Sample records for analogue study sites

  1. Understanding Rubredoxin Redox Sites by Density Functional Theory Studies of Analogues

    PubMed Central

    Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko

    2012-01-01

    Determining the redox energetics of redox site analogues of metalloproteins is essential in unraveling the various contributions to electron transfer properties of these proteins. Since studies of the [4Fe-4S] analogues show that the energies are dependent on the ligand dihedral angles, broken symmetry density functional theory (BS-DFT) with the B3LYP functional and double-? basis sets calculations of optimized geometries and electron detachment energies of [1Fe] rubredoxin analogues are compared to crystal structures and gas-phase photoelectron spectroscopy data, respectively, for [Fe(SCH3)4]0/1-/2-, [Fe(S2-o-xyl2)]0/1-/2-, and Na+[Fe(S2-o-xyl)2]1-/2- in different conformations. In particular, the study of Na+[Fe(S2-o-xyl)2]1-/2- is the only direct comparison of calculated and experimental gas phase detachment energies for the 1-/2- couple found in the rubredoxins. These results show that variations in the inner sphere energetics by up to ~0.4 eV can be caused by differences in the ligand dihedral angles in either or both redox states. Moreover, these results indicate that the protein stabilizes the conformation that favors reduction. In addition, the free energies and reorganization energies of oxidation and reduction as well as electrostatic potential charges are calculated, which can be used as estimates in continuum electrostatic calculations of electron transfer properties of [1Fe] proteins. PMID:22881577

  2. The Rio Tinto Mars Analogue site: An extremophilic Raman spectroscopic study

    NASA Astrophysics Data System (ADS)

    Edwards, Howell G. M.; Vandenabeele, Peter; Jorge-Villar, Susana E.; Carter, Elizabeth A.; Perez, Fernando Rull; Hargreaves, Michael D.

    2007-12-01

    The Rio Tinto site is recognised as a terrestrial Mars analogue because of the presence of jarosite and related sulfates which have recently been identified by the NASA Mars Exploration Rover "Opportunity" in the El Capitan region of Meridiani Planum on Mars. It has long been known that acidophilic microbial action is responsible for the deep blood-red colour of the water in Rio Tinto, where the pH varies from about 1.5 to 3.0 and the water is rich in iron and sulfur. Following recent Raman spectroscopic characterisation of the mineral phases of the Rio Tinto system, we report here a study of the biological components found in several specimens of deposited minerals and near the waterside that were collected during a GeoRaman VI Conference organized field trip in 2006. Key biosignatures were found for carotenoids, scytonemin and mycosporine-like amino acids, which are indicative of the biological colonisation of exposed mineral substrates; information from this study will be useful for targeting Martian sites using a miniaturized Raman instrument where the biosignatures of relict or extant life could remain in the geological record.

  3. The Rio Tinto Mars analogue site: an extremophilic Raman spectroscopic study.

    PubMed

    Edwards, Howell G M; Vandenabeele, Peter; Jorge-Villar, Susana E; Carter, Elizabeth A; Perez, Fernando Rull; Hargreaves, Michael D

    2007-12-15

    The Rio Tinto site is recognised as a terrestrial Mars analogue because of the presence of jarosite and related sulfates which have recently been identified by the NASA Mars Exploration Rover "Opportunity" in the El Capitan region of Meridiani Planum on Mars. It has long been known that acidophilic microbial action is responsible for the deep blood-red colour of the water in Rio Tinto, where the pH varies from about 1.5 to 3.0 and the water is rich in iron and sulfur. Following recent Raman spectroscopic characterisation of the mineral phases of the Rio Tinto system, we report here a study of the biological components found in several specimens of deposited minerals and near the waterside that were collected during a GeoRaman VI Conference organized field trip in 2006. Key biosignatures were found for carotenoids, scytonemin and mycosporine-like amino acids, which are indicative of the biological colonisation of exposed mineral substrates; information from this study will be useful for targeting Martian sites using a miniaturized Raman instrument where the biosignatures of relict or extant life could remain in the geological record. PMID:17600759

  4. Gamma-ray characterization of uranium-series nuclides and its application to the study of the Pena Blanca natural analogue site, Chihuahua, Mexico

    NASA Astrophysics Data System (ADS)

    Wong, Virgina

    Two natural analogue sites located in the Pena Blanca Uranium District, Chihuahua, Mexico were characterized for radionuclide mobility. Analogue I is used to assess the long-term behavior of uranium-series nuclides in a host rock and geochemical environment that is similar to the proposed high-level waste repository at Yucca Mountain, Nevada. Analogue II represents a former dump site to assess short-term radionuclide mobility. Gamma-ray spectroscopy analysis was used to measure radioactivity of the U-series nuclides. Samples analyzed from Analogue I consist of: (1) fracture-infillings associated with different alteration assemblages collected within and outside the breccia pipe from various levels of the deposit and (2) fracture-infillings collected along an east-west trending fracture which intersects the breccia pipe and extends into the host rock. Alteration mineralogy, established via X-ray diffraction analysis, consists of pure kaolinite, a mixture of Fe-oxyhydroxide (goethite, hematite) With inclusions of jarosite and alunite, and carbonates. Results from activity ratios of 230Th/238U versus 226Ra/230Th indicate that majority of the Fe-oxyhydroxides from the breccia zone show a slight disequilibrium with respect to Ra enrichment and U depletion. This observation is modeled as requiring a multiple-event history of U mobility. An amorphous Fe sample distal to the breccia zone shows similar behavior but to a greater extent. This extreme behavior is ascribed to initially low U content and greater late-stage U removal. Two Fe-oxyhydroxide samples from Within the breccia pipe also display multiple-event stages but exhibit both Ra and U leaching. This behavior is shared by Fe-oxyhydroxide samples collected inside and peripheral to the breccia zone from the east-west trending fracture. Finally, three samples, two Fe phase samples outside the breccia zone and a kaolinite inside the breccia zone, show Ra and U enrichment. Also, a distal Fe-oxyhydroxide sample from the east-west fracture shares this mobility trend. The enrichment event is modeled as a single-stage Ra and U precipitation event. Activity results from surface samples collected from Analogue II strengthen the mobility trends documented from Analogue I. Isotopic data reveal leaching of U and Ra from the stockpile into the alluvium and bedrock. Thorium, on the other hand, has not experienced mobility. Lead exhibits variable mobility behavior. Correlation of isotope data with mineralogy indicates that the Fe-oxyhydroxide and clay minerals appear to be excellent scavengers of U. This observation has been documented in other natural analogue studies, for example, the Oklo natural reactor, the Pocos de Caldas Natural Analogue Project, the Koongarra U Deposit, and the Shinkolobwe U Deposit.

  5. /sup 1/H nuclear magnetic resonance studies of the conformation of an ATP analogue at the active site of Na,K-ATPase from kidney medulla

    SciTech Connect

    MacD. Stewart, J.M.; Grisham, C.M.

    1988-06-28

    /sup 1/H nuclear magnetic relaxation measurements have been used to determine the three-dimensional conformation of an ATP analogue, Co(NH/sub 3/)/sub 4/ATP, at the active site of sheep kidney Na,K-ATPase. Previous studies have shown that Co(NH/sub 4/)/sub 4/ATP is a competitive inhibitor with respect to MnATP for the Na,K-ATPase and that Mn/sup 2 +/ bound to a single, high-affinity site on the ATPase can be an effective paramagnetic probe for nuclear relaxation studies of the Na-K-ATPase. From the paramagnetic effect of Mn/sup 2 +/ bound to the APTase on the longitudinal relaxation rates of the protons of Co(NH/sub 3/)/sub 4/ATP at the substrate site (at 300 and 361 MHz), Mn-H distances to seven protons on the bound nucleotide were determined. Taken together with previous /sup 31/P nuclear relaxation data, these measurements are consistent with a single nucleotide conformation at the active site. The nucleotide adopts a bent configuration, in which the triphosphate chain lies nearly parallel to the adenine moiety. The glycosidic torsion angle is 35/sup 0/, and the conformation of the ribose ring is slightly N-type. The bound Mn/sup 2 +/ lies above and in the plane of the adenine ring. The distances from Mn/sup 2 +/ to N/sub 6/ and N/sub 7/ are too large for first coordination sphere complexes but are appropriate for second-sphere complexes involving, for example, intervening hydrogen-bonded water molecules. The NMR data also indicate that the structure of the bound ATP analogue is independent of the conformational state of the enzyme.

  6. X-ray absorption fine-structure spectroscopy studies of Fe sites in natural human neuromelanin and synthetic analogues.

    PubMed Central

    Kropf, A J; Bunker, B A; Eisner, M; Moss, S C; Zecca, L; Stroppolo, A; Crippa, P R

    1998-01-01

    X-ray absorption fine-structure spectroscopy is used to study the local environment of the iron site in natural (human) neuromelanin extracted from substantia nigra tissue and in various synthetic neuromelanins. All the materials show Fe centered in a nearest neighbor sixfold (distorted) oxygen octahedron; the Fe-O distances, while slightly different in the natural and synthetic neuromelanin, are both approximately 2.0 A. Appreciable differences arise, however, in the second (and higher) coordination shells. In this case the synthetic melanin has the four planar oxygens bound to carbon rings with Fe-C distances of approximately 2.82 and 4.13 A; the human sample does not show the 2.82 A link but instead indicates a double shell at approximately 3.45 and 3.78 A. PMID:9826634

  7. Multiple techniques for mineral identification on Mars:. a study of hydrothermal rocks as potential analogues for astrobiology sites on Mars

    NASA Astrophysics Data System (ADS)

    Bishop, Janice L.; Murad, Enver; Lane, Melissa D.; Mancinelli, Rocco L.

    2004-06-01

    Spectroscopic studies of Mars analog materials combining multiple spectral ranges and techniques are necessary in order to obtain ground truth information for interpretation of rocks and soils on Mars. Two hydrothermal rocks from Yellowstone National Park, Wyoming, were characterized here because they contain minerals requiring water for formation and they provide a possible niche for some of the earliest organisms on Earth. If related rocks formed in hydrothermal sites on Mars, identification of these would be important for understanding the geology of the planet and potential habitability for life. XRD, thermal properties, VNIR, mid-IR, and Raman spectroscopy were employed to identify the mineralogy of the samples in this study. The rocks studied here include a travertine from Mammoth Formation that contains primarily calcite with some aragonite and gypsum and a siliceous sinter from Octopus Spring that contains a variety of poorly crystalline to amorphous silicate minerals. Calcite was detected readily in the travertine rock using any one of the techniques studied. The small amount of gypsum was uniquely identified using XRD, VNIR, and mid-IR, while the aragonite was uniquely identified using XRD and Raman. The siliceous sinter sample was more difficult to characterize using each of these techniques and a combination of all techniques was more useful than any single technique. Although XRD is the historical standard for mineral identification, it presents some challenges for remote investigations. Thermal properties are most useful for minerals with discrete thermal transitions. Raman spectroscopy is most effective for detecting polarized species such as CO 3, OH, and CH, and exhibits sharp bands for most highly crystalline minerals when abundant. Mid-IR spectroscopy is most useful in characterizing Si-O (and metal-O) bonds and also has the advantage that remote information about sample texture (e.g., particle size) can be determined. Mid-IR spectroscopy is also sensitive to structural OH, CO 3, and SO 4 bonds when abundant. VNIR spectroscopy is best for characterizing metal excitational bands and water, and is also a good technique for identification of structural OH, CO 3, SO 4, or CH bonds. Combining multiple techniques provides the most comprehensive information about mineralogy because of the different selection rules and particle size sensitivities, in addition to maximum coverage of excitational and vibrational bands at all wavelengths. This study of hydrothermal rocks from Yellowstone provides insights on how to combine information from multiple instruments to identify mineralogy and hence evidence of water on Mars.

  8. Comparative studies of 193-nm photodissociation and TOF-TOFMS analysis of bradykinin analogues: The effects of charge site(s) and fragmentation timescales

    Microsoft Academic Search

    Joseph W. Morgan; David H. Russell

    2006-01-01

    The dissociation reactions of [M+H]+, [M+Na]+, and [M+Cu]+ ions of bradykinin (amino acid sequence RPPGFSPFR) and three bradykinin analogues (RPPGF, RPPGFSPF, PPGFSPFR) are examined by using 193-nm photodissociation and post-source decay (PSD) TOF-TOF-MS techniques. The photodissociation\\u000a apparatus is equipped with a biased activation cell, which allows us to detect fragment ions that are formed by dissociation\\u000a of short-lived (<1 µs)

  9. Space analogue studies in Antarctica

    NASA Astrophysics Data System (ADS)

    Lugg, D.; Shepanek, M.

    1999-09-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mltogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  10. Space analogue studies in Antarctica

    NASA Technical Reports Server (NTRS)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  11. Carbon storage at defect sites in mantle mineral analogues

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Buseck, Peter R.

    2013-10-01

    A significant fraction of Earth's carbon resides in the mantle, but the mode of carbon storage presents a long-standing problem. The mantle contains fluids rich in carbon dioxide and methane, carbonate-bearing melts, carbonate minerals, graphite, diamond and carbides, as well as dissolved carbon atoms in metals. However, it is uncertain whether these can sufficiently account for the total amount of carbon thought to be stored in the mantle and the volume of carbon degassed from the mantle at volcanoes. Moreover, such carbon hosts should significantly affect the physical and chemical behaviour of the mantle, including its melting temperature, electrical conductivity and oxidation state. Here we use in situ transmission electron microscopy to measure the storage of carbon within common mantle mineral analogues--nickel-doped lanthanum chromate perovskite and titanium dioxide--in laboratory experiments at high pressure and temperature. We detect elevated carbon concentrations at defect sites in the nanocrystals, maintained at high pressures within annealed carbon nanocages. Specifically, our experiments show that small stacking faults within the mantle analogue materials are effective carbon sinks at mantle conditions, potentially providing an efficient mechanism for carbon storage in the mantle. Furthermore, this carbon can be readily released under lower pressure conditions, and may therefore help to explain carbon release in volcanic eruptions.

  12. Upheaval Dome, An Analogue Site for Gale Center

    NASA Technical Reports Server (NTRS)

    Conrad, P. G.; Eignebrode, J. L.

    2011-01-01

    We propose Upheaval Dome in southeastern Utah as an impact analogue site on Earth to Mars Science Laboratory candidate landing site Gale Crater. The genesis of Upheaval Dome was a mystery for some time--originally thought to be a salt dome. The 5 km crater was discovered to possess shocked quartz and other shock metamorphic features just a few years ago, compelling evidence that the crater was formed by impact, although the structural geology caused Shoemaker and Herkenhoff to speculate an impact origin some 25 years earlier. The lithology of the crater is sedimentary. The oldest rocks are exposed in the center of the dome, upper Permian sandstones, and progressively younger units are well exposed moving outward from the center. These are Triassic sandstones, siltstones and shales, which are intruded by clastic dikes. There are also other clay-rich strata down section, as is the case with Gale Crater. There is significant deformation in the center of the crater, with folding and steeply tilted beds, unlike the surrounding Canyonlands area, which is relatively undeformed. The rock units are well exposed at Upheaval Dome, and there are shatter cones, impactite fragments, shocked quartz grains and melt rocks present. The mineral shock features suggest that the grains were subjected to dynamic pressures> 10 GPa.

  13. Spectroscopic study of solar twins and analogues

    NASA Astrophysics Data System (ADS)

    Datson, Juliet; Flynn, Chris; Portinari, Laura

    2015-02-01

    Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims: This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48 000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods: The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar analogues versus a reference solar reflection spectrum. Results: We derive spectroscopic parameters for 148 solar analogues (about 70 are new entries to the literature) and verify with a-posteriori differential tests that our values are well-centred on the solar values. We use our dataset to assess the two alternative calibrations of the GCS parameters; our methods favour the latest revision. We show that the choice of spectral line list or the choice of asteroid or time of observation does not affect the results. We also identify seven solar twins in our sample, three of which are published here for the first time. Conclusions: Our methods provide an independent means to differentially test the calibration of stellar catalogues around the values of a well-known benchmark star, which makes our work interesting for calibration tests of upcoming Galactic surveys. Based on observations made with ESO Telescopes at the La Silla Observatory under programme ID 077.D-0525 and 090.D-0133.Table 1 is also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/574/A124Full Table 5 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/574/A124

  14. The microbiology of the Maqarin site, Jordan -- A natural analogue for cementitious radioactive waste repositories

    SciTech Connect

    West, J.M.; Coombs, P.; Gardner, S.J.; Rochelle, C.A. [British Geological Survey, Keyworth (United Kingdom). Fluid Processes Group

    1995-12-31

    The Maqarin site, Jordan is being studied as a natural analogue of a cementitious radioactive waste repository. The microbiology has been studied and diverse microbial populations capable of tolerating alkaline pH were detected at all sampling localities. Dissolved organic carbon was identified as the potentially most important reductant with sulfate identified as the main oxidant, both supply energy for microbial life. Calculations on upper limits of microbial numbers were made with a microbiology code (MGSE) using existing information but the results are overestimates when compared with field observations. This indicates that the model is very conservative and that more information on, for example, carbon sources is required.

  15. NASA/ESMD Analogue Mission Plans

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  16. Preparing to return to the Moon: Lessons from science-driven analogue missions to the Mistastin Lake impact structure, Canada, a unique lunar analogue site

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Barfoot, T.; Chanou, A.; Daly, M. G.; Francis, R.; Hodges, K. V.; Jolliff, B. L.; Mader, M. M.; McCullough, E. M.; Moores, J. E.; Pickersgill, A.; Pontefract, A.; Preston, L.; Shankar, B.; Singleton, A.; Sylvester, P.; Tornabene, L. L.; Young, K. E.

    2013-12-01

    Impact cratering is the dominant geological process on the Moon, Near Earth Asteroids (NEAs) and the moons of Mars - the objectives for the new Solar System Exploration Research Virtual Institute (SSERVI). Led by members of the Canadian Lunar Research Network (CLRN), funded by the Canadian Space Agency, and with participants from the U.S., we carried out a series of analogue missions on Earth in order to prepare and train for future potential robotic and human sample return missions. Critically, these analogue missions were driven by the paradigm that operational and technical objectives are conducted while conducting new science and addressing real overarching scientific objectives. An overarching operational goal was to assess the utility of a robotic field reconnaissance mission as a precursor to a human sortie sample return mission. Here, we focus on the results and lessons learned from a robotic precursor mission and follow on human-robotic mission to the Mistastin Lake impact structure in Labrador, northern Canada (55°53'N; 63°18'W). The Mistastin structure was chosen because it represents an exceptional analogue for lunar craters. This site includes both an anorthositic target, a central uplift, well-preserved impact melt rocks - mostly derived from melting anorthosite - and is (or was) relatively unexplored. This crater formed ~36 million years ago and has a diameter of ~28 km. The scientific goals for these analogue missions were to further our understanding of impact chronology, shock processes, impact ejecta and potential resources within impact craters. By combining these goals in an analogue mission campaign key scientific requirements for a robotic precursor were determined. From the outset, these analogue missions were formulated and executed like an actual space mission. Sites of interest were chosen using remote sensing imagery without a priori knowledge of the site through a rigorous site selection process. The first deployment occurred in August and September 2010 and involved simulated robotic surveying of selected 'landing sites' at the Mistastin structure. The second deployment took place at the same location in 2011, which included simulated astronaut surface operations with, and without, the aid of a robotic assistant. A mission control team, based at the University of Western Ontario, London, Ontario, 1,900 km from the field site, oversaw operations. Our study showed the value of precursor reconnaissance missions in providing surface geology visualization at resolutions and from viewpoints not achievable from orbit, including high-resolution surface imagery on the scale of 10s of metres to kilometres. Indeed, data collected during the robotic precursor mission led to the formulation of a hypothesis that a large impact melt outcrop - named Discovery Hill - represents an impact melt pond in the terraced region of the crater, analogous to similar ponds of melt documented around the rim of well-preserved lunar craters such as Tycho. Further discoveries, that will be highlight here, include documentation of ejecta deposits for the first time at Mistastin, quantification of shock in anorthosites, and refined age estimates for the Mistastin impact event.

  17. Analogue sites for Mars missions: NASA's Mars Science Laboratory and beyond - Overview of an international workshop held at The Woodlands, Texas, on March 5-6, 2011

    NASA Astrophysics Data System (ADS)

    Hipkin, V. J.; Voytek, M. A.; Meyer, M. A.; Léveillé, R.; Domagal-Goldman, S. D.

    2013-06-01

    Recent research results from analogue sites, with a strong focus on astrobiology-related investigations, are presented in this special issue on 'Analogue sites for Mars missions'. In addition, this article describes workshop discussions and a resulting improved framework for reporting, evaluating, and comparing analogue sites. Developed through consideration of a broad range of sites, including many of those described in this special issue, this framework comprises an analogue site abstract, a rubric for the scientific evaluation of analogue sites, and a rubric for logistical information. An overview of the Mars Analogues Workshop is provided, and the rubrics are presented for further discussion.

  18. Ground water chemistry and geochemical modeling of water-rock interactions at the Osamu Utsumi mine and the Morro do Ferro analogue study sites, Poc??os de Caldas, Minas Gerais, Brazil

    USGS Publications Warehouse

    Nordstrom, D.K.; McNutt, R.H.; Puigdomenech, I.; Smellie, J.A.T.; Wolf, M.

    1992-01-01

    Surface and ground waters, collected over a period of three years from the Osamu Utsumi uranium mine and the Morro do Ferro thorium/rare-earth element (Th/REE) deposits, were analyzed and interpreted to identify the major hydrogeochemical processes. These results provided information on the current geochemical evolution of ground waters for two study sites within the Poc??os de Caldas Natural Analogue Project. The ground waters are a KFeSO4F type, a highly unusual composition related to intense weathering of a hydrothermally altered and mineralized complex of phonolites. Tritium and stable isotope data indicate that ground waters are of meteoric origin and are not affected significantly by evaporation or water-rock interactions. Recharging ground waters at both study sites demonstrate water of less than about 35 years in age, whereas deeper, more evolved ground waters are below 1 TU but still contain in most cases detectable tritium. These deeper ground waters may be interpreted as being of 35 to 60 or more years in age, resulting mainly from an admixture of younger with older ground waters and/or indicating the influence of subsurface produced tritium. Geochemical processes involving water-rock-gas interactions have been modeled using ground water compositions, mineralogic data, ion plots and computations of speciation, non-thermodynamic mass balance and thermodynamic mass transfer. The geochemical reaction models can reproduce the water chemistry and mineral occurrences and they were validated by comparing the results of thermodynamic mass transfer calculations (using the PHREEQE program, Parkhurst et al., 1980). The results from the geochemical reaction models reveal that the dominant processes are production of CO2 in the soil zone through aerobic decay of organic matter, dissolution of fluorite, calcite, K-feldspar, albite, chlorite and manganese oxides, oxidation of pyrite and sphalerite, and precipitation of ferric oxides, silica and kaolinite. Gibbsite precipitation can be modeled for the shallow (recharge) water chemistry at Morro do Ferro, consistent with known mineralogy. Recharge waters are undersaturated with respect to barite and discharging waters and deeper ground waters are saturated to supersaturated with respect to barite demonstrating a strong solubility control. Strontium isotope data demonstrate that sources other than calcium-bearing minerals are required to account for the dissolved strontium in the ground waters. These may include K-feldspar, smectite-chlorite mixed-layer clays and goyazite [SrAl3(PO4)2(OH)5??H2O]. ?? 1992.

  19. A Laboratory Analogue for the Study of Peer Sexual Harassment

    ERIC Educational Resources Information Center

    Mitchell, Damon; Hirschman, Richard; Angelone, D. J.; Lilly, Roy S.

    2004-01-01

    The purpose of this study was to develop a laboratory analogue for the study of peer sexual harassment, and to examine person and situational factors associated with male on female peer sexual harassment. One hundred twenty-two male participants were given the opportunity to tell jokes to a female confederate from a joke list that included…

  20. Site-specific incorporation of tryptophan analogues into recombinant proteins in bacterial cells.

    PubMed

    Kwon, Inchan; Tirrell, David A

    2007-08-29

    A designed yeast phenylalanyl-tRNA synthetase (yPheRS (T415G)) activates four tryptophan (Trp) analogues (6-chlorotryptophan (6ClW), 6-bromotryptophan (6BrW), 5-bromotryptophan (5BrW), and benzothienylalanine (BT)) that are not utilized by the endogenous E. coli translational apparatus. Introduction of yPheRS (T415G) and a mutant yeast phenylalanine amber suppressor tRNA (ytRNAPheCUA_UG) into an E. coli expression host allowed site-specific incorporation of three of these analogues (6ClW, 6BrW, and BT) into recombinant murine dihydrofolate reductase in response to amber stop codons with at least 98% fidelity. All three analogues were introduced at the Trp66 position in the chromophore of a cyan fluorescent protein variant (CFP6) to investigate the attendant changes in spectral properties. Each of the analogues caused blue shifts in the fluorescence emission and absorption maxima. The CFP6 variant bearing BT at position 66 exhibited an unusually large Stokes shift (56 nm). An expanded set of genetically encoded Trp analogues should enable the design of new proteins with novel spectral properties. PMID:17685515

  1. FIGIFIGO as a tool to characterize and identify planetary analogue sites

    NASA Astrophysics Data System (ADS)

    Gritsevich, M.; Peltoniemi, J.; Hakala, T.; Muinonen, K.

    2014-07-01

    We present an overview of the Finnish Geodetic Institute's field goniospectrometer (FIGIFIGO) and highlight its usability to study extraterrestrial analogues on the Earth. The design concept of this custom-made instrument has been proved to have a number of advantages, such as a well-adopted user-friendly interface, a high level of automation, and excellent suitability for field measurements within a wide range of weather conditions. It is perfect for collection of reference data on a given target in natural undisturbed (and well-recorded for further data interpretation) conditions. The instrument communicates via a controlled computer with an implemented simple and user-friendly interface. This allows users to easily set up optional parameters at the beginning of the measurement series. Thus a number of details may be modified, such as the initial position of the sensor, the range and speed of further automated zenith turns, and length of the turnable arm holding the selected optics (including an option for a computer-turned linear polarizer) above the target. The assembly and operation of the instrument are fast and efficient in both laboratory and field conditions. It is battery powered and easily portable, including possible transportation by plane, car, boat, or sledge. The system includes a sky camera to detect the goniometer orientation and a pyranometer to monitor the actual illumination conditions. A fine-tune mirror is used for spatial correction of the optics footprint. Recent calibration of the system has significantly increased the measurement robustness and data reliability, and has provided the operators with information on how to operate the instrument in the most efficient and accurate way. Measurement campaigns are organized frequently and significant amount of reference data has been already collected. The identification of new planetary analogue sites and characterization of known ones using FIGIFIGO could offer new possibilities and provide great insights for the planetary research community.

  2. Dynamics of water in prussian blue analogues: Neutron scattering study

    SciTech Connect

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Mukhopadhyay, R., E-mail: mukhop@barc.gov.in [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Juranyi, Fanni [Laboratory for Neutron Scattering, Paul Scherrer Institut, Villigen (Switzerland)

    2014-07-21

    Dynamics of crystal water in Prussian blue (PB), Fe(III){sub 4}[Fe(II)(CN){sub 6}]{sub 3}.14H{sub 2}O and its analogue Prussian green (PG), ferriferricynaide, Fe(III){sub 4}[Fe(III)(CN){sub 6}]{sub 4}.16H{sub 2}O have been investigated using Quasielastic Neutron Scattering (QENS) technique. PB and its analogue compounds are important materials for their various interesting multifunctional properties. It is known that crystal water plays a crucial role towards the multifunctional properties of Prussian blue analogue compounds. Three structurally distinguishable water molecules: (i) coordinated water molecules at empty nitrogen sites, (ii) non-coordinated water molecules in the spherical cavities, and (iii) at interstitial sites exist in PB. Here spherical cavities are created due to the vacant sites of Fe(CN){sub 6} units. However, PG does not have any such vacant N or Fe(CN){sub 6} units, and only one kind of water molecules, exists only at interstitial sites. QENS experiments have been carried out on both the compounds in the temperature range of 260–360?K to elucidate the dynamical behavior of different kinds of water molecules. Dynamics is found to be much more pronounced in case of PB, compared to PG. A detailed data analysis showed that localized translational diffusion model could describe the observed data for both PB and PG systems. The average diffusion coefficient is found to be much larger in the PB than PG. The obtained domain of dynamics is found to be consistent with the geometry of the structure of the two systems. Combining the data of the two systems, a quantitative estimate of the dynamics, corresponding to the water molecules at different locations is made.

  3. Reactive transport modeling of the clogging process at Maqarin natural analogue site

    NASA Astrophysics Data System (ADS)

    Shao, Haibing; Kosakowski, Georg; Berner, Urs; Kulik, Dmitrii A.; Mäder, Urs; Kolditz, Olaf

    The Maqarin site in Jordan has been investigated for three decades as a natural analogue for the long term changes of materials in contact with hyper-alkaline solutions. Similar processes are expected in radioactive waste disposal sites, where cement based materials are in contact with natural rocks or other e.g. clay based materials. In this context, a numerical reactive transport model was used to study local geochemical alterations and induced porosity changes for the Maqarin marl rock in contact with the hyper-alkaline solution. The geochemical setup for the rock mineralogy and the pore water was calibrated to match measurements from the Maqarin site. The setup includes several clay and zeolite minerals, considers cation exchange processes, and a state-of-the-art model for cement phases. Similar to earlier calculations by Steefel and Lichtner (1998) who used a much simpler geochemical model, the pore clogging occurred after several hundred years at a distance of 5-10 mm from the contact to the hyper-alkaline solution. In our calculations, this was caused by a massive precipitation of ettringite and C-S-H minerals. We performed a sensitivity study by varying the intrinsic diffusion coefficient, the Archie's law exponential factor, and the mineral surface area available for dissolution and precipitation. We found that the dissolution of clay minerals controls the availability of Al, which is needed for ettringite and C-S-H phase precipitation. Thus, the amount and kinetically controlled dissolution of clay minerals controls the spatial and temporal evolution of porosity changes. The simulations reveal that neither cation exchange processes nor the formation of zeolite minerals strongly influence the geochemical evolution of the system.

  4. Animal analogues for the study of dental and oral diseases.

    PubMed

    Levy, B M

    1980-01-01

    The usual laboratory animals, such as rats and hamsters, may not fit the criteria for an analogue of human periodontal disease, although they may be useful in the study of dental caries. Rats, hamsters, mice, guinea pigs and rabbits have been the animals of choice in studies relating nutritional deficiencies and excesses to the dental and oral tissues. Gerbils, dogs, cats, horses, cows and fowl are useful in the study of mineralized tissues of teeth and bones. Recently, primate analogues have been developed for the study of periodontal diseaes and dental caries, the two most important dental diseases afflicting man. The use of a wide variety of laboratory animals in basic dental research makes it timely to review some of the guidelines for the selection of specific animals for particular diseases. PMID:6772511

  5. Furan Decorated Nucleoside Analogues as Fluorescent Probes: synthesis, photophysical evaluation and site-specific incorporation

    PubMed Central

    Greco, Nicholas J.; Tor, Yitzhak

    2007-01-01

    The synthesis and photophysical evaluation of modified nucleoside analogues in which a five-membered heterocycle (furan, thiophene, oxazole and thiazole) is attached to the 5 position of 2?-deoxyuridine are reported. The furan containing derivative is identified as the most promising responsive nucleoside of this family due to its emission quantum efficiency and degree of sensitivity to its microenvironment. The furan moiety was then attached to the 5 position of 2?-deoxycytidine as well as the 8 position of adenosine and guanosine. Photophysical evaluation of these four furan containing nucleoside analogues reveal distinct differences in the absorption, emission and quantum efficiency depending upon the class of nucleoside (pyrimidine or purine). Comparing the photophysical properties of all furan containing nucleosides, identifies the furan thymidine analogue, 5-(fur-2-yl)-2?-deoxyuridine, as the best candidate for use as a responsive fluorescent probe in nucleic acids. 5-(fur-2-yl)-2?-deoxyuridine was then converted to the corresponding phosphoramidite and site specifically incorporated into DNA oligonucleotides with greater than 88% coupling efficiency. Such furan-modified oligonucleotides form stable duplexes upon hybridization to their complementary DNA strands and display favorable fluorescent features. PMID:18431439

  6. Scientific results and lessons learned from an integrated crewed Mars exploration simulation at the Rio Tinto Mars analogue site

    NASA Astrophysics Data System (ADS)

    Orgel, Csilla; Kereszturi, Ákos; Váczi, Tamás; Groemer, Gernot; Sattler, Birgit

    2014-02-01

    Between 15 and 25 April 2011 in the framework of the PolAres programme of the Austrian Space Forum, a five-day field test of the Aouda.X spacesuit simulator was conducted at the Rio Tinto Mars-analogue site in southern Spain. The field crew was supported by a full-scale Mission Control Center (MCC) in Innsbruck, Austria. The field telemetry data were relayed to the MCC, enabling a Remote Science Support (RSS) team to study field data in near-real-time and adjust the flight planning in a flexible manner. We report on the experiences in the field of robotics, geophysics (Ground Penetrating Radar) and geology as well as life sciences in a simulated spaceflight operational environment. Extravehicular Activity (EVA) maps had been prepared using Google Earth and aerial images. The Rio Tinto mining area offers an excellent location for Mars analogue simulations. It is recognised as a terrestrial Mars analogue site because of the presence of jarosite and related sulphates, which have been identified by the NASA Mars Exploration Rover "Opportunity" in the El Capitan region of Meridiani Planum on Mars. The acidic, high ferric-sulphate content water of Rio Tinto is also considered as a possible analogue in astrobiology regarding the analysis of ferric sulphate related biochemical pathways and produced biomarkers. During our Mars simulation, 18 different types of soil and rock samples were collected by the spacesuit tester. The Raman results confirm the presence of minerals expected, such as jarosite, different Fe oxides and oxi-hydroxides, pyrite and complex Mg and Ca sulphates. Eight science experiments were conducted in the field. In this contribution first we list the important findings during the management and realisation of tests, and also a first summary of the scientific results. Based on these experiences suggestions for future analogue work are also summarised. We finish with recommendations for future field missions, including the preparation of the experiments, communication and data transfer - as an aid to the planning of future simulations.

  7. Simulation and preparation of surface EVA in reduced gravity at the Marseilles Bay subsea analogue sites

    NASA Astrophysics Data System (ADS)

    Weiss, P.; Gardette, B.; Chirié, B.; Collina-Girard, J.; Delauze, H. G.

    2012-12-01

    Extravehicular activity (EVA) of astronauts during space missions is simulated nowadays underwater in neutral buoyancy facilities. Certain aspects of weightlessness can be reproduced underwater by adding buoyancy to a diver-astronaut, therefore exposing the subject to the difficulties of working without gravity. Such tests were done at the COMEX' test pool in Marseilles in the 1980s to train for a French-Russian mission to the MIR station, for the development of the European HERMES shuttle and the COLUMBUS laboratory. However, space agencies are currently studying missions to other destinations than the International Space Station in orbit, such as the return to the Moon, NEO (near-Earth objects) or Mars. All these objects expose different gravities: Moon has one sixth of Earth's gravity, Mars has a third of Earth's gravity and asteroids have virtually no surface gravity; the astronaut "floats" above the ground. The preparation of such missions calls for a new concept in neutral buoyancy training, not on man-made structures, but on natural terrain, underwater, to simulate EVA operations such as sampling, locomotion or even anchoring in low gravity. Underwater sites can be used not only to simulate the reduced gravity that astronauts will experience during their field trips, also human factors like stress are more realistically reproduced in such environment. The Bay of Marseille hosts several underwater sites that can be used to simulate various geologic morphologies, such as sink-holes which can be used to simulate astronaut descends into craters, caves where explorations of lava tubes can be trained or monolithic rock structures that can be used to test anchoring devices (e.g., near Earth objects). Marseilles with its aerospace and maritime/offshore heritage hosts the necessary logistics and expertise that is needed to perform such simulations underwater in a safe manner (training of astronaut-divers in local test pools, research vessels, subsea robots and submarines). COMEX is currently preparing a space mission simulation in the Marseilles Bay (foreseen in June 2012), and the paper will give an overview of the different underwater analogue sites that are available to the scientific community for the simulation of surface EVA or the test of scientific instruments and devices.

  8. Photochemical dihydrogen production using an analogue of the active site of [NiFe] hydrogenase.

    PubMed

    Summers, Peter A; Dawson, Joe; Ghiotto, Fabio; Hanson-Heine, Magnus W D; Vuong, Khuong Q; Davies, E Stephen; Sun, Xue-Z; Besley, Nicholas A; McMaster, Jonathan; George, Michael W; Schröder, Martin

    2014-05-01

    Photoproduction of dihydrogen (H2) by a low molecular weight analogue of the active site of [NiFe] hydrogenase has been investigated by reduction of the [NiFe2] cluster, 1, by a photosensitier PS (PS = [ReCl(CO)3(bpy)] or [Ru(bpy)3][PF6]2). Reductive quenching of the (3)MLCT excited state of the photosensitizer by NEt3 or N(CH2CH2OH)3 (TEOA) generates PS(•-), and subsequent intermolecular electron transfer to 1 produces the reduced anionic form of 1. Time-resolved infrared spectroscopy (TRIR) has been used to probe the intermediates throughout the reduction of 1 and subsequent photocatalytic H2 production from [HTEOA][BF4], which was monitored by gas chromatography. Two structural isomers of the reduced form of 1 (1a(•-) and 1b(•-)) were detected by Fourier transform infrared spectroscopy (FTIR) in both CH3CN and DMF (dimethylformamide), while only 1a(•-) was detected in CH2Cl2. Structures for these intermediates are proposed from the results of density functional theory calculations and FTIR spectroscopy. 1a(•-) is assigned to a similar structure to 1 with six terminal carbonyl ligands, while calculations suggest that in 1b(•-) two of the carbonyl groups bridge the Fe centers, consistent with the peak observed at 1714 cm(-1) in the FTIR spectrum for 1b(•-) in CH3CN, assigned to a ?(CO) stretching vibration. Formation of 1a(•-) and 1b(•-) and production of H2 was studied in CH3CN, DMF, and CH2Cl2. Although the more catalytically active species (1a(•-) or 1b(•-)) could not be determined, photocatalysis was observed only in CH3CN and DMF. PMID:24749646

  9. Rapid on-site detection of ephedrine and its analogues used as adulterants in slimming dietary supplements by TLC-SERS.

    PubMed

    Lv, Diya; Cao, Yan; Lou, Ziyang; Li, Shujin; Chen, Xiaofei; Chai, Yifeng; Lu, Feng

    2015-02-01

    Ephedrine and its analogues are in the list of prohibited substance in adulteration to botanical dietary supplements (BDS) for their uncontrollable stimulating side effects. However, they were always adulterated illegally in BDS to promote losing weight. In order to avoid detection, various kinds of ephedrine analogues were added rather than ephedrine itself. This has brought about great difficulties in authentication of BDS. In this study, we put forward for the first time a method which combined thin-layer chromatography (TLC) and surface-enhanced Raman scattering (SERS) to directly identify trace adulterant. Ephedrine, pseudoephedrine, methylephedrine, and norephedrine were mixed and used in this method to develop an analytical model. As a result, the four analogues were separated efficiently in TLC analysis, and trace-components and low-background SERS detection was realized. The limit of detection (LOD) of the four analogues was 0.01 mg/mL. Eight common Raman peaks (???=?620, 1003, 1030, 1159, 1181, 1205, 1454, 1603 cm(-1)) were extracted experimentally and statistically to characterize the common feature of ephedrine analogues. A TLC-SERS method coupled with common-peak model was adopted to examine nine practical samples, two of which were found to be adulterated with ephedrine analogues. Identification results were then confirmed by UPLC-QTOF/MS analysis. The proposed method was simple, rapid, and accurate and can also be employed to trace adulterant identification even when there are no available reference derivatives on-site or unknown types of ephedrine analogues are adulterated. PMID:25542571

  10. Multiphase flow above explosion sites in debris-filled volcanic vents: Insights from analogue experiments

    NASA Astrophysics Data System (ADS)

    Ross, Pierre-Simon; White, James D. L.; Zimanowski, Bernd; Büttner, Ralf

    2008-11-01

    Discrete explosive bursts are known from many volcanic eruptions. In maar-diatreme eruptions, they have occurred in debris-filled volcanic vents when magma interacted with groundwater, implying that material mobilized by such explosions passed through the overlying and enclosing debris to reach the surface. Although other studies have addressed the form and characteristics of craters formed by discrete explosions in unconsolidated material, no details are available regarding the structure of the disturbed debris between the explosion site and the surface. Field studies of diatreme deposits reveal cross-cutting, steep-sided zones of non-bedded volcaniclastic material that have been inferred to result from sedimentation of material transported by "debris jets" driven by explosions. In order to determine the general processes and deposit geometry resulting from discrete, explosive injections of entrained particles through a particulate host, we ran a series of analogue experiments. Specific volumes of compressed (0.5-2.5 MPa) air were released in bursts that drove gas-particle dispersions through a granular host. The air expanded into and entrained coloured particles in a small crucible before moving upward into the host (white particles). Each burst drove into the host an expanding cavity containing air and coloured particles. Total duration of each run, recorded with high-speed video, was approximately 0.5-1 s. The coloured beads sedimented into the transient cavity. This same behaviour was observed even in runs where there was no breaching of the surface, and no coloured beads ejected. A steep-sided body of coloured beads was left that is similar to the cross-cutting pipes observed in deposits filling real volcanic vents, in which cavity collapse can result not only from gas escape through a granular host as in the experiments, but also through condensation of water vapour. A key conclusion from these experiments is that the geometry of cross-cutting volcaniclastic deposits in volcanic vents is not directly informative of the geometry of the "intrusions" that formed them. An additional conclusion is that complex structures can form quickly from discrete events.

  11. Geochemistry of a continental site of serpentinization, the Tablelands Ophiolite, Gros Morne National Park: A Mars analogue

    NASA Astrophysics Data System (ADS)

    Szponar, Natalie; Brazelton, William J.; Schrenk, Matthew O.; Bower, Dina M.; Steele, Andrew; Morrill, Penny L.

    2013-06-01

    The presence of aqueously altered, olivine-rich rocks along with carbonate on Mars suggest that serpentinization may have occurred in the past and may be occurring presently in the subsurface, and possibly contributing methane (CH4) to the martian atmosphere. Serpentinization, the hydration of olivine in ultramafic rocks, yields ultra-basic fluids (pH ? 10) with unique chemistry (i.e. Ca2+-OH- waters) and hydrogen gas, which can support abiogenic production of hydrocarbons (i.e. Fischer-Tropsch Type synthesis) and subsurface chemosynthetic metabolisms. Mars analogue sites of present-day serpentinization can be used to determine what geochemical measurements are required for determining the source methane at sites of serpentinization on Earth and possibly on Mars. The Tablelands Ophiolite is a continental site of present-day serpentinization and a Mars analogue due to the presence of altered olivine-rich ultramafic rocks with both carbonate and serpentine signatures. This study describes the geochemical indicators of present-day serpentinization as evidenced by meteoric ultra-basic reducing groundwater discharging from ultramafic rocks, and travertine and calcium carbonate sediment, which form at the discharge points of the springs. Dissolved hydrogen concentrations (0.06-1.20 mg/L) and methane (0.04-0.30 mg/L) with ?13CCH4 values (-28.5‰ to -15.6‰) were measured in the spring fluids. Molecular and isotopic analyses of CH4, ethane, propane, butane, pentane and hexane suggest a non-microbial source of methane, and attribute the origin of methane and higher hydrocarbon gases to either thermogenic or abiogenic pathways.

  12. Natural analogue studies of the role of colloids, natural organics and microorganisms on radionuclide transport

    SciTech Connect

    McCarthy, J.F.

    1994-10-01

    Colloids may be important as a geochemical transport mechanism for radionuclides at geological repositories if they are (1) present in the groundwater, (2) stable with respect to both colloidal and chemical stabilities, (3) capable of adsorbing radionuclides, especially if the sorption is irreversible, and (4) mobile in the subsurface. The available evidence from natural analogue and other field studies relevant to these issues is reviewed, as is the potential role of mobile microorganisms ({open_quotes}biocolloids{close_quotes}) on radionuclide migration. Studies have demonstrated that colloids are ubiquitous in groundwater, although colloid concentrations in deep, geochemically stable systems may be too low to affect radionuclide transport. However, even low colloid populations cannot be dismissed as a potential concern because colloids appear to be stable, and many radionuclides that adsorb to colloids are not readily desorbed over long periods. Field studies offer somewhat equivocal evidence concerning colloid mobility and cannot prove or disprove the significance of colloid transport in the far-field environment. Additional research is needed at new sites to properly represent a repository far-field. Performance assessment would benefit from natural analogue studies to examine colloid behavior at sites encompassing a suite of probable groundwater chemistries and that mimic the types of formations selected for radioactive waste repositories.

  13. Molecular modeling of methyl-?-Neu5Ac analogues docked against cholera toxin - a molecular dynamics study.

    PubMed

    Blessy, J Jino; Sharmila, D Jeya Sundara

    2015-02-01

    Molecular modeling of synthetic methyl-?-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-?-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-?-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-?-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-?-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-?-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-?-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-?-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-?-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-?-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease. PMID:25676314

  14. Suramin and the suramin analogue NF307 discriminate among calmodulin-binding sites.

    PubMed Central

    Klinger, M; Bofill-Cardona, E; Mayer, B; Nanoff, C; Freissmuth, M; Hohenegger, M

    2001-01-01

    Calmodulin-binding sites on target proteins show considerable variation in primary sequence; hence compounds that block the access of calmodulin to these binding sites may be more selective than compounds that inactivate calmodulin. Suramin and its analogue NF307 inhibit the interaction of calmodulin with the ryanodine receptor. We have investigated whether inhibition of calmodulin binding to target proteins is a general property of these compounds. Suramin inhibited binding of [(125)I]calmodulin to porcine brain membranes and to sarcoplasmic reticulum from skeletal muscle (IC(50)=4.9+/-1.2 microM and 19.9+/-1.8 microM, respectively) and blocked the cross-linking of [(125)I]calmodulin to some, but not all, target proteins in brain membranes by [(125)I]calmodulin. Four calmodulin-binding proteins were purified [ryanodine receptor-1 (RyR1) from rabbit skeletal muscle, neuronal NO synthase (nNOS) from Sf9 cells, G-protein betagamma dimers (Gbetagamma) from porcine brain and a glutathione S-transferase-fusion protein comprising the C-terminal calmodulin-binding domain of the metabotropic glutamate receptor 7A (GST-CmGluR7A) from bacterial lysates]. Three of the proteins employed (Gbetagamma, GST-CmGluR7A and RyR1) display a comparable affinity for calmodulin (in the range of 50-70 nM). Nevertheless, suramin and NF307 only blocked the binding of Gbetagamma and RyR1 to calmodulin-Sepharose. In contrast, the association of GST-CmGluR7A and nNOS was not impaired, whereas excess calmodulin uniformly displaced all proteins from the matrix. Thus suramin and NF307 are prototypes of a new class of calmodulin antagonists that do not interact directly with calmodulin but with calmodulin-recognition sites. In addition, these compounds discriminate among calmodulin-binding motifs. PMID:11311147

  15. 2009 Arctic Mars Analogue Svalbard Expedition (AMASE) Evolved Gas Studies

    NASA Astrophysics Data System (ADS)

    Mahaffy, P. R.; McAdam, A.; Eigenbrode, J.; Steele, A.

    2009-12-01

    The Arctic Mars Analogue Svalbard Expedition (AMASE) continued its multi-year campaign in August 2009 to study selected sedimentary and igneous environments in this geological diverse archipelago using a variety of measurement techniques and protocols that are candidates for future Mars missions. The X-ray diffraction mineralogical and evolved gas analysis (EGA) employed during the AMASE-2009 campaign closely mimicked similar experiments that are planned for the 2011 Mars Science Laboratory (MSL). Field instruments similar to those under development for the ESA ExoMars or other rover missions provided imaging, spectroscopic, and subsurface sounding data. A variety of microbiology and field life detection techniques rounded out the AMASE-2009 analytical tools. The evolved gas mass spectrometer utilized on AMASE-2009 was designed to model elements of the Sample Analysis at Mars (SAM) suite of instruments on MSL. Powdered rock samples were heated from ambient to 1000 C in a helium stream and evolved gases continuously analyzed by a mass spectrometer. A continued focus of AMASE-2009 was analysis of carbonates from the Spitsbergen Sverrefjell volcano [1]. The similarity of macromolecular carbon (MMC) associated with magnetite in carbonate globules found in an ice cave in Sverrefjell to those studied in the Mars meteorite ALH84001 has been a motivation for their intensive study. The MMC associated with these carbonates appears to have been formed abiotically [2] following the eruption of the Sverrefjell volcano into glacial ice. The AMASE-2008 EGA studies of microsampled carbonate layers are described and the ability and limitations of these in situ tools to distinguish biomarkers. [1] H. Amundsen, Nature 327, 692-695 (1987). [2] A. Steele et al., Meteoritics and Planetary Science 42, 1549-1566 (2007) Acknowledgement: Support of this work is from the NASA ASTEP program with A. Steele AMASE PI and H. Amundsen Expedition lead.

  16. Emotions and Habitability study in Moon Mars Analogue.

    NASA Astrophysics Data System (ADS)

    Mertens, Alexandre; Lia Schlacht, Irene

    Euro Moon Mars mission have been conducted by students and field researchers in the Mars Desert Research Station (MDRS) a habitat installed by the Mars Society (MS) in the Utah desert. The campaign was supported by ILEWG International Lunar Exploration Working Group, ESTEC, NASA Ames, and partners. It investigated human aspects of isolation in a Mars analogue base. The project is in line with the ILEWG which coordinates several MDRS missions, and contributes to the preparation of future Mars sample return missions. The objective is to study and improve the habitat dynamics in a closed and small environment. Investigation cover different fields as emotional, sociological and psychological aspects and a food study but also habitability aspects. The study has been conducted by asking to the crew members to perform task and fill in questionnaires before, during and after the simulation. Video recovering, pictures and heart rate counting will also be used. One of the main study subject, conducted by Bernard Rimé, concerns the sharing of emotions in an isolated environ-e ment. Another is "Mars Habitability Experiment", which responsible is Irene Schlacht, will try to determine whether humans need variability of stimuli such as it happens in the natural environment -e.g. seasonal changing -to gain efficiency, reliability and well-being. This study have been conducted from February 19 to April 19 on two crews presenting different aspects that could lead to various behaviours. The first crew is made of people from different countries that don't know each other very well. On the opposite, the second crew members have the same cultural background -they come from the same country, university -and they know each other for at least six months. This allow studying how the extreme conditions of the isolation affect the crew efficiency, creativity and sanity according to its homogeneity. Report on the science and technical results, and implications for Earth-Mars comparative stud-ies, will be present. Main co-sponsors (SKOR, ILEWG, ESA ESTEC, COSPAR, DAAD, MARS SOCIETY).

  17. Multipurpose ligand, DAKLI (Dynorphin A-analogue Kappa LIgand), with high affinity and selectivity for dynorphin (. kappa. opioid) binding sites

    SciTech Connect

    Goldstein, A.; Nestor, J.J. Jr.; Naidu, A.; Newman, S.R. (Stanford Univ., CA (USA))

    1988-10-01

    The authors describe a synthetic ligand, DALKI (Dynorphin A-analogue Kappa LIgand), related to the opioid peptide dynorphin A. A single reactive amino group at the extended carboxyl terminus permits various reporter groups to be attached, such as {sup 125}I-labeled Bolton-Hunter reagent, fluorescein isothiocyanate, or biotin. These derivatives have high affinity and selectivity for the dynorphin ({kappa} opioid) receptor. An incidental finding is that untreated guinea pig brain membranes have saturable avidin binding sites.

  18. Martian Feeling: An Analogue Study to Simulate a Round-Trip to Mars using the International Space Station

    NASA Astrophysics Data System (ADS)

    Felix, C. V.; Gini, A.

    When talking about human space exploration, Mars missions are always present. It is clear that sooner or later, humanity will take this adventure. Arguably the most important aspect to consider for the success of such an endeavour is the human element. The safety of the crew throughout a Martian mission is a top priority for all space agencies. Therefore, such a mission should not take place until all the risks have been fully understood and mitigated. A mission to Mars presents unique human and technological challenges in terms of isolation, confinement, autonomy, reliance on mission control, communication delays and adaptation to different gravity levels. Analogue environments provide the safest way to simulate these conditions, mitigate the risks and evaluate the effects of long-term space travel on the crew. Martian Feeling is one of nine analogue studies, from the Mars Analogue Path (MAP) report [1], proposed by the TP Analogue group of ISU Masters class 2010. It is an integrated analogue study which simulates the psychological, physiological and operational conditions that an international, six-person, mixed gender crew would experience on a mission to Mars. Set both onboard the International Space Station (ISS) and on Earth, the Martian Feeling study will perform a ``dress rehearsal'' of a mission to Mars. The study proposes to test both human performance and operational procedures in a cost-effective manner. Since Low Earth Orbit (LEO) is more accessible than other space-based locations, an analogue studies in LEO would provide the required level of realism to a simulated transit mission to Mars. The sustained presence of microgravity and other elements of true spaceflight are features of LEO that are neither currently feasible nor possible to study in terrestrial analogue sites. International collaboration, economics, legal and ethical issues were considered when the study was proposed. As an example of international collaboration, the ISS would demonstrate an effective model for an international effort to send humans to Mars. The proposed starting date is the year 2017, before the planned retirement of the ISS, which is currently scheduled for 2020.

  19. Combined QM/MM Study of Thyroid and Steroid Hormone Analogue Interactions with ?v?3 Integrin

    PubMed Central

    Freindorf, Marek; Furlani, Thomas R.; Kong, Jing; Cody, Vivian; Davis, Faith B.; Davis, Paul J.

    2012-01-01

    Recent biochemical studies have identified a cell surface receptor for thyroid and steroid hormones that bind near the arginine-glycine-aspartate (RGD) recognition site on the heterodimeric ?v?3 integrin. To further characterize the intermolecular interactions for a series of hormone analogues, combined quantum mechanical and molecular mechanical (QM/MM) methods were used to calculate their interaction energies. All calculations were performed in the presence of either calcium (Ca2+) or magnesium (Mg2+) ions. These data reveal that 3,5?-triiodothyronine (T3) and 3,5,3?,5?-tetraiodothyroacetic acid (T4ac) bound in two different modes, occupying two alternate sites, one of which is along the Arg side chain of the RGD cyclic peptide site. These orientations differ from those of the other ligands whose alternate binding modes placed the ligands deeper within the RGD binding pocket. These observations are consistent with biological data that indicate the presence of two discrete binding sites that control distinct downstream signal transduction pathways for T3. PMID:22547930

  20. Using stressful films to analyze risk factors for PTSD in analogue experimental studies – which film works best?

    Microsoft Academic Search

    Anke Weidmann; Ania Conradi; Kathrin Gröger; Lydia Fehm; Thomas Fydrich

    2009-01-01

    To understand mental disorders, analogue paradigms provide an indispensable contribution. In posttraumatic stress disorder (PTSD), the stressful film paradigm is a frequently used analogue approach: Films depicting traumatic events are shown to non-clinical participants in order to elicit stress responses analogue to responses to traumatic events in real life. Previous studies used a large variety of films, which is problematic

  1. Natural analogue studies as supplements to biomineralization research

    SciTech Connect

    McNeil, M.B. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu{sub 4}SO{sub 4}(OH){sub 6{center_dot}}H{sub 2}O] and mineral morphologies unusual in corrosion [malachite, Cu{sub 2}CO{sub 3}(OH){sub 2}, rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena].

  2. Analogues of gamma-hydroxybutyric acid. Synthesis and binding studies.

    PubMed

    Bourguignon, J J; Schoenfelder, A; Schmitt, M; Wermuth, C G; Hechler, V; Charlier, B; Maitre, M

    1988-05-01

    Substituted 4-hydroxybutyric (GHB) or trans-4-hydroxycrotonic acids (T-HCA) and structurally related compounds were synthesized and submitted to [3H]GHB binding. Structure-activity relationships studies highlighted for [3H]GHB binding (a) the necessity of a nonlactonic, relatively extended conformation of the gamma-hydroxybutyric chain, (b) the existence of some bulk tolerance in the vicinity of the hydroxyl group, and (c) the high sensitivity toward isosteric replacements of the carboxyl or the hydroxyl groups. T-HCA has been recently identified as a naturally occurring substance in the central nervous system (CNS) and shows a better affinity than GHB. Our findings are in favor of the presence in the CNS of specific GHB binding sites, which are different from the GABA and the picrotoxin binding sites, and for which T-HCA may be an endogenous ligand. PMID:3361576

  3. The Manicouagan impact structure as a terrestrial analogue site for lunar and martian planetary science

    Microsoft Academic Search

    John G. Spray; Lucy M. Thompson; Marc B. Biren; Catherine O'Connell-Cooper

    2010-01-01

    The 90 km diameter, late Triassic Manicouagan impact structure of Québec, Canada, is a well-preserved, undeformed complex crater possessing an anorthositic central uplift and a 55 km diameter melt sheet. As such, it provides a valuable terrestrial analogue for impact structures developed on other planetary bodies, especially the Moon and Mars, which are currently the focus of exploration initiatives. The

  4. The Manicouagan impact structure as a terrestrial analogue site for lunar and martian planetary science

    Microsoft Academic Search

    John G. Spray; Lucy M. Thompson; Marc B. Biren; Catherine O’Connell-Cooper

    2010-01-01

    The 90km diameter, late Triassic Manicouagan impact structure of Québec, Canada, is a well-preserved, undeformed complex crater possessing an anorthositic central uplift and a 55km diameter melt sheet. As such, it provides a valuable terrestrial analogue for impact structures developed on other planetary bodies, especially the Moon and Mars, which are currently the focus of exploration initiatives. The scientific value

  5. Lithic microbial communities from a Mars analogue site in Utah desert

    NASA Astrophysics Data System (ADS)

    Rodrigues, L.; Foing, B. H.; Davies, G. R.; Stoker, C.; Clarke, J.; Correia, A.; Alves, A.

    2012-09-01

    Several rock samples have been collected as part of a Mars field analogue campaign (NASA DOMEXILEWG EuroMoonMars) at Mars Desert Research Station (MDRS) area (Utah Desert, USA), and were analyzed with respect to the microbial diversity they support; a culture-independent approach resulted in DGGE band profiles descriptive of the composition of the 3 domains, Bacteria, Archaea and Eukarya.

  6. Okinoshima site study

    NASA Astrophysics Data System (ADS)

    Yoshioka, Masakazu; Hasegawa, Takuya; Hirabayashi, Osamu; Kaneta, Tokiyoshi; Kawakami, Kiyokazu; Kimura, Nobuhiro; Maruyama, Takasumi; Nishikawa, Koichiro; Oshimo, Tetsunori; Rubbia, André; Taguchi, Satoshi; Tanaka, Masashi

    2011-07-01

    The Okinoshima Islands are located on an off-axis of 0.76 degree (almost on-axis) with the same neutrino beam setting as T2K (2.5 degree off- axis to Kamioka). The distance of Okinoshima from the neutrino source, KEK/J-PARC, is 658 km. This configuration enables to conduct precision measurement of the 1st and 2nd neutrino oscillation maxima of the appearance electron neutrino energy spectrum. We have made studies of the Okinoshima Island site from the geological, geographic and infrastructure points of view to investigate the possibility of building a large underground cavern there to install a 100 kton class Giant Liquid Argon Time Projection Chamber (TPC) detector for a neutrino oscillation and proton decay experiment. We have found that the Okinoshima Island site is a good candidate site for such an observatory.

  7. Mechanistic Studies of Substrate-assisted Inhibition of Ubiquitin-activating Enzyme by Adenosine Sulfamate Analogues

    PubMed Central

    Chen, Jesse J.; Tsu, Christopher A.; Gavin, James M.; Milhollen, Michael A.; Bruzzese, Frank J.; Mallender, William D.; Sintchak, Michael D.; Bump, Nancy J.; Yang, Xiaofeng; Ma, Jingya; Loke, Huay-Keng; Xu, Qing; Li, Ping; Bence, Neil F.; Brownell, James E.; Dick, Lawrence R.

    2011-01-01

    Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate intermediate and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2). MLN4924 is an adenosine sulfamate analogue that was identified as a selective, mechanism-based inhibitor of NEDD8-activating enzyme (NAE), another E1 enzyme, by forming a NEDD8-MLN4924 adduct that tightly binds at the active site of NAE, a novel mechanism termed substrate-assisted inhibition (Brownell, J. E., Sintchak, M. D., Gavin, J. M., Liao, H., Bruzzese, F. J., Bump, N. J., Soucy, T. A., Milhollen, M. A., Yang, X., Burkhardt, A. L., Ma, J., Loke, H. K., Lingaraj, T., Wu, D., Hamman, K. B., Spelman, J. J., Cullis, C. A., Langston, S. P., Vyskocil, S., Sells, T. B., Mallender, W. D., Visiers, I., Li, P., Claiborne, C. F., Rolfe, M., Bolen, J. B., and Dick, L. R. (2010) Mol. Cell 37, 102–111). In the present study, substrate-assisted inhibition of human UAE (Ube1) by another adenosine sulfamate analogue, 5?-O-sulfamoyl-N6-[(1S)-2,3-dihydro-1H-inden-1-yl]-adenosine (Compound I), a nonselective E1 inhibitor, was characterized. Compound I inhibited UAE-dependent ATP-PPi exchange activity, caused loss of UAE thioester, and inhibited E1-E2 transthiolation in a dose-dependent manner. Mechanistic studies on Compound I and its purified ubiquitin adduct demonstrate that the proposed substrate-assisted inhibition via covalent adduct formation is entirely consistent with the three-step ubiquitin activation process and that the adduct is formed via nucleophilic attack of UAE thioester by the sulfamate group of Compound I after completion of step 2. Kinetic and affinity analysis of Compound I, MLN4924, and their purified ubiquitin adducts suggest that both the rate of adduct formation and the affinity between the adduct and E1 contribute to the overall potency. Because all E1s are thought to use a similar mechanism to activate their cognate ubiquitin-like proteins, the substrate-assisted inhibition by adenosine sulfamate analogues represents a promising strategy to develop potent and selective E1 inhibitors that can modulate diverse biological pathways. PMID:21969368

  8. The Manicouagan impact structure as a terrestrial analogue site for lunar and martian planetary science

    NASA Astrophysics Data System (ADS)

    Spray, John G.; Thompson, Lucy M.; Biren, Marc B.; O'Connell-Cooper, Catherine

    2010-03-01

    The 90 km diameter, late Triassic Manicouagan impact structure of Québec, Canada, is a well-preserved, undeformed complex crater possessing an anorthositic central uplift and a 55 km diameter melt sheet. As such, it provides a valuable terrestrial analogue for impact structures developed on other planetary bodies, especially the Moon and Mars, which are currently the focus of exploration initiatives. The scientific value of Manicouagan has recently been enhanced due to the production, between 1994 and 2006, of ˜18 km of drill core from 38 holes by the mineral exploration industry. Three of these holes are in excess of 1.5 km deep, with the deepest reaching 1.8 km. Here we combine recent field work, sampling and the drill core data with previous knowledge to provide insight into processes occurring at Manicouagan and, by inference, within extraterrestrial impact structures. Four areas of comparative planetology are discussed: impact melt sheets, central uplifts, impact-generated hydrothermal regimes and footwall breccias. Human training and instrument testing opportunities are also considered. The drill core reveals that the impact melt and clast-bearing impact melts in the centre of the structure reach thicknesses of 1.4 km. The 1.1 km thick impact melt has undergone differentiation to yield a lower monzodiorite, a transitional quartz monzodiorite and an upper quartz monzonite sequence. This calls into question the previous citing of Manicouagan as an exemplar of a relatively large crater possessing an undifferentiated melt sheet, which was used as a rationale for assigning different composition lunar impact melts and clast-bearing impact melts to separate cratering events. The predominantly anorthositic central uplift at Manicouagan is comparable to certain lunar highlands material, with morphometric analogies to the King, Tycho, Pythagoras, Jackson, and Copernicus impact structures, which have similar diameters and uplift structure. Excellent exposure of the Manicouagan uplift facilitates mapping and an appraisal of its formation and collapse mechanisms, enhanced by drill core data from the centre of the structure. Recent field studies at the edge of the central island at Manicouagan, and multiple drill core sections through footwall lithologies, provide insight into allochthonous (clastic and suevitic) and autochthonous breccia formation, as well as shock effects. The hydrothermal regimes developed at Manicouagan are akin to systems proposed for Noachian (>3.5 Ga) Mars that involve alteration of impact melts via meteoritic and surface waters, with the generation of phyllosilicates, zeolites, hematite, sulfates and sulfides that can contribute to martian soil formation and sedimentation processes.

  9. What can be learned from natural analogues studies in view of CO2 leakage issues in1 Carbon Capture and Storage applications? Geochemical case study of Sainte-2

    E-print Network

    Paris-Sud XI, Université de

    What can be learned from natural analogues studies in view of CO2 leakage issues in1 Carbon Capture.34 35 Keywords36 Natural analogue37 Carbon Capture and Storage38 Soil gas monitoring39 Water monitoring

  10. Novel biological effects of alloferon and its selected analogues: structure-activity study.

    PubMed

    Kuczer, Mariola; Czarniewska, El?bieta; Rosi?ski, Grzegorz

    2013-05-10

    The subject of this paper is a search for new biological properties of alloferon (H-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly-OH) and a series of its analogues. The studies on structure/activity relationship in alloferon, the synthesis of a series of 28 analogues were performed. The analogues were modified at position 1 or 6, and other were oligopeptides with a shortened peptide sequence. Biological effects of the peptides were evaluated by the pro-apoptotic action in vivo on haemocytes of Tenebrio molitor and in the cardiotropic test in vitro on the heart of T. molitor and Zophobas atratus. In the in vivo bioassays, new biological activities of alloferon and its analogues were discovered. In haemocytotoxic bioassay, alloferon strongly induces T. molitor haemocytes to undergo apoptosis at a dose of 10 nM. Moreover, [Phe(p-NH2)(1)]-, [Tyr(6)]- and [1-10]-alloferon exhibit a two-fold increase of caspases activation in comparison with the alloferon. However, alloferon and its analogues show a weak cardiostimulatory activity in Z. atratus but the heart of T. molitor is not sensitive to these peptides. The results obtained here suggest that alloferon plays pleiotropic functions in insects. PMID:23499798

  11. Theoretical study on absorption and emission spectra of pyrrolo-C analogues

    NASA Astrophysics Data System (ADS)

    Liu, Hongxia; Liu, Jianhua; Yang, Yan; Li, Yan; Wang, Haijun

    2015-01-01

    Fluorescent nucleoside analogues have attracted much attention in studying the structure and dynamics of nucleic acids in recent years. In the present work, we use theoretical calculations to investigate the structural and optical properties of Pyrrolo-C (PyC) and its analogues which are modified via the conjugation or fusion of different aromatic ring to the PyC core. We also consider the effects of aqueous solution and base pairing. The results show that the fluorescent pyrrolo-C analogues can pair with guanosine to form stable H-bonded WC base pairs. The calculated absorption peaks of modified deoxyribonucleosides agree well with the measured data. The absorption and emission maxima of the pyrrolo-C analogues are greatly red shifted compared with nature C. The solvent effects can induce wavelength blue shift and increase the oscillator strengths in both the absorption and emission spectra. With regard to the WC base pairs, the B3LYP functional reveals that the lowest energy transitions of modified GC base pairs are charge transfer excitation while the CAM-B3LYP functional predicts that all the lowest transitions are localised on the pyrrolo-C analogues. The M062X and CAM-B3LYP functionals show good agreement with respect to both the value of the lowest energy transitions as well as the oscillator strengths.

