: supporting the preparation, submittal, and review of a license application to the Nuclear Regulatory Commission (NRC) to authorize the construction of a geologic repository; responding to requests for information from parties affectedmore » by and/or interested in the program; and providing evidence of compliance with all relevant Federal, State, local, and Indian Tribe regulations, statutes, and/or treaties. The OCRWM Telecommunications Network Plan (TNP) is intended to identify, as well as to present the current strategy for satisfying, the telecommunications requirements of the civilian radioactive waste management program. The TNP will set forth the plan for integrating OCRWM`s information resources among major program sites. Specifically, this plan will introduce a telecommunications network designed to establish communication linkages across the program`s Washington, DC; Chicago, Illinois; and Las Vegas, Nevada, sites. The linkages across these and associated sites will comprise Phase I of the proposed OCRWM telecommunications network. The second phase will focus on the modification and expansion of the Phase I network to fully accommodate access to the OCRWM Licensing Support System (LSS). The primary components of the proposed OCRWM telecommunications network include local area networks; extended local area networks; and remote extended (wide) area networks. 10 refs., 6 figs.« less

32 CFR 806.15 - FOIA exemptions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... safeguarding social security numbers (SSN). It states: “SSNs are personal and unique to each individual... accessible DoD web sites unless to do so is clearly authorized by law and implementing regulation and policy. Personal information should not be posted at nonpublicly accessible web sites unless it is mission...

1 CFR 301.1 - Establishment and location.

Code of Federal Regulations, 2012 CFR

2012-01-01

... information about the Conference either by accessing its Web site at http://www.acus.gov, by calling the Conference offices at (202) 480-2080, or by contacting [email protected]gov. The Conference's recommendations may be obtained by accessing its Web site or by visiting the reading room at its offices. ...

40 CFR 1400.3 - Public access to paper copies of off-site consequence analysis information.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Public access to paper copies of off-site consequence analysis information. 1400.3 Section 1400.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY AND DEPARTMENT OF JUSTICE ACCIDENTAL RELEASE PREVENTION REQUIREMENTS; RISK MANAGEMENT...

Site Environmental Report for 2004. Volume 1, Environment, Health, and Safety Division

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

None

2005-09-30

Each year, Ernest Orlando Lawrence Berkeley National Laboratory prepares an integrated report on its environmental programs to satisfy the requirements of United States Department of Energy Order 231.1A, Environment, Safety, and Health Reporting.1 The Site Environmental Report for 2004 summarizes Berkeley Lab’s environmental management performance, presents environmental monitoring results, and describes significant programs for calendar year 2004. (Throughout this report, Ernest Orlando Lawrence Berkeley National Laboratory is referred to as “Berkeley Lab,” “the Laboratory,” “Lawrence Berkeley National Laboratory,” and “LBNL.”) The report is separated into two volumes. Volume I contains an overview of the Laboratory, the status of environmental programs,more » and summarized results from surveillance and monitoring activities. Volume II contains individual data results from these activities. This year, the Site Environmental Report was distributed by releasing it on the Web from the Berkeley Lab Environmental Services Group (ESG) home page, which is located at http://www.lbl.gov/ehs/esg/. Many of the documents cited in this report also are accessible from the ESG Web page. CD and printed copies of this Site Environmental Report are available upon request.« less

A Multi-season Investigation of Microbial Extracellular Enzyme Activities in Two Temperate Coastal North Carolina Rivers: Evidence of Spatial but Not Seasonal Patterns.

PubMed

Bullock, Avery; Ziervogel, Kai; Ghobrial, Sherif; Smith, Shannon; McKee, Brent; Arnosti, Carol

2017-01-01

Riverine systems are important sites for the production, transport, and transformation of organic matter. Much of the organic matter processing is carried out by heterotrophic microbial communities, whose activities may be spatially and temporally variable. In an effort to capture and evaluate some of this variability, we sampled four sites-two upstream and two downstream-at each of two North Carolina rivers (the Neuse River and the Tar-Pamlico River) ca. twelve times over a time period of 20 months from 2010 to 2012. At all of the sites and dates, we measured the activities of extracellular enzymes used to hydrolyze polysaccharides and peptides, and thus to initiate heterotrophic carbon processing. We additionally measured bacterial abundance, bacterial production, phosphatase activities, and dissolved organic carbon (DOC) concentrations. Concurrent collection of physical data (stream flow, temperature, salinity, dissolved oxygen) enabled us to explore possible connections between physiochemical parameters and microbial activities throughout this time period. The two rivers, both of which drain into Pamlico Sound, differed somewhat in microbial activities and characteristics: the Tar-Pamlico River showed higher β-glucosidase and phosphatase activities, and frequently had higher peptidase activities at the lower reaches, than the Neuse River. The lower reaches of the Neuse River, however, had much higher DOC concentrations than any site in the Tar River. Both rivers showed activities of a broad range of polysaccharide hydrolases through all stations and seasons, suggesting that the microbial communities are well-equipped to access enzymatically a broad range of substrates. Considerable temporal and spatial variability in microbial activities was evident, variability that was not closely related to factors such as temperature and season. However, Hurricane Irene's passage through North Carolina coincided with higher concentrations of DOC at the downstream sampling sites of both rivers. This DOC maximum persisted into the month following the hurricane, when it continued to stimulate bacterial protein production and phosphatase activity in the Neuse River, but not in the Tar-Pamlico River. Microbial community activities are related to a complex array of factors, whose interactions vary considerably with time and space.

