Science.gov

Sample records for analogue study sites

  1. Analogue Study of Actinide Transport at Sites in Russia

    SciTech Connect

    Novikov, A P; Simmons, A M; Halsey, W G

    2003-02-12

    The U. S. Department of Energy (DOE) and the Russian Academy of Sciences (RAS) are engaged in a three-year cooperative study to observe the behavior of actinides in the natural environment at selected disposal sites and/or contamination sites in Russia. The purpose is to develop experimental data and models for actinide speciation, mobilization and transport processes in support of geologic repository design, safety and performance analyses. Currently at the mid-point of the study, the accomplishments to date include: evaluation of existing data and data needs, site screening and selection, initial data acquisition, and development of preliminary conceptual models.

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

    SciTech Connect

    Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko

    2012-09-06

    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-ζ 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-xyl)2]0/1-/2-, and Na+[Fe(S2-oxyl) 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.

  3. 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.

  4. 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.

  5. Theoretical study on the reactive sites and intramolecular interactions in taxol and its four analogues

    NASA Astrophysics Data System (ADS)

    Zhou, Hongwei; Zhang, Zhiqiang; Cheung, Hon-Yeung

    A density-functional study of the paclitaxel (Taxol) molecule and its four analogues has been performed. The theory of Bader's atoms in molecules (AIM) was applied to examine the electronic structure of these molecules at their ground state. Topological analysis reveals that the esterification of hydroxyl group attached to the oxetane ring results in great change of conformation of the taxane ring, and thus is responsible for bioactivity of the oxetane oxygen atom. It was found that there exists some intramolecular interactions in the molecule, including normal hydrogen bonds (HBs) and double HBs. Visualization of the molecule shows that the central bodies (the four fused rings) of the molecules are wrapped by the intramolecular interactions. It is supposed that these intramolecular interactions lower the aqueous solubility and protect the flexible oxetane ring, which is regarded as the dominating bioactivity site of the drug, from being opened. Our results provide an extended and consistent set of data to gauge classical force fields in view of the atomistic investigations of the interaction of the bioactive molecules.

  6. Combined Quantum Chemistry and Photoelectron Spectroscopy Study of the Electronic Structure and Reduction Potentials of Rubredoxin Redox Site Analogues

    SciTech Connect

    Niu, Shuqiang; Wang, Xue B.; Nichols, J. A.; Wang, Lai S.; Ichiye, Toshiko

    2003-04-24

    Iron-sulfur proteins are an important class of electron carriers in a wide variety of biological reactions. Determining the intrinsic contribution of the metal site to the redox potential is crucial in understanding how the protein environment influences the overall redox properties of the Fe-S proteins. Here we combine density functional theory and coupled cluster methods with photodetachment spectroscopy to study the electronic structures and gas-phase redox potentials of the [Fe(SCH3)(4)](2-/-/0) and [Fe(SCH3)(3)](-/0) analogues of the rubredoxin redox site. The calculations show that oxidations of [Fe(SCH3)(4)](2-) and [Fe(SCH3)(4)](-) involve mainly the Fe 3d and S 3p orbitals, respectively. The calculated adiabatic and vertical detachment energies are in good agreement with the experiment for [Fe(SCH3)(3)](-) and [Fe(SCH3)(4)](-). The current results further confirm the "inverted level scheme" for the high-spin [1Fe] systems. The redox couple, [Fe(SCH3)(4)](- /2), which is the one found in rubredoxin, but cannot be accessed experimentally in the gas phase, was investigated using a thermodynamic cycle that relates it to the [Fe(SCH3)(3)](-/0) couple and the ligand association reaction, [Fe(SCH3)(3)](0/-) + SCH3- --> [Fe(SCH3)(4)](-/2-). The calculated reduction energy of [Fe(SCH3)(4)](-) (1.7 eV) compares well with the value (1.6 eV) estimated from the calculated bond energies and the experimental detachment energy of [Fe(SCH3)(3)](-). Thus, this thermodynamic cycle method can be used to estimate metal-ligand bonding energies and determine intrinsic reduction potentials from photodetachment experiments when the reduced forms are not stable in the gas phase.

  7. 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

  8. The Canadian Analogue Research Network (CARN): Opportunities for Terrestrial Analogue Studies in Canada and Abroad

    NASA Astrophysics Data System (ADS)

    Hipkin, V.; Osinski, G. R.; Berinstain, A.; Léveillé, R.

    2007-03-01

    We will present an overview of the Canadian Analogue Research Network (CARN), including a description of the various analogue sites in CARN, potential new sites, and a discussion regarding how CARN is applicable to the global exploration strategy.

  9. 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

  10. Analogue Sites for Mars Missions - A report from two workshops

    NASA Astrophysics Data System (ADS)

    Hipkin, V.; Voytek, M. A.; Glamoclija, M.

    2014-12-01

    Fieldwork, at terrestrial sites that are analogous in some way to Mars, has a key role in defining questions addressed by Mars missions. For MSL, the question is whether its landing site was habitable, and for Mars 2020, the question is how do we search for and what are signs of life in ancient habitable environments. Implementing these investigations by means of a rover mission on a distant planetary surface has challenges due to a limited set of tools and period of operations. Using this context of planetary missions is important in shaping how analog research can be used to advance planetary science. Following a successful 2010 AGU fall meeting session entitled "Analogue Sites for Mars Missions", two community workshops were held at The Woodlands, TX March 2011 and the Carnegie Institute of Washington in July 2013. These activities represent an ongoing dialogue with the analogue and mission communities. The AGU session solicited presentations of current analogue research relevant to MSL, at which time the landing site selection process was still considering four final sites. The 2011 Woodlands workshop solicited details on representative science questions and analogue sites by means of an abstract template. The output from The Woodlands workshop was an initial metric to assess the utility of analogue sites against specific science questions, as well as recommendations for future activities. The 2013 Carnegie workshop, followed up on some of the recommendations from 2011. Both on-line interactive dialogue and in person discussions targeted broad topics, including 'the advantages and problems of using a great terrestrial analog for field testing', and 'knowing what we currently do about Mars, what would be the best place on the planet to collect the first suite of samples to be returned to Earth? What would be appropriate analog sites on Earth?'. The results and recommendations from both workshops are summarized to publicize and stimulate this ongoing discussion.

  11. Space analogue studies in Antarctica.

    PubMed

    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.

  12. 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.

  13. 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.

  14. The Canadian Analogue Research Network (CARN): Opportunities for Mars Analogue Studies in the Canadian Arctic

    NASA Astrophysics Data System (ADS)

    Osinski, G. R.; Berinstain, A.; Lebeuf, M.; Léveillé, R.

    2006-10-01

    The Canadian Analogue Research Network has been established by the Canadian Space Agency. This network of analogue sites, many of which are in the Arctic, provides a unique opportunity to further our understanding of the polar regions of Earth and Mars.

  15. Using fuzzy sets for data interpretation in natural analogue studies

    SciTech Connect

    De Lemos, F.L.; Sullivan, T.; Hellmuth, K.H.

    2008-07-01

    Natural analogue studies can play a key role in deep geological radioactive disposal systems safety assessment. These studies can help develop a better understanding of complex natural processes and, therefore, provide valuable means of confidence building in the safety assessment. In evaluation of natural analogues, there are, however, several sources of uncertainties that stem from factors such as complexity; lack of data; and ignorance. Often, analysts have to simplify the mathematical models in order to cope with the various sources of complexity and this ads uncertainty to the model results. The uncertainties reflected in model predictions must be addressed to understand their impact on safety assessment and therefore, the utility of natural analogues. Fuzzy sets can be used to represent the information regarding the natural processes and their mutual connections. With this methodology we are able to quantify and propagate the epistemic uncertainties in both processes and, thereby, assign degrees of truth to the similarities between them. An example calculation with literature data is provided. In conclusion: Fuzzy sets are an effective way of quantifying semi-quantitative information such as natural analogues data. Epistemic uncertainty that stems from complexity and lack of knowledge regarding natural processes are represented by the degrees of membership. It also facilitates the propagation of this uncertainty throughout the performance assessment by the extension principle. This principle allows calculation with fuzzy numbers, where fuzzy input results in fuzzy output. This may be one of the main applications of fuzzy sets theory to radioactive waste disposal facility performance assessment. Through the translation of natural data into fuzzy numbers, the effect of parameters in important processes in one site can be quantified and compared to processes in other sites with different conditions. The approach presented in this paper can be extended to

  16. 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.