  12. The interaction of new piroxicam analogues with lipid bilayers--a calorimetric and fluorescence spectroscopic study.

    PubMed

    Maniewska, Jadwiga; Szcz??niak-Si?ga, Berenika; Po?a, Andrzej; Sroda-Pomianek, Kamila; Malinka, Wies?aw; Michalak, Krystyna

    2014-01-01

    The purpose of the present paper was to assess the ability of new piroxicam analogues to interact with the lipid bilayers. The results of calorimetric and fluorescence spectroscopic experiments of two new synthesized analogues of piroxicam, named PR17 and PR18 on the phase behavior of phospholipid bilayers and fluorescence quenching of fluorescent probes (Laurdan and Prodan), which molecular location within membranes is known with certainty, are shown in present work. The presented results revealed that, depending on the details of chemical structure, the studied compounds penetrated the lipid bilayers. PMID:25856831

  13. Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

    PubMed Central

    Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, Christopher J.; Turkenburg, Johan P.; Jirá?ek, Ji?í; Brzozowski, Andrzej M.

    2014-01-01

    The structural characterization of the insulin–insulin receptor (IR) interaction still lacks the conformation of the crucial B21–B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms. PMID:25286859

  14. Gas geochemistry of natural analogues for the studies of geological CO 2 sequestration

    Microsoft Academic Search

    N. Voltattorni; A. Sciarra; G. Caramanna; D. Cinti; L. Pizzino; F. Quattrocchi

    2009-01-01

    Geological sequestration of anthropogenic CO2 appears to be a promising method for reducing the amount of greenhouse gases released to the atmosphere. Geochemical modelling of the storage capacity for CO2 in saline aquifers, sandstones and\\/or carbonates should be based on natural analogues both in situ and in the laboratory. The main focus of this paper has been to study natural

  15. A photoactive isoprenoid diphosphate analogue containing a stable phosphonate linkage: synthesis and biochemical studies with prenyltransferases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A number of biochemical processes rely on isoprenoids, including the post-translational modification of signaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and pren...

  16. A new method for studying pituitary responsiveness in vivo using pulses of LH-RH analogue

    E-print Network

    Paris-Sud XI, Université de

    pituitary gland (for review : Martin, 1984). However, it has been difficult to determine experimentally Agricultural Research Centre, Private Bag, Mosgiel, New Zealand. #12;pituitary glands, the surgery is complexA new method for studying pituitary responsiveness in vivo using pulses of LH-RH analogue in ewes

  17. Attributions about Perpetrators and Victims of Interpersonal Abuse: Results from an Analogue Study

    ERIC Educational Resources Information Center

    Langhinrichsen-Rohling, Jennifer; Shlien-Dellinger, Rania K.; Huss, Matthew T.; Kramer, Vertrie L.

    2004-01-01

    This analogue study (written vignettes and videotapes) examines the influence of victim-perpetrator relationship (spouse or acquaintance), sex of perceiver, and type of abuse (psychological vs. physical) on attributions about victims and perpetrators of domestic abuse. College student participants (73 men, 108 women) were randomly assigned to…

  18. In vitro studies of antifreeze glycoprotein (AFGP) and a C-linked AFGP analogue.

    PubMed

    Liu, Suhuai; Wang, Wenjun; Moos, Elisabeth von; Jackman, Jessica; Mealing, Geoff; Monette, Robert; Ben, Robert N

    2007-05-01

    Antifreeze glycoproteins (AFGPs) are a subclass of biological antifreezes found in deep sea Teleost fish. These compounds have the ability to depress the freezing point of the organism such that it can survive the subzero temperatures encountered in its environment. This physical property is very attractive for the cryopreservation of cells, tissues, and organs. Recently, our laboratory has designed and synthesized a functional carbon-linked (C-linked) AFGP analogue (1) that demonstrates tremendous promise as a novel cryoprotectant. Herein we describe the in vitro effects and interactions of C-linked AFGP analogue 1 and native AFGP 8. Our studies reveal that AFGP 8 is cytotoxic to human embryonic liver and human embryonic kidney cells at concentrations higher than 2 and 0.63 mg/mL, respectively, whereas lower concentrations are not toxic. The mechanism of this cytotoxicity is consistent with apoptosis because caspase-3/7 levels are significantly elevated in cell cultures treated with AFGP 8. In contrast, C-linked AFGP analogue 1 displayed no in vitro cytotoxicity even at high concentrations, and notably, caspase-3/7 activities were suppressed well below background levels in cell lines treated with 1. Although the results from these studies limit the human applications of native AFGP, they illustrate the benefits of developing functional C-linked AFGP analogues for various medical, commercial and industrial applications. PMID:17411090

  19. A new analogue computer for the study of pumping tests under falling water-table conditions

    NASA Astrophysics Data System (ADS)

    Herbert, Robin; Croxford, Russell

    1986-01-01

    A new electrical analogue can simulate the continuous fall of the water table around a pumping well. Solid state switching devices follow the fall of the water table, and well water level cutting out that area of the resistor mesh above the saturated zone. Three pumping tests in aquifers of increasing complexity are simulated; these show how early-time behaviour in pumping tests can be affected significantly by well storage and aquifer compressibility in unconfined aquifers. Also, predicted drawdowns, when large, are significantly different from those predicted using most commonly used theoretical methods. In addition, these simulations confirm there are significant vertical head gradients during the early phases of a pumping test. These vertical gradients must affect behaviour of observation wells which have long, perforated screens. Such complexities can now be studied in detail without fear of truncation errors caused by discretisation of time as is necessary in digital models. The new analogue, by physically changing mesh resistor and capacitor values, can also simulate layered aquifers and wells having thick gravel packs and complex well screen geometries. Such analogue simulations of pumping tests have been shown to be significantly cheaper than equivalent runs using digital modelling techniques. Development work is still underway to help broaden the analogues' use to the study of recovery as well as the drawdown phase.

  20. Binding of a possible transition state analogue to the active site of carboxypeptidase A.

    PubMed Central

    Christianson, D W; Lipscomb, W N

    1985-01-01

    The mode of binding of the competitive inhibitor 2-benzyl-3-formylpropanoic acid to the active site of carboxypeptidase A has been studied by x-ray diffraction methods to a resolution of 1.7 A. The actual species bound to the enzyme was determined to be the gem-diol resulting from covalent hydration at the aldehyde carbonyl. Details relating to the process of association of inhibitor with enzyme are unknown at this time: the free aldehyde could initially bind to the enzyme and subsequently undergo catalytic hydration; or, the hydrate itself could be the species initially binding to the enzyme, because it does exist to a high degree (25%) in aqueous solution. Nevertheless, the structure of the complex reported is reminiscent of a possible tetrahedral intermediate that would be encountered in a general base hydrolytic mechanism. Of course, other mechanistic proposals, such as the anhydride pathway, cannot be ruled out simply on the basis of the structure of this enzyme-inhibitor complex. PMID:3863130

  1. Characterization of U-series disequilibria at the Pena Blanca natural analogue site, Chihuahua, Mexico

    SciTech Connect

    Wong, V.; Goodell, P.C.; Anthony, E.Y.

    1999-07-01

    The purpose of this study was to evaluate radionuclide migration from a uranium-mineralized breccia pipe. The site provides an excellent opportunity to evaluate radionuclide mobility in a geochemical environment similar to that around the proposed high-level waste repository at Yucca Mountain, Nevada. Samples represent fracture-infillings from both within and outside the breccia pipe. Mineral assemblages within the fractures include (1) pure kaolinite, (2) a mixture of iron-oxyhydroxides (goethite and hematite) with associated alunite and jarosite, which the authors refer to as the Fe-mineral assemblage, and (3) carbonates. Uranophane, weeksite, soddyite, and boltwoodite are associated with samples from within the breccia zone. The authors obtain radionuclide activities from gamma-ray rather than alpha spectroscopy, and the methodology for these measurements is presented in detail. Plots of {sup 230}Th/{sup 238}U vs. {sup 226}Ra/{sup 230}Th show three distinct mobility trends. (1) The majority of the Fe-mineral samples from within the breccia pipe yield values between 1.0 and 1.1 for both ratios, (2) Fe-mineral samples from outside the ore zone and a kaolinite from within the ore zone have {sup 230}Th/{sup 238}U of 0.58 to 0.83 and {sup 226}Ra/{sup 230}Th of 1.09 to 1.42, and (3) some Fe-mineral samples from within the breccia pipe have values of 1.2 and 0.9 respectively. These data, combined with those from other studies at Pena Blanca suggest that U and Ra are sometimes mobile in the near-surface environment and that multiple episodes of enrichment and leaching are required to explain the trends.

  2. Mapping a Study Site

    NSDL National Science Digital Library

    Lawrence Hall of Science

    1982-01-01

    In this outdoor activity, learners use a mapping technique to become oriented to the major features of an outdoor site. Learners become aware of both physical and biological features including trees, rocks, water, signs of human activity. After completing this activity, learners can try the OBIS Terrestrial Hi-Lo Hunt and add more detail to their map.

  3. A Spectral, Chemical and Mineralogical Study of Mars Analogue Rocks

    NASA Technical Reports Server (NTRS)

    Bishop, J. L.; Pieters, C. M.; Dyar, M. D.; Hamilton, V. E.; Harloff, J.

    2002-01-01

    The macroscopic and microscopic properties of basaltic and andesitic rocks are under study for integration of diverse spectroscopic approaches to evaluate the composition and texture of Mars materials using both in situ and remote sensing techniques. Additional information is contained in the original extended abstract.

  4. Gale Crater Analogue Geology Studies at Multiple Scales

    NASA Astrophysics Data System (ADS)

    Foing, B. H.; Orgel, C.; Stoker, C.; Ehrenfreund, P.; Rammos, I.; Rodrigues, L.; Svendsen, A.; Oltheten, D.; Schlacht, I.; Nebergall, K.; Battler, M.; v'T Houd, H.; Bruneau, A.; Cross, M.; Maivald, V.; Elsaesser, A.; Direito, S. O.; Röling, W. F.; Davies, G. R.; ILEWG Euromoonmars 2013 Team

    2014-07-01

    We study the terrestrial analog of Gale crater during a field campaign (ILEWG EuroMoonMars) at MDRS, Utah to diagnose the geology at multiple scales and help in the interpretation of measurements from orbit (Mars Express, MRO) and Curiosity rover.

  5. Planetary habitability: lessons learned from terrestrial analogues

    NASA Astrophysics Data System (ADS)

    Preston, Louisa J.; Dartnell, Lewis R.

    2014-01-01

    Terrestrial analogue studies underpin almost all planetary missions and their use is essential in the exploration of our Solar system and in assessing the habitability of other worlds. Their value relies on the similarity of the analogue to its target, either in terms of their mineralogical or geochemical context, or current physical or chemical environmental conditions. Such analogue sites offer critical ground-truthing for astrobiological studies on the habitability of different environmental parameter sets, the biological mechanisms for survival in extreme environments and the preservation potential and detectability of biosignatures. The 33 analogue sites discussed in this review have been selected on the basis of their congruence to particular extraterrestrial locations. Terrestrial field sites that have been used most often in the literature, as well as some lesser known ones which require greater study, are incorporated to inform on the astrobiological potential of Venus, Mars, Europa, Enceladus and Titan. For example, the possibility of an aerial habitable zone on Venus has been hypothesized based on studies of life at high-altitudes in the terrestrial atmosphere. We also demonstrate why many different terrestrial analogue sites are required to satisfactorily assess the habitability of the changing environmental conditions throughout Martian history, and recommend particular sites for different epochs or potential niches. Finally, habitable zones within the aqueous environments of the icy moons of Europa and Enceladus and potentially in the hydrocarbon lakes of Titan are discussed and suitable analogue sites proposed. It is clear from this review that a number of terrestrial analogue sites can be applied to multiple planetary bodies, thereby increasing their value for astrobiological exploration. For each analogue site considered here, we summarize the pertinent physiochemical environmental features they offer and critically assess the fidelity with which they emulate their intended target locale. We also outline key issues associated with the existing documentation of analogue research and the constraints this has on the efficiency of discoveries in this field. This review thus highlights the need for a global open access database for planetary analogues.

  6. Characterization of electronic structure and physicochemical properties of antiparasitic nifurtimox analogues: A theoretical study

    NASA Astrophysics Data System (ADS)

    Soriano-Correa, Catalina; Raya, A.; Esquivel, Rodolfo O.

    American trypanosomiasis, also known as Chagas' disease, is caused by Trypanosoma cruzi (T. cruzi). It is well known that trypanosomes, and particularly T. cruzi, are highly sensitive towards oxidative stress, i.e., to compounds than are able to produce free radicals. Generally, nifurtimox (NFX) and benznidazol are most effective in the acute phase of the disease; therefore, nitroheterocycles constitute good models to design other nitrocompounds with specific biological characteristics. Thus, we have performed an ab initio study at the Hartree-Fock and Density Functional Theory levels of theory of several NFX analogues recently synthesized, to characterize them by obtaining their electronic, structural, and physicochemical properties, which might be linked to the observed antichagasic activity. The antitrypanosomal activity scale previously reported for the NFX analogues studied in this work is in good agreement with our theoretical results, from which we can conclude that the activity seems to be related to the reactivity along with the acidity observed for the most active molecules.

  7. QM/MM Study of Dehydro and Dihydro ?-Ionone Retinal Analogues in Squid and Bovine Rhodopsins: Implications for Vision in Salamander Rhodopsin

    PubMed Central

    Sekharan, Sivakumar; Altun, Ahmet; Morokuma, Keiji

    2010-01-01

    Visual pigment rhodopsin provides a decisive crossing point for interaction between organisms and environment. Naturally occurring visual pigments contain only PSB11 and 3,4-dehydro-PSB11 as chromophores. Therefore, the ability of visual opsin to discriminate between the retinal geometries is investigated by means of QM/MM incorporation of PSB11, 6-s-cis and 6-s-trans forms of 3,4-dehydro-PSB11, 3,4-dehydro-5,6-dihydro-PSB11, 5,6-dihydro-PSB11 analogues into squid and bovine rhodopsin environments. The analogue-protein interaction reveals the binding site of squid rhodopsin to be malleable and ductile, while that of bovine rhodopsin to be rigid and stiff. On the basis of these studies, a tentative model of salamander rhodopsin binding site is also proposed. PMID:20964383

  8. Synthesis of fluorophosphate nucleotide analogues and their characterization as tools for (19)f NMR studies.

    PubMed

    Baranowski, Marek R; Nowicka, Anna; Rydzik, Anna M; Warminski, Marcin; Kasprzyk, Renata; Wojtczak, Blazej A; Wojcik, Jacek; Claridge, Timothy D W; Kowalska, Joanna; Jemielity, Jacek

    2015-04-17

    To broaden the scope of existing methods based on (19)F nucleotide labeling, we developed a new method for the synthesis of fluorophosphate (oligo)nucleotide analogues containing an O to F substitution at the terminal position of the (oligo)phosphate moiety and evaluated them as tools for (19)F NMR studies. Using three efficient and comprehensive synthetic approaches based on phosphorimidazolide chemistry and tetra-n-butylammonium fluoride, fluoromonophosphate, or fluorophosphate imidazolide as fluorine sources, we prepared over 30 fluorophosphate-containing nucleotides, varying in nucleobase type (A, G, C, U, m(7)G), phosphate chain length (from mono to tetra), and presence of additional phosphate modifications (thio, borano, imido, methylene). Using fluorophosphate imidazolide as fluorophosphorylating reagent for 5'-phosphorylated oligos we also synthesized oligonucleotide 5'-(2-fluorodiphosphates), which are potentially useful as (19)F NMR hybridization probes. The compounds were characterized by (19)F NMR and evaluated as (19)F NMR molecular probes. We found that fluorophosphate nucleotide analogues can be used to monitor activity of enzymes with various specificities and metal ion requirements, including human DcpS enzyme, a therapeutic target for spinal muscular atrophy. The compounds can also serve as reporter ligands for protein binding studies, as exemplified by studying interaction of fluorophosphate mRNA cap analogues with eukaryotic translation initiation factor (eIF4E). PMID:25816092

  9. A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis

    PubMed Central

    Paran, D; Elkayam, O; Mayo, A; Paran, H; Amit, M; Yaron, M; Caspi, D

    2001-01-01

    OBJECTIVE—To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA).?METHODS—Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20).?RESULTS—Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1).?CONCLUSION—Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.?? PMID:11502617

  10. Life detection at a Mars analogue site of present-day serpentinization in the Tablelands Ophiolite of Newfoundland (Invited)

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

    The Tableland Ophiolite was created during the collision of Laurentia and Gondwana continents ca. 470 million years ago. Ultramafic mantle rocks, from the ancient sea bed that once separated these continents, were thrusted westward onto the old continental margin, which is now Western Newfoundland. Weathering due to recent glaciations has left large areas of ultramafic rock at the surface and created fissures for fluid flow. As a result serpentinization is occurring as fresh water penetrates the unaltered ultramafic rock. Serpentinization is of particular interest because, through hydration of ultramafic rock, this reaction produces H2 and the reducing conditions necessary for abiogenic hydrocarbon synthesis, while also producing conditions amenable for chemolithotrophic life. Therefore sites of active serpentinization can be the source of either abiogenic or biogenic organics, or both. Serpentinization is a suspected (past or present) source of (detected or putative) hydrocarbons on Mars, Titan and Europa, hence these astrobodies may be potentially habitable or once habitable environments. The Tablelands Ophiolite is an analogue site that is ideal for testing methods of life detection in an extreme environment of high pH and low microbial biomass characteristic of sites of serpentinization. Multiple ultrabasic reducing springs characteristic of present-day serpentinization have been identified and characterized based on their geochemistry and microbiology. Field-based instruments were deployed for the detection of microbial activity (ATP), microbial cell wall material, and mineralogy, in yet untested high pH and low biomass environment. In this talk I will give an overview of the in situ measurements of life detection and put these measurements in context of geochemistry, microbiology, carbon source and reaction pathways, and I will discuss what we have learned that will help us plan for future mission measurements.

  11. Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases beta and lambda

    Microsoft Academic Search

    Emmanuele Crespan; Samantha Zanoli; Anastasiya Khandazhinskaya; Igor Shevelev; Maxim Jasko; Ludmila Alexandrova; Marina Kukhanova; Giuseppina Blanca; Giuseppe Villani; Ulrich Hübscher; Silvio Spadari; Giovanni Maga

    2005-01-01

    A novel class of non-nucleoside triphosphate analogues, bearing hydrophobic groups sterically similar to nucleosides linked to the a-phosphate but lacking the chemical functional groups of nucleic acids, were tested against six different DNA poly- merases (polymerases). Human polymerases a, b and l, and Saccharomyces cerevisiae polymerase IV, were inhibited with different potencies by these analogues. On the contrary, Escherichia coli

  12. Study Site Inventory Balance Report

    Cancer.gov

    NIH-986 (REV. 02/04) 12/00 Study Site Inventory Balance Report DCP Version of NIH Form 986 Address: (Including Institution) Email address: Re: Inventory balance return for Dr. study entitled FOR NCI USE ONLY DIVISION OF

  13. Comparison of shallow aquifer and soil gas monitoring approaches for detecting CO2 leakage at a natural analogue site in France

    NASA Astrophysics Data System (ADS)

    Widory, D.; Gal, F.; Proust, E.; Mayer, B.

    2011-12-01

    Natural analogue sites where geologic CO2 is leaking to the surface provide excellent opportunities to test approaches suitable for monitoring for potential CO2 leakage at carbon capture and storage sites. We tested isotope monitoring approaches for CO2 detection in shallow aquifers and the overlying soil zone at a CO2 analogue site near Sainte-Marguerite in the Massif Central (France). The Sainte-Marguerite area is located in the southern part of the Limagne graben (French Massif Central). The basement, composed of highly fractured granite, outcrops toward the west of the study area, notably around the Saladis spring. An intercalated arkosic permeable interval between fractured granite and Oligocene marls and limestones acts as a stratiform drain for fluid migration while the overlying thick Oligocene interval is impermeable and acts as a seal. The Allier river bed is located near the contact between the basement and the sedimentary rocks. Deep CO2-ladden fluids migrate through the arkose interval toward the Sainte-Marguerite area and sustain a number of local springs. The Sainte-Marguerite area is known for the travertine deposits associated with the CO2-rich natural springs. We collected water samples and effervescent gases at the springs as well as soil gases for chemical and isotopic analyses. The analytical parameters included major anions and cations, ?13C & ?18O of CO2, ?D & ?18O of H2O and ?13C of dissolved inorganic carbon (DIC). Preliminary results revealed that ?13C values of CO2 in most groundwater and soil samples were similar. Oxygen isotope measurements revealed equilibrium between CO2 and H2O-oxygen in most samples, but except for a limited number of samples, ?18O values of water did not deviate significantly from the local meteoric water line. Our preliminary results suggest that both the groundwater and the soil sampling approaches should be capable of detecting leakage of CO2 provided that the leaking gas has a distinct isotopic composition. The thresholds of leakage detection are currently determined in laboratory column experiments, where CO2 of known isotopic composition is bubbled through a water-saturated sand at different rates and continuously measured for its ?13C and ?18O isotope composition using laser spectroscopy. The potential for isotope exchange between oxygen from water and oxygen from bubbling CO2 is also evaluated.

  14. Novel high-affinity and selective biaromatic 4-substituted gamma-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies.

    PubMed

    Høg, Signe; Wellendorph, Petrine; Nielsen, Birgitte; Frydenvang, Karla; Dahl, Ivar F; Bräuner-Osborne, Hans; Brehm, Lotte; Frølund, Bente; Clausen, Rasmus P

    2008-12-25

    Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands. PMID:19053823

  15. Synthesis of diosgenin analogues as potential anti-inflammatory agents.

    PubMed

    Singh, Monika; Hamid, A A; Maurya, Anil K; Prakash, Om; Khan, Feroz; Kumar, Anant; Aiyelaagbe, O O; Negi, Arvind S; Bawankule, Dnyaneshwar U

    2014-09-01

    We herein report the synthesis of diosgenin analogues from commercially available diosgenin as the starting material. The structures of newly synthesised compounds were confirmed by (1)H NMR, (13)C NMR and mass spectrometry. All analogues were evaluated for in-vitro anti-inflammatory profile against LPS-induced inflammation in primary peritoneal macrophages isolated from mice by quantification of pro-inflammatory (TNF-?, IL-6 and IL-1?) cytokines in cell culture supernatant using the ELISA technique followed by in-vitro cytotoxicity study. Among the synthesised analogues, analogue 15 [(E) 26-(3',4',5'-trimethoxybenzylidene)-furost-5en-3?-acetate)] showed significant anti-inflammatory activity by inhibiting LPS-induced pro-inflammatory cytokines in a dose-dependent manner without any cytotoxicity. Efficacy and safety of analogue 15 were further validated in an in-vivo system using LPS-induced sepsis model and acute oral toxicity in mice. Oral administration of analogue 15 inhibited the pro-inflammatory cytokines in serum, attenuated the liver and lung injury and reduced the mortality rate in sepsis mice. Acute oral toxicity study showed that analogue 15 is non-toxic at higher dose in BALB/c mice. Molecular docking study revealed the strong binding affinity of diosgenin analogues to the active site of the pro-inflammatory proteins. These findings suggested that analogue 15 may be a useful therapeutic candidate for the treatment of inflammatory diseases. PMID:24816230

  16. Synthesis and polymerase-mediated bypass studies of the n(2)-deoxyguanosine DNA damage caused by a lucidin analogue.

    PubMed

    Ghodke, Pratibha P; Harikrishna, S; Pradeepkumar, P I

    2015-02-20

    Lucidin is a genotoxic and mutagenic hydroxyanthraquinone metabolite, which originates from the roots of Rubia tinctorum L. (madder root). It reacts with exocyclic amino groups of DNA nucleobases and forms adducts/lesions leading to carcinogenesis. To study the effect of lucidin-induced DNA damage, herein, we report the first synthesis of a structural analogue of lucidin [N(2)-methyl-(1,3-dimethoxyanthraquinone)-deoxyguanosine, LdG] embedded DNAs utilizing phosphoramidite strategy. LdG modification in a DNA duplex imparts destabilization (?Tm ?5 °C/modification), which is attributed to the unfavorable contribution from the enthalpy. Primer extension studies using the Klenow fragment (exo(-)) of Escherichia coli DNA polymerase I demonstrate that bypass of LdG modification is error prone as well as slow compared to that across the unmodified sites. Molecular dynamics simulations of the binary complex of Bacillus fragment polymerase (homologue of the Klenow fragment) and LdG-DNA duplex elucidate the structural fluctuations imparted by the LdG lesion, as well as the molecular mechanism of bypass at the lesion site. Overall, the results presented here show that the lucidin adduct destabilizes DNA structure and reduces fidelity and processivity of DNA synthesis. PMID:25574682

  17. Studies of inositol 1-phosphate analogues as inhibitors of the phosphatidylinositol phosphate synthase in mycobacteria.

    PubMed

    Morii, Hiroyuki; Okauchi, Tatsuo; Nomiya, Hiroki; Ogawa, Midori; Fukuda, Kazumasa; Taniguchi, Hatsumi

    2013-03-01

    We previously reported a novel pathway for the biosynthesis of phosphatidylinositol in mycobacteria via phosphatidylinositol phosphate (PIP) [Morii H., Ogawa, M., Fukuda, K., Taniguchi, H., and Koga, Y (2010) J. Biochem. 148, 593-602]. PIP synthase in the pathway is a promising target for the development of new anti-mycobacterium drugs. In the present study, we evaluated the characteristics of the PIP synthase of Mycobacterium tuberculosis. Four types of compounds were chemically synthesized based on the assumption that structural homologues of inositol 1-phosphate, a PIP synthase substrate, would act as PIP synthase inhibitors, and the results confirmed that all synthesized compounds inhibited PIP synthase activity. The phosphonate analogue of inositol 1-phosphate (Ino-C-P) had the greatest inhibitory effect among the synthesized compounds examined. Kinetic analysis indicated that Ino-C-P acted as a competitive inhibitor of inositol 1-phosphate. The IC(50) value for Ino-C-P inhibition of the PIP synthase activity was estimated to be 2.0 mM. Interestingly, Ino-C-P was utilized in the same manner as the normal PIP synthase substrate, leading to the synthesis of a phosphonate analogue of PIP (PI-C-P), which had a structure similar to that of the natural product, PIP. In addition, PI-C-P had high inhibitory activity against PIP synthase. PMID:23225597

  18. Biological Evaluation and 3D-QSAR Studies of Curcumin Analogues as Aldehyde Dehydrogenase 1 Inhibitors

    PubMed Central

    Wang, Hui; Du, Zhiyun; Zhang, Changyuan; Tang, Zhikai; He, Yan; Zhang, Qiuyan; Zhao, Jun; Zheng, Xi

    2014-01-01

    Aldehyde dehydrogenase 1 (ALDH1) is reported as a biomarker for identifying some cancer stem cells, and down-regulation or inhibition of the enzyme can be effective in anti-drug resistance and a potent therapeutic for some tumours. In this paper, the inhibitory activity, mechanism mode, molecular docking and 3D-QSAR (three-dimensional quantitative structure activity relationship) of curcumin analogues (CAs) against ALDH1 were studied. Results demonstrated that curcumin and CAs possessed potent inhibitory activity against ALDH1, and the CAs compound with ortho di-hydroxyl groups showed the most potent inhibitory activity. This study indicates that CAs may represent a new class of ALDH1 inhibitor. PMID:24840575

  19. Mars Analog Site Study (MASS)

    NASA Technical Reports Server (NTRS)

    Greeley, R.; Kuzmin, R.; Costard, F.; Anderson, F. S.; Geringer, M. A.; Landheim, R.; Wenrich, M. L.

    1993-01-01

    Many proposed missions to Mars involve landing vehicles, including the Mars 94/96 (Russia), Mars Environmental Survey (MESUR, US), and the Marsnet (ESA) missions. Most landers involve in situ measurements of rock and soil compositions, study of local geology by imaging, and establishment of seismic and meteorological networks. The selection of landing sites on Mars is a complex process that must meet engineering constraints and scientific objectives, using available and anticipated data. The goal of the MASS project is to conduct an 'end-to-end' test of the site selection process using Earth analogs.

  20. Simulation of traumatic brain injury symptoms on the personality assessment inventory: an analogue study.

    PubMed

    Keiski, Michelle A; Shore, Douglas L; Hamilton, Joanna M; Malec, James F

    2015-04-01

    The purpose of this study was to characterize the operating characteristics of the Personality Assessment Inventory (PAI) validity scales in distinguishing simulators feigning symptoms of traumatic brain injury (TBI) while completing the PAI (n = 84) from a clinical sample of patients with TBI who achieved adequate scores on performance validity tests (n = 112). The simulators were divided into two groups: (a) Specific Simulators feigning cognitive and somatic symptoms only or (b) Global Simulators feigning cognitive, somatic, and psychiatric symptoms. The PAI overreporting scales were indeed sensitive to the simulation of TBI symptoms in this analogue design. However, these scales were less sensitive to the feigning of somatic and cognitive TBI symptoms than the feigning of a broad range of cognitive, somatic, and emotional symptoms often associated with TBI. The relationships of TBI simulation to consistency and underreporting scales are also explored. PMID:24965838

  1. Deception island, Antarctica: a terrestrial analogue for the study and understanding of the martian permafrost and subsurface glaciers

    NASA Astrophysics Data System (ADS)

    Hernandez de Pablo, M. A.; Ramos, M.; Vieira, G.; Gilichinsky, D.; Gómez, F.; Molina, A.; Segovia, R.

    2009-04-01

    The existence of permafrost on Mars was widely studied since Viking era and its presence is fundamental in the understanding of the water-cycle, the geological history of Mars, and the evolution of the martian hydrosphere. Viking, MOC, THEMIS, HRSC and HiRISE images allowed increase our knowledge about the role of ice on the martian landscapes. Polygonal terrains, glacial-like features, "basketball terrain" or pingos are some of the landforms that reveal the existence of frozen ice near the surface and in the ground forming the martian permafrost on present, recent or ancient times. The field observations and analyses done by Phoenix mission seem to confirm the existence of the martian permafrost hypothesized by the analyses of the images acquired by the previous missions to Mars. Moreover, the recent interpretations of the (RADAR) sensor on board of MRO mission also revealed that the surface of Mars seems to cover an important volume of ice forming glaciers covered by different materials. Here we propose the study of the glaciers and permafrost of Deception Island (Antarctica) such as a terrestrial analogue of the glaciers and permafrost of Mars. This active volcanic island is an exceptional site to study the permafrost since the climatic conditions maintain the surface covered by the ice and snow during the main part of the year. This characteristic allows the existence of an important permafrost layer also during the summer, and permanent glaciers in the higher part of the island. In addition, Deception Island is an active volcano. Some of the glaciers are covered by the ash and tephra what made difficult to distinguish between the covered glacier and the permafrost. The eruptive volcanic materials could have similar characteristics than some martian regolith by lithology, granulometry and texture. In this way, the study of the permafrost and glaciers in Deception Island could help to understand the martian permafrost and glaciers at present. On the other hand, the objectives of our Antarcti research program in this island include some activities focused on drill shallow and depth (about 25 m) boreholes to extract ice-rich permafrost cores that will be analyzed to study the habitability on the permafrost. Results of these analyses could also used in astrobiological studies of the martian permafrost. In this work we show the most important characteristics of glaciers and permafrost in Deception Island, and some possible analogues from Mars.

  2. Comparative study on the in vitro cytotoxicity of linear, dendritic, and hyperbranched polylysine analogues.

    PubMed

    Kadlecova, Zuzana; Baldi, Lucia; Hacker, David; Wurm, Florian Maria; Klok, Harm-Anton

    2012-10-01

    Lysine-based polycations are widely used as nonviral carriers for gene delivery. This manuscript reports the results of a comparative study on the in vitro cytotoxicity of a library of three structural polylysine variants, namely, linear polylysine (LPL), dendritic polylysine (DPL), and hyperbranched polylysine (HBPL). The aim of this study was to identify possible effects of polymer molecular weight and architecture on both immediate and delayed cytotoxicity and also to provide a mechanistic understanding for possible differences. Acute cytotoxicities were evaluated using cell viability assays with CHO DG44 cells. At comparable molecular weights, the EC(50) values for the LPL analogues were ?5-250 times higher as compared to the DPL and HBPL samples. For low molecular weight polycations, osmotic shock was found to be an important contributor to immediate cell death, whereas for the higher molecular weight analogues, direct cell membrane disruption was identified to play a role. Delayed cytotoxicity (?3 h) was assessed by identifying several of the hallmark events that characterize apoptosis, including phosphatidyl serine translocation, mitochondrial membrane depolarization, cytoplasmic cytochrome C release, and caspase 3 activation. At comparable molecular weights, apoptosis was found to be more pronounced for DPL and HBPL as compared to LPL. This difference was ascribed to the fact that LPL is completely enzymatically degradable, in contrast to DPL and HBPL, which also contain ?-peptidic bonds and are only partially degradable. Because their toxicity profiles are similar, HBPL is an interesting (i.e., synthetically easily accessible and inexpensive) alternative to DPL for the nonviral delivery of DNA. PMID:22931162

  3. Selection of Actinide Chemical Analogues for WIPP Tests: Potential Nonradioactive Sorbing and Nonsorbing Tracers for Study of Ion Transport in the Environment

    SciTech Connect

    Dale Spall; Robert Villarreal

    1998-08-01

    Chemical characteristics of the actinides (Th, U, Np, Pu, Am) have been studied relative to nonradioactive chemical elements that have similar characteristics in an attempt to identify a group of actinide chemical analogues that are nonradioactive. In general, the chemistries of the actinides, especially U, Np, Pu, and Am, are very complex and attempts to identify a single chemical analogue for each oxidation state were not successful. However, the rationale for selecting a group of chemical analogues that would mimic the actinides as a group is provided. The categorization of possible chemical analogues (tracers) with similar chemical properties was based on the following criteria. Categorization was studied according.

  4. Nonstationary analogue black holes

    E-print Network

    Gregory Eskin

    2014-11-26

    We study the existence of analogue nonstationary spherically symmetric black holes. The prime example is the acoustic model (cf. [V], [U]). We consider also a more general class of metrics that could be useful in other physical models of analogue black and white holes. We give examples of the appearance of black holes and of disappearance of white holes. We also discuss the relation between the apparent and the event horizons for the case of analogue black holes. In the end we study the inverse problem of determination of black or white holes by boundary measurements for the spherically symmetric nonstationary metrics.

  5. Mauna Kea, Hawaii as an Analogue Site for Future Planetary Resource Exploration: Results from the 2010 ILSO-ISRU Field-Testing Campaign

    NASA Technical Reports Server (NTRS)

    ten Kate, I. L.; Armstrong, R.; Bernhardt, B.; Blummers, M.; Boucher, D.; Caillibot, E.; Captain, J.; Deleuterio, G.; Farmer, J. D.; Glavin, D. P.; Hamilton, J. C.; Klingelhoefer, G.; Morris, R. V.; Nunez, J. I.; Quinn, J. W.; Sanders, G. B.; Sellar, R. G.; Sigurdson, L.; Taylor, R.; Zacny, K.

    2010-01-01

    Within the framework of the International Lunar Surface Operation - In-Situ Resource Utilization Analogue Test held on January 27 - February 11, 2010 on the Mauna Kea volcano in Hawaii, a number of scientific instrument teams collaborated to characterize the field site and test instrument capabilities outside laboratory environments. In this paper, we provide a geological setting for this new field-test site, a description of the instruments that were tested during the 2010 ILSO-ISRU field campaign, and a short discussion for each instrument about the validity and use of the results obtained during the test. These results will form a catalogue that may serve as reference for future test campaigns. In this paper we provide a description and regional geological setting for a new field analogue test site for lunar resource exploration, and discuss results obtained from the 2010 ILSO-ISRU field campaign as a reference for future field-testing at this site. The following instruments were tested: a multispectral microscopic imager, MMI, a Mossbauer spectrometer, an evolved gas analyzer, VAPoR, and an oxygen and volatile extractor called RESOLVE. Preliminary results show that the sediments change from dry, organic-poor, poorly-sorted volcaniclastic sand on the surface, containing basalt, iron oxides and clays, to more water- and organic-rich, fine grained, well-sorted volcaniclastic sand, primarily consisting of iron oxides and depleted of basalt and clays. Furthermore, drilling experiments showed a very close correlation between drilling on the Moon and drilling at the test site. The ILSO-ISRU test site was an ideal location for testing strategies for in situ resource exploration at the lunar or martian surface.

  6. Synthesis and enzymatic studies of bisubstrate analogues for farnesyl diphosphate synthase.

    PubMed

    Ramamoorthy, Gurusankar; Pugh, Mark L; Tian, Bo-Xue; Phan, Richard M; Perez, Lawrence B; Jacobson, Matthew P; Poulter, C Dale

    2015-04-17

    Farnesyl diphosphate synthase catalyzes the sequential chain elongation reactions between isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) to form geranyl diphosphate (GPP) and between IPP and GPP to give farnesyl diphosphate (FPP). Bisubstrate analogues containing the allylic and homoallylic substrates were synthesized by joining fragments for IPP and the allylic diphosphates with a C-C bond between the methyl group at C3 in IPP and the Z-methyl group at C3 in DMAPP (3-OPP) and GPP (4-OPP), respectively. These constructs placed substantial limits on the conformational space available to the analogues relative to the two substrates. The key features of the synthesis of bisubstrate analogues 3-OPP and 4-OPP are a regioselective C-alkylation of the dianion of 3-methyl-3-buten-1-ol (5), a Z-selective cuprate addition of alkyl groups to an ?,?-alkynyl ester intermediate, and differential activation of allylic and homoallylic alcohols in the analogues, followed by a simultaneous displacement of the leaving groups with tris(tetra-n-butylammonium) hydrogen diphosphate to give the corresponding bisdiphosphate analogues. The bisubstrate analogues were substrates for FPP synthase, giving novel seven-membered ring analogues of GPP and FPP. The catalytic efficiencies for cyclization of 3-OPP and 4-OPP were similar to those for chain elongation with IPP and DMAPP. PMID:25734506

  7. Synthesis, biological activity, and conformational study of N-methylated allatostatin analogues inhibiting juvenile hormone biosynthesis.

    PubMed

    Xie, Yong; Zhang, Li; Zhang, Chuanliang; Wu, Xiaoqing; Deng, Xile; Yang, Xinling; Tobe, Stephen S

    2015-03-25

    An allatostatin (AST) neuropeptide mimic (H17) is a potential insect growth regulator, which inhibits the production of juvenile hormone (JH) by the corpora allata. To determine the effect of conformation of novel AST analogues and their ability to inhibit JH biosynthesis, eight insect AST analogues were synthesized using H17 as the lead compound by N-methylation scanning, which is a common strategy for improving the biological properties of peptides. A bioassay using JH production by corpora allata of the cockroach Diploptera punctata indicated that single N-methylation mimics (analogues 1-4) showed more activity than double N-methylation mimics (analogues 5-8). Especially, analogues 1 and 4 showed roughly equivalent activity to that of H17, with IC50 values of 5.17 × 10(-8) and 6.44 × 10(-8) M, respectively. Molecular modeling based on nuclear magnetic resonance data showed that the conformation of analogues 1 and 4 seems to be flexible, whereas analogues 2 and 3 showed a type IV ?-turn. This flexible linear conformation was hypothesized to be a new important and indispensable structural element beneficial to the activity of AST mimics. PMID:25751662

  8. Studies towards the total synthesis of Disorazole C1 and its analogues 

    E-print Network

    Ralston, Kevin John

    2014-11-27

    Structure–activity relationships (SARs) in the disorazole family have been revealed through the biological testing of natural disorazoles and their synthetic analogues, but little is known about the contribution of the ...

  9. Assessing the bioequivalence of analogues of endogenous substances (‘endogenous drugs’): considerations to optimize study design

    PubMed Central

    Dissanayake, Sanjeeva

    2010-01-01

    BACKGROUND Assessment of the bioequivalence of generic versions of certain reference drugs is complicated by the presence of endogenous levels of said compounds which cannot be distinguished from externally derived compound levels following drug administration. If unaccounted for, the presence of endogenous compound biases towards equivalence in bioequivalence studies of these drugs. Bioequivalence assessments may be complicated further as disposition of the exogenous analogue can be subject to various endogenous processes resulting in nonlinear pharmacokinetics. To overcome these inherent biases a number of different strategies have been employed. AIMS To critically review methods used to overcome confounding biases in bioequivalence studies of ‘endogenous’ drugs. METHODS A literature search of the EMBASE and PubMed databases was performed. RESULTS The following strategies were identified: ablation/modulation of baseline endogenous substance levels; recruitment of ‘substance-deficient’ populations; restriction of dietary intake of the relevant substance; standardization of conditions with the potential to affect relevant homeostatic mechanisms; correction for baseline substance levels; and administration of supra-therapeutic drug doses. CONCLUSIONS On the basis of this review key study design concepts, intended to optimize the design of future bioequivalence studies of these so-called ‘endogenous drugs’, are described. The dual stable isotope method, which could be used in a specific context, is also discussed. PMID:20233194

  10. Measuring Fast-Temporal Sediment Fluxes with an Analogue Acoustic Sensor: A Wind Tunnel Study

    PubMed Central

    Poortinga, Ate; van Minnen, Jan; Keijsers, Joep; Riksen, Michel; Goossens, Dirk; Seeger, Manuel

    2013-01-01

    In aeolian research, field measurements are important for studying complex wind-driven processes for land management evaluation and model validation. Consequently, there have been many devices developed, tested, and applied to investigate a range of aeolian-based phenomena. However, determining the most effective application and data analysis techniques is widely debated in the literature. Here we investigate the effectiveness of two different sediment traps (the BEST trap and the MWAC catcher) in measuring vertical sediment flux. The study was performed in a wind tunnel with sediment fluxes characterized using saltiphones. Contrary to most studies, we used the analogue output of five saltiphones mounted on top of each other to determine the total kinetic energy, which was then used to calculate aeolian sediment budgets. Absolute sediment losses during the experiments were determined using a balance located beneath the test tray. Test runs were conducted with different sand sizes and at different wind speeds. The efficiency of the two traps did not vary with the wind speed or sediment size but was affected by both the experimental setup (position of the lowest trap above the surface and number of traps in the saltation layer) and the technique used to calculate the sediment flux. Despite this, good agreement was found between sediment losses calculated from the saltiphone and those measured using the balance. The results of this study provide a framework for measuring sediment fluxes at small time resolution (seconds to milliseconds) in the field. PMID:24058512

  11. New Insights into the Design of Inhibitors of Human S-Adenosylmethionine Decarboxylase: Studies of Adenine C8 Substitution in Structural Analogues of S-Adenosylmethionine†

    PubMed Central

    2009-01-01

    S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C8-substituted adenine analogues bound in the active site. PMID:19209891

  12. Phenylpropanoid Glycoside Analogues: Enzymatic Synthesis, Antioxidant Activity and Theoretical Study of Their Free Radical Scavenger Mechanism

    PubMed Central

    López-Munguía, Agustín; Hernández-Romero, Yanet; Pedraza-Chaverri, José; Miranda-Molina, Alfonso; Regla, Ignacio; Martínez, Ana; Castillo, Edmundo

    2011-01-01

    Phenylpropanoid glycosides (PPGs) are natural compounds present in several medicinal plants that have high antioxidant power and diverse biological activities. Because of their low content in plants (less than 5% w/w), several chemical synthetic routes to produce PPGs have been developed, but their synthesis is a time consuming process and the achieved yields are often low. In this study, an alternative and efficient two-step biosynthetic route to obtain natural PPG analogues is reported for the first time. Two galactosides were initially synthesized from vanillyl alcohol and homovanillyl alcohol by a transgalactosylation reaction catalyzed by Kluyveromyces lactis ?-galactosidase in saturated lactose solutions with a 30%–35% yield. To synthesize PPGs, the galactoconjugates were esterified with saturated and unsaturated hydroxycinnamic acid derivatives using Candida antarctica Lipase B (CaL-B) as a biocatalyst with 40%–60% yields. The scavenging ability of the phenolic raw materials, intermediates and PPGs was evaluated by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) method. It was found that the biosynthesized PPGs had higher scavenging abilities when compared to ascorbic acid, the reference compound, while their antioxidant activities were found similar to that of natural PPGs. Moreover, density functional theory (DFT) calculations were used to determine that the PPGs antioxidant mechanism proceeds through a sequential proton loss single electron transfer (SPLET). The enzymatic process reported in this study is an efficient and versatile route to obtain PPGs from different phenylpropanoid acids, sugars and phenolic alcohols. PMID:21674039

  13. Site locality identification study: Hanford Site. Volume II. Data cataloging

    SciTech Connect

    Not Available

    1980-07-01

    Data compilation and cataloging for the candidate site locality identification study were conducted in order to provide a retrievable data cataloging system for the present siting study and future site evaluation and licensng processes. This task occurred concurrently with and also independently of other tasks of the candidate site locality identification study. Work in this task provided the data utilized primarily in the development and application of screening and ranking processes to identify candidate site localities on the Hanford Site. The overall approach included two steps: (1) data acquisition and screening; and (2) data compilation and cataloging. Data acquisition and screening formed the basis for preliminary review of data sources with respect to their probable utilization in the candidate site locality identification study and review with respect to the level of completeness and detail of the data. The important working assumption was that the data to be used in the study be based on existing and available published and unpublished literature. The data compilation and cataloging provided the basic product of the Task; a retrievable data cataloging system in the form of an annotated reference list and key word index and an index of compiled data. The annotated reference list and key word index are cross referenced and can be used to trace and retrieve the data sources utilized in the candidate site locality identification study.

  14. Structure-activity relationship study of permethyl ningalin B analogues as P-glycoprotein chemosensitizers.

    PubMed

    Bin, Jin Wen; Wong, Iris L K; Hu, Xuesen; Yu, Zhang Xiao; Xing, Li Fu; Jiang, Tao; Chow, Larry M C; Biao, Wan Sheng

    2013-11-27

    A novel series of permethyl ningalin B analogues were synthesized and evaluated for their P-glycoprotein (P-gp)-modulating activities in a P-gp-overexpressing breast cancer cell line (LCC6MDR). Compounds 35 and 37, which possess one methoxy group and one benzyloxy group at aryl ring C, displayed the most potent P-gp-modulating activity. A 1 ?M concentration of 35 and 37 resensitized LCC6MDR cells toward paclitaxel by 42.7-fold, with respective EC50 values of 93.5 and 110.0 nM. Their mechanism of P-gp modulation is associated with an increase in intracellular drug accumulation. Their advantages also include low cytotoxicity (IC50 for L929 fibroblast >100 ?M) and high therapeutic indexes (>909 after normalization with their EC50 values). 35 is not a substrate of P-gp. They are potentially dual-selective modulators for both P-gp and breast cancer resistance protein transporters. The present study demonstrates that these new compounds can be employed as effective and safe modulators of P-gp-mediated drug resistance in cancer cells. PMID:24171478

  15. A theoretical study of the conformational behavior of analogues of alpha-L-rhamnose-1-phosphate.

    PubMed

    Compostella, Federica; Albini, Franca Marinone; Ronchetti, Fiamma; Toma, Lucio

    2004-05-17

    The conformational behavior of methyl(2-O-methyl-alpha-L-rhamnopyranosyl)phosphate, together with a group of potentially more stable analogues, was investigated through a DFT approach at the B3LYP/6-31G(d) level; the energy of all the optimized structures was recalculated using a continuum solvent model, C-PCM, choosing water as the solvent. The compounds exhibited several, sometimes tenths of populated conformations so that the overall properties of flexibility and mobility were evaluated. The analogue in which the pyranose oxygen atom is replaced by a methylene group emerges as the best candidate as a mimic of the reference 1-phosphate, in spite of the fact that it lacks the anomeric and exo-anomeric effects. The other analogues result poorer mimics because of a conformational equilibrium at the pyranose ring or of an excessive rigidity of the aglycone moiety. PMID:15113670

  16. Interaction of tachykinins with their receptors studied with cyclic analogues of substance P and neurokinin B

    SciTech Connect

    Ploux, O.; Lavielle, S.; Chassaing, G.; Julien, S.; Marquet, A.; D'Orleans-Juste, P.; Dion, S.; Regoli, D.; Beaujouan, J.C.; Bergstroem, L.

    1987-11-01

    The activities of two groups of cyclic agonists of substance P (SP) have been studied. The disulfide bridge constraints have been designed on the basis of conformational studies on SP and physalaemin indicating an ..cap alpha..-helical structure for the core of these two tachykinins (group I) and a folding of the C-terminal carboxamide towards the side chains of the glutamines 5 and 6 (group II). Only peptides simulating the ..cap alpha..-helix present substantial potencies. (Cys/sup 3,6/)SP is as active as SP in inhibiting /sup 125/I-labeled Bolton and Hunter SP-specific binding on rat brain synaptosomes and on dog carotid bioassay, two assays specific for the neurokinin 1 receptor. Moreover, (Cys/sup 3,6/)SP is a potent as neurokinin B in inhibiting /sup 125/I-labeled Bolton and Hunter eledoisin-specific binding on rat cortical synaptosomes as well as in stimulating rat portal vein, two tests specific for the neurokinin 3 receptor. Interestingly, in contrast to neurokinin B, (Cys/sup 3,6/)SP is a weak agonist of the neurokinin 2 receptor subtype, as evidenced by its binding potency in inhibiting /sup 3/H-labeled neurokinin A-specific binding on rat duodenum and in inducing the contractions of the rabbit pulmonary artery, a neurokinin 2-type bioassay. To increase the specificity of the cyclic analogue (Cys/sup 3,6/)SP positions 8 and 9 were modified. Collectively, these results suggest that the neurokinin 1 and neurokinin 3 tachykinin receptors may recognize a similar three-dimensional structure of the core of the tachykinins. Different orientations of the common C-terminal tripeptide may be related to the selectivity for the different receptor subtypes.

  17. Chain elongation of polyunsaturated fatty acids by vascular endothelial cells: studies with arachidonate analogues.

    PubMed

    Garcia, M C; Sprecher, H; Rosenthal, M D

    1990-04-01

    This study has utilized radiolabeled analogues of arachidonic acid to study the substrate specificity of elongation of long-chain polyunsaturated fatty acids. Human umbilical vein endothelial cells were incubated for 2-72 hr in medium supplemented with 0.9-2.6 microM [14C]fatty acid, and cellular glycerolipids were analyzed by gas-liquid chromatography with radioactivity detection. Elongation of naturally occurring C20 polyunsaturated fatty acids occurred with eicosapentaenoate (20:5(n-3] greater than Mead acid (20:3(n-9] greater than arachidonate (20:4(n-6]. Chain length markedly influenced the extent of elongation of 5,8,11,14-tetraenoates (18:4 greater than 19:4 greater than 20:4 greater than 21:4); effects of initial double bond position were also observed (6,9,12,15-20:4 greater than 4,7,10,13-20:4. Neither 5,8,14- nor 5,11,14-20:3 was elongated to the extent of 5,8,11-20:3. Differences between polyunsaturated fatty acids were observed both in the initial rates and in the maximal percentages of elongation, suggesting that the content of cellular C20 and C22 fatty acids may represent a balance between chain elongation and retroconversion. Umbilical vein endothelial cells do not exhibit significant desaturation of either 22:4(n-6) or 22:5(n-3). By contrast, incubation with 5,8,11,14-[14C]18:4(n-4) resulted in formation of both [14C]20:5(n-4) and [14C]22:5(n-4). The respective time courses for the appearances of [14C]22:5(n-4) and [14C]20:5(n-5) suggests delta 6 desaturation of [14C]22:4(n-4) rather than delta 4 desaturation of [14C]20:4(n-4). PMID:2345494

  18. Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer

    PubMed Central

    O'Byrne, K J; Dobbs, N; Propper, D J; Braybrooke, J P; Koukourakis, M I; Mitchell, K; Woodhull, J; Talbot, D C; Schally, A V; Harris, A L

    1999-01-01

    RC-160 (octastatin/vapreotide) is a potent octapeptide analogue of somatostatin with growth inhibitory activity in experimental tumours in vitro and in vivo, including breast cancer. We evaluated the efficacy and tolerability of high-dose RC-160, 3 mg day?1 on week 1 increased to 4.5 mg day?1 for weeks 2–4 and subsequently 6 mg day?1 until the end of treatment, administered by continuous subcutaneous infusion in the management of 14 women with previously treated metastatic breast cancer. The age range was 37–80 years (median 58.5 years) and performance status 0–2. The treatment was well tolerated with no dose reductions being required. No grade 3 or 4 toxicities were seen. Abscess formation developed at the infusion site in eight patients and erythema and discomfort was seen in a further three patients. A significant reduction in IGF-I levels occurred by day 7 and was maintained throughout the treatment. The lowest dose of RC-160 produced the maximal IGF-I response. Although there was no reduction in prolactin levels in patients whose baseline levels were normal, elevated prolactin levels found in three patients fell to within the normal range 7 days after commencing RC-160 treatment. A small but significant rise in fasting blood glucose levels was also recorded, the highest level on treatment being 7.6 mmol l?1. No objective tumour responses were observed, all patients showing disease progression within 3 months of commencing treatment. These findings demonstrate that high-dose RC-160, administered as a continuous subcutaneous infusion, can reduce serum levels of the breast growth factors IGF-I and prolactin but is ineffective in the management of metastatic breast cancer. Encouraging preclinical anti-tumour activity and the favourable toxicity profile in patients suggest the merit of future studies combining RC-160 with anti-oestrogen, cytotoxic and anti-angiogenic agents. © 1999 Cancer Research Campaign PMID:10188884

  19. Phase I–II study of the somatostatin analogue lanreotide in hormone-refractory prostate cancer

    Microsoft Academic Search

    C. Maulard; P. Richaud; J. P. Droz; D. Jessueld; F. Dufour-Esquerré; M. Housset

    1995-01-01

    Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin growth factor 1 (IGF1). A total of 30

  20. Experimental study of radon production and transport in an analogue for the Martian regolith

    NASA Astrophysics Data System (ADS)

    Meslin, P. Y.; Sabroux, J. C.; Bassot, S.; Chassefière, E.

    2011-05-01

    The suggestion that radon could be used as a radioactive tracer of regolith-atmosphere exchanges and as a proxy for subsurface water on Mars, as well as its indirect detection in the Martian atmosphere by the rover Opportunity, have raised the need for a better characterization of its production process and transport efficiency in the Martian soil. More specifically, a proper estimation of radon exhalation rate on Mars requires its emanation factor and diffusion length to be determined. The dependence of the emanation factor as a function of pore water content (at 267 and 293 K) and the dependence of the adsorption coefficient on temperature, specific surface area and nature of the carrier gas (He, He + CO 2) have been measured on a Martian soil analogue (Hawaiian palagonitized volcanic ash, JSC Mars-1), whose radiometric analysis has been performed. An estimation of radon diffusion lengths on Mars is provided and is used to derive a global average emanation factor (2-6.5%) that accounts for the exhalation rate inferred from the 210Po surface concentration detected on Martian dust and from the 214Bi signal measured by the Mars Odyssey Gamma Ray Spectrometer. It is found to be much larger than emanation factors characterizing lunar samples, but lower than the emanation factor of the palagonite samples obtained under dry conditions. This result probably reflects different degrees of aqueous alteration and could indicate that the emanation factor is also affected by the current presence of pore water in the Martian soil. The rationale of the "radon method" as a technique to probe subsurface water on Mars, and its sensitivity to soil parameters are discussed. These experimental data are useful to perform more detailed studies of radon transport in the Martian atmosphere using Global Climate Models and to interpret neutron and gamma data from Mars Odyssey Gamma Ray Spectrometer.

  1. A comparative study of proapoptotic potential of cyano analogues of boswellic acid and 11-keto-boswellic acid.

    PubMed

    Kaur, Rajbir; Khan, Sheema; Chib, Renu; Kaur, Tandeep; Sharma, Parduman Raj; Singh, Jaswant; Shah, Bhahwal Ali; Taneja, Subhash Chandra

    2011-04-01

    Semi-synthetic analogues of ?-boswellic acid (BA) and 11-keto-?-boswellic acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with the two molecules to induce cytotoxicity in HL-60 cells, where one of them showed early proapoptotic effect as evidenced by several biological end-points of the apoptosis such as annexinV binding, DNA fragmentation and increase in sub-G0 DNA fraction and apoptotic bodies formation (Hoechst 33258 staining and SEM studies). PMID:21334793

  2. A comparative study of web site performance

    Microsoft Academic Search

    JungKook Lee; Alastair M. Morrison

    2010-01-01

    Purpose – The purpose of this paper is to develop a set of criteria and an instrument for evaluating upscale hotel web sites and test these in a comparative study of South Korean and the US upscale hotel web sites. Design\\/methodology\\/approach – The hotel web sites are assessed by a team of 25 trained evaluators. The study measures and compares

  3. TREATABILITY STUDIES FOR WOOD PRESERVING SITES

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA), National Risk Management Research Laboratory (NRMRL), Site Management Support Branch, conducted a comprehensive treatability project for wood preserving sites in 1995 and 1996. This is a compilation report on the treatability studi...

  4. Ab Initio Conformational Study of Two Lewis X Analogues Gabor I. Csonka*

    E-print Network

    Csonka, Gábor István

    similar. 1. Introduction The search for analogues of sialyl Lex (sLex, NeuAc-R-2,3- Gal- -1,4-[Fuc-R-1,2 and the key structural features3 of sLex, required for recognition, were reviewed recently.4 The 2-, 3-, and 4 of sialic acid play essential roles in the E-, P-, and L-selectin recognition of sLex.5 It has been found

  5. Developing Study Stations on Your School Site.

    ERIC Educational Resources Information Center

    Ohio State Dept. of Natural Resources, Columbus. Office of Information and Education.

    The school site is a convenient location for study stations since it is available for short periods of time and can be used consistently. Special preparations, such as transportation, required for off-site fieldtrips can be eliminated. In addition, on-site activities provide students with concrete experiences necessary to understand difficult…

  6. TAME5OX, abiotic siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: Thermodynamic and photophysical studies.

    PubMed

    Akbar, Rifat; Baral, Minati; Kanungo, B K

    2015-05-01

    The synthesis, thermodynamic and photophysical properties of trivalent metal complexes of biomimetic nonadentate analogue, 5,5'-(2-(((8-hydroxyquinolin-5-yl)methylamino)methyl)-2-methylpropane-1,3-diyl)bis(azanediyl)bis(methylene)diquinolin-8-ol (TAME5OX), have been described. Combination of absorption and emission spectrophotometry, potentiometry, electrospray mass spectrometry, IR, and theoretical investigation were used to fully characterize metal (Fe(+3), Al(+3) and Cr(+3)) chelates of TAME5OX. In solution, TAME5OX forms protonated complexes [M(H3L)](3+) below pH 3.4, which consecutively deprotonates through one to three-proton processes with rise of pH. The formation constants (Log?11n) of neutral complexes formed at or above physiological pH, have been determined to be 30.18, 23.27 and 22.02 with pM values of 31.16, 18.07 and 18.12 for Fe(+3), Al(+3) and Cr(+3) ions, respectively, calculated at pH 7.4, indicating TAME5OX is a powerful among synthetic metal chelator. The results clearly demonstrate that the ligand in a tripodal orchestration firmly binds these ions over wide pH range and forms distorted octahedral complexes. The binding and the coordination event could be monitored from absorption and fluorescence spectroscopy. The high thermodynamic stability in water at physiological pH of ferric complex of TAME5OX indicates that these complexes are resistant to hydrolysis and therefore are well suited for the development of device for applications as probes. The ligand displays high sensitive fluorescence enhancement to Al(3+) at pH 7.4, in water. Moreover, TAME5OX can distinguish Al(3+) from Fe(3+) and Cr(3+) via two different sensing mechanisms: photoinduced electron transfer (PET) for Al(3+) and internal charge transfer (ICT) for Fe(3+) and Cr(3+). Density functional theory was employed for optimization and evaluation of vibrational modes, NBO analysis, excitation and emission properties of the different species of metal complexes observed by solution studies. PMID:25703371

  7. Determination of the substrate binding mode to the active site iron of (S)-2-hydroxypropylphosphonic acid epoxidase using 17O-enriched substrates and substrate analogues.

    PubMed

    Yan, Feng; Moon, Sung-Ju; Liu, Pinghua; Zhao, Zongbao; Lipscomb, John D; Liu, Aimin; Liu, Hung-wen

    2007-11-01

    (S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an O2-dependent, nonheme Fe(II)-containing oxidase that converts (S)-2-hydroxypropylphosphonic acid ((S)-HPP) to the regio- and enantiomerically specific epoxide, fosfomycin. Use of (R)-2-hydroxypropylphosphonic acid ((R)-HPP) yields the 2-keto-adduct rather than the epoxide. Here we report the chemical synthesis of a range of HPP analogues designed to probe the basis for this specificity. In past studies, NO has been used as an O2 surrogate to provide an EPR probe of the Fe(II) environment. These studies suggest that O2 binds to the iron, and substrates bind in a single orientation that strongly perturbs the iron environment. Recently, the X-ray crystal structure showed direct binding of the substrate to the iron, but both monodentate (via the phosphonate) and chelated (via the hydroxyl and phosphonate) orientations were observed. In the current study, hyperfine broadening of the homogeneous S = 3/2 EPR spectrum of the HppE-NO-HPP complex was observed when either the hydroxyl or the phosphonate group of HPP was enriched with 17O (I = 5/2). These results indicate that both functional groups of HPP bind to Fe(II) ion at the same time as NO, suggesting that the chelated substrate binding mode dominates in solution. (R)- and (S)-analogue compounds that maintained the core structure of HPP but added bulky terminal groups were turned over to give products analogous to those from (R)- and (S)-HPP, respectively. In contrast, substrate analogues lacking either the phosphonate or hydroxyl group were not turned over. Elongation of the carbon chain between the hydroxyl and phosphonate allowed binding to the iron in a variety of orientations to give keto and diol products at positions determined by the hydroxyl substituent, but no stable epoxide was formed. These studies show the importance of the Fe(II)-substrate chelate structure to active antibiotic formation. This fixed orientation may align the substrate next to the iron-bound activated oxygen species thought to mediate hydrogen atom abstraction from the nearest substrate carbon. PMID:17927218

  8. Impact of GnRH analogues on oocyte\\/embryo quality and embryo development in in vitro fertilization\\/intracytoplasmic sperm injection cycles: a case control study

    Microsoft Academic Search

    Ákos Murber; Péter Fancsovits; Nóra Ledó; Zsuzsa Tóthné Gilán; János Rigó Jr; János Urbancsek

    2009-01-01

    BACKGROUND: Despite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte\\/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH

  9. ATBC Study - Links to Related Sites

    Cancer.gov

    Skip to Main Content Home Contact Us Links Study Details Questionnaires & Forms Current Projects ATBC Study Bibliography Study Investigators & Collaborators Proposal Review & Collaboration Research Consortium Projects Links to Related Sites National

  10. Three-dimensional quantitative structure-activity relationship study on antioxidant capacity of curcumin analogues

    NASA Astrophysics Data System (ADS)

    Chen, Bohong; Zhu, Zhibo; Chen, Min; Dong, Wenqi; Li, Zhen

    2014-03-01

    A comparative molecular similarity indices analysis (CoMSIA) was performed on a set of 27 curcumin-like diarylpentanoid analogues with the radical scavenging activities. A significant cross-validated correlation coefficient Q2 (0.784), SEP (0.042) for CoMSIA were obtained, indicating the statistical significance of the correlation. Further we adopt a rational approach toward the selection of substituents at various positions in our scaffold,and finally find the favored and disfavoured regions for the enhanced antioxidative activity. The results have been used as a guide to design compounds that, potentially, have better activity against oxidative damage.

  11. Theoretical study of the hydrogen abstraction from vitamin-E analogues. The usefulness of DFT descriptors.

    PubMed

    Gutiérrez-Oliva, Soledad

    2011-03-01

    The activation and reaction energies governing hydrogen atom transfer between ?-tocopherol analogues and methylperoxyl radical were determined using the B3LYP/6-311++G(d,p) method. An a priori qualitative estimation of the charge transfer involved in the formation process of the two-fragment reaction between ?-tocopherol-like molecules and the methylperoxyl radical was used as a predictive tool to determine antioxidant activity. Consistency between the energetic data and reactivity criterion was nicely reached indicating that the electronic nature of the substituents in the heterocyclic ring in ?-tocopherol-like molecules strongly influences the activation and reaction energies. PMID:20517626

  12. 2,14-Dithiacalix[4]arene and its homooxa analogues: synthesis and dynamic NMR study of conformational behaviour.