Systematic Perturbations of Binuclear Non-heme Iron Sites: Structure and Dioxygen Reactivity of de Novo Due Ferri Proteins.

PubMed

Snyder, Rae Ana; Betzu, Justine; Butch, Susan E; Reig, Amanda J; DeGrado, William F; Solomon, Edward I

2015-08-04

DFsc (single-chain due ferri) proteins allow for modeling binuclear non-heme iron enzymes with a similar fold. Three 4A → 4G variants of DFsc were studied to investigate the effects of (1) increasing the size of the substrate/solvent access channel (G4DFsc), (2) including an additional His residue in the first coordination sphere along with three additional helix-stabilizing mutations [3His-G4DFsc(Mut3)], and (3) the three helix-stabilizing mutations alone [G4DFsc(Mut3)] on the biferrous structures and their O2 reactivities. Near-infrared circular dichroism and magnetic circular dichroism (MCD) spectroscopy show that the 4A → 4G mutations increase coordination of the diiron site from 4-coordinate/5-coordinate to 5-coordinate/5-coordinate, likely reflecting increased solvent accessibility. While the three helix-stabilizing mutations [G4DFsc(Mut3)] do not affect the coordination number, addition of the third active site His residue [3His-G4DFsc(Mut3)] results in a 5-coordinate/6-coordinate site. Although all 4A→ 4G variants have significantly slower pseudo-first-order rates when reacting with excess O2 than DFsc (∼2 s(-1)), G4DFsc and 3His-G4DFsc(Mut3) have rates (∼0.02 and ∼0.04 s(-1)) faster than that of G4DFsc(Mut3) (∼0.002 s(-1)). These trends in the rate of O2 reactivity correlate with exchange coupling between the Fe(II) sites and suggest that the two-electron reduction of O2 occurs through end-on binding at one Fe(II) rather than through a peroxy-bridged intermediate. UV-vis absorption and MCD spectroscopies indicate that an Fe(III)Fe(III)-OH species first forms in all three variants but converts into an Fe(III)-μ-OH-Fe(III) species only in the 2-His forms, a process inhibited by the additional active site His ligand that coordinatively saturates one of the iron centers in 3His-G4DFsc(Mut3).

I need to know! Timely accessing of perioperative user manuals.

PubMed

Landreneau, Raphael

2010-12-01

Ready access to equipment or product information is essential for the safe operation of the many items that a perioperative nurse is asked to use, troubleshoot, or maintain. One institution's solution for making manufacturer information available in the practice setting was to create a facility intranet site dedicated to OR equipment manuals. This site provides information access to perioperative nurses and support staff members and, ultimately, helps improve patient care. Published by Elsevier Inc. All rights reserved.

Inhibitory Mechanism of Apigenin on α-Glucosidase and Synergy Analysis of Flavonoids.

PubMed

Zeng, Li; Zhang, Guowen; Lin, Suyun; Gong, Deming

2016-09-21

Inhibition of α-glucosidase activity may suppress postprandial hyperglycemia. The inhibition kinetic analysis showed that apigenin reversibly inhibited α-glucosidase activity with an IC50 value of (10.5 ± 0.05) × 10(-6) mol L(-1), and the inhibition was in a noncompetitive manner through a monophasic kinetic process. The fluorescence quenching and conformational changes determined by fluorescence and circular dichroism were due to the formation of an α-glucosidase-apigenin complex, and the binding was mainly driven by hydrophobic interactions and hydrogen bonding. The molecular simulation showed that apigenin bound to a site close to the active site of α-glucosidase, which may induce the channel closure to prevent the access of substrate, eventually leading to the inhibition of α-glucosidase. Isobolographic analysis of the interaction between myricetin and apigenin or morin showed that both of them exhibited synergistic effects at low concentrations and tended to exhibit additive or antagonistic interaction at high concentrations.