  17. 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

  18. Site-specific and regiospecific installation of methylarginine analogues into recombinant histones and insights into effector protein binding.

    PubMed

    Le, Daniel D; Cortesi, Arianna T; Myers, Samuel A; Burlingame, Alma L; Fujimori, Danica Galonić

    2013-02-27

    Arginine methylation has emerged as a widespread post-translational modification with influence over myriad cellular processes. However, the molecular mechanisms underlying such methylarginine-dependent phenomena remain unclear. To aid in this research, a facile method was developed to install methylarginine analogues on recombinant protein for use in biochemical, biophysical, and structural studies. Through chemical conjugation of novel α,β-unsaturated amidine precursors with proteins, methylarginine mimics can be displayed with control of methylation site, extent, and regiospecificity. Analogue installation into histones using this strategy produced modified proteins that were recognized by antibodies specific to endogenous methylarginine, and these histones retained the capacity to form mononucleosomes. Moreover, a native methylarginine-specific binding domain was shown to interact with methylarginine analogue-modified substrates. This chemical conjugation method for installing methylarginine analogues provides an efficient route to produce homogeneous modified proteins for subsequent investigations of methylarginine-dependent processes.

  19. 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.

  20. 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

  1. A neurosteroid analogue photolabeling reagent labels the colchicine binding site on tubulin: A mass spectrometric analysis

    PubMed Central

    Chen, Zi-Wei; Chen, Li-Hai; Akentieva, Natalia; Lichti, Cheryl F.; Darbandi, Ramin; Hastings, Randy; Covey, Douglas F.; Reichert, David E.; Townsend, R. Reid; Evers, Alex S.

    2013-01-01

    Previous studies have shown that the neurosteroid analogue, 6-Azi-pregnanolone (6-AziP), photolabels voltage-dependent anion channels and proteins of approximately 55 kDa in rat brain membranes. The present study used two dimensional electrophoresis and nano-electrospray ionization ion trap mass spectrometry (nano-ESI-MS) to identify the 55 kDa proteins (pI 4.8) as isoforms of β-tubulin. This identification was confirmed by immuno-blot and immunoprecipitation of photolabeled protein with anti-β-tubulin antibody and by the demonstration that 6-AziP photolabels purified bovine brain tubulin in a concentration-dependent pattern. To identify the photolabeling sites, purified bovine brain tubulin was photolabeled with 6-AziP, digested with trypsin, and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI). A 6-AziP adduct of TAVCDIPPR (m/z=1287.77), a β-tubulin specific peptide, was detected by MALDI. High resolution LC-MS/MS analysis identified that 6-AziP was covalently bound to cysteine 354 (Cys-354), previously identified as a colchicine binding site. 6-AziP photolabeling was inhibited by 2-methoxyestradiol, an endogenous derivative of estradiol thought to bind to the colchicine site. Structural modeling predicted that neurosteroids could dock in this colchicine site at the interface between α- and β-tubulin with the photolabeling group of 6-AziP positioned proximate to Cys-354. PMID:22451060

  2. A readily synthesized cyclic pyrrolysine analogue for site-specific protein "click" labeling.

    PubMed

    Hao, Ziyang; Song, Yanqun; Lin, Shixian; Yang, Maiyun; Liang, Yujie; Wang, Jing; Chen, Peng R

    2011-04-21

    A concise route was developed for the facile synthesis of a cyclic pyrrolysine analogue bearing an azide handle. Directed evolution enabled the encoding of this non-natural amino acid in both prokaryotic and eukaryotic cells, which offers a highly efficient approach for the site-specific protein labeling using click chemistry.

  3. 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.

  4. 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

  5. Theoretical study on absorption and emission spectra of adenine analogues.

    PubMed

    Liu, Hongxia; Song, Qixia; Yang, Yan; Li, Yan; Wang, Haijun

    2014-04-01

    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 four adenine analogues (termed as A1, A2, A3, and A4), and also consider the effects of aqueous solution and base pairing. The results show that the fluorescent adenine analogues can pair with thymine to form stable H-bonded WC base pairs. The excited geometries of both adenine analogues and WC base pairs are similar to the ground geometries. The absorption and emission maxima of adenine analogues are greatly red shifted compared with nature adenine, the oscillator strengths of A1 and A2 are stronger than A3 and A4 in both absorption and emission spectra. The calculated low-energy peaks in the absorption spectra are in good agreement with the experimental data. In general, the aqueous solution and base pairing can slightly red-shift both the absorption and emission maxima, and can increase the oscillator strengths of absorption spectra, but significantly decrease the oscillator strengths of A3 in emission spectra.

  6. 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…

  7. Heterogeneous seepage at the Nopal I natural analogue site, Chihuahua, Mexico

    SciTech Connect

    Dobson, Patrick F.; Cook, Paul J.; Ghezzehei, Teamrat A.; Rodriguez, J. Alfredo; Villalba, Lourdes; de la Garza, Rodrigo

    2008-10-25

    An integrated field, laboratory, and modeling study of the Pena Blanca (Chihuahua, Mexico) natural analogue site is being conducted to evaluate processes that control the mobilization and transport of radionuclides from a uranium ore deposit. One component of this study is an evaluation of the potential for radionuclide transport through the unsaturated zone (UZ) via a seepage study in an adit at the Nopal I uranium mine, excavated 10 m below a mined level surface. Seasonal rainfall on the exposed level surface infiltrates into the fractured rhyolitic ash-flow tuff and seeps into the adit. An instrumented seepage collection system and local automated weather station permit direct correlation between local precipitation events and seepage within the Nopal I +00 adit. Monitoring of seepage within the adit between April 2005 and December 2006 indicates that seepage is highly heterogeneous with respect to time, location, and quantity. Within the back adit area, a few zones where large volumes of water have been collected are linked to fast flow path fractures (0-4 h transit times) presumably associated with focused flow. In most locations, however, there is a 1-6 month time lag between major precipitation events and seepage within the adit, with longer residence times observed for the front adit area. Seepage data obtained from this study will be used to provide input to flow and transport models being developed for the Nopal I hydrogeologic system.

  8. Natural analogue studies: present status and performance assessment implications

    NASA Astrophysics Data System (ADS)

    Smellie, John A. T.; Karlsson, Fred; Alexander, W. Russell

    1997-04-01

    Studies of natural geological and archaeological systems as analogues to long-term processes, which are predicted to occur within a radioactive waste repository environment, have become increasingly popular over the last 10 years or so, to the extent that such studies form an integral part of many national programmes for radioactive waste disposal. There is now a common consensus that the natural analogue approach is a very useful scientific methodology to: (a) identify and understand processes and mechanisms analogous to those which could occur in the vicinity of a repository over realistic timescales, (b) derive input data which have been successfully used to test some of the laboratory-based models which form the basis of long-term repository performance assessment, and (c) to produce data which can be input directly to performance assessment models. Increasingly, analogues are playing an important role in public awareness, enabling the layman to understand better the concept of radioactive disposal and demonstrating the reliability of the disposal system over long periods of geological time. The complexity of geological systems means that it is very often difficult and sometimes impossible to quantify precisely the physico-chemical boundary conditions necessary to model a particular geochemical process or mechanism. Consequently, the availability of quantitative analogue data is limited when repository performance assessments are considered. However, this in no way detracts from their value in building confidence by demonstrating that important processes do exist and by showing qualitatively that they behave in a way predicted by models based on laboratory-derived data. The transfer of natural analogue data from the complexity of field studies to simplistic models which, by necessity, are used in performance assessments, is an area of activity which is presently being addressed. Field analogue studies are now being planned to interface with laboratory

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

    SciTech Connect

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Mukhopadhyay, R.; Juranyi, Fanni

    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.