    PubMed

    Huc Combining Breve Ko, Michal; Dvor Combining Breve Áková, Hana; Eigner, Václav; Lhoták, Pavel

    2015-04-25

    A simple and scalable synthesis of 2,14-dithiacalix[4]arene with alternating bridges (-CH2- and -S-) is reported. Proper selection of the bisphenol-based starting building blocks can provide not only the title compound (58%) but also yet unreported homooxa analogues possessing three different bridging units (-CH2-, -S- and -CH2-O-CH2-) in the molecule. These systems exhibit interesting conformational behaviour allowing for the study of flip-flop motion of the circular hydrogen bond arrays using dynamic NMR techniques. PMID:25807186

  13. Design and Synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (Citalopram) Analogues as Novel Probes for the Serotonin Transporter S1 and S2 Binding Sites

    PubMed Central

    Banala, Ashwini K.; Zhang, Peng; Plenge, Per; Cyriac, George; Kopajtic, Theresa; Katz, Jonathan L.; Loland, Claus Juul; Newman, Amy Hauck

    2013-01-01

    The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N-, 4, 5, and 4’-positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51.) In addition, 8 analogues were identified with similar potencies to S-1 for decreasing the dissociation of [3H]S-1 from the S1 site, via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki=19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [3H]S-1 via S2. PMID:24237160

  14. Total syntheses, fragmentation studies, and antitumor/antiproliferative activities of FR901464 and its low picomolar analogue.

    PubMed

    Albert, Brian J; Sivaramakrishnan, Ananthapadmanabhan; Naka, Tadaatsu; Czaicki, Nancy L; Koide, Kazunori

    2007-03-01

    FR901464 is a potent anticancer natural product that lowers the mRNA levels of oncogenes and tumor suppressor genes. In this article, we report a convergent enantioselective synthesis of FR901464, which was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6-C7 olefin without the use of protecting groups as the final step. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 stereocenter, a mild and chemoselective Red-Al reduction, a reagent-controlled stereoselective Mislow-Evans-type [2,3]-sigmatropic rearrangement to install the C5 stereocenter, a Carreira asymmetric alkynylation to generate the C4' stereocenter, and a highly efficient ring-closing metathesis-allylic oxidation sequence to form an unsaturated lactone. The decomposition pathways of FR901464's right fragment were studied under physiologically relevant conditions. Facile epoxide opening by beta-elimination gave two enones, one of which could undergo dehydration via its hemiketal to form a furan. To prevent this decomposition pathway, a right fragment was rationally designed and synthesized. This analogue was 12 times more stable than the right fragment of the natural product. Using this more stable right fragment analogue, an FR901464 analogue, meayamycin, was prepared in 13 linear steps. The inhibitions of human breast cancer MCF-7 cell proliferation by synthetic FR901464 and meayamycin were studied, and the GI50 values for these compounds were determined to be 1.1 nM and 10 pM, respectively. Thus, meayamycin is among the most potent anticancer small molecules that do not bind to either DNA or microtubule. PMID:17279752

  15. Maltose neopentyl glycol-3 (MNG-3) analogues for membrane protein study.

    PubMed

    Cho, Kyung Ho; Husri, Mohd; Amin, Anowarul; Gotfryd, Kamil; Lee, Ho Jin; Go, Juyeon; Kim, Jin Woong; Loland, Claus J; Guan, Lan; Byrne, Bernadette; Chae, Pil Seok

    2015-05-01

    Detergents are typically used to both extract membrane proteins (MPs) from the lipid bilayers and maintain them in solution. However, MPs encapsulated in detergent micelles are often prone to denaturation and aggregation. Thus, the development of novel agents with enhanced stabilization characteristics is necessary to advance MP research. Maltose neopentyl glycol-3 (MNG-3) has contributed to >10 crystal structures including G-protein coupled receptors. Here, we prepared MNG-3 analogues and characterised their properties using selected MPs. Most MNGs were superior to a conventional detergent, n-dodecyl-?-d-maltopyranoside (DDM), in terms of membrane protein stabilization efficacy. Interestingly, optimal stabilization was achieved with different MNG-3 analogues depending on the target MP. The origin for such detergent specificity could be explained by a novel concept: compatibility between detergent hydrophobicity and MP tendency to denature and aggregate. This set of MNGs represents viable alternatives to currently available detergents for handling MPs, and can be also used as tools to estimate MP sensitivity to denaturation and aggregation. PMID:25813698

  16. Insulin analogues: an example of applied medical science.

    PubMed

    Sheldon, B; Russell-Jones, D; Wright, J

    2009-01-01

    Insulin analogues were developed to try and achieve more physiological insulin replacement from injection in the subcutaneous site. Their pharmacokinetics and pharmacodynamics differ from human insulin when injected subcutaneously because of alterations in the amino acid sequence of the insulin molecule. The rapid-acting insulin analogues, lispro, aspart and glulisine, have a rapid onset of action and shorter duration of action because of changes to the B26-30 portion of insulin inhibiting formation of dimers and hexamers. They appear to improve postprandial glucose, incidence of hypoglycaemia and patient satisfaction and, when used in combination with basal insulin analogues, improve glycosylated haemoglobin in comparison to conventional insulin therapy. Additionally, they have been successfully used in children, pregnant women, in pump therapy and as part of premixed biphasic regimens. The two basal insulin analogues, glargine and detemir, developed by adjusting the isoelectric point and adding a fatty acid residue, respectively, have a protracted duration of action and a relatively smooth profile. Their pharmacokinetic and pharmacodynamic profiles have been assessed using euglycaemic clamp protocols. Both analogues have a longer duration of action, less of a peak of activity and a reduced variability with repeated injection. There is some evidence to suggest that detemir may have a slight hepatoselective effect. Clinical studies have shown a lower relative risk of hypoglycaemia and detemir appears to have a weight-sparing action. Insulin analogues represent a successful example of applied medical science. PMID:19120431

  17. Fluvial sediments, concretions, evaporates at Hanksville, Utah: An analogue field study for Gale crater, Mars

    NASA Astrophysics Data System (ADS)

    Orgel, C.; Battler, M.; Foing, B. H.; Van't Woud, H.; Maiwald, V.; Cross, M.; Ono, A.

    2013-09-01

    On 6th August 2012, Curiosity landed in Gale crater, Mars. Initial measurements and pictures showed sedimentary rocks that had been deposited by fluvial activity, e.g., alluvial fan and stream deposits. Such deposits are common in desert environments on Earth. The goal of the ILEWG EuroMoonMars project (February 23rd-March 9th,2013)was to conduct field studies in order to identify and study environments that are analogous to those that Curiosity has studied and will study at Gale crater. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) had been conducted at the Mars Desert Research Station (MDRS) [3] near Hanksville, Utah, in the vicinity of the San Rafael swell. The aim of the ILEWG EuroMoonMars 2013 project was to identify terrestrial analog sites for Curiosity exploration. The stratigraphy of the area consists of Jurassic and Cretaceous strat a[5] of which the Summerville Formation, the Brushy Basin Member of the Morrison Formation, and the Dakota Sandstone were studied. Widespread inverted channels on Mars have been identified through orbiter imagery data [6], e.g., at Gale crater. Concretions also appear to be common on Mars and have been found by the Opportunity rover at Meridiani Planum [4] and the Curiosity rover at Yellowknife Bay (Fig. 1).

  18. WSSLinks: Women and Gender Studies Web Sites

    NSDL National Science Digital Library

    The Women's Studies Section of the Association of College and Research Libraries maintains this site, which is an excellent example of a distributed meta-resource. The thirteen major thematic sections at this time include art and film, health, history, and science and technology, among others. Each section is maintained by a subject librarian at a different university library; the quality of selected sites listed demonstrates a cumulative expertise across these subject areas pertaining to women's studies. This information-rich site would benefit from the addition of an overall search engine.

  19. Diagramming the Study Site for Others

    NSDL National Science Digital Library

    The GLOBE Program, University Corporation for Atmospheric Research (UCAR)

    2003-08-01

    The purpose of this resource is to develop the best possible representation of the study site as a system. Students visit a study site, where they observe and recall their existing knowledge of air, water, soil, and living things to make a list of interconnections among the four Earth system components. They make predictions about the effects of a change in a system, inferring ways these changes affect the characteristics of other related components.

  20. Evidence for a two-state transition in papain that may have no close analogue in ficin. Differences in the disposition of cationic sites and hydrophobic binding areas in the active centres of papain and ficin.

    PubMed Central

    Brocklehurst, K; Malthouse, J P

    1980-01-01

    The kinetics of the reactions of the active-centre thiol groups of papain (EC 3.4.22.2) and ficin (EC 3.4.22.3) with the two-protonic-state reactivity probes 2,2'-dipyridyl disulphide, n-propyl 2-pyridyl disulphide and 4-(N-aminoethyl 2'-pyridyl disulphide)- 7-nitrobenzo-2-oxa-1,3-diazole (compound I) were studied over a wide range of pH. Differences between the reactivities of ficin and papain towards the cationic forms of the alkyl 2-pyridyl disulphide probes suggest that ficin contains a cationic site without exact analogue in papain, and the striking difference in the shapes of the pH-rate profiles for the reactions of the two enzymes with compound (1) suggests differences in the mobilities or dispositions of the active-centre histidine imidazole groups with respect to relevant hydrophobic binding areas. The evidence from reactivity-probe studies that the papain catalytic mechanism involves substantial repositioning of the active-centre imidazole group during the catalytic act does not apply also to ficin. If ficin contains an aspartic acid residue analogous to aspartic acid-158 in papain, the pKa of its carboxy group is probably significantly lower than the pKa of the analogous group in papain. PMID:7025834

  1. XANES Study of Cu2+ -Binding Sites

    E-print Network

    Frenkel, Anatoly

    XANES Study of Cu2+ -Binding Sites in Aquatic Humic Substances A N A T O L Y I . F R E N K E L and composition of the inner shell of copper (II) complexes with aquatic humic substances (HS) were studied by X

  2. Migrastatin analogues target fascin to block tumour metastasis

    SciTech Connect

    Chen, L.; Jakoncic, J.; Yang, S.; Zhang, J.; Huang, X.Y.

    2010-04-15

    Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.

  3. A computational ONIOM model for the description of the H-bond interactions between NU2058 analogues and CDK2 active site

    NASA Astrophysics Data System (ADS)

    Alzate-Morales, Jans H.; Caballero, Julio; Gonzalez-Nilo, Fernando D.; Contreras, Renato

    2009-09-01

    The ONIOM method was applied to study the hydrogen bond interactions between some CDK2 inhibitors and various models of the active site in CDK2/CyclinA system. It was found that according with the model's size, a good description of the molecular interactions inside the active site can be obtained. From best model, it was possible to obtain a reliable correlation between the total ONIOM energy and the biological activity reported for compounds studied. The results show that H-bond interaction energy is the principal component in this protein-ligand interaction and residues Lys89 and Asp86 are essential for great potency of compound NU6102.

  4. The binding of amide substrate analogues to phospholipase A2. Studies by 13C-nuclear-magnetic-resonance and infrared spectroscopy.

    PubMed Central

    Slaich, P K; Primrose, W U; Robinson, D H; Wharton, C W; White, A J; Drabble, K; Roberts, G C

    1992-01-01

    (R)-(2-dodecanamidoisohexyl)phosphocholine (DAHPC), labelled with 13C at the amide carbonyl group, has been synthesized and its binding to bovine pancreatic phospholipase A2 (PLA2) studied by n.m.r. and i.r. spectroscopy. Two-dimensional 1H-n.m.r. spectra show that, in the presence of Ca2+, DAHPC binds to the active site of the enzyme in a similar manner to other phospholipid amide substrate analogues. The environment of the labelled carbonyl group has been investigated by a combination of 13C n.m.r. and difference-Fourier-transform i.r. spectroscopy. The carbonyl resonance shifts 3 p.p.m. downfield on the binding of DAHPC to PLA2. The carbonyl absorption frequency decreases by 14-18 cm-1, accompanied by a marked sharpening of the absorption band. These results indicate that the carbonyl bond undergoes significant polarization in the enzyme-ligand complex, facilitated by the enzyme-bound Ca2+ ion. This suggests that ground-state strain is likely to promote catalysis in the case of substrate binding. Simple calculations, based on the i.r. data, indicate that the carbonyl bond is weakened by 5-9 kJ.mol-1. This is the first report of observation of the amide vibration of a bound ligand against the strong background of protein amide vibrations. PMID:1445261

  5. Simulations & Case Studies. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    Seymour, Cathy R., Ed.

    This document contains the following papers on simulations and case studies from the SITE (Society for Information Technology & Teacher Education) 2002 conference: "3-D Virtual Classroom Technology" (Kimberly Arseneau Miller, Angela Glod); "Simulated Lesson Design Studios" (Willis Copeland); "Lights, Camera, Integration: Presentation Programs and…

  6. Pre-clinical and Clinical Safety Studies of CMX-2043: A Cytoprotective Lipoic Acid Analogue for Ischaemia–Reperfusion Injury

    PubMed Central

    Kates, Steven A; Lader, Alan S; Casale, Ralph; Beeuwkes, Reinier

    2014-01-01

    CMX-2043 is an ?-lipoic acid analogue targeted to reduction of cellular injury and organ damage due to ischaemia–reperfusion injury (IRI). It has been shown to be effective in a rat model of cardiac IRI. The studies here reported evaluate its safety and pharmacokinetic profile in preparation for human clinical studies in procedures associated with IRI. Safety and tolerability were tested in standard pre-clinical in vitro and animal models and in a Phase 1 human clinical trial. CMX-2043 did not bind to a wide range of receptors and specific targets at approximately 4 ?g/mL (10 ?M). It was not mutagenic by Ames assay, did not produce chromosome aberrations in Chinese hamster ovary (CHO) cells, and was negative for clastogenic potential. Toxicological studies in rats including both single and 14-day repeat intravenous doses and in dogs (single intravenous dose) with a 2-week recovery period were conducted. The NOAEL in rats and dogs was 30 and >10 mg/kg, respectively. No serious adverse events were reported in a placebo-controlled, sequential dose escalation Phase 1 clinical trial. The low toxicity in the pre-clinical studies and the absence of adverse events in the Phase 1 trial have supported investigation of CMX-2043 in a human efficacy trial. PMID:24751172

  7. Anesthesia and critical-care delivery in weightlessness: A challenge for research in parabolic flight analogue space surgery studies

    NASA Astrophysics Data System (ADS)

    Ball, Chad G.; Keaney, Marilyn A.; Chun, Rosaleen; Groleau, Michelle; Tyssen, Michelle; Keyte, Jennifer; Broderick, Timothy J.; Kirkpatrick, Andrew W.

    2010-03-01

    BackgroundMultiple nations are actively pursuing manned exploration of space beyond low-earth orbit. The responsibility to improve surgical care for spaceflight is substantial. Although the use of parabolic flight as a terrestrial analogue to study surgery in weightlessness (0 g) is well described, minimal data is available to guide the appropriate delivery of anesthesia. After studying anesthetized pigs in a 0 g parabolic flight environment, our group developed a comprehensive protocol describing prolonged anesthesia in a parabolic flight analogue space surgery study (PFASSS). Novel challenges included a physically remote vivarium, prolonged (>10 h) anesthetic requirements, and the provision of veterinary operating room/intensive care unit (ICU) equivalency on-board an aircraft with physical dimensions of <1.5 m 2 (Falcon 20). Identification of an effective anesthetic regime is particularly important because inhalant anesthesia cannot be used in-flight. MethodsAfter ethical approval, multiple ground laboratory sessions were conducted with combinations of anesthetic, pre-medication, and induction protocols on Yorkshire-cross specific pathogen-free (SPF) pigs. Several constant rate infusion (CRI) intravenous anesthetic combinations were tested. In each regimen, opioids were administered to ensure analgesia. Ventilation was supported mechanically with blended gradients of oxygen. The best performing terrestrial 1 g regime was flight tested in parabolic flight for its effectiveness in sustaining optimal and prolonged anesthesia, analgesia, and maintaining hemodynamic stability. Each flight day, a fully anesthetized, ventilated, and surgically instrumented pig was transported to the Flight Research Laboratory (FRL) in a temperature-controlled animal ambulance. A modular on-board surgical/ICU suite with appropriate anesthesia/ICU and surgical support capabilities was employed. ResultsThe mean duration of anesthesia (per flight day) was 10.28 h over four consecutive days. A barbiturate and ketamine-based CRI anesthetic regimen supplemented with narcotic analgesia by bolus administration offered the greatest prolonged hemodynamic stability through an IV route (within multiple transport vehicles and differing gravitational environments). Standardization and pre-packaging of anesthesia, emergency pharmaceuticals, and consumables were found to facilitate the interchange of the veterinary anesthesia team members between flights. This operational process was extremely challenging. ConclusionsWith careful organization of caregivers, equipment and protocols, providing anesthesia and life support in weightlessness is theoretically possible. Unfortunately, human resource costs are extensive and likely overwhelming. Comprehensive algorithms for extended spaceflight must recognize these costs prior to making assumptions or attempting to provide critical care in space.

  8. Structure-toxicity relationship study of para-halogenated styrene analogues in CYP2E1 transgenic cells

    PubMed Central

    Chung, Jou-Ku; Shen, Shuijie; Jiang, Zhiteng; Yuan, Wei; Zheng, Jiang

    2012-01-01

    Styrene is one of the most important industrial intermediates consumed in the world and is mainly used as a monomer for reinforced plastics and rubber. Styrene has been found to be hepatotoxic and pneumotoxic in humans and experimental animals. The toxicity of styrene is suggested to be metabolism-dependent. Styrene-7,8-oxide has been considered as the major metabolite responsible for styrene-induced cytotoxicity. The objective of the study was to investigate the correlation between cytotoxicity of styrene and chemical and biochemical properties of the vinyl group of styrene by development of structure activity relationships (SAR). 4-Fluorostyrene, 4-chlorostyrene and 4-bromostyrene were selected for the SAR study. Cytotoxicity of styrene and the halogenated styrene derivatives with an order of 4-bromostyrene > 4-chlorostyrene > 4-fluorostyrene ? styrene was observed in CYP2E1 transgenic cells. Similar orders in the efficiency of the metabolism of styrene and the halogenated styrene analogues to their oxides and in the electrophilicity of the corresponding oxides were observed. Additionally, the order of the potency of cellular glutathione depletion and the degree of protein adduction induced by styrene and the halogenated styrenes were consistent with that of their cytotoxicities. The wild-type cells were less susceptible to the toxicity of the corresponding model compounds than CYP2E1 cells. The present study provided insight into the roles of the biochemical and chemical properties of styrene in its cytotoxicity. PMID:22366341

  9. Influence of the Charge State on the Structures and Interactions of Vancomycin Antibiotics with Cell-Wall Analogue Peptides: Experimental and Theoretical Studies

    SciTech Connect

    Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

    2009-02-16

    In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the non-covalent complex between the vancomycin and the cell wall peptide analogue N?,N?-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac2KDADA). The binding energies between the vancomycin and the peptide were obtained from the RRKM modeling of the time- and energy resolved surface-induced dissociation (SID) experiments. Our results demonstrate that the stability of the complex toward fragmentation increases in the order: [V+Ac2KDADA+H]+2 < [V+Ac2KDADA+H]+ < [V+Ac2KDADA-H]-. Dissociation of the singly protonated and singly deprotonated complex is characterized by very large entropy effects indicating substantial increase in the conformational flexibility of the resulting products. The experimental threshold energies of 1.75 eV and 1.34 eV obtained for the [V+Ac2KDADA-H]- and [V+Ac2KDADA+H]+ , respectively, are in excellent agreement with the results of density functional theory (DFT) calculations. The increased stability of the deprotonated complex observed experimentally is attributed to the presence of three charged sites in the deprotonated complex as compared to only one charged site in the singly protonated complex. The low binding energy of 0.93 eV obtained for the doubly protonated complex suggests that this ion is destabilized by Coulomb repulsion between the singly protonated vancomycin and the singly protonated peptide comprising the complex.

  10. Is the clogging process in Maqarin natural analogue controlled by accessory clay minerals? A reactive transport study with new data.

    NASA Astrophysics Data System (ADS)

    Shao, H.; Kosakowski, G.; Berner, U.; Kulik, D.; Mäder, U.; Kolditz, O.

    2012-04-01

    The safety of nuclear waste repositories is based on the functionality of multiple natural and engineered barriers for very long time. The barrier system typically combines geochemically different materials that might interact with each other. One example is the long term alteration of sedimentary host rocks by the interaction with high pH pore water from cement materials used for tunnel support, seals and as backfill material. Within this context the Maqarin site in Jordan was investigated since more than 20 years as a natural analogue for rock alterations and pore clogging due to ingress of high pH solutions. In this work we examine the geochemical evolution of Maqarin marl rock in contact with a fracture through which a hyper-alkaline groundwater is circulating. The new reactive transport calculations were performed with the code OpenGeoSys-GEMS and utilize a state-of-the-art geochemical model for cement-clay interactions. The simulations reveal that the precipitation of ettringite, and to a smaller extent the precipitation of calcium-silicate-hydrate (CSH), is responsible for pore clogging in the rock matrix. Clogging of the pore space effectively seals the rock matrix on a centimeter scale after some hundreds of years and suppresses mass transfer of solutes from the fracture into the adjacent rock. In our Maqarin marl rock model typical clay minerals like kaolinite and illite are present in accessory mineral quantities only. A sensitivity analysis reveals that in this setup clay minerals are the main source for Al, necessary for the formation of ettringite-type solid solutions. It is thus the clay mineral content and the dissolution reactions that to a large degree control the spatial and temporal precipitation of ettringites and the associated pore clogging. Recently collected mineralogy and porosity data will be used to re-calibrate the model and to verify our improved findings that overall Maqarin system is controlled by accessory clay minerals.

  11. Novel radioiodinated {gamma}-hydroxybutyric acid analogues for radiolabeling and Photolinking of high-affinity {gamma}-hydroxybutyric acid binding sites.

    PubMed

    Wellendorph, Petrine; Høg, Signe; Sabbatini, Paola; Pedersen, Martin H F; Martiny, Lars; Knudsen, Gitte M; Frølund, Bente; Clausen, Rasmus P; Bräuner-Osborne, Hans

    2010-11-01

    ?-Hydroxybutyric acid (GHB) is a therapeutic drug, a drug of abuse, and an endogenous substance that binds to low- and high-affinity sites in the mammalian brain. To target the specific GHB binding sites, we have developed a (125)I-labeled GHB analog and characterized its binding in rat brain homogenate and slices. Our data show that [(125)I]4-hydroxy-4-[4-(2-iodobenzyloxy)phenyl]butanoate ([(125)I]BnOPh-GHB) binds to one site in rat brain cortical membranes with low nanomolar affinity (K(d), 7 nM; B(max), 61 pmol/mg protein). The binding is inhibited by GHB and selected analogs, but not by ?-aminobutyric acid. Autoradiography using horizontal slices from rat brain demonstrates the highest density of binding in hippocampus and cortical regions and the lowest density in the cerebellum. Altogether, the findings correlate with the labeling and brain regional distribution of high-affinity GHB sites or [(3)H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([(3)H]NCS-382) binding sites. Using a (125)I-labeled photoaffinity derivative of the new GHB ligand, we have performed denaturing protein electrophoresis and detected one major protein band with an apparent mass of 50 kDa from cortical and hippocampal membranes. [(125)I]BnOPh-GHB is the first reported (125)I-labeled GHB radioligand and is a useful tool for in vitro studies of the specific high-affinity GHB binding sites. The related photoaffinity linker [(125)I]4-hydroxy-4-[4-(2-azido-5-iodobenzyloxy)phenyl]butanoate can be used as a probe for isolation of the elusive GHB binding protein. PMID:20696866

  12. Representing the Study Site in a Diagram

    NSDL National Science Digital Library

    The GLOBE Program, University Corporation for Atmospheric Research (UCAR)

    2003-08-01

    The purpose of this resource is to help students learn the skills and value of the translating complex interactions among Earth System components into a simplified diagram. Students visit a study site, where they observe and recall their existing knowledge of air, water, soil, and living things to make a list of interconnections among the four Earth system components. They make predictions about the effects of a change in a system, inferring ways these changes affect the characteristics of other related components.

  13. Design, synthesis, and in vitro pharmacology of new radiolabeled gamma-hydroxybutyric acid analogues including photolabile analogues with irreversible binding to the high-affinity gamma-hydroxybutyric acid binding sites.

    PubMed

    Sabbatini, Paola; Wellendorph, Petrine; Høg, Signe; Pedersen, Martin H F; Bräuner-Osborne, Hans; Martiny, Lars; Frølund, Bente; Clausen, Rasmus P

    2010-09-01

    Gamma-hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report the design and synthesis of the first (125)I-labeled radioligands in the field, one of which contains a photoaffinity label which enables it to bind irreversibly to the high-affinity GHB binding sites. PMID:20715819

  14. Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone.

    PubMed

    Al-Salem, Huda S A; Hegazy, Gehan H; El-Taher, Kamal E H; El-Messery, Shahenda M; Al-Obaid, Abdulrahman M; El-Subbagh, Hussein I

    2015-04-01

    A new series of quinazoline analogues was designed and synthesized to get the target compounds 18-21, 30-41, 46-53, and 57-76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization. PMID:25754489

  15. Alternative administration of camptothecin analogues.

    PubMed

    Glaberman, Ursa; Rabinowitz, Ian; Verschraegen, Claire F

    2005-03-01

    In order to improve the therapeutic index of camptothecin (CPT) analogues, alternative administration of CPT analogues is being evaluated. Topotecan, irinotecan, rubitecan, lurtotecan and 9-aminocamptothecin have been administered orally with response rates equivalent to that seen after intravenous administration, where applicable. Oral availability and administration of some of the newer CPT analogues, including diflomotecan (BN80915) and grimatecan (ST1481), have also shown promising results. Aerosolisation of liposomal 9-nitrocamptothecin has been studied in patients with advanced malignancies involving the lung, demonstrating systemic antitumour activity. Intrathecal administration of topotecan has been studied in children with refractory neoplastic meningitis. It is well tolerated and associated with some antitumour activity. Intraperitoneal administration of topotecan as consolidation therapy in patients with ovarian cancer has shown promising results. Transdermal administration of rubitecan has been studied in mice. So far, no CPT has been approved for an alternative route of administration. PMID:16296757

  16. Women’s Preference of Therapist Based on Sex of Therapist and Presenting Problem: An Analogue Study

    PubMed Central

    Landes, Sara J.; Burton, Jessica R.; King, Kevin M.; Sullivan, Bryce F.

    2013-01-01

    An analogue study was conducted to examine differences in women’s preference for and anticipated comfort self-disclosing to hypothetical therapists of different sexes based on the type of hypothetical presenting problem. The impact of general level of self-disclosure was also examined. Participants included female college students (n=187). Anticipated comfort self-disclosing to male or female therapist was rated by subjects when presented with therapists of each sex with the same qualifications. Women preferred and reported higher levels of anticipated comfort self-disclosing to a female therapist. Type of hypothetical presenting problem and general level of self-disclosure also impacted anticipated comfort self-disclosing. There was an interaction between general level self-disclosure and the sex of therapist on anticipated comfort self-disclosing. General level of self-disclosure only impacted anticipated comfort self-disclosing when the therapist was male. This information is relevant for therapists or organizations that provide psycho-social services to women. Organizations may want to inquire about a client’s preferences about sex of therapist beforehand and, if possible, cater to the client’s preference. PMID:24578592

  17. Attachment Anxiety, Verbal Immediacy, and Blood Pressure: Results from a Laboratory-Analogue Study Following Marital Separation

    PubMed Central

    Lee, Lauren A.; Sbarra, David A.; Mason, Ashley E.; Law, Rita W.

    2011-01-01

    Marital separation and divorce increase risk for all-cause morbidity and mortality. Using a laboratory analogue paradigm, the present study examined attachment anxiety, language use, and blood pressure (BP) reactivity among 119 (n = 43 men, 76 women) recently separated adults who were asked to mentally reflect on their relationship history and separation experience. We created a language use composite of verbal immediacy from participants’ stream-of-consciousness recordings about their separation experience as a behavioral index of attachment-related hyperactivation. Verbal immediacy moderated the association between attachment anxiety and BP at the beginning of a divorce-specific activation task. Participants reporting high attachment anxiety who discussed their separation in a first-person, present-oriented and highly engaged manner evidenced the highest levels of BP at the start of the divorce-specific task. Results provide a deeper understanding of the association between marital dissolution and health and suggest that verbal immediacy may be a useful behavioral index of hyperactivating coping strategies. PMID:21647240

  18. The Media and Communications Studies Site

    NSDL National Science Digital Library

    Chandler, Daniel.

    This is a British-based gateway from University of Wales professor, Daniel Chandler, to Web resources useful in the academic study of media and communication. As the server is located in Wales, the initial loading of the homepage may require some patience for those users located in other areas, but once the icons are loaded navigation is straightforward. The site is organized into twenty areas, including film studies, media influence, textual analysis, and gender, & ethnicity. Several of the links are preformatted searches of the Alta Vista index, providing up-to-date information on media-related topics.

  19. Application of molecular docking and ONIOM methods for the description of interactions between anti-quorum sensing active (AHL) analogues and the Pseudomonas aeruginosa LasR binding site.

    PubMed

    Ahumedo, Maicol; Drosos, Juan Carlos; Vivas-Reyes, Ricardo

    2014-05-01

    Molecular docking methods were applied to simulate the coupling of a set of nineteen acyl homoserine lactone analogs into the binding site of the transcriptional receptor LasR. The best pose of each ligand was explored and a qualitative analysis of the possible interactions present in the complex was performed. From the results of the protein-ligand complex analysis, it was found that residues Tyr-64 and Tyr-47 are involved in important interactions, which mainly determine the antagonistic activity of the AHL analogues considered for this study. The effect of different substituents on the aromatic ring, the common structure to all ligands, was also evaluated focusing on how the interaction with the two previously mentioned tyrosine residues was affected. Electrostatic potential map calculations based on the electron density and the van der Waals radii were performed on all ligands to graphically aid in the explanation of the variation of charge density on their structures when the substituent on the aromatic ring is changed through the elements of the halogen group series. A quantitative approach was also considered and for that purpose the ONIOM method was performed to estimate the energy change in the different ligand-receptor complex regions. Those energy values were tested for their relationship with the corresponding IC50 in order to establish if there is any correlation between energy changes in the selected regions and the biological activity. The results obtained using the two approaches may contribute to the field of quorum sensing active molecules; the docking analysis revealed the role of some binding site residues involved in the formation of a halogen bridge with ligands. These interactions have been demonstrated to be responsible for the interruption of the signal propagation needed for the quorum sensing circuit. Using the other approach, the structure-activity relationship (SAR) analysis, it was possible to establish which structural characteristics and chemical requirements are necessary to classify a compound as a possible agonist or antagonist against the LasR binding site. PMID:24626770

  20. Comparison of GLP-1 Analogues versus Sitagliptin in the Management of Type 2 Diabetes: Systematic Review and Meta-Analysis of Head-to-Head Studies

    PubMed Central

    Wang, Tiansheng; Gou, Zhuoyue; Wang, Fei; Ma, Manling; Zhai, Suo-di

    2014-01-01

    Background Incretin–based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone. The purpose of this study is to perform a systematic review with meta-analysis of existing head to head studies to compare the efficacy and safety of GLP-1 analogues with DPP-4 inhibitors. Methods We performed a systematic review and meta-analysis of head-to-head studies to compare GLP-1 analogues with DPP-4 inhibitors in the management of type 2 diabetes. A random effects model was selected to perform the meta-analyses, results were expressed as weighted mean differences for continuous outcomes and relative risks for dichotomous outcomes, both with 95% confidence intervals, and with I2 values and P values as markers of heterogeneity. Results Four head-to-head randomized controlled studies with 1755 patients were included. Compared to sitagliptin, GLP-1 analogues are more effective in reducing HbA1C (weight mean difference ?0.41%, 95% CI ?0.51 to ?0.31) and body weight (weight mean difference ?1.55 kg, 95% CI ?1.98 to ?1.12). Conversely, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events compared to sitagliptin: nausea (relative risk 3.14, 95% CI 2.15 to 4.59), vomiting (relative risk 2.60, 95% CI 1.48 to 4.56), diarrhea (relative risk 1.82, 95% CI 1.24 to 2.69), and constipation (relative risk 2.50, 95% CI 1.33 to 4.70). Conclusions The result of this meta-analysis demonstrates that compared to sitagliptin, GLP-1 analogues are more effective for glycemic control and weight loss, but have similar efficacy in reducing blood pressure and lipid parameters, however, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events and a similar incidence of hypoglycemia compared to sitagliptin. PMID:25089625

  1. Inter-year repeatability study of volatile organic compounds from surface decomposition of human analogues.

    PubMed

    Stadler, Sonja; Desaulniers, Jean-Paul; Forbes, Shari L

    2015-05-01

    Decomposition odour and volatile organic compounds (VOCs) have gained considerable attention recently due to their use by insects and scent detection canines to locate remains. However, a comprehensive and accurate profile of decomposition odour is yet to be confirmed. This is, in part, due to the geographical diversity in the studies conducted and the variation in the methodology and compounds being reported. To date, no repeatability studies of decomposition odour have been conducted in the same environment. In order to address this current gap in the scientific literature, this study conducted three replicate trials in order to evaluate the inter-year repeatability of the decomposition VOC profile in a southern Canadian environment. Surface decomposition trials were conducted during the spring and summer months and the VOCs were analysed by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). This study was able to demonstrate that decomposition VOCs are produced consistently during their characteristic stages and that this relationship is maintained under varying environmental factors which influence the rate of decomposition. This consistent production of decomposition VOCs can lead to a better understanding of the mechanisms of soft tissue decomposition and their sources of variation, and it could potentially lead to improved applications of these compounds for the detection of decomposed remains. PMID:24867182

  2. Medical Diagnostic Consultation concerning Mental Retardation: An Analogue Study of School Psychologists' Attitudes

    ERIC Educational Resources Information Center

    Wodrich, David L.; Tarbox, Jennifer; Balles, John; Gorin, Joanna

    2010-01-01

    Recent research of relevance to school psychologists suggests that the cause, or etiology, of mental retardation can be established by medical diagnosticians in approximately one-half of cases. In the current study, 109 practicing school psychologists considered a hypothetical case of an elementary student with mental retardation and indicated…

  3. Pico de Orizaba as an analogue to study planetary ecosynthesis on Mars

    Microsoft Academic Search

    R. Navarro-González

    2010-01-01

    Studies of Mars by spacecrafts, landers and rovers have indicated that it was once a wetter, more habitable world than the cold desert planet of today. If water was once stable as a liquid on the surface and flowed in such vast quantities, then the atmosphere must have been denser and the climate warmer in the past. The same processes

  4. Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis

    PubMed Central

    2011-01-01

    Background Fluoroquinolone resistance is a serious threat in the battle against the treatment of multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Fluoroquinolone resistant isolates from India had shown to have evolved several mutants in the quinolone resistance determining region (QRDR) of DNA gyrase A subunit (GyrA), the target of fluoroquinolone. In view of high prevalence of mutations in the 'hot spot' region, a study on combinatorial drug design was carried out to identify better analogues for the treatment of MDR-TB. The gyrA subunit 'hot spot' region of codons 90, 94 and 95 were modeled into their corresponding protein folds and used as receptors for the docking studies. Further, invitro tests were carried using the parent compounds, namely gatifloxacin and moxifloxacin and correlated with the obtained docking scores. Results Molecular docking and in vitro studies correlated well in demonstrating the enhanced activity of moxifloxacin, when compared to gatifloxacin, on ofloxacin sensitive and resistant strains comprising of clinical isolates of MDR-TB. The evolved lead structures targeting against mutant QRDR receptors were guanosine and cholesteryl esters of gatifloxacin and moxifloxacin. They showed consistently high binding affinity values of -10.3 and -10.1 kcal/mol respectively with the target receptors. Of these, the guanosine ester showed highest binding affinity score and its log P value lied within the Lipinski's range indicating that it could have better absorptivity when it is orally administered thereby having an enhanced activity against MTB. Conclusions The docking results showed that the addition of the cholesteryl and guanosine esters to the 'DNA gyrase binding' region of gatifloxacin and moxifloxacin enhanced the binding affinity of these parent molecules with the mutant DNA gyrase receptors. Viewing the positive correlation for the docking and in vitro results with the parent compounds, these lead structures could be further evaluated for their in vitro and in vivo activity against MDR-TB. PMID:22152119

  5. Electron paramagnetic resonance study of doped synthetic crystals of struvite and its zinc analogue

    NASA Astrophysics Data System (ADS)

    Chand, Prem; Agarwal, O. P.

    The electron paramagnetic resonance (EPR) technique has been used to study the Mn 2+ paramagnetic impurity complexes in synthetic struvite (MgNH 4PO 4?6H 2O) and the zinc isomorph (ZnNH 4PO 4?6H 2O). EPR of VO 2+ ion complexes in vanadyl doped crystals of the zinc isomorph of struvite has also been studied. Two differently oriented, but otherwise identical complexes of both Mn 2+ ion and VO 2+ ion are found in these crystals. The spin Hamiltonian parameters indicate a large orthorhombic distortion of the [Mn 2+(H 2O) 6] octahedra and an axial symmetry of the vanadyl complexes. The results indicate that in both manganese and vanadyl complexes, the metal ions have covalent bonding with the ligands.

  6. Reducing vividness and emotional intensity of recurrent "flashforwards" by taxing working memory: an analogue study.

    PubMed

    Engelhard, Iris M; van den Hout, Marcel A; Dek, Eliane C P; Giele, Catharina L; van der Wielen, Jan-Willem; Reijnen, Marthe J; van Roij, Birgit

    2011-05-01

    Several studies have found that making eye movements while retrieving visual images about past negative events reduces their vividness and emotional intensity. A working memory account states that eye movements tax working memory and interfere with visual imagery, thus degrading images. This study examined whether eye movements also affect recurrent, intrusive visual images about potential future catastrophes ("flashforwards") in a sample of female undergraduates who had indicated on a screening-scale that they suffer from such intrusions. They were asked to recall two intrusive images with or without making eye movements. Before and after each condition, participants retrieved the image, and rated its vividness and emotionality. Results showed that vividness of intrusive images was lower after recall with eye movement, relative to recall only, and there was a similar trend for emotionality. Potential implications are discussed. PMID:21376527

  7. Astrobiology in the Field: Studying Mars by Analogue Expeditions on Earth

    NASA Technical Reports Server (NTRS)

    Conrad, Pamela G.

    2011-01-01

    We will present a strategy for how one prepares to engage in fieldwork on another planets by practicing in analogous environments on the Earth, including at Mono Lake. As an example, we will address the problem of how to study the habitability of an environment when you have no idea what kind of life might be there to exploit it. This will all be related to the upcoming launch of the Mars Science Laboratory to Mars in late November this year.

  8. Impact of informed-choice invitations on diabetes screening knowledge, attitude and intentions: an analogue study

    E-print Network

    Mann, Eleanor; Kellar, Ian; Sutton, Stephen; Kinmonth, Ann Louise; Hankins, Matthew; Griffin, Simon J; Marteau, Theresa M

    2010-12-17

    ’ contributions EM conducted statistical analysis and drafted the manuscript; IK is the study coordinator; MH provided statistical analysis support; TMM, ALK, SG and SS are Principal Investigators; TMM is the paper guarantor. All authors read and approved... health imperative or matter for informed choice. British Medical Journal 2002, 325:78-80. 8. Norris S, Kansagara D, Bougatsos C, Fu R: Screening adults for type 2 diabetes: a review of the evidence for the US Preventive Services Task Force. Annals...

  9. Outcrop Analogue Studies in Geothermal Exploration - Characterization of fault zones in Triassic Muschelkalk limestones of the Upper Rhine Graben

    NASA Astrophysics Data System (ADS)

    Meier, S.; Bauer, J. F.; Philipp, S. L.

    2013-12-01

    The characterization of fault zones is of particular importance in geothermal reservoirs since there may be great effects on fluid flow. Fault zones generally consist of two major hydromechanical units: the fault core and the damage zone, surrounded by the host rock. To improve predictions of fracture system parameters for each unit and resulting estimations of reservoir permeabilities at depths we perform outcrop analogue studies. We analyze Middle Triassic Muschelkalk limestones that form one geothermal reservoir formation in the Upper Rhine Graben (southwest Germany) in quarries on its eastern graben shoulder. We measure the orientations and displacements of various fault zones and characterize the fracture systems within the fault zone units and in the host rock. Our studies show that damage zones are well developed even in smaller fault zones. Their fault cores, however, are narrow compared with that of fault zones with large displacements and comprise brecciated material, clay smear, host rock lenses or zones of mineralization. Based on the field data we use analytical models to estimate the permeabilities of the analyzed fracture systems. Results show increased fracture frequencies in the fault zone damage zones and larger fracture apertures parallel or subparallel to fault zone strike that lead to enhanced permeability compared with other orientations. Mineralized fractures accumulated in this direction in the 'Nussloch'-quarry indicate that these fractures were pathways for fault zone parallel fluid flow in the past. This shows that open fractures with orientations parallel to fault zones may be pathways for fault zone parallel fluid flow in geothermal reservoirs. By contrast, well-developed fault cores may be potential barriers for fluid flow in inactive fault zones. To build numerical models to analyze local stress fields and effects on fracture propagation for different fault zone types and geometries information on rock mechanical properties is necessary. Therefore we take representative rock samples in the quarries to determine uniaxial compressive and tensile strengths as well as Young's Moduli in the laboratory. Additionally we measure the rebound hardness distribution across fault zones with a 'Schmidt-Hammer' to analyze mechanical property variations. First results show that the rebound hardness increases with increasing distance from the fault core. The presented studies help to predict the permeability of fault-related geothermal reservoir rocks and minimize the exploration risk of geothermal projects. This project is part of the Research and Development Project AuGE (Outcrop Analogue Studies in Geothermal Exploration). Project partners are the companies Geothermal Engineering GmbH and GeoEnergy GmbH as well as the Universities of Heidelberg and Erlangen. The project is funded by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) within the framework of the 5th Energy Research Program (FKZ 0325302).

  10. Reproductive toxicity study with a novel deoxyguanosine analogue (Metacavir) in pregnant SD rats.

    PubMed

    Luo, Qihui; Chen, Zhengli; Cheng, Anchun; Wang, Mingshu; Fang, Jing; Peng, Xi; Tang, Li

    2015-03-01

    Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6-15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6-20 pregnant days were significantly different (P < 0.01, P < 0.05). Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group (P < 0.05), while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg·d) there is no teratogenic side effects. PMID:25523750

  11. Connecting the Parts of the Study Site

    NSDL National Science Digital Library

    The GLOBE Program, University Corporation for Atmospheric Research (UCAR)

    2003-08-01

    The purpose of this resource is to help students articulate and integrate their existing knowledge about the air, water, soil, and living things by viewing them as interacting parts of a system. Students visit a study site, where they observe and recall their existing knowledge of air, water, soil, and living things to make a list of interconnections among the four Earth system components. They make predictions about the effects of a change in a system, inferring ways these changes affect the characteristics of other related components.

  12. Analytic Study of Three-Dimensional Rupture Propagation in Strike-Slip Faulting with Analogue Models

    NASA Astrophysics Data System (ADS)

    Chan, Pei-Chen; Chu, Sheng-Shin; Lin, Ming-Lang

    2014-05-01

    Strike-slip faults are high angle (or nearly vertical) fractures where the blocks have moved along strike way (nearly horizontal). Overburden soil profiles across main faults of Strike-slip faults have revealed the palm and tulip structure characteristics. McCalpin (2005) has trace rupture propagation on overburden soil surface. In this study, we used different offset of slip sandbox model profiles to study the evolution of three-dimensional rupture propagation by strike -slip faulting. In strike-slip faults model, type of rupture propagation and width of shear zone (W) are primary affecting by depth of overburden layer (H), distances of fault slip (Sy). There are few research to trace of three-dimensional rupture behavior and propagation. Therefore, in this simplified sandbox model, investigate rupture propagation and shear zone with profiles across main faults when formation are affecting by depth of overburden layer and distances of fault slip. The investigators at the model included width of shear zone, length of rupture (L), angle of rupture (?) and space of rupture. The surface results was follow the literature that the evolution sequence of failure envelope was R-faults, P-faults and Y-faults which are parallel to the basement fault. Comparison surface and profiles structure which were curved faces and cross each other to define 3-D rupture and width of shear zone. We found that an increase in fault slip could result in a greater width of shear zone, and proposed a W/H versus Sy/H relationship. Deformation of shear zone showed a similar trend as in the literature that the increase of fault slip resulted in the increase of W, however, the increasing trend became opposite after a peak (when Sy/H was 1) value of W was reached (small than 1.5). The results showed that the W width is limited at a constant value in 3-D models by strike-slip faulting. In conclusion, this study helps evaluate the extensions of the shear zone influenced regions for strike-slip faults.

  13. Procedural justice in the context of civil commitment: an analogue study.

    PubMed

    Cascardi, M; Poythress, N G; Hall, A

    2000-01-01

    Procedural justice theory posits that the process by which disputes are resolved influences perceptions of fairness and satisfaction with outcomes, even if the outcomes are unfavorable. Within the context of civil commitment, Tyler (1992) has suggested that enhancing respondents' perceptions of procedural justice (i.e., participation, dignity, and trust) during commitment proceedings might facilitate accommodation to an adverse judicial determination (i.e., commitment) and subsequently enhance therapeutic outcomes. The study reported here used videotapes of mock commitment hearings to examine whether patients committed for involuntary treatment are sensitive to procedural justice manipulations. Results suggest that patients are sensitive to procedural justice manipulations and, further, that such manipulations are likely to influence the patients' attitude toward psychiatric care. These findings suggest that the development of strategies to enhance patients' perceptions of procedural justice in commitment hearings may indeed have positive therapeutic implications and warrants further investigation. PMID:11180419

  14. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Harry Cordatos

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  15. Monomeric sarcosine oxidase: 2. Kinetic studies with sarcosine, alternate substrates, and a substrate analogue.

    PubMed

    Wagner, M A; Jorns, M S

    2000-08-01

    Monomeric sarcosine oxidase (MSOX) is a flavoenzyme that catalyzes the oxidative demethylation of sarcosine (N-methylglycine) to yield glycine, formaldehyde, and hydrogen peroxide. MSOX can oxidize other secondary amino acids (N-methyl-L-alanine, N-ethylglycine, and L-proline), but N,N-dimethylglycine, a tertiary amine, is not a substrate. N-Methyl-L-alanine is a good alternate substrate, exhibiting a k(cat) value (8700 min(-)(1)) similar to sarcosine (7030 min(-)(1)). Turnover with L-proline (k(cat) = 25 min(-)(1)) at 25 degrees C occurs at less than 1% of the rate observed with sarcosine. MSOX is converted to a two-electron reduced form upon anaerobic reduction with sarcosine or L-proline. No evidence for a spectrally detectable intermediate was obtained in reductive half-reaction studies with L-proline. The reductive half-reaction with L-proline at 4 degrees C exhibited saturation kinetics (k(lim) = 6.0 min(-)(1), K(d) = 260 mM) and other features consistent with a mechanism in which a practically irreversible reduction step (E(ox). S --> E(red).P) with a rate constant, k(lim), is preceded by a rapidly attained equilibrium (K(d)) between free E and the E.S complex. Steady-state kinetic studies with sarcosine and N-methyl-L-alanine in the absence or presence of a dead-end inhibitor (pyrrole-2-carboxylate) indicate that catalysis proceeds via a "modified" ping pong mechanism in which oxygen reacts with E(red).P prior to the dissociation of the imino acid product. In this mechanism, double reciprocal plots will appear nearly parallel (as observed) if the reduction step is nearly irreversible. A polar mechanism, involving formation of a covalent 4a-flavin-substrate adduct is one of several plausible mechanisms for sarcosine oxidation. Thiols are known to form similar 4a-flavin adducts. MSOX does not form a 4a-adduct with thioglycolate but does form a charge-transfer complex that undergoes an unanticipated one-electron-transfer reaction to yield the anionic flavin radical. PMID:10913293

  16. Potential desiccation cracks on Mars: A synthesis from modeling, analogue-field studies, and global observations

    NASA Astrophysics Data System (ADS)

    El-Maarry, M. R.; Watters, W.; McKeown, N. K.; Carter, J.; Noe Dobrea, E.; Bishop, J. L.; Pommerol, A.; Thomas, N.

    2014-10-01

    Potential desiccation polygons (PDPs) are polygonal surface patterns that are a common feature in Noachian-to-Hesperian-aged phyllosilicate- and chloride-bearing terrains and have been observed with size scales that range from cm-wide (by current rovers) to 10s of meters-wide. The global distribution of PDPs shows that they share certain traits in terms of morphology and geologic setting that can aid identification and distinction from fracturing patterns caused by other processes. They are mostly associated with sedimentary deposits that display spectral evidence for the presence of Fe/Mg smectites, Al-rich smectites or less commonly kaolinites, carbonates, and sulfates. In addition, PDPs may indicate paleolacustrine environments, which are of high interest for planetary exploration, and their presence implies that the fractured units are rich in smectite minerals that may have been deposited in a standing body of water. A collective synthesis with new data, particularly from the HiRISE camera suggests that desiccation cracks may be more common on the surface of Mars than previously thought. A review of terrestrial research on desiccation processes with emphasis on the theoretical background, field studies, and modeling constraints is presented here as well and shown to be consistent with and relevant to certain polygonal patterns on Mars.

  17. Novel computational study on ?-stacking to understand mechanistic interactions of Tryptanthrin analogues with DNA.

    PubMed

    Terryn, Raymond J; German, Helen W; Kummerer, Theresa M; Sinden, Richard R; Baum, J Clayton; Novak, Mark J

    2014-01-01

    Based on recently published initial experimental results on the intercalation of a class of broad spectrum antiparasitic compounds, we present a purely theoretical approach for determining if these compounds may preferentially intercalate with guanosine/cytosine (GC)-rich or adenosine/thymidine (TA)-rich regions of DNA. The predictive model presented herein is based upon utilization of density functional theory (DFT) to determine a priori how the best intercalator may energetically and sterically interact with each of the nucleoside base pairs. A potential new method using electrostatic potential maps (EPMs) to visually select the best poses is introduced and compared to the existing brute-force center of mass (COM) approach. The EPM and COM predictions are in agreement with each other, but the EPM method is potentially much more efficient. We report that 4-azatryptantrin, the best intercalator, is predicted to favor ?-stacking with GC over that of TA by approximately 2-4?kcal/mol. This represents a significant difference if one takes into account the Boltzmann distribution at physiological temperature. This theoretical method will be utilized to guide future experimental studies on the elucidation of possible mechanism(s) for the action of these antiparasitic compounds at the molecular level. PMID:24156546

  18. Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue.

    PubMed

    Sobolevsky, Tim; Prasolov, Ilya; Rodchenkov, Grigory

    2015-02-01

    The data are reported for an in vitro metabolism study of two novel synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and its fluorinated analog N-(1-adamantyl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (5F-APICA, STS-135), which are active ingredients of smoking mixtures sold in Russia since 2012. The cannabinoids were isolated from herbal mixtures using preparative liquid chromatography and then incubated with human liver microsomes (HLMs). The formed metabolites were characterized by liquid chromatography - triple quadrupole mass spectrometry and high-resolution mass spectrometry with electrospray ionization in positive ion mode. It was found that HLMs produce mono-, di-, and trihydroxylated metabolites, as well as N-desalkyl metabolites, which can be further hydroxylated; the amide bond resisted the metabolic cleavage. For 5F-APICA, a series of oxidative defluorination products formed as well. For in vivo confirmation of the formed in vitro metabolites, spot urine samples from drug users were analyzed with the created method. It was shown that for the detection of APICA abuse, the preferred metabolites are the di- and tri-hydroxylated species, while in case of 5F-APICA, a monohydroxy metabolite is a better target. The N-despentyl (desfluoropentyl) hydroxyadamantyl metabolite also provides good retrospectivity to confirm the administration of any of these cannabinoids. PMID:25428705

  19. Theoretical Studies on the Intermolecular Interactions of Potentially Primordial Base-Pair Analogues

    SciTech Connect

    Leszczynski, Jerzy [Computational Center for Molecular Structure and Interactions, Jackson, MS; Sponer, Judit [Academy of Sciences of the Czech Republic; Sponer, Jiri [Academy of Sciences of the Czech Republic; Sumpter, Bobby G [ORNL; Fuentes-Cabrera, Miguel A [ORNL; Vazquez-Mayagoitia, Alvaro [ORNL

    2010-01-01

    Recent experimental studies on the Watson Crick type base pairing of triazine and aminopyrimidine derivatives suggest that acid/base properties of the constituent bases might be related to the duplex stabilities measured in solution. Herein we use high-level quantum chemical calculations and molecular dynamics simulations to evaluate the base pairing and stacking interactions of seven selected base pairs, which are common in that they are stabilized by two NH O hydrogen bonds separated by one NH N hydrogen bond. We show that neither the base pairing nor the base stacking interaction energies correlate with the reported pKa data of the bases and the melting points of the duplexes. This suggests that the experimentally observed correlation between the melting point data of the duplexes and the pKa values of the constituent bases is not rooted in the intrinsic base pairing and stacking properties. The physical chemistry origin of the observed experimental correlation thus remains unexplained and requires further investigations. In addition, since our calculations are carried out with extrapolation to the complete basis set of atomic orbitals and with inclusion of higher electron correlation effects, they provide reference data for stacking and base pairing energies of non-natural bases.

  20. A NEW VIEW ON INTERSTELLAR DUST HIGH FIDELITY STUDIES OF INTERSTELLAR DUST ANALOGUE TRACKS IN STARDUST FLIGHT SPARE AEROGEL

    E-print Network

    IN STARDUST FLIGHT SPARE AEROGEL F. Postberg, C. Allen, S. Bajt, H. A. Bechtel, J. Borg, F. Brenker, J the Stardust Mission exposed aerogel collector panels for a total of about 200 days to the stream - 30km/s] interstellar dust (ISD) analogues onto Stardust aerogel flight spares. This en- ables

  1. Collaborative Student Laboratory Exercise Using FT-IR Spectroscopy for the Kinetics Study of a Biotin Analogue

    ERIC Educational Resources Information Center

    Leong, Jhaque; Ackroyd, Nathan C.; Ho, Karen

    2014-01-01

    The synthesis of N-methoxycarbonyl-2-imidazolidone, an analogue of biotin, was conducted by organic chemistry students and confirmed using FT-IR and H NMR. Spectroscopy students used FT-IR to measure the rate of hydrolysis of the product and determined the rate constant for the reaction using the integrated rate law. From the magnitude of the rate…

  2. Development of Stable Phosphohistidine Analogues

    PubMed Central

    Kee, Jung-Min; Villani, Bryeanna; Carpenter, Laura R.

    2011-01-01

    Protein phosphorylation is one of the most common and extensively studied posttranslational modifications (PTMs). Compared to the O-phosphorylation of Ser, Thr, and Tyr residues, our understanding of histidine phosphorylation is relatively limited, particularly in higher eukaryotes, due to technical difficulties stemming from the intrinsic instability and isomerism of phosphohistidine (pHis). We report the design and synthesis of stable and nonisomerizable pHis analogues. These pHis analogues were successfully utilized in solid-phase peptide synthesis and semi-synthesis of histone H4. Significantly, the first antibody that specifically recognizes pHis was obtained using the synthetic peptide as the immunogen. PMID:20879710

  3. Natural glass analogues to alteration of nuclear waste glass: A review and recommendations for further study

    SciTech Connect

    McKenzie, W.F.

    1990-01-01

    The purpose of this report is to review previous work on the weathering of natural glasses; and to make recommendations for further work with respect to studying the alteration of natural glasses as it relates quantifying rates of dissolution. the first task was greatly simplified by the published papers of Jercinovic and Ewing (1987) and Byers, Jercinovic, and Ewing (1987). The second task is obviously the more difficult of the two and the author makes no claim of completeness in this regard. Glasses weather in the natural environment by reacting with aqueous solutions producing a rind of secondary solid phases. It had been proposed by some workers that the thickness of this rind is a function of the age of the glass and thus could be used to estimate glass dissolution rates. However, Jercinovic and Ewing (1987) point out that in general the rind thickness does not correlate with the age of the glass owing to the differences in time of contact with the solution compared to the actual age of the sample. It should be noted that the rate of glass dissolution is also a function of the composition of both the glass and the solution, and the temperature. Quantification of the effects of these parameters (as well as time of contact with the aqueous phase and flow rates) would thus permit a prediction of the consequences of glass-fluid interactions under varying environmental conditions. Defense high- level nuclear waste (DHLW), consisting primarily of liquid and sludge, will be encapsulated by and dispersed in a borosilicate glass before permanent storage in a HLW repository. This glass containing the DHLW serves to dilute the radionuclides and to retard their dispersion into the environment. 318 refs.

  4. Pico de Orizaba as an analogue to study planetary ecosynthesis on Mars

    NASA Astrophysics Data System (ADS)

    Navarro-González, R.

    2010-03-01

    Studies of Mars by spacecrafts, landers and rovers have indicated that it was once a wetter, more habitable world than the cold desert planet of today. If water was once stable as a liquid on the surface and flowed in such vast quantities, then the atmosphere must have been denser and the climate warmer in the past. The same processes that led to the origin of life on Earth may have occurred simultaneously on Mars, and living organisms may have colonized the planet. It is unclear how or when Mars lost its thicker atmosphere and as a result lost its habitable environment. The Viking landers of the mid-1970s carried experiments designed to detect the presence of extant life and showed the martian soil to be lifeless on the surface. Future space missions will continue to explore if there was or still is life on Mars, perhaps in the subsurface. However, if there is no life on Mars, there is an opportunity to explore the potential for survival and biological evolution for terrestrial life beyond their place of origin, and do planetary ecosynthesis on Mars, a process of making the planet habitable for terrestrial organisms. The evidence that Mars was once habitable is important for planetary ecosynthesis as it provides a proof in principle that Mars can support a habitable state on timescales that, while short over the age of the solar system, are long in human terms. Artificial greenhouse gases, such as perfluorocarbons, appear to be the best method for warming Mars and increase its atmospheric density so that liquid water becomes stable. The process of introducing terrestrial ecosystems to Mars can be compared with a descent down a high mountain. Each drop in elevation results in a warmer, wetter climate and more diverse biological community. This is shown in Pico de Orizaba which is located at 19.03°N, 97.27°W and rises 5,636 meters above sea level. It is the highest mountain in Mexico, the third highest in the tropics after Mount Kilimanjaro (5,892) in Tanzania and Pico Cristóbal Colón (5,700 m) in Columbia but with the highest tropical treeline in the world. Pico de Orizaba is a good analog on Earth of a warmer and wetter Mars with trees confined to tropical regions.

  5. Pena Blanca Natural Analogue Project: Summary of activities

    SciTech Connect

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  6. Pena blanca natural analogue project: summary of activities

    SciTech Connect

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  7. MASTER CLINICAL RESEARCH STUDY SITE AGREEMENT THIS MASTER CUNICAL RESEARCH STUDY SITE AGREEMENT ("Master Agreement")

    E-print Network

    Cui, Yan

    ("Master Agreement") is entered into as of the 14th day of May, 2009 ("Effective Date"), by and between UT "clinies in the Memphis,Shelby County, Tennessee area that serve as study sites for r~search studies by The University, pursuant to the terms and conditions of this Master ~~~~. . ..- T~RMS AND CONDITIONS 1. REQUEST

  8. Mapping the Catechol Binding Site in Dopamine D1 Receptors: Synthesis and Evaluation of Two Parallel Series of Bicyclic Dopamine Analogues

    PubMed Central

    Bonner, Lisa A.; Laban, Uros; Chemel, Benjamin R.; Juncosa, Jose I.; Lill, Markus A.; Watts, Val J.; Nichols, David E.

    2012-01-01

    A novel class of isochroman dopamine analogues, 1, originally reported by Abbott Laboratories, had greater than 100-fold selectivity for D1-like vs. D2-like receptors. We synthesized a parallel series of chroman compounds, 2, and showed that repositioning the oxygen in the heterocyclic ring reduced potency and conferred D2-like receptor selectivity to these compounds. In silico modeling supported the hypothesis that the altered pharmacology for 2 was due to potential intramolecular hydrogen bonding between the oxygen in the chroman ring and the meta-hydroxyl of the catechol moiety. This interaction realigns the catechol hydroxyl groups and disrupts key interactions between these ligands and critical serine residues in TM5 of the D1-like receptors. This hypothesis was tested by the synthesis and pharmacological evaluation of a parallel series of carbocyclic compounds, 3. Our results suggest that when the potential for intramolecular hydrogen bonding is removed, D1-like receptor potency and selectivity is restored. PMID:21538900

  9. Photochemical and photobiological studies of tirapazamine (SR 4233) and related quinoxaline 1,4-Di-N-oxide analogues.

    PubMed

    Inbaraj, J Johnson; Motten, Ann G; Chignell, Colin F

    2003-02-01

    Tirapazamine, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide (TPZ; SR 4233), is currently undergoing phase II and III clinical trials as an antitumor agent. We have studied the photochemical properties of TPZ, and the related analogues 3-amino-2-quinoxalinecarbonitrile 1,4-di-N-oxide (TPZCN) and quinoxaline-1,4-di-N-oxide (quindoxin) with respect to their potential to photodamage DNA both oxidatively and reductively. We have found that TPZ, TPZCN, and quindoxin photosensitized the generation of singlet oxygen with quantum yields of 0.007, 0.19, and 0.02, respectively, in acetonitrile. Irradiation (lambda > 300 nm) of TPZ at pH 9.4 in the presence of a reducing agent, NADH, generated the corresponding nitroxide radical. At pH 7.4, photoirradiation of either TPZ or TPZCN in the presence of NADH in air saturated buffer gave the superoxide radical, which was trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). In the absence of a reducing agent, singlet oxygen generated from TPZCN oxidized DMPO to 5,5-dimethyl-2-oxopyrrolin-1-oxyl (DMPOX). No spin adducts were detected during photoirradiation of TPZ, NADH, and DMPO in nitrogen-saturated buffer. However, when DMSO was also present, the DMPO/(*)CH(3) adduct was observed, indicating the generation of the free hydroxyl radical. Both TPZ and TPZCN photooxidized reduced glutathione and azide to the glutathiyl and azidyl radicals, respectively. Under anaerobic conditions, NADH increased photoinduced strand breaks in pBR322 plasmid DNA caused by TPZ or TPZCN. For TPZ, the reactive species is probably the aforementioned nitroxide radical or the hydroxyl radical generated from its decomposition. In contrast, DNA damage by quindoxin was not affected by NADH, suggesting a different mechanism, possibly involving a photogenerated oxaziridine intermediate. These studies show that the photochemistry of TPZ, TPZCN, and quindoxin is complex and depends on the redox environment and whether oxygen is present. PMID:12588187

  10. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies

    Microsoft Academic Search

    A Flint; A Raben; JE Blundell; A Astrup

    2000-01-01

    OBJECTIVE: To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days.DESIGN: On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postprandial period under exactly the same conditions.SUBJECTS: 55 healthy men (age 25.6±0.6

  11. Structure-activity relationship studies of 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine derivatives and their N-analogues: evaluation of O-and N-analogues and their binding to monoamine transporters.

    PubMed

    Dutta, A K; Fei, X S; Beardsley, P M; Newman, J L; Reith, M E

    2001-03-15

    In our effort to develop a pharmacotherapy for the treatment of cocaine addiction, we embarked on synthesizing novel molecules targeting the dopamine transporter (DAT) molecule in the brain as DAT has been implicated strongly in the reinforcing effect of cocaine. Our previously developed DAT-selective piperidine analogue, 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, was the basis for our current structure-activity relationship (SAR) studies exploring the significance of the contribution of the benzhydryl O- and N-atoms in these molecules in interacting with the DAT. Thus, we replaced the benzhydryl O-atom with an N-atom, altered the location of the benzhydryl N-atom to an adjacent position, and in one other occasion converted the benzhydryl O-ether linkage into an oxime-type derivative. Furthermore, we also evaluated the important contribution of the piperidine N-atom to binding by altering its pK(a) value chemically. Novel analogues were tested for potency in inhibiting [3H]WIN 35,428, [3H]citalopram, and [3H]nisoxetine binding at the DAT, serotonin transporter (SERT), and norepinepherine transporter (NET). [3H]DA was used to measure DA reuptake inhibition. The results indicated that the benzhydryl O- and N-atoms are exchangeable for the most part. On the other hand, an enhanced interaction with the SERT was observed when the benzhydryl N-atom moved to an adjacent position (21a; DAT (IC(50)) = 19.7, SERT (IC(50)) = 137 nM, NET (IC(50)) = 1111 nM). In either cases, further alkylation of the N-atom reduced the activity for the transporter. The presence of a powerful electron-withdrawing cyano group in compound 5d expectedly produced the most potent and selective ligand for the DAT (DAT (IC(50)) = 3.7 nM, DAT/SERT = 615). Selected compounds were further analyzed in the dopamine reuptake inhibition assay. Preliminary behavioral assessment of some of the selected compounds in mice indicated that these compounds are much less stimulating when compared with cocaine at comparable doses. In drug-discrimination studies these selected compounds incompletely generalized from the cocaine stimulus in mice trained to discriminate 10 mg/kg cocaine from vehicle. PMID:11300876

  12. Survey of Analogue Spacetimes

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    Analogue spacetimes (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole,(mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid—and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  13. Combined use of growth hormone and gonadotropin-releasing hormone analogues: the national cooperative growth study experience.