Web Accessibility and Accessibility Instruction

ERIC Educational Resources Information Center

Green, Ravonne A.; Huprich, Julia

2009-01-01

Section 508 of the Americans with Disabilities Act (ADA) mandates that programs and services be accessible to people with disabilities. While schools of library and information science (SLIS*) and university libraries should model accessible Web sites, this may not be the case. This article examines previous studies about the Web accessibility of…

Accessing Electronic Journals.

ERIC Educational Resources Information Center

McKay, Sharon Cline

1999-01-01

Discusses issues librarians need to consider when providing access to electronic journals. Topics include gateways; index and abstract services; validation and pay-per-view; title selection; integration with OPACs (online public access catalogs)or Web sites; paper availability; ownership versus access; usage restrictions; and services offered…

Exploring the Structure of the Voltage-gated Na+ Channel by an Engineered Drug Access Pathway to the Receptor Site for Local Anesthetics*

PubMed Central

Lukacs, Peter; Gawali, Vaibhavkumar S.; Cervenka, Rene; Ke, Song; Koenig, Xaver; Rubi, Lena; Zarrabi, Touran; Hilber, Karlheinz; Stary-Weinzinger, Anna; Todt, Hannes

2014-01-01

Despite the availability of several crystal structures of bacterial voltage-gated Na+ channels, the structure of eukaryotic Na+ channels is still undefined. We used predictions from available homology models and crystal structures to modulate an external access pathway for the membrane-impermeant local anesthetic derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel. Potassium channel-based homology models predict amino acid Ile-1575 in domain IV segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop selectivity filter. The mutation K1237E has been shown previously to increase the diameter of the selectivity filter. We found that an access pathway for external QX-222 created by mutations of Ile-1575 was abolished by the additional mutation K1237E, supporting the notion of a close spatial relationship between sites 1237 and 1575. Crystal structures of bacterial voltage-gated Na+ channels predict that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into the space between domain IV segment 6 and domain III pore-loop and, therefore, should obstruct the putative external access pathway. Indeed, mutations W1531A and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G created a second non-selective ion-conducting pore, bypassing the outer vestibule but probably merging into the internal vestibule, allowing for control by the activation gate. These data suggest a strong structural similarity between bacterial and eukaryotic voltage-gated Na+ channels. PMID:24947510

Environmental and policy factors related to physical activity in rural white women.

PubMed

Eyler, Amy A; Vest, Joshua R

2002-01-01

Physical activity is an important aspect of health promotion and disease prevention. However, women often have lower rates of physical activity than men. The purpose of this study was to identify environmental and policy determinants to physical activity among rural white women. Six focus groups were conducted with women aged 20-50 years who were not currently regular exercisers. Women reported that the social environment had a strong impact on physical activity level. Factors of the social environment included guilt, family responsibility, and social support. Environmental and policy barriers such as lack of access to places to exercise and safety concerns were also discussed. Intervention suggestions included family exercise and work-site programs. Information gained from this study can be used to fuel further research and inform future physical activity interventions.

Crystallographic analysis of 1,2,3-trichloropropane biodegradation by the haloalkane dehalogenase DhaA31.

PubMed

Lahoda, Maryna; Mesters, Jeroen R; Stsiapanava, Alena; Chaloupkova, Radka; Kuty, Michal; Damborsky, Jiri; Kuta Smatanova, Ivana

2014-02-01

Haloalkane dehalogenases catalyze the hydrolytic cleavage of carbon-halogen bonds, which is a key step in the aerobic mineralization of many environmental pollutants. One important pollutant is the toxic and anthropogenic compound 1,2,3-trichloropropane (TCP). Rational design was combined with saturation mutagenesis to obtain the haloalkane dehalogenase variant DhaA31, which displays an increased catalytic activity towards TCP. Here, the 1.31 Å resolution crystal structure of substrate-free DhaA31, the 1.26 Å resolution structure of DhaA31 in complex with TCP and the 1.95 Å resolution structure of wild-type DhaA are reported. Crystals of the enzyme-substrate complex were successfully obtained by adding volatile TCP to the reservoir after crystallization at pH 6.5 and room temperature. Comparison of the substrate-free structure with that of the DhaA31 enzyme-substrate complex reveals that the nucleophilic Asp106 changes its conformation from an inactive to an active state during the catalytic cycle. The positions of three chloride ions found inside the active site of the enzyme indicate a possible pathway for halide release from the active site through the main tunnel. Comparison of the DhaA31 variant with wild-type DhaA revealed that the introduced substitutions reduce the volume and the solvent-accessibility of the active-site pocket.

Structural asymmetry and intersubunit communication in muscle creatine kinase.