  10. Natural analogues for CO2 storage sites - analysis of a global dataset

    NASA Astrophysics Data System (ADS)

    Miocic, Johannes; Gilfillan, Stuart; McDermott, Christopher; Haszeldine, R. Stuart

    2013-04-01

    Carbon Capture and Storage is the only industrial scale technology currently available to reduce CO2 emissions from fossil-fuelled power plants and large industrial source to the atmosphere and thus mitigate climate change. CO2 is captured at the source and transported to subsurface storage sites, such as depleted oil and gas fields or saline aquifers. In order to have an effect on emissions and to be considered safe it is crucial that the amount of CO2 leaking from storage sites to shallow aquifers or the surface remains very low (<1% over 1000 years). Some process that influence the safety of a reservoir, such as CO2-rock-brine interactions, can be studied using experiments on both laboratory and field-scale. However, long-term processes such as the development of leakage pathways can only be understood by either predictive modelling or by studying natural CO2 reservoirs as analogues for long term CO2 storage sites. Natural CO2 reservoirs have similar geological trapping mechanisms as anticipated for CO2 storage sites and often have held CO2 for a geological period of time (millions of years) without any indication for leakage. Yet, migration of CO2 from reservoirs to the surface is also common and evidenced by gas seeps such as springs and soil degassing. We have compiled and analysed a dataset comprising of more than 50 natural CO2 reservoirs from different settings all around the globe to provide an overview of the factors that are important for the retention of CO2 in the subsurface and what processes lead to leakage of CO2 from the reservoir. Initial results indicate that if the reservoir is found to be leaking, CO2 migration is along faults and not through caprock layers. This indicates that faults act as fluid pathways and play an important role when characterizing a storage site. Additionally, it appears that overpressure of the overburden and the state of CO2 in the reservoir influence the likelihood of migration and hence the safety of a reservoir.

  11. Police Applicant Screening: An Analogue Study.

    ERIC Educational Resources Information Center

    Costello, Raymond M.; And Others

    1982-01-01

    Studied the effect of different base rates of a target phenomenon on psychometric efficiency when an explicit decision-making rule was used to evaluate police officers. Concluded that numerous predictive indices would be required to screen such a heterogeneous population. (Author/JAC)

  12. Laboratory studies of cometary ice analogues

    NASA Astrophysics Data System (ADS)

    Schmitt, B.; Espinasse, S.; Grim, R. J. A.; Greenberg, J. M.; Klinger, J.

    1989-12-01

    Laboratory studies were performed in order to simulate the physico-chemical processes that are likely to occur in the near surface layers of short and intermediate period comets. Pure H2O ice as well as CO:H2O, CO2:H2O, CH4:H2O, CO:CO2:H2O, and NH3:H2O ice mixtures were studied in the temperature range between 10 and 180 K. The evolution of the composition of ice mixtures, the crystallization of H2O ice as well as the formation and decompostion of clathrate hydrate by different processes were studied as a function of temperature and time. Using the results together with numerical modeling, predictions are made about the survival of amorphous ice, CO, CO2, CH4, and NH3 in the near surface layers of short period comets. The likeliness of finding clathrate and molecular hydrates is discussed. It is proposed that the analytical methods developed here could be fruitfully adapted to the analysis of returned comet samples.

  13. Confocal {mu}-XRF, {mu}-XAFS, and {mu}-XRD Studies of Sediment from a Nuclear Waste Disposal Natural Analogue Site and Fractured Granite Following a Radiotracer Migration Experiment

    SciTech Connect

    Denecke, Melissa A.; Brendebach, Boris; Rothe, Joerg; Simon, Rolf; Janssens, Koen; Nolf, Wout de; Vekemans, Bart; Falkenberg, Gerald; Somogyi, Andrea; Noseck, Ulrich

    2007-02-02

    Combined {mu}-XRF, {mu}-XAFS, and {mu}-XRD investigations of a uranium-rich tertiary sediment, from a nuclear repository natural analogue site, and a fractured granite bore core section after a column tracer experiment using a Np(V) containing cocktail have been performed. Most {mu}-XRF/{mu}-XAFS measurements are recorded in a confocal geometry to provide added depth information. The U-rich sediment results show uranium to be present as a tetravalent phosphate and that U(IV) is associated with As(V). Arsenic present is either As(V) or As(0). The As(0) forms thin coatings on the surface of pyrite nodules. A hypothesis for the mechanism of uranium immobilization is proposed, where arsenopyrite acted as reductant of ground water dissolved U(VI) leading to precipitation of less soluble U(IV) and thereby forming As(V). Results for the granite sample show the immobilized Np to be tetravalent and associated with facture material.

  14. 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

  15. Millimeter and Submillimeter Studies of Interstellar Ice Analogues

    NASA Astrophysics Data System (ADS)

    Mesko, AJ; Wagner, Ian C.; Smith, Houston Hartwell; Milam, Stefanie N.; Widicus Weaver, Susanna L.

    2015-06-01

    The chemistry of interstellar ice analogues has been a topic of great interest to astrochemists over the last 20 years. Currently, the models of interstellar chemistry feature icy-grain reactions as a primary mechanism for the formation of many astrochemical species as well as potentially astrobiologically-relevant complex organic molecules. This talk presents new spectral results collected by a millimeter and submillimeter spectrometer coupled to a vacuum chamber designed to study the sublimation or sputtered products of icy-grain reactions initiated by thermal-processing or photo-processing of interstellar ice analogues. Initial results from thermal desorption and UV photoprocessing experiments of pure water ice and water + methanol ice mixtures will be presented.

  16. 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

  17. 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 (△υ = 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.

  18. 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 δ13CCH4 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.

  19. Capsaicin and its analogues: structure-activity relationship study.

    PubMed

    Huang, X-F; Xue, J-Y; Jiang, A-Q; Zhu, H-L

    2013-01-01

    Capsaicin, the main ingredient responsible for the hot pungent taste of chilli peppers, is an alkaloid found in the Capsicum family. Capsaicin was traditionally used for muscular pain, headaches, to improve circulation and for its gastrointestinal protective effects. It was also commonly added to herbal formulations because it acts as a catalyst for other herbs and aids in their absorption. In addition, capsaicin and other capsaicinoid compounds showed strong evidence of having promising potential in the fight against many types of cancer. The mechanism of action of capsaicin has been extensively studied over the past decade. It has been established that capsaicin binds to the transient receptor potential vanilloid 1 receptor which was expressed predominantly by sensory neurons. And many analogues of capsaicin have been synthesized and evaluated for diverse bioactivities. In this review, we will attempt to summarize the biology and structure-activity relationship of capsaicinoids.

  20. Further studies on conformationally constrained tricyclic tropane analogues and their uptake inhibition at monoamine transporter sites: synthesis of (Z)-9-(substituted arylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes as a novel class of serotonin transporter inhibitors.

    PubMed

    Zhang, Ao; Zhou, Guochun; Hoepping, Alexander; Mukhopadhyaya, Jayanta; Johnson, Kenneth M; Zhang, Mei; Kozikowski, Alan P

    2002-04-25

    A novel series of conformationally constrained tricyclic tropane analogues, (Z)-9-(substituted arylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes, were prepared, and their abilities to inhibit high-affinity uptake of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) into rat brain nerve endings (synaptosomes) were evaluated. First, a systematic screening of a variety of different substituents on the phenyl ring indicated that the substitution pattern plays an important role in the monoamine transporter activity. Most compounds in this series possessed a very low activity at the DA transporter (DAT) but a good to excellent affinity for the 5-HT transporter (SERT). In the case of para-substituted phenyl analogues, the electronic character of the substituent did not affect uptake inhibition as dramatically as observed in some benztropine analogues. Among these compounds, the 4-bromophenyl and 4-isopropylphenyl analogues 8d and 8j exhibited the highest potency at the SERT with a K(i) value of 10 nM. In the 3,4-disubstituted phenyl series, even more potent and highly selective compounds were discovered. Compound 8o has a K(i) value of 2.3 nM for uptake inhibition at the SERT, a DAT/SERT uptake ratio of 2360, and a NET/SERT uptake ratio of 200. Compound 8p exhibited a K(i) value of 1.8 nM for uptake inhibition at the SERT, a DAT/SERT uptake ratio of 1740, and a NET/SERT uptake ratio of 151. These compounds are 3-4-fold more potent than the antidepressant medication fluoxetine, and the selectivities for SERT over DAT and NET are also better than those of fluoxetine. Second, a variety of functional modifications on the ester moiety were investigated. Substitution by other esters or amides as well as alkenes did not increase potency, while most of the acetates or benzoates (16-21, 23, and 24) and the ketone 28 exhibited significantly improved activity. A good hydrogen-bonding ability of the substituent is believed to be required for high activity. The most potent and

  1. Bacterial Motility As a Biosignature: Tests at Icy Moon Analogue Sites

    NASA Astrophysics Data System (ADS)

    Nadeau, J. L.; Lindensmith, C.; Deming, J. W.; Stocker, R.; Graff, E.; Serabyn, E.; Wallace, J. K.; Liewer, K.; Kuhn, J.