    PubMed

    Kohn, B; Julius, J R; Blethen, S L

    1999-10-01

    Gonadotropin-releasing hormone ana-logues (GnRHa) are used to treat central precocious puberty. They also are used to delay puberty in short children with a prognosis for impaired adult height. In both cases, growth hormone (GH) treatment is sometimes added. To determine how North American pediatric endocrinologists are using the combination of GH and GnRHa, we searched the National Cooperative Growth Study (NCGS) database and identified 509 patients who were treated with both. Among them were 139 patients with a diagnosis of precocious puberty. Most of these (82%) also had GH deficiency (GHD). Of the 370 patients who did not have precocious puberty, 71% had GHD. There were 200 patients with precocious puberty who were treated with GH but not with GnRHa. The children who were given GH alone (77% of whom had GHD) were much younger than the children who were given both GH and GnRHa (5.7 +/- 2.9 years for those who were not treated with GnRHa vs 9.1 +/- 2.7 years for those who were). Data on both predicted adult height before GH treatment and near- adult height were available for 141 of the patients who were given both GH and GnRHa. There was a statistically significant increase in near-adult height over pre-GH predicted adult height in girls with precocious puberty (5.4 +/- 4.3 cm) and without precocious puberty (3.0 +/- 6.1 cm). There was no statistically significant gain in height for boys who did not have precocious puberty (1.3 +/- 6.8 cm). There were too few boys with precocious puberty (n = 7) to enable meaningful conclusions. In a multiple regression analysis of data on girls who did not have precocious puberty, duration of GH treatment was the most important variable predictive of height gain.gonadotropin-releasing hormone, growth hormone, precocious puberty, idiopathic growth hormone deficiency, organic growth deficiency, idiopathic short stature. PMID:10506254

  14. Density Functional Theory Calculations of Redox Properties of Iron–Sulphur Protein Analogues

    SciTech Connect

    Niu, Shuqiang; Ichiye, Toshiko

    2011-06-08

    A central issue in understanding redox properties of iron–sulphur (Fe–S) proteins is determining the factors that tune the reduction potentials of the Fe–S clusters. Studies of redox site analogues play an important role, particularly because individual factors can be examined independently of the environment by combining calculations and experiments of carefully designed ligands for the analogues. For iron–sulphur analogues, our study has shown that broken-symmetry density functional theory gives good energetics when the geometry is optimised using B3LYP with a double-? basis set with polarisation functions, and the energies of these geometries are calculated using B3LYP with additional diffuse functions added to the sulphurs. A comparison of our calculated energies for redox site analogues in the gas phase against electron detachment energies measured by a combination of electrospray ionisation and photoelectron spectroscopy (EI–PES) by Wang and co-workers has been essential because the comparison is for exactly the same molecule with no approximation for the environment. Overall, the correlation of our B3LYP/ 6-31(++)SG**//B3LYP/6-31G** detachment energies with EI–PES experiments is excellent for a wide variety of analogues. Moreover, our calculations at this level have provided insight into a wide variety of properties of iron–sulphur proteins.

  15. Analysis of the RNA-Editing Reaction of ADAR2 with Structural and Fluorescent Analogues of the GluR-B R/G Editing Site

    E-print Network

    Beal, Peter A.

    17, 2000 ABSTRACT: ADARs are adenosine deaminases responsible for RNA editing reactions that occur the deamination active site (9, 10). Nucleoside deaminases, such as adenosine deaminase (ADA) and cytidine deaminates an adenosine in the sequence context of a natural editing site >90-fold more rapidly

  16. Site locality identification study: Hanford Site. Volume I. Methodology, guidelines, and screening

    SciTech Connect

    Not Available

    1980-07-01

    Presented in this report are the results of the site locality identification study for the Hanford Site using a screening process. To enable evaluation of the entire Hanford Site, the screening process was applied to a somewhat larger area; i.e., the Pasco Basin. The study consisted of a series of screening steps that progressively focused on smaller areas which are within the Hanford Site and which had a higher potential for containing suitable repository sites for nuclear waste than the areas not included for further study. Five site localities, designated H-1, H-2, H-3, H-4, H-5 (Figure A), varying in size from approximately 10 to 50 square miles, were identified on the Hanford Site. It is anticipated that each site locality may contain one or more candidate sites suitable for a nuclear waste repository. The site locality identification study began with definition of objectives and the development of guidelines for screening. Three objectives were defined: (1) maximize public health and safety; (2) minimize adverse environmental and socioeconomic impacts; and (3) minimize system costs. The screening guidelines have numerical values that provided the basis for the successive reduction of the area under study and to focus on smaller areas that had a higher likelihood of containing suitable sites.

  17. Substituted 3-(5-Imidazo[2,1-b]thiazolylmethylene)-2-indolinones and Analogues: Synthesis, Cytotoxic Activity and Study of the Mechanism of Action1

    PubMed Central

    Andreani, Aldo; Granaiola, Massimiliano; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla; Calonghi, Natalia; Cappadone, Concettina; Farruggia, Giovanna; Stefanelli, Claudio; Masotti, Lanfranco; Nguyen, Tam L.; Hamel, Ernest; Shoemaker, Robert H.

    2012-01-01

    The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly. PMID:22283430

  18. School Counseling Site Supervisor Training: An Exploratory Study

    ERIC Educational Resources Information Center

    DeKruyf, Lorraine; Pehrsson, Dale-Elizabeth

    2011-01-01

    This study explored the supervision training needs of site supervisors of master's program school counseling interns via the construct of self-efficacy. Using the Site Supervisor Self-Efficacy Survey developed for this study, the authors surveyed school counseling site supervisors in the states of Oregon and Washington (N = 147) regarding their…

  19. Anti-tumour and pharmacokinetics study of 2-Formyl-8-hydroxy-quinolinium chloride as Galipea longiflora alkaloid analogue.

    PubMed

    Lam, Kim-Hung; Lee, Kenneth Ka-Ho; Gambari, Roberto; Kok, Stanton Hon-Lung; Kok, Tsz-Wai; Chan, Albert Sun-Chi; Bian, Zhao-Xiang; Wong, Wai-Yeung; Wong, Raymond Siu-Ming; Lau, Fung-Yi; Tong, See-Wai; Chan, Kit-Wah; Cheng, Chor-Hing; Chui, Chung-Hin; Tang, Johnny Cheuk-On

    2014-05-15

    The quinolinium chloride salt of 8-hydroxyqinolinecarbaldehyde (2-Formyl-8-hydroxy-quinolinium chloride) was prepared as Galipea longiflora alkaloid analogue and its anticancer activity was evaluated both in vitro and in vivo. This chloride salt was found to show certain degree of selectivity between hepatoma cells and normal hepatocytes in vitro. Athymic nude mice Hep3B xenograft model further demonstrated that this 2-Formyl-8-hydroxy-quinolinium chloride could execute strong anti-tumour activity with the identification of extensive necrotic feature from the tumour xenograft and limited adverse toxicological effect. PMID:24680618

  20. A New View on Interstellar Dust - High Fidelity Studies of Interstellar Dust Analogue Tracks in Stardust Flight Spare Aerogel

    NASA Technical Reports Server (NTRS)

    Zolensky, Michael E.; Postberg F.; Allen, C.; Bajt, S.; Bechtel, H. A.; Borg, J.; Brenker, F.; Bridges, J.; Brownlee, D. E.; Bugiel, S.; Burchell, M.; Burghammer, M.; Butterworth, A. L.; Cloetens, P.; Davis, A. M.; Floss, C.; Flynn, G. J.; Frank, D.; Gainsforth, Z.

    2011-01-01

    In 2000 and 2002 the Stardust Mission exposed aerogel collector panels for a total of about 200 days to the stream of interstellar grains sweeping through the solar system. The material was brought back to Earth in 2006. The goal of this work is the laboratory calibration of the collection process by shooting high speed [5 - 30km/s] interstellar dust (ISD) analogues onto Stardust aerogel flight spares. This enables an investigation into both the morphology of impact tracks as well as any structural and chemical modification of projectile and collector material. First results indicate a different ISD flux than previously assumed for the Stardust collection period.

  1. Plant Volatile Analogues Strengthen Attractiveness to Insect

    PubMed Central

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A.; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of ?-ionone and benzaldehyde. The stabilities of ?-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than ?-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than ?-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  2. Plant volatile analogues strengthen attractiveness to insect.

    PubMed

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of ?-ionone and benzaldehyde. The stabilities of ?-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than ?-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than ?-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  3. SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION - THE DELAWARE SITE STUDY, 1989

    EPA Science Inventory

    The 1989 Delaware Superfund Innovative Technology Evaluation (SITE) Field Study vas a cooperative effort between the Atmospheric Research and Exposure Assessment Laboratory and the Environmental Monitoring Systems Laboratory located in Las Vegas. he SITE was established to satisf...

  4. Total Synthesis of Vinblastine, Related Natural Products, and Key Analogues and Development of Inspired Methodology Suitable for the Systematic Study of Their Structure–Function Properties

    PubMed Central

    2015-01-01

    Conspectus Biologically active natural products composed of fascinatingly complex structures are often regarded as not amenable to traditional systematic structure–function studies enlisted in medicinal chemistry for the optimization of their properties beyond what might be accomplished by semisynthetic modification. Herein, we summarize our recent studies on the Vinca alkaloids vinblastine and vincristine, often considered as prototypical members of such natural products, that not only inspired the development of powerful new synthetic methodology designed to expedite their total synthesis but have subsequently led to the discovery of several distinct classes of new, more potent, and previously inaccessible analogues. With use of the newly developed methodology and in addition to ongoing efforts to systematically define the importance of each embedded structural feature of vinblastine, two classes of analogues already have been discovered that enhance the potency of the natural products >10-fold. In one instance, remarkable progress has also been made on the refractory problem of reducing Pgp transport responsible for clinical resistance with a series of derivatives made accessible only using the newly developed synthetic methodology. Unlike the removal of vinblastine structural features or substituents, which typically has a detrimental impact, the additions of new structural features have been found that can enhance target tubulin binding affinity and functional activity while simultaneously disrupting Pgp binding, transport, and functional resistance. Already analogues are in hand that are deserving of full preclinical development, and it is a tribute to the advances in organic synthesis that they are readily accessible even on a natural product of a complexity once thought refractory to such an approach. PMID:25586069

  5. Total synthesis of vinblastine, related natural products, and key analogues and development of inspired methodology suitable for the systematic study of their structure-function properties.

    PubMed

    Sears, Justin E; Boger, Dale L

    2015-03-17

    Biologically active natural products composed of fascinatingly complex structures are often regarded as not amenable to traditional systematic structure-function studies enlisted in medicinal chemistry for the optimization of their properties beyond what might be accomplished by semisynthetic modification. Herein, we summarize our recent studies on the Vinca alkaloids vinblastine and vincristine, often considered as prototypical members of such natural products, that not only inspired the development of powerful new synthetic methodology designed to expedite their total synthesis but have subsequently led to the discovery of several distinct classes of new, more potent, and previously inaccessible analogues. With use of the newly developed methodology and in addition to ongoing efforts to systematically define the importance of each embedded structural feature of vinblastine, two classes of analogues already have been discovered that enhance the potency of the natural products >10-fold. In one instance, remarkable progress has also been made on the refractory problem of reducing Pgp transport responsible for clinical resistance with a series of derivatives made accessible only using the newly developed synthetic methodology. Unlike the removal of vinblastine structural features or substituents, which typically has a detrimental impact, the additions of new structural features have been found that can enhance target tubulin binding affinity and functional activity while simultaneously disrupting Pgp binding, transport, and functional resistance. Already analogues are in hand that are deserving of full preclinical development, and it is a tribute to the advances in organic synthesis that they are readily accessible even on a natural product of a complexity once thought refractory to such an approach. PMID:25586069

  6. The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K-ATPase.

    PubMed

    De Pont, Jan Joep H H M; Swarts, Herman G P; Karawajczyk, Anna; Schaftenaar, Gijs; Willems, Peter H G M; Koenderink, Jan B

    2009-01-01

    Based on studies with chimeras between (non-)gastric H,K-ATPase and Na,K-ATPase, a model for the ouabain binding site has recently been presented (Qiu et al. J.Biol.Chem. 280 (2005) 32349). In this model, hydrogen bonds between specific amino acid residues of Na,K-ATPase and hydroxyl groups of ouabain play a crucial role. In the present study, a series of ouabain analogues were tested on baculovirus-expressed Na,K-ATPase and an ouabain-sensitive mutant of non-gastric H,K-ATPase (D312E/ S319G/ A778P/ I795L/ F802C). For each analogue, the results obtained by measuring ATPase inhibition and [(3)H]ouabain replacement agreed rather well. In Na,K-ATPase, strophanthidin had a 7-10 times higher and digoxin a 4-12 times lower affinity than ouabain. The results of the non-gastric H,K-ATPase mutant were rather similar to that of Na,K-ATPase with exception of dihydro-ouabain that showed a much lower affinity with the non-gastric H,K-ATPase mutant. Docking studies showed that all analogues bind to the same pocket in Na,K-ATPase. However, the amino acids to which hydrogen bonds were formed differed and depended on the availability of hydroxyl or keto groups in the ouabain analogues. PMID:18324411

  7. Mineralogical, chemical, organic and microbial properties of subsurface soil cores from Mars Desert Research Station (Utah, USA): Phyllosilicate and sulfate analogues to Mars mission landing sites

    NASA Astrophysics Data System (ADS)

    Stoker, Carol R.; Clarke, Jonathan; Direito, Susana O. L.; Blake, David; Martin, Kevin R.; Zavaleta, Jhony; Foing, Bernard

    2011-07-01

    We collected and analysed soil cores from four geologic units surrounding Mars Desert Research Station (MDRS) Utah, USA, including Mancos Shale, Dakota Sandstone, Morrison formation (Brushy Basin member) and Summerville formation. The area is an important geochemical and morphological analogue to terrains on Mars. Soils were analysed for mineralogy by a Terra X-ray diffractometer (XRD), a field version of the CheMin instrument on the Mars Science Laboratory (MSL) mission (2012 landing). Soluble ion chemistry, total organic content and identity and distribution of microbial populations were also determined. The Terra data reveal that Mancos and Morrison soils are rich in phyllosilicates similar to those observed on Mars from orbital measurements (montmorillonite, nontronite and illite). Evaporite minerals observed include gypsum, thenardite, polyhalite and calcite. Soil chemical analysis shows sulfate the dominant anion in all soils and SO4>>CO3, as on Mars. The cation pattern Na>Ca>Mg is seen in all soils except for the Summerville where Ca>Na. In all soils, SO4 correlates with Na, suggesting sodium sulfates are the dominant phase. Oxidizable organics are low in all soils and range from a high of 0.7% in the Mancos samples to undetectable at a detection limit of 0.1% in the Morrison soils. Minerals rich in chromium and vanadium were identified in Morrison soils that result from diagenetic replacement of organic compounds. Depositional environment, geologic history and mineralogy all affect the ability to preserve and detect organic compounds. Subsurface biosphere populations were revealed to contain organisms from all three domains (Archaea, Bacteria and Eukarya) with cell density between 3.0×106 and 1.8×107 cells ml-1 at the deepest depth. These measurements are analogous to data that could be obtained on future robotic or human Mars missions and results are relevant to the MSL mission that will investigate phyllosilicates on Mars.

  8. Immediate, non-submerged, root-analogue direct laser metal sintering (DLMS) implants: a 1-year prospective study on 15 patients.

    PubMed

    Mangano, Francesco Guido; De Franco, Michele; Caprioglio, Alberto; Macchi, Aldo; Piattelli, Adriano; Mangano, Carlo

    2014-07-01

    This study evaluated the 1-year survival and success rate of root-analogue direct laser metal sintering (DLMS) implants, placed into the extraction sockets of 15 patients. DLMS is a technology which allows solids with complex geometry to be fabricated by annealing metal powder microparticles in a focused laser beam, according to a computer-generated three-dimensional (3D) model; the fabrication process involves the laser-induced fusion of titanium microparticles, in order to build, layer-by-layer, the desired object. Cone-beam computed tomography (CBCT) acquisition and 3D image conversion, combined with the DLMS process, allow the fabrication of custom-made, root-analogue implants (RAIs). CBCT images of 15 non-restorable premolars (eight maxilla; seven mandible) were acquired and transformed into 3D models: from these, custom-made, root-analogue DLMS implants with integral abutment were fabricated. Immediately after tooth extraction, the RAIs were placed in the sockets and restored with a single crown. One year after implant placement, clinical and radiographic parameters were assessed: success criteria included absence of pain, suppuration, and exudation; absence of implant mobility and absence of continuous peri-implant radiolucency; distance between the implant shoulder and the first visible bone-to-implant contact <1.5 mm from initial surgery; and absence of prosthetic complications. At the 1-year follow-up, no implants were lost, for a survival rate of 100 %. All implants were stable, with no signs of infection. The good conditions of the peri-implant tissues were confirmed by the radiographic examination, with a mean DIB of 0.7 mm (±0.2). The possibility of fabricating custom-made, RAI DLMS implants opens new interesting horizons for immediate placement of dental implants. PMID:23494103

  9. Aqueous extracts of a Mars analogue regolith that mimics the Phoenix landing site do not inhibit spore germination or growth of model spacecraft contaminants Bacillus subtilis 168 and Bacillus pumilus SAFR-032

    NASA Astrophysics Data System (ADS)

    Nicholson, Wayne L.; McCoy, Lashelle E.; Kerney, Krystal R.; Ming, Douglas W.; Golden, D. C.; Schuerger, Andrew C.

    2012-08-01

    Because Mars is a primary target for life detection and habitability assessment missions, its exploration is also by necessity a Planetary Protection issue. The recent finding of significant levels of perchlorate (ClO4-) in regolith sampled from the Phoenix landing site raises the question of its potential biotoxicity to putative indigenous martian life, microbial forward contaminants from Earth, or future human visitors. To address this issue, an analogue regolith was constructed based on regolith chemistry data from the Phoenix landing site. A Mars Aqueous Regolith Extract (MARE) was prepared from the Phoenix analogue regolith and analyzed by ion chromatography. The MARE contained (mg/L) the cations Na+ (1411 ± 181), Mg2+ (1051 ± 160), Ca2+ (832 ± 125), and K+ (261 ± 29), and the anions SO42-(5911±993), ClO4-(5316±1767), Cl(171±25) and F- (2.0 ± 0.4). Nitrogen-containing species NO3-(773±113) and NO2-(6.9±2.3) were also present as a result of regolith preparation procedures, but their relevance to Mars is at present unknown. The MARE was tested for potential toxic effects on two model spacecraft contaminants, the spore-forming bacteria Bacillus subtilis strain 168 and Bacillus pumilus strain SAFR-032. In B. subtilis, spore germination and initial vegetative growth (up to ˜5 h) was not inhibited in a rich complex medium prepared with the MARE, but growth after 5 h was significantly suppressed in medium prepared using the MARE. Both B. subtilis and B. pumilus exhibited significantly higher rates of spore germination and growth in the MARE vs. DW with no additions (likely due to endogenous spore nutrients), but germination and growth was further stimulated by addition of glucose and a combination of buffered inorganic salts (K2HPO4, KH2PO4, (NH4)2SO4, and MgSO4). The data indicate that the aqueous environment in the regolith from the Phoenix landing site containing high levels of perchlorate does not pose a significant barrier to growth of putative forward contaminants such as B. subtilis and B. pumilus under Earth laboratory conditions.

  10. Thiol-yne radical reaction mediated site-specific protein labeling via genetic incorporation of an alkynyl-L-lysine analogue.

    PubMed

    Li, Yiming; Pan, Man; Li, Yitong; Huang, Yichao; Guo, Qingxiang

    2013-04-28

    Three alkyne-containing pyrrolysine derivatives were synthesized and genetically encoded into proteins by a mutant PylRS-tRNA pair with high efficiencies. With these alkyne handles, site-specific dual labeling of proteins can be achieved via a bioorthogonal thiol-yne ligation reaction. PMID:23450369

  11. Kynurenic acid analogues with improved affinity and selectivity for the glycine site on the N-methyl-D-aspartate receptor from rat brain.

    PubMed

    Foster, A C; Kemp, J A; Leeson, P D; Grimwood, S; Donald, A E; Marshall, G R; Priestley, T; Smith, J D; Carling, R W

    1992-05-01

    The glycine site on the N-methyl-D-aspartate (NMDA) subtype of receptors for the excitatory neurotransmitter glutamate is a potential target for the development of neuroprotective drugs. We report here two chemical series of glycine site antagonists derived from kynurenic acid (KYNA), with greatly improved potency and selectivity. Disubstitution with chlorine or bromine in the 5- and 7-positions of KYNA increased affinity for [3H]glycine binding sites in rat cortex/hippocampus P2 membranes, with a parallel increase of potency for antagonism of NMDA-evoked responses in the rat cortical wedge preparation. The optimal compound was 5-I,7-Cl-KYNA, with an IC50 for [3H]glycine binding of 29 nM and an apparent Kb in the cortical wedge preparation of 0.41 microM. Reduction of the right-hand ring of 5,7-diCl-KYNA reduced affinity by 10-fold, but this was restored by substitution in the 4-position with the trans-phenylamide and further improved in the trans-benzylamide. The optimal compound was the transphenylurea (L-689,560), with an IC50 of 7.4 nM and an apparent Kb of 0.13 microM. Both series of compounds displayed a high degree of selectivity for the glycine site, having IC50 values of greater than 10 microM versus radioligand binding to the glutamate recognition sites of NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors and the strychnine-sensitive glycine receptor. Selectivity versus AMPA receptor-mediated responses was also apparent in the rat cortical wedge and in patch-clamp recordings of cortical neurons in culture. Experiments using [3H]dizocilpine (MK-801) binding indicated that 5,7-diBr-KYNA, 5,7-diCl-KYNA, 5-I,7-Cl-KYNA, and L-689,560 all behaved as full antagonists and were competitive with glycine. Patch-clamp recordings of cortical neurons in culture also indicated that NMDA-induced currents were antagonized by competition for the glycine site, and gave no evidence for partial agonist activity. pKi values for 5,7-diBr-KYNA and L-689,560 in these experiments were 7.2 and 7.98, respectively, similar to the affinities of these compounds in the glycine binding assay. The high affinity and selectivity of these new derivatives make them useful tools to investigate the function of the glycine site on the NMDA receptor. PMID:1375317

  12. Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

    PubMed Central

    Brock, Nelson L; Citron, Christian A; Zell, Claudia; Berger, Martine; Wagner-Döbler, Irene; Petersen, Jörn; Brinkhoff, Thorsten; Simon, Meinhard

    2013-01-01

    Summary Members of the marine Roseobacter clade can degrade dimethylsulfoniopropionate (DMSP) via competing pathways releasing either methanethiol (MeSH) or dimethyl sulfide (DMS). Deuterium-labeled [2H6]DMSP and the synthetic DMSP analogue dimethyltelluriopropionate (DMTeP) were used in feeding experiments with the Roseobacter clade members Phaeobacter gallaeciensis DSM 17395 and Ruegeria pomeroyi DSS-3, and their volatile metabolites were analyzed by closed-loop stripping and solid-phase microextraction coupled to GC–MS. Feeding experiments with [2H6]DMSP resulted in the incorporation of a deuterium label into MeSH and DMS. Knockout of relevant genes from the known DMSP demethylation pathway to MeSH showed in both species a residual production of [2H3]MeSH, suggesting that a second demethylation pathway is active. The role of DMSP degradation pathways for MeSH and DMS formation was further investigated by using the synthetic analogue DMTeP as a probe in feeding experiments with the wild-type strain and knockout mutants. Feeding of DMTeP to the R. pomeroyi knockout mutant resulted in a diminished, but not abolished production of demethylation pathway products. These results further corroborated the proposed second demethylation activity in R. pomeroyi. Isotopically labeled [2H3]methionine and 34SO4 2?, synthesized from elemental 34S8, were tested to identify alternative sulfur sources besides DMSP for the MeSH production in P. gallaeciensis. Methionine proved to be a viable sulfur source for the MeSH volatiles, whereas incorporation of labeling from sulfate was not observed. Moreover, the utilization of selenite and selenate salts by marine alphaproteobacteria for the production of methylated selenium volatiles was explored and resulted in the production of numerous methaneselenol-derived volatiles via reduction and methylation. The pathway of selenate/selenite reduction, however, proved to be strictly separated from sulfate reduction. PMID:23766810

  13. The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

    PubMed Central

    Wu, Hui; Xu, Hui; Xia, Fangzhen; Zhai, Hualing; Zhang, Huixin; Weng, Pan; Han, Bing; Du, Sichun; Lu, Yingli

    2014-01-01

    Objective. Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity. PMID:25580440

  14. Desferrithiocin Analogue Uranium Decorporation Agents

    PubMed Central

    Bergeron, Raymond J.; Wiegand, Jan; Singh, Shailendra

    2010-01-01

    Purpose Previous systematic structure-activity studies of the desferrithiocin (DFT) platform have allowed the design and synthesis of analogues and derivatives of DFT that retain the exceptional iron-clearing activity of the parent, while eliminating its adverse effects. We hypothesized that a similar approach could be adopted to identify DFT-related analogues that could effectively decorporate uranium. Materials and Methods The decorporation properties of nine DFT-related analogues were determined in a bile duct-cannulated rat model. Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected ligands also underwent multiple and delayed dosing regimens. Uranium excretion in urine and bile or stool was determined by inductively coupled plasma mass spectroscopy (ICP-MS); tissue levels of uranium were also assessed. Results The two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction on p.o. administration. The majority of the metal excretion promoted by these analogues is in the bile, thus further reducing kidney actinide exposure. Conclusions While 9 administered p.o. or subcutaneously (s.c.) immediately post-metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h reduced the activity of the compound. Conversion of 9 to its isopropyl ester may circumvent this issue. PMID:19399680

  15. Site study plan for Transportation, Deaf Smith County Site, Texas: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    This site study plan describes transportation field studies to be conducted during the characterization of the Deaf Smith County, Texas, site for the US Department of Energy's Salt Repository Project. The studies are needed to identify and assess potential project impacts to transportation infrastructure and systems in the project vicinity and along potential transportation routes to the site across the State of Texas. The studies are also needed to locate and design project transportation facilities, and to evaluate and design impact mitigation. After identifying the transportation information requirements needed to comply with Federal, State, and local regulations and repository program requirements, the site study plan describes the study design and rationale, the field data collection procedures and equipment, the data analysis methods and application of results, the data management strategy, the schedule of field activities, the management of the study, and the study's quality assurance program. The field data collection activities are organized into programs for the characterization of site vicinity rail corridors and highway corridors, characterization of alternative statewide transportation routes, monitoring of site characterization effects on transportation, characterization of aircraft overflight patterns and hazardous material transportation patterns, and assessment of emergency response preparedness along alternative statewide transportation routes. 34 refs., 10 figs., 2 tabs.

  16. Site study plan for cultural resources, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    The Cultural Resources Site Study Plan describes a field program to identify and evaluate the archaeological, historical, and Native American Indian resources of the site on local and regional perspectives; monitor and manage discovered cultural resources; and establish a worker education program. The archaeological field program consists of three pedestrian surveys: Survey 1 includes two EDBH seismic survey lines and the area within the exploratory shaft facility (ESF); Survey 2 includes the remainder of the site plus a 1/4 to 3/4-mi border area; and Survey 3 includes an assortment of offsite areas. The historical studies will identify and evaluate known and discovered historical sites and structures and the Native American Indian will identify and evaluate cultural and religious concerns expressed by Indian tribal groups. Prehistoric and historic sites will be evaluated to determine if they meet eligibility criteria for listing on the National Register of Historic Places. This site study plan describes the need for each study; its design and design rationale; analysis, management, and use of data; schedule of field activities; organization of field personnel and sample management; and quality assurance requirements. The cultural resource studies will provide data for satisfying the Programmatic Agreement, engineering design needs, and SRP requirements for permits and approvals, and for minimizing effects to any cultural properties discovered during site characterization. 75 refs., 10 figs., 2 tabs.

  17. Therapeutically interchangeable? A study of real-world outcomes associated with switching basal insulin analogues among US patients with type 2 diabetes mellitus using electronic medical records data

    PubMed Central

    Levin, P; Wei, W; Miao, R; Ye, F; Xie, L; Baser, O; Gill, J

    2015-01-01

    Aims To evaluate real-world clinical outcomes for switching basal insulin analogues [insulin glargine (GLA) and insulin detemir (DET)] among US patients with type 2 diabetes mellitus (T2DM). Methods Using the GE Centricity Electronic Medical Records database, this retrospective study examined two cohorts: cohort 1, comprising patients previously on GLA and then either switching to DET (DET-S) or continuing with GLA (GLA-C); and cohort 2, comprising patients previously on DET and then either switching to GLA (GLA-S) or continuing with DET (DET-C). Within each cohort, treatment groups were propensity-score-matched on baseline characteristics. At 1-year follow-up, insulin treatment patterns, glycated haemoglobin (HbA1c) levels, hypoglycaemic events, weight and body mass index (BMI) were evaluated. Results The analysis included 13?942 patients: cohort 1: n?=?10?657 (DET-S, n?=?1797 matched to GLA-C, n?=?8860) and cohort 2: n?=?3285 (GLA-S, n?=?858 matched to DET-C, n?=?2427). Baseline characteristics were similar between the treatment groups in each cohort. At 1-year follow-up, in cohort 1, patients in the DET-S subgroup were significantly less persistent with treatment, more likely to use a rapid-acting insulin analogue, had higher HbA1c values, lower HbA1c reductions and lower proportions of patients achieving HbA1c <7.0 or <8.0% compared with patients in the GLA-C subgroup, while hypoglycaemia rates and BMI/weight values and change from baseline were similar in the two subgroups. In cohort 2, overall, there were contrasting findings between patients in the GLA-S and those in the DET-C subgroup. Conclusions This study showed contrasting results when patients with T2DM switched between basal insulin analogues, although these preliminary results may be subject to limitations in the analysis. Nevertheless, this study calls into question the therapeutic interchangeability of GLA and DET, and this merits further investigation. PMID:25359227

  18. Picosecond time-resolved fluorescence of ribonuclease T1. A pH and substrate analogue binding study.

    PubMed Central

    Chen, L X; Longworth, J W; Fleming, G R

    1987-01-01

    The tryptophyl fluorescence of ribonuclease T1 decays monoexponentially at pH 5.5, tau = 4.04 ns but on increasing pH, a second short-lived component of 1.5 ns appears with a midpoint between pH 6.5 and 7.0. Both components have the same fluorescence spectrum. Acrylamide quenches both fluorescence components, and the short-lived component is quenched fivefold faster than the predominant long component. Binding of the substrate analogue 2'-guanylic acid at pH 5.5 quenches the fluorescence by 20% and introduces a second decay component, tau = 1.16 ns. Acrylamide quenches both tryptophyl decay components, with similar quenching rates. The fluorescence anisotropy decay of ribonuclease T1 was consistent with a molecule the size of ribonuclease T1 surrounded by a single layer of water at pH 7.4, even though the anisotropy decay at pH 5.5 deviated from Stokes-Einstein behavior. The fluorescence data were interpreted with a model where the tryptophyl residue exists in two conformations, remaining in a hydrophobic pocket. The acrylamide quenching is interpreted with electron transfer theory and suggests that one conformer has the nearest atom approximately 3 A from the protein surface, and the other, approximately 2 A. PMID:3038204

  19. Structural characterisation of the natural membrane-bound state of melittin: a fluorescence study of a dansylated analogue.

    PubMed

    Pérez-Payá, E; Dufourcq, J; Braco, L; Abad, C

    1997-10-23

    The binding of a dansylated analogue of melittin (DNC-melittin) to natural membranes is described. The cytolytic peptide from honey bee venom melittin was enzymatically labelled in its glutamine-25 with the fluorescent probe monodansylcadaverine using guinea pig liver transglutaminase. The labelled peptide was characterised functionally in cytolytic assays, and spectroscopically by circular dichroism and fluorescence. The behaviour of DNC-melittin was, in all respects, indistinguishable from that of the naturally occurring peptide. We used resonance energy transfer to measure the state of aggregation of melittin on the membrane plane in synthetic and natural lipid bilayers. When bound to erythrocyte ghost membranes, the extent of energy transfer was found to be equivalent to when bound to small unilamellar vesicles of phosphatidylcholine. Our results correlate best with a proposed model in which the initial interaction between melittin and the red blood cells could be merely electrostatic and the peptide remains in a low alpha-helical conformation. The next step would be a peptide stabilisation in the membrane in a monomeric alpha-helical conformation that would imply the collapse of the membrane structure and liberation of the cell contents. PMID:9371414

  20. Multidisciplinary study on Wyoming test sites

    NASA Technical Reports Server (NTRS)

    Houston, R. S. (principal investigator); Marrs, R. W.; Borgman, L. E.

    1975-01-01

    The author has identified the following significant results. Ten EREP data passes over the Wyoming test site provided excellent S190A and S190B coverage and some useful S192 imagery. These data were employed in an evaluation of the EREP imaging sensors in several earth resources applications. Boysen Reservoir and Hyattsville were test areas for band to band comparison of the S190 and S192 sensors and for evaluation of the image data for geologic mapping. Contrast measurements were made from the S192 image data for typical sequence of sedimentary rocks. Histograms compiled from these measurements show that near infrared S192 bands provide the greatest amount of contrast between geologic units. Comparison was also made between LANDSAT imagery and S190B and aerial photography for regional land use mapping. The S190B photography was found far superior to the color composite LANDSAT imagery and was almost as effective as the 1:120,000 scale aerial photography. A map of linear elements prepared from LANDSAT and EREP imagery of the southwestern Bighorn Mountains provided an important aid in defining the relationship between fracture and ground water movement through the Madison aquifer.

  1. The Valles natural analogue project

    SciTech Connect

    Stockman, H.; Krumhansl, J.; Ho, C. [Sandia National Labs., Albuquerque, NM (United States); McConnell, V. [Alaska Univ., Fairbanks, AK (United States). Geophysical Inst.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  2. Blocking of Na+/K+ transport by the MgPO4 complex analogue Co(NH3)4PO4 leaves the Na+/Na(+)-exchange reaction of the sodium pump unaltered and shifts its high-affinity ATP-binding site to a Na(+)-like form.

    PubMed

    Buxbaum, E; Schoner, W

    1990-10-24

    Inactivation of Na+/K(+)-ATPase activity by the MgPO4 complex analogue Co(NH3)4PO4 leads, in everted red blood cell vesicles, to the parallel inactivation of 22Na+/K+ flux and 86Rb/Rb+ exchange, but leaves the 22Na+/Na(+)-exchange activity and the uncoupled ATP-supported 22Na+ transport unaffected. Furthermore, inactivation of purified Na+/K(+)-ATPase by Co(NH3)4PO4 leads to a parallel decrease of the capacity of the [3H]ouabain receptor site, when binding was studied by the Mg2+/Pi-supported pathway (ouabain-enzyme complex II) but the capacity of the ouabain receptor site was unaltered, when the Na+/Mg2+/ATP-supported pathway (ouabain-enzyme complex I) was used. No change in the dissociation constants of either ouabain receptor complex was observed following inactivation of Na+/K(+)-ATPase. When eosin was used as a marker for the high-affinity ATP-binding site of the E1 conformation, formation of stable E'2.Co(NH3)4PO4 complex led to a shift in the high-affinity ATP-binding site towards the sodium form. This led to an increase in the dissociation constant of the enzyme complex with K+, from 1.4 mM with the unmodified enzyme to 280 mM with the Co(NH3)4PO4-inactivated enzyme. It was concluded, that the effects of Co(NH3)4PO4 on the partial activities of the sodium pump are difficult to reconcile with an alpha, beta-protomeric enzyme working according the Albers-Post scheme. The data are consistent with an alpha 2, beta 2 diprotomeric enzyme of interacting catalytic subunits working with a modified version of the Albers-Post model. PMID:1699757

  3. Double-blind, randomized, placebo-controlled study of safety, tolerability, pharmacokinetics and pharmacodynamics of TAK-683, an investigational metastin analogue in healthy men

    PubMed Central

    Scott, Graham; Ahmad, Irfan; Howard, Katy; MacLean, David; Oliva, Cristina; Warrington, Steve; Wilbraham, Darren; Worthington, Paul

    2013-01-01

    Aims Two randomized, double-blind, placebo-controlled studies were performed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the investigational metastin analogue, TAK-683, in healthy men. Methods We first investigated a single subcutaneous (s.c.) dose of TAK-683 (0.01–2.0 mg) in 60 subjects (TAK-683, n = 42; placebo, n = 18). We then assessed a single s.c. bolus of 0.03–1.0 mg TAK-683 on day 1, followed by a 0.01–2.0 mg day?1 continuous infusion on days 2–13, to simulate a depot formulation, in 30 subjects (TAK-683, n = 25; placebo, n = 5) for 14 days. Results TAK-683 was well tolerated up to a dose of 2.0 mg day?1 by continuous s.c. infusion for 14 days. Adverse events were similar between TAK-683 and placebo subjects at all dose levels. TAK-683 plasma concentrations generally increased in proportion to dose with single and continuous dosing, with steady-state concentrations achieved by day 2 of continuous dosing. TAK-683 at 2.0 mg day?1 suppressed testosterone below castration level (<50 ng dl?1) in four of five subjects by day 7 of continuous dosing. Luteinizing hormone and follicle stimulating hormone concentrations were suppressed with TAK-683 continuous dosing compared with placebo by up to 70 and 43%, respectively, but this was not consistently dose-dependent. Conclusions In healthy men, s.c. administration of TAK-683 was well tolerated at all dose levels. The PK profile of TAK-683 was favourable, and TAK-683 suppressed testosterone profoundly during continuous dosing. Further investigation of metastin analogues is warranted for the treatment of castration-resistant prostate cancer. PMID:22803642

  4. Characterisation of [3H]gabapentin binding to a novel site in rat brain: homogenate binding studies.

    PubMed

    Suman-Chauhan, N; Webdale, L; Hill, D R; Woodruff, G N

    1993-02-15

    The binding characteristics of [3H]gabapentin, the radiolabelled analogue of the novel anticonvulsant gabapentin (1-(aminomethyl)cyclohexaneacetic acid) were studied using purified synaptic plasma membranes prepared from rat cerebral cortex. In 10 mM HEPES buffer [3H]gabapentin bound to a single population of sites with high affinity (KD = 38 +/- 2.8 nM) with a maximum binding capacity of 4.6 +/- 0.4 pmol/mg protein, reaching equilibrium after 30 min at 20 degrees C. This novel site was unique to the central nervous system with little or no specific [3H]gabapentin being measurable in a range of peripheral tissues. Binding was potently inhibited by a range of gabapentin analogues and 3-alkyl substituted gamma-aminobutyric acid (GABA) derivates although GABA itself and the selective GABAB receptor ligand baclofen, were only weakly active. Gabapentin itself (IC50 = 80 nM) and 3-isobutyl GABA (IC50 = 80 nM) which also has anticonvulsant properties, showed the highest affinity for the binding site. Of a wide range of other pharmacologically active compounds only the polyamines spermine and spermidine influenced [3H]gabapentin binding, with both compounds producing a maximum of 50% inhibition of specific binding. Magnesium ions produced a similar pattern of inhibition but the effect of the polyamines and magnesium ions were not additive. The data provide evidence for the existence in brain of a novel binding site that may mediate the anticonvulsant effects of gabapentin and other potential anticonvulsant compounds. PMID:8384570

  5. Site Study Plan for Acoustics, Deaf Smith County Site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    The Acoustics site study plan describes a field program which characterizes existing sound levels, determines the area's sound propagation characteristics, and monitors the project-related sound emissions. The plan describes for each study: the need for the study, study design, data management and use, schedule, and quality assurance requirements. These studies will provide data needed to satisfy requirements contained in, or derived from, the Salt Repository Requirements Document. 37 refs., 9 figs., 3 tabs.

  6. What Makes a Good Site for Field Study?

    NSDL National Science Digital Library

    After learning how scientists at the museum decide on which sites to study, students select sites to study and map in this activity. It's designed to be completed in three to six sessions and has information for teachers, including tips on how to select, map out, and measure team plots within the class site. Perhaps the best way to get students invested in the topic of biodiversity is to get them involved in discovering for themselves the breadth and scope of the variety of life-forms that exist locally. At their own site, they will conduct systematic observations of plants, animals, or both. You will pick a specific site in which your students will work, and they will mark their team plots and record observations in their field journals. In this way, students will emulate the fieldwork carried out by biologists. They will observe, record, identify specimens, collect data, communicate, and share results.

  7. 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.

  8. A visual analogue thermometer for measuring pain intensity

    Microsoft Academic Search

    Manon Choinière; Rhonda Amsel

    1996-01-01

    A new instrument for measuring pain intensity—the visual analogue thermometer (VAT)—was developed to overcome limitations and disadvantages, of the conventional visual analogue scale (VAS). Two studies were performed to assess eke validity and utility of the VAT as compares to conventional pain instruments whose psychometric qualities are scientifically recognized. The fist study was carried out ;with a group of 65

  9. The Need for Analogue Missions in Scientific Human and Robotic Planetary Exploration

    NASA Technical Reports Server (NTRS)

    Snook, K. J.; Mendell, W. W.

    2004-01-01

    With the increasing challenges of planetary missions, and especially with the prospect of human exploration of the moon and Mars, the need for earth-based mission simulations has never been greater. The current focus on science as a major driver for planetary exploration introduces new constraints in mission design, planning, operations, and technology development. Analogue missions can be designed to address critical new integration issues arising from the new science-driven exploration paradigm. This next step builds on existing field studies and technology development at analogue sites, providing engineering, programmatic, and scientific lessons-learned in relatively low-cost and low-risk environments. One of the most important outstanding questions in planetary exploration is how to optimize the human and robotic interaction to achieve maximum science return with minimum cost and risk. To answer this question, researchers are faced with the task of defining scientific return and devising ways of measuring the benefit of scientific planetary exploration to humanity. Earth-based and spacebased analogue missions are uniquely suited to answer this question. Moreover, they represent the only means for integrating science operations, mission operations, crew training, technology development, psychology and human factors, and all other mission elements prior to final mission design and launch. Eventually, success in future planetary exploration will depend on our ability to prepare adequately for missions, requiring improved quality and quantity of analogue activities. This effort demands more than simply developing new technologies needed for future missions and increasing our scientific understanding of our destinations. It requires a systematic approach to the identification and evaluation of the categories of analogue activities. This paper presents one possible approach to the classification and design of analogue missions based on their degree of fidelity in ten key areas. Various case studies are discussed to illustrate the approach.

  10. Site study plan for borehole search and characterization, Deaf Smith County Site, Texas: Revision 1

    SciTech Connect

    Not Available

    1987-12-22

    This site study plan describes the Borehole Search and Characterization field activities to be conducted during the early stages of Site Characterization at the Deaf Smith County site, Texas. The field program has been designed to provide data useful in addressing information/data needs resulting from Federal/State/Local regulatory requirements and repository program requirements. Air and ground surveys, an extensive literature search, and landowner interviews will be conducted to locate wells within and adjacent to the proposed nuclear waste repository site in Deaf Smith County. Initially, the study will center around the planned Exploratory Shaft Facilities location and will expand outward from that location. Findings from this study may lead to preparation of a new site study plan to search suspected borehole locations, and excavate or reenter known boreholes for additional characterization or remedial action. The Salt Repository Project (SRP) Networks specify the schedule under which the program will operate. The Technical Field Services Contractor (TFSC) is responsible for conducting the field program. Data will be handled and reported in accordance with established SRP procedures. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that appropriate documentation is maintained. 13 refs., 6 figs., 3 tabs.

  11. Site study plan for routine laboratory rock mechanics, Deaf Smith County Site, Texas: Revision 1

    SciTech Connect

    Not Available

    1987-12-01

    This Site Study Plan for Routine Laboratory Rock Mechanics describes routine laboratory testing to be conducted on rock samples collected as part of the characterization of the Deaf Smith County site, Texas. This study plan describes the early laboratory testing. Additional testing may be required and the type and scope of testing will be dependent upon the results of the early testing. This study provides for measurements of index, hydrological, mechanical, and chemical properties with tests which are standardized and used widely in geotechnical investigations. Another Site Study Plan for Nonroutine Laboratory Rock Mechanics describes laboratory testing of samples from the site to determine mechanical, thermomechanical, and thermal properties by less widely used methods, many of which have been developed specifically for characterization of the site. Data from laboratory tests will be used for characterization of rock strata, design of shafts and underground facilities, and modeling of repository behavior in support of resolution of both preclosure and postclosure issues. A tentative testing schedule and milestone log are given. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that appropriate documentation is maintained. 18 refs., 8 figs., 3 tabs.

  12. Site Study Plan for salt, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    The Salt Site Study Plan (SSP) describes a program for characterizing the existing salt environment in the site vicinity. A step-by-step approach is described which proceeds from published data and planned theoretical studies, to planned laboratory studies, and finally to planned field studies, to provide the necessary data to meet program requirements contained in the Salt Repository Project - Requirements Document (SRP-RD). The plan also draws on the results of other SSP's for certain data; for example, soil salinity data are to be provided under the Soils SSP. The salt studies consist of evaluation of control and mitigation measures, salt monitoring studies, emission factors development, air models development and validation, and risk assessment. For each study, its design and design rationale; analysis, management, and use of data; schedule of activities; organization of personnel and sample management; and quality assurance requirements are described. 90 refs., 9 figs., 7 tabs.

  13. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins.

    PubMed

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    2014-05-21

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin. PMID:24589992

  14. Quantum Analogue Computing

    E-print Network

    Vivien M. Kendon; Kae Nemoto; William J. Munro

    2010-01-13

    We briefly review what a quantum computer is, what it promises to do for us, and why it is so hard to build one. Among the first applications anticipated to bear fruit is quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data is encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data is encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous variable quantum computers (CVQC) becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  15. Quantum analogue computing.

    PubMed

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future. PMID:20603371

  16. Bioremediation demonstration on Kwajalein Island: Site characterization and on-site biotreatability studies

    SciTech Connect

    Siegrist, R.L.; Korte, N.E.; Pickering, D.A. (Oak Ridge National Lab., TN (United States)); Phelps, T.J. (Tennessee Univ., Knoxville, TN (United States))

    1991-09-01

    An environmental study was conducted during February 1991 on Kwajalein Island, a US Army Kwajalein Atoll (USAKA) Base in the Republic of the Marshall Islands (RMI). This study was undertaken for the US Department of Energy (DOE) Hazardous Waste Remedial Actions Program (HAZWRAP) acting in behalf of USAKA. The purpose of the study was to determine if selected locations for new construction on Kwajalein Island were contaminated by petroleum hydrocarbons as suspected and, if so, whether bioremediation appeared to be a feasible technology for environmental restoration. Two different sites were evaluated: (1) the site planned freshwater production facility and (2) a site adjacent to an aboveground diesel fuel storage tank. Within the proposed construction zone for the freshwater production facility (a.k.a desalination plant), total petroleum hydrocarbons (TPH) where either absent or at low levels. Characterization data for another potential construction site adjacent to an aboveground diesel fuel storage tank southeast of the old diesel power plant revealed high concentrations of diesel fuel in the soil and groundwater beneath the site. Results of this investigation indicate that there are petroleum-contaminated soils on Kwajalein Island and bioremediation appears to be a viable environmental restoration technique. Further experimentation and field demonstration are required to determine the design and operating conditions that provide for optimum biodegradation and restoration of the petroleum-contaminated soils. 17 refs., 7 figs., 26 figs.

  17. Emerald Lake Watershed study: Introduction and site description

    Microsoft Academic Search

    Kathy A. Tonnessen

    1991-01-01

    The Emerald Lake Watershed study was organized to investigate the effects of acidic deposition on high-elevation watersheds and surface waters of the Sierra Nevada, California. Some of the results of this comprehensive study of aquatic and terrestrial ecosystems at a small, headwater basin are presented in four papers in this series. The watershed study site is in Sequoia National Park,

  18. Second Information Technology in Education Study: SITES 2006 Technical Report

    ERIC Educational Resources Information Center

    Carstens, Ralph, Ed.; Pelgrum, Willem J., Ed.

    2009-01-01

    The International Association for the Evaluation of Educational Achievement (IEA) has been conducting comparative studies for 50 years. SITES 2006 is the fifth wave of surveys related to information and communication technology (ICT), a wave that IEA started with its Computers in Education Study (two studies with data collection in 1989 and 1992),…

  19. Natural analogue synthesis report, TDR-NBS-GS-000027 rev00 icn02

    SciTech Connect

    Simmons, A.; Nieder-Westermann, G.; Stuckless, J.; Dobson, P.; Unger, A.J.A.; Kwicklis, E.; Lichtner, P.; Carey, B.; Wolde, G.; Murrel,M.; Kneafsey, T.J.; Meijer, A.; Faybishenko, B.

    2002-04-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M&O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide release on the biosphere, and potentially disruptive events. Results of these studies will be used to corroborate estimates of the magnitude and limitation of operative processes in order to build realism into conceptual and numerical process models used as a foundation for PA in the representative case of postclosure safety.

  20. Site Study Plan for laboratory soil mechanics, Deaf Smith County site, Texas: Revision 1

    SciTech Connect

    Not Available

    1987-12-01

    This Site Study Plan for laboratory soil mechanics describes the laboratory testing to be conducted on soil samples collected as part of the characterization of the Deaf Smith County site, Texas. This study provides for measurements of index, mechanical, thermal, hydrologic, chemical, and mineral properties of soils from boring throughout the site. Samples will be taken from Playa Borings/Trenching, Transportation/Utilities Foundation Borings, Repository Surface Facilities Design Foundation Borings, and Exploratory Shaft Facilities Design Foundation Borings. Data from the laboratory tests will be used for soil strata characterization, design of foundations for surface structures, design of transportation facilities and utility structures, design of impoundments, design of shaft lining, design of the shaft freeze wall, shaft permitting, performance assessment calculations, and other program requirements. A tentative testing schedule and milestone log are given. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that appropriate documentation is maintained. 18 refs., 6 figs., 3 tabs.

  1. TWRS privatization phase I site development engineering study

    SciTech Connect

    Shord, A.L.

    1996-09-30

    The DOE-RL is pursuing a new business strategy of hiring private contractors for treatment of Hanford Site tank wastes. This strategy is called `privatization` and includes design, permitting, construction, operation and deactivation of facilities for tank waste treatment. The TWRS Privatization Infrastructure Project consists of several sub-projects which will provide key services needed to support the privatization mission. One sub-project is to develop the selected site for the privatization facilities. This study addresses the pertinent issues related to the development of the site and specific parcels to be assigned to each of two private contractors. It also summarizes other studies that address provisions for utilities and other site services.

  2. Site-specific magnetization reversal studies of magnetite

    SciTech Connect

    Cady, A.; Haskel, D.; Lang, J. C.; Islam, Z.; Srajer, G. [Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Ankudinov, A. [Department of Physics, University of Washington, Seattle, Washington 98195 (United States); Subias, G.; Garcia, J. [Instituto de Ciencia de Materiales de Aragon, CSIC-Universidad de Zaragoza, Pza. San Francisco s/n 50009 Zaragoza (Spain)

    2006-04-01

    The mechanism of magnetization reversal in magnetite (Fe{sub 3}O{sub 4}) single crystals was studied using site-specific magnetic sensitive diffraction anomalous near-edge structure. By exploiting the angular dependence of the cross section, we are able to show that the mechanism of reversal involves a mixture of coherent rotation and domain formation. The results reveal additional details to that provided by XMCD measurements, which average over nonequivalent sites.

  3. Microbial studies of a selenium-contaminated mine site and potential for on-site remediation

    Microsoft Academic Search

    Heather M. Knotek-Smith; Don L. Crawford; Gregory Möller; Rachel A. Henson

    2006-01-01

    Surface water Selenium (Se) concentrations are above regulatory standards at several active and inactive phosphate mine sites in the US Western Phosphate Resource Area. The focus of the present study was to examine the impacts of the microbial communities on the oxidation state of Se in overburden waste from the Smoky Canyon phosphate mine in Idaho, USA. Microbial populations were

  4. Quantitative comparisons of analogue models of brittle wedge dynamics

    Microsoft Academic Search

    Guido Schreurs

    2010-01-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct

  5. Long-term effects of CO2 on the mechanical behaviour of faults - a study of samples from a natural CO2 analogue (Entrada Sandstone, Utah, USA)

    NASA Astrophysics Data System (ADS)

    Bakker, E.; Hangx, S.; Spiers, C. J.

    2012-12-01

    CO2 capture followed by storage in depleted oil and gas reservoirs is currently seen as one of the most promising CO2-mitigation strategies. An important issue in relation to long-term CO2 storage is the prediction of the effects of fluid-rock interaction on the mechanical integrity and sealing capacity of the reservoir-seal system, on timescales of the order of 103 or 104 years. However, the assumed chemical interactions in the rock/CO2/brine system are slow, so that their long-term effects on rock composition, microstructure, mechanical properties and transport properties cannot be reproduced in laboratory experiments. One way to address this is to study the effects of reactions in natural CO2 reservoirs, using a so-called natural analogue approach. We tackled the question of how reactions characterizing natural CO2 fields affect fault friction, fault reactivation potential and seismic vs. aseismic slip stability, as well as transmissivity evolution during and after fault reactivation. Simulated fault gouges were prepared by crushing material obtained from surface outcrops of the Entrada Sandstone, a locally CO2-bearing formation forming an analogue field under the Colorado Plateau, Utah, USA . We used three types of starting material: 1) CO2 unaffected (unbleached) samples consisting mainly of quartz and feldspar, 2) "bleached" samples, and 3) heavily cemented/altered fault rock containing a high percentage of carbonates (> 40 wt%). The latter two were altered as a result of interaction with CO2-rich fluids over geological time. We performed triaxial direct shear experiments on these materials at room temperature under nominally dry conditions, at normal stresses up to 90 MPa and shear velocities of 0.22 -10.9 ?m/s. The results of the experiments yielded friction coefficients (?= ?/?n) of 0.55-0.85 for unbleached sandstone gouge and 0.45-0.80 for bleached material, while the fault material showed systematically higher friction coefficients (0.60-0.95). All simulated gouges showed a decrease in friction coefficient of 20-30% with increasing normal stress up to 90 MPa, with almost all samples showing velocity-strengthening (stable) slip behaviour. Permeability measurements show only minor changes during shear. Overall, our results demonstrated that higher (CO2-related) carbonate content leads to higher frictional strength and increased velocity strengthening (slip stability), notably at low normal stresses. However, preliminary results recently obtained at elevated temperatures show that carbonate-rich samples show velocity-weakening behaviour at 100°C, which is in line with previous studies on pure carbonates. A natural analogue from The Netherlands shows similar results for the chemical alteration of reservoir rock by the presence of naturally long-term stored CO2.

  6. Site Study Plan for Aesthetics, Deaf Smith County Site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    The Aesthetic Site Study Plan describes a field program consisting of identification of the visually affected area; determination of scenic quality, visual sensitivity, and visual management classes of the site and vicinity; and analysis of the level of visual contrast that would be created by the project. Field ratings of scenic quality, visual sensitivity, and visual contrast will be supplemented by a public perception survey designed to incorporate the views of the public. This plan describes the need for the study, the study design, data management and use, schedule for proposed activities, and quality assurance program. This study will provide data needed to satisfy requirements contained in, or derived from, SRPO Requirement Document (SRP-RD). 35 refs., 6 figs., 2 tabs.

  7. Study Abroad in Venezuela ON-SITE GUIDE 201415

    E-print Network

    Weiblen, George D

    Study Abroad in Venezuela ON-SITE GUIDE 2014­15 S T U D Y A B R O A D THE AMERICAS #12;2 Important Names & Addresses In the United States Learning Abroad Center Study, Work, Intern, Volunteer, & Travel Abroad Center at 612.626.9000 at any time. If it is after business hours, there will be a recording

  8. Modelling Data from Different Sites, Times or Studies

    E-print Network

    Fletcher, David

    Modelling Data from Different Sites, Times or Studies: Weighted versus Unweighted Regression David 91 #12;Examples Meta-regression of emergence time in plants (Verd and Travaset 2005): results from 55 studies to assess effect of emergence time on survival, growth and fecundity. Allow for differences

  9. Hanford Site Annual Treatability Studies Report Calendar Year 2001

    Microsoft Academic Search

    Grohs; Eugene L

    2002-01-01

    This report provides information required to be reported annually by the Washington Administrative Code (WAC) 173-303-071 (3)(r)(ii)(F) and (3)(s)(ix) on the treatability studies conducted on the Hanford Site in 2000. These studies were conducted as required by WAC 173-303-071, \\

  10. Analogue-to-Digital and Digital-to-Analogue Conversion.

    ERIC Educational Resources Information Center

    Gregory, Martin

    1997-01-01

    Discusses circuits for three-bit and four-bit analogue digital converters and digital analogue converters. These circuits feature slow operating speeds that enable the circuitry to be used to demonstrate the mode of operation using oscilloscopes and signal generators. (DDR)

  11. Design of insulin analogues for meal-related therapy.

    PubMed

    Brange, J

    1993-01-01

    The human insulin in replacement therapy has a hexameric structure. Hexamerization of the insulin molecule facilitates biosynthesis and beta-cell storage of insulin, but is unnecessary for biologic activity and appears to contribute to delayed absorption of exogenous insulin from the subcutis. Insulin analogues with reduced self-association that are produced through recombinant DNA techniques have been shown to have in vivo activity comparable to that of human insulin and absorption kinetics characterized by higher and more constant rates of disappearance from the subcutaneous injection site. In preliminary studies in patients receiving insulin therapy, monomeric insulin analogues have been found to provide glycemic control in the postprandial period that is at least equivalent to that of human insulin. Findings in these studies suggest that the use of such analogues may provide meal-related insulin effects closer to those observed in the physiologic state by limiting excessive postprandial glucose excursions and decreasing the risk of late hypoglycemia. Banting and Best revolutionized diabetes therapy 70 years ago with the extraction of insulin from animal pancreas glands (J Lab Clin Med 7:464-472, 1922). Since that time, many refinements of the therapeutic properties of pharmaceutical preparations of the hormone have been introduced. Until recently, however, such advances have been limited to improvements in insulin purity, insulin species, and adjustment of the composition of the vehicle with respect to auxiliary substances and other additives. With the advent of recombinant DNA techniques, it has become possible to optimize the insulin molecule itself for purposes of replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8518452

  12. Late Pleniglacial vegetation in eastern-central Europe: are there modern analogues in Siberia?

    NASA Astrophysics Data System (ADS)

    Magyari, Enik? Katalin; Kuneš, Petr; Jakab, Gusztáv; Sümegi, Pál; Pelánková, Barbora; Schäbitz, Frank; Braun, Mihály; Chytrý, Milan

    2014-07-01

    To characterize Late Pleniglacial (LPG: 26.5-15 ka cal BP) and particularly Last Glacial Maximum (LGM: 21 ± 2 ka cal BP) vegetation and climate, fossil pollen assemblages are often compared with modern pollen assemblages. Given the non-analogue climate of the LPG, a key question is how glacial pollen assemblages and thereby vegetation compare with modern vegetation. In this paper we present three LPG pollen records from the Carpathian Basin and the adjoining Carpathian Mountains to address this question and provide a concise compositional characterization of the LPG vegetation. Fossil pollen assemblages were compared with surface pollen spectra from the Altai-Sayan Mountains in southern Siberia. This area shows many similarities with the LPG vegetation of eastern-central Europe, and has long been considered as its best modern analogue. Ordination and analogue matching were used to characterize vegetation composition and find the best analogues. Our results show that few LPG pollen assemblages have statistically significant analogues in southern Siberia. When analogue pairings occur they suggest the predominance of wet and mesic grasslands and dry steppe in the studied region. Wooded vegetation types (continental and suboceanic hemiboreal forest, continental taiga) appear as significant analogues only in a few cases during the LGM and more frequently after 16 ka cal BP. These results suggest that the LPG landscape of the Carpathian Basin was dominated by dry steppe that occurred outside the river floodplains, while wet and mesic grasslands occurred in the floodplains and on other sites influenced by ground water. Woody vegetation mainly occurred in river valleys, on wet north-facing hillsides, and scattered trees were likely also present on the loess plateaus. The dominant woody species were Larix, Pinus sylvestris, Pinus mugo, Pinus cembra, Picea abies, Betula pendula/pubescens, Betula nana, Juniperus, Hippophaë rhamnoides, Populus, Salix and Alnus. The pollen records suggest uninterrupted presence of mesophilous temperate trees (Quercus, Ulmus, Corylus, Fagus and Fraxinus excelsior) in the Eastern Carpathian Mountains throughout the LPG. We demonstrate that the LPG vegetation in this area was characterized by increasing grass cover and high frequency of wildfires. We conclude that pollen spectra over represent trees in the forest-steppe landscape of the LPG, furthermore pollen-based quantitative climate reconstructions for the LPG are challenging in this area due to the scarcity of modern analogues.

  13. Hanford Site Annual Treatability Studies Report: Calendar Year 2000

    Microsoft Academic Search

    McCoy; Michael W

    2001-01-01

    This report provides information required to be reported annually by the Washington Administrative Code (WAC) 173-303-071 (3)(r)(ii)(F) and (3)(s)(ix) on the treatability studies conducted on the Hanford Site in 2000. These studies were conducted as required by WAC 173-303-071, ?Excluded Categories of Waste,? sections (3)(r) and (s). Unless otherwise noted, the waste samples were provided by and the treatability studies

  14. Hanford Site Annual Treatability Studies Report, Calendar Year 2002

    Microsoft Academic Search

    Grohs; Eugene L

    2003-01-01

    This report provides information required to be reported annually by the Washington Administrative Code (WAC) 173-303-071 (3)(r)(ii)(F) and (3)(s)(ix) on the treatability studies conducted on the Hanford Site in 2002. These studies were conducted as required by WAC 173-303-071, Excluded Categories of Waste, sections (3)(r) and (s). Unless otherwise noted, the waste samples were provided by and the treatability studies

  15. Energy conserving site design case study: Shenandoah, Georgia. Final report

    SciTech Connect

    Not Available

    1980-01-01

    The case study examines the means by which energy conservation can be achieved at an aggregate community level by using proper planning and analytical techniques for a new town, Shenandoah, Georgia, located twenty-five miles southwest of Atlanta's Hartsfield International Airport. A potentially implementable energy conservation community plan is achieved by a study team examining the land use options, siting characteristics of each building type, alternate infrastructure plans, possible decentralized energy options, and central utility schemes to determine how community energy conservation can be achieved by use of pre-construction planning. The concept for the development of mixed land uses as a passively sited, energy conserving community is based on a plan (Level 1 Plan) that uses the natural site characteristics, maximizes on passive energy siting requirement, and allows flexibility for the changing needs of the developers. The Level 2 Plan is identical with Level 1 plan plus a series of decentraized systems that have been added to the residential units: the single-family detached, the apartments, and the townhouses. Level 3 Plan is similar to the Level 1 Plan except that higher density dwellings have been moved to areas adjacent to central site. The total energy savings for each plan relative to the conventional plan are indicated. (MCW)

  16. Repeat Hydrography at the Endeavour Integrated Study Site, 2004 - 2006

    Microsoft Academic Search

    J. P. Kellogg; R. E. McDuff; R. E. Thomson; F. R. Stahr

    2006-01-01

    Significant differences exist between hydrographic transects made in the summers from 2004 to 2006 at the Endeavour Segment Integrated Study Site on the Juan de Fuca Ridge. Along and across axis sections describe the hydrographic conditions above the segment in three dimensions. The resulting sections allow for rapid evaluation of the characteristics of the neutrally buoyant plume over each of

  17. Repeat Hydrography at the Endeavour Integrated Study Site, 2004 - 2005

    Microsoft Academic Search

    J. P. Kellogg; R. E. McDuff; R. E. Thomson; F. R. Stahr

    2005-01-01

    Significant differences exist between hydrographic transects made in 2004 and 2005 at the Endeavour Segment Integrated Study Site on the Juan de Fuca Ridge. Sections that describe the conditions above the segment utilize twenty-one nearly uniformly spaced hydrographic stations from south of Mothra to north of the Sasquatch hydrothermal vent fields. Criteria used in choosing station locations included depth, ~500

  18. Study Abroad in Tanzania ON-SITE GUIDE 201415

    E-print Network

    Netoff, Theoden

    Study Abroad in Tanzania ON-SITE GUIDE 2014­15 AFRICA &THE MIDDLE EASTS T U D Y A B R O A D #12 staff. In Tanzania Telephone Codes 011--International access code from the US. The code from other countries will probably be different. 255--Tanzania country code used for dialing from outside Tanzania 27

  19. Human Factor Studies on a Mars Analogue During Crew 100b International Lunar Exploration Working Group EuroMoonMars Crew: Proposed New Approaches for Future Human Space and Interplanetary Missions

    PubMed Central

    Rai, Balwant; Kaur, Jasdeep

    2012-01-01

    Knowing the risks, costs, and complexities associated with human missions to Mars, analogue research can be a great (low-risk) tool for exploring the challenges associated with the preparation for living, operating, and undertaking research in interplanetary missions. Short-duration analogue studies, such as those being accomplished at the Mars Desert Research Station (MDRS), offer the chance to study mission operations and human factors in a simulated environment, and therefore contribute to exploration of the Moon and Mars in planned future missions. This article is based upon previously published articles, abstracts, and presentations by a series of independent authors, human factor studies performed on mars analogue station by Crew 100B. The MDRS Crew 100B performed studies over 15 days providing a unique insight into human factor issues in simulated short-duration Mars mission. In this study, 15 human factors were evaluated and analyzed by subjective and objective means, and from the summary of results it was concluded that optimum health of an individual and the crew as a whole is a necessity in order to encourage and maintain high performance and the satisfaction of project goals. PMID:23181225

  20. Human Factor Studies on a Mars Analogue During Crew 100b International Lunar Exploration Working Group EuroMoonMars Crew: Proposed New Approaches for Future Human Space and Interplanetary Missions.

    PubMed

    Rai, Balwant; Kaur, Jasdeep

    2012-11-01

    Knowing the risks, costs, and complexities associated with human missions to Mars, analogue research can be a great (low-risk) tool for exploring the challenges associated with the preparation for living, operating, and undertaking research in interplanetary missions. Short-duration analogue studies, such as those being accomplished at the Mars Desert Research Station (MDRS), offer the chance to study mission operations and human factors in a simulated environment, and therefore contribute to exploration of the Moon and Mars in planned future missions. This article is based upon previously published articles, abstracts, and presentations by a series of independent authors, human factor studies performed on mars analogue station by Crew 100B. The MDRS Crew 100B performed studies over 15 days providing a unique insight into human factor issues in simulated short-duration Mars mission. In this study, 15 human factors were evaluated and analyzed by subjective and objective means, and from the summary of results it was concluded that optimum health of an individual and the crew as a whole is a necessity in order to encourage and maintain high performance and the satisfaction of project goals. PMID:23181225

  1. Site Study Plan for soils, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    The Soils Site Study Plan describes a field program consisting of a soil characterization survey, impact monitoring of soils, predisturbance soil salinity survey, and a reclamation suitability study. This information will be used to plan for soil stripping, stockpiling, and replacement; reclamation of soils; determining predisturbance chemical and physical characteristics of the soils; including salinity levels; and monitoring for changes in chemical and physical characteristics of the soil. The SSP describes for each study the need for the study, the study design, data management and use, schedule of proposed activities, and the quality assurance program. These studies will provide data needed to satisfy requirements contained in, or derived from, the Salt Repository Project Requirements Document. 75 refs., 10 figs., 5 tabs.