PubMed

Ohren, Jeffrey F; Kundracik, Melisa L; Borders, Charles L; Edmiston, Paul; Viola, Ronald E

2007-03-01

The structure of a transition-state analog complex of a highly soluble mutant (R134K) of rabbit muscle creatine kinase (rmCK) has been determined to 1.65 A resolution in order to elucidate the structural changes that are required to support and regulate catalysis. Significant structural asymmetry is seen within the functional homodimer of rmCK, with one monomer found in a closed conformation with the active site occupied by the transition-state analog components creatine, MgADP and nitrate. The other monomer has the two loops that control access to the active site in an open conformation and only MgADP is bound. The N-terminal region of each monomer makes a substantial contribution to the dimer interface; however, the conformation of this region is dramatically different in each subunit. Based on this structural evidence, two mutational modifications of rmCK were conducted in order to better understand the role of the amino-terminus in controlling creatine kinase activity. The deletion of the first 15 residues of rmCK and a single point mutant (P20G) both disrupt subunit cohesion, causing the dissociation of the functional homodimer into monomers with reduced catalytic activity. This study provides support for a structural role for the amino-terminus in subunit association and a mechanistic role in active-site communication and catalytic regulation.

Active Duty Access to Specialty Care Within the Great Plains Regional Medical Command: A Cost Benefit Analysis

DTIC Science & Technology

1998-06-01

Spondylosis of unspecified site without mention of myelopathy Scar conditions and fibrosis of skin Lumbar intervertebral disc without myelopathy Table 16...SOOH 20 HAND SURGERY MMU 17 PULMONARY DISEASE SOOL 13 DISC SURGERY ( LUMBAR ) MMC 12 CARDIOLOGY SSO 11 OPTHAMOLOGY MMR 10 RHEUMATOLOGY (Froom...SSU 56 Urology MMG 44 Gastroenterology MMC 43 Cardiology SOOL 43 Disk Surgery ( Lumbar ) SSR 42 Otorhinolaryngology MMO 37 Oncology (Medical) MMU

Occidental vertical modified in situ process for the recovery of oil from oil shale. Phase II. Quarterly progress report, September 1-November 30, 1979

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

McDermott, William F.

1979-12-01

The major activities at OOSI's Logan Wash site during the quarter were: driving the access drifts towards the underground locations for Retorts 7 and 8; manway raise boring; constructing the change house; rubbling the first lift of Mini-Retort (MR)1; preparing the Mini-Retorts for tracer testing; coring of Retort 3E; and beginning the DOE instrumentation program.

Protecting intellectual property associated with Canadian academic clinical trials - approaches and impact

PubMed Central

2012-01-01

Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation. The ‘open access’ approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism. The ‘restricted access’ approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who ‘needs to know’ about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial. It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results. PMID:23270486

Bringing home sustainability and climate change research and developments via on-line virtual reality

NASA Astrophysics Data System (ADS)

Granshaw, F. D.

2016-12-01

One of the key challenges of sustainability and climate education is one of accessibility. For example many of the sites where significant climate research is taking place in National Parks are largely inaccessible to the average park visitor. Likewise, taking students to visit exemplary efforts in environmentally sustainable design or habitat restoration projects may be logistically difficult or impossible for the average class. Yet despite these difficulties, finding ways to give students, park visitors, and the general public a chance to explore these areas is critical to their developing sustainability and climate literacy. To address this issue, the author has been working with National Park staff and community groups to develop desktop virtual reality environments that showcase glacier-climate research sites, developments designed with environmental sustainability in mind, and urban watersheds being rehabilitated by volunteer groups and public agencies. These environments provide the user with a chance to take a virtual walk through a site of interest, access data collected at the site, and even listen to researchers and site stewards talk about key activities taking place there. Though they are used as proxies for actual visits via independent on-line exploration, media for public talks, or the framework for student lab exercises, they these virtual environments have also been used to encourage and guide actual sites visits. A focus of this talk will be a recently launched project involving the construction of a library showcasing environmental sustainability projects in the Portland Metropolitan area. In addition to being a resource for local sustainability educators, the library will be a contribution to international sustainability education efforts as it is being developed under the umbrella of a UN affiliate (Greater Portland Sustainability Education Network).

Social networking site (SNS) use by adolescent mothers: Can social support and social capital be enhanced by online social networks? - A structured review of the literature.