    2014-12-01

    Extraterrestrial life in our Solar System, if present, is almost certain to be microbial. Methods and technologies for unambiguous detection of living or extinct microorganisms are needed for life-detection missions to the Jovian and Saturnian moons, where liquid water is known to exist. Our research focuses specifically on microbial meaningful motion as a biosignature—"waving crowds" at the micron scale. Digital Holographic Microscopy (DHM) is an excellent tool for unambiguous identification of bacterial and protozoal swimming, even in the presence of turbidity, drift, and currents. The design of a holographic instrument with bacteria scale resolution was described in the previous talk. In this presentation, we will illustrate the design challenges for construction of a field instrument for extreme environments and space, and present plans for scientific investigations at analogue sites for the coming season. The challenges of creating a field instrument involve performance trade-offs, the ability to operate at extreme temperatures, and handling large volumes of data. A fully autonomous instrument without external cables or power is also desirable, and this is something that previous holographic instruments have not achieved. The primary issues for space exploration are identification of a laser and drive electronics that are qualified for the expected radiation environments of the moons around gas giant planets. Tests in Earth analogue environments will establish performance parameters as well as answer scientific questions that traditional microscopic techniques cannot. Specifically, we will visit a Greenland field site to determine whether or not microorganisms are motile within the brine-filled interior network of sea ice, and if they can be autonomously tracked using the instrument. Motility within the liquid phase of a frozen matrix has been hypothesized to explain how bacteria contribute to the biogeochemical signatures detected in ice, but observational

  2. Affinity labeling of hepatitis C virus replicase with a nucleotide analogue: identification of binding site.

    PubMed

    Manvar, Dinesh; Singh, Kamlendra; Pandey, Virendra N

    2013-01-15

    We have used an ATP analogue 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSBA) to modify HCV replicase in order to identify the ATP binding site in the enzyme. FSBA inactivates HCV replicase activity in a concentration-dependent manner with a binding stoichiometry of 2 moles of FSBA per mole of enzyme. The enzyme activity is protected from FSBA in the presence of rNTP substrates or double-stranded RNA template primers that do not support ATP as the incoming nucleotide but not in the presence of polyrU.rA(26). HPLC analysis of tryptic peptides of FSBA-modified enzyme revealed the presence of two distinct peptides eluted at 23 and 36 min; these were absent in the control. Further we noted that both peptides were protected from FSBA modification in the presence of Mg·ATP. The LC/MS/MS analysis of the affinity-labeled tryptic peptides purified from HPLC, identified two major modification sites at positions 382 (Tyr), and 491 (Lys) and a minor site at position 38 (Tyr). To validate the functional significance of Tyr38, Tyr382, and Lys491 in catalysis, we individually substituted these residues by alanine and examined their ability to catalyze RdRp activity. We found that both Y382A and K491A mutants were significantly affected in their ability to catalyze RdRp activity while Y38A remained unaffected. We further observed that both Y382A and K491A mutants were not affected in their ability to bind template primer but were significantly affected in their ability to photo-cross-link ATP in the absence or presence of template primer. PMID:23268692

  3. Nucleotide Excision Repair of Chemically Stabilized Analogues of DNA Interstrand Cross-Links Produced from Oxidized Abasic Sites

    PubMed Central

    2015-01-01

    Nucleotide excision repair is a primary pathway in cells for coping with DNA interstrand cross-links (ICLs). Recently, C4′-oxidized (C4-AP) and C5′-oxidized abasic sites (DOB) that are produced following hydrogen atom abstraction from the DNA backbone were found to produce ICLs. Because some of the ICLs derived from C4-AP and DOB are too unstable to characterize in biochemical processes, chemically stable analogues were synthesized [Ghosh, S., and Greenberg, M. M. (2014) J. Org. Chem.79, 5948–5957]. UvrABC incision of DNA substrates containing stabilized analogues of the ICLs derived from C4-AP and DOB was examined. The incision pattern for the ICL related to the C4′-oxidized abasic site was typical for UvrABC substrates. UvrABC cleaved both strands of the substrate containing the C4-AP ICL analogue, but it was a poor substrate. UvrABC incised <30% of the C4-AP ICL analogue over an 8 h period, raising the possibility that this cross-link will be inefficiently repaired in cells. Furthermore, double-strand breaks were not detected upon incision of an internally labeled hairpin substrate containing the C4-AP ICL analogue. UvrABC incised the stabilized analogue of the DOB ICL more efficiently (∼20% in 1 h). Furthermore, the incision pattern was unique, and the cross-linked substrate was converted into a single product, a double-strand break. The template strand was exclusively incised on the template strand on the 3′-side of the cross-linked dA. Although the outcomes of the interaction between UvrABC and these two cross-linked substrates are different from one another, they provide additional examples of how seemingly simple lesions (C4-AP and DOB) can potentially exert significant deleterious effects on biochemical processes. PMID:25208227

  4. Nucleotide excision repair of chemically stabilized analogues of DNA interstrand cross-links produced from oxidized abasic sites.

    PubMed

    Ghosh, Souradyuti; Greenberg, Marc M

    2014-09-23

    Nucleotide excision repair is a primary pathway in cells for coping with DNA interstrand cross-links (ICLs). Recently, C4'-oxidized (C4-AP) and C5'-oxidized abasic sites (DOB) that are produced following hydrogen atom abstraction from the DNA backbone were found to produce ICLs. Because some of the ICLs derived from C4-AP and DOB are too unstable to characterize in biochemical processes, chemically stable analogues were synthesized [Ghosh, S., and Greenberg, M. M. (2014) J. Org. Chem. 79, 5948-5957]. UvrABC incision of DNA substrates containing stabilized analogues of the ICLs derived from C4-AP and DOB was examined. The incision pattern for the ICL related to the C4'-oxidized abasic site was typical for UvrABC substrates. UvrABC cleaved both strands of the substrate containing the C4-AP ICL analogue, but it was a poor substrate. UvrABC incised <30% of the C4-AP ICL analogue over an 8 h period, raising the possibility that this cross-link will be inefficiently repaired in cells. Furthermore, double-strand breaks were not detected upon incision of an internally labeled hairpin substrate containing the C4-AP ICL analogue. UvrABC incised the stabilized analogue of the DOB ICL more efficiently (~20% in 1 h). Furthermore, the incision pattern was unique, and the cross-linked substrate was converted into a single product, a double-strand break. The template strand was exclusively incised on the template strand on the 3'-side of the cross-linked dA. Although the outcomes of the interaction between UvrABC and these two cross-linked substrates are different from one another, they provide additional examples of how seemingly simple lesions (C4-AP and DOB) can potentially exert significant deleterious effects on biochemical processes.

  5. Multicomponent reactive transport in discrete fractures. II: Infiltration of hyperalkaline groundwater at Maqarin, Jordan, a natural analogue site

    NASA Astrophysics Data System (ADS)

    Steefel, C. I.; Lichtner, P. C.

    1998-08-01

    A numerical multicomponent reactive transport model described fully in Steefel and Lichtner (1998)[Steefel, C.I., Lichtner, P.C., 1998. Multicomponent reactive transport in discrete fractures, I. Controls on reaction front geometry. J. Hydrol. (in press)] is used to simulate the infiltration of hyperalkaline groundwater along discrete fractures at Maqarin, Jordan, a site considered as a natural analogue to cement-bearing nuclear waste repositories. In the Eastern Springs area at Maqarin, two prominent sets of sub-parallel fractures trending NW-SE are approximately perpendicular to the local water table contours, with the slope of the water table indicating north-westward flow. Extensive mineralogic investigations [Alexander W.R. (Ed.), 1992. A natural analogue study of cement-buffered, hyperalkaline groundwaters and their interaction with a sedimentary host rock. NAgrA Technical Report (NTB 91-10), Wettingen, Switzerland; Milodowski, A.E., Hyslop, E.K., Pearce, J.M., Wetton, P.D., Kemp, S.J., Longworth, G., Hodginson, E., and Hughes, C.R., 1998. Mineralogy and geochemistry of the western springs area. In: Smellie, J.A.T. (ed.), 1998: Maqarin Natural Analogue Study: Phase III. SKB Technical Report TR98-04, Stockholm, Sweden] indicate that the width of intense rock alteration zone bordering the fractures changes from about 4 mm at one locality (the M1 sampling site) to approximately 1 mm 100 m to the north-west in the flow direction (the M2 site), suggesting a lessening of alteration intensity in that direction. Using this information, the dimensionless parameter δ v/φ D' (φ=porosity, D'=effective diffusion coefficient in rock matrix, δ=fracture aperture, and v=fluid velocity in the fracture) and measurements of the local hydraulic head gradient and effective diffusion coefficient in the rock matrix, a mean fracture aperture of 0.194 mm is calculated assuming the cubic law applies. This information, in combination with measured groundwater compositions at the

  6. 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.