  2. Site matching of wind turbine generators: A case study

    SciTech Connect

    Jangamshetti, S.H.; Rau, V.G.

    1999-12-01

    Site matching of wind turbine generators is investigated based on appropriate selection of statistical models and means of wind speed data. The wind speed means are computed using arithmetic mean, root mean square and cubic mean cuberoot. Wind Speed frequency distributions are modeled using Weibull and Rayleigh probability density functions. Wind speed data of an existing wind power station, located at Kappadagudda, Karnataka, India, is used for computational purposes. The analytically obtained capacity factors are validated by comparing with the actual capacity factors obtained at Kappadagudda. It is observed that the capacity factors computed from the Weibull statistical model using cubic mean of wind speed data fairly match the actual capacity factors obtained from Kappadagudda wind power station. Various commercially available wind turbine generators are used for site matching study. The model described in the paper is useful for planning of wind power stations as it can be applied for accurate assessment of wind power potential at a site.

  3. Wildlife studies on the Hanford site: 1994 Highlights report

    SciTech Connect

    Cadwell, L.L. [ed.

    1995-04-01

    The purposes of the project are to monitor and report trends in wildlife populations; conduct surveys to identify, record, and map populations of threatened, endangered, and sensitive plant and animal species; and cooperate with Washington State and federal and private agencies to help ensure the protection afforded by law to native species and their habitats. Census data and results of surveys and special study topics are shared freely among cooperating agencies. Special studies are also conducted as needed to provide additional information that may be required to assess, protect, or manage wildlife resources at Hanford. This report describes highlights of wildlife studies on the Site in 1994. Redd counts of fall chinook salmon in the Hanford Reach suggest that harvest restrictions directed at protecting Snake River salmon may have helped Columbia River stocks as well. The 1994 count (5619) was nearly double that of 1993 and about 63% of the 1989 high of approximately 9000. A habitat map showing major vegetation and land use cover types for the Hanford Site was completed in 1993. During 1994, stochastic simulation was used to estimate shrub characteristics (height, density, and canopy cover) across the previously mapped Hanford landscape. The information provided will be available for use in determining habitat quality for sensitive wildlife species. Mapping Site locations of plant species of concern continued during 1994. Additional sensitive plant species data from surveys conducted by TNC were archived. The 10 nesting pairs of ferruginous hawks that used the Hanford Site in 1993 represented approximately 25% of the Washington State population.

  4. Veterans aging cohort three-site study (VACS 3)

    Microsoft Academic Search

    S Smola; A. C Justice; J Wagner; L Rabeneck; S Weissman; M Rodriguez-Barradas

    2001-01-01

    Outcomes for middle-aged and older individuals with HIV infection are poor, and are likely to be mediated by age-related differences in risks and resources (access to care, relationship with the provider, comorbid conditions, health habits, and changes brought about by aging). The goal of the Veterans Aging Cohort Three-Site Study (VACS 3) is to study the influence of age and

  5. HANFORD SITE ANNUAL TREATABILITY STUDIES REPORT CY2003

    Microsoft Academic Search

    2004-01-01

    This report provides information required to be reported annually by the Washington Administrative Code (WAC) 173-303-071 (3)(r)(ii)(F) and (3)(s)(ix) on the treatability studies conducted by various laboratories for the Hanford Site in 2003. These studies were conducted in accordance with WAC 173-303-071, ''Excluded Categories of Waste,'' to determine whether the waste is amenable to the treatment process, what pre-treatment may

  6. The spectral properties and photosensitivities of analogue photopigments regenerated with 10- and 14-substituted retinal analogues.

    PubMed

    Crescitelli, F; Liu, R S

    1988-02-23

    Analogues of 11-cis- and 9-cis-retinal with substitutions at positions 10 and 14 were used to regenerate analogue photopigments with two opsins: that of the transmuted (cone-like) 521-pigment of Gekko gekko and that of the rhodopsin of Porichthys notatus. The spectral absorbances and photosensitivities of the regenerated photopigments were determined and compared, first, between the two systems of analogue photopigments, and second, in the responses to the two opsins. Unlike the 10-fluoropigments, the comparable 14-compounds were significantly red-shifted by 19-30 nm and their sensitivity to light was similar to that of the parent 11-cis- and 9-cis-pigments. These were the results for both analogue pigments. In contrast, the 10-pigments were spectrally located close to the wavelengths of the parent compounds and the photosensitivity was significantly reduced, especially in the case of the 9-cis-analogues. Evidence was obtained for a steric hindrance effect at position 14, for no regeneration was obtained when methyl or ethyl groups were at this carbon. In the 10-substituted retinals, steric hindrance was noted only for the gecko; only the fluorosubstituted, but not the chloro-, the methyl- or the ethyl-substituted, retinals reacted. With the fish opsin, pigments were regenerated with all but the ethyl-substituted retinal. The gecko opsin appears to have a more restricted binding site. Another feature of the gecko was related to the chloride bathochromic and hyperchromic effects, in which the 521-pigment prepared in a chloride-deficient state has a blue-shifted spectrum compared with the spectrum obtained after the addition of chloride, and its extinction is raised by the addition of chloride to give a mean ratio of 1.23 for the two extinctions, one with, the other without, added chloride. The 11-cis-10-F-analogue pigment gave both chloride effects and the hyperchromic ratio was the same as that recorded for the native visual pigment. In contrast, the pigment formed with 11-cis-14-F-retinal gave a hyperchromic ratio significantly greater than 1.23. A similar contrast in the responses to chloride was obtained with the analogue photopigments regenerated with the 9-cis-10-F- and 9-cis-14-F-chromophores. This difference between the two systems is interpreted as the result of a specific configurational feature of the gecko opsin when in the chloride-deficient state that is relevant to the binding of the retinal analogue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2895933

  7. sup 1 H and sup 31 P nuclear magnetic resonance and kinetic studies of the active site structure of chloroplast CF sub 1 ATP synthase

    SciTech Connect

    Devlin, C.C.; Grisham, C.M. (Univ. of Virginia, Charlottesville (USA))

    1990-07-03

    The interaction of nucleotides and nucleotide analogues and their complexes with Mn{sup 2+} bound to both the latent and dithiothreitol-activated CF{sub 1} ATP synthase has been examined by means of steady-state kinetics, water proton relaxation rate (PRR) measurements, and {sup 1}H and {sup 31}P nuclear relaxation measurements. Titration of both the latent and activated Mn{sup 2+}-CF{sub 1} complexes with ATP, ADP, P{sub i}, Co(NH{sub 3}){sub 4}ATP, Co(NH{sub 3}){sub 4}ADP, and Co(NH{sub 3}){sub 4}AMPPCP leads to increases in the water relaxation enhancement, consistent with enhanced metal binding and a high ternary complex enhancement. Steady-state kinetic studies are consistent with competitive inhibition of CF{sub 1} by Co(NH{sub 3}){sub 4}AMPPCP with respect to CaATP. {sup 1}H and {sup 31}P nuclear relaxation measurements in solutions of CF{sub 1} and Co(NH{sub 3}){sub 4}AMPPCP were used to determine the conformation of the bound substrate analogue and the arrangement with respect to this structure of high- and low-affinity sites for Mn{sup 2+}. The bound nucleotide analogue adopts a bent conformation, with the low-affinity sites for Mn{sup 2+}. The bound nucleotide analogue adopts a bent conformation, with the low-affinity Mn{sup 2+} site situated between the adenine and triphosphate moieties and the high-affinity metal site located on the far side of the triphosphate chain. The low-affinity metal forms a distorted inner-sphere complex with the {beta}-P and {gamma}-P of the substrate. The distances from Mn{sup 2+} to the triphosphate chain are too large for first coordination sphere complexes but are appropriate for second-sphere complexes involving, for example, intervening hydrogen-bonded water molecules or residues from the protein.

  8. A Combined Gas-Phase Photoelectron Spectroscopic and Theoretical Study of Zeise's Anion and Its Bromine and Iodine Analogues

    SciTech Connect

    Hou, Gaolei; Wen, Hui; Lopata, Kenneth A.; Zheng, Weijun; Kowalski, Karol; Govind, Niranjan; Wang, Xue B.; Xantheas, Sotiris S.

    2012-06-25

    We report the first photoelectron spectroscopic study of Zeise’s anion, [PtCl3(C2H4)], and its Br- and I- analogs in the gas phase. Well-resolved and rich spectral features are obtained for each species, yielding detailed electronic structure information, which is assigned with the aid of highlevel electronic structure calculations at the Coupled Cluster (CC) level of theory. The electron binding energies of [PtX3(C2H4)] are found to decrease with the size of halogen (4.57, 4.51, and 4.18 eV for X = Cl, Br, and I, respectively). The calculations indicate a synergistic ?2 interaction [with interaction strengths of 1.54 (Cl), 1.37 (Br) and 1.10 eV (I)] between the perpendicular C2H4 fragment and the nearly horizontal planar PtX3- anions, resulting in activating the ethylene molecule. The detailed insights of the chemical bonding and underlying electronic structure can be used to benchmark interactions between olefins and transition metal complexes, which are crucial to a wide range of catalytic processes.

  9. Hanford Site Annual Treatability Studies Report, Calendar Year 2002

    SciTech Connect

    Grohs, Eugene L.

    2003-02-28

    This report provides information required to be reported annually by the Washington Administrative Code (WAC) 173-303-071 (3)(r)(ii)(F) and (3)(s)(ix) on the treatability studies conducted on the Hanford Site in 2002. These studies were conducted as required by WAC 173-303-071, “Excluded Categories of Waste,” sections (3)(r) and (s). Unless otherwise noted, the waste samples were provided by and the treatability studies were performed for the U.S. Department of Energy, Richland Operations Office, P.O. Box 550, Richland, Washington 99352. The U.S. Environmental Protection Agency identification number for these studies is WA7890008967.

  10. MODE OF ACTION OF ACETYLXYLAN ESTERASE FROM STREPTOMYCES LIVIDANS: A STUDY WITH DEOXY AND DEOXY-FLUORO ANALOGUES OF ACETYLATED METHYL BETA-D-XYLOPYRANOSIDE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The action of Streptomyces lividans acetylxylan esterase on methyl 2,4-di-O-acetyl- and 3,4-di-O-acetyl beta-D-xylopyranoside was compared with its action on the 2- and 3-deoxy and 2- and 3-deoxy-fluoro-analogues of the two diacetates in order to elucidate the role of the free hydroxyl group in the ...

  11. Utility of the Mild Brain Injury Atypical Symptoms Scale to detect symptom exaggeration: an analogue simulation study.

    PubMed

    Lange, Rael T; Edmed, Shannon L; Sullivan, Karen A; French, Louis M; Cooper, Douglas B

    2013-01-01

    Brief self-report symptom checklists are often used to screen for postconcussional disorder (PCD) and posttraumatic stress disorder (PTSD) and are highly susceptible to symptom exaggeration. This study examined the utility of the five-item Mild Brain Injury Atypical Symptoms Scale (mBIAS) designed for use with the Neurobehavioral Symptom Inventory (NSI) and the PTSD Checklist-Civilian (PCL-C). Participants were 85 Australian undergraduate students who completed a battery of self-report measures under one of three experimental conditions: control (i.e., honest responding, n?=?24), feign PCD (n?=?29), and feign PTSD (n?=?32). Measures were the mBIAS, NSI, PCL-C, Minnesota Multiphasic Personality Inventory-2, Restructured Form (MMPI-2-RF), and the Structured Inventory of Malingered Symptomatology (SIMS). Participants instructed to feign PTSD and PCD had significantly higher scores on the mBIAS, NSI, PCL-C, and MMPI-2-RF than did controls. Few differences were found between the feign PCD and feign PTSD groups, with the exception of scores on the NSI (feign PCD > feign PTSD) and PCL-C (feign PTSD > feign PCD). Optimal cutoff scores on the mBIAS of ?8 and ?6 were found to reflect "probable exaggeration" (sensitivity = .34; specificity = 1.0; positive predictive power, PPP = 1.0; negative predictive power, NPP = .74) and "possible exaggeration" (sensitivity = .72; specificity = .88; PPP = .76; NPP = .85), respectively. Findings provide preliminary support for the use of the mBIAS as a tool to detect symptom exaggeration when administering the NSI and PCL-C. PMID:23419145

  12. Self-association of long-acting insulin analogues studied by size exclusion chromatography coupled to multi-angle light scattering.

    PubMed

    Jensen, Malene H; Wahlund, Per-Olof; Jacobsen, Jes K; Vestergaard, Bente; van de Weert, Marco; Havelund, Svend

    2011-10-15

    Two structurally very different insulin analogues analysed here, belong to a class of analogues of which two have been reported to have a protracted action through self-assembly to high molar mass in subcutis. The process of self-association of insulin analogues Lys(B29) (N(?)?-carboxyheptadecanoyl) des(B30) human insulin and Lys(B29) (N(?)-lithocholyl) des(B30) human insulin was investigated using size exclusion chromatography (SEC) in connection with multi-angle light-scattering. Self-assembly to high molar mass was obtained by exchanging the formulation containing phenolic preservatives with an isotonic eluent during SEC. It was shown that increasing amounts of zinc in the formulations of the two analogues increased the size of the self assemblies formed during gel filtration. The addition of 0.2 mM phenol to the elution buffer slowed down the self-association process of zinc containing formulations and shed light on the initial association process. The results indicated that a dihexamer is a possible building block during self-association of Lys(B29) (N(?)?-carboxyheptadecanoyl) des(B30) human insulin. Surprisingly, in the absence of zinc the two analogues behaved very differently. Lys(B29) (N(?)?-carboxyheptadecanoyl) des(B30) human insulin was in equilibrium between oligomers smaller than a hexamer, whereas Lys(B29) (N(?)-lithocholyl) des(B30) human insulin self-associated and formed even larger complexes than in the presence of zinc. PMID:21937288

  13. Polyamine analogues targeting epigenetic gene regulation

    PubMed Central

    Huang, Yi; Marton, Laurence J.; Woster, Patrick M.; Casero, Robert A.

    2013-01-01

    Over the past three decades the metabolism and functions of the polyamines have been actively pursued as targets for antineoplastic therapy. Interactions between cationic polyamines and negatively charged nucleic acids play a pivotal role in DNA stabilization and RNA processing that may affect gene expression, translation and protein activity. Our growing understanding of the unique roles that the polyamines play in chromatin regulation, and the discovery of novel proteins homologous with specific regulatory enzymes in polyamine metabolism, have led to our interest in exploring chromatin remodelling enzymes as potential therapeutic targets for specific polyamine analogues. One of our initial efforts focused on utilizing the strong affinity that the polyamines have for chromatin to create a backbone structure, which could be combined with active-site-directed inhibitor moieties of HDACs (histone deacetylases). Specific PAHAs (polyaminohydroxamic acids) and PABAs (polyaminobenzamides) polyamine analogues have demonstrated potent inhibition of the HDACs, re-expression of p21 and significant inhibition of tumour growth. A second means of targeting the chromatin-remodelling enzymes with polyamine analogues was facilitated by the recent identification of flavin-dependent LSD1 (lysine-specific demethylase 1). The existence of this enzyme demonstrated that histone lysine methylation is a dynamic process similar to other histone post-translational modifications. LSD1 specifically catalyses demethylation of mono- and di-methyl Lys4 of histone 3, key positive chromatin marks associated with transcriptional activation. Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1. Cellular inhibition of LSD1 by these unique compounds led to the re-activation of multiple epigenetically silenced genes important in tumorigenesis. The use of these novel polyamine-based HDAC or LSD1 inhibitors represents a highly promising and novel approach to cancer prevention and therapy. PMID:20095972

  14. Nevada Test Site tortoise population monitoring study. Final report

    SciTech Connect

    Mueller, J.M.; Zander, K.K.

    1994-12-01

    A Tortoise Population Monitoring Study was initiated to determine and monitor the density of desert tortoises (Gopherus agassizii) on the Nevada Test Site. Quadrat sampling was conducted following methodology described in the Draft Desert Tortoise Recovery Plan (FWS, 1993). So few tortoises were found that densities could not be calculated. Based on estimates of capture probabilities and densities from other studies, it was determined that 1-km{sup 2} (0.4 mi{sup 2}) plots did not contain enough tortoises for estimating densities with the Recovery Plan methods. It was recommended that additional surveys on the Nevada Test Site using those methods not be conducted. Any future efforts to monitor desert tortoise densities should start by identifying other possible methods, determining their relative power to detect changes, and estimating their cost.

  15. Inhibition of monoamine oxidase by (E)-styrylisatin analogues

    PubMed Central

    Van der Walt, Elizna M.; Milczek, Erika M.; Malan, Sarel F.; Edmondson, Dale E.; Castagnoli, Neal; Bergh, Jacobus J.; Petzer, Jacobus P.

    2009-01-01

    Previous studies have shown that (E)-8-(3-chlorostyryl)caffeine (CSC) is a specific reversible inhibitor of human monoamine oxidase B (MAO-B) and does not bind to human MAO-A. Since the small molecule isatin is a natural reversible inhibitor of both MAO-B and MAO-A, (E)-5-styrylisatin and (E)-6-styrylisatin analogues were synthesized in an attempt to identify inhibitors with enhanced potencies and specificities for MAO-B. The (E)-styrylisatin analogues were found to exhibit higher binding affinities than isatin with the MAO preparations tested. The (E)-5-styrylisatin analogues bound more tightly than the (E)-6 analogue although the latter exhibits the highest MAO-B selectivity. Molecular docking studies with MAO-B indicate that the increased binding affinity exhibited by the (E)-styrylisatin analogues, in comparison to isatin, is best explained by the ability of the styrylisatins to bridge both the entrance cavity and the substrate cavity of the enzyme. Experimental support for this model is shown by the weaker binding of the analogues to the Ile199Ala mutant of human MAO-B. The lower selectivity of the (E)-styrylisatin analogues between MAO-A and MAO-B, in contrast to CSC, is best explained by the differing relative geometries of the aromatic rings for these two classes of inhibitors. PMID:19342233

  16. Behavior-based safety on construction sites: a case study.

    PubMed

    Choudhry, Rafiq M

    2014-09-01

    This work presents the results of a case study and describes an important area within the field of construction safety management, namely behavior-based safety (BBS). This paper adopts and develops a management approach for safety improvements in construction site environments. A rigorous behavioral safety system and its intervention program was implemented and deployed on target construction sites. After taking a few weeks of safety behavior measurements, the project management team implemented the designed intervention and measurements were taken. Goal-setting sessions were arranged on-site with workers' participation to set realistic and attainable targets of performance. Safety performance measurements continued and the levels of performance and the targets were presented on feedback charts. Supervisors were asked to give workers recognition and praise when they acted safely or improved critical behaviors. Observers were requested to have discussions with workers, visit the site, distribute training materials to workers, and provide feedback to crews and display charts. They were required to talk to operatives in the presence of line managers. It was necessary to develop awareness and understanding of what was being measured. In the process, operatives learned how to act safely when conducting site tasks using the designed checklists. Current weekly scores were discussed in the weekly safety meetings and other operational site meetings with emphasis on how to achieve set targets. The reliability of the safety performance measures taken by the company's observers was monitored. A clear increase in safety performance level was achieved across all categories: personal protective equipment; housekeeping; access to heights; plant and equipment, and scaffolding. The research reveals that scores of safety performance at one project improved from 86% (at the end of 3rd week) to 92.9% during the 9th week. The results of intervention demonstrated large decreases in unsafe behaviors and significant increases in safe behaviors. The results of this case study showed that an approach based on goal setting, feedback, and an effective measure of safety behavior if properly applied by committed management, can improve safety performance significantly in construction site environments. The results proved that the BBS management technique can be applied to any country's culture, showing that it would be a good approach for improving the safety of front-line workers and that it has industry wide application for ongoing construction projects. PMID:24686162

  17. Comparing the Study Site to One in Another Region

    NSDL National Science Digital Library

    The GLOBE Program, University Corporation for Atmospheric Research (UCAR)

    2003-08-01

    The purpose of this resource is to deepen students understanding of the Earth as a system, and their appreciation for the value of diagrams as tools. Students visit a study site, where they observe and recall their existing knowledge of air, water, soil, and living things to make a list of interconnections among the four Earth system components. They make predictions about the effects of a change in a system, inferring ways these changes affect the characteristics of other related components.

  18. Rigid Analogues of Antimitotic Indolobenzazepinones: New Insights into Tubulin Binding via Molecular Modeling

    PubMed Central

    2011-01-01

    Two rigid analogues of 5-ethylindolobenzazepinone 4, a potent cytotoxic agent and inhibitor of tubulin polymerization, were prepared. The first was the indane derivative 5, in which the ethyl group is attached to the benzo moiety. The second was the pyrrolidine analogue 6, in which the ethyl chain was bound to the lactam nitrogen. While both compounds were considerably less active inhibitors of KB cell growth as compared to 4, inhibition of tubulin polymerization was only moderately reduced. Tubulin docking studies indicated that the aR and aS atropoisomers of 5 and 6 occupy different binding pockets at the colchicine binding site. Conversely, both aS-5 and aS-6 occupy the same binding pocket as aSS-4 but do not benefit from the favorable hydrophobic interactions provided by the C5 alkyl group of 4, thus possibly explaining their lower activities. PMID:24900350

  19. Overview of the Ridge 2000 Integrated Studies Sites

    NASA Astrophysics Data System (ADS)

    Fisher, C.

    2005-12-01

    The Ridge 2000 program is in its fourth year and fieldwork at each of the Integrated Studies Sites (ISS) is in full swing. Multidisciplinary monitoring continues at the EPR ISS with seismic, temperature, and current data being continuously recorded. Long-term fluid sampling programs aimed at furthering our understanding of temporal variations in the chemistry of high-temperature hydrothermal vents are continuing. In situ fluid chemistry monitors have been deployed for weeks, and longer deployments are planned as the technology matures. Nested within these monitoring studies are experiments addressing larval dispersal and changes in microbial and macrobiological communities. In early 2006, geodetic monitoring will begin, with an array of pressure gauges as well as a detailed compliance study. By early 2007, a 3-D multichannel seismic survey will have provided unprecedented details of the crustal structure at 9°50'N. Together these studies provide a strong framework for an interdisciplinary understanding of the links between the forces that produce a mid-ocean ridge spreading center and their manifestation on the seafloor. Fieldwork on the Endeavour segment of the Juan de Fuca ridge in 2005 also included a balance of monitoring, experimental, and sampling programs across a wide range of disciplines. Four interdisciplinary field programs were conducted to maintain and expand ongoing Ridge 2000 and proto-NEPTUNE experiments. These research programs continued development and testing in situ chemical and microbial sensors, conducted co-registered sampling of fluids, fauna, and chimney material, and recovered moorings that measured heat and chemical fluxes at the segment scale. High-resolution mapping was also completed at this site, which has been chosen for one of the two initial NEPTUNE Canada nodes to prepare the way for the collaborative, cabled observatory projects. The mapping cruise included 5 secondary school teachers as part of the REVEL outreach and education program. Live transmission of high-definition video from the seafloor to land stations provided an exciting preview of the potential of high-bandwidth communication with the seafloor. The first round of fieldwork at the East Lau Spreading Center ISS was completed in 2005. Building upon the two R2K-funded cruises in 2004, three cruises in 2005 sampled 7 hydrothermal vent sites. Four of these sites were discovered by the collaborative efforts of R2K scientists, working together across cruises, and one site by Japanese colleagues collaborating with R2K scientists in 2004. Another of the sites was discovered during the first R2K cruise of 2005. The SM2000 mounted on Jason II in 2005 was used to create fine-scale bathymetric maps of six of the sites and high-resolution imagery was collected for photomosaics of selected areas of hydrothermal activity within the sites. These maps and imagery guided even finer scale surveys, equipment deployments and sampling of basalt, hydrothermal deposits, vent fluids, microbial mats, and benthic organisms. Some of the fauna collected are still alive and under study in pressure vessels in R2K-supported laboratories. Results from these cruises have improved our understanding of this back-arc spreading center, "from mantle to microbe," and are invaluable for selection of the focus area, or bull's eye, for the next generation of integrated, interdisciplinary studies in this region.

  20. Towards adaptive Web sites: Conceptual framework and case study

    Microsoft Academic Search

    Mike Perkowitz; Oren Etzioni

    2000-01-01

    Today's Web sites are intricate but not intelligent; while Web navigation is dynamic and idiosyncratic, all too often Web sites are fossils cast in HTML. In response, this paper investigates adaptive Web sites: sites that automatically improve their organization and presentation by learning from visitor access patterns. Adaptive Web sites mine the data buried in Web server logs to produce

  1. Desferrithiocin Analogues and Nephrotoxicity

    PubMed Central

    Bergeron, Raymond J.; Wiegand, Jan; McManis, James S.; Bharti, Neelam; Singh, Shailendra

    2009-01-01

    The syntheses of a series of 4?-O-alkylated (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid and 5?-O-alkylated (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid ligands are described. Their partition between octanol and water, logPapp, is determined, along with their iron-clearing efficiency (ICE) in both non-iron-overloaded, bile duct-cannulated rodents and in iron-overloaded primates. The ligand-promoted biliary ferrokinetics in rats are described for each of the chelators. Plots of logPapp versus ICE in a rodent model for both the 4?-O-alkylated-2,4-dihydroxy and 5?-O-alkylated-2,5-dihydroxy series produced an inverse parabola plot with r2 values of 0.97 and 0.81, respectively. The plots indicate an optimum logPapp/ICE relationship. Because of the nature of the data spread in the 4?-O-alkylated 2,4-dihydroxy series, it will be used to help assess the origin of nephrotoxicity in desferrithiocin analogues: is toxicity simply related to lipophilicity, ICE, or a combination of these properties? PMID:18788724

  2. Summary of 1990 eolian characterization studies, Hanford Site, Washington

    SciTech Connect

    Gaylord, D.R.; Stetler, L.D.; Smith, G.D. [Washington State Univ., Pullman, WA (United States); Mars, R.W. [Wyoming Univ., Laramie, WY (United States)

    1993-12-01

    A study of eolian activity was initiated to improve understanding of past climate change and the likely effect of wind on engineered protective barriers at the Hanford Site. Eolian features from a Holocene sand dune field located in the southeastern portion of the Hanford Site were investigated using a variety of field and laboratory techniques including stratigraphic examinations of hand-dug pits, textural and compositional analyses of dune sand and potential source detritus, and air photo interpretations. These investigations were undertaken to evaluate the provenance and eolian dynamics of the sand dunes. Interpretations of sand dune migration using archival air photo stereopairs document a 20% reduction in the volume of active sand dunes (measured from an approximate 15-km{sup 2} test area) between 1948 and 1987. Changes in annual precipitation appear to have influenced active dune migration strongly.

  3. [Paleoclimatology studies for Yucca Mountain site characterization]. Final report

    SciTech Connect

    NONE

    1996-05-03

    This report consists of two separate papers: Fernley Basin studies; and Influence of sediment supply and climate change on late Quaternary eolian accumulation patterns in the Mojave Desert. The first study involved geologic mapping of late Quaternary sediments and lacustrine features combined with precise control of elevations and descriptions of sediments for each of the major sedimentary units. The second paper documents the response of a major eolian sediment transport system in the east-central Mojave Desert: that which feeds the Kelso Dune field. Information from geomorphic, stratigraphic, and sedimentologic studies of eolian deposits and landforms is combined with luminescence dating of these deposits to develop a chronology of periods of eolian deposition. Both studies are related to site characterization studies of Yucca Mountain and the forecasting of rainfall patterns possible for the high-level radioactive waste repository lifetime.

  4. Choose study sites carefully | accrualnet.cancer.gov

    Cancer.gov

    In some cases, sites are selected from a pool of potentials. This is especially true for earlier phase (phase I or II trials) clinical trials. In recruitment, a site’s past performance can predict future success.

  5. A flash photolysis and stopped-flow spectroscopy study of 3',4'-dihydroxy-7-O-?-D-glucopyranosyloxyflavylium chloride, an anthocyanin analogue exhibiting efficient photochromic properties.

    PubMed

    Petrov, Vesselin; Gavara, Raquel; Dangles, Olivier; Al Bittar, Sheiraz; Mora-Soumille, Nathalie; Pina, Fernando

    2013-03-01

    The complete determination of all rate and equilibrium constants of the network of reversible chemical reactions involving the anthocyanin analogue, 3',4'-dihydroxy-7-O-?-D-glucopyranosyloxyflavylium chloride, was achieved by means of UV-visible spectroscopy, flash photolysis and pH jumps monitored by stopped-flow. An energy level diagram containing all the data was obtained. A detailed step by step procedure illustrating all the calculations is reported. PMID:23280153

  6. Preliminary site studies for critical facilities using geotechnical units derived from engineering geologic analyses

    E-print Network

    Conover, Dale Everette

    1985-01-01

    on proper site selection. The test site is located just west of the Brazos River near Bryan/College Station, Texas and is known as the East-Central Texas Site. The geologic and geotechnical setting of the Site was investigated by field reconnaissance... of Study. PROPOSEO INVESTIGATION METHOD. X1 I . 6 Selection of a Site. GEOLOGIC ANALYSIS, EAST-CENTRAL TEXAS SITE Study Area. Data Acquisition. Literature Search. Field Studies. Core Sampling and Testing. Other Sources of Data. Analysis of Data...

  7. CONFIDENTIAL [Name of Site] UBC File No. [to be added] Page 1 of 14 CLINICAL STUDY SUB-SITE AGREEMENT

    E-print Network

    Ollivier-Gooch, Carl

    CONFIDENTIAL [Name of Site] UBC File No. [to be added] Page 1 of 14 CLINICAL STUDY SUB grant/funding] for the Study from [Name of Funding Source]. #12;CONFIDENTIAL [Name of Site] UBC File No to be so engaged. THE PARTIES AGREE AS FOLLOWS: 1.0 DEFINITIONS 1.1 In the Agreement: (a) "Confidential

  8. Site study plan for exploratory shaft monitoring wells, Deaf Smith County Site, Texas: Preliminary Draft

    SciTech Connect

    Not Available

    1988-01-01

    As part of site characterization studies, two exploratory shafts will be constructed at the Deaf Smith County site, Texas. Twelve wells at five locations have been proposed to monitor potential impacts of shaft construction on water-bearing zones in the Ogallala Formation and the Dockum Group. In addition, tests have been proposed to determine the hydraulic properties of the water-bearing zones for use in design and construction of the shafts. Samples of the Blackwater Draw Formation, Ogallala Formation, and Dockum Group will be obtained during construction of these wells. Visual indentification, laboratory testing, and in situ testing will yield data necessary for Exploratory Shaft Facility design and construction. This activity provides the earliest data on the Blackwater Drew Formation, Ogallala Formation, and Dockum Group near the exploratory shaft locations. Drilling and hydrologic testing are scheduled prior to other subsurface activity at the Exploratory Shaft Facility to establish ground-water baseline conditions. The Technical Field Services Contractor is responsible for conducting the field program of drilling and testing. Samples and data will be handled and reported in accordance with established Salt Repository Project procedures. A quality assurance program will be utilized to assure that activities affecting quality are performed correctly and that the appropriate documentation is maintained. 45 refs., 11 figs., 4 tabs.

  9. Evaluation Of Microdosing Strategies For Studies In Preclinical Drug Development: Demonstration Of Linear Pharmacokinetics In Dogs Of A Nucleoside Analogue Over A 50-Fold Dose Range

    SciTech Connect

    Sandhu, P; Vogel, J S; Rose, M J; Ubick, E A; Brunner, J E; Wallace, M A; Adelsberger, J K; Baker, M P; Henderson, P T; Pearson, P G; Baillie, T A

    2004-04-22

    The technique of accelerator mass spectrometry (AMS) was validated successfully and utilized to study the pharmacokinetics and disposition in dogs of a preclinical drug candidate (Compound A), after oral and intravenous administration. The primary objective of this study was to examine whether Compound A displayed linear kinetics across sub-pharmacological (microdose) and pharmacological dose ranges in an animal model, prior to initiation of a human microdose study. The AMS-derived disposition properties of Compound A were comparable to data obtained via conventional techniques such as LC-MS/MS and liquid scintillation counting analyses. Thus, Compound A displayed multiphasic kinetics and possessed low plasma clearance (4.4 mL/min/kg), a long terminal elimination half-life (19.4 hr) and high oral bioavailability (82%). Currently there are no published comparisons of the kinetics of a pharmaceutical compound at pharmacological versus sub-pharmacological doses employing microdosing strategies. The present study thus provides the first description of the pharmacokinetics of a drug candidate assessed under these two dosing regimens. The data demonstrated that the pharmacokinetic properties of Compound A were similar following dosing at 0.02 mg/kg as at 1 mg/kg, indicating that in the case of Compound A, the kinetics of absorption, distribution and elimination in the dog appear to be linear across this 50-fold dose range. Moreover, the exceptional sensitivity of AMS provided a pharmacokinetic profile of Compound A, even following a microdose, which revealed aspects of the disposition of this agent that were inaccessible by conventional techniques. The applications of accelerator mass spectrometry (AMS) are broad ranging and vary from studying environmental and ecological issues such as the isotopic composition of the atmosphere, soil and water (Hughen et al., 2000; Beck et al., 2001; Keith-Roach et al., 2001; Mironov et al., 2002), to archaeology and volcanology (Stafford et al., 1984; Vogel et al., 1990; Smith et al., 1999) to its use as a bioanalytical tool for nutritional research (Buchholz et al., 1999; Deuker et al., 2000; Weaver and Liebman, 2002). Biomedical applications of AMS and its use in the arena of pharmaceutical research also have been detailed in review articles (Barker and Garner, 1999; Garner, 2000; Turteltaub and Vogel, 2000). To date, most studies on the metabolism and disposition of xenobiotics by AMS have focused on how carcinogens bind to DNA and proteins to form adducts (Turteltaub et al., 1990, 1997; Frantz et al., 1995; Dingley et al., 1999; Li et al., 2003). Its application to the field of pharmaceutical sciences has been limited to a few studies (Kaye et al., 1997; Young et al., 2001; Garner et al., 2002). However, the pharmaceutical industry is becoming increasingly aware of the potential benefits that may accrue from the ultra high sensitivity afforded by AMS in terms of evaluating the pharmacokinetics of lead drug candidates in early development. Specifically, AMS allows administration of sub-pharmacological doses (microdoses) of carbon-14 or tritium-labeled investigational drugs to animals or humans at radiologically insignificant levels with the goal of obtaining preliminary information regarding the absorption, distribution, metabolism, and excretion of test compounds (Turteltaub and Vogel, 2000). An unresolved issue, however, is whether the pharmacokinetics determined following a microdose are representative of those following a conventional (pharmacological) dose (Lappin and Garner, 2003). This paper examines the linearity of kinetics of an antiviral nucleoside analogue, Compound A, across sub-pharmacological and pharmacological dose ranges in the dog prior to initiation of a human microdose study. The specific objectives of this study, therefore, were (1) to assess the pharmacokinetics of Compound A in dogs by a conventional dosing approach utilizing LC-MS/MS for sample analysis, (2) to assess the pharmacokinetics of Compound A in dogs by the microdose approach utilizing AMS for sample ana

  10. Synthesis of [bis(Inosine5?)]-tetraphosphate and [bis(Inosine5?)]-pentaphosphate Analogues Bearing the Residues of Methylenediphosphonic Acid

    Microsoft Academic Search

    A. V. Shipitsyn; N. B. Tarussova; E. A. Shirokova; A. A. Krayevsky

    2000-01-01

    Various methods of synthesis of metabolically stable phosphonate analogues of bisnucleoside oligophosphates containing two residues of methylenediphosphonic acid in the oligophosphate chain are studied. Phosphonate analogues of Ip4I and Ip5I are prepared.

  11. Synthesis of [bis(inosine-5')]-tetraphosphate and [bis(inosine-5')]-pentaphosphate analogues bearing the residues of methylenediphosphonic acid.

    PubMed

    Shipitsyn, A V; Tarussova, N B; Shirokova, E A; Krayevsky, A A

    2000-01-01

    Various methods of synthesis of metabolically stable phosphonate analogues of bisnucleoside oligophosphates containing two residues of methylenediphosphonic acid in the oligophosphate chain are studied. Phosphonate analogues of Ip4I and Ip5I are prepared. PMID:10893708

  12. Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

    PubMed Central

    Kaš?áková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

    2014-01-01

    Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

  13. A nuclear magnetic resonance study of the topography of binding sites of Escherichia coli carbamoyl-phosphate synthetase.

    PubMed

    Raushel, F M; Anderson, P M; Villafranca, J J

    1983-04-12

    Two paramagnetic probes, viz., Mn2+ and Cr3+-ATP, were used to map distances to various loci on carbamoyl-phosphate synthetase by using NMR measurements. The paramagnetic influence of Mn2+ on the 1H of L-glutamate and L-ornithine was measured at 200 and 360 MHz. On the basis of these data, a correlation time for the paramagnetic interaction was determined (2 X 10(-9) s) and used to compute distances. These were in the range 7-9 A. Distances were also calculated from Mn2+ to the 13C-5 atom of glutamate (8.6 A), to the monovalent cation site (approximately 8 A), and to the phosphorus atoms of ATP in the Co(NH3)4ATP complex. For studies of the monovalent cation site relaxation rates of 6Li+, 7Li+, and 15NH4+ were measured. With Cr3+ ATP as a paramagnetic substrate analogue, Cr3+ to 13C distances were measured with the substrates HCO3(-) and [5-13C]glutamate. These NMR data provide the first topographical map of the arrangement of substrates, metal ion activators, and allosteric modifiers on the Escherichia coli carbamoyl-phosphate synthetase dimer. PMID:6342670

  14. Premixed insulin analogues for the treatment of diabetes mellitus.

    PubMed

    Garber, Alan J

    2006-01-01

    Premixed insulin analogues, consisting of rapid-acting and intermediate-acting insulin analogues, were developed to more closely mimic physiological endogenous insulin secretion and meet the needs of patients who require both basal and prandial insulin but wish to limit the number of daily injections. There is considerable variability in onset and duration of action, as well as peak insulin levels, obtained with human insulin formulations such as premixed human insulin 70/30. To overcome these limitations, premixed insulin analogues were developed. Peak insulin levels are twice as high and reached in half the time with the rapid-acting insulin component of a premixed insulin analogue. In the US, two premixed insulin analogue formulations are currently available: insulin lispro 75/25 (75% insulin lispro protamine suspension and 25% insulin lispro) and biphasic insulin aspart 70/30 (BIAsp 70/30; 70% insulin aspart protamine suspension and 30% insulin aspart). They are generally administered twice daily, just before breakfast and dinner. Data from various randomised trials show that both insulin lispro 75/25 and BIAsp 70/30 provide more effective postprandial control of blood glucose than premixed human insulin 70/30 or human insulin isophane suspension (NPH insulin). Longer-term glycaemic control, evaluated as changes in glycosylated haemoglobin, is comparable for premixed insulin analogues and premixed human insulin 70/30 in most studies. Three comparative, randomised trials have shown that patients with type 2 diabetes mellitus using premixed insulin analogues twice daily are more likely to reach glycaemic goals than those using only insulin glargine once daily. Some patients can also reach glycaemic goals with once-daily administration of a premixed insulin analogue. Although the incidence of hypoglycaemia is low, direct comparison across trials of premixed insulin analogues is difficult because of inconsistencies in reporting. Within trials, the incidence of both major (rare) and minor hypoglycaemic episodes during treatment with premixed insulin analogues is low and comparable with rates found with human insulin 70/30. Premixed insulin analogues can be safely used, and are effective and convenient for achieving overall glycaemic control in patients with diabetes. In addition, given the convenience of mealtime dose administration, compliance with insulin therapy may increase with premixed insulin analogues. PMID:16398567

  15. An electrical analogue of the entire human circulatory system

    Microsoft Academic Search

    L. de Pater; Jw. van den Berg

    1964-01-01

    To study the human cardiovascular system an electrical analogue has been designed. This analogue consists of two parts: An\\u000a active part, the heart; and a passive part, the vessels. A fourfold pulse generator represents the action of the heart. The\\u000a various parameters such as heart rate, A.V. delay, duration of systole and diastole, contraction speed and contraction force\\u000a can be

  16. Cardiac specific effects of thyroid hormone analogues.

    PubMed

    Danzi, S; Klein, I

    2011-10-01

    There is significant interest in development of thyroid hormone analogues to harness specific properties as therapeutic agents for a variety of clinical indications including obesity, hypercholesterolemia, heart failure, and thyrotoxicosis. To date, most analogues have been designed to target liver specific effects, which can promote weight loss and lipid lowering through either tissue specific uptake or thyroid hormone receptor (TR) ? isoform selectivity at the same time minimizing the unwanted cardiac and bone effects. We have developed a molecular biomarker assay to study the induction of the transcription of the cardiac specific ?-myosin heavy chain (MHC) gene as a more sensitive and specific measure of thyroid hormone action on cardiac myocytes. We tested 5 TR? and 1 TR? selective agonists as well as 2 putative TR antagonists in our ?-MHC hnRNA assay. Using reverse transcription and polymerase chain reaction, we measured the induction of the ?-MHC primary transcript in response to administration of drug. The TR? and only 2 of the TR? agonists were highly active, when compared to the effect of T3, at the level of the cardiac myocyte. In addition, our data suggests that the reason that the antagonist NH-3 is not able to block the T3-mediated induction of ?-MHC is that it does not get transported into the cardiac myocyte. Our data suggest that this assay will be useful in preclinical studies of the potential cardiac specific effects of thyroid hormone analogues and that predictions of function based on structure are not necessarily accurate or complete. PMID:22009366

  17. SHRINE: Enabling Nationally Scalable Multi-Site Disease Studies

    PubMed Central

    McMurry, Andrew J.; Murphy, Shawn N.; MacFadden, Douglas; Weber, Griffin; Simons, William W.; Orechia, John; Bickel, Jonathan; Wattanasin, Nich; Gilbert, Clint; Trevvett, Philip; Churchill, Susanne; Kohane, Isaac S.

    2013-01-01

    Results of medical research studies are often contradictory or cannot be reproduced. One reason is that there may not be enough patient subjects available for observation for a long enough time period. Another reason is that patient populations may vary considerably with respect to geographic and demographic boundaries thus limiting how broadly the results apply. Even when similar patient populations are pooled together from multiple locations, differences in medical treatment and record systems can limit which outcome measures can be commonly analyzed. In total, these differences in medical research settings can lead to differing conclusions or can even prevent some studies from starting. We thus sought to create a patient research system that could aggregate as many patient observations as possible from a large number of hospitals in a uniform way. We call this system the ‘Shared Health Research Information Network’, with the following properties: (1) reuse electronic health data from everyday clinical care for research purposes, (2) respect patient privacy and hospital autonomy, (3) aggregate patient populations across many hospitals to achieve statistically significant sample sizes that can be validated independently of a single research setting, (4) harmonize the observation facts recorded at each institution such that queries can be made across many hospitals in parallel, (5) scale to regional and national collaborations. The purpose of this report is to provide open source software for multi-site clinical studies and to report on early uses of this application. At this time SHRINE implementations have been used for multi-site studies of autism co-morbidity, juvenile idiopathic arthritis, peripartum cardiomyopathy, colorectal cancer, diabetes, and others. The wide range of study objectives and growing adoption suggest that SHRINE may be applicable beyond the research uses and participating hospitals named in this report. PMID:23533569

  18. New materials for analogue experiments: Preliminary tests of magnetorheological fluids

    NASA Astrophysics Data System (ADS)

    Cavozzi, C.; Storti, F.; Nestola, Y.; Salvi, F.; Davoli, G.

    2014-09-01

    New materials and related apparatuses are welcome to advance analogue modelling techniques. In this contribution, we report on a first attempt to use magnetorheological (MR) fluids as analogue materials for simulating the mechanical behavior of mobile décollement layers that change their mechanical properties during deformation. For this purpose, a specific sandbox was designed to include the possibility of quickly applying and removing a magnetic field below a MR fluid layer, in order to induce an instantaneous change from a frictional to a viscous behavior in the basal décollement material. The simulation of gravitational gliding and sediment progradation above a basal mobile shale layer provided results that compare well with analogue models produced with other experimental techniques, and with natural structures like those developed in the Niger delta region. This pilot study thus encourages further research for optimizing the applicability of MR fluids to the analogue simulation of geological processes.

  19. Fluorescence studies on association of human translation initiation factor eIF4E with mRNA cap-analogues.

    PubMed

    Wieczorek, Z; Nied?wiecka-Korna?, A; Chlebicka, L; Jankowska, M; Kiraga, K; Stepi?ski, J; Dadlez, M; Drabent, R; Darzynkiewicz, E; Stolarski, R

    1999-01-01

    Binding of a long series of mono- and dinucleotide analogues of the 7-methylguanosine containing 5'-mRNA-cap to human protein translation initiation factor eIF4E has been investigated by means of fluorescence. A new methodological approach in gathering and analysis of the fluorescence data provided us with very accurate values of the association equilibrium constant K and normalized, maximal quenching of the protein fluorescence delta Fmax, during titration of eIF4E by various cap-analogues. The results confirm participation of at least two conserved tryptophan residues of eIF4E in interaction with 7-methylguanine, as has been described recently for murine eIF4E, complexed with 7-methyl-GDP in crystal (Marcotrigiano et al., 1997, Cell 89, 951), and for yeast eIF4E, complexed with the same ligand in solution (Matsuo et al., 1997, Nature Struct. Biol. 4, 717). On the other hand binding by eIF4E of unmethylated guanine nucleotides and N2,N2,7-trimethylguanine containing nucleotides differ substantially from the way of binding of the regular mRNA-cap. Influence of the structural features of the cap-analogues, especially the type of the second nucleoside in the dinucleotide caps, on their association with eIF4E and biological activities in in vitro protein translation systems has been discussed in light of the known structures of the eIF4E-7-methyl-GDP complexes in crystal and solution. PMID:10349744

  20. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity. PMID:24918540

  1. Analogue Missions on Earth, a New Approach to Prepare Future Missions on the Moon

    NASA Astrophysics Data System (ADS)

    Lebeuf, Martin

    Human exploration of the Moon is a target by 2020 with an initial lunar outpost planned in polar regions. Current architectures maintain a capability for sorties to other latitudes for science activities. In the early stages of design of lunar outpost infrastructure and science activity planning, it has been recognized that analogue missions could play a major role in Moon mission design. Analogue missions, as high fidelity simulations of human and robotic surface operations, can help field scientists and engineers develop and test strategies as well as user requirements, as they provide opportunities to groundtruth measurements, and for the team to share understanding of key science needs and key engineering trades. These types of missions also provide direct training in planning science operations, and in team building and communication. The Canadian Space Agency's Exploration Core Program targets the development of technology infrastructure elements in key areas of science, technology and robotics in preparation for its role in the future exploration of the Moon and Mars. Within this Program, Analogue Missions specifically target the operations requirements and lessons learned that will reduce costs and lower the risk of planetary surface missions. Analogue missions are simulations of planetary surface operations that take place at analogue sites on Earth. A terrestrial analogue site resembles in some key way: eg. geomorphologically or geochemically, a surface environment of another planet. An analogue mission can, therefore, be defined as an integrated set of activities that represent (or simulate) entire mission designs or narrowly focus on specific aspects of planned or potential future planetary exploration missions. Within the CSA's Exploration Core Program, Analogue Missions facilitate the maturation of science instruments and mission concepts by integrating ongoing space instrument and technology development programs with science and analogue elements. As well as using analogue missions to meet agency programmatic needs, the Canadian Space Agency encourages scientists and engineers to make use of opportunities presented by analogue missions to further their own research objectives. Specific objectives of Analogue Missions are to (1) foster a multidisciplinary approach to planning, data acquisition, processing and interpretation, calibration of instruments, and telemetry during mission operations; (2) integrate new science with emerging technologies; and (3) develop an expertise on exploration architecture design from projects carried out at terrestrial analogue sites. Within Analogue Missions, teams develop planning tools, use mission-specific software and technology, and communicate results as well as lessons learned during tactical operations. The expertise gained through Analogue Missions will contribute to inform on all aspects of exploration architectures, including planetary mobility requirements and astronaut training.

  2. Analogue modelling of syntectonic leucosomes in migmatitic schists

    NASA Astrophysics Data System (ADS)

    Druguet, Elena; Carreras, Jordi

    2006-10-01

    Migmatites from the Cap de Creus tectonometamorphic belt display a wide variety of structures, from those formed when the leucosomes were melt-bearing, to those developed during solid-state deformation. The observed field structures have been modelled by means of analogue experiments. The materials used in the models are layered plasticine as a schist analogue, and chocolate as analogue of the crystallizing leucosome. A model for the development of syntectonic migmatites is proposed in which initial melt-bearing patches, preferentially formed within fertile pelitic layers, progressively evolve towards lens-shaped veins. Furthermore, heterogeneous deformation of anisotropic metasediments facilitates formation of extensional sites for further melt accumulation and transport. Melt crystallization implies a rapid increase in effective viscosity of leucosomes producing a reversal in competence contrast with respect to the enclosing schists. During the whole process, deformation localizes around crystallizing veins, giving rise to different and contrasting structures for melt-bearing and for solid-state stages.

  3. BIOREMEDIATION TREATABILITY STUDIES OF CONTAMINATED SOILS AT WOOD PRESERVING SITES

    EPA Science Inventory

    Bioremediationis used frequently at sites contaminated with organic hazardous chemical where releases from processing vessels and the mismanagement of reagents and generated waste have contributed to significant impairment of the environment. At wood treater sites, process reagen...

  4. A Cross-site Qualitative Study of Physician Order Entry

    PubMed Central

    Ash, Joan S.; Gorman, Paul N.; Lavelle, Mary; Payne, Thomas H.; Massaro, Thomas A.; Frantz, Gerri L.; Lyman, Jason A.

    2003-01-01

    Objective: To describe the perceptions of diverse professionals involved in computerized physician order entry (POE) at sites where POE has been successfully implemented and to identify differences between teaching and nonteaching hospitals. Design: A multidisciplinary team used observation, focus groups, and interviews with clinical, administrative, and information technology staff to gather data at three sites. Field notes and transcripts were coded using an inductive approach to identify patterns and themes in the data. Measurements: Patterns and themes concerning perceptions of POE were identified. Results: Four high-level themes were identified: (1) organizational issues such as collaboration, pride, culture, power, politics, and control; (2) clinical and professional issues involving adaptation to local practices, preferences, and policies; (3) technical/implementation issues, including usability, time, training and support; and (4) issues related to the organization of information and knowledge, such as system rigidity and integration. Relevant differences between teaching and nonteaching hospitals include extent of collaboration, staff longevity, and organizational missions. Conclusion: An organizational culture characterized by collaboration and trust and an ongoing process that includes active clinician engagement in adaptation of the technology were important elements in successful implementation of physician order entry at the institutions that we studied. PMID:12595408

  5. Isotopic Studies of Contaminant Transport at the Hanford Site, Washington.

    SciTech Connect

    Christensen, John N.; Conrad, Mark E.; DePaolo, Donald J.; Dresel, P. Evan

    2007-11-01

    Processes of fluid flow and chemical transport through the vadose zone can be characterized through the isotopic systematics of natural soils, minerals, pore fluids and groundwater. In this contribution, we first review our research using measured isotopic variations, due both to natural and site related processes, of the elements H, O, N, Sr and U, to study the interconnection between vadose zone and groundwater contamination at the Hanford Site in south-central Washington. We follow this brief review with a presentation of new data pertaining to vadose zone and groundwater contamination in the WMA T-TX-TY vicinity. Uranium (U) isotopic data for the C3832 core (WMA TX) indicates the involvement of processed natural U fuel, and links the observed U contamination to the nearby single shelled tank TX-104. The data also precludes contamination from an early 1970’s TX-107 leak. In the case of the C4104 core (WMA T), the U isotopic data indicates a mixture of processed natural and enriched U fuels consistent with the major leak from T-106 in 1973. Uranium and Strontium isotopic data for the cores also provides direct evidence for chemical interaction between high-pH waste fluid and sediment. Isotopic data for groundwater nitrate contamination in the vicinity of WMA-T strongly suggests high-level tank waste (most likely from T-106) as the source of very high 99Tc concentrations recently observed at the NE corner of WMAT.

  6. Tetragonal Lysozyme Interactions Studied by Site Directed Mutagenesis

    NASA Technical Reports Server (NTRS)

    Crawford, Lisa; Karr, Laurel J.; Nadarajah, Arunan; Pusey, Marc

    1999-01-01

    A number of recent experimental and theoretical studies have indicated that tetragonal lysozyme crystal growth proceeds by the addition of aggregates, formed by reversible self association of the solute molecules in the bulk solution. Periodic bond chain and atomic force microscopy studies have indicated that the probable growth unit is at minimum a 43 tetramer, and most likely an octamer composed of two complete turns about the 43 axis. If these results are correct, then there are intermolecular interactions which are only formed in the solution and others only formed at the joining of the growth unit to the crystal surface. We have set out to study these interactions, and the correctness of this hypothesis, using site directed mutagenesis of specific amino acid residues involved in the different bonds. We had initially expressed wild type lysozyme in S. cervasiae with yields of approximately 5 mg/L, which were eventually raised to approximately 40 mg/L. We are now moving the expression to the Pichia system, with anticipated yields of 300 to (3)500 mg/L, comparable to what can be obtained from egg whites. An additional advantage of using recombinant protein is the greater genetic homogeneity of the material obtained and the absence of any other contaminating egg proteins. The first mutation experiments are TYR 23 (Registered) PHE or ALA and ASN 113 (Registered) ALA or ASP. Both TYR 23 and ASN 113 form part of the postulated dimerization intermolecular binding site which lead to the formation of the 43 helix. Tyrosine also participates in an intermolecular hydrogen bond with ARG 114. The results of these and subsequent experiments will be discussed.

  7. Tetragonal Lysozyme Interactions Studied by Site Directed Mutagenesis

    NASA Technical Reports Server (NTRS)

    Crawford, Lisa; Karr, Laurel; Pusey, Marc

    1998-01-01

    A number of recent experimental and theoretical studies have indicated that tetragonal lysozyme crystal growth proceeds by the addition of aggregates, formed by reversible self association of the solute molecules in the bulk'solution. Periodic bond chain and atomic force microscopy studies have indicated that the probable growth unit is at minimum a 43 tetramer, and most likely an octamer composed of two complete turns about the 4(sub 3) axis. If these results are correct, then there are intermolecular interactions which are only formed in the solution and others only formed at the joining of the growth unit to the crystal surface. We have set out to study these interactions, and the correctness of this hypothesis, using site directed mutagenesis of specific amino acid residues involved in the different bonds. We had initially expressed wild type lysozyme in S. cervasiae with yields of approximately 5 mg/L, which were eventually raised to approximately 40 mg/L. We are now moving the expression to the Pichia system, with anticipated yields of 300 to greater than 500 mg/L, comparable to what can be obtained from egg whites. An additional advantage of using recombinant protein is the greater genetic homogeneity of the material obtained and the absence of any other contaminating egg proteins. The first mutation experiments are TYR 23 yields PHE or ALA and ASN 113 yields ALA or ASP. Both TYR 23 and ASN 113 form part of the postulated dimerization intermolecular binding site which lead to the formation of the 4(sub 3) helix. Tyrosine also participates in an intermolecular hydrogen bond with ARG 114. The results of these and subsequent experiments will be discussed.

  8. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    PubMed

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain. PMID:18984021

  9. A Study of Automated Web Site Evaluation Tools

    Microsoft Academic Search

    Melody Y. Ivory

    2002-01-01

    Web site usability and accessibility continues to be a pressing problem. Hence, there are over 30automated evaluation tools to help designers to improve their sites. Unfortunately, there is little evidenceabout whether these tools actually improve sites from both the designer's and the user's perspectives.

  10. Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

    PubMed Central

    2015-01-01

    2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (±)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent binding mode, novel thio- and sulfinylacetamide and ethanamine analogues of (±)-1 were synthesized wherein (1) the diphenyl rings were substituted with methyl, trifluoromethyl, and halogen substituents and (2) substituents were added to the terminal amide/amine nitrogen. Halogen substitution of the diphenyl rings of (±)-1 gave several amide analogues with improved binding affinity for DAT and robust selectivity over the serotonin transporter (SERT), whereas affinity improved at SERT over DAT for the p-halo-substituted amine analogues. Molecular docking studies, using a subset of analogues with DAT and SERT homology models, and functional data obtained with DAT (A480T) and SERT (T497A) mutants defined a role for TM10 in the substrate/inhibitor S1 binding sites of DAT and SERT. PMID:24494745

  11. Kinetic and in silico analysis of the slow-binding inhibition of human poly(A)-specific ribonuclease (PARN) by novel nucleoside analogues.

    PubMed

    Balatsos, Nikolaos; Vlachakis, Dimitrios; Chatzigeorgiou, Vassiliki; Manta, Stella; Komiotis, Dimitri; Vlassi, Metaxia; Stathopoulos, Constantinos

    2012-01-01

    Poly(A)-specific ribonuclease (PARN) is a 3'-exoribonuclease that efficiently degrades poly(A) tails and regulates, in part, mRNA turnover rates. We have previously reported that adenosine- and cytosine-based glucopyranosyl nucleoside analogues with adequate tumour-inhibitory effect could effectively inhibit PARN. In the present study we dissect the mechanism of a more drastic inhibition of PARN by novel glucopyranosyl analogues bearing uracil, 5-fluorouracil or thymine as the base moiety. Kinetic analysis showed that three of the compounds are competitive inhibitors of PARN with K(i) values in the low ?M concentration and significantly lower (11- to 33-fold) compared to our previous studies. Detailed kinetic analysis of the most effective inhibitor, the uracil-based nucleoside analogue (named U1), revealed slow-binding behaviour. Subsequent molecular docking experiments showed that all the compounds which inhibited PARN can efficiently bind into the active site of the enzyme through specific interactions. The present study dissects the inhibitory mechanism of this novel uracil-based compound, which prolongs its inhibitory effect through a slow-binding and slow-release mode at the active site of PARN, thus contributing to a more efficient inhibition. Such analogues could be used as leading compounds for further rationale design and synthesis of efficient and specific therapeutic agents. Moreover, our data reinforce the notion that human PARN can be established as a novel molecular target of potential anti-cancer agents through lowering mRNA turnover rates. PMID:22041582

  12. Condensed matter analogues of cosmology

    NASA Astrophysics Data System (ADS)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the liveliest. A number of new experiments are reported here studying the dynamical evolution of domains and defects. Another phenomenon that played a key early role was the formation of vortices in the normal-to-superfluid transition in liquid helium-3. The complicated nature of the order parameter energy surface gives rise to a variety of intriguing effects. This too is still a vigorous field. Superconductivity is a special case because the symmetry that is broken is a gauge symmetry. This is also true in fundamental particle physics theories of relevance to cosmology, and for that reason experiments on superconductors are of particular interest to cosmologists. The situation in this case is more complicated because there are competing mechanisms of defect formation. Experiments in the field have not proved easy, either to perform or to interpret, but the papers in this collection show that good progress has been made of late. In recent years a new type of system has proved immensely fruitful, namely atomic Bose-Einstein or Fermi-gas condensates. Experiments on condensates with tunable parameters have in general provided broad support for the theory, and have also revealed a wide range of interesting and novel features, with intriguing possible analogues in cosmology (e.g. causal horizons and particle creation). The basic idea of the Kibble-Zurek mechanism has been shown to be relevant in this whole range of systems. But numerous complexities have also emerged, concerned for example with the role of inhomogeneity or the existence of composite defects. The field is still developing rapidly. Acknowledgments Finally, we would like to thank all the authors who have contributed to this issue, and the staff of Journal of Physics: Condensed Matter who have made it possible. Condensed matter analogues of cosmology contents Condensed matter analogues of cosmologyTom Kibble and Ajit Srivastava Symmetry breaking in nematic liquid crystals: analogy with cosmology and magnetismR Repnik, A Ranjkesh, V Simonka, M Ambrozic, Z Bradac and S Kralj Morphogenesis of defects and tactoids

  13. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    NASA Astrophysics Data System (ADS)

    Foing, Bernard

    2014-05-01

    We performed a series of field research campaigns (ILEWG EuroMoonMars) in the extreme Utah desert relevant to Mars environments, and in order to help in the interpretation of Mars missions measurements from orbit (MEX, MRO) or from the surface (MER, MSL), or Moon geochemistry (SMART-1, LRO). We shall give an update on the sample analysis in the context of habitability and astrobiology. Methods & Results: In the frame of ILEWG EuroMoonMars campaigns (2009 to 2013) we deployed at Mars Desert Research station, near Hanksville Utah, a suite of instruments and techniques [A, 1, 2, 9-11] including sample collection, context imaging from remote to local and microscale, drilling, spectrometers and life sensors. We analyzed how geological and geochemical evolution affected local parameters (mineralogy, organics content, environment variations) and the habitability and signature of organics and biota. Among the important findings are the diversity in the composition of soil samples even when collected in close proximity, the low abundances of detectable PAHs and amino acids and the presence of biota of all three domains of life with significant heterogeneity. An extraordinary variety of putative extremophiles was observed [3,4,9]. A dominant factor seems to be soil porosity and lower clay-sized particle content [6-8]. A protocol was developed for sterile sampling, contamination issues, and the diagnostics of biodiversity via PCR and DGGE analysis in soils and rocks samples [10, 11]. We compare the 2009 campaign results [1-9] to new measurements from 2010-2013 campaigns [10-12] relevant to: comparison between remote sensing and in-situ measurements; the study of minerals; the detection of organics and signs of life. Keywords: field analogue research, astrobiology, habitability, life detection, Earth-Moon-Mars, organics References [A] Foing, Stoker & Ehrenfreund (Editors, 2011) "Astrobiology field Research in Moon/Mars Analogue Environments", Special Issue of International Journal of Astrobiology , IJA 2011, 10, vol. 3. 137-305 [1] Foing B. et al. (2011) Field astrobiology research at Moon-Mars analogue site: Instruments and methods, IJA 2011, 10 (3), 141;[2] Clarke, J., Stoker, C. Concretions in exhumed & inverted channels near Hanksville Utah: implications for Mars, (IJA 2011, 10 (3), 162;[3] Thiel et al., (2011) PCR-based analysis of microbial communities during the EuroGeoMars campaign at Mars Desert Research Station, Utah. (IJA 2011, 10 (3), 177;[4] Direito et al. (2011). A wide variety of putative extremophiles and large beta-diversity at the Mars Desert Research Station (Utah). (IJA 2011, 10 (3), 191;[5] Orzechowska, G. et al (20110 analysis of Mars Analog soils using solid Phase Microextraction, Organics solvent extraction and GCMS, (IJA 2011, 10 (3), 209; [6] Kotler et al. (2011). Analysis of mineral matrices of planetary soils analogs from the Utah Desert. (IJA 2011, 10 (3), 221; [7] Martins et al. (2011). Extraction of amino acids from soils close to the Mars Desert Research Station (MDRS), Utah. (IJA 2011, 10 (3), 231; [8] Ehrenfreund et al. (2011) Astrobiology and habitability studies in preparation for future Mars missions: trends from investigating minerals, organics and biota. (IJA 2011, 10 (3), 239; [9] Stoker C. et al (2011) Mineralogical, Chemical, Organic & Microbial Properties of Subsurface Soil Cores from Mars Desert Research Station, a Phyllosilicate and Sulfate Rich Mars Analog Site, IJA 2011, 10 (3), 269; [10] Rodrigues L. et al (2014, in preparation) Preventing biocontamination during sterile sampling; [11] Rodrigues L. et al (2014, in preparation) Microbial diversity in MDRS rocks and soils; [12] ILEWG EuroMoonMars Team, (2014, special issue in preparation) Results from ILEWG EuroMoonMars campaign 2013 **Acknowledgements: B.H.Foing (1, 2, 6), C. Stoker (3), P. Ehrenfreund (4, 5), I. Rammos (2), L. Rodrigues (2), A. Svendsen (2), D. Oltheten (2), K. Nebergall (6), M. Battler (6, 7), H. v't Houd (8), A. Bruneau (6,9), M. Cross (6,7), V. Maivald (10), C. Orgel (6), A. Elsaesser (4),

  14. Emerald Lake Watershed study: Introduction and site description

    SciTech Connect

    Tonnessen, K.A. (California Air Resources Board, Sacramento (United States))

    1991-07-01

    The Emerald Lake Watershed study was organized to investigate the effects of acidic deposition on high-elevation watersheds and surface waters of the Sierra Nevada, California. Some of the results of this comprehensive study of aquatic and terrestrial ecosystems at a small, headwater basin are presented in four papers in this series. The watershed study site is in Sequoia National Park, on the western slope of the Sierra Nevada. This glacial cirque is located in the upper Marble Fork of the Kaweah River. This 120-ha watershed ranges from Alta Peak (3,416 m) down to Emerald Lake (2,400 m). Most of the watershed surface area is exposed granite and granodiorite rocks, with limited coverage (about 20%) by thin, acidic soils. The hydrology of the basin is dominated by snowmelt runoff during March-June. Emerald Lake, a glacial tarn, is 2.72 ha in area, with a maximum depth of 10.5 m. Surface waters are poorly buffered and dominated by calcium and bicarbonate. Most of the yearly precipitation falls as dilute snow (pH5.2-5.4), with acidic rain storms sampled during May-October.

  15. Arctic Mars Analogue Svalbard Expedition 2007

    NASA Astrophysics Data System (ADS)

    Steele, A.; Amundsen, H. E. F.

    2007-03-01

    This abstract summarizes the rover, space flight hardware testing and human rover interactions that took place on the Arctic Mars Analogue Svalbard Expedition 2006 and will present the results of life detection analysis undertaken in this Mars analogue en

  16. SUPERFUND TREATABILITY CLEARINGHOUSE: SOIL STABILIZATION PILOT STUDY, UNITED CHROME NPL SITE PILOT STUDY AND HEALTH AND SAFETY PROGRAM, UNITED CHROME NPL SITE PILOT STUDY

    EPA Science Inventory

    This document is a project plan for a pilot study at the United Chrome NPL site, Corvallis, Oregon and includes the health and safety and quality assurance/quality control plans. The plan reports results of a bench-scale study of the treatment process as iieasured by the ...

  17. MONITORED NATURAL ATTENUATION FOR INORGANIC CONTAMINANT REMEDIATION IN GROUND WATER: SITE STUDIES

    EPA Science Inventory

    Two site studies are presented from Superfund Fund Sites in the US where monitored natural attenuation is a component of overall site restoration efforts. The presentation emphasizes the development of site-specific transport and fate models for contaminants at these hazardous w...