PubMed

Nolan, Samantha; Hendricks, Joyce; Ferguson, Sally; Towell, Amanda

2017-05-01

to critically appraise the available literature and summarise the evidence relating to adolescent mothers' use of social networking sites in terms of any social support and social capital they may provide and to identify areas for future exploration. social networking sites have been demonstrated to provide social support to marginalised individuals and provide psycho-social benefits to members of such groups. Adolescent mothers are at risk of; social marginalisation; anxiety disorders and depressive symptoms; and poorer health and educational outcomes for their children. Social support has been shown to benefit adolescent mothers thus online mechanisms require consideration. a review of original research articles METHOD: key terms and Boolean operators identified research reports across a 20-year timeframe pertaining to the area of enquiry in: CINAHL, Cochrane Library, Medline, Scopus, ERIC, ProQuest, PsychINFO, Web of Science, Health Collection (Informit) and Google Scholar databases. Eight original research articles met the inclusion criteria for this review. studies demonstrate that adolescent mothers actively search for health information using the Internet and social networking sites, and that social support and social capital can be attributed to their use of specifically created online groups from within targeted health interventions. Use of a message board forum for pregnant and parenting adolescents also demonstrates elements of social support. There are no studies to date pertaining to adolescent mothers' use of globally accessible social networking sites in terms of social support provision and related outcomes. further investigation is warranted to explore the potential benefits of adolescent mothers' use of globally accessible social networking sites in terms of any social support provision and social capital they may provide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genome accessibility is widely preserved and locally modulated during mitosis

PubMed Central

Hsiung, Chris C.-S.; Morrissey, Christapher S.; Udugama, Maheshi; Frank, Christopher L.; Keller, Cheryl A.; Baek, Songjoon; Giardine, Belinda; Crawford, Gregory E.; Sung, Myong-Hee; Hardison, Ross C.

2015-01-01

Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements. PMID:25373146

Urban Environmental Excursions: Designing field trips to demonstrate sustainable connections between natural and engineered systems in urban environments

NASA Astrophysics Data System (ADS)

Lemke, L. D.

2012-12-01

Field trips are a proven and effective instructional tool to connect students with the world around them. In most communities, opportunities abound to allow students to make connections between concepts introduced in classroom or lab activities and the urban environment that surrounds them. Potential destinations include solid and liquid waste disposal sites, brownfield redevelopment sites, hazardous waste sites, industrial complexes, or sites with ongoing environmental restoration efforts. Each of these locations presents opportunities to explore sustainable aspects of anthropogenic activities in relation to the natural systems that they seek to modify or exploit. Early planning is essential, however, because it can sometimes take several months lead time to arrange for a large group tour of industrial or municipal sites. Several practices may be employed to design effective learning experiences for students when visiting such sites. These include: 1) choose local sites to keep trips relevant and practical; 2) balance sites of environmental concern with those where significant progress is being made in environmental restoration or stewardship; 3) connect sites with a pertinent theme (e.g., air quality, water quality, economic development, environmental justice, etc.); 4) develop a sense of location among student participants by providing a map showing the relationship between campus and the field sites; 5) prepare a guidebook containing one-page descriptions of each stop along with a list of questions to stimulate discussion and promote active engagement among all participants; 6) employ expert guides to maximize students' access to authoritative information; 7) tie each field experience to your curriculum; and 8) model active learning by asking genuine questions and engaging in open discussions with experts and student participants. In this presentation, urban field trip design will be illustrated with examples from trips run in conjunction with freshman-level introductory courses in Physical and Environmental Geology, as well as a junior-level course in Environmental Systems Analysis at Wayne State University in Detroit, Michigan, USA. Ties to environmental systems and sustainability, emphasizing systems boundaries, fluxes, and transformations of systems components, will be described along with logistical tips to help instructors prepare meaningful and memorable field trips.

Utilizing social networking sites to promote adolescents' health: a pragmatic review of the literature.

PubMed

Francomano, Jesse A; Harpin, Scott B

2015-01-01

Social networking site use has exploded among youth in the last few years and is being adapted as an important tool for healthcare interventions and serving as a platform for adolescents to gain access to health information. The aim of this study was to examine the strengths, weaknesses, and best practices of utilizing Facebook in adolescent health promotion and research via pragmatic literature review. We also examine how sites can facilitate ethically sound healthcare for adolescents, particularly at-risk youth. We conducted a literature review of health and social sciences literature from the past 5 years related to adolescent health and social network site use. Publications were grouped by shared content then categorized by themes. Five themes emerged: access to healthcare information, peer support and networking, risk and benefits of social network site use in care delivery, overcoming technological barriers, and social network site interventions. More research is needed to better understand how such Web sites can be better utilized to provide access to adolescents seeking healthcare. Given the broad reach of social network sites, all health information must be closely monitored for accurate, safe distribution. Finally, consent and privacy issues are omnipresent in social network sites, which calls for standards of ethical use.