  7. Stability studies of a somatostatin analogue in biodegradable implants.

    PubMed

    Rothen-Weinhold, A; Besseghir, K; Vuaridel, E; Sublet, E; Oudry, N; Gurny, R

    1999-02-15

    In recent years, peptides and proteins have received much attention as drug candidates. For many polypeptides, particularly hormones, it is desirable to release the drug continuously at a controlled rate over a period of weeks or even months, and thus a controlled release system is needed. Polylactic acid (PLA) is a biocompatible and biodegradable material with wide utility for many applications, including the design of controlled release systems for pharmaceutical agents. Pharmaceutical development of these delivery systems presents new problems in the area of stability assessment, especially for peptide drugs. In this study, we aimed to investigate the influence of different steps, during the manufacturing of an implant, on peptide stability in the polymeric matrix. Polylactic acid implants containing vapreotide, a somatostatin analogue, were prepared by extrusion. The effects of time, extrusion and temperature on the peptide stability were studied. The influence of various gamma sterilization doses, as well as the conditions under which the implants were irradiated, were also investigated. Peptide stability in the polymeric matrix was evaluated at various temperatures and at various time intervals up to 9 months. PMID:10205641

  8. Co-Operative Human-Robotic Exploration of Lunar Analogue Sites

    NASA Astrophysics Data System (ADS)

    Francis, R.; Osinski, G. R.; Moores, J.; Barfoot, T.; Ilsr Team

    2012-03-01

    Operational capacity and performance comparison of lunar analogue missions using robot-only, astronaut-only, and joint robotic-astronaut mission architectures, at the Sudbury and Mistastin Lake impact structures in Canada.

  9. 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. )

    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.

  10. 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.

  11. Heterogeneous seepage at the Nopal I natural analogue site, Chihuahua, Mexico

    NASA Astrophysics Data System (ADS)

    Dobson, Patrick F.; Ghezzehei, Teamrat A.; Cook, Paul J.; Rodríguez-Pineda, J. Alfredo; Villalba, Lourdes; de La Garza, Rodrigo

    2012-02-01

    A study of seepage occurring in an adit at the Nopal I uranium mine in Chihuahua, Mexico, was conducted as part of an integrated natural analogue study to evaluate the effects of infiltration and seepage on the mobilization and transport of radionuclides. An instrumented seepage collection system and local automated weather station permit direct correlation between local precipitation events and seepage. Field observations recorded between April 2005 and December 2006 indicate that seepage is highly heterogeneous with respect to time, location, and quantity. Seepage, precipitation, and fracture data were used to test two hypotheses: (1) that fast flow seepage is triggered by large precipitation events, and (2) that an increased abundance of fractures and/or fracture intersections leads to higher seepage volumes. A few zones in the back adit recorded elevated seepage volumes immediately following large (>20 mm/day) precipitation events, with transit times of less than 4 h through the 8-m thick rock mass. In most locations, there is a 1-6 month time lag between the onset of the rainy season and seepage, with longer times observed for the front adit. There is a less clear-cut relation between fracture abundance and seepage volume; processes such as evaporation and surface flow along the ceiling may also influence seepage.

  12. Synthetic isoprenoid analogues for the study of prenylated proteins: Fluorescent imaging and proteomic applications.

    PubMed

    Wang, Yen-Chih; Distefano, Mark D

    2016-02-01

    Protein prenylation is a posttranslational modification catalyzed by prenyltransferases involving the attachment of farnesyl or geranylgeranyl groups to residues near the C-termini of proteins. This irreversible covalent modification is important for membrane localization and proper signal transduction. Here, the use of isoprenoid analogues for studying prenylated proteins is reviewed. First, experiments with analogues containing small fluorophores that are alternative substrates for prenyltransferases are described. Those analogues have been useful for quantifying binding affinity and for the production of fluorescently labeled proteins. Next, the use of analogues that incorporate biotin, bioorthogonal groups or antigenic moieties is described. Such probes have been particularly useful for identifying proteins that are naturally prenylated within mammalian cells. Overall, the use of isoprenoid analogues has contributed significantly to the understanding of protein prenlation.

  13. Compound Lava Flow Fields on Planetary Surfaces: Hawaiian Analogue Studies

    NASA Astrophysics Data System (ADS)

    Crown, D. A.; Byrnes, J. M.; Ramsey, M. S.

    2002-12-01

    Quantitative, process-oriented analyses of planetary volcanism have primarily been based on analogue studies of single-lobed lava flows emplaced as discrete units. Comparative analyses of compound lava flow fields on the Earth and terrestrial planets are being conducted in order to include volcanic styles characterized by complex distributary systems, stratigraphic relationships, and emplacement histories. Field observations, differential Global Positioning Systems (dGPS) measurements, and visible, thermal, and radar remote sensing are being used to characterize Hawaiian lava flow fields and develop techniques for analyses of planetary flow fields using datasets with high spatial and/or spectral resolution, such as MOC and THEMIS. These terrestrial studies allow flow field surface morphology, topography, and lava textures as well as detailed maps of distributary networks to be used to examine flow field growth and development. Information on flow field evolution is provided by delineating relationships between remote sensing signatures, surface morphology, and lava transport processes and by identifying input parameters for flowfield emplacement models. Investigations of the Mauna Ulu (1969-1974) and Puu Oo (1983-present) flow fields (Kilauea Volcano, HI) have focused on understanding the nature of distributary networks at various scales in order to determine spatial and temporal variations in lava transport. Initial work at Mauna Ulu has included analyses of 1) the distribution, network morphometry, and volumetric significance of lava channels in the medial zone of the flow field, and 2) the distribution, lava texture, and volumetric significance of breakouts from surface conduits and subsurface storage. Analyses of the temporal evolution of individual conduit systems provide the basis for interpretation of complex patterns of overlapping surface units that characterize local flow stratigraphy. Reconstruction of lava transport networks and relationships to surface

  14. 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

  15. 3CAPS – a structural AP–site analogue as a tool to investigate DNA base excision repair

    PubMed Central

    Schuermann, David; Scheidegger, Simon P.; Weber, Alain R.; Bjørås, Magnar; Leumann, Christian J.; Schär, Primo

    2016-01-01

    Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP–sites. With its 3′–phosphate replaced by methylene, the abasic site analogue 3CAPS was suggested to circumvent some of these limitations. Here, we evaluated the properties of 3CAPS in biochemical BER assays with mammalian proteins. 3CAPS-containing DNA substrates were processed by APE1, albeit with comparably poor efficiency. APE1-cleaved 3CAPS can be extended by DNA polymerase β but repaired only by strand displacement as the 5′–deoxyribophosphate (dRP) cannot be removed. DNA glycosylases physically and functionally interact with 3CAPS substrates, underlining its structural integrity and biochemical reactivity. The AP lyase activity of bifunctional DNA glycosylases (NTH1, NEIL1, FPG), however, was fully inhibited. Notably, 3CAPS-containing DNA also effectively inhibited the activity of bifunctional glycosylases on authentic substrates. Hence, the chemically stable 3CAPS with its preserved hemiacetal functionality is a potent tool for BER research and a potential inhibitor of bifunctional DNA glycosylases. PMID:26733580

  16. Natural analogue studies as supplements to biomineralization research

    SciTech Connect

    McNeil, M.B.

    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].

  17. 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

  18. Synthesis and study of new paramagnetic resveratrol analogues.

    PubMed

    Kálai, Tamás; Borza, Erzsébet; Antus, Csenge; Radnai, Balázs; Gulyás-Fekete, Gergely; Fehér, Andrea; Sümegi, Balázs; Hideg, Kálmán

    2011-12-15

    New resveratrol analogues containing five- and six-membered nitroxides and isoindoline nitroxides were synthesized. These new compounds were compared to resveratrol based on their ABTS radical scavenging ability as well on their capacity to suppress inflammatory process in macrophages induced by lipopolysaccharides. The ABTS and ROS scavenging activities of new molecules were the same or weaker than that of resveratrol, but some of paramagnetic resveratrol derivatives suppressed nitrite and TNFα production more efficiently than resveratrol. Based on these results the new nitroxide and phenol containing hybrid molecules can be considered as new antioxidant and anti-inflammatory agents.

  19. Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites.