  18. The Effectiveness of Course Web Sites in Higher Education: An Exploratory Study.

    ERIC Educational Resources Information Center

    Comunale, Christie L.; Sexton, Thomas R.; Voss, Diana J. Pedagano

    2002-01-01

    Describes an exploratory study of the educational effectiveness of course Web sites among undergraduate accounting students and graduate students in business statistics. Measured Web site visit frequency, usefulness of each site feature, and the impacts of Web sites on perceived learning and course performance. (Author/LRW)

  19. Study of A2A adenosine receptor gene deficient mice reveals that adenosine analogue CGS?21680 possesses no A2A receptor-unrelated lymphotoxicity

    PubMed Central

    Apasov, Sergey G; Chen, Jiang-Fan; Smith, Patrick T; Schwarzschild, Michael A; Fink, J Stephen; Sitkovsky, Michail V

    2000-01-01

    Cell surface A2A adenosine receptor (A2AR) mediated signalling affects a variety of important processes and adenosine analogues possess promising pharmacological properties. Demonstrating the receptor specificity of potentially lymphotoxic adenosine-based drugs facilitates their development for clinical applications. To distinguish between the receptor-dependent and -independent lymphotoxicity and apoptotic activity of adenosine and its analogues we used lymphocytes from A2AR-deficient mice. Comparison of A2AR-expressing (+/+) and A2AR-deficient (?/?) cells in cyclic AMP accumulation assays confirmed that the A2AR agonist CGS?21680 is indeed selective for A2A receptors in T-lymphocytes. Incubation of A2AR-expressing thymocytes with extracellular adenosine or CGS?21680 in vitro results in the death of about 7–15% of thymocytes. In contrast, no death was induced in parallel assays in cells from A2AR-deficient mice, providing genetic evidence that CGS?21680 does not display adenosine receptor-independent intracellular cytotoxicity. The A2A receptor-specific lymphotoxicity of CGS 21680 is also demonstrated in a long-term (6-day) in vitro model of thymocyte positive selection where addition of A2AR antagonist ZM?241,385 did block the effects of CGS?21680, allowing the survival of T cells. The use of cells from adenosine receptor-deficient animals is proposed as a part of the screening process for potential adenosine-based drugs for their receptor-independent cytotoxicity and lymphotoxicity. PMID:10960067

  20. A Virtual Collaborative Environment for Mars Surveyor Landing Site Studies

    NASA Astrophysics Data System (ADS)

    Gulick, V. C.; Deardorff, D. G.; Briggs, G. A.; Hand, K. P.; Sandstrom, T. A.

    1999-06-01

    Over the past year and a half, the Center for Mars Exploration (CMEX) at NASA Ames Research Center (ARC) has been working with the Mars Surveyor Project Office at JPL to promote interactions among the planetary community and to coordinate landing site activities for the Mars Surveyor Project Office. To date, CMEX has been responsible for organizing the first two Mars Surveyor Landing Site workshops, web-archiving resulting information from these workshops, aiding in science evaluations of candidate landing sites, and serving as a liaison between the community and the Project. Most recently, CMEX has also been working with information technologists at Ames to develop a state-of-the-art collaborative web site environment to foster interaction of interested members of the planetary community with the Mars Surveyor Program and the Project Office. The web site will continue to evolve over the next several years as new tools and features are added to support the ongoing Mars Surveyor missions.

  1. A Virtual Collaborative Environment for Mars Surveyor Landing Site Studies

    NASA Technical Reports Server (NTRS)

    Gulick, V. C.; Deardorff, D. G.; Briggs, G. A.; Hand, K. P.; Sandstrom, T. A.

    1999-01-01

    Over the past year and a half, the Center for Mars Exploration (CMEX) at NASA Ames Research Center (ARC) has been working with the Mars Surveyor Project Office at JPL to promote interactions among the planetary community and to coordinate landing site activities for the Mars Surveyor Project Office. To date, CMEX has been responsible for organizing the first two Mars Surveyor Landing Site workshops, web-archiving resulting information from these workshops, aiding in science evaluations of candidate landing sites, and serving as a liaison between the community and the Project. Most recently, CMEX has also been working with information technologists at Ames to develop a state-of-the-art collaborative web site environment to foster interaction of interested members of the planetary community with the Mars Surveyor Program and the Project Office. The web site will continue to evolve over the next several years as new tools and features are added to support the ongoing Mars Surveyor missions.

  2. 64Cu-Labeled Somatostatin Analogues Conjugated with Cross-Bridged Phosphonate-Based Chelators via Strain-Promoted Click Chemistry for PET Imaging: In silico through in Vivo Studies

    PubMed Central

    Cai, Zhengxin; Ouyang, Qin; Zeng, Dexing; Nguyen, Kim N.; Modi, Jalpa; Wang, Lirong; White, Alexander G.; Rogers, Buck E.; Xie, Xiang-Qun; Anderson, Carolyn J.

    2014-01-01

    Somatostatin receptor subtype 2 (sstr2) is a G-protein-coupled receptor (GPCR) that is overexpressed in neuroendocrine tumors. The homology model of sstr2 was built and was used to aid the design of new somatostatin analogues modified with phosphonate-containing cross-bridged chelators for evaluation of using them as PET imaging radiopharmaceuticals. The new generation chelators were conjugated to Tyr3-octreotate (Y3-TATE) through bioorthogonal, strain-promoted alkyne azide cycloaddition (SPAAC) to form CB-TE1A1P–DBCO–Y3-TATE (AP) and CB-TE1K1P–PEG4–DBCO–Y3-TATE (KP) in improved yields compared to standard direct conjugation methods of amide bond formation. Consistent with docking studies, the clicked bioconjugates showed high binding affinities to sstr2, with Kd values ranging from 0.6 to 2.3 nM. Selected isomers of the clicked products were used in biodistribution and PET/CT imaging. Introduction of the bulky dibenzocyclooctyne group in AP decreased clearance rates from circulation. However, the additional carboxylate group and PEG linker from the KP conjugate significantly improved labeling conditions and in vivo stability of the copper complex and ameliorated the slower pharmacokinetics of the clicked somatostatin analogues. PMID:24983404

  3. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    SciTech Connect

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  4. Repeat Hydrography at the Endeavour Integrated Study Site, 2004 - 2006

    NASA Astrophysics Data System (ADS)

    Kellogg, J. P.; McDuff, R. E.; Thomson, R. E.; Stahr, F. R.

    2006-12-01

    Significant differences exist between hydrographic transects made in the summers from 2004 to 2006 at the Endeavour Segment Integrated Study Site on the Juan de Fuca Ridge. Along and across axis sections describe the hydrographic conditions above the segment in three dimensions. The resulting sections allow for rapid evaluation of the characteristics of the neutrally buoyant plume over each of the vent fields and its location relative to the ridge axis. Results indicate heat content over the northern vent fields, Salty Dawg and Sasquatch, significantly increased between the summers of 2004 and 2005. In 2004, the plumes over these vent fields were barely discernable while in 2005 prominent plumes existed with potential temperature anomalies over 0.1°C. At the time of a rapid response cruise in March 2005, no significant change in the heat content of the water column was detected. By July 2005, dramatic changes had occurred in the overlying water column structure. The potential temperature anomaly section from 2005 is indicative of a thicker (about 75 m) neutrally buoyant plume with and substantially more heat at the north end of the valley. In 2004, the shallowest plume depth was 1900 m contrasted with 1830 m in 2005. Vent data being obtained by other RIDGE 2000 and UW Keck investigators will help constrain the underlying causes of these changes. New hydrography will be collected in August September 2006.

  5. Repeat Hydrography at the Endeavour Integrated Study Site, 2004 - 2005

    NASA Astrophysics Data System (ADS)

    Kellogg, J. P.; McDuff, R. E.; Thomson, R. E.; Stahr, F. R.

    2005-12-01

    Significant differences exist between hydrographic transects made in 2004 and 2005 at the Endeavour Segment Integrated Study Site on the Juan de Fuca Ridge. Sections that describe the conditions above the segment utilize twenty-one nearly uniformly spaced hydrographic stations from south of Mothra to north of the Sasquatch hydrothermal vent fields. Criteria used in choosing station locations included depth, ~500 m spacing from other stations, and being centrally located in the valley. The resulting sections allow for rapid evaluation of the characteristics of the neutrally buoyant plume over each of the vent fields. Preliminary results indicate heat content over the northern vent fields, Salty Dawg and Sasquatch, significantly increased between the summers of 2004 and 2005. In 2004, the plumes over these vent fields were barely discernable while in 2005 prominent plumes existed with potential temperature anomalies over 0.1°C. Vent data being obtained by other RIDGE 2000 and UW Keck investigators will help constrain the underlying causes of these changes. Isopycnals in the 2005 sections are also elevated along the entire length of the transect by approximately 50 m or more. The potential temperature anomaly section from 2005 is indicative of a thicker (about 75 m) neutrally buoyant plume and substantially more heat at the north end of the valley. In 2004, the shallowest plume depth was 1900 m contrasted with 1830 m in 2005.

  6. Report of the Fermilab Committee for Site Studies

    SciTech Connect

    Steve Holmes, Vic Kuchler et. al.

    2001-09-10

    Fermilab is the flagship laboratory of the U.S. high-energy physics program. The Fermilab accelerator complex has occupied the energy frontier nearly continuously since its construction in the early 1970s. It will remain at the frontier until the Large Hadron Collider at CERN begins operating in 2006-7. A healthy future for Fermilab will likely require construction of a new accelerator in the post-LHC era. The process of identifying, constructing and operating a future forefront facility will require the support of the world high-energy-physics community, the governments and funding agencies of many nations and the people of surrounding communities. This report explores options for construction of a new facility on or near the existing Fermilab site. We began the study that forms the basis of this report with the idea that Fermilab, and the surrounding area of northeastern Illinois, possesses attributes that make it an attractive candidate for a new accelerator construction project: excellent geology; a Fermilab staff and local contractors who are experienced in subsurface construction; abundant energy supplies; good access to transportation networks; the presence of local universities with strong interest and participation in the Fermilab research program; Fermilab's demonstrated ability to mount large accelerator construction projects and operate complex accelerator facilities; and a surrounding community that is largely supportive of Fermilab's presence. Our report largely confirms these perceptions.

  7. NREL Studies Wind Farm Aerodynamics to Improve Siting (Fact Sheet)

    SciTech Connect

    Not Available

    2012-04-01

    NREL researchers have used high-tech instruments and high-performance computing to understand atmospheric turbulence and turbine wake behavior in order to improve wind turbine design and siting within wind farms.

  8. Further Studies on 2-Arylacetamide Pyridazin-3(2H)-ones: Design, Synthesis and Evaluation of 4,6-Disubstituted Analogues as Formyl Peptide Receptors (FPRs) Agonists

    PubMed Central

    Giovannoni, Maria Paola; Schepetkin, Igor A.; Cilibrizzi, Agostino; Crocetti, Letizia; Khlebnikov, Andrei I.; Dahlgren, Claes; Graziano, Alessia; Piaz, Vittorio Dal; Kirpotina, Liliya N.; Zerbinati, Serena; Vergelli, Claudia; Quinn, Mark T.

    2013-01-01

    Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and tested for FPR agonist activity. The pyridazin-3(2H)-one ring was confirmed to be an appropriate scaffold to support FPR agonist activity, and its modification at the 4 and 6 positions led to the identification of additional active agonists, which induced intracellular Ca2+ flux in HL-60 cells transfected with either FPR1, FPR2, or FPR3. Seven formyl peptide receptor 1 (FPR1)-specific and several mixed FPR1/FPR2 dual agonists were identified with low micromolar EC50 values. Furthermore, these agonists also activated human neutrophils, inducing intracellular Ca2+ flux and chemotaxis. Finally, molecular docking studies indicated that the most potent pyridazin-3(2H)-ones overlapped in their best docking poses with fMLF and WKYMVM peptides in the FPR1 and FPR2 ligand binding sites, respectively. Thus, pyridazinone-based compounds represent potential lead compounds for further development of selective and/or potent FPR agonists. PMID:23685570

  9. RADIATIVE CLOSURE STUDIES AT THE NSA ACRF SITE Delamere, J., Atmospheric and Environmental Research, Inc.

    E-print Network

    RADIATIVE CLOSURE STUDIES AT THE NSA ACRF SITE Delamere, J., Atmospheric and Environmental Research from the Broadband Heating Rate Profile (BBHRP) Project for the NSA site. Among the goals of the BBHRP

  10. Somatostatin analogues suppress the inflammatory reaction in vivo.

    PubMed Central

    Karalis, K; Mastorakos, G; Chrousos, G P; Tolis, G

    1994-01-01

    Somatostatin (Sms) and its agonist analogues inhibit the secretory activities of endocrine and neural cells. Recent studies have suggested that Sms has significant immunomodulatory properties. In this study, we examine the effects of two Sms octapeptide analogues on the inflammatory reaction in vivo. BIM 23014 (Somatulin) and Sandostatin were administered to male Sprague-Dawley rats subject to carrageenin-induced aseptic inflammation, at doses of 2-10 micrograms/rat, given either systemically or locally. Animals were killed 7 h after the induction of the inflammation, and the inflammatory exudates were aspirated and quantitated in terms of volume and leukocyte concentration. Sms analogues, administered via either route, significantly reduced the volume and the leukocyte concentration of the exudate in a time- and dose-dependent fashion. In corroboration of these, immunohistochemical evaluation of the levels of local inflammatory mediators, such as immunoreactive (Ir) TNF-alpha, Irsubstance P, and Ircorticotropin-releasing hormone, was inhibited significantly by Sms analogue treatment. These findings suggest that Sms analogues have significant antiinflammatory effects in vivo, associated with suppression of proinflammatory cytokines and neuropeptides. Furthermore, these data suggest that Sms agonists may be useful in the control of inflammatory reaction. Images PMID:7514191

  11. Increased free water in the substantia nigra of Parkinson's disease: a single-site and multi-site study.

    PubMed

    Ofori, Edward; Pasternak, Ofer; Planetta, Peggy J; Burciu, Roxana; Snyder, Amy; Febo, Marcelo; Golde, Todd E; Okun, Michael S; Vaillancourt, David E

    2015-02-01

    Measures from diffusion magnetic resonance imaging reflect changes in the substantia nigra of Parkinson's disease. It is the case, however, that partial volume effects from free water can bias diffusion measurements. The bi-tensor diffusion model was introduced to quantify the contribution of free water and eliminates its bias on estimations of tissue microstructure. Here, we test the hypothesis that free water is elevated in the substantia nigra for Parkinson's disease compared with control subjects. This hypothesis was tested between large cohorts of Parkinson's disease and control participants in a single-site study and validated against a multisite study using multiple scanners. The fractional volume of free water was increased in the posterior region of the substantia nigra in Parkinson's disease compared with control subjects in both the single-site and multi-site studies. We did not observe changes in either cohort for free-water-corrected fractional anisotropy or free-water-corrected mean diffusivity. Our findings provide new evidence that the free-water index reflects alteration of the substantia nigra in Parkinson's disease, and this was evidenced across both single-site and multi-site cohorts. PMID:25467638

  12. Parametric Studies for Scenario Earthquakes: Site Effects and Differential Motion

    NASA Astrophysics Data System (ADS)

    Panza, G. F.; Panza, G. F.; Romanelli, F.

    2001-12-01

    In presence of strong lateral heterogeneities, the generation of local surface waves and local resonance can give rise to a complicated pattern in the spatial groundshaking scenario. For any object of the built environment with dimensions greater than the characteristic length of the ground motion, different parts of its foundations can experience severe non-synchronous seismic input. In order to perform an accurate estimate of the site effects, and of differential motion, in realistic geometries, it is necessary to make a parametric study that takes into account the complex combination of the source and propagation parameters. The computation of a wide set of time histories and spectral information, corresponding to possible seismotectonic scenarios for different source and structural models, allows us the construction of damage scenarios that are out of reach of stochastic models. Synthetic signals, to be used as seismic input in a subsequent engineering analysis, e.g. for the design of earthquake-resistant structures or for the estimation of differential motion, can be produced at a very low cost/benefit ratio. We illustrate the work done in the framework of a large international cooperation following the guidelines of the UNESCO IUGS IGCP Project 414 "Realistic Modeling of Seismic Input for Megacities and Large Urban Areas" and show the very recent numerical experiments carried out within the EC project "Advanced methods for assessing the seismic vulnerability of existing motorway bridges" (VAB) to assess the importance of non-synchronous seismic excitation of long structures. >http://www.ictp.trieste.it/www_users/sand/projects.html

  13. Fuel quality/processing study. Volume 4: On site processing studies

    NASA Technical Reports Server (NTRS)

    Jones, G. E., Jr.; Cutrone, M.; Doering, H.; Hickey, J.

    1981-01-01

    Fuel treated at the turbine and the turbine exhaust gas processed at the turbine site are studied. Fuel treatments protect the turbine from contaminants or impurities either in the upgrading fuel as produced or picked up by the fuel during normal transportation. Exhaust gas treatments provide for the reduction of NOx and SOx to environmentally acceptable levels. The impact of fuel quality upon turbine maintenance and deterioration is considered. On site costs include not only the fuel treatment costs as such, but also incremental costs incurred by the turbine operator if a turbine fuel of low quality is not acceptably upgraded.

  14. Preliminary study on calcium aluminosilicate glass as a potential host matrix for radioactive 90Sr--an approach based on natural analogue study.

    PubMed

    Sengupta, Pranesh; Fanara, Sara; Chakraborty, Sumit

    2011-06-15

    Given the environmental-, safety- and security risks associated with sealed radioactive sources it is important to identify suitable host matrices for (90)Sr that is used for various peaceful applications. As SrO promotes phase separation within borosilicate melt, aluminosilicate bulk compositions belonging to anorthite-wollastonite-gehlenite stability field are studied in this work. Tests for their homogeneity, microstructural characteristics and resistance to phase separation narrowed the choice down to the composition CAS11 (CaO=35 wt%, Al(2)O(3)=20 wt%, SiO(2)=45 wt%). We find that up to 30 wt% SrO can be loaded in this glass without phase separation (into Ca, Sr-rich and Sr-poor, Si-rich domains). Leaching behaviour of the glasses differs depending on the content and distribution of Sr. In general, the elemental leach rates determined from conventional PCT experimental procedure yield values better than 10(-7)gcm(-2)day(-1) for both CAS11 base glass as well as SrO doped glass. It was noted that leach rates calculated on the basis of Ca(2+) and Sr(2+) were of the same order and bit higher compared to those calculated on the basis of Si(4+) and Al(3+). During accelerated leaching tests, zeolite and zeolite+epidote were found to have developed on CAS11 base glass and SrO doped glasses respectively. The Sr bulk diffusion coefficients is found to vary from ? 10(-15) to 10(-13)cm(2)/s at temperature intervals as high as 725-850°C. Based on the experimental observations, it is suggested that CAS11 glass can be used as host matrix of (90)Sr for various applications of radioactive Sr-pencils. PMID:21477923

  15. Mechanism of Carboxypeptidase A: Hydration of a Ketonic Substrate Analogue

    Microsoft Academic Search

    David W. Christianson; Peter R. David; William N. Lipscomb

    1987-01-01

    The structure of the complex between carboxypeptidase Aalpha (EC 3.4.17.1) and the ketonic substrate analogue 5-benzamido-2-benzyl-4-oxopentanoic acid (BOP) has been determined by x-ray crystallographic methods to a resolution of 1.7 angstrom (final R = 0.191). Interestingly, BOP was observed to bind to the active site of carboxypeptidase Aalpha as the covalent hydrate adduct. Because BOP is probably less than 0.2%

  16. Optical Properties of Titan's Aerosol Analogues

    NASA Astrophysics Data System (ADS)

    Ramirez, Sandra I.; Contreras, G.; Agarwal, V.

    2006-09-01

    In the upper Titan's atmosphere its main constituents, CH4 and N2, are photolyzed and radiolyzed by solar photons and magnetospheric electrons. The primary products of these chemical interactions evolve to heavier organic compounds which are likely to associate to form the haze layers observed on Titan's upper atmosphere. Different theories and models have been used to explain the physical, chemical and optical properties of the haze material, but only with limited success. Among the parameters involved in these models, the complex refractive index is one of the most critical due to the influence that chemical composition and structural organization of the solid have on the n and k values. As part of a continued systematical study for the synthesis and characterization of Titan's aerosol analogues initiated in our group, we have subjected mixtures of CH4 in N2 to laser irradiation to produce layer of aerosol analogues. A set of optical properties values directly calculated from the transmission and reflectance curves, as well as a chemical characterization, by tandem mass spectroscopy, of the laboratory analogues will be presented. Our experimental protocol avoids some of the difficulties usually faced on laboratory simulations (over-irradiation, contamination with atmospheric oxygen, accurate ratio of initial gas mixture), porosity influences will also be discussed. The optical values can be used to determine how the chemical and optical properties of these aerosols influence the matching with the observed geometric albedo spectrum and how they participate in the radiative equilibrium processes in Titan's atmosphere. They will certainly help in the interpretation of the observations made by the Huygens descend through Titan's atmosphere last January and in all the new information about Titan generated since then. Financial support from CONACyT (40449) and PROMEP (103.5/03/1134) is acknowledged. SIRJ acknowledges a travel grant from PIFI 3.2.

  17. Substrate analogues for isoprenoid enzymes

    SciTech Connect

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  18. A femtosecond transient absorption spectroscopic study on a carbonyl-containing carotenoid analogue, 2-(all-trans-retinylidene)-indan-1,3-dione

    PubMed Central

    Kusumoto, Toshiyuki; Kosumi, Daisuke; Uragami, Chiasa; Frank, Harry A.; Birge, Robert R.; Cogdell, Richard J.; Hashimoto, Hideki

    2011-01-01

    The photophysical properties of a carbonyl-containing carotenoid analogue in an s-cis configuration, relative to the conjugated ? system, 2-(all-trans-retinylidene)-indan-1,3-dione (C20Ind), were investigated by femtosecond time-resolved spectroscopy in various solvents. The lifetime of the optically forbidden S1 state of C20Ind becomes long as solvent polarity increases. This trend is completely opposite to the situation of S1-ICT dynamics of carbonyl-containing carotenoids, such as peridinin and fucoxanthin. Excitation energy dependence of the transient absorption measurements shows that the transient absorption spectra in non-polar solvents were originated from two distinct transient species, while those in polar and protic solvents are due to a single transient species. By referring to the results of MNDO-PSDCI (modified neglect of differential overlap with partial single- and double-configuration interaction) calculations, we conclude: (1) In polar and protic solvents, the S1 state is generated following excitation up to the S2 state; (2) In non-polar solvents, however, both the S1 and 1n?* states are generated; and (3) C20Ind does not generate the S1-ICT state, despite the fact that it has two conjugated carbonyl groups. PMID:21361262

  19. Transition States and transition state analogue interactions with enzymes.

    PubMed

    Schramm, Vern L

    2015-04-21

    Enzymatic transition states have lifetimes of a few femtoseconds (fs). Computational analysis of enzyme motions leading to transition state formation suggests that local catalytic site motions on the fs time scale provide the mechanism to locate transition states. An experimental test of protein fs motion and its relation to transition state formation can be provided by isotopically heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states without altered electrostatic properties, according to the Born-Oppenheimer approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent with altered protein bond frequencies slowing the search for the transition state. In other heavy enzymes, structural changes involved in reactant binding and release are also influenced. Slow protein motions associated with substrate binding and catalytic site preorganization are essential to allow the subsequent fs motions to locate the transition state and to facilitate the efficient release of products. In the catalytically competent geometry, local groups move in stochastic atomic motion on the fs time scale, within transition state-accessible conformations created by slower protein motions. The fs time scale for the transition state motions does not permit thermodynamic equilibrium between the transition state and stable enzyme states. Isotopically heavy enzymes provide a diagnostic tool for fast coupled protein motions to transition state formation and mass-dependent conformational changes. The binding of transition state analogue inhibitors is the opposite in catalytic time scale to formation of the transition state but is related by similar geometries of the enzyme-transition state and enzyme-inhibitor interactions. While enzymatic transition states have lifetimes as short as 10(-15) s, transition state analogues can bind tightly to enzymes with release rates greater than 10(3) s. Tight-binding transition state analogues stabilize the rare but evolved enzymatic geometry to form the transition state. Evolution to efficient catalysis optimized this geometry and its stabilization by a transition state mimic results in tight binding. Release rates of transition state analogues are orders of magnitude slower than product release in normal catalytic function. During catalysis, product release is facilitated by altered chemistry. Compared to the weak associations found in Michaelis complexes, transition state analogues involve strong interactions related to those in the transition state. Optimum binding of transition state analogues occurs when the complex retains the system motions intrinsic to transition state formation. Conserved dynamic motion retains the entropic components of inhibitor complexes, improving the thermodynamics of analogue binding. PMID:25848811

  20. Site study plan for utilities and solid waste, Deaf Smith County Site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    This site plan describes utilities and solid waste studies to be conducted during the characterization of the Deaf Smith County, Texas, site for the US Department of Energy's Salt Repository Project. After utilities and solid waste information needs derived from Federal, State, and local statutes and regulations and the project specifications are briefly described, the site study plan describes the study design and rationale, the field data collection procedures and equipment, and data analysis methods and application of results, the data management strategy, the schedule of field activities, the management of the study, and the study's quality assurance program. The field data collection activities are organized into programs to characterize electrical power, natural gas, communication, water, wastewater sludge, nonradiological solid waste, nonradiological hazardous waste, and low-level radiological waste. These programs include details for the collection of project needs, identification of utilities and solid waste disposal contractor capabilities, and verification of the obtained data. Utilities and solid waste field activities will begin approximately at the time of site access. Utilities and solid waste characterization will be completed within the first year of activity. 29 refs., 6 figs., 2 tabs.

  1. The active site topology of Aspergillus niger endopolygalacturonase II as studied by site-directed mutagenesis.

    PubMed

    Armand, S; Wagemaker, M J; Sánchez-Torres, P; Kester, H C; van Santen, Y; Dijkstra, B W; Visser, J; Benen, J A

    2000-01-01

    Strictly conserved charged residues among polygalacturonases (Asp-180, Asp-201, Asp-202, His-223, Arg-256, and Lys-258) were subjected to site-directed mutagenesis in Aspergillus niger endopolygalacturonase II. Specific activity, product progression, and kinetic parameters (K(m) and V(max)) were determined on polygalacturonic acid for the purified mutated enzymes, and bond cleavage frequencies on oligogalacturonates were calculated. Depending on their specific activity, the mutated endopolygalacturonases II were grouped into three classes. The mutant enzymes displayed bond cleavage frequencies on penta- and/or hexagalacturonate different from the wild type endopolygalacturonase II. Based on the biochemical characterization of endopolygalacturonase II mutants together with the three-dimensional structure of the wild type enzyme, we suggest that the mutated residues are involved in either primarily substrate binding (Arg-256 and Lys-258) or maintaining the proper ionization state of a catalytic residue (His-223). The individual roles of Asp-180, Asp-201, and Asp-202 in catalysis are discussed. The active site topology is different from the one commonly found in inverting glycosyl hydrolases. PMID:10617668

  2. Technical procedures for implementation of aesthetics site studies, Deaf Smith County site, Texas: Environmental Field Program

    SciTech Connect

    Not Available

    1987-06-01

    This chapter introduces the purpose and scope of the visually affected areas determination, as well as definitions, interfaces, and concurrent data needs. This procedure provides a method for determining the extent of visibility of the project. This area is identified as the visually affected area, and becomes the area within which all visual analysis is conducted. The visually affected area analysis of the Deaf Smith County site will involve identifying and mapping the visibility of all major proposed project features. Baseline analysis will be conducted within the overall visually affected area; impact assessment will be conducted within the visually affected area of each major project feature. This procedure presents the guidelines for determining the visually affected area will be in computer data base construction; viewshed modeling, and site visit and verification of results. Computer data base construction will involve digitizing topographic and project facility data from available data source. The extent of the visible area from each major project feature will then be plotted. Finally, these computer-generated visibility plots will be verified in the field.

  3. Site study plan for Deep Hydronest Test Wells, Deaf Smith County Site, Texas: Preliminary draft

    SciTech Connect

    Not Available

    1987-05-01

    Wells called Deep Hydronest Wells will be installed at six locations at the Deaf Smith County Site to characterize hydraulic parameters in the geologic column between the top of the San Andres Formation and the base of Pennsylvanian System. Three hydronests will be drilled during early stages of site characterization to provide data for performance assessment modeling. Four wells are proposed for each of these 3 nests. Results of drilling, testing, and preliminary modeling will direct drilling and testing activities at the last 3 nests. Two wells are proposed at each of the last 3 nests for a total of 18 wells. The Salt Repository Project (SRP) Networks specify the schedule under which this program will operate. Drilling and hydrologic testing of the first Deep Hydronest will begin early in the Surface Investigation Program. Drilling and testing of the first three Deep Hydronests will require about 18 months. After 12 months of evaluating and analyzing data from the first three hydronests, the remaining three hydronests will be drilled during a 12-month period. The Technical Field Services Contractor is responsible for conducting the field program. Samples and data will be handled and reported in accordance with established SRP procedures. A quality assurance program will be used to assure that activities affecting quality are performed correctly and that the appropriate documentation is maintained. 36 refs., 20 figs., 6 tabs.

  4. Variation effect on the insecticide activity of DDT analogues. A chemometric approach

    NASA Astrophysics Data System (ADS)

    Itoh, S.; Nagashima, U.

    2002-08-01

    We investigated a variation effect on the insecticide activity of DDT analogues by using the first principles electronic structure calculations and the neural network analysis. It has been found that the charge distribution at the specific atomic sites in the DDT molecule is related to their toxicity. This approach can contribute to designing a new insecticide and a new harmlessness process of the DDT analogues.

  5. Bioluminescent properties of obelin and aequorin with novel coelenterazine analogues.

    PubMed

    Gealageas, Ronan; Malikova, Natalia P; Picaud, Sandrine; Borgdorff, Aren J; Burakova, Ludmila P; Brûlet, Philippe; Vysotski, Eugene S; Dodd, Robert H

    2014-04-01

    The main analytical use of Ca(2+)-regulated photoproteins from luminous coelenterates is for real-time non-invasive visualization of intracellular calcium concentration ([Ca(2+)]i) dynamics in cells and whole organisms. A limitation of this approach for in vivo deep tissue imaging is the fact that blue light emitted by the photoprotein is highly absorbed by tissue. Seven novel coelenterazine analogues were synthesized and their effects on the bioluminescent properties of recombinant obelin from Obelia longissima and aequorin from Aequorea victoria were evaluated. Only analogues having electron-donating groups (m-OCH3 and m-OH) on the C6 phenol moiety or an extended resonance system at the C8 position (1-naphthyl and ?-styryl analogues) showed a significant red shift of light emission. Of these, only the ?-styryl analogue displayed a sufficiently high light intensity to allow eventual tissue penetration. The possible suitability of this compound for in vivo assays was corroborated by studies with aequorin which allowed the monitoring of [Ca(2+)]i dynamics in cultured CHO cells and in hippocampal brain slices. Thus, the ?-styryl coelenterazine analogue might be potentially useful for non-invasive, in vivo bioluminescence imaging in deep tissues of small animals. PMID:24553660

  6. Synthesis, stereochemistry and SAR of a series of minodronate analogues as RGGT inhibitors.

    PubMed

    B?a?ewska, Katarzyna M; Ni, Feng; Haiges, Ralf; Kashemirov, Boris A; Coxon, Fraser P; Stewart, Charlotte A; Baron, Rudi; Rogers, Michael J; Seabra, Miguel C; Ebetino, Frank H; McKenna, Charles E

    2011-10-01

    Phosphonocarboxylate (PC) analogues of bisphosphonates are of interest due to their selective inhibition of a key enzyme in the mevalonate pathway, Rab geranylgeranyl transferase (RGGT). The dextrarotatory enantiomer of 2-hydroxy-3-(imidazo[1,2-a]pyridin-3-yl)-2-phosphonopropanoic acid (3-IPEHPC, 1) is the most potent PC-type RGGT inhibitor thus far identified. The absolute configuration of (+)-1 in the active site complex has remained unknown due to difficulties in obtaining RGGT inhibitor complex crystals suitable for X-ray diffraction analysis. However, we have now succeeded in crystallizing (-)-1 and here report its absolute configuration (AC) obtained by X-ray crystallography, thus also defining the AC of (+)-1. An Autodock Vina 1.1 computer modeling study of (+)-1 in the active site of modified RGGT binding GGPP (3DSV) identifies stereochemistry-dependent interactions that could account for the potency of (+)-1 and supports the hypothesis that this type of inhibitor binds at the TAG tunnel, inhibiting the second geranylgeranylation step. We also report a convenient (31)P NMR method to determine enantiomeric excess of 1 and its pyridyl analogue 2, using ?- and ?-cyclodextrins as chiral solvating agents, and describe the synthesis of a small series of 1 ?-X (X = H, F, Cl, Br; 7a-d) analogues to assess the contribution of the ?-OH group to activity at enzyme and cellular levels. The IC(50) of 1 was 5-10× lower than 7a-d, and the LED for inhibition of Rab11 prenylation in vitro was 2-8× lower than for 7a-d. However, in a viability reduction assay with J774 cells, 1 and 7b had similar IC(50) values, ~10× lower than those of 7a and 7c-d. PMID:21889236

  7. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    SciTech Connect

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory analysis of the saturated zone water chemistry. The results of the field investigations and laboratory analyses of rock and water samples collected at Nopal I are used to calibrate the Pena Blanca Natural Analogue Model.

  8. A Preliminary Case Study for Rectenna Sites in Indonesia

    NASA Astrophysics Data System (ADS)

    Purwanto, Y.; Collins, P.

    2004-12-01

    Electricity power generation using alternative energy sources in Indonesia has become an important policy. Until now, the contribution from alternative energy sources (especially from renewable energy sources) is very small, only about 1% of the total energy supply. It is expected that in the next 10 years this contribution will be raised to 20%. The development of renewable energy sources is primarily performed in remote areas, that are poor in infrastructure facilities. This is considered to be a good policy since there are many such remote areas in Indonesia that need development programs. The existence of Solar Power Satellite system will open a new horizon in alternative energy supply, including Indonesia, because of its higher efficiency compared to conventional terrestrial solar cells, with almost no influence from either climate or solar position. Like other countries in the world, Indonesia, although one of the largest mineral energy producers in the world (i.e. oil, coal, and natural gas), still gives attention to energy diversification programs, including solar energy utilization. SPS, being based on solar energy, could be a good choice. The Indonesian archipelago consists of thousands of islands (more than 13,000) and is the equatorial country with the longest equatorial extent (more than 5000 km). This condition is very good for energy reception from the SPS 2000 pilot plant since the energy transmitting system (spacetenna) will orbit above the equator. Along the equator there could be placed more than four receiving stations (rectenna), especially in remote areas. Thus, it is very important to consider the involvement of Indonesia in SPS energy reception research. This paper describes a preliminary study of the development possibilities in SPS energy reception in Indonesia. To define the rectenna sites and physical development aspect, this study considers some major aspects: environmental, technical, social, and economic aspects. Environmental aspects include the possibilities of environmental damage due to the high intensity electromagnetic energy from outer space. As is well known, most Indonesian land areas consist of tropical forest which is rich with flora and fauna; these may face risks from receiving such electromagnetic energy illumination. It is considered that rectenna location selection in the main islands (like Java, Sumatra, Kalimantan, Sulawesi, Irian, etc.) which are densely populated should be avoided. The same conditions should also be considered for the location in the forest, due to the flora and fauna damage possibilities during the physical development process. From this study it can be considered that the appropriate rectenna location should be placed on uninhabited small coral islands (atoll) sized about 5x5 km 2 , which are located along the equator. Such coral islands are vailable in the western and eastern parts of Indonesia. It is also considered that such coral islands should be located not too far from major inhabited islands, that is about 5-10 km offshore due to the convenience of physical rectenna development and electric energy distribution to the mainland. Such a coral island is to be considered to suffer minimal effects if the surface is illuminated by microwave energy. The same effect suffered by resident creatures like birds and reptiles should also be minimal. Because of the very limited infrastructure available on the mainland (and likely no facilities at all), a rectenna development study should consider all technical risks. For example, antenna installation and building of other support components should be done in such a location so that sea surface transportation can be easily performed. Communication system may be performed only by radio transceivers and satellite systems. The existence of human resources, that are needed to physically develop buildings, must be considered since the location is a remote island. There will also be no expert staff available, so that they will need to be recruited on the mainland (i.e. Java). From these considerations it can be seen

  9. Federated Search and the Library Web Site: A Study of Association of Research Libraries Member Web Sites

    ERIC Educational Resources Information Center

    Williams, Sarah C.

    2010-01-01

    The purpose of this study was to investigate how federated search engines are incorporated into the Web sites of libraries in the Association of Research Libraries. In 2009, information was gathered for each library in the Association of Research Libraries with a federated search engine. This included the name of the federated search service and…

  10. GROUNDWATER AND LEACHATE TREATABILITY STUDIES AT FOUR SUPERFUND SITES

    EPA Science Inventory

    Selected wastewater treatment processes were evaluated in bench-scale tests using contaminated groundwaters and leachates from four hazardous waste problem sites. The processes investigated were selected on the basis of an extensive literature review and desktop analysis of 18 ca...

  11. Nuclear energy center site survey: fuel cycle studies

    SciTech Connect

    Not Available

    1976-05-01

    Background information for the Nuclear Regulatory Commission Nuclear Energy Center Site Survey is presented in the following task areas: economics of integrated vs. dispersed nuclear fuel cycle facilities, plutonium fungibility, fuel cycle industry model, production controls and failure contingencies, environmental impact, waste management, emergency response capability, and feasibility evaluations. (DG)

  12. Site matching of wind turbine generators: a case study

    Microsoft Academic Search

    S. H. Jangamshetti; V. G. Rau

    1999-01-01

    Site matching of wind turbine generators is investigated based on the appropriate selection of statistical models and means of wind speed data. The wind speed means are computed using arithmetic mean, root mean square and cubic mean cuberoot. Wind speed frequency distributions are modelled using Weibull and Rayleigh probability density functions. Wind speed data of an existing wind power station,

  13. RESEARCH STUDIES AT THE GILT EDGE MINE SUPERFUND SITE

    EPA Science Inventory

    A collaborative effort is being implemented at the Gilt Edge Mine Superfund site near Lead, SD. The partnerships involves the Mine Waste Technology Program (MWTP) with the USEPA's NRMRL, Region VIII Superfund program, the DOE, MSE Technology Application, Inc (MSE) and CDM Federal...

  14. CASE STUDY: SITE CONCEPTUAL MODEL FOR ENHANCED MNA OF ARSENIC

    EPA Science Inventory

    Field investigations have been conducted to understand the fate of arsenic in contaminated ground water during discharge into the Halls Brook Holding Area (HBHA) Pond at the Industri-Plex Superfund Site in Massachusetts. The ground water plume contains elevated levels of arsenic...

  15. Current Research at the Endeavour Ridge 2000 Integrated Studies Site

    NASA Astrophysics Data System (ADS)

    Butterfield, D. A.; Kelley, D. S.; Ridge 2000 Community, R.

    2004-12-01

    Integrated geophysical, geological, chemical, and biological studies are being conducted on the Endeavour segment with primary support from NSF, the W.M. Keck Foundation, and NSERC (Canada). The research includes a seismic network, physical and chemical sensors, high-precision mapping and time-series sampling. Several research expeditions have taken place at the Endeavour ISS in the past year. In June 2003, an NSF-sponsored cruise with R.V. al T.G.Thompson/ROV al Jason2 installed microbial incubators in drill-holes in the sides of active sulfide chimneys and sampled rocks, fluids, and microbes in the Mothra and Main Endeavour Field (MEF). In July 2003, with al Thompson/Jason2, an NSF-LEXEN project at Baby Bare on Endeavour east flank conducted sampling through seafloor-penetrating probes, plus time-series sampling of fluids, microbes, and rocks at the MEF. In September 2003, with al Thompson/ROV al ROPOS, the Keck Proto-Neptune project installed a seismic network consisting of 1 broadband and 7 short-period seismometers, installation of chemical/physical sensors and time-series samplers for chemistry and microbiology in the MEF and Clam Bed sites, collection of rocks, fluids, animals, and microbes. In May/June 2004, an NSF-sponsored al Atlantis/Alvin cruise recovered sulfide incubators installed in 2003, redeployed a sulfide incubator, mapped MEF and Mothra vent fields with high-resolution Imagenix sonar, sampled fluids from MEF, Mothra, and Clam Bed, recovered year-long time-series fluid and microbial samplers from MEF and Clam Bed, recovered and installed hot vent temperature-resistivity monitors, cleaned up the MEF and deployed new markers at major sulfide structures. In August 2004, there were two MBARI/Keck-sponsored cruises with R.V. al Western Flyer/ROV al Tiburon. The first cruise completed the seismic network with addition of two more broadband seismometers and serviced all 7 short-period seismometers. al Tiburon then performed microbial and chemical investigations at MEF, Mothra, Sasquatch, and Middle Valley, collecting fluid, particle, and animal samples for culture and phylogenetic analysis. al Tiburon continued in late August/September with detailed petrological sampling. A Keck-sponsored al Thompson/ROPOS cruise in September continued work on chemical/physical sensor deployments and time-series chemical and microbial sampling. A graduate student workshop at Friday Harbor beginning October 2004 will analyze the first year of data from the seismic network and begin to correlate seismic activity with hydrothermal activity. The Endeavour ISS is still in a phase of data collection and sensor development, but moving toward data integration.

  16. 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…

  17. A Study of the Hotel Industry's Application of the Web Site as a Marketing Tool

    Microsoft Academic Search

    Jun Wu

    2010-01-01

    The purpose of this study is to provide a direction on developing effective web site marketing strategy for China hotels by evaluating, analyzing and comparing the web sites between China hotels and U.S. hotels. In the article, the web site marketing attributes were identified and categorized into four groups “information”, “communication”, “distribution” and “transaction” based on the ICDT model and

  18. Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up.

    PubMed Central

    Bontenbal, M.; Foekens, J. A.; Lamberts, S. W.; de Jong, F. H.; van Putten, W. L.; Braun, H. J.; Burghouts, J. T.; van der Linden, G. H.; Klijn, J. G.

    1998-01-01

    Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase III trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy. PMID:9459155

  19. Using an emissive uridine analogue for assembling fluorescent HIV-1 TAR constructs

    PubMed Central

    Srivatsan, Seergazhi G.; Tor, Yitzhak

    2007-01-01

    Emissive nucleoside analogues that are sensitive to their microenvironment can serve as probes for exploring RNA folding and recognition. We have previously described the synthesis of an environmentally sensitive furan-containing uridine and its triphosphate, and have demonstrated that T7 RNA polymerase recognizes this modified ribonucleoside triphosphate as a substrate in in vitro transcription reactions. Here we report the enzymatic preparation of fluorescently tagged HIV-1 TAR constructs and study their interactions with a Tat peptide. Two extreme labeling protocols are examined, where either all native uridine residues are replaced with the corresponding modified fluorescent analogue, or only key residues are site-specifically modified. For the HIV-1 Tat–TAR system, labeling all native uridine residues resulted in relatively small changes in emission upon increasing concentrations of the Tat peptide. In contrast, when the two bulge U residues were site-specifically labeled, a reasonable fluorescence response was observed upon Tat titration. The scope and limitations of such fluorescently tagged RNA systems are discussed. PMID:18431440

  20. Site Study Plan for background environmental radioactivity, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-06-01

    The Background Environmental Radioactivity Site Study Plan describes a field program consisting of an initial radiological survey and a radiological sampling program. The field program includes measurement of direct radiation and collection and analysis of background radioactivity samples of air, precipitation, soil, water, milk, pasture grass, food crops, meat, poultry, game, and eggs. The plan describes for each study: the need for the study, the study design, data management and use, schedule of proposed activities, and quality assurance requirements. These studies will provide data needed to satisfy requirements contained in, or derived from, the Salt Repository Project (SRP) Requirements Document. 50 refs., 11 figs., 7 tabs.

  1. Expansion of structure-activity studies of piperidine analogues of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12935) compounds by altering substitutions in the N-benzyl moiety and behavioral pharmacology of selected molecules.

    PubMed

    Dutta, Aloke K; Davis, Matthew C; Fei, Xiang-Shu; Beardsley, Patrick M; Cook, Charles D; Reith, Maarten E A

    2002-01-31

    A series of substituted N-benzyl analogues of the dopamine transporter (DAT) specific compound, 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine were synthesized and biologically characterized. Different 4'-alkyl, 4'-alkenyl, and 4'-alkynyl substituents were introduced in the phenyl ring of the benzyl moiety along with the replacement of the same phenyl ring by the isomeric alpha- and beta-naphthyl groups. Different polar substitutions at the 3'- and 4'-position were also introduced. Novel compounds were tested for their binding affinity at the dopamine, serotonin, and norepinephrine transporter systems in the brain by competing for [(3)H]WIN 35 428, [(3)H]citalopram, and [(3)H]nisoxetine, respectively. Selected compounds were also evaluated for their activity in inhibiting the uptake of [(3)H]dopamine. Binding results demonstrated that alkenyl and alkynyl substitutions at the 4'-position produced potent compounds in which compound 6 with a vinyl substitution was the most potent. In vivo evaluation of three selected compounds indicated that despite their high potency at the DAT, these compounds stimulated locomotor activity (LMA) less than cocaine when tested across similar dose ranges. In a drug discrimination study procedure, none of these three compounds generalized from cocaine in mice trained to discriminate 10 mg/kg cocaine from vehicle. In a 4 h time course LMA experiment, one of our previous lead piperidine derivatives (1a) showed considerable prolonged action. Thus, in this report, we describe a structure-activity relationship study of novel piperidine analogues assessed by both in vitro transporter assays and in vivo behavioral activity measurements. PMID:11806716

  2. New rubrolide analogues as inhibitors of photosynthesis light reactions.

    PubMed

    Varejão, Jodieh O S; Barbosa, Luiz C A; Ramos, Gabriela Álvarez; Varejão, Eduardo V V; King-Díaz, Beatriz; Lotina-Hennsen, Blas

    2015-04-01

    Natural products called rubrolides have been investigated as a model for the development of new herbicides that act on the photosynthesis apparatus. This study comprises a comprehensive analysis of the photosynthesis inhibitory ability of 27 new structurally diverse rubrolide analogues. In general, the results revealed that the compounds exhibited efficient inhibition of the photosynthetic process, but in some cases low water solubility may be a limiting factor. To elucidate their mode of action, the effects of the compounds on PSII and PSI, as well as their partial reaction on chloroplasts and the chlorophyll a fluorescence transients were measured. Our results showed that some of the most active rubrolide analogues act as a Hill reaction inhibitors at the QB level by interacting with the D1 protein at the reducing side of PSII. All of the active analogues follow Tice's rule of 5, which indicates that these compounds present physicochemical properties suitable for herbicides. PMID:25748644

  3. Design of novel CSA analogues as potential safeners and fungicides.

    PubMed

    Zheng, Yang; Liu, Bin; Gou, Zhaopin; Li, Yao; Zhang, Xiao; Wang, Yanqing; Yu, Shujing; Li, Yonghong; Sun, Dequn

    2015-02-15

    Study of safeners has been seldom reported in literature. In this work, a series of novel acylsulfamoylbenzamide analogues was designed and synthesized with newly developed safener cyprosulfamide (CSA) as the leading compound. The activity assay against the herbicide thiencarbazone-methyl (TCM) on maize revealed that fifteen compounds showed better protective effect than CSA on the fresh weight of aerial parts, twelve compounds exhibited better activity on the dry weight of aerial parts. Remarkably, two compounds (6Ih, 7II) had protective effect on the four aspects of TCM treated maize. Further antifungal assay showed their excellent activity against Physollospora piricola. The structure-activity relationships of CSA analogues as safeners and fungicides were discussed and it might be valuable for further molecular modification of new CSA analogues. PMID:25582601

  4. Synthesis and Biological Evaluation of Carbocyclic Analogues of Pachastrissamine

    PubMed Central

    Kwon, Yongseok; Song, Jayoung; Bae, Hoon; Kim, Woo-Jung; Lee, Joo-Youn; Han, Geun-Hee; Lee, Sang Kook; Kim, Sanghee

    2015-01-01

    A series of carbocyclic analogues of naturally-occurring marine sphingolipid pachastrissamine were prepared and biologically evaluated. The analogues were efficiently synthesized via a tandem enyne/diene-ene metathesis reaction as a key step. We found that the analogue 4b exhibited comparable cytotoxicity and more potent inhibitory activity against sphingosine kinases, compared to pachastrissamine. Molecular modeling studies were conducted to provide more detailed insight into the binding mode of 4b in sphingosine kinase. In our docking model, pachastrissamine and 4b were able to effectively bind to the binding pocket of sphingosine kinase 1 as co-crystalized sphingosine. However, 4b showed a hydrophobic interaction with Phe192, which suggests that it contributes to its increased inhibitory activity against sphingosine kinase 1. PMID:25654428

  5. Synthesis and antifungal activity of novel streptochlorin analogues.

    PubMed

    Zhang, Ming-Zhi; Chen, Qiong; Xie, Cai-Hong; Mulholland, Nick; Turner, Sarah; Irwin, Dianne; Gu, Yu-Cheng; Yang, Guang-Fu; Clough, John

    2015-03-01

    Streptochlorin, first isolated as a new antibiotic in 1988 from the lipophilic extracts of the mycelium of a Streptomyces sp, is an indole natural products with a variety of biological activities. Based on the methods developed for the synthesis of pimprinine in our laboratory, we have synthesized a series of indole-modified streptochlorin analogues and measured their activities against seven phytopathogenic fungi. Some of the analogues displayed good activity in the primary assays, and the seven compounds 10b, 10c, 11e, 13e, 21, 22c and 22e (shown in Figure 1) were identified as the most promising candidates for further study. Structural optimization is still ongoing with the aim of discovering synthetic analogues with improved antifungal activity. PMID:25633493

  6. PAC Analogues of Perceptron and Winnow via Boosting the Margin Rocco A. Servedio \\Lambda

    E-print Network

    Servedio, Rocco

    PAC Analogues of Perceptron and Winnow via Boosting the Margin Rocco A. Servedio \\Lambda Division of known online algorithms such as Perceptron and Winnow, thus suggesting that these well­studied online, by taking p = 2 and p = 1 we obtain natural boosting­ based PAC analogues of Perceptron and Winnow

  7. PAC Analogues of Perceptron and Winnow via Boosting the Margin Rocco A. Servedio

    E-print Network

    Servedio, Rocco

    PAC Analogues of Perceptron and Winnow via Boosting the Margin Rocco A. Servedio Division of known online algorithms such as Perceptron and Winnow, thus suggesting that these well-studied online, by taking ¡£¢¥¤ and ¡£¢¥¦ we obtain natural boosting- based PAC analogues of Perceptron and Winnow

  8. Making Connections in Math: Activating a Prior Knowledge Analogue Matters for Learning

    ERIC Educational Resources Information Center

    Sidney, Pooja G.; Alibali, Martha W.

    2015-01-01

    This study investigated analogical transfer of conceptual structure from a prior-knowledge domain to support learning in a new domain of mathematics: division by fractions. Before a procedural lesson on division by fractions, fifth and sixth graders practiced with a surface analogue (other operations on fractions) or a structural analogue (whole…

  9. Long-term effects of CO2 on the mechanical behaviour of faults - a study of samples from a natural CO2 analogue (Entrada Sandstone, Utah, USA)

    NASA Astrophysics Data System (ADS)

    Hangx, S. J. T.; Bakker, E.; Spiers, C. J.

    2012-04-01

    In an attempt to reduce CO2 emissions, CO2 capture and storage in depleted oil and gas reservoirs is seen as one of the most important mitigation strategies. However, in order to achieve safe storage on geological timescales, it is key to maintain integrity of the caprock and any faults penetrating the seal. One of the largest uncertainties lies in the prediction of the effects of fluid-rock interaction on the mechanical integrity and sealing capacity of the reservoir-seal system in the very long term, i.e. on timescales of the order of 103 or 104 years. As chemical interactions in the rock/CO2/brine system are slow, their long-term effects on rock composition, microstructure, mechanical properties and transport properties cannot be properly reproduced in laboratory experiments. One way of addressing this issue is to conduct experiments on reservoir, caprock and fault rock samples taken from natural CO2 reservoir-seal systems, which can serve as natural analogues for CO2 storage fields. The transport and mechanical properties of these rock samples, which have reacted with CO2 over geological timescales, can then be compared with data obtained for laterally equivalent materials that are unaffected by CO2. The observed changes in rock properties can subsequently be used as input for numerical models aimed at assessing the long-term effects of CO2 on reservoir compaction, caprock damage, fault reactivation and fault permeability. We assessed the mechanical behaviour and transport properties of fault rocks. To this end, we performed triaxial direct shear experiments at room temperature under nominally dry conditions, at normal stresses up to 90 MPa and shear velocities of 0.22 -10.9 ?m/s. Simulated fault rocks were prepared by crushing material obtained from surface outcrops of the Entrada Sandstone, one of the CO2-bearing formations from an analogue field under the Colorado Plateau, Utah, USA. Three types of starting material were obtained: 1) red-coloured samples consisting mainly of quartz and feldspar, some minor clay minerals and hematite/goethite grain coatings, 2) yellow-coloured, (so-called) bleached samples additionally containing various amounts of kaolinite, calcite and dolomite, and 3) heavily cemented samples from the surface outcrop of the fault core of the Little Grand Wash Fault, containing a high percentage of carbonates (> 40 wt%). Previous work demonstrates that the bleached samples and the material from the fault were altered as a result of interaction with CO2-rich fluids. Over the experimental range investigated, we measured friction coefficients of 0.55-0.85 for unbleached material and 0.55-0.80 for bleached material, while the fault core material showed higher friction coefficients (0.60-0.95), all showing a minor decrease with decreasing shear velocity and normal stress. Almost all samples showed velocity-strengthening slip behaviour. Overall, the frictional behaviour of Entrada Sandstone does not seem to be strongly influenced by CO2/brine/rock interactions.

  10. Correlations Between Electrically Quantified Pain Degree, Subjectively Assessed Visual Analogue Scale, and the McGill Pain Questionnaire: A Pilot Study

    PubMed Central

    Kim, Junho; Lee, Kyung Soo; Kong, Sang Won; Kim, Taikon; Kim, Mi Jung; Park, Si-Bog

    2014-01-01

    Objective To evaluate the clinical utility of the electrically calculated quantitative pain degree (QPD) and to correlate it with subjective assessments of pain degree including a visual analogue scale (VAS) and the McGill Pain Questionnaire (MPQ). Methods We recruited 25 patients with low back pain. Of them, 21 patients suffered from low back pain for more than 3 months. The QPD was calculated using the PainVision (PV, PS-2100; Nipro Co., Osaka, Japan). We applied electrodes to the medial forearm of the subjects and the electrical stimulus was amplified sequentially. Minimum perceived current (MPC) and pain equivalent current (PEC) were defined as minimum electrical stimulation that could be sensed by the subject and electrical stimulation that could trigger actual pain itself. To eliminate individual differences, we defined QPD as the following: QPD=PEC-MPC/MPC. We scored pre-treatment QPD three times at admission and post-treatment QPD once at discharge. The VAS, MPQ, and QPD were evaluated and correlations between the scales were analyzed. Results Result showed significant test-retest reliability (ICC=0.967, p<0.001) and the correlation between QDP and MPQ was significant (at admission SRCC=0.619 and p=0.001; at discharge SRCC=0.628, p=0.001). However, the correlation between QPD and VAS was not significant (at admission SRCC=0.240, p=0.248; at discharge SRCC=0.289, p=0.161). Conclusion Numerical values measured with PV showed consistent results with repeated calculations. Electrically measured QPD showed an excellent correlation with MPQ but not with VAS. These results demonstrate that PV is a significantly reliable device for quantifying the intensity of low back pain. PMID:25379496

  11. Bioremediation demonstration on Kwajalein Island: Site characterization and on-site biotreatability studies

    Microsoft Academic Search

    R. L. Siegrist; N. E. Korte; D. A. Pickering; T. J. Phelps

    1991-01-01

    An environmental study was conducted during February 1991 on Kwajalein Island, a US Army Kwajalein Atoll (USAKA) Base in the Republic of the Marshall Islands (RMI). This study was undertaken for the US Department of Energy (DOE) Hazardous Waste Remedial Actions Program (HAZWRAP) acting in behalf of USAKA. The purpose of the study was to determine if selected locations for

  12. Site study plan for EDBH (Engineering Design Boreholes) seismic surveys, Deaf Smith County site, Texas: Revision 1

    SciTech Connect

    Hume, H.

    1987-12-01

    This site study plan describes seismic reflection surveys to run north-south and east-west across the Deaf Smith County site, and intersecting near the Engineering Design Boreholes (EDBH). Both conventional and shallow high-resolution surveys will be run. The field program has been designed to acquire subsurface geologic and stratigraphic data to address information/data needs resulting from Federal and State regulations and Repository program requirements. The data acquired by the conventional surveys will be common-depth- point, seismic reflection data optimized for reflection events that indicate geologic structure near the repository horizon. The data will also resolve the basement structure and shallow reflection events up to about the top of the evaporite sequence. Field acquisition includes a testing phase to check/select parameters and a production phase. The field data will be subjected immediately to conventional data processing and interpretation to determine if there are any anamolous structural for stratigraphic conditions that could affect the choice of the EDBH sites. After the EDBH's have been drilled and logged, including vertical seismic profiling, the data will be reprocessed and reinterpreted for detailed structural and stratigraphic information to guide shaft development. The shallow high-resulition seismic reflection lines will be run along the same alignments, but the lines will be shorter and limited to immediate vicinity of the EDBH sites. These lines are planned to detect faults or thick channel sands that may be present at the EDBH sites. 23 refs. , 7 figs., 5 tabs.

  13. Leonhard Euler and a q-analogue of the logarithm

    E-print Network

    Koelink, Erik

    2007-01-01

    We study a q-logarithm which was introduced by Euler and give some of its properties. This q-logarithm did not get much attention in the recent literature. We derive basic properties, some of which were already given by Euler in a 1751-paper and 1734-letter to Daniel Bernoulli. The corresponding q-analogue of the dilogarithm is introduced. The relation to the values at 1 and 2 of a q-analogue of the zeta function is given. We briefly describe some other q-logarithms that have appeared in the recent literature.

  14. Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors

    PubMed Central

    Florence, Gordon J.; Fraser, Andrew L.; Gould, Eoin R.; King, Elizabeth F.; Menzies, Stefanie K.; Morris, Joanne C.; Tulloch, Lindsay B.; Smith, Terry K.

    2015-01-01

    A series of novel bis-tetrahydropyran 1,4-triazole analogues based on the acetogenin framework display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness. A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure activity relationship studies. PMID:25145275

  15. Martian Habitability Studies in Two Field Earth Analogues: the Permafrost in the Imuruk Lake Basaltic Field (alaska) and the Atacama Desert

    NASA Astrophysics Data System (ADS)

    Gómez-Gómez, Felipe; Rodriguez-Manfredi, Jose-Antonio; Perez, Lidia; Prieto-Ballesteros, Olga; Amils, Ricardo; Gomez-Elvira, Javier

    We are developing a Universal Habitability Index for life prospection studies in space missions. Authors will present in this abstract the results of the application of the habitability index in two field case studies: Alaskan permafrost and Atacama Desert. We are using extreme envi-ronments as test facilities from an Astrobiological perspective, in order to reach three main objectives: 1) Define preservation patterns of biosignatures in extreme environments (cold, low water stress, high radiation. . . ) that may be used in future space exploration missions; 2) develop new instrumentation for detecting life in situ or remotely, and for new instrumenta-tion for detection and mapping of extreme niches where life (or biochemical tracers of past life) may be preserved and 3) develop an Universal Habitability Index for space astrobiolog-ical mission application (Mars or Europa life prospection). These aims will be achieved by selected site characterization using geophysical sounding and drilling, atmospheric characteri-zation by meteorological analysis, soil water and temperature profile analysis and, finally, by sampling different levels of the rock cores and analyzing their mineralogy, geochemistry and microbiology in laboratory. First case: studying the permafrost in the Imuruk lake volcanic field area (Alaska): In order to map the permafrost underground, electric tomography sounding was performed. Resulting tomographic data indicate that the permafrost of the studied area is at a mean depth of 0.50 meter from the surface, sometimes even shallower. Drilling points were selected depending on the permafrost depth known from the tomographic data analysis. Three perforations were done all along the hill. Samples were collected at several depths in the three holes for mineralogical, geochemical and biological analysis. They were in situ fixed with formaldehyde in order to be maintained till laboratory analysis was developed. Several growth fresh media were inoculated with samples from different depths in the field for microor-ganism's enrichment. First results report enrichment in several inoculated media including some specific for heterotrophic aerobic bacteria, anaerobic chemolithotrophic and methanogen bacteria. Two different molecular methods are being used for microbial determination: "In situ" hybridizitation (was used for microbial determination and cell counting also) and 16S rRNA genes amplification, cloning and sequencing. First results in cell counting determined a population density gradient vs. depth. Second case: studying Atacama Desert: Habitability studies in the Atacama Desert were developed by the selection of a 36 square meters area where an atmospheric station was installed. The following parameters were measured: UV radiation, atmosphere temperature, ground temperature at three different depths, wind direction. Sam-ples at the pre-selected depths were taken in order to develop microbiological studies in the laboratory. Interesting results that will be presented at the COSPAR session were obtained with decreasing levels of life presence along the core profile. Acknowledgments: Centro de Astrobiologia INTA/CSIC (Spain) supported the expedition to Imuruk Lake. The Atacama expedition was supported with the Grant ESP 2004-05008 "De-teccién de biomoléculas en exploracién planetaria" from the Spanish Government. Laboratory analysis was supported with the Grant ESP-2006/06640 "Desarrollo de Tecnologé para la ?a Identificacién de Vida de forma Automética (DTIVA)"

  16. Charged analogue of Finch-Skea stars

    E-print Network

    S. Hansraj; S. D. Maharaj

    2006-05-11

    We present solutions to the Einstein-Maxwell system of equations in spherically symmetric gravitational fields for static interior spacetimes with a specified form of the electric field intensity. The condition of pressure isotropy yields three category of solutions. The first category is expressible in terms of elementary functions and does not have an uncharged limit. The second category is given in terms of Bessel functions of half-integer order. These charged solutions satisfy a barotropic equation of state and contain Finch-Skea uncharged stars. The third category is obtained in terms of modified Bessel functions of half-integer order and does not have an uncharged limit. The physical features of the charged analogue of the Finch-Skea stars are studied in detail. In particular the condition of causality is satisfied and the speed of sound does not exceed the speed of light. The physical analysis indicates that this analogue is a realistic model for static charged relativistic perfect fluid spheres.

  17. A Hierarchical Modeling Approach to Data Analysis and Study Design in a Multi-Site Experimental fMRI Study

    ERIC Educational Resources Information Center

    Zhou, Bo; Konstorum, Anna; Duong, Thao; Tieu, Kinh H.; Wells, William M.; Brown, Gregory G.; Stern, Hal S.; Shahbaba, Babak

    2013-01-01

    We propose a hierarchical Bayesian model for analyzing multi-site experimental fMRI studies. Our method takes the hierarchical structure of the data (subjects are nested within sites, and there are multiple observations per subject) into account and allows for modeling between-site variation. Using posterior predictive model checking and model…

  18. Wildlife studies on the Hanford Site: 1993 Highlights report

    SciTech Connect

    Cadwell, L.L. [ed.

    1994-04-01

    The Pacific Northwest Laboratory (PNL) Wildlife Resources Monitoring Project was initiated by DOE to track the status of wildlife populations to determine whether Hanford operations affected them. The project continues to conduct a census of wildlife populations that are highly visible, economically or aesthetically important, and rare or otherwise considered sensitive. Examples of long-term data collected and maintained through the Wildlife Resources Monitoring Project include annual goose nesting surveys conducted on islands in the Hanford Reach, wintering bald eagle surveys, and fall Chinook salmon redd (nest) surveys. The report highlights activities related to salmon and mollusks on the Hanford Reach of the Columbia River; describes efforts to map vegetation on the Site and efforts to survey species of concern; provides descriptions of shrub-steppe bird surveys, including bald eagles, Canada geese, and hawks; outlines efforts to monitor mule deer and elk populations on the Site; and describes development of a biological database management system.

  19. Studies of Current Circulation at Ocean Waste Disposal Sites

    NASA Technical Reports Server (NTRS)

    Klemas, V. (principal investigator); Davis, G.; Henry, R.

    1976-01-01

    The author has identified the following significant results. Acid waste plume was observed in LANDSAT imagery fourteen times ranging from during dump up to 54 hours after dump. Circulation processes at the waste disposal site are highly storm-dominated, with the majority of the water transport occurring during strong northeasterlies. There is a mean flow to the south along shore. This appears to be due to the fact that northeasterly winds produce stronger currents than those driven by southeasterly winds and by the thermohaline circulation. During the warm months (May through October), the ocean at the dump site stratifies with a distinct thermocline observed during all summer cruising at depths ranging from 10 to 21 m. During stratified conditions, the near-bottom currents were small. Surface currents responded to wind conditions resulting in rapid movement of surface drogues on windy days. Mid-depth drogues showed an intermediate behavior, moving more rapidly as wind velocities increased.

  20. UV disinfection pilot plant study at the Savannah River Site

    SciTech Connect

    Huffines, R.L.; Beavers, B.A.

    1993-01-01

    An ultraviolet light disinfection system pilot plant was operated at the Savannah River Site Central Shops sanitary wastewater treatment package plant July 14, 1992 through August 13, 1992. The purpose was to determine the effectiveness of ultraviolet light disinfection on the effluent from the small package-type wastewater treatment plants currently used on-site. This pilot plant consisted of a rack of UV lights suspended in a stainless steel channel through which a sidestream of effluent from the treatment plant clarifier was pumped. Fecal coliform analyses were performed on the influent to and effluent from the pilot unit to verify the disinfection process. UV disinfection was highly effective in reducing fecal coliform colonies within NPDES permit limitations even under process upset conditions. The average fecal coliform reduction exceeded 99.7% using ultraviolet light disinfection under normal operating conditions at the package treatment plants.