Tracking the route of molecular oxygen in O2-tolerant membrane-bound [NiFe] hydrogenase

PubMed Central

Kalms, Jacqueline; Schmidt, Andrea; Utesch, Tillmann; von Stetten, David; van der Linden, Peter; Royant, Antoine; Mroginski, Maria Andrea; Carpentier, Philippe; Scheerer, Patrick

2018-01-01

[NiFe] hydrogenases catalyze the reversible splitting of H2 into protons and electrons at a deeply buried active site. The catalytic center can be accessed by gas molecules through a hydrophobic tunnel network. While most [NiFe] hydrogenases are inactivated by O2, a small subgroup, including the membrane-bound [NiFe] hydrogenase (MBH) of Ralstonia eutropha, is able to overcome aerobic inactivation by catalytic reduction of O2 to water. This O2 tolerance relies on a special [4Fe3S] cluster that is capable of releasing two electrons upon O2 attack. Here, the O2 accessibility of the MBH gas tunnel network has been probed experimentally using a “soak-and-freeze” derivatization method, accompanied by protein X-ray crystallography and computational studies. This combined approach revealed several sites of O2 molecules within a hydrophobic tunnel network leading, via two tunnel entrances, to the catalytic center of MBH. The corresponding site occupancies were related to the O2 concentrations used for MBH crystal derivatization. The examination of the O2-derivatized data furthermore uncovered two unexpected structural alterations at the [4Fe3S] cluster, which might be related to the O2 tolerance of the enzyme. PMID:29463722

The digital divide in public e-health: barriers to accessibility and privacy in state health department websites.

PubMed

West, Darrell M; Miller, Edward Alan

2006-08-01

State health departments have placed a tremendous amount of information, data, and services online in recent years. With the significant increase in online resources at official health sites, though, have come questions concerning equity of access and the confidentiality of electronic medical materials. This paper reports on an examination of public health department websites maintained by the 50 state governments. Using a content analysis of health department sites undertaken each year from 2000 to 2005, we investigate several dimensions of accessibility and privacy: readability levels, disability access, non-English accessibility, and the presence of privacy and security statements. We argue that although progress has been made at improving the accessibility and confidentiality of health department electronic resources, there remains much work to be done to ensure quality access for all Americans in the area of public e-health.

Optimization of Photoactive Protein Z for Fast and Efficient Site-Specific Conjugation of Native IgG

PubMed Central

2015-01-01

Antibody conjugates have been used in a variety of applications from immunoassays to drug conjugates. However, it is becoming increasingly clear that in order to maximize an antibody’s antigen binding ability and to produce homogeneous antibody-conjugates, the conjugated molecule should be attached onto IgG site-specifically. We previously developed a facile method for the site-specific modification of full length, native IgGs by engineering a recombinant Protein Z that forms a covalent link to the Fc domain of IgG upon exposure to long wavelength UV light. To further improve the efficiency of Protein Z production and IgG conjugation, we constructed a panel of 13 different Protein Z variants with the UV-active amino acid benzoylphenylalanine (BPA) in different locations. By using this panel of Protein Z to cross-link a range of IgGs from different hosts, including human, mouse, and rat, we discovered two previously unknown Protein Z variants, L17BPA and K35BPA, that are capable of cross-linking many commonly used IgG isotypes with efficiencies ranging from 60% to 95% after only 1 h of UV exposure. When compared to existing site-specific methods, which often require cloning or enzymatic reactions, the Protein Z-based method described here, utilizing the L17BPA, K35BPA, and the previously described Q32BPA variants, represents a vastly more accessible and efficient approach that is compatible with nearly all native IgGs, thus making site-specific conjugation more accessible to the general research community. PMID:25121619

Optimization of photoactive protein Z for fast and efficient site-specific conjugation of native IgG.

PubMed

Hui, James Z; Tsourkas, Andrew

2014-09-17

Antibody conjugates have been used in a variety of applications from immunoassays to drug conjugates. However, it is becoming increasingly clear that in order to maximize an antibody's antigen binding ability and to produce homogeneous antibody-conjugates, the conjugated molecule should be attached onto IgG site-specifically. We previously developed a facile method for the site-specific modification of full length, native IgGs by engineering a recombinant Protein Z that forms a covalent link to the Fc domain of IgG upon exposure to long wavelength UV light. To further improve the efficiency of Protein Z production and IgG conjugation, we constructed a panel of 13 different Protein Z variants with the UV-active amino acid benzoylphenylalanine (BPA) in different locations. By using this panel of Protein Z to cross-link a range of IgGs from different hosts, including human, mouse, and rat, we discovered two previously unknown Protein Z variants, L17BPA and K35BPA, that are capable of cross-linking many commonly used IgG isotypes with efficiencies ranging from 60% to 95% after only 1 h of UV exposure. When compared to existing site-specific methods, which often require cloning or enzymatic reactions, the Protein Z-based method described here, utilizing the L17BPA, K35BPA, and the previously described Q32BPA variants, represents a vastly more accessible and efficient approach that is compatible with nearly all native IgGs, thus making site-specific conjugation more accessible to the general research community.