    PubMed

    Wong, Michael H L; Bryan, Holly K; Copple, Ian M; Jenkins, Rosalind E; Chiu, Pak Him; Bibby, Jaclyn; Berry, Neil G; Kitteringham, Neil R; Goldring, Christopher E; O'Neill, Paul M; Park, B Kevin

    2016-03-24

    Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.

  20. Pyrrolidine analogues of lobelane: relationship of affinity for the dihydrotetrabenazine binding site with function of the vesicular monoamine transporter 2 (VMAT2).

    PubMed

    Vartak, Ashish P; Nickell, Justin R; Chagkutip, Jaturaporn; Dwoskin, Linda P; Crooks, Peter A

    2009-12-10

    Ring size reduction of the central piperidine ring of lobelane yielded pyrrolidine analogues that showed marked inconsistencies in their ability to bind to the dihydrotetrabenazine (DTBZ) binding site on the vesicular monoamine transporter-2 (VMAT2) and their ability to inhibit VMAT2 function. The structure-activity relationships indicate that structural modification within the pyrrolidine series resulted in analogues that interact with two different sites, i.e., the DTBZ binding site and an alternative site on VMAT2 to inhibit transporter function.

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

    PubMed

    DeGraw, Amanda J; Zhao, Zongbao; Strickland, Corey L; Taban, A Huma; Hsieh, John; Jefferies, Michael; Xie, Wenshuang; Shintani, David K; McMahan, Colleen M; Cornish, Katrina; Distefano, Mark D

    2007-06-22

    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 prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross-linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyl diphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics, photolabeling experiments, as well as X-ray crystallographic analysis with a protein prenyltransferase are described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this new analogue was explored by using it to photoaffinity label crude protein extracts obtained from Hevea brasiliensis latex. Those experiments suggest that a small protein, rubber elongation factor, interacts directly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as a substrate.

  2. Optimization of Spin-Unrestricted Density Functional Theory for Redox Properties of Rubredoxin Redox Site Analogues

    SciTech Connect

    Niu, Shuqiang; Nichols, Jeffery A.; Ichiye, Toshiko

    2009-05-01

    Systematic studies of the accuracy of density functional theory (DFT) methods, especially the recently developed hybrid generalized gradient approximation (GGA) functionals, for structural and energetic properties of iron-sulfur redox sites are essential before these methods can be used to answer important biological questions about these systems. Here, the geometries, electronic structures, and reduction potentials of redox site analogs of the iron-sulfur protein rubredoxin are investigated using DFT (B3LYP, B97gga1 and BHandH), the Moller-Plesset perturbation theory series (MP2, MP3, MP4SDQ), and coupled cluster (CCSD, CCSD(T)) methods. For the geometries of [Fe(SCH3)4]2-/1- and [Fe(SCH3)3]1-/0, the DFT optimizations give reasonable values and the inclusion of a core electron basis substantially reduces the errors in the calculated geometries. However, for the vertical detachment energy (VDE) and adiabatic detachment energy (ADE) of [Fe(SCH3)4]1- and [Fe(SCH3)3]1-, the B3LYP functional gives the most accurately computed ADE and VDE using DFT, which are comparable with those at the CCSD level of theory. When diffuse functions are added to the sulfur basis set, they have little effect on the geometry optimization but significantly improve the calculated VDE and ADE, which is important for the anionic reduced sites. When multiple polarization functions are added to the sulfur basis set, they lead to a slightly better description of the geometry by giving more angular flexibility but underestimate ADE and VDE, most likely due to overestimating the stabilizing energy of the oxidized sites. Overall, the B3LYP calculations with the more flexible full-core basis sets give a reasonable description both of the geometry and of the ADE and VDE. Thus, improving the basis sets seems to be an efficient and convenient way to obtain reliable reduction potentials of the high-spin iron-sulfur redox sites.

  3. Natural Analogue Synthesis Report

    SciTech Connect

    A. M. Simmons

    2002-05-01

    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 and 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

  4. Automated docking of monosaccharide substrates and analogues and methyl alpha-acarviosinide in the glucoamylase active site.

    PubMed

    Coutinho, P M; Dowd, M K; Reilly, P J

    1997-02-01

    Glucoamylase is an important industrial glucohydrolase with a large specificity range. To investigate its interaction with the monosaccharides D-glucose, D-mannose, and D-galactose and with the substrate analogues 1-deoxynojirimycin, D-glucono-1,5-lactone, and methyl alpha-acarviosinide, MM3(92)-optimized structures were docked into its active site using AutoDock 2.1. The results were compared to structures of glucoamylase complexes obtained by protein crystallography. Charged forms of some substrate analogues were also docked to assess the degree of protonation possessed by glucoamylase inhibitors. Many forms of methyl alpha-acarviosinide were conformationally mapped by using MM3(92), characterizing the conformational pH dependence found for the acarbose family of glucosidase inhibitors. Their significant conformers, representing the most common states of the inhibitor, were used as initial structures for docking. This constitutes a new approach for the exploration of binding modes of carbohydrate chains. Docking results differ slightly from x-ray crystallographic data, the difference being of the order of the crystallographic error. The estimated energetic interactions, even though agreeing in some cases with experimental binding kinetics, are only qualitative due to the large approximations made by AutoDock force field.

  5. A natural analogue for high-level waste in tuff: Chemical analysis and modeling of the Valles site

    SciTech Connect

    Stockman, H.W.; Krumhansl, J.L.; Ho, C.K.; Kovach, L.; McConnell, V.S.

    1995-03-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a high-level 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 40}Ar 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 m 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.

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

    SciTech Connect

    Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, Christopher J.; Turkenburg, Johan P.; Jiráček, Jiří; Brzozowski, Andrzej M.

    2014-10-01

    [AsnB26]- and [GlyB26]-insulin mutants attain a B26-turn like fold without assistance of chemical modifications. Their structures match the insulin receptor interface and expand the spectrum of insulin conformations. 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.

  7. Characterization and comparison of perezone with some analogues. Experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Escobedo-González, Rene Gerardo; Bahena, Luis; Arias Tellez, José Luis; Hinojosa Torres, Jaime; Ruvalcaba, Rene Miranda; Aceves-Hernández, Juan Manuel

    2015-10-01

    Perezone had been used for centuries in the traditional Mexican medicine, it is useful and a handful of illness. Perezone and other derivatives also present activity against certain lines of cancer, such as the myeloblastoid leukemia cell line K-562 and carcinoma cell lines (PC-3 and SKLU-1) with IC50 <10 μM. Perezone and isoperezone have shown the major cytotoxic potency. Characterization of perezone was carried out by UV-Visible, IR, DSC, TGA and powder X-ray diffraction, as well as docking studies using caspase-3 structures as receptors. Theoretical studies for optimizing the geometry of perezone were carried out and the results compared with values of single crystal X-ray diffraction. The experimental values of atomic distances, angles and dihedral angles are in good agreement with the theoretical values. Interaction of perezone with the cysteine catalytic site with the caspase-3 was found in the docking studies. A docking study of perezone, with horminone, thymoquinone and isoperezone as ligands and the protein apoptein, caspase-3 as receptor, was carried to demonstrate that the hindrance steric factor, chemical structure and the functional groups are important in the biological activity of these natural products. The docking score energetic values are in good agreement with the experimental cytotoxic results obtained from the experiments when perezone and analogues were studied in different types of cancer.

  8. 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.

  9. 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.

  10. 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...

  11. Mixed valence Creutz-Taube ion analogues incorporating thiacrowns: synthesis, structure, physical properties, and computational studies.