  1. UV disinfection pilot plant study at the Savannah River Site

    SciTech Connect

    Huffines, R.L.; Beavers, B.A.

    1993-05-01

    An ultraviolet light disinfection system pilot plant was operated at the Savannah River Site Central Shops sanitary wastewater treatment package plant July 14, 1992 through August 13, 1992. The purpose was to determine the effectiveness of ultraviolet light disinfection on the effluent from the small package-type wastewater treatment plants currently used on-site. This pilot plant consisted of a rack of UV lights suspended in a stainless steel channel through which a sidestream of effluent from the treatment plant clarifier was pumped. Fecal coliform analyses were performed on the influent to and effluent from the pilot unit to verify the disinfection process. UV disinfection was highly effective in reducing fecal coliform colonies within NPDES permit limitations even under process upset conditions. The average fecal coliform reduction exceeded 99.7% using ultraviolet light disinfection under normal operating conditions at the package treatment plants.

  2. Application of studies on the overboard placement of dredged sediments to the management of disposal sites

    USGS Publications Warehouse

    Panageotou, William; Halka, Jeffrey

    1994-01-01

    From the mid 1960's until 1991, dredging and disposal occurred in the northern Chesapeake Bay without guidelines to maximize the capacity and to minimize the spread of the deposits beyond the disposal sites, particularly toward the navigation channel. Planning for future dredging projects is dependant upon the remaining site capacity and the behavior of the disposed sediment. Recent studies have shown that the fate of the deposited sediments is determined primarily by the water depth and bathymetry in the vicinity of the disposal site, and the method of dredging and disposal utilized. Currently used open-water disposal sites in the northern Chesapeake Bay are reaching their maximum capacity. This makes the application of the information from these studies critical, both for the optimal use of current sites and for the evaluation of new sites. Management scenarios utilizing these studies are applied to a disposal site in the northern Chesapeake Bay.

  3. Site study plan for intermediate hydrology clusters tests wells Deaf Smith County Site, Texas

    SciTech Connect

    Not Available

    1988-01-01

    To characterize the geologic, geochemical, and hydrologic characteristics of intermediate-depth formations at the proposed Deaf Smith County, Texas, repository site, wells called Intermediate Hydrology clusters will test the Dewey Lake, Alibates, Salado, Yates, Upper and Lower Seven Rivers, and Queen Grayburg Formations. Sixteen wells will be installed at six locations. One location will have four wills, two locations will have three wells, and three locations will have two wells for a total of 16 wells. Testing of the formations is to proceed from the bottom up, with 2-day pumping tests at the less permeable formations. Tracer tests and tests for verticall hydraulic properties will be designed and performed after other hydrologic tests are completed. After testing, selected wells are to be completed as single or possibly dual monitoring wells to observe water-level trends. To develop a hydrogeologic testing plan, the response of each formation to potential testing procedures was evaluated using design values and an assumend range for hydraulic parameters. These evaluations indicate that hydraulic properties of a sandy zone of the Dockum, the lower Sever Rivers, and possibly the Alibates and Queen/Grayburg can be determined by pumping tests. Standard of shut-in slug tests must be conducted in the remaining formations. Tests of very long duration would be required to determine the verticla properties of less permeable formations. Tracer tests would also require weeks or months. 61 figs., 34 refs., 4 tabs.

  4. Farnesyl diphosphate analogues with aryl moieties are efficient alternate substrates for protein farnesyltransferase.

    PubMed

    Subramanian, Thangaiah; Pais, June E; Liu, Suxia; Troutman, Jerry M; Suzuki, Yuta; Leela Subramanian, Karunai; Fierke, Carol A; Andres, Douglas A; Spielmann, H Peter

    2012-10-16

    Farnesylation is an important post-translational modification essential for the proper localization and function of many proteins. Transfer of the farnesyl group from farnesyl diphosphate (FPP) to proteins is catalyzed by protein farnesyltransferase (FTase). We employed a library of FPP analogues with a range of aryl groups substituting for individual isoprene moieties to examine some of the structural and electronic properties of the transfer of an analogue to the peptide catalyzed by FTase. Analysis of steady-state kinetics for modification of peptide substrates revealed that the multiple-turnover activity depends on the analogue structure. Analogues in which the first isoprene is replaced with a benzyl group and an analogue in which each isoprene is replaced with an aryl group are good substrates. In sharp contrast with the steady-state reaction, the single-turnover rate constant for dansyl-GCVLS alkylation was found to be the same for all analogues, despite the increased chemical reactivity of the benzyl analogues and the increased steric bulk of other analogues. However, the single-turnover rate constant for alkylation does depend on the Ca(1)a(2)X peptide sequence. These results suggest that the isoprenoid transition-state conformation is preferred over the inactive E·FPP·Ca(1)a(2)X ternary complex conformation. Furthermore, these data suggest that the farnesyl binding site in the exit groove may be significantly more selective for the farnesyl diphosphate substrate than the active site binding pocket and therefore might be a useful site for the design of novel inhibitors. PMID:22989235

  5. Compressed-air energy storage: Preliminary design and site-development program in an aquifer. Volume 3: Site-selection study, part 2

    NASA Astrophysics Data System (ADS)

    1982-09-01

    The behavior and suitability of an aquifer based compressed air energy storage (CAES) facility was investigated. Aspects of the site selection were studied. Aquifer sites in the Illinois and Indiana portions of the Illinois Basin were identified and ranked. A site was selected from the four top ranked sites and was utilized as the host site for the preliminary design of a compressed air energy storage facility.

  6. Cross-site studies "by design:" Experiments and observations that provide new insights

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cross-site comparisons presented in the previous chapters are all conducted after the individual studies are completed. The differences in experimental design in individual studies in a posteriori cross-site studies limit the scope of questions that can be addressed, and the powerfulness and co...

  7. Template polymerization of nucleotide analogues

    NASA Technical Reports Server (NTRS)

    Orgel, L. E.

    1991-01-01

    Recent work on the template-directed reactions of the natural D-nucleotides has made it clear that l-nucleotides and nucleotide-like derivatives of other sugars would strongly inhibit the formation of long oligonucleotides. Consequently, attention is focusing on molecules simpler than nucleotides that might have acted as monomers of an information transfer system. We have begun a general exploration of the template directed reactions of diverse peptide analogues. I will present work by Dr. Taifeng Wu on oxidative oligomerization of phosphorothioates and of Dr. Mary Tohidi on the cyclic polymerization of nucleoside and related cyclic pyrophosphates.

  8. Space Analogue Environments: Are the Populations Comparable?

    NASA Astrophysics Data System (ADS)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that were assessed. Most of the polar expeditionners had the combination of high scores on positive expressivity and high achievement motivation- a profile which has sometimes been characterized as "the right stuff" for coping in confined and isolated settings. Conclusion: The findings from this study suggest that populations in various space-analogue environments differ in personality traits which might impact on the comparability of psychological findings obtained in different setting. Gender differences in personality also represent a potential source of variance that need to be addressed when generalizing results across space analogue environments.

  9. Biodegradation of bisphenol A and its halogenated analogues by Cunninghamella elegans ATCC36112.

    PubMed

    Keum, Young Soo; Lee, Hye Ri; Park, Hee Won; Kim, Jeong-Han

    2010-11-01

    Bisphenol A and its halogenated analogues are commonly used industrial chemicals with strong toxicological effects over many organisms. In this study, metabolic fate of bisphenol A and its halogenated analogues were evaluated with Cunninghamella elegans ATCC36112. Bisphenol A and related analogues were rapidly transformed into several metabolites by C. elegans within 2-4 days. Detailed analysis of metabolites reveals that both phase I and II metabolism occurred in C. elegans. Cytochrome P450-dependent hydroxylation was observed in BPA. However, major reaction with bisphenol A and analogues with 1-2 halogen atoms were the formation of glucose-conjugate, not being inhibited by cytochrome P450 inhibitor. Overall metabolic rates decreased with increasing number of substitution at 2- and 6-position of BPA structures, which may be consequences of limited bioavailability or steric hindrance to conjugate-forming reaction. Information from the current study will provide detailed insights over the fungal metabolism of BPA and analogues. PMID:20455075

  10. New photochemically stable riboflavin analogue—3-Methyl-riboflavin tetraacetate

    Microsoft Academic Search

    Ma?gorzata Insi?ska-Rak; Ewa Sikorska; Jose L. Bourdelande; Igor V. Khmelinskii; Wies?aw Pruka?a; Krzysztof Dobek; Jerzy Karolczak; Isabel F. Machado; Luis F. V. Ferreira; Ewa Dulewicz; Anna Komasa; David R. Worrall; Maciej Kubicki; Marek Sikorski

    2007-01-01

    Spectroscopic and photophysical properties of a flavin analogue – 3-methyl-riboflavin tetraacetate – were studied in methanol, ethanol, water and acetonitrile. We compared experimental spectroscopic data with the results of theoretical predictions, obtained using the TD-DFT method. Based on these calculations, we assigned (?,?*) symmetry to both the lowest excited singlet and triplet states. We found the title compound to be

  11. Synthesis of Oxadiazole-2-oxide Analogues as Potential Antischistosomal Agents

    PubMed Central

    Rai, Ganesha; Thomas, Craig J.; Leister, William; Maloney, David J.

    2009-01-01

    The synthesis of several 1,2,5-oxadiazole-2-oxide (Furoxan) analogues is described herein. These compounds were prepared in an effort to probe the SAR around the phenyl substituent and oxadiazole core for our studies toward thioredoxin-glutathione reductase (TGR) inhibition and anti-schistosomal activity. PMID:19802367

  12. Groundwater hydrology study of the Ames Chemical Disposal Site

    SciTech Connect

    Stickel, T.

    1996-05-09

    The Ames Laboratory Chemical Disposal Site is located in northwestern Ames, Iowa west of Squaw Creek. From 1957 to 1966, Ames Laboratory conducted research to develop processes to separate uranium and thorium from nuclear power fuel and to separate yttrium from neutron shielding sources. The wastes from these processes, which contained both hazardous and radiological components, were placed into nine burial pits. Metal drums, plywood boxes, and steel pails were used to store the wastes. Uranium was also burned on the ground surface of the site. Monitoring wells were placed around the waste burial pits. Groundwater testing in 1993 revealed elevated levels of Uranium 234, Uranium 238, beta and alpha radiation. The north side of the burial pit had elevated levels of volatile organic compounds. Samples in the East Ravine showed no volatile organics; however, they did contain elevated levels of radionuclides. These analytical results seem to indicate that the groundwater from the burial pit is flowing down hill and causing contamination in the East Ravine. Although there are many avenues for the contamination to spread, the focus of this project is to understand the hydrogeology of the East Ravine and to determine the path of groundwater flow down the East Ravine. The groundwater flow data along with other existing information will be used to assess the threat of chemical migration down the East Ravine and eventually off-site. The primary objectives of the project were as follows: define the geology of the East Ravine; conduct slug tests to determine the hydraulic conductivity of both oxidized and unoxidized till; develop a three-dimensional mathematical model using ModIME and MODFLOW to simulate groundwater flow in the East Ravine.

  13. Residual herbicide study on selected Hanford Site roadsides

    SciTech Connect

    Smith, J.L.; Kemp, C.J.; Sackschewsky, M.R.

    1993-08-01

    Westinghouse Hanford Company routinely treats roadsides with herbicides to control undesirable plant growth. An experiment was conducted to test perennial grass germination in soils adjacent to roadways of the Hanford Site. The primary variable was the distance from the roadside. A simple germination test was executed in a controlled-environment chamber to determine the residual effects of these applications. As expected, the greatest herbicide activity was found directly adjacent to the roadway, approximately 0 to 20 ft (0 to 6.3 m) from the roadway.

  14. Prostacyclin receptor in the brain and central terminals of the primary sensory neurons: An autoradiographic study using a stable prostacyclin analogue [ 3H]iloprost

    Microsoft Academic Search

    K. Matsumura; Yu. Watanabe; H. Onoe; Y. Watanabe

    1995-01-01

    Presence and localization of the prostacyclin receptor in the rat brain and spinal cord were examined by in vitro autoradiography using [3H]iloprost, a highly specific and stable agonist for this receptor. Density of specific binding sites for iloprost was generally high in four regions of the lower brain stem, that is, the medial and commissural subnuclei of the nucleus tractus

  15. Complex between carboxypeptidase A and a hydrated ketomethylene substrate analogue.

    PubMed Central

    Shoham, G; Christianson, D W; Oren, D A

    1988-01-01

    The complex of carboxypeptidase A (CPA) with 5-amino-(N-t-butoxycarbonyl)-2-benzyl-4-oxo-6-phenylhexanoic acid (BBP), the ketomethylene substrate analogue of the peptide substrate N-(t-butoxycarbonyl)-L-phenylalanyl-L-phenylalanine, was studied by x-ray crystallographic methods. Interestingly, the enzyme specifically binds only one of four stereoisomers of BBP that were present in the buffer solution in which the CPA crystals were soaked. Furthermore, the species observed to bind to the enzyme is the hydrated form of the ketone. This is rather surprising since the hydrated form of BBP is expected to be present in aqueous solution at a concentration of less than 0.2%. Hence, the enzyme-inhibitor complex is most stable with a species resembling a structure along the reaction coordinate of a chemical reaction rather than a species resembling a reactant or a product. Important structural information regarding the catalytic conformations of active-site residues spanning the S'1-S2 subsites of the enzyme is provided from the results of these x-ray diffraction experiments. The structure of the CPA-hydrated BBP complex provides support for a promoted-water hydrolytic mechanism, although it is not certain whether the enzyme has actually participated in the hydration reaction at the ketone carbonyl of BBP. PMID:3422451

  16. Web Site Usability: A Case Study of Student Perceptions of Educational Web Sites

    ERIC Educational Resources Information Center

    Ballard, Joyce Kimberly

    2010-01-01

    The purpose of this research study was to understand the construct of usability from the perspective of 74 students enrolled in six online courses offered by one online and distance learning program at a large, public university in the Midwest. Six courses, designed and developed by two different groups, professional and nonprofessional…

  17. Analogues of diverse structure are unable to differentiate native melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores.

    PubMed Central

    Pickering, H.; Sword, S.; Vonhoff, S.; Jones, R.; Sugden, D.

    1996-01-01

    1. The pineal hormone melatonin exerts its biological effects through specific, high affinity G-protein coupled receptors. Recently, three melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) have been cloned. Neither the cloned subtypes, nor the native receptors have yet been compared in a detailed pharmacological analysis. 2. The present study examined the structure-activity relationships of a series of 21 melatonin analogues, by comparing their potency on the pigment aggregation response in Xenopus laevis melanophores with their affinity in radioligand binding competition studies in chicken retina and sheep pars tuberalis (PT), two tissues in which melatonin is known to mediate a biological response. 3. All but four of the analogues were full melatonin receptor agonists producing a concentration-related redistribution of pigment granules in cultured Xenopus melanophores. The remaining analogues produced little pigment aggregation at 10 microM. 4. Saturation studies with 2-[125I]-iodomelatonin identified a single binding site in the chicken retina and sheep PT membranes, with a KD of 36.6 +/- 2.8 and 37.3 +/- 4.3 pM, and a maximal number of binding sites (Bmax) of 16.6 +/- 0.5, and 40.1 +/- 1.7 fmol mg-1 protein, respectively. 5. Comparison of the potency/affinity of the analogues for the binding sites gave a highly significant correlation in each case, retina/melanophore, r = 0.97 (P < 0.001, n = 17), PT/melanophore, r = 0.97 (P < 0.001, n = 17) and PT/retina, r = 0.98 (P < 0.001, n = 21). 6. Despite their large range in affinity and structural diversity these melatonin agonists were unable to distinguish between melatonin receptors in the chicken retina, sheep pars tuberalis and Xenopus melanophores. Images Figure 1 PMID:8886424

  18. Analogue gravity in hyperbolic metamaterials

    E-print Network

    Igor I. Smolyaninov

    2013-09-09

    Sub-wavelength confinement of light in nonlinear hyperbolic metamaterials due to formation of spatial solitons has attracted much recent attention because of its seemingly counter-intuitive behavior. In order to achieve self-focusing in a hyperbolic wire medium, a nonlinear self-defocusing Kerr medium must be used as a dielectric host. Here we demonstrate that this behavior finds natural explanation in terms of analogue gravity. Wave equation describing propagation of extraordinary light inside hyperbolic metamaterials exhibits 2+1 dimensional Lorentz symmetry. The role of time in the corresponding effective 3D Minkowski spacetime is played by the spatial coordinate aligned with the optical axis of the metamaterial. Nonlinear optical Kerr effect bends this spacetime resulting in effective gravitational force between extraordinary photons. In order for the effective gravitational constant to be positive, negative self-defocusing Kerr medium must be used as a host. If gravitational self-interaction is strong enough, spatial soliton may collapse into a black hole analogue.

  19. Characterize and explore potential sites and prepare research and development plan (site investigation study). Final draft. Task 2. Milestone report

    SciTech Connect

    None

    1980-12-01

    A specific research and development plan to investigate the behavior and suitability of aquifers as compressed air energy storage (CAES) sites is presented. The proposed effort will evaluate present uncertainties in the performance of the underground energy storage subsystem and its impact on above ground plant design and cost. The project is planned to provide the utility industry with a quantitative basis for confidence that financial commitment to a demonstration plant and subsequent expansion is justified and poses acceptable risks. Activities in Phase II of a 5-phase overall CAES development program are reported. Information is included on the development of field testing specifications and schedules; selection of specific site for the conceptual design; development plan and schedule for the media site; development of analytical models of aquifer airflow; and well drilling requirements. As a result of these studies 14 sites in Illinois and Indiana were evaluated, 7 were ranked for suitability for CAES, and 4 were selected for possible use in the field testing program. Test procedures, the mathematical models and drilling requirments were developed. (LCL)

  20. Crystallographic studies on multiple conformational states of active-site loops in pyrrolysyl-tRNA synthetase.

    PubMed

    Yanagisawa, Tatsuo; Ishii, Ryohei; Fukunaga, Ryuya; Kobayashi, Takatsugu; Sakamoto, Kensaku; Yokoyama, Shigeyuki

    2008-05-01

    Pyrrolysine, a lysine derivative with a bulky pyrroline ring, is the "22nd" genetically encoded amino acid. In the present study, the carboxy-terminal catalytic fragment of Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS) was analyzed by X-ray crystallography and site-directed mutagenesis. The catalytic fragment ligated tRNA(Pyl) with pyrrolysine nearly as efficiently as the full-length PylRS. We determined the crystal structures of the PylRS catalytic fragment in the substrate-free, ATP analogue (AMPPNP)-bound, and AMPPNP/pyrrolysine-bound forms, and compared them with the previously-reported PylRS structures. The ordering loop and the motif-2 loop undergo conformational changes from the "open" states to the "closed" states upon AMPPNP binding. On the other hand, the beta 7-beta 8 hairpin exhibits multiple conformational states, the open, intermediate (beta 7-open/beta 8-open and beta 7-closed/beta 8-open), and closed states, which are not induced upon substrate binding. The PylRS structures with a docked tRNA suggest that the active-site pocket can accommodate the CCA terminus of tRNA when the motif-2 loop is in the closed state and the beta 7-beta 8 hairpin is in the open or intermediate state. The entrance of the active-site pocket is nearly closed in the closed state of the beta 7-beta 8 hairpin, which may protect the pyrrolysyladenylate intermediate in the absence of tRNA(Pyl). Moreover, a structure-based mutational analysis revealed that hydrophobic residues in the amino acid-binding tunnel are important for accommodating the pyrrolysine side chain and that Asn346 is essential for anchoring the side-chain carbonyl and alpha-amino groups of pyrrolysine. In addition, a docking model of PylRS with tRNA was constructed based on the aspartyl-tRNA synthetase/tRNA structure, and was confirmed by a mutational analysis. PMID:18387634

  1. Synthesis and evaluation of heterocyclic analogues of bromoxynil.

    PubMed

    Cutulle, Matthew A; Armel, Gregory R; Brosnan, James T; Best, Michael D; Kopsell, Dean A; Bruce, Barry D; Bostic, Heidi E; Layton, Donovan S

    2014-01-15

    One attractive strategy to discover more active and/or crop-selective herbicides is to make structural changes to currently registered compounds. This strategy is especially appealing for those compounds with limited herbicide resistance and whose chemistry is accompanied with transgenic tools to enable herbicide tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor registered for control of broadleaf weeds in several agronomic and specialty crops. Recently at the University of Tennessee-Knoxville several analogues of bromoxynil were synthesized including a previously synthesized pyridine (2,6-dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6-dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N-oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of bromoxynil were also evaluated for their herbicidal activity on soybean (Glycine max), cotton (Gossypium hirsutum), redroot pigweed (Amaranthus retroflexus), velvetleaf (Abutilon theophrasti), large crabgrass (Digitaria sanguinalis), and pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second study was conducted on a glyphosate-resistant weed (Amaranthus palmeri) with the compounds being applied at 0.56 kg ha(-1). Although all compounds were believed to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus retroflexus. However, application of the pyrimidine herbicide resulted in the least injury to all species tested. These variations in efficacy were investigated using molecular docking simulations, which indicate that the pyridine analogue may form a stronger hydrogen bond in the pocket of the D1 protein than the original bromoxynil. A pyridine analogue was able to control the glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine analogues of bromoxynil showed potential to have a different weed control spectrum compared to bromoxynil. A pyridine analogue of bromoxynil synthesized in this research controlled several weed species greater than bromoxynil itself, potentially due to enhanced binding within the PSII binding pocket. Future research should compare this analogue to bromoxynil using optimized formulations at higher application rates. PMID:24354444

  2. Natural analogues of nuclear waste glass corrosion.

    SciTech Connect

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  3. Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases*

    PubMed Central

    Zhang, Yong; Evans, Gary B.; Clinch, Keith; Crump, Douglas R.; Harris, Lawrence D.; Fröhlich, Richard F. G.; Tyler, Peter C.; Hazleton, Keith Z.; Cassera, María B.; Schramm, Vern L.

    2013-01-01

    The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nm. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5?-phosphate bound to OPRTs with Kd values near 40 nm. Analogues designed with a C5-pyrimidine carbon–carbon bond to ribocation mimics gave Kd values in the range of 80–500 nm. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5?-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

  4. Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.

    PubMed

    Zhang, Yong; Evans, Gary B; Clinch, Keith; Crump, Douglas R; Harris, Lawrence D; Fröhlich, Richard F G; Tyler, Peter C; Hazleton, Keith Z; Cassera, María B; Schramm, Vern L

    2013-11-29

    The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nM. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5'-phosphate bound to OPRTs with Kd values near 40 nM. Analogues designed with a C5-pyrimidine carbon-carbon bond to ribocation mimics gave Kd values in the range of 80-500 nM. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5'-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

  5. Case study of landfill reclamation at a Florida landfill site.

    PubMed

    Jain, Pradeep; Townsend, Timothy G; Johnson, Patrick

    2013-01-01

    A landfill reclamation project was considered to recover landfill airspace and soil, reduce future groundwater impacts by removing the waste buried in the unlined area, and optimize airspace use at the site. A phased approach was utilized to evaluate the technical and economic feasibility of the reclamation project; based on the results of these evaluations, approximately 6.8 ha of the unlined cells were reclaimed. Approximately 371,000 in-place cubic meters of waste was mined from 6.8 ha in this project. Approximately 230,600 cubic meters of net airspace was recovered due to beneficial use of the recovered final cover soil and reclaimed soil as intermediate and daily cover soil, respectively, for the current landfill operations. This paper presents the researchers' landfill reclamation project experience, including a summary of activities pertaining to reclamation operations, an estimation of reclamation rates achieved during the project, project costs and benefits, and estimated composition of the reclaimed materials. PMID:23089299

  6. Studies of Current Circulation at Ocean Waste Disposal Sites. [Delaware

    NASA Technical Reports Server (NTRS)

    Klemas, V. (principal investigator); Davis, G.; Henry, R.

    1975-01-01

    The author has identified the following significant results. Circulation processes at the acid waste disposal site are highly event-dominated, with the majority of the water transport occurring during strong northeasters. There is a mean flow to the south alongshore. This appears to be due to the fact that northeasterly winds produce stronger currents than those driven by southeasterly winds and by the thermohaline circulation. During the warm months, the ocean stratifies with warm water over cold water. A distinct thermocline was observed with expendable bathythermographs during all summer cruises at depths ranging from 10 to 21 meters. During stratified conditions, the near-bottom drogues showed very little movements. The duPont waste plume was observed in LANDSAT satellite imagery during dump up to 54 hours after dump.

  7. Docking and binding mode analysis of aryl diketoacids (ADK) at the active site of HCV RNA-dependent RNA polymerase

    Microsoft Academic Search

    J. Kim; Y. Chong

    2006-01-01

    The pharmacophore-guided docking study of aryl diketoacid (ADK) analogues revealed two distinctive hydrophobic binding sites (a pocket and a groove) around the UTP-binding site of hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp). Interestingly, the hydrophobic binding sites have appropriate shape and size to specifically substituted aromatic rings, which suggests the specific role of substituents on the aromatic ring in

  8. Lactam-stabilized helical analogues of the analgesic ?-conotoxin KIIIA

    PubMed Central

    Khoo, Keith K.; Wilson, Michael J.; Smith, Brian J.; Zhang, Min-Min; Gulyas, Joszef; Yoshikami, Doju; Rivier, Jean E.; Bulaj, Grzegorz; Norton, Raymond S.

    2011-01-01

    ?-Conotoxin KIIIA (?-KIIIA) blocks mammalian voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. Previous structure-activity studies of ?-KIIIA identified a helical pharmacophore for VGSC blockade. This suggested a route for designing truncated analogues of ?-KIIIA by incorporating the key residues into an ?-helical scaffold. As (i, i+4) lactam bridges constitute a proven approach for stabilizing ?-helices, we designed and synthesized six truncated analogues of ?-KIIIA containing single lactam bridges at various locations. The helicity of these lactam analogues was analysed by NMR spectroscopy, and their activities were tested against mammalian VGSC subtypes NaV1.1 through 1.7. Two of the analogues, Ac-cyclo9/13[Asp9,Lys13]KIIIA7–14 and Ac-cyclo9/13[Lys9,Asp13]KIIIA7–14, displayed µM activity against VGSC subtypes NaV1.2 and NaV1.6; importantly, the subtype selectivity profile for these peptides matched that of ?-KIIIA. Our study highlights structure-activity relationships within these helical mimetics and provides a basis for the design of additional truncated peptides as potential analgesics. PMID:21962108

  9. Base-modified Donor Analogues Reveal Novel Dynamic Features of a Glycosyltransferase*

    PubMed Central

    Jørgensen, René; Pesnot, Thomas; Lee, Ho Jun; Palcic, Monica M.; Wagner, Gerd K.

    2013-01-01

    Glycosyltransferases (GTs) are enzymes that are involved, as Nature's “glycosylation reagents,” in many fundamental biological processes including cell adhesion and blood group biosynthesis. Although of similar importance to that of other large enzyme families such as protein kinases and proteases, the undisputed potential of GTs for chemical biology and drug discovery has remained largely unrealized to date. This is due, at least in part, to a relative lack of GT inhibitors and tool compounds for structural, mechanistic, and cellular studies. In this study, we have used a novel class of GT donor analogues to obtain new structural and enzymological information for a representative blood group GT. These analogues interfere with the folding of an internal loop and the C terminus, which are essential for catalysis. Our experiments have led to the discovery of an entirely new active site folding mode for this enzyme family, which can be targeted in inhibitor development, similar to the DFG motif in protein kinases. Taken together, our results provide new insights into substrate binding, dynamics, and utilization in this important enzyme family, which can very likely be harnessed for the rational development of new GT inhibitors and probes. PMID:23836908

  10. Site selection study for Sandia National Laboratories/New Mexico as an alternative site for the National Ignition Facility

    SciTech Connect

    Miller, D.; Wheeler, T.; McClellan, Y.

    1996-03-01

    The Department of Energy (DOE) proposes to construct and operate the National Ignition Facility (NIF) in support of the Stockpile Stewardship and Management (SSM) Programmatic Environmental impact Statement (PEIS). The National Environmental Policy Act requires the DOE to look at alternative sites for the NIF. The SSM PEIS will evaluate four alternative locations for the NIF. This study documents the process and results of a site selection study for a preferred site for the NIF at SNL/NM. The NIF research objectives are to provide the world`s most powerful laser systems to be used in ignition of fusion fuel and energy gain to perform high energy density and radiation effects experiments in support of the DOE`s national security, energy, and basic science research mission. The most immediate application of the NIF will be to provide nuclear-weapon-related physics data, since many phenomena occurring on the laboratory scale are similar to those that occur in weapons. The NIF may also provide an important capability for weapons effects simulation. The NIF is designed to achieve propagating fusion bum and modest energy gain for development as a source of civilian energy.

  11. Site study plan for non-routine laboratory rock mechanics, Deaf Smith County Site, Texas: Revision 1

    SciTech Connect

    Not Available

    1987-12-01

    This Site Study Plan describes the non-routine rock mechanics and thermal properties laboratory testing program planned for the characterization of site-specific geologic materials for the Deaf Smith County site, Texas. The study design provides for measurements of index, mechanical, thermomechanical, thermal and special properties for the host salt, and where appropriate, for nonhost lithologies. The types of tests which will be conducted are constant stress (creep) tests, constant strain (stress relaxation) tests, constant strain-rate tests, constant stress-rate tests, cyclic loading tests, hollow cylinder tests, uniaxial and triaxial compression tests, direct tension tests, indirect (triaxial) shear tests, thermal property determinations (conductivity, specific heat, expansivity, and diffusivity), fracture healing tests, thermal decrepitation tests, moisture content determinations, and petrographic and micromechanics analyses. Tests will be conducted at confining pressures up to 30 MPa and temperatures up to 300/degree/C. These data are used to construct mathematical models for the phenomenology of salt deformation. The models are then used in finite-element codes to predict repository response. A tentative testing schedule and milestone log are given. The duration of the testing program is expected to be approximately 5 years. 44 refs., 13 figs., 13 tabs.

  12. Railroad Lines as Study Sites in Plant Biology.

    ERIC Educational Resources Information Center

    Arnold, Robert M.

    1979-01-01

    Presents reasons for utilizing abandoned railroad tracks in ecology field trip studies. Explanations are given for the factors influencing railroad vegetation. Activities for students are suggested. (SA)

  13. The Arctic Mars Analogue Svalbard Expedition 2006

    NASA Astrophysics Data System (ADS)

    Steele, A.; Amundsen, H. E. F.; Botta, O.

    2007-10-01

    In order to prepare for future exploration of Mars, both by robotic and human missions, a number of Mars Analog studies are currently being carried out. In the high Canadian arctic the NASA Houghton Mars Project (HMP) is operating a station on Devon island that supports a geobiological science program but also supports an exploration program aimed at the development of new technologies, strategies and operations. At the same location, the Mars society operates the Flashlight Mars Arctic Research Station (FMARS) habitat. A similar station is located in Utah called the Mars Desert Research Station (MDRS). Both of these stations follow an advanced science and human exploration portfolio. The Arctic Mars Analogue Svalbard Expedition (AMASE) in 2006 was the latest of a series of expeditions whose primary goals are: to test portable instruments for their robustness as field instruments for life detection (for future human missions to Mars); to assess the Mars analogue environments for signs of life and/or abiotic organic synthesis processes; to refine protocols for contamination reduction and to understand the effects of transport on sample integrity by assessing bioloads immediately in the field and then comparing these with laboratory measurements made after transportation. There have been three previous expeditions that were run by the Department of Physics of Geological Processes at the University of Oslo in collaboration with the Carnegie Institution of Washington (CIW), NASA-JPL, NASA-Ames, the Lunar and Planetary Institute, University of Leeds, University of Burgos, Penn State University, MacQuarie University (GEMOC) and the Smithsonian Institution, and with invaluable support from the Norwegian Space Centre, the University Studies on Svalbard (UNIS) and the Norwegian Polar Institute.

  14. Lessons Learned from Natural and Industrial Analogues for Storage of Carbon Dioxide

    NASA Astrophysics Data System (ADS)

    Jeandel, E.; Battani, A.; Sarda, P.

    2009-04-01

    The development of reliable monitoring tools to ensure the sustainability and the safety of geological storage is a prerequisite for the implementation of such sites. In this framework, a geochemical method using noble gas and carbon isotopes geochemistry has been tested on natural and industrial analogues of CO2 storage. Our approach was to compare data obtained at different time scales, as natural analogues may be a proof that long term storage of CO2 is feasible, whereas industrial analogues may demonstrate the ability to inject and monitor fluids at human time scales. To this end, gases were sampled in different natural analogues (located in two CO2 province, i.e. the Colorado Plateau and the French carbo-gaseous province) and in an industrial analogue (i.e. a natural gas storage located in the Paris Basin). Analyses of noble gas concentrations (He, Ne, Ar, Kr and Xe) and isotopic ratios (3He/4He, 20Ne/22Ne, 21Ne/22Ne, 38Ar/36Ar, and 40Ar/36Ar) were performed at IFP and IPGP Geochemistry laboratories. The concentrations and carbon isotopic ratios of associated major compounds (C1-C5and CO2) were also determined. First, the study of natural analogues showed systematic behaviours of the geochemical parameters, depending on the containment sites and the geological context. The main common point of all the case studies is the omnipresence of a mantle-derived helium component, whatever the geological context (sedimentary basins or geothermal areas). This component seems to be a sine qua non condition of the existence of any natural CO2 accumulation or leaks, and attests to a transfer between deep fluids and the sedimentary crust. This study also yields geochemical criteria to evaluate the containment of a natural CO2 analogue. On the one hand, all the gases sampled in CO2-leaking sites have CO2/ 3He ratios above the MORB (mid-ocean-ridge basalt) range of 1 x 109 to 1 x 1010(Marty and Jambon, 1987), pointing to CO2 predominantly derived from a crustal source. These samples paradoxically exhibit high R/Ra ratios (between 1,39 and 3,96Ra), attesting to a dominant mantle-derived helium component. Thus, in such CO2-leaking sites, the origin of CO2 seems to be related to the addition of crustal- CO2, poor in helium, during gas migration. On the other hand, gases sampled in good containment sites exhibit lower R/Ra ratio (0,36-1,07Ra), still indicating a present but smaller mantle-derived helium component, and associated to a typical MORB CO2/3He ratio: these features highlight a dominant mantle source for the CO2 in these gases. Isotopic fractionation of noble gases appears also to be closely linked to the quality of the containment, since a mass-related isotopic fractionation of neon and argon has been observed in all the CO2-leaking sites. This enrichment in the lightest noble gas isotope can be interpreted as a geochemical footprint of the rapid gas migration toward surface. Second, a 2-years geochemical tracing experiment on a natural gas storage site exploited by the GDF SUEZ Company was performed. Gas sampling was done every month during both the injection (usually in summer) and withdrawal (usually in winter) periods. This monitoring test demonstrates the possibility to identify physico-chemical processes taking place in the reservoir at a human time scale. More specifically, the gases sampled at the producing wells exhibit mixing trends between the different injected gas end-members, depending on the sampling date and the location of the wells. A significant partitioning between water and the gas phase has also been identified and is apparently related to changes of the gas to water volume ratio during gas withdrawal. These two complementary studies proved the effectiveness of noble gases and carbon isotopes in terms of leak detection and as tracers of the CO2 behaviour, thus increasing interest in the proposed method and providing general information on its use. References: Marty, B. and Jambon, A., 1987. C/3He in volatile fluxes from the solid Earth: implications for carbon geodynamics. Earth Planet. Sci. Lett. 83, pp

  15. THE TRITIUM UNDERFLOW STUDY AT THE SAVANNAH RIVER SITE

    SciTech Connect

    Hiergesell, R; Daniel Kaplan,D

    2007-05-21

    An issue of concern at the Savannah River Site (SRS) over the past 20 years is whether tritiated groundwater originating at SRS might be the cause of low levels of tritium measured in certain domestic wells in Georgia. Tritium activity levels in several domestic wells have been observed to occur at levels comparable to what is measured in rainfall in areas surrounding SRS. Since 1988, there has been speculation that tritiated groundwater from SRS could flow under the river and find its way into Georgia wells. A considerable effort was directed at assessing the likelihood of trans-river flow, and 44 wells have been drilled by the USGS and the Georgia Department of Natural Resources. Also, as part of the data collection and analysis, the USGS developed a numerical model during 1997-98 (Ref. 1) to assess the possibility for such trans-river flow to occur. The model represented the regional groundwater flow system surrounding the Savannah River Site (SRS) in seven layers corresponding to the underlying hydrostratigraphic units, which was regarded as sufficiently detailed to evaluate whether groundwater originating at SRS could possibly flow beneath the Savannah River into Georgia. The model was calibrated against a large database of water-level measurements obtained from wells on both sides of the Savannah River and screened in each of the hydrostratigraphic units represented within the model. The model results verified that the groundwater movement in all hydrostratigraphic units proceeds laterally toward the Savannah River from both South Carolina and Georgia, and discharges into the river. Once the model was calibrated, a particle-track analysis was conducted to delineate areas of potential trans-river flow. Trans-river flow can occur in either an eastward or westward direction. The model indicated that all locations of trans-river flow are restricted to the Savannah River's floodplain, where groundwater passes immediately prior to discharging into the river. Whether the trans-river flow is eastward or westward depends primarily on the position of the Savannah River as it meanders back and forth within the floodplain and is limited to narrow sections of land adjacent to the river. With respect to ''westward'' trans-river flow, the model indicates that it primarily occurs in locations south of SRS and within the deeper aquifers (Crouch Branch and McQueen Branch). Particle-tracking analysis of westward trans-river flow in these aquifers indicates that the groundwater crossing from South Carolina into Georgia originates as recharge in upland areas well to the east and south of SRS. The model identified one location (an area of less than one square mile) where westward trans-river flow originating as recharge within the boundaries of SRS and which could conceivably receive tritium or other contaminants from SRS as a result. The one-square-mile area occurs immediately adjacent to the Savannah River, where groundwater within the Gordon Aquifer flows immediately prior to discharging into the river and is indicated in Figure 1. Reverse particle tracking indicates that recharge zones associated with the one square mile are located in the upland areas between D-Area and K-Area. There is no known subsurface contamination at these recharge zones. The travel times associated with the particles were calculated to range from 90 to 820 years, although these estimates are shorter than actual travel times since no accounting of groundwater transit time across the uppermost aquifer was included in the model. It is important to note that the range of travel times represents seven to 66 half-lives of tritium (12.33 years), suggesting that even if tritium contamination existed at the recharge areas, it likely would decay away prior to discharging into the Savannah River.

  16. Siderophore receptor-mediated uptake of lactivicin analogues in gram-negative bacteria.

    PubMed

    Starr, Jeremy; Brown, Matthew F; Aschenbrenner, Lisa; Caspers, Nicole; Che, Ye; Gerstenberger, Brian S; Huband, Michael; Knafels, John D; Lemmon, M Megan; Li, Chao; McCurdy, Sandra P; McElroy, Eric; Rauckhorst, Mark R; Tomaras, Andrew P; Young, Jennifer A; Zaniewski, Richard P; Shanmugasundaram, Veerabahu; Han, Seungil

    2014-05-01

    Multidrug-resistant Gram-negative pathogens are an emerging threat to human health, and addressing this challenge will require development of new antibacterial agents. This can be achieved through an improved molecular understanding of drug-target interactions combined with enhanced delivery of these agents to the site of action. Herein we describe the first application of siderophore receptor-mediated drug uptake of lactivicin analogues as a strategy that enables the development of novel antibacterial agents against clinically relevant Gram-negative bacteria. We report the first crystal structures of several sideromimic conjugated compounds bound to penicillin binding proteins PBP3 and PBP1a from Pseudomonas aeruginosa and characterize the reactivity of lactivicin and ?-lactam core structures. Results from drug sensitivity studies with ?-lactamase enzymes are presented, as well as a structure-based hypothesis to reduce susceptibility to this enzyme class. Finally, mechanistic studies demonstrating that sideromimic modification alters the drug uptake process are discussed. PMID:24694215

  17. Compressed-Air Energy Storage: Preliminary design and site development program in an aquifer. Volume 3A: Site selection study, part 1

    NASA Astrophysics Data System (ADS)

    Walke, W. C.

    1981-07-01

    A preferred ranking for aquifer sites potentially capable of supporting a CAES facility is provided. The study area that was investigated for possible aquifer storage sites comprises roughly the Illinois and Indiana portions of the geologic structure known as the Illinois Basin. Sites in Illinois and Indiana adjacent to the Illinois Basin that appeared suitable geologically were also investigated. Potential sites in this area were identified by the Illinois State Geological Survey (ISGS) and the Indiana Geological Survey (IGS).

  18. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    SciTech Connect

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  19. Methylated N?-Hydroxy-L-arginine Analogues as Mechanistic Probes for the Second Step of the Nitric Oxide Synthase-Catalyzed Reaction†

    PubMed Central

    Labby, Kristin Jansen; Li, Huiying; Roman, Linda J.; Martásek, Pavel; Poulos, Thomas L.; Silverman, Richard B.

    2013-01-01

    Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrulline through the intermediate N?-hydroxy-L-arginine (NHA), producing nitric oxide, an important mammalian signaling molecule. Several disease states are associated with improper regulation of nitric oxide production, making NOS a therapeutic target. The first step of the NOS reaction has been well-characterized and is presumed to proceed through a compound I heme species, analogous to the cytochrome P450 mechanism. The second step, however, is enzymatically unprecedented and is thought to occur via a ferric peroxo heme species. To gain insight into the details of this unique second step, we report here the synthesis of NHA analogues bearing guanidinium-methyl or -ethyl substitutions and their investigation as either inhibitors of or alternate substrates for NOS. Radiolabeling studies reveal that N?-methoxy-L-arginine, an alternative NOS substrate, produces citrulline, nitric oxide, and methanol. On the basis of these results we propose a mechanism for the second step of NOS catalysis in which a methylated nitric oxide species is released and is further metabolized by NOS. Crystal structures of our NHA analogues bound to nNOS have been solved, revealing the presence of an active site water molecule only in the presence of singly methylated analogues. Bulkier analogues displace this active site water molecule; a different mechanism is proposed in the absence of the water molecule. Our results provide new insight into the steric and stereochemical tolerance of the NOS active site and substrate capabilities of NOS. PMID:23586781

  20. Synthetic Neurotensin Analogues Are Nontoxic Analgesics for the Rabbit Cornea

    PubMed Central

    Kim, Charles; Barbut, Denise; Heinemann, Murk H.; Pasternak, Gavril; Rosenblatt, Mark I.

    2014-01-01

    Purpose. To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Methods. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. Results. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Conclusions. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. PMID:24825106

  1. Conformational freedom in tight binding enzymatic transition-state analogues.

    PubMed

    Motley, Matthew W; Schramm, Vern L; Schwartz, Steven D

    2013-08-22

    Transition-state analogues of bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidases (MTANs) disrupt quorum-sensing pathways in Escherichia coli and Vibrio cholerae, demonstrating the potential to limit pathogenicity without placing bacteria under intense selective pressure that leads to antibiotic resistance. Despite the similarity of the crystal structures of E. coli MTAN (EcMTAN) and V. cholerae MTAN (VcMTAN) bound to DADMe-Immucillin-A transition-state (TS) analogues, EcMTAN demonstrates femtomolar affinity for BuT-DADMe-Immucillin-A (BDIA) whereas VcMTAN possesses only picomolar affinity. Protein dynamic interactions are therefore implicated in this inhibitor affinity difference. We conducted molecular dynamics simulations of both EcMTAN and VcMTAN in complex with BDIA to explore differences in protein dynamic architecture. Simulations revealed that electrostatic and hydrophobic interactions with BDIA are similar for both enzymes and thus unlikely to account for the difference in inhibitor affinity. The EcMTAN-BDIA complex reveals a greater flexibility and conformational freedom of catalytically important atoms. We propose that conserved motions related to the EcMTAN transition state correlate with the increased affinity of BDIA for EcMTAN. Transition-state analogues permitting protein motion related to formation of the transition state are better mimics of the enzymatic transition state and can bind more tightly than those immobilizing catalytic site dynamics. PMID:23895500

  2. Technical procedures for implementation of acoustics site studies, Deaf Smith County site, Texas: Environmental Field Program: Preliminary draft

    SciTech Connect

    Not Available

    1987-09-01

    The purpose and scope of the technical procedure for processing data from the tethered meteorological system are covered. Definitions, interfaces, and concurrent data needs are also addressed. This technical procedure describes how to control, organize, verify, and archive tethered meteorological system data. These data will be received at the processing location from the field measurement location and are part of the characterization of the Deaf Smith County Site, Texas for the salt repository program. These measurements will be made in support of the sound propagation study and are a result of environmental data requirements for acoustics. 6 refs., 15 figs., 5 tabs.

  3. Analysis of structural requirements for TRH-potentiating peptide receptor binding by analogue design.

    PubMed

    Ladram, A; Montagne, J J; Bulant, M; Nicolas, P

    1994-01-01

    Previous studies established that the [125I-Tyr0]Ps4 derivative of TRH-potentiating peptide (Ps4), Ser-Phe-Pro-Trp-Met-Glu-Ser-Asp-Val-Thr, displays high affinity and selectivity for an orphan membrane receptor in rat anterior pituitary. To identify the sites in Ps4 that determine receptor binding affinity, we have synthesized and screened a panel of 15 single-point substituted analogues for their ability to displace bound [125I-Tyr0]Ps4. The affinity of [Tyr0]Ps4 for rat anterior pituitary membranes [inhibitory constant (Ki), approximately 5 nM] was drastically reduced by the substitution of either Tyr0 with Gly or Asp8 with Asn (Ki approximately 95 and approximately 51 nM, respectively). Deamination of [Tyr0]Ps4 also sharply reduced affinity (Ki approximately 1100 nM). In contrast, Ser1-->Ala, Pro3-->Ala and Thr10-->Val substitutions led to analogues showing a tenfold increase in binding affinity relative to the parent peptide. The change of Phe2-->Leu, Trp4-->Ala, Glu6-->Gln, Val9-->Thr and carboxamidation of Thr10 had no effect on binding affinity. The data suggest that substitutions of the amino-terminal group, Asp8 and Tyr0, have a marked effect on the ability of [Tyr0]Ps4 to compete with [125I-Tyr0]Ps4 for binding to TRH-potentiating peptide pituitary receptor. PMID:7937314

  4. SOLVENT EXTRACTION AND SOIL WASHING TREATMENT OF CONTAMINATED SOILS FROM WOOD PRESERVING SITES: BENCH SCALE STUDIES

    EPA Science Inventory

    Bench-scale solvent extraction and soil washing studies were performed on soil samples obtained from three abandoned wood preserving sites that included in the NPL. The soil samples from these sites were contaminated with high levels of polyaromatic hydrocarbons (PAHs), pentachlo...

  5. NTS (Nevada Test Site) Mesa recharge study FY 1988: Letter report

    Microsoft Academic Search

    B. F. Lyles; T. M. Mihevc

    1990-01-01

    Pahute Mesa is a large geomorphic feature that is located in Areas 19 and 20 of the Nevada Test Site (NTS) and a portion of the Nellis Air Force Range. The identification of radionuclide migration at the U20n site has resulted in an increased interest in the hydrology of Pahute Mesa. An important aspect of groundwater studies is to estimate

  6. NTS (Nevada Test Site) Mesa recharge study FY 1989: Letter report

    Microsoft Academic Search

    B. F. Lyles; T. M. Mihevc

    1990-01-01

    Pahute Mesa is a large geomorphic feature that is located in Areas 19 and 20 of the Nevada Test Site (NTS) and a portion of the Nellis Air Force Range. The identification of radionuclide migration at the U20n site has resulted in an increased interest in the hydrology of Pahute Mesa. An important aspect of groundwater studies is to estimate

  7. Summary of some feasibility studies for site-specific solar industrial process heat

    SciTech Connect

    none,

    1982-01-01

    Some feasibility studies for several different site specific solar industrial process heat applications are summarized. The followng applications are examined. Leather Tanning; Concrete Production: Lumber and Paper Processing; Milk Processing; Molding, Curing or Drying; Automobile Manufacture; and Food Processing and Preparation. For each application, site and process data, system design, and performance and cost estimates are summarized.

  8. Study of New Youth Initiatives in Apprenticeship. Interim Report. Volume 2: Site Visit Reports.

    ERIC Educational Resources Information Center

    CSR, Inc., Washington, DC.

    This second volume of the interim report provides detailed case study reports on each of the eight Youth Apprenticeship Projects. (Volume 1, an overview of data from the site visits, is available separately as CE 032 791.) Discussion areas covered in each site visit report are local context/operational environment, administrative information,…

  9. The Costs of Pursuing Accreditation for Methadone Treatment Sites: Results from a National Study

    ERIC Educational Resources Information Center

    Zarkin, Gary A.; Dunlap, Laura J.; Homsi, Ghada

    2006-01-01

    The use of accreditation has been widespread among medical care providers, but accreditation is relatively new to the drug abuse treatment field. This study presents estimates of the costs of pursuing accreditation for methadone treatment sites. Data are from 102 methadone treatment sites that underwent accreditation as part of the Center for…

  10. Why We Are Not Google: Lessons from a Library Web Site Usability Study

    ERIC Educational Resources Information Center

    Swanson, Troy A.; Green, Jeremy

    2011-01-01

    In the Fall of 2009, the Moraine Valley Community College Library, using guidelines developed by Jakob Nielsen, conducted a usability study to determine how students were using the library Web site and to inform the redesign of the Web site. The authors found that Moraine Valley's current gateway design was a more effective access point to library…

  11. The seasonal distribution of bioaerosols in municipal landfill sites: a 3-yr study

    Microsoft Academic Search

    Chu-Yun Huang; Ching-Chang Lee; Fang-Chun Li; Yu-Pei Ma; Huey-Jen Jenny Su

    2002-01-01

    Landfill is the most common way to dispose waste in many countries, and most landfill sites after closure are often considered for public recreation purposes. It is important that the pollutant levels of closed landfill areas are free of adverse health concerns. However, only limited studies have investigated the airborne biological contamination in closed landfill sites. The objective of this

  12. An Explorative Study of Korean Consumer Participation in Virtual Brand Communities in Social Network Sites

    Microsoft Academic Search

    Yongjun Sung; Yoojung Kim; Ohyoon Kwon; Jangho Moon

    2010-01-01

    The importance of virtual brand communities in social network sites has received increasing attention from both academia and industry. In surveying a sample of 333 virtual brand community members in Korean social network sites, the current study provides a baseline understanding of the antecedents and consequences of virtual brand communities. The findings here suggest that members of brand communities have

  13. ALUMINUM SITING IN THE ZSM-22 AND THETA-1 ZEOLITES REVISITED: A QM/MM STUDY

    E-print Network

    Sklenak, Stepan

    ALUMINUM SITING IN THE ZSM-22 AND THETA-1 ZEOLITES REVISITED: A QM/MM STUDY Stepan SKLENAKa1 on the occasion of his 80th birthday. The Al siting in the silicon rich ZSM-22 and Theta-1 zeolites of the TON. Keywords: QM/MM calculations; Ab initio calculations; BLYP; GIAO; Zeolites; 27 Al 3Q MAS NMR spectroscopy

  14. COAL MINE SITING FOR THE OHIO RIVER BASIN ENERGY STUDY

    EPA Science Inventory

    This report was prepared as part of the Ohio River Basin Energy Study (ORBES), a multidisciplinary policy research program supported by the Environmental Protection Agency. In part 1, an overview of the ORBES-region coal industry is presented. (The region consists of all of Kentu...

  15. Programs of Study: What "Mature" Sites Tell Us

    ERIC Educational Resources Information Center

    Alfeld, Corinne; Bhattacharya, Sharika

    2012-01-01

    Although career and technical education (CTE) Programs of Study (POS) were introduced in the Perkins IV legislation, neither the spirit nor the elements of POS are new in the history of CTE as a vehicle for high school reform. POS have evolved over several decades of efforts to create effective transition programs from secondary to postsecondary…

  16. Current Research at the Endeavour Ridge 2000 Integrated Studies Site

    Microsoft Academic Search

    D. A. Butterfield; D. S. Kelley

    2004-01-01

    Integrated geophysical, geological, chemical, and biological studies are being conducted on the Endeavour segment with primary support from NSF, the W.M. Keck Foundation, and NSERC (Canada). The research includes a seismic network, physical and chemical sensors, high-precision mapping and time-series sampling. Several research expeditions have taken place at the Endeavour ISS in the past year. In June 2003, an NSF-sponsored

  17. Biological evaluation of a novel sorafenib analogue, t-CUPM.

    PubMed

    Wecksler, Aaron T; Hwang, Sung Hee; Liu, Jun-Yan; Wettersten, Hiromi I; Morisseau, Christophe; Wu, Jian; Weiss, Robert H; Hammock, Bruce D

    2015-01-01

    Sorafenib (Nexavar®) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib. PMID:25413440

  18. Case study: using sequence homology to identify putative phosphorylation sites in an evolutionarily distant species (honeybee).

    PubMed

    Trost, Brett; Napper, Scott; Kusalik, Anthony

    2014-11-01

    The majority of scientific resources are devoted to studying a relatively small number of model species, meaning that the ability to translate knowledge across species is of considerable importance. Obtaining species-specific knowledge enables targeted investigations of the biology and pathobiology of a particular species, and facilitates comparative analyses. Phosphorylation is the most widespread posttranslational modification in eukaryotes, and although many phosphorylation sites have been experimentally identified for some species, little or no data are available for others. Using the honeybee as a test organism, this case study illustrates the process of using protein sequence homology to identify putative phosphorylation sites in a species of interest using experimentally determined sites from other species. A number of issues associated with this process are examined and discussed. Several databases of experimentally determined phosphorylation sites exist; however, it can be difficult for the nonspecialist to ascertain how their contents compare. Thus, this case study assesses the content and comparability of several phosphorylation site databases. Additional issues examined include the efficacy of homology-based phosphorylation site prediction, the impact of the level of evolutionary relatedness between species in making these predictions, the ability to translate knowledge of phosphorylation sites across large evolutionary distances and the criteria that should be used in selecting probable phosphorylation sites in the species of interest. Although focusing on phosphorylation, the issues discussed here also apply to the homology-based cross-species prediction of other posttranslational modifications, as well as to sequence motifs in general. PMID:25380664

  19. Site-Specific Proteomics Approach for Study Protein S-Nitrosylation

    SciTech Connect

    Liu, Miao; Hou, Jinxuan; Huang, Lin; Huang, Xin; Heibeck, Tyler H.; Zhao, Rui; Pasa-Tolic, Ljiljana; Smith, Richard D.; Li, Yan; Fu, Kai; Zhang, Zhixin; Hinrichs, Steven; Ding, Shi-Jian

    2010-09-01

    Here we present a novel and robust method for the identification of protein S-nitrosylation sites in complex protein mixtures. The approach utilizes the cysteinyl affinity resin to selectively enrich S-nitrosylated peptides reduced by ascorbate followed by nanoscale liquid chromatography tandem mass spectrometry. Two alkylation agents with different added masses were employed to differentiate the S-nitrosylation sites from the non-Snitrosylation sites. We applied this approach to MDA-MB-231 cells treated with Angeli’s salt, a nitric oxide donor that has been shown to inhibit breast tumor growth and angiogenesis. A total of 162 S-nitrosylation sites were identified and an S-nitrosylation motif was revealed in our study. The 162 sites are significantly more than the number reported by previous methods, demonstrating the efficiency of our approach. Our approach will further facilitate the functional study of protein S-nitrosylation in cellular processes and may reveal new therapeutic targets.

  20. Synthesis of Phosphatidylcholine Analogues Derived from Glyceric Acid: a New Class of Biologically Active Phospholipid Compounds

    PubMed Central

    Rosseto, Renato; Tcacenco, Celize M.; Ranganathan, Radha; Hajdu, Joseph

    2009-01-01

    Synthesis of a new class of phosphatidylcholine analogues derived from glyceric acid is reported for spectroscopic studies of phospholipases and conformation of phospholipid side-chains in biological membranes, using fluorescence resonance energy transfer (FRET) techniques. PMID:19844592

  1. Astrobiology Field Research in Moon/Mars Analogue Environments: Preface

    NASA Technical Reports Server (NTRS)

    Foing, B. H.; Stoker, C.; Ehrenfreund, P.

    2011-01-01

    Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on Astrobiology field research in Moon/Mars analogue environments relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

  2. Astrobiology field research in Moon/Mars analogue environments

    NASA Astrophysics Data System (ADS)

    Foing, B. H.; Stoker, C.; Ehrenfreund, P.

    2011-07-01

    Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on ‘Astrobiology field research in Moon/Mars analogue environments’ relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

  3. Site characterization and impact study prototype for secondary schools

    SciTech Connect

    Davin, R.G. [Durango High School, Las Vegas, NV (United States)

    1995-12-01

    Secondary Education tends to be departmentalized to a degree that science disciplines are taught as separate entities with concepts and programs that are fragmented from the aggregate base of scientific knowledge. There is a need to synthesize these disciplines into one curricula that will provide a holistic approach rather than a narrow focus. Isolated disciplines foster isolated and disjointed strategies in environmental problem solving. Real world solutions to environmental challenges require an interdisciplinary team of specialists if goals are to be realized. This prototype incorporates various aspects of an impact study, including air and water quality, wildlife resources, agriculture and forest land, geologic data, socioeconomic impacts, historic and cultural preservation, politics and aesthetics into one curriculum to demonstrate the interconnectedness of these subjects.

  4. Brookland Site Development Study, Brookland, bounded by B&O Railroad Tracks, ...

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

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

  5. Promoting Waste Diversion through Site Specific Waste Bin Dalhousie University Case Study

    E-print Network

    Brownstone, Rob

    Promoting Waste Diversion through Site Specific Waste Bin Standards Dalhousie University Case Study and Grounds and trucking for access to warehouse for waste audits. Figure 1: Bin System at Agricultural Campus ........................................................ 2 2.2 Lab Waste Management

  6. Binding of a new bisphenol analogue, bisphenol S to bovine serum albumin and calf thymus DNA.

    PubMed

    Wang, Yan-Qing; Zhang, Hong-Mei; Cao, Jian; Tang, Bo-Ping

    2014-09-01

    Interactions of bisphenol S, a new bisphenol analogue with bovine serum albumin and calf thymus DNA were investigated using different spectroscopic methods and molecular modeling calculation. According to the analysis of experimental and theoretical data, we concluded that hydrophobic interactions and hydrogen bonding primarily mediated the binding processes of bisphenol S with bovine serum albumin and DNA. In addition, the electrostatic force should not be excluded. Molecular modeling studies indicated that the binding site of bisphenol S to bovine serum albumin located in the subdomain IB, while bisphenol S was a groove binder of DNA. In addition, BPS did not obviously induce second structural changes of bovine serum albumin, but it induced a conformational change of calf thymus DNA. PMID:24972352

  7. Study of the Nevada Test Site using Landsat satellite imagery

    SciTech Connect

    Zimmerman, P.D. [Georgetown Univ., Washington, DC (United States). Center for Strategic and International Studies

    1993-07-01

    In the period covered by the purchase order CSIS has obtained one Landsat image and determined that two images previously supplied to the principal investigator under a subcontract with George Washington University were inherently defective. We have negotiated with EOSAT over the reprocessing of those scenes and anticipate final delivery within the next few weeks. A critical early purchase during the subcontract period was of an EXABYTE tape drive, Adaptec SCSI interface, and the appropriate software with which to read Landsat images at CSIS. This gives us the capability of reading and manipulating imagery in house without reliance on outside services which have not proven satisfactory. In addition to obtaining imagery for the study, we have also performed considerable analytic work on the newly and previously purchased images. A technique developed under an earlier subcontract for identifying underground nuclear tests at Pahute Mesa has been significantly refined, and similar techniques were applied to the summit of Rainier Mesa and to the Yucca Flats area. An entirely new technique for enhancing the spectral signatures of different regions of NTS was recently developed, and appears to have great promise of success.

  8. Severe malaria in children in Yemen: two site observational study

    PubMed Central

    Al-Taiar, Abdullah; Jaffar, Shabbar; Assabri, Ali; Al-Habori, Molham; Azazy, Ahmed; Al-Mahdi, Nagiba; Ameen, Khaled; Greenwood, Brian M; Whitty, Christopher J M

    2006-01-01

    Objectives To assess the burden of malaria on health services, describe the clinical presentation of severe malaria in children, and identify factors associated with mortality by means of a prospective observational study. Setting Two public hospitals in Taiz (mountain hinterland) and Hodeidah (coastal plain), Yemen. Participants Children aged 6 months to 10 years. Results Of 12 301 paediatric admissions, 2071 (17%) were for suspected severe malaria. The proportion of such admissions varied according to the season (from 1% to 40%). Falciparum malaria was confirmed in 1332 children; 808 had severe disease as defined by the World Health Organization. Main presentations were respiratory distress (322/808, 40%), severe anaemia (291/800, 37%), and cerebral malaria (60/808, 8%). Twenty two of 26 children who died had a neurological presentation. No deaths occurred in children with severe anaemia but no other signs of severity. In multivariate analysis, a Blantyre coma score ? 2, history of fits, female sex, and hyperlactataemia predicted mortality; severe anaemia, respiratory distress, and hyperparasitaemia were not significant predictors of mortality. Conclusions Severe malaria puts a high burden on health services in Yemen. Although presentation is similar to African series, some important differences exist. Case fatality is higher in girls. PMID:17053235

  9. New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation.

    PubMed

    Baud, Matthias G J; Leiser, Thomas; Meyer-Almes, Franz-Josef; Fuchter, Matthew J

    2011-02-01

    New synthetic routes towards the natural product psammaplin A were developed with the particular view to preparing diverse analogues for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A analogues not accessible via currently reported methods. Preliminary biological studies revealed these compounds to be the most potent non peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our synthetic analogues show class I selectivity in vitro, an important feature for the design and synthesis of future isoform selective inhibitors. PMID:21113514

  10. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

    PubMed Central

    Rabe, Patrick; Klapschinski, Tim A; Brock, Nelson L; Citron, Christian A; D’Alvise, Paul; Gram, Lone

    2014-01-01

    Summary Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed. PMID:25161739

  11. Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid.

    PubMed

    Rabe, Patrick; Klapschinski, Tim A; Brock, Nelson L; Citron, Christian A; D'Alvise, Paul; Gram, Lone; Dickschat, Jeroen S

    2014-01-01

    Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure-activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed. PMID:25161739

  12. Chimpanzees as fauna: comparisons of sympatric large mammals across long-term study sites.

    PubMed

    Russak, Samantha M; McGrew, W C

    2008-04-01

    Although much research has shown otherwise, chimpanzees are still often classed as rainforest-dwellers. Most long-term studies of wild chimpanzees (Pan troglodytes) are not situated in evergreen, closed-canopy equatorial forests, but instead are conducted in more open habitats. This study aims to elucidate the extent of chimpanzee ecological diversity by scrutinizing (recently) sympatric mammalian fauna at established study sites. We compiled presence or absence data on large mammal species at eight sites: Assirik, Bossou, Budongo, Gombe, Kibale, Lopé, Mahale, and Tai. The sites were rank ordered on the most basic ecological variable: annual total rainfall. Only three of the 65 mammalian genera compiled were sympatric with chimpanzees at all sites: Potamochoerus (bushpig), Syncerus (buffalo), and Panthera pardus (leopard). Some subfamilies (e.g. colobines) were present at most sites, but some families (e.g. hyenids) were absent at most sites. Some taxa (e.g. suids, cercopithecines) correlated better than others (e.g. canids) with basic ecological variables. The most extreme chimpanzee study site for which data are available is Assirik, Senegal. Nowhere else are chimpanzees sympatric with Erythrocebus, Alcelaphus, Hippotragus, and Ourebia. As chimpanzees are often behavioral models for extinct hominins, these living faunal assemblages have implications for paleo-ecological reconstructions of ancestral habitats. PMID:18246594

  13. Ecological studies related to construction of the Defense Waste Processing Facility on the Savannah River Site

    SciTech Connect

    Scott, D.E.; Pechmann, J.H.K.; Knox, J.N.; Estes, R.A.; McGregor, J.H.; Bailey, K. (ed.)

    1988-12-01

    The Savannah River Ecology Laboratory has completed 10 years of ecological studies related to the construction of the Defense Waste Processing Facility (DWPF) on the Savannah River Site. This progress report examines water quality studies on streams peripheral to the DWPF construction site and examines the effectiveness of refuge ponds'' in ameliorating the effects of construction on local amphibians. Individual papers on these topics are indexed separately. 93 refs., 15 figs., 15 tabs. (MHB)

  14. Effect of caspase cleavage-site phosphorylation on proteolysis.

    PubMed Central

    Tözsér, József; Bagossi, Péter; Zahuczky, Gábor; Specht, Suzanne I; Majerova, Eva; Copeland, Terry D

    2003-01-01

    Caspases are important mediators of apoptotic cell death. Several cellular protein substrates of caspases contain potential phosphorylation site(s) at the cleavage-site region, and some of these sites have been verified to be phosphorylated. Since phosphorylation may affect substantially the substrate susceptibility towards proteolysis, phosphorylated, non-phosphorylated and substituted oligopeptides representing such cleavage sites were studied as substrates of apoptotic caspases 3, 7 and 8. Peptides containing phosphorylated serine residues at P4 and P1' positions were found to be substantially less susceptible towards proteolysis as compared with the serine-containing analogues, while phosphoserine at P3 did not have a substantial effect. P1 serine as well as P1-phosphorylated, serine-containing analogues of an oligopeptide representing the poly(ADP-ribose) polymerase cleavage site of caspase-3 were not hydrolysed by any of these enzymes, whereas the P1 aspartate-containing peptides were efficiently hydrolysed. These findings were interpreted with the aid of molecular modelling. Our results suggest that cleavage-site phosphorylation in certain positions could be disadvantageous or detrimental with respect to cleavability by caspases. Cleavage-site phosphorylation may therefore provide a regulatory mechanism to protect substrates from caspase-mediated degradation. PMID:12589706

  15. The Spectral Properties and Photosensitivities of Analogue Photopigments Regenerated with 10- and 14-Substituted Retinal Analogues

    Microsoft Academic Search

    F. Crescitelli; R. S. H. Liu

    1988-01-01

    Analogues of 11-cis- and 9-cis-retinal with substitutions at positions 10 and 14 were used to regenerate analogue photopigments with two opsins: that of the transmuted (cone-like) 521-pigment of Gekko gekko and that of the rhodopsin of Porichthys notatus. The spectral absorbances and photosensitivities of the regenerated photopigments were determined and compared, first, between the two systems of analogue photopigments, and

  16. Cold, Gas-Phase UV and IR Spectroscopy of Protonated Leucine Enkephalin and its Analogues

    NASA Astrophysics Data System (ADS)

    Burke, Nicole L.; Redwine, James; Dean, Jacob C.; McLuckey, Scott A.; Zwier, Timothy S.