Accredited hand surgery fellowship Web sites: analysis of content and accessibility.

PubMed

Trehan, Samir K; Morrell, Nathan T; Akelman, Edward

2015-04-01

To assess the accessibility and content of accredited hand surgery fellowship Web sites. A list of all accredited hand surgery fellowships was obtained from the online database of the American Society for Surgery of the Hand (ASSH). Fellowship program information on the ASSH Web site was recorded. All fellowship program Web sites were located via Google search. Fellowship program Web sites were analyzed for accessibility and content in 3 domains: program overview, application information/recruitment, and education. At the time of this study, there were 81 accredited hand surgery fellowships with 169 available positions. Thirty of 81 programs (37%) had a functional link on the ASSH online hand surgery fellowship directory; however, Google search identified 78 Web sites. Three programs did not have a Web site. Analysis of content revealed that most Web sites contained contact information, whereas information regarding the anticipated clinical, research, and educational experiences during fellowship was less often present. Furthermore, information regarding past and present fellows, salary, application process/requirements, call responsibilities, and case volume was frequently lacking. Overall, 52 of 81 programs (64%) had the minimal online information required for residents to independently complete the fellowship application process. Hand fellowship program Web sites could be accessed either via the ASSH online directory or Google search, except for 3 programs that did not have Web sites. Although most fellowship program Web sites contained contact information, other content such as application information/recruitment and education, was less frequently present. This study provides comparative data regarding the clinical and educational experiences outlined on hand fellowship program Web sites that are of relevance to residents, fellows, and academic hand surgeons. This study also draws attention to various ways in which the hand surgery fellowship application process can be made more user-friendly and efficient. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Self-assembly of protein-based biomaterials initiated by titania nanotubes.

PubMed

Forstater, Jacob H; Kleinhammes, Alfred; Wu, Yue

2013-12-03

Protein-based biomaterials are a promising strategy for creating robust highly selective biocatalysts. The assembled biomaterials must sufficiently retain the near-native structure of proteins and provide molecular access to catalytically active sites. These requirements often exclude the use of conventional assembly techniques, which rely on covalent cross-linking of proteins or entrapment within a scaffold. Here we demonstrate that titania nanotubes can initiate and template the self-assembly of enzymes, such as ribonuclease A, while maintaining their catalytic activity. Initially, the enzymes form multilayer thick ellipsoidal aggregates centered on the nanotube surface; subsequently, these nanosized entities assemble into a micrometer-sized enzyme material that has enhanced enzymatic activity and contains as little as 0.1 wt % TiO2 nanotubes. This phenomenon is uniquely associated with the active anatase (001)-like surface of titania nanotubes and does not occur on other anatase nanomaterials, which contain significantly fewer undercoordinated Ti surface sites. These findings present a nanotechnology-enabled mechanism of biomaterial growth and open a new route for creating stable protein-based biomaterials and biocatalysts without the need for chemical modification.

Structures of almond hydroxynitrile lyase isoenzyme 5 provide a rationale for the lack of oxidoreductase activity in flavin dependent HNLs.

PubMed

Pavkov-Keller, Tea; Bakhuis, Janny; Steinkellner, Georg; Jolink, Fenneke; Keijmel, Esther; Birner-Gruenberger, Ruth; Gruber, Karl

2016-10-10

Hydroxynitrile lyases (HNLs) catalyze the asymmetric addition of HCN to aldehydes producing enantiomerically pure cyanohydrins. These enzymes can be heterologously expressed in large quantities making them interesting candidates for industrial applications. The HNLs from Rosaceae evolved from flavin dependent dehydrogenase/oxidase structures. Here we report the high resolution X-ray structure of the highly glycosylated Prunus amygdalus HNL isoenzyme5 (PaHNL5 V317A) expressed in Aspergillus niger and its complex with benzyl alcohol. A comparison with the structure of isoenzyme PaHNL1 indicates a higher accessibility to the active site and a larger cavity for PaHNL5. Additionally, the PaHNL5 complex structure with benzyl alcohol was compared with the structurally related aryl-alcohol oxidase (AAO). Even though both enzymes contain an FAD-cofactor and histidine residues at crucial positions in the active site, PaHNL5 lacks the oxidoreductase activity. The structures indicate that in PaHNLs benzyl alcohol is bound too far away from the FAD cofactor in order to be oxidized. Copyright © 2016 Elsevier B.V. All rights reserved.