    PubMed

    Adams, Harry; Costa, Paulo J; Newell, Mike; Vickers, Steven J; Ward, Michael D; Félix, Vítor; Thomas, Jim A

    2008-12-15

    A series of nine new complexes incorporating [Ru(II)Cl([n]aneS(3))] (n = 12, 14, 16) metal centers bridged by three ditopic ligands containing two monodentate sites (pyrazine, 4,4'-bipyridine, and 3,6-bis(4-pyridyl)-1,2,4,5-tetrazine) have been synthesized and fully characterized. The solid-state structures of three of the complexes have been further characterized by X-ray crystallography studies. Intermetallic interactions within the new systems have been probed using electrochemistry and optical spectroscopy. Cyclic voltammetry reveals that the three pyrazine bridged systems display two separate Ru(III)/(II) redox couples. Using spectroelectrochemistry, we have investigated the optical properties of these mixed valence, Creutz-Taube ion analogues. An analysis of the intervalence charge transfer bands for the complexes revealed that, despite possessing the same donor sets, the electronic delocalization within these systems is modulated by the nature of the coordinated thiacrown. Computational modeling using density function theory offers further evidence of interaction between metal centers and provides insights into how these interactions are mediated. PMID:19012395

  12. Endo-S-c-di-GMP analogues-polymorphism and binding studies with class I riboswitch.

    PubMed

    Zhou, Jie; Sayre, David A; Wang, Jingxin; Pahadi, Nirmal; Sintim, Herman O

    2012-01-01

    C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become drug leads for the development of anti-biofilm compounds. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogues, which have both phosphate and sugar moieties simultaneously modified (called endo-S-c-di-GMP analogues). We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the polymorphism of c-di-GMP can be tuned with conservative modifications to the phosphate and sugar moieties (conformational steering). Binding studies with Vc2 RNA (a class I c-di-GMP riboswitch) revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class I riboswitch. PMID:23143150

  13. Perspective of Using the Results of Monitoring and Modeling of the Chernobyl Nuclear Power Plant's Cooling Pond as Analogue for the US DOE Contaminated Sites

    NASA Astrophysics Data System (ADS)

    Faybishenko, B.; Voitsekhovich, O. V.; Bugay, D.; Skalskjj, A.; Shestopalov, V. M.; Zheleznyak, M.; Kashparov, V. A.; Antropov, A. S.; Kireev, S. I.; Bondarkov, M. D.; Ivanov, Y.; Oskolkov, B.; Marra, J.; Jannik, T.; Farfan, E.; Monken-Fernandes, H.; Hinton, T.; Smith, J.; Onishi, Y.; Konoplev, A.

    2010-12-01

    Although there are many contaminated sites that may be suitable candidates for providing analogue information for the development and testing of environmental modeling and risk assessment approaches, of particular scientific and practical interests is the feasibility study of planned decommissioning and remediation of the highly contaminated Chernobyl Cooling Pond (CP), located within the Chernobyl Exclusion Zone (ChEZ). The presence of the CP has caused an artificially high groundwater table within the ChEZ. After the planned cessation of water pumping from the Pripyat River to the CP, substantial areas of sediments, containing 137Cs, 90Sr, and hot particles with U, Pu, and Am. will be exposed to the atmosphere, and the groundwater level is expected to decline by as much as 7 m. The areal extent of the exposed zone, the dissolution rate, mobility and bioavailability of radionuclides will vary over time, depending on the dynamics of seepage losses from the pond and climatic conditions. The objective of the presentation is to discuss hydrological and geochemical processes, a conceptual model, and the results and perspectives of numerical modeling of coupled surface water-groundwater flow and transport, including the parameter estimation and uncertainty evaluation for various decommissioning and remediation options of the CP. In particular, the results of 1D, 2D, and 3D simulations of radionuclide transport in surface water and groundwater will be discussed, along with the evaluation of Kd parameters from the results of field monitoring and modeling of seasonal variations of 137Cs concentrations in pond water and sediments. It will be shown that the results of field monitoring and modeling of the Chernobyl CP can be used as analogue for several US DOE sites to improve scientific and practical understanding of subsurface hydrological and geochemical processes, as well as to obtain a better understanding of processes affecting natural attenuation of radionuclides in

  14. Activation of multiple sites by adenosine analogues in the rat isolated aorta.

    PubMed Central

    Prentice, D. J.; Hourani, S. M.

    1996-01-01

    1. The presence of A2 receptors mediating relaxation in the rat isolated aorta has been previously demonstrated. However, agonist dependency of the degree of rightward shift elicited by 8-sulphophenyltheophylline (8-SPT) led to the suggestion that the population of receptors in this tissue is not a homogeneous one. In this study we have re-examined the effects of 8-SPT in the absence and presence of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) and investigated antagonism of responses by the potent A2a receptor ligands PD 115,199 (N-[2-dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3 dipropyl-1H-purin-8-yl)) benzene sulphonamidexanthine), ZM 241385 (4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol), and CGS 21680 (2-[p-(2-carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine). We have also investigated the antagonist effects of BWA1433 (1,3-dipropyl-8-(4-acrylate)phenylxanthine) which has been shown to have affinity at rat A3 receptors. 2. Adenosine, R-PIA (N6-R-phenylisopropyl adenosine), CPA (N6-cyclopentyladenosine) and NECA (5'-N-ethylcarboxamidoadenosine) all elicited relaxant responses in the phenylephrine pre-contracted rat isolated aorta with the following potency order (p[A50] values in parentheses): NECA (7.07 +/- 0.11) > R-PIA (5.65 +/- 0.10) > CPA (5.05 +/- 0.12) > adenosine (4.44 +/- 0.12). 3. 8-SPT (10-100 microM) caused parallel rightward shifts of the E/[A] curves to NECA (pKB = 5.23 +/- 0.16). A smaller rightward shift of E/[A] curves to CPA was observed (pA2 = 4.85 +/- 0.17). However, no significant shifts of E/[A] curves to either adenosine or R-PIA were observed. 4. In the absence of endothelium E/[A] curves to NECA and CPA were right-shifted compared to controls. However, removal of the endothelium did not produce a substantial shift of adenosine E/[A] curves, and E/[A] curves to R-PIA were unaffected by removal of the endothelium. 5. In the presence of L-NAME (100

  15. 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.

  16. 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.

  17. Isolation of a family of resistance gene analogue sequences of the nucleotide binding site (NBS) type from Lens species.

    PubMed

    Yaish, M W F; Sáenz de Miera, L E; Pérez de la Vega, M

    2004-08-01

    Most known plant disease-resistance genes (R genes) include in their encoded products domains such as a nucleotide-binding site (NBS) or leucine-rich repeats (LRRs). Sequences with unknown function, but encoding these conserved domains, have been defined as resistance gene analogues (RGAs). The conserved motifs within plant NBS domains make it possible to use degenerate primers and PCR to isolate RGAs. We used degenerate primers deduced from conserved motifs in the NBS domain of NBS-LRR resistance proteins to amplify genomic sequences from Lens species. Fragments from approximately 500-850 bp were obtained. The nucleotide sequence analysis of these fragments revealed 32 different RGA sequences in Lens species with a high similarity (up to 91%) to RGAs from other plants. The predicted amino acid sequences showed that lentil sequences contain all the conserved motifs (P-loop, kinase-2, kinase-3a, GLPL, and MHD) present in the majority of other known plant NBS-LRR resistance genes. Phylogenetic analyses grouped the Lens NBS sequences with the Toll and interleukin-1 receptor (TIR) subclass of NBS-LRR genes, as well as with RGA sequences isolated from other legume species. Using inverse PCR on one putative RGA of lentil, we were able to amplify the flanking regions of this sequence, which contained features found in R proteins.

  18. 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

  19. 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.

  20. Biological and quantitative-SAR evaluations, and docking studies of (E)-N -benzylidenebenzohydrazide analogues as potential antibacterial agents

    PubMed Central

    Alam, Mohammad Sayed; Jebin, Sefat; Rahman, M. Mostafizur; Bari, Md. Latiful; Lee, Dong-Ung

    2016-01-01

    A series of 15 (E)-N'-benzylidenebenzohydrazide analogues were evaluated for their antimicrobial activities against eleven pathogenic and food-borne microbes, namely, S. aureus (G+), L. monocytogenes (G+), B. subtilis (G+), K. pneumonia (G¯), C. sakazakii (G¯), C. freundii (G¯), S. enterica (G¯), S. enteritidis (G¯), E. coli (G¯), Y. pestis (G¯), and P. aeruginosa (G¯). Most of the compounds exhibited selective activity against some Gram-negative bacterial strains. Of the compounds tested (3a-o), 3b and 3g were most active against C. freundii (MIC = ~19 µg mL-1). Whereas, compounds 3d, 3i, 3k and 3n exhibited MIC values ranging from 37.5 to 75 μg mL-1 against C. freundii, and compounds 3e, 3l and 3n had MIC values of ~75 μg mL-1 against K. pneumonia. Quantitative structure-antibacterial activity relationships were studied using physicochemical parameters and a good correlation was found between calculated octanol-water partition coefficients (clogP; a lipophilic parameter) and antibacterial activities. In silico screening was also performed by docking high (3b and 3g) and low (3n) activity compounds on the active site of E. coli FabH receptor, which is an important therapeutic target. The findings of these in silico screening studies provide a theoretical basis for the design and synthesis of novel benzylidenebenzohydrazide analogues that inhibit bacterial FabH. PMID:27540348

  1. Biological and quantitative-SAR evaluations, and docking studies of (E)-N -benzylidenebenzohydrazide analogues as potential antibacterial agents.