    2014-06-01

    The conformational preferences of peptide backbones and the resulting hydrogen bonding patterns provide critical biochemical information regarding the structure-function relationship of peptides and proteins. The spectroscopic study of cryogenically-cooled peptide ions in a mass spectrometer probes these H-bonding arrangements and provides information regarding the influence of a charge site. Leucine enkephalin, a biologically active endogenous opiod peptide, has been extensively studied as a model peptide in mass spectrometry. This talk will present a study of the UV and IR spectroscopy of protonated leucine enkephalin [YGGFL+H]+ and two of its analogues: the sodiated [YGGFL+Na]+ and C-terminally methyl esterified [YGGFL-OMe+H]+ forms. All experiments were performed in a recently completed multi-stage mass spectrometer outfitted with a cryocooled ion trap. Ions are generated via nano-electrospray ionization and the analyte of interest is isolated in a linear ion trap. The analyte ions are trapped in a 22-pole ion trap held at 5 K by a closed cycle helium cryostat and interrogated via UV and IR lasers. Photofragments are trapped and isolated in a second LIT and mass analyzed. Double-resonance UV and IR methods were used to assign the conformation of [YGGFL+H]+, using the NH/OH stretch, Amide I, and Amide II regions of the infrared spectrum. The assigned structure contains a single backbone conformation at vibrational/rotational temperatures of 10 K held together with multiple H-bonds that self-solvate the NH3+ site. A "proton wire" between the N and C termini reinforces the H-bonding activity of the COO-H group to the F-L peptide bond, whose cleavage results in formation of the b4 ion, which is a prevalent, low-energy fragmentation pathway for [YGGFL+H]+. The reinforced H-bonding network in conjunction with the mobile proton theory may help explain the prevalence of the b4 pathway. In order to elucidate structural changes caused by modifying this H-bonding activity, structural analogues were investigated. Determining the [YGGFL+Na]+ structure will lend insight as to the impact of the ammonium group and methyl esterification of the C-terminus eliminates the carboxy proton. The talk will also report on high resolution, cold UV spectra, non-conformation specific IR gain spectra and conformation specific IR dip spectra for the analogues.

  17. An examination of cancer epidemiology studies among populations living close to toxic waste sites

    PubMed Central

    Russi, Mark B; Borak, Jonathan B; Cullen, Mark R

    2008-01-01

    Background Toxic waste sites contain a broad range of suspected or confirmed human carcinogens, and remain a source of concern to many people, particularly those living in the vicinity of a site. Despite years of study, a consensus has not emerged regarding the cancer risk associated with such sites. Methods We examined the published, peer-reviewed literature addressing cancer incidence or mortality in the vicinity of toxic waste sites between 1980 and 2006, and catalogued the methods employed by such studies. Results Nineteen studies are described with respect to eight methodological criteria. Most were ecological, with minimal utilization of hydrogeological or air pathway modeling. Many did not catalogue whether a potable water supply was contaminated, and very few included contaminant measurements at waste sites or in subjects' homes. Most studies did not appear to be responses to a recognized cancer mortality cluster. Studies were highly variable with respect to handling of competing risk factors and multiple comparisons. Conclusion We conclude that studies to date have generated hypotheses, but have been of limited utility in determining whether populations living near toxic waste sites are at increased cancer risk. PMID:18578889

  18. Arctic Mars Analogue Svalbard Expedition (AMASE) 2009

    NASA Astrophysics Data System (ADS)

    Steele, A.; Amundsen, H. E. F.; Conrad, P.; Benning, L.; Amase 2009 Team

    2010-03-01

    The Arctic Mars Analogue Svalbard Expeditions (AMASE) 2009 was the latest of a series of expeditions that are NASA ASTEP and ESA funded and have as among their primary goals sample acquisition, collection and caching on rover platforms.

  19. Synthesis and SAR of vinca alkaloid analogues

    Microsoft Academic Search

    Matthew E. Voss; Jeffery M. Ralph; Dejian Xie; David D. Manning; Xinchao Chen; Anthony J. Frank; Andrew J. Leyhane; Lei Liu; Jason M. Stevens; Cheryl Budde; Matthew D. Surman; Thomas Friedrich; Denise Peace; Ian L. Scott; Mark Wolf; Randall Johnson

    2009-01-01

    Versatile intermediates 12?-iodovinblastine, 12?-iodovincristine and 11?-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity

  20. Acoustic clouds: standing sound waves around a black hole analogue

    E-print Network

    Benone, Carolina L; Herdeiro, Carlos; Radu, Eugen

    2014-01-01

    Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

  1. Acoustic clouds: standing sound waves around a black hole analogue

    E-print Network

    Carolina L. Benone; Luis C. B. Crispino; Carlos Herdeiro; Eugen Radu

    2015-01-28

    Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

  2. Separation of structurally similar nocathiacin analogues by reversed phase chromatography.

    PubMed

    Wei, Maochen; Wang, Suzhen; He, Yunmian; Fang, Yongliang; Chen, Yijun

    2010-04-30

    The complete separation of structurally similar compounds has been a challenge due mainly to their similarity on physical and chemical properties. In the present study, a simple and effective chromatographic method to separate and purify nocathiacin acid from its structural analogue nocathiacin I was developed. After evaluating mobile phase compositions on the retention characteristics by reversed phase high-performance liquid chromatography (HPLC), the elution order of nocathiacin I and nocathiacin acid was completely reversed, and the resolution value between the two analogues was improved, by varying pH value and ionic strength, to greater than 10 from merged peaks under initial conditions. In addition, a preparative isolation of nocathiacin acid was performed by reversed phase column chromatography under the guidance of the HPLC study. This chromatographic method resulted in an efficient process to obtain pure nocathiacin acid with a recovery rate of 83%. The present approach offers a new methodology for the separation of structurally closely related secondary metabolites. PMID:20303091

  3. Synthetic Analogues of Cysteinate-Ligated Non-Heme Iron and Non-Corrinoid Cobalt Enzymes

    E-print Network

    Kovacs, Julie

    Synthetic Analogues of Cysteinate-Ligated Non-Heme Iron and Non-Corrinoid Cobalt Enzymes Julie A June 24, 2003 Contents 1. Introduction to Non-Heme Iron Enzymes 825 2. Nitrile Hydratase (NHase) 826 2.1. Enzyme Function 826 2.2. Enzyme Active Site Structure 826 2.3. Spectroscopic Properties 827 2

  4. Isolation and diversity analysis of resistance gene analogues (RGAs) from cultivated and wild strawberries

    Microsoft Academic Search

    M. G. Martínez Zamora; A. P. Castagnaro; J. C. Díaz Ricci

    2004-01-01

    Degenerate oligonucleotide primers, designed based on conserved regions of Nucleotide Binding Site (NBS) domains from previously cloned plant resistance genes, were used to isolate Resistance Gene Analogues (RGAs) from wild and cultivated strawberries. Seven distinct families of RGAs of the NBS-LRR type were identified from two related wild species, Fragaria vesca and F. chiloensis, and six different Fragaria × ananassa

  5. Site specific metals criteria as determined by Water Effect Ratio studies

    SciTech Connect

    Castle, C.J.; Neserke, G. [Commercial Testing and Engineering Co., Denver, CO (United States)

    1994-12-31

    Water Effect Ratios (WER) are being used to implement site-specific water quality criteria to address the variability of physical and chemical characteristics of site water and metals that may influence toxicity. A case in point, Coors Brewing Company in Golden, Colorado, has been granted site-specific criteria for the discharge of copper and zinc based on results of WER studies. Acute bioassays were conducted to determine seasonal WER values for copper, zinc and silver. The tests exposed Ceriodaphnia dubia and Pimephales promelas to graduated levels of metals in Clear Creek site water (below discharge mixing zone), reconstituted laboratory water and effluent. Final WER values, calculated by the ratio of LC50`s determined in site water and laboratory water, were multiplied by the standard metals criteria to develop the site specific values incorporated into the Coors Brewing Company permit to discharge. It is suggested that the high LC50 values for metals in site water is a factor of the effluent`s binding capacity that may reduce the bioavailability of metals in site water.

  6. Implementation of Action Sequences by a Neostriatal Site: A Lesion Mapping Study of Grooming Syntax

    E-print Network

    Berridge, Kent

    Implementation of Action Sequences by a Neostriatal Site: A Lesion Mapping Study of Grooming Syntax ("action syntax") as well as simpler as- pects of movement. This study focused on sequential organi- zation of rodent grooming. Grooming syntax provides an op- portunity to study how neural systems coordinate natural

  7. Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers.

    PubMed

    Bartlett, J B; Michael, A; Clarke, I A; Dredge, K; Nicholson, S; Kristeleit, H; Polychronis, A; Pandha, H; Muller, G W; Stirling, D I; Zeldis, J; Dalgleish, A G

    2004-03-01

    We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID trade mark ), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected. This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer. PMID:14997189

  8. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Microsoft Academic Search

    Edgar J. Rolleman; Marleen Melis; Roelf Valkema; Otto C. Boerman; Eric P. Krenning; Marion de Jong

    2010-01-01

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled\\u000a somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption\\u000a and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has\\u000a been described in several patients. Studies on the mechanism and localization demonstrate that

  9. Leonhard Euler and a q-analogue of the logarithm

    Microsoft Academic Search

    Erik Koelink; Walter Van Assche

    2007-01-01

    We study a q-logarithm which was introduced by Euler and give some of its properties. This q-logarithm did not get much attention in the recent literature. We derive basic properties, some of which were already given by Euler in a 1751-paper and 1734-letter to Daniel Bernoulli. The corresponding q-analogue of the dilogarithm is introduced. The relation to the values at

  10. Leonhard Euler and a $q$-analogue of the logarithm

    Microsoft Academic Search

    Erik Koelink; Walter Van Assche

    2008-01-01

    We study a q-logarithm which was introduced by Euler and give some of its\\u000aproperties. This q-logarithm did not get much attention in the recent\\u000aliterature. We derive basic properties, some of which were already given by\\u000aEuler in a 1751-paper and 1734-letter to Daniel Bernoulli. The corresponding\\u000aq-analogue of the dilogarithm is introduced. The relation to the values at

  11. Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors.

    PubMed

    Wang, Ning-Yu; Zuo, Wei-Qiong; Xu, Ying; Gao, Chao; Zeng, Xiu-Xiu; Zhang, Li-Dan; You, Xin-Yu; Peng, Cui-Ting; Shen, Yang; Yang, Sheng-Yong; Wei, Yu-Quan; Yu, Luo-Ting

    2014-03-15

    Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50=3.3?M, SI >30.3, 12b, EC50=3.5?M, SI >28.6, 10l, EC50=3.9?M, SI >25.6, 12o, EC50=4.5?M, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents. PMID:24529869

  12. Role of polymeric endosomolytic agents in gene transfection: a comparative study of poly(L-lysine) grafted with monomeric L-histidine analogue and poly(L-histidine).

    PubMed

    Hwang, Hee Sook; Hu, Jun; Na, Kun; Bae, You Han

    2014-10-13

    Endosomal entrapment is one of the main barriers that must be overcome for efficient gene expression along with cell internalization, DNA release, and nuclear import. Introducing pH-sensitive ionizable groups into the polycationic polymers to increase gene transfer efficiency has proven to be a useful method; however, a comparative study of introducing equal numbers of ionizable groups in both polymer and monomer forms, has not been reported. In this study, we prepared two types of histidine-grafted poly(L-lysine) (PLL), a stacking form of poly(L-histidine) (PLL-g-PHis) and a mono-L-histidine (PLL-g-mHis) with the same number of imidazole groups. These two types of histidine-grafted PLL, PLL-g-PHis and PLL-g-mHis, showed profound differences in hemolytic activity, cellular uptake, internalization, and transfection efficiency. Cy3-labeled PLL-g-PHis showed strong fluorescence in the nucleus after internalization, and high hemolytic activity upon pH changes was also observed from PLL-g-PHis. The arrangement of imidazole groups from PHis also provided higher gene expression than mHis due to its ability to escape the endosome. mHis or PHis grafting reduced the cytotoxicity of PLL and changed the rate of cellular uptake by changing the quantity of free ?-amines available for gene condensation. The subcellular localization of PLL-g-PHis/pDNA measured by YOYO1-pDNA intensity was highest inside the nucleus, while the lysotracker, which stains the acidic compartments was lowest among these polymers. Thus, the polymeric histidine arrangement demonstrate the ability to escape the endosome and trigger rapid release of polyplexes into the cytosol, resulting in a greater amount of pDNA available for translocation to the nucleus and enhanced gene expression. PMID:25144273

  13. Using the Moon as a high-fidelity analogue environment to study biological and behavioral effects of long-duration space exploration

    NASA Astrophysics Data System (ADS)

    Goswami, Nandu; Roma, Peter G.; De Boever, Patrick; Clément, Gilles; Hargens, Alan R.; Loeppky, Jack A.; Evans, Joyce M.; Peter Stein, T.; Blaber, Andrew P.; Van Loon, Jack J. W. A.; Mano, Tadaaki; Iwase, Satoshi; Reitz, Guenther; Hinghofer-Szalkay, Helmut G.

    2012-12-01

    Due to its proximity to Earth, the Moon is a promising candidate for the location of an extra-terrestrial human colony. In addition to being a high-fidelity platform for research on reduced gravity, radiation risk, and circadian disruption, the Moon qualifies as an isolated, confined, and extreme (ICE) environment suitable as an analog for studying the psychosocial effects of long-duration human space exploration missions and understanding these processes. In contrast, the various Antarctic research outposts such as Concordia and McMurdo serve as valuable platforms for studying biobehavioral adaptations to ICE environments, but are still Earth-bound, and thus lack the low-gravity and radiation risks of space. The International Space Station (ISS), itself now considered an analog environment for long-duration missions, better approximates the habitable infrastructure limitations of a lunar colony than most Antarctic settlements in an altered gravity setting. However, the ISS is still protected against cosmic radiation by the Earth magnetic field, which prevents high exposures due to solar particle events and reduces exposures to galactic cosmic radiation. On Moon the ICE environments are strengthened, radiations of all energies are present capable of inducing performance degradation, as well as reduced gravity and lunar dust. The interaction of reduced gravity, radiation exposure, and ICE conditions may affect biology and behavior - and ultimately mission success - in ways the scientific and operational communities have yet to appreciate, therefore a long-term or permanent human presence on the Moon would ultimately provide invaluable high-fidelity opportunities for integrated multidisciplinary research and for preparations of a manned mission to Mars.

  14. The Biostructural Features of Additional Jasplakinolide (Jaspamide) Analogues

    PubMed Central

    Watts, Katharine R.; Morinaka, Brandon I.; Amagata, Taro; Robinson, Sarah J.; Tenney, Karen; Bray, Walter M.; Gassner, Nadine C.; Lokey, R. Scott; Media, Joseph; Valeriote, Frederick A.; Crews, Phillip

    2011-01-01

    The cyclodepsipeptide jasplakinolide (1) (a.k.a. jaspamide), isolated previously from the marine sponge Jaspis splendens, is a unique cytotoxin and molecular probe that operates through stabilization of filamentous actin (F-actin). We have recently disclosed that two analogues of 1, jasplakinolides B (3) and E, were referred to the National Cancer Institute's (NCI) Biological Evaluation Committee and the objective of this study was to re-investigate a Fijian collection of J. splendens in an effort to find jasplakinolide congeners with similar biological properties. The current efforts have afforded six known jasplakinolide analogues (4 - 7, 9 - 10), two structures requiring revision (8 and 14) and four new congeners of 1 (11 - 13, 15) including open chain derivatives and structures with modified ?-tyrosine residues. Compounds were evaluated for biological activity in the NCI's 60 cell line screen and in a microfilament disruption assay in both HCT-116 and HeLa cells. These two phenotypic screens provide evidence that each cytotoxic analogue, including jasplakinolide B (3), operates by modification of microfilaments. The new structure jasplakinolide V (13) has also been selected for study by the NCI's Biological Evaluation Committee. In addition, the results of a clonogenic dose response study on jasplakinolide are presented. PMID:21241058

  15. Imperial College London EEE 1L4 Autumn 2009 E2.2 Analogue Electronics More transistor amplifiers

    E-print Network

    Papavassiliou, Christos

    Imperial College London ­ EEE 1L4 Autumn 2009 E2.2 Analogue Electronics More transistor amplifiers Base ­ Common Collector · Study the single transistor MOSFET amplifiers #12;Imperial College London London ­ EEE 3L4 Autumn 2009 E2.2 Analogue Electronics The 2nd form of the Miller theorem · consider

  16. Imperial College London EEE 1L6 Autumn 2009 E2.2 Analogue Electronics Multiple stage amplifiers

    E-print Network

    Papavassiliou, Christos

    Imperial College London ­ EEE 1L6 Autumn 2009 E2.2 Analogue Electronics Multiple stage amplifiers amplifiers #12;Imperial College London ­ EEE 2L6 Autumn 2009 E2.2 Analogue Electronics Two stage BJT of 2 single stage transistor amplifiers. We will study the shaded ones. #12;Imperial College London

  17. Autocyclic behaviour of fan deltas: an analogue experimental MAURITS VAN DIJK*, GEORGE POSTMA* and MAARTEN G. KLEINHANS

    E-print Network

    Autocyclic behaviour of fan deltas: an analogue experimental study MAURITS VAN DIJK*, GEORGE POSTMA ABSTRACT Fan deltas are excellent recorders of fan-building processes because of their high sedimentation of autogenically forced facies and stratigraphy. Analogue experiments were performed on fan deltas with constant

  18. Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues

    PubMed Central

    Liu, Xiaodan; Sturla, Shana J.

    2010-01-01

    Acylfulvenes (AFs) are a class of antitumor agents with favorable cytotoxic selectivity profiles compared to their natural product precursor, illudin S. Like many alkylating agents, illudin S and AFs readily react with thiol-containing small molecules such as cysteine, glutathione and cysteine-containing peptides; reduced cellular glutathione levels can affect illudin S toxicity. Glutathione reductase (GR) is a critical cellular anti-oxidant enzyme that regulates the intracellular ratio of reduced:oxidized glutathione. In this study, we found that acylfulvene analogues are GR inhibitors, and evaluated aspects of the drug-enzyme interactions as compared with the structurally related natural product illudin S and the known irreversible GR inhibitor, carmustine. Acylfulvene analogues exhibited concentration-dependent GR inhibitory activity with micromolar IC50s; however, up to 2 mM illudin S did not inhibit GR activity. The absence of NADPH attenuates GR inhibition by AFs and the presence of glutathione disulfide (GSSG), the natural GR substrate, which binds to the enzyme active site, has a minimal effect in protecting GR from AFs. Furthermore, each compound can induce GR conformation changes independent of the presence of NADPH or GSSG. These results, together with gel filtration analysis results and mass spectrometry data indicate AF is a reversible inhibitor and HMAF an irreversible inhibitor that can form a bis-adduct with GR by reacting with active site cysteines. Finally in a cell-based assay, illudin S and HMAF were found to inhibit GR activity, but this inhibition was not associated with the reduction of GR levels in the cell. A model accounting for differences in mechanisms of GR inhibition by the series of compounds is discussed. PMID:19668867

  19. Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues.

    PubMed

    Liu, Xiaodan; Sturla, Shana J

    2009-09-01

    Acylfulvenes (AFs) are a class of antitumor agents with favorable cytotoxic selectivity profiles compared to their natural product precursor, illudin S. Like many alkylating agents, illudin S and AFs readily react with thiol-containing small molecules such as cysteine, glutathione and cysteine-containing peptides; reduced cellular glutathione levels can affect illudin S toxicity. Glutathione reductase (GR) is a critical cellular antioxidant enzyme that regulates the intracellular ratio of reduced-oxidized glutathione. In this study, we found that acylfulvene analogues are GR inhibitors, and evaluated aspects of the drug-enzyme interactions as compared with the structurally related natural product illudin S and the known irreversible GR inhibitor, carmustine. Acylfulvene analogues exhibited concentration-dependent GR inhibitory activity with micromolar IC(50)s; however, up to 2 mM illudin S did not inhibit GR activity. The absence of NADPH attenuates GR inhibition by AFs and the presence of glutathione disulfide (GSSG), the natural GR substrate, which binds to the enzyme active site, has a minimal effect in protecting GR from AFs. Furthermore, each compound can induce GR conformation changes independent of the presence of NADPH or GSSG. These results, together with gel-filtration analysis results and mass spectrometry data, indicate AF is a reversible inhibitor and HMAF an irreversible inhibitor that can form a bis-adduct with GR by reacting with active site cysteines. Finally in a cell-based assay, illudin S and HMAF were found to inhibit GR activity, but this inhibition was not associated with the reduction of GR levels in the cell. A model accounting for differences in mechanisms of GR inhibition by the series of compounds is discussed. PMID:19668867

  20. Ecological studies related to construction of the Defense Waste Processing Facility on the Savannah River Site

    SciTech Connect

    Pechmann, J.H.K.; Scott, D.E.; McGregor, J.H.; Estes, R.A.; Chazal, A.C.

    1993-02-01

    The Defense Waste Processing Facility (DWPF) was built on the Savannah River Site (SRS) during the mid-1980's. The Savannah River Ecology Laboratory (SREL) has completed 12 years of ecological studies related to the construction of the DWPF complex. Prior to construction, the 600-acre site (S-Area) contained a Carolina bay and the headwaters of a stream. Research conducted by the SREL has focused primarily on four questions related to these wetlands: (1) Prior to construction, what fauna and flora were present at the DWPF site and at similar, yet undisturbed, alternative sites (2) By comparing the Carolina bay at the DWPF site (Sun Bay) with an undisturbed control Carolina bay (Rainbow Bay), what effect is construction having on the organisms that inhabited the DWPF site (3) By comparing control streams with streams on the periphery of the DWPF site, what effect is construction having on the peripheral streams (4) How effective have efforts been to lessen the impacts of construction, both with respect to erosion control measures and the construction of refuge ponds'' as alternative breeding sites for amphibians that formerly bred at Sun Bay Through the long-term census-taking of biota at the DWPF site and Rainbow Bay, SREL has begun to evaluate the impact of construction on the biota and the effectiveness of mitigation efforts. Similarly, the effects of erosion from the DWPF site on the water quality of S-Area peripheral streams are being assessed. This research provides supporting data relevant to the National Environmental Policy Act (NEPA) of 1969, the Endangered Species Act of 1973, Executive Orders 11988 (Floodplain Management) and 11990 (Protection of Wetlands), and United States Department of Energy (DOE) Guidelines for Compliance with Floodplain/Wetland Environmental Review Requirements (10CFR1022).

  1. Antifouling Activity of Bromotyrosine-Derived Sponge Metabolites and Synthetic Analogues

    Microsoft Academic Search

    Sofia Ortlepp; Martin Sjögren; Mia Dahlström; Horst Weber; Rainer Ebel; RuAngelie Edrada; Carsten Thoms; Peter Schupp; Lars Bohlin; Peter Proksch

    2007-01-01

    Eighteen brominated sponge-derived metabolites and synthetic analogues were analyzed for antilarval settlement of Balanus improvisus. Only compounds exhibiting oxime substituents including bastadin-3 (4), ?4 (1), ?9 (2), and ?16 (3), hemibastadin-1 (6), aplysamine-2 (5), and psammaplin A (10) turned out to inhibit larval settling at 1 to 10 ?M. Analogues of hemibastadin-1 (6) were synthesized and tested for structure activity studies.

  2. Curcumin analogues as possible anti-proliferative & anti-inflammatory agents

    Microsoft Academic Search

    A.-M. Katsori; M. Chatzopoulou; K. Dimas; C. Kontogiorgis; A. Patsilinakos; T. Trangas; D. Hadjipavlou-Litina

    2011-01-01

    A series of novel curcumin analogues has been designed, synthesized and tested in vitro\\/in vivo as potential multi-target agents. Their anti-proliferative and anti-inflammatory activities were studied. Compounds 1b and 2b were stronger inhibitors of soybean lipoxygenase (LOX) than curcumin. Analogue 1b was also the most potent aldose reductase (ALR2) inhibitor. Two compounds, (1a and 1f) exhibited in vivo anti-inflammatory activity

  3. Multiplex tandem mass spectrometry analysis of novel plasma lyso-Gb?-related analogues in Fabry disease.

    PubMed

    Boutin, Michel; Auray-Blais, Christiane

    2014-04-01

    Fabry disease is a multisystemic, X-linked lysosomal storage disorder caused by a deficit in ?-galactosidase A enzyme activity leading to glycosphingolipid accumulation, mainly globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3). Recent metabolomic studies have led to the discovery of novel biomarkers related to lyso-Gb3 in plasma and urine. These biomarkers show modifications of the sphingosine moiety of the lyso-Gb3 molecule. The objectives of this study were to develop and validate a liquid chromatography-tandem mass spectrometry method for the relative quantification of novel plasma lyso-Gb3-related analogues, to evaluate their levels in plasma of 74 Fabry patients and 41 healthy controls and to correlate these results with patient gender, enzyme replacement therapy treatment, and lyso-Gb3 analogue levels previously measured in urine for the same patients. As expected, the concentrations of lyso-Gb3 and its related analogues in plasma are higher in Fabry males compared to Fabry females and higher for untreated males compared to treated males. The concentration of lyso-Gb3 and its related analogues in plasma decrease significantly after the beginning of enzyme replacement therapy (ERT) treatment and remain stable for 30 months of monitored therapy in a Fabry male. In plasma, lyso-Gb3 is significantly more abundant than its related analogues, which differs from urine where the majority of the lyso-Gb3 analogues are more increased than lyso-Gb3 itself. In contrast to urine, the relative distribution of lyso-Gb3 and its analogues in plasma is similar from one individual to another in the same group of Fabry patients, irrespective of ERT. This study revealed a large discrepancy between the relative abundance of lyso-Gb3 and its analogues in urine and plasma. Further studies will thus be needed to better understand the metabolic relationship between plasma and urine lyso-Gb3-related biomarkers. PMID:24634980

  4. Effect of Oxytocin and its Analogues on the Phagocytosis of Tetrahymena: Outstanding Impact of Isotocin

    Microsoft Academic Search

    Gyrgy CSABA

    Summary. The influence on the phagocytosis of Tetrahymena pyriformis of oxytocin and its analogues (derivatives) tocinoic acid, isotocin and the tyrosin supplemented tail part (Tyr-Pro-Leu-Gly=Tyr) as well, as the impact of oxytocin and its analogues on the phagocytosis of the populations of Tetrahymena selected to itself and to the three latter molecules were studied in the experiments. The molecules tested

  5. Membrane Protein Structure and Dynamics Studied by Site-Directed SpinLabeling ESR

    Microsoft Academic Search

    Enrica Bordignon; Heinz-Jürgen Steinhoff

    ESR spectroscopy of site-directed spin-labeled biomolecules (Site-Directed Spin Labeling, SDSL) has emerged as a powerful\\u000a method for studying the structure and conformational dynamics of proteins and nucleic acids under conditions relevant to function\\u000a (for reviews see, e.g., Feix and Klug 1998; Hubbell et al. 1996; Hubbell et al. 1998, 2002). In this technique a spin-label side chain is introduced at

  6. Deformation patterns associated with an eruption at Mount Etna volcano: a combined study of the 2001 episode using geodesy and analogue modelling.

    NASA Astrophysics Data System (ADS)

    Le Corvec, N.; Walter, T. R.; Puglisi, G.; Bonforte, A.

    2009-04-01

    Ground deformation studies of volcanoes have provided much information on the pattern of flank movements. Mount Etna volcano, situated on the eastern coast of Sicily has grown in the vicinity the Malta escarpment probably linked on shore to the Timpe Fault System (TFS) dissecting the volcano's eastern flank. The eastern flank is, in addition to this regional faulting, subjected to gravitational spreading, as seaward horizontal displacements are constrained by geodetic studies. Therefore, the question arises how tectonic faulting and gravitational spreading of the Mount Etna eastern flank are related and how this complex deformation is associated with eruptive activity. Here we investigate the 2001 eruptive period in an attempt to elaborate the mutual influence of tectonic faulting, spreading and intrusion. Associated with this eruption, GPS and InSAR data revealed that the eastern flank has been affected by significant ground deformation, moreover the pattern of geodetically-detected ground displacements abruptly changed before, during and after the eruption. The pre-eruptive deformation (January to July 2001) is characterized by the displacement and subsidence of the lower part of the eastern flank affecting the TFS's footwall and hangingwall. The co-eruptive deformation (July to September 2001) is characterized by movement of the entire flank with stronger displacements at higher altitudes, and the post-eruptive deformation (September to October 2001) shows a similar displacement as during the pre-eruptive period, but with stronger displacements at lower altitudes. To better understand this changing behaviour, we reproduced Mount Etna volcano in a sandbox model and recorded its internal deformation with a digital image correlation technique. We considered the volcano morphology as a half ridge, and (1) defined an underlying weak decollement surface (silicone) to simulate gravitational spreading, (2) defined displacement of the Malta escarpment and hence of the TFS using a motor-controlled normal fault originating in the solid basement, and (3) forcefully intruded dikes along the axis of symmetry (N-S) that intend to push the eastern flank. Thus gravitational spreading and tectonic faulting were simulated concurrently with intermittent intrusions. Two main sets have been tested, first gravitational deformation (non-intruding period) followed by a period of intrusion together with normal faulting; and second an intrusion period followed by gravitational deformation together with normal faulting. The experiments showed that intrusive activity at Etna volcano change the intensity of spreading and affect displacement at the TFS. For instance, horizontal velocities at either side of the TFS are strongly affected by periods of shallow magmatic activity. Our experiments may help to explain the horizontal displacement changes found by the geodetic data associated with the 2001 eruptive cycle, including the pre-eruptive spreading, the dike intrusion event and the following eastern flank movements.

  7. Resistance Studies of a Dithiazol Analogue, DBPR110, as a Potential Hepatitis C Virus NS5A Inhibitor in Replicon Systems

    PubMed Central

    Lin, Hui-Mei; Wang, Jing-Chyi; Hu, Han-Shu; Wu, Pei-Shan; Wang, Wen-Hung; Wu, Su-Ying; Yang, Chi-Chen; Yeh, Teng-Kuang; Hsu, Tsu-An; Jiaang, Weir-Torn; Chao, Yu-Sheng

    2013-01-01

    Hepatitis C virus (HCV), a member of the Flaviviridae family, affects approximately 3% of the world's population and is becoming the leading cause of liver disease in the world. Therefore, the development of novel or more effective treatment strategies to treat chronic HCV infection is urgently needed. In our previous study, we identified a potential HCV NS5A inhibitor, BP008. After further systemic optimization, we discovered a more potent HCV inhibitor, DBPR110. DBPR110 reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC50) and a selective index value of 3.9 ± 0.9 pM and >12,800,000, respectively. DBPR110 reduced HCV2a replicon activity with an EC50 and a selective index value of 228.8 ± 98.4 pM and >173,130, respectively. Sequencing analyses of several individual clones derived from the DBPR110-resistant RNAs purified from cells harboring genotype 1b and 2a HCV replicons revealed that amino acid substitutions mainly within the N-terminal region (domain I) of NS5A were associated with decreased inhibitor susceptibility. P58L/T and Y93H/N in genotype 1b and T24A, P58L, and Y93H in the genotype 2a replicon were the key substitutions for resistance selection. In the 1b replicon, V153M, M202L, and M265V play a compensatory role in replication and drug resistance. Moreover, DBPR110 displayed synergistic effects with alpha interferon (IFN-?), an NS3 protease inhibitor, and an NS5B polymerase inhibitor. In summary, our results present an effective small-molecule inhibitor, DBPR110, that potentially targets HCV NS5A. DBPR110 could be part of a more effective therapeutic strategy for HCV in the future. PMID:23165461

  8. Technical procedures for the implementation of cultural resource site studies, Deaf Smith County, Texas: Preliminary draft

    SciTech Connect

    Not Available

    1987-09-30

    Cultural resources at the Deaf Smith County site will be identified, evaluated and managed through the implementation of studies detailed in the Site Study Plan for Cultural Resources. This technical procedure outlines the conduct of pedestrian survey and the documentation of identified cultural resources. The purpose of the field surveys is to identify and document cultural resources in the areas that will be affected by site characterization activities and to record the environmental setting of identified cultural resources. Three pedestrian surveys will cover 100 percent of the on-site and off-site project areas. Survey 1 will provide coverage of the Repository Surface Facility (RSF) area, which includes the Exploratory Shaft Facility (ESF) and two linear engineering design borehole (EDBH) seismic survey corridors. Survey 2 will provide coverage of a 39 km/sup 2/ (15 mi/sup 2/) area that includes the 23 km/sup 2/ (9 mi/sup 2/) Deaf Smith County site plus a 0.4 to 0.8 kM (1/4 to 1/2 mi) border area but excludes the area covered by Survey 1. Survey 3 will cover offsite geotechnical test areas, such as the locations of playa boreholes, deep playa wells, hydrologic tests, site foundation borings, and their access routes. The purpose of site documentation or recording is to address the project information needs for land use permits and approvals, engineering design support, and cultural resource evaluation for National Register of Historic Places eligibility. Site documentation will consist of gathering sufficient data on identified resources to complete Texas Natural Resource Information System (TNRIS). 7 refs., 3 figs.

  9. Optical analogue of relativistic Dirac solitons in binary waveguide arrays

    SciTech Connect

    Tran, Truong X., E-mail: truong.tran@mpl.mpg.de [Department of Physics, Le Quy Don University, 236 Hoang Quoc Viet str., 10000 Hanoi (Viet Nam); Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); Longhi, Stefano [Department of Physics, Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle Ricerche, Piazza L. da Vinci 32, I-20133 Milano (Italy)] [Department of Physics, Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle Ricerche, Piazza L. da Vinci 32, I-20133 Milano (Italy); Biancalana, Fabio [Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany) [Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); School of Engineering and Physical Sciences, Heriot-Watt University, EH14 4AS Edinburgh (United Kingdom)

    2014-01-15

    We study analytically and numerically an optical analogue of Dirac solitons in binary waveguide arrays in the presence of Kerr nonlinearity. Pseudo-relativistic soliton solutions of the coupled-mode equations describing dynamics in the array are analytically derived. We demonstrate that with the found soliton solutions, the coupled mode equations can be converted into the nonlinear relativistic 1D Dirac equation. This paves the way for using binary waveguide arrays as a classical simulator of quantum nonlinear effects arising from the Dirac equation, something that is thought to be impossible to achieve in conventional (i.e. linear) quantum field theory. -- Highlights: •An optical analogue of Dirac solitons in nonlinear binary waveguide arrays is suggested. •Analytical solutions to pseudo-relativistic solitons are presented. •A correspondence of optical coupled-mode equations with the nonlinear relativistic Dirac equation is established.

  10. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    SciTech Connect

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  11. A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert

    1994-04-01

    EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

  12. Enzymatic and cryoreduction EPR studies of the hydroxylation of methylated N(?)-hydroxy-L-arginine analogues by nitric oxide synthase from Geobacillus stearothermophilus.

    PubMed

    Davydov, Roman; Labby, Kristin Jansen; Chobot, Sarah E; Lukoyanov, Dmitriy A; Crane, Brian R; Silverman, Richard B; Hoffman, Brian M

    2014-10-21

    Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrulline and NO in a two-step process involving the intermediate N(?)-hydroxy-L-arginine (NHA). It was shown that Cpd I is the oxygenating species for L-arginine; the hydroperoxo ferric intermediate is the reactive intermediate with NHA. Methylation of the N(?)-OH and N(?)-H of NHA significantly inhibits the conversion of NHA into NO and L-citrulline by mammalian NOS. Kinetic studies now show that N(?)-methylation of NHA has a qualitatively similar effect on H?O?-dependent catalysis by bacterial gsNOS. To elucidate the effect of methylating N(?)-hydroxy L-arginine on the properties and reactivity of the one-electron-reduced oxy-heme center of NOS, we have applied cryoreduction/annealing/EPR/ENDOR techniques. Measurements of solvent kinetic isotope effects during 160 K cryoannealing cryoreduced oxy-gsNOS/NHA confirm the hydroperoxo ferric intermediate as the catalytically active species of step two. Product analysis for cryoreduced samples with methylated NHA's, NHMA, NMOA, and NMMA, annealed to 273 K, show a correlation of yields of L-citrulline with the intensity of the g 2.26 EPR signal of the peroxo ferric species trapped at 77 K, which converts to the reactive hydroperoxo ferric state. There is also a correlation between the yield of L-citrulline in these experiments and k(obs) for the H?O?-dependent conversion of the substrates by gsNOS. Correspondingly, no detectable amount of cyanoornithine, formed when Cpd I is the reactive species, was found in the samples. Methylation of the NHA guanidinium N(?)-OH and N(?)-H inhibits the second NO-producing reaction by favoring protonation of the ferric-peroxo to form unreactive conformers of the ferric-hydroperoxo state. It is suggested that this is caused by modification of the distal-pocket hydrogen-bonding network of oxy gsNOS and introduction of an ordered water molecule that facilitates delivery of the proton(s) to the one-electron-reduced oxy-heme moiety. These results illustrate how variations in the properties of the substrate can modulate the reactivity of a monooxygenase. PMID:25251261

  13. Stereoelectronic interaction effects on the conformational properties of hydrogen peroxide and its analogues containing S and Se atoms: an ab initio, hybrid-DFT study and NBO analysis.

    PubMed

    Nori-Shargh, Davood; Yahyaei, Hooriye; Boggs, James E

    2010-06-01

    Ab initio molecular orbital (MP2/6-311+G**//MP2/6-31G+G**) and hybrid-density functional theory (B3LYP/6-311+G**//MP2/6-311+G**) methods and NBO analysis were used to study the stereoelectronic interaction effects on the conformational properties of hydrogen peroxide (1), hydrogen disulfide (2) and hydrogen diselenide (3). The results showed that the Gibbs free energy difference (G(T)-G(S)) values at 298.15K and 1atm between the skew (S) and trans (T) conformations (DeltaG(T-S)) increase from compound 1 to compound 2 but decrease from compound 2 to compound 3. The C conformations of compounds 1-3 are less stable than their S and T conformations. Based on these results, the racemization processes of the axial symmetrical (C(2) symmetry) conformations of compounds 1-3 take place via their T conformations. Based on the optimized ground state geometries using the MP2/6-311+G** level of theory, the NBO analysis of donor-acceptor (bond-antibond) interactions revealed that the stabilization (resonance) energy associated with LP(2)M2-->sigma*(M3-H4) electronic delocalization for the S conformations of compounds 1-3 are 1.35, 5.94 and 4.68 kcal mol(-1), respectively. There is excellent agreement between the variations of the calculated DeltaG(T-S) and stabilization (resonance) energies associated with LP(2)M2-->sigma*(M3-H4) electronic delocalization for the S conformations of compounds 1-3. The correlations between resonance energies, orbital integrals, dipole moments, bond orders, structural parameters and conformational behaviors of compounds 1-3 have been investigated. Test were made of complete basis set methods (CBS-QB3, CBS-4 and CBS-Q), the first two gave results essentially indistinguishable from those we used, but the CBS-Q results were in disagreement with experimental and other theoretical results. PMID:20207563

  14. Structural Insight into Methyl-Coenzyme M Reductase Chemistry Using Coenzyme B Analogues

    SciTech Connect

    Cedervall, Peder E.; Dey, Mishtu; Pearson, Arwen R.; Ragsdale, Stephen W.; Wilmot, Carrie M. (Michigan); (UMM)

    2010-09-07

    Methyl-coenzyme M reductase (MCR) catalyzes the final and rate-limiting step in methane biogenesis: the reduction of methyl-coenzyme M (methyl-SCoM) by coenzyme B (CoBSH) to methane and a heterodisulfide (CoBS-SCoM). Crystallographic studies show that the active site is deeply buried within the enzyme and contains a highly reduced nickel-tetrapyrrole, coenzyme F430. Methyl-SCoM must enter the active site prior to CoBSH, as species derived from methyl-SCoM are always observed bound to the F430 nickel in the deepest part of the 30 {angstrom} long substrate channel that leads from the protein surface to the active site. The seven-carbon mercaptoalkanoyl chain of CoBSH binds within a 16 {angstrom} predominantly hydrophobic part of the channel close to F430, with the CoBSH thiolate lying closest to the nickel at a distance of 8.8 {angstrom}. It has previously been suggested that binding of CoBSH initiates catalysis by inducing a conformational change that moves methyl-SCoM closer to the nickel promoting cleavage of the C-S bond of methyl-SCoM. In order to better understand the structural role of CoBSH early in the MCR mechanism, we have determined crystal structures of MCR in complex with four different CoBSH analogues: pentanoyl, hexanoyl, octanoyl, and nonanoyl derivatives of CoBSH (CoB5SH, CoB6SH, CoB8SH, and CoB9SH, respectively). The data presented here reveal that the shorter CoB5SH mercaptoalkanoyl chain overlays with that of CoBSH but terminates two units short of the CoBSH thiolate position. In contrast, the mercaptoalkanoyl chain of CoB6SH adopts a different conformation, such that its thiolate is coincident with the position of the CoBSH thiolate. This is consistent with the observation that CoB6SH is a slow substrate. A labile water in the substrate channel was found to be a sensitive indicator for the presence of CoBSH and HSCoM. The longer CoB8SH and CoB9SH analogues can be accommodated in the active site through exclusion of this water. These analogues react with Ni(III)-methyl, a proposed MCR catalytic intermediate of methanogenesis. The CoB8SH thiolate is 2.6 {angstrom} closer to the nickel than that of CoBSH, but the additional carbon of CoB9SH only decreases the nickel thiolate distance a further 0.3 {angstrom}. Although the analogues do not induce any structural changes in the substrate channel, the thiolates appear to preferentially bind at two distinct positions in the channel, one being the previously observed CoBSH thiolate position and the other being at a hydrophobic annulus of residues that lines the channel proximal to the nickel.

  15. A Study Plan for Determining Recharge Rates at the Hanford Site Using Environmental Tracers

    SciTech Connect

    Murphy,, E. M.; Szecsody,, J. E.; Phillips,, S. J.

    1991-02-01

    This report presents a study plan tor estimating recharge at the Hanford Site using environmental tracers. Past operations at the Hanford Site have led to both soil and groundwater contamination, and recharge is one of the primary mechanisms for transporting contaminants through the vadose zone and into the groundwater. The prediction of contaminant movement or transport is one aspect of performance assessment and an important step in the remedial investigation/feasibility study (RI/FS) process. In the past, recharge has been characterized by collecting lysimeter data. Although lysimeters can generate important and reliable data, their limitations include 1) fixed location, 2) fixed sediment contents, 3) edge effects, 4) low rates, and 5) relatively short duration of measurement. These limitations impact the ability to characterize the spatial distribution of recharge at the Hanford Site, and thus the ability to predict contaminant movement in the vadose zone. An alternative to using fixed lysimeters for determining recharge rates in the vadose zone is to use environmental tracers. Tracers that have been used to study water movement in the vadose zone include total chloride, {sup 36}CI, {sup 3}H, and {sup 2}H/{sup 18}O. Atmospheric levels of {sup 36}CI and {sup 3}H increased during nuclear bomb testing in the Pacific, and the resulting "bomb pulse" or peak concentration can be measured in the soil profile. Locally, past operations at the Hanford Site have resu~ed in the atmospheric release of numerous chemical and isotopic tracers, including nitrate, {sup 129}I, and {sup 99}Tc. The radionuclides, in particular, reached a well-defined atmospheric peak in 1945. Atmospheric releases of {sup 129}I and {sup 99}Tc were greatly reduced by mid-1946, but nitrogen oxides continued to be released from the uranium separations facilities. As a result, the nitrate concentrations probably peaked in the mid-1950s, when the greatest number of separations facilities were operating. Seven study sites on the Hanford Site have been selected, in two primary soil types that are believed to represent the extremes in recharge, the Quincy sand and the Warden silt loam. An additional background study site upwind of the Hanford facilities has been chosen at the Yakima Firing Center. Study sites at Hanford were chosen close to micrometeorology stations on downwind transects from the operational facilities. Initial testing will be done on sites that lack perennial vegetation. Six tracer techniques (total chlortde, {sup 36}Cl, {sup 3}H, nitrate, {sup 129}I, and {sup 99}Tc) will be tested on at least one site in the Quincy sand, one site in the Warden si~ loam, and the background site, to determine which combination of tracers wortks best for a given soil type. In subsequent years, additional sites will be investigated to determine the effect of vegetation on recharge estimates and on the performance of individual tracers. The use of environmental tracers is perhaps the only cost-effective method for estimating the spatial vartability of recharge at a site as large as Hanford. The tracer techniques used at Hanford have wide applicability at other and sites operated by the U.S. Department of Energy as well as at low-level radioactive waste disposal sites.

  16. Benzofuran analogues of amphetamine and methamphetamine: studies on the metabolism and toxicological analysis of 5-APB and 5-MAPB in urine and plasma using GC-MS and LC-(HR)-MS(n) techniques.

    PubMed

    Welter, Jessica; Kavanagh, Pierce; Meyer, Markus R; Maurer, Hans H

    2015-02-01

    5-APB (5-(2-aminopropyl)benzofuran) and its N-methyl derivative 5-MAPB (N-methyl-5-(2-aminopropyl)benzofuran) are analogues of amphetamine and methamphetamine, respectively, and belong to the so-called novel psychoactive substances (NPS). They were consumed as stimulants or entactogens with euphoric and empathogenic effects. Being controlled in some countries, both compounds should be covered by drug testing in clinical and forensic toxicology. Therefore, metabolism studies have been performed by working up rat urine samples after a high single dose of the corresponding NPS with solid-phase extraction without and after enzymatic conjugates cleavage. The phase I metabolites were separated and identified after acetylation by GC-MS and/or LC-HR-MS(n) and the phase II metabolites by LC-HR-MS(n). The main metabolite of 5-APB was 3-carboxymethyl-4-hydroxy amphetamine and the main metabolites of 5-MAPB were 5-APB (N-demethyl metabolite) and 3-carboxymethyl-4-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 5-MAPB N-demethylation were CYP1A2, CYP2B6, CYP2C19, and CYP2D6, and according to the kinetic parameters, CYP2B6 was responsible for the main part of the total CYP-dependent clearance. An intake of a common users' dose of 5-APB or 5-MAPB could be confirmed in rat urine using the authors' GC-MS and the LC-MS(n) standard urine screening approaches with the corresponding parent drugs as major target. In authentic human urine samples after ingestion of unknown doses of 5-MAPB, both metabolites could also be detected besides the parent drug. The plasma concentrations determined in six clinical cases ranged from 5 to 124 ?g/L for 5-MAPB and from 1 to 38 ?g/L for its N-demethyl metabolite 5-APB. PMID:25471293

  17. The Cottonwood Lake study area, a long-term wetland ecosystem monitoring site

    USGS Publications Warehouse

    Mushet, David M.; Euliss, Ned H.

    2012-01-01

    The Cottonwood Lake study area is one of only three long-term wetland ecosystem monitoring sites in the prairie pothole region of North America; the other two are Orchid Meadows in South Dakota and St. Denis in Saskatchewan. Of the three, Cottonwood Lake has, by far, the longest continuous data-collection record. Research was initiated at the study area in 1966, and intensive investigations of the hydrology, chemistry, and biology of prairie pothole wetlands continue at the site today. This fact sheet describes the study area, provides an overview of wetland ecology research that has been conducted at the site in the past, and provides an introduction to current work being conducted at the study area by USGS scientists.

  18. Site Sampling and Treatability Studies for Demonstration of WasteChem’s Asphalt Encapsulation Technology Under EPA’s SITE Program

    Microsoft Academic Search

    Jack Hubbard; Steve Tsadwa; Nancy Willis; Mark Evans

    1990-01-01

    This paper presents a sampling approach that was used to determine whether there were adequate quantities and concentrations of wastes at the Woodland Township Route 532 Site for demonstration of the asphalt encapsulation technology. This paper also presents the result of a bench-scale treatability study on wastes from this site. The preliminary sampling and analysis confirmed most of the types

  19. IN-SITU DUOX¿ CHEMICAL OXIDATION TECHNOLOGY TO TREAT CHLORINATED ORGANICS AT THE ROOSEVELT MILLS SITE, VERNON, CT: SITE CHARACTERIZATION AND TREATABILITY STUDY

    EPA Science Inventory

    A study was performed investigating the feasibility of applying the DUOX¿ chemical oxidation technology to chlorinated solvent contaminated media at the Roosevelt Mills site in Vernon, Connecticut. The Roosevelt Mills site is a former woolen mill that included dry cleaning operat...

  20. Studies of infiltration and lead-soil interactions at the Radioactive Waste Management Site in Area 5 of the Nevada Test Site

    Microsoft Academic Search

    C. M. Case; J. O. Davis; J. C. Heidker; M. R. Whitbeck

    1992-01-01

    Several studies were conducted to investigate the possibility of buried lead being transported by water in the unsaturated zone at the Area 5 Radioactive Waste Management Site (RWMS) on the Nevada Test Site. All involved soil from a 37-m soil core collected at the RWMS. The core consisted primarily of sand and small pebbles, with occasional layers of loose rocks.

  1. Contact zones and hydrothermal systems as analogues to repository conditions

    SciTech Connect

    Wollenberg, H.A.; Flexser, S.

    1984-10-01

    Radioactive waste isolation efforts in the US are currently focused on examining basalt, tuff, salt, and crystalline rock as candidate rock types to encompass waste repositories. As analogues to near-field conditions, the distributions of radio- and trace-elements have been examined across contacts between these rocks and dikes and stocks that have intruded them. The intensive study of the Stripa quartz monzonite has also offered the opportunity to observe the distribution of uranium and its daughters in groundwater and its relationship to U associated with fracture-filling and alteration minerals. Investigations of intrusive contact zones to date have included (1) a tertiary stock into Precambrian gneiss, (2) a stock into ash flow tuff, (3) a rhyodacite dike into Columbia River basalt, and (4) a kimberlite dike into salt. With respect to temperature and pressure, these contact zones may be considered "worst-case scenario" analogues. Results indicate that there has been no appreciable migration of radioelements from the more radioactive intrusives into the less radioactive country rocks, either in response to the intrusions or in the fracture-controlled hydrological systems that developed following emplacement. In many cases, the radioelements are locked up in accessory minerals, suggesting that artificial analogues to these would make ideal waste forms. Emphasis should now shift to examination of active hydrothermal systems, studying the distribution of key elements in water, fractures, and alteration minerals under pressure and temperature conditions most similar to those expected in the near-field environment of a repository. 14 refs.

  2. Transdermal delivery of a melanotropic peptide hormone analogue

    SciTech Connect

    Dawson, B.V.; Hadley, M.E.; Kreutzfeld, K.; Dorr, R.T.; Hruby, V.J.; Al-Obeidi, F.; Don, S.

    1988-01-01

    We previously reported that topical application of (Nl3/sup 4/,D-Phe/sup 7/)alpha-MSH, a superpotent analogue of alpha-melanocyte stimulating hormone, to mice induces a darkening of follicular melanocytes throughout the skin. We now report that the melanotropin analogue can be delivered across mouse but not rat skin in an in vitro model system. Passage of the analogue from the topically applied vehicle (polyethylene glycol) across the skin into a subcutaneous receiving vessel was demonstrated by both bioassay as well as by radioimmunoassay. The bioassay data demonstrate that percutaneous absorption of the melanotropin did not result in loss of biological activity of the peptide. The differential penetration of the peptide across rodent skin reveals that one cannot predict percutaneous absorption of a substance across the stratum corneum from studies on a single species. The present results are the first to demonstrate, by direct quantitative measurements, that a bioactive peptide can be delivered across the vertebrate integument in vitro. These studies point out the potential of a topically applied melanotropin for tanning of the skin and possibly for treatment of certain hypopigmentary disorders.

  3. Rational design of ?-helix-stabilized exendin-4 analogues.

    PubMed

    Rovó, Petra; Farkas, Viktor; Stráner, Pál; Szabó, Mária; Jermendy, Agnes; Hegyi, Orsolya; Tóth, Gábor K; Perczel, András

    2014-06-10

    Exendin-4 (Ex4) is a potent glucagon-like peptide-1 receptor agonist, a drug regulating the plasma glucose level of patients suffering from type 2 diabetes. The molecule's poor solubility and its readiness to form aggregates increase the likelihood of unwanted side effects. Therefore, we designed Ex4 analogues with improved structural characteristics and better water solubility. Rational design was started from the parent 20-amino acid, well-folded Trp cage (TC) miniprotein and involved the step-by-step N-terminal elongation of the TC head, resulting in the 39-amino acid Ex4 analogue, E19. Helical propensity coupled to tertiary structure compactness was monitored and quantitatively analyzed by electronic circular dichroism and nuclear magnetic resonance (NMR) spectroscopy for the 14 peptides of different lengths. Both (15)N relaxation- and diffusion-ordered NMR measurements were established to investigate the inherent mobility and self-association propensity of Ex4 and E19. Our designed E19 molecule has the same tertiary structure as Ex4 but is more helical than Ex4 under all studied conditions; it is less prone to oligomerization and has preserved biological activity. These conditions make E19 a perfect lead compound for further drug discovery. We believe that this structural study improves our understanding of the relationship between local molecular features and global physicochemical properties such as water solubility and could help in the development of more potent Ex4 analogues with improved pharmacokinetic properties. PMID:24828921

  4. Study plan for urban stream indicator sites of the National Water-Quality Assessment Program

    USGS Publications Warehouse

    Lopes, T.J.; Price, C.V.

    1997-01-01

    Urban Indicator Sites are one component of the U.S. Geological Survey?s National Water- Quality Assessment (NAWQA) Program. The objectives of monitoring at the Urban Indicator Sites are to: (1) characterize stream quality from drainage basins with predominantly residential and commercial land use, and (2) determine which selected natural and human factors most strongly affect stream quality. Urban Indicator Sites will be distributed across the United States in settings with statistically different climate and in metropolitan areas that have a population of 250,000 or more. Multiple sites in the same climatic setting will have a range in population density. Ideally, Urban Indicator Sites will monitor drainage basins that have only residential and commercial land use, are 50 square kilometers or larger, are in the same physiographic setting as other Indicator Sites, have sustained flow, and overlap other NAWQA study components. Ideal drainage basins will not have industrial or agricultural land use and will not have point-source-contamination discharges. Stream quality will be characterized by collecting and analyzing samples of streamflow, bed sediment, and tissue of aquatic organisms for selected constituents. Factors affecting stream quality will be determined by statistical analysis of ancillary data associated with Urban Indicator Sites and stream-quality samples.

  5. Compressed-air energy storage: Preliminary design and site development program in an aquifer. Volume 3B: Site selection study, part 2

    NASA Astrophysics Data System (ADS)

    Walke, W. C.

    1981-07-01

    Fourteen sites considered to have potential for development with a 1000 MW compressed air energy storage (CAES) plant were identified by the Illinois State Geological Survey (ISGS) and the Indiana Geological Survey (IGS). The relative desirability of developing each of these sites was evaluated from the standpoints of geology, economics, air quality/meteorology, cultural resources, and ecology. Preliminary site layouts were developed for each of the 14 sites. Sites that were found to be incapable of supporting a 1000 MW plat, or that would require more than 2000 air injection-withdrawal wells to do so, were eliminated from consideration. The seven remaining top-ranked sites were then selected for further study.

  6. A structural study of the proton conducting B-site ordered perovskite Ba3Ca1.18Ta1.82O8.73.

    PubMed

    Verbraeken, Maarten C; Viana, Hermenegildo A L; Wormald, Philip; Irvine, John T S

    2011-06-15

    The proton conducting material Ba(3)Ca(1.18)Ta(1.82)O(8.73) (BCT18) was synthesized and characterized using diffraction methods and thermal analysis. It was shown that BCT18 is structurally similar to its niobium analogue (BCN18). At synthesis temperatures up to 1500?°C however, BCT18 forms a mixture of Ca- and Ta-site ordered phases, with both 1:1 type and 1:2 type ordering. The phase ratio seems to depend solely on the synthesis conditions, with 1:1 type ordering being the dominant form in most cases. Thermal treatment in vacuum, wet and dry hydrogen, and CO(2) suggests that both forms contain defects (Ca(Ta)(''') and V(O)(··)), allowing the material to absorb water and CO(2). The uptake and the release of H(2)O and of CO(2) are all reversible, as evidenced by x-ray diffraction studies and thermal analysis, suggesting that the molecules are present as structural defects (OH(O)(·) and CO(3O)(×)), rather than surface species or separate hydroxide or carbonate phases. Solid state (1)H nuclear magnetic resonance also confirms the presence of protons, and the peak broadening suggests that they are mobile at room temperature. PMID:21613698

  7. Deformation effects on isospin mixing and isobar analogue resonance for 74-80Kr isotopes

    NASA Astrophysics Data System (ADS)

    Aygör, Hasan; Ünlü, Serdar; Çakmak, Neçla; Selam, Cevat

    2014-07-01

    Pyatov's method has been applied to investigate Fermi beta transitions in deformed 74-80Kr isotopes. This self-consistent method, which was used to study the isobar analogue states in the spherical odd-odd nuclei, has to date not been applied for the isobar analogue states in deformed nuclei. The nucleon-nucleon residual interaction has been included so that the broken isospin symmetry in the mean field approximation has been restored and the strength parameter of the effective interaction has been taken out to be a free parameter. The energies and wave functions of the isobaric analogue excitations in 74-80Rb isotopes have been obtained within the framework of the pnQRPA method. The probability of the isospin mixing in the ground states and the centroid energies of the isobar analogue resonance have been presented and the deformation effects on these quantities have been quantified.

  8. Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro

    NASA Astrophysics Data System (ADS)

    Dechristopher, Brian A.; Loy, Brian A.; Marsden, Matthew D.; Schrier, Adam J.; Zack, Jerome A.; Wender, Paul A.

    2012-09-01

    Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues using a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current clinical candidate for latent virus induction. This study provides the first demonstration that designed, synthetically accessible bryostatin analogues could serve as superior candidates for the eradication of HIV/AIDS through induction of latent viral reservoirs in conjunction with current antiretroviral therapy.

  9. PM2.5 Indoor Air Quality at Two Sites in London Ontario - A Case Study

    NASA Astrophysics Data System (ADS)

    Mates, A. V.; Xu, X.; Gilliland, J.; Maltby, M. J.

    2010-12-01

    Studies have shown an association between ambient fine particulate matter (PM2.5) and health impacts, particularly for the elderly and children. As part of a larger study, PM2.5 concentrations were measured using the DustTrak (Model 8520, TSI, St. Paul, MN, USA) at two schools within the city of London, Ontario (Canada). Site A was in a suburban environment while site B was in an urban setting. Monitoring took place for 3 weeks during winter (Feb. 16 - Mar. 8) and 3 weeks during spring (May 05 - 25) of 2010. The winter campaign monitored indoor PM2.5 only, while the spring campaign added outdoor monitors (PM2.5 and CO2) after the first week. Ten min. concentrations were used for analysis. Indoor measurements were split into weekday and weekend. For the same time interval, the outdoor concentrations showed mean values of 18 and 21 ?g/m3 for sites A & B, respectively, both under the Canada Wide Standard of 30 ?g/m3. Measurements at the two sites showed good associations (R^2 = 0.44), during the spring campaign. This indicates that the outdoor PM2.5 had similar sources. For indoor concentrations, Site B showed a significantly different mean concentration 5 times higher compared to site A during the winter ( 8.1 vs. 1.5 ?g/m3 ) and 3 times higher (11.9 vs. 3.7 ?g/m3) during the spring campaign. Since the outdoor concentrations were similar the large difference in indoor concentrations could be attributed to the following factors: site B being an older building, and the different physical characteristics between the two sites. The spring measurements showed an increase of 50% from weekday to weekend for site A and 22% for site B. The higher level of PM2.5 during weekends is possibly due to the infiltration of outdoor air while the ventilation/filtration system is shut off. During the winter campaign, Site A showed a 14% higher concentration during weekdays compared to weekends while site B weekend concentrations were 17% higher compared to weekday, which will be further investigated. The CO2 levels will be analyzed for the effect of outdoor air infiltration. The weekday data will be further split into activity and non-activity hours to explore the PM2.5 concentration increases associated with activity.

  10. Web-site-based recruitment for research studies on abdominal aortic and intracranial aneurysms.

    PubMed

    Salkowski, A; Tromp, G; Greb, A; Womble, D; Kuivaniemi, H

    2001-01-01

    Our current understanding on the pathogenesis of abdominal aortic and intracranial aneurysms is limited, but genetic and environmental factors as well as their interactions are likely to play important roles in the development and rupture of aneurysms. To identify genetic factors contributing to these diseases, we are carrying out genome-wide screening studies, which require a large number of patients and family members. Current methods of finding patients who qualify for genetic studies are, however, often costly and ineffective. To improve patient recruitment, a Web site was developed (cmmg.biosci.wayne.edu/ags). The site gives general information about our study, solicits participation into the study, and provides links to relevant medical and educational sites. During the time period of July, 1999, to December, 2000, the site received 5, 108 visits (13 visits/day). Approximately 20 research study applications are received each month. A total of 49% (57/117) of the individuals responding to the aortic aneurysm and 63% (84/134) responding to the intracranial aneurysm study report at least two affected blood relatives in the family and, therefore, qualify for our genetic studies. In conclusion, Web-based patient recruitment is successful and provides an improved success rate due to the fact that the responders are more motivated to participate in research studies. PMID:11960575

  11. Why people use social networking sites: An empirical study integrating network externalities and motivation theory

    Microsoft Academic Search

    Kuan-Yu Lin; Hsi-Peng Lu

    2011-01-01

    Fast-developing social networking sites (SNS) have become the major media by which people develop their personal network online in recent years. To explore factors affecting user’s joining SNS, this study applies network externalities and motivation theory to explain why people continue to join SNS. This study used an online questionnaire to conduct empirical research, and collected and analyzed data of

  12. Information revelation and internet privacy concerns on social network sites: a case study of facebook

    Microsoft Academic Search

    Alyson L. Young; Anabel Quan-Haase

    2009-01-01

    Despite concerns raised about the disclosure of personal information on social network sites, research has demonstrated that users continue to disclose personal information. The present study employs surveys and interviews to examine the factors that influence university students to disclose personal information on Facebook. Moreover, we study the strategies students have developed to protect themselves against privacy threats. The results

  13. Professional-Patron Influence on Site-Based Governance Councils: A Confounding Case Study.

    ERIC Educational Resources Information Center

    Malen, Betty; Ogawa, Rodney T.

    1988-01-01

    A case study of site-based governance councils in Salt Lake City (Utah) is described. The study was a test of whether building-based councils actually enable teachers and parents to exert substantial influence on school policy. The reason why research findings did not fit expectations is discussed. (SLD)

  14. Spectral study of suggested Apollo sites. [proposals for financial support and the electronic spectra of pyroxenes

    NASA Technical Reports Server (NTRS)

    Mccord, T. B.

    1973-01-01

    The spectrophotometry (0.3 to 1.1 microns) of visited and proposed Apollo landing sites is presented along with proposals for financial support of the spectral study. The electronic spectra of pyroxenes is investigated along with an interpretation of telescopic spectral reflectivity curves of the moon. Reprints of published articles related to these studies are included.

  15. Preliminary 3-D site-scale studies of radioactive colloid transport in the unsaturated zone at

    E-print Network

    Hu, Qinhong "Max"

    Preliminary 3-D site-scale studies of radioactive colloid transport in the unsaturated zone investigate, by means of numerical simulation, the transport of radioactive colloids under ambient conditions. The study of migration and retardation of colloids accounts for the complex processes in the unsaturated

  16. Specific binding of (/sup 3/H)LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

    SciTech Connect

    Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

    1989-05-01

    LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for (/sup 3/H)LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound (/sup 3/H)LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that (/sup 3/H)LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs.

  17. Electrical studies at the proposed Wahmonie and Calico Hills nuclear waste sites, Nevada Test Site, Nye Co., Nevada

    Microsoft Academic Search

    D. B. Hoover; M. P. Chornack; K. H. Nervick; M. M. Broker

    1982-01-01

    These two sites in the southwest quadrant of NTS were investigated as potential repositories for high-level nuclear waste. The emplacement medium at both sites was to be an inferred intrusive body at shallow depth; the inference of the presence of the body was based on aeromagnetic and regional gravity data. This report summarizes results of Schlumberger VES, induced polarization dipole-dipole

  18. U.S. Department of Energy remediation and restoration of radioactive sites: Project chariot case study

    SciTech Connect

    Hopkins, A.; Mayasich, S.A. [International Technology Corp., Las Vegas, NV (United States); Wright, S.J. [Alaska Dept. of Natural Resources, Palmer, AK (United States); Hanson, W.C. [Hanson Environmental Research Services, Bellingham, WA (United States); Cabble, K.J. [Dept. of Energy, Las Vegas, NV (United States)

    1994-12-31

    The Project Chariot Site in the Cape Thompson Region of northwest Alaska was studied under the US Atomic Energy Commission`s Plowshare Program between 1958 and 1962 to determine environmental conditions and background radiation levels. Although no nuclear explosives were ever brought to the site, radioactive tracer studies were conducted by the US Geological Survey in 1962. The US Department of Energy took action to remediate the site in response to the concerns of local inhabitants. The remediation in July--August, 1993 involved sampling the environment for possible contamination, removing contaminated soils, and revegetating the disturbed tundra. Contaminated soil was excavated, packaged, and transported to the Nevada Test Site for disposal. Surface water, soil and sediment from surrounding areas and samples of small mammals, caribou, and vegetation were analyzed for radioisotopes. These results showed that the past risk to human health from site contamination was well within acceptable ranges. No unusual amounts of radioisotopes were detected in the biota. The site was successfully remediated, and no future risk to human health or the environment is expected. Disturbed areas were reseeded and fertilized, and Curlex Excelsior{trademark} blankets were used to keep soil in place. Results of reseeding and natural vegetation recovery were assessed one year after remediation.