Using the WWW to Make YOHKOH SXT Images Available to the Public: The YOHKOH Public Outreach Project

NASA Astrophysics Data System (ADS)

Larson, M.; McKenzie, D.; Slater, T.; Acton, L.; Alexander, D.; Freeland, S.; Lemen, J.; Metcalf, T.

1997-05-01

The Yohkoh Public Outreach Project (YPOP) is funded by NASA as one of the Information Infrastructure Technology and Applications Cooperative Agreement Teams to create public access to high quality Yohkoh SXT data via the World Wide Web. These products are being made available to the scientific research community, K-12 schools, and informal education centers including planetaria, museums, and libraries. The project aims to utilize the intrinsic excitement of the SXT data, and in particular the SXT movies, to develop science learning tools and classroom activities. The WWW site at URL: http://www.space.lockheed.com/YPOP/ uses a movie theater theme to highlight available Yohkoh movies in a non-intimidating and entertaining format for non-scientists. The site features lesson plans, 'solar' activities, slide shows and, of course, a variety of movies about the Sun. Classroom activities are currently undergoing development with a team of scientists and K-12 teachers for distribution in late 1997. We will display the products currently online, which include a solar classroom with activities for teachers, background resources, and a virtual tour of our Sun.

An industry perspective on commercial radioactive waste disposal conditions and trends.

PubMed

Romano, Stephen A

2006-11-01

The United States is presently served by Class-A, -B and -C low-level radioactive waste and naturally-occurring and accelerator-produced radioactive material disposal sites in Washington and South Carolina; a Class-A and mixed waste disposal site in Utah that also accepts naturally-occurring radioactive material; and hazardous and solid waste facilities and uranium mill tailings sites that accept certain radioactive materials on a site-specific basis. The Washington site only accepts low-level radioactive waste from 11 western states due to interstate Compact restrictions on waste importation. The South Carolina site will be subject to geographic service area restrictions beginning 1 July 2008, after which only three states will have continued access. The Utah site dominates the commercial Class-A and mixed waste disposal market due to generally lower state fees than apply in South Carolina. To expand existing commercial services, an existing hazardous waste site in western Texas is seeking a Class-A, -B and -C and mixed waste disposal license. With that exception, no new Compact facilities are proposed. This fluid, uncertain situation has inspired national level rulemaking initiatives and policy studies, as well as alternative disposal practices for certain low-activity materials.

Prioritizing Sites for Protection and Restoration for Grizzly Bears (Ursus arctos) in Southwestern Alberta, Canada.

PubMed

Braid, Andrew C R; Nielsen, Scott E

2015-01-01

As the influence of human activities on natural systems continues to expand, there is a growing need to prioritize not only pristine sites for protection, but also degraded sites for restoration. We present an approach for simultaneously prioritizing sites for protection and restoration that considers landscape patterns for a threatened population of grizzly bears (Ursus arctos) in southwestern Alberta, Canada. We considered tradeoffs between bottom-up (food resource supply) and top-down (mortality risk from roads) factors affecting seasonal habitat quality for bears. Simulated annealing was used to prioritize source-like sites (high habitat productivity, low mortality risk) for protection, as well as sink-like sites (high habitat productivity, high mortality risk) for restoration. Priority source-like habitats identified key conservation areas where future developments should be limited, whereas priority sink-like habitats identified key areas for mitigating road-related mortality risk with access management. Systematic conservation planning methods can be used to complement traditional habitat-based methods for individual focal species by identifying habitats where conservation actions (both protection and restoration) have the highest potential utility.

Redirection of the Reaction Specificity of a Thermophilic Acetolactate Synthase toward Acetaldehyde Formation

PubMed Central

Cheng, Maria; Yoshiyasu, Hayato; Okano, Kenji; Ohtake, Hisao; Honda, Kohsuke

2016-01-01

Acetolactate synthase and pyruvate decarboxylase are thiamine pyrophosphate-dependent enzymes that convert pyruvate into acetolactate and acetaldehyde, respectively. Although the former are encoded in the genomes of many thermophiles and hyperthermophiles, the latter has been found only in mesophilic organisms. In this study, the reaction specificity of acetolactate synthase from Thermus thermophilus was redirected to catalyze acetaldehyde formation to develop a thermophilic pyruvate decarboxylase. Error-prone PCR and mutant library screening led to the identification of a quadruple mutant with 3.1-fold higher acetaldehyde-forming activity than the wild-type. Site-directed mutagenesis experiments revealed that the increased activity of the mutant was due to H474R amino acid substitution, which likely generated two new hydrogen bonds near the thiamine pyrophosphate-binding site. These hydrogen bonds might result in the better accessibility of H+ to the substrate-cofactor-enzyme intermediate and a shift in the reaction specificity of the enzyme. PMID:26731734