    PubMed

    Alam, Mohammad Sayed; Jebin, Sefat; Rahman, M Mostafizur; Bari, Md Latiful; Lee, Dong-Ung

    2016-01-01

    A series of 15 (E)-N'-benzylidenebenzohydrazide analogues were evaluated for their antimicrobial activities against eleven pathogenic and food-borne microbes, namely, S. aureus (G(+)), L. monocytogenes (G(+)), B. subtilis (G(+)), K. pneumonia (G¯), C. sakazakii (G¯), C. freundii (G¯), S. enterica (G¯), S. enteritidis (G¯), E. coli (G¯), Y. pestis (G¯), and P. aeruginosa (G¯). Most of the compounds exhibited selective activity against some Gram-negative bacterial strains. Of the compounds tested (3a-o), 3b and 3g were most active against C. freundii (MIC = ~19 µg mL(-1)). Whereas, compounds 3d, 3i, 3k and 3n exhibited MIC values ranging from 37.5 to 75 μg mL(-1) against C. freundii, and compounds 3e, 3l and 3n had MIC values of ~75 μg mL(-1) against K. pneumonia. Quantitative structure-antibacterial activity relationships were studied using physicochemical parameters and a good correlation was found between calculated octanol-water partition coefficients (clogP; a lipophilic parameter) and antibacterial activities. In silico screening was also performed by docking high (3b and 3g) and low (3n) activity compounds on the active site of E. coli FabH receptor, which is an important therapeutic target. The findings of these in silico screening studies provide a theoretical basis for the design and synthesis of novel benzylidenebenzohydrazide analogues that inhibit bacterial FabH.

  2. Biological and quantitative-SAR evaluations, and docking studies of (E)-N -benzylidenebenzohydrazide analogues as potential antibacterial agents.

    PubMed

    Alam, Mohammad Sayed; Jebin, Sefat; Rahman, M Mostafizur; Bari, Md Latiful; Lee, Dong-Ung

    2016-01-01

    A series of 15 (E)-N'-benzylidenebenzohydrazide analogues were evaluated for their antimicrobial activities against eleven pathogenic and food-borne microbes, namely, S. aureus (G(+)), L. monocytogenes (G(+)), B. subtilis (G(+)), K. pneumonia (G¯), C. sakazakii (G¯), C. freundii (G¯), S. enterica (G¯), S. enteritidis (G¯), E. coli (G¯), Y. pestis (G¯), and P. aeruginosa (G¯). Most of the compounds exhibited selective activity against some Gram-negative bacterial strains. Of the compounds tested (3a-o), 3b and 3g were most active against C. freundii (MIC = ~19 µg mL(-1)). Whereas, compounds 3d, 3i, 3k and 3n exhibited MIC values ranging from 37.5 to 75 μg mL(-1) against C. freundii, and compounds 3e, 3l and 3n had MIC values of ~75 μg mL(-1) against K. pneumonia. Quantitative structure-antibacterial activity relationships were studied using physicochemical parameters and a good correlation was found between calculated octanol-water partition coefficients (clogP; a lipophilic parameter) and antibacterial activities. In silico screening was also performed by docking high (3b and 3g) and low (3n) activity compounds on the active site of E. coli FabH receptor, which is an important therapeutic target. The findings of these in silico screening studies provide a theoretical basis for the design and synthesis of novel benzylidenebenzohydrazide analogues that inhibit bacterial FabH. PMID:27540348

  3. Donor-site morbidity after fibula free flap transfer: a comparison of subjective evaluation using a visual analogue scale and point evaluation system.

    PubMed

    Vittayakittipong, P

    2013-08-01

    The aims of this study were: (1) to compare the visual analogue scale (VAS) with the point evaluation system (PES) in the subjective evaluation of donor-site morbidity after fibula free flap transfer; (2) to compare the functional outcomes of fibula free flap surgery between patients with a normal body mass index (BMI) and patients with a high BMI, and between skin paddle and non-skin paddle harvesting; and (3) to determine the correlation between functional outcomes and related factors. This study included 15 patients who underwent a vascularized fibula free flap transfer for oral and maxillofacial reconstruction. Demographic data, preoperative, intraoperative, and postoperative data were collected. Subjective self-evaluation of functional outcomes was done using a VAS followed by a PES. Comparison of the VAS and PES scores was assessed with Pearson's correlation coefficient. The statistical significance was set at P<0.05. The VAS score was significantly correlated with the PES score (r=0.63, P=0.01). The tourniquet times for the skin paddle group were longer than for the non-skin paddle group (P=0.02), while the satisfaction score of the non-skin paddle group was higher than that of the skin paddle group (P=0.03). The VAS is a potential option for the subjective evaluation of donor-site morbidity after fibula free flap transfer.

  4. Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues

    DOE PAGESBeta

    Pereira, Jose H.; Petchprayoon, Chutima; Hoepker, Alexander C.; Moriarty, Nigel W.; Fink, Sarah J.; Cecere, Giuseppe; Paterson, Ian; Adams, Paul D.; Marriott, Gerard

    2014-07-22

    The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region tomore » the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. In conclusion, structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.« less

  5. Structural and Biochemical Studies of Actin in Complex with Synthetic Macrolide Tail Analogues

    SciTech Connect

    Pereira, Jose H.; Petchprayoon, Chutima; Hoepker, Alexander C.; Moriarty, Nigel W.; Fink, Sarah J.; Cecere, Giuseppe; Paterson, Ian; Adams, Paul D.; Marriott, Gerard

    2014-07-22

    The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. In conclusion, structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.

  6. Dihydrogen activation by a diruthenium analogue of the Fe-only hydrogenase active site.

    PubMed

    Justice, Aaron K; Linck, Rachel C; Rauchfuss, Thomas B; Wilson, Scott R

    2004-10-20

    The photochemical reaction of Ru2(S2C3H6)(CO)4(PCy3)2 (1) and H2 gives the dihydride Ru2(S2C3H6)(mu-H)(H)(CO)3(PCy3)2 (2). NMR and crystallographic studies reveal mutually trans basal phosphine ligands and both bridging and terminal hydrides. Ru2(S2C2H4)(CO)4(PCy3)2 behaves similarly. Other HX substrates undergo photoaddition to 1, affording Ru2(S2C3H6)(mu-H)(X)(CO)3(PCy3)2 for X = OTs (3a), Cl (3b), and SPh (3c). Treatment of Ru2(S2C3H6)(mu-H)(H)(CO)3(PCy3)2 with [H(OEt2)]BArF4 (ArF = B(C6H3-3,5-(CF3)2) in CD2Cl2 gives [Ru2(S2C3H6)(mu-H)(CO)3(PCy3)2(H2)]+ (4), which catalyzes H2-D2 exchange. The reaction of 2 with [D(OEt2)]BArF4 gave [Ru2(S2C3H6)(mu-H)(CO)3(PCy3)2(HD)]+ (JH-D = 31 Hz). These studies provide the first models for the Fe-only hydrogenases that bear dihydrogen and terminal hydrido ligands. PMID:15479062

  7. 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, δ13C & δ18O of CO2, δD & δ18O of H2O and δ13C of dissolved inorganic carbon (DIC). Preliminary results revealed that δ13C 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, δ18O 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

  8. FMR thermomagnetic studies up to 900 C of lunar soils and potential magnetic analogues. [Ferromagnetic Resonance studies

    NASA Technical Reports Server (NTRS)

    Morris, R. V.; Gibbons, R. V.; Hoerz, F.

    1975-01-01

    Using a recently developed furnace, ferromagnetic resonance (FMR) thermomagnetic studies up to 900 C were employed to measure the Curie points of the superparamagnetic (SP) and single domain (SD) particles in lunar soils and potential magnetic analogue materials. Based on measured Curie points of 775 C, the SP and SD particles in lunar soils 10084-853, 12070-29, 14161-46, and 67010-4 are essentially pure metallic Fe. Synthetic and terrestrial samples containing magnetite, titanomaghemites, and magnetite-like particles have measured Curie points below 600 C are thus not magnetic analogues of lunar soils.

  9. Synthetic and Organocatalytic Studies of Quinidine Analogues with Ring-Size Modifications in the Quinuclidine Moiety.

    PubMed

    Breman, Arjen C; van der Heijden, Gydo; van Maarseveen, Jan H; Ingemann, Steen; Hiemstra, Henk

    2016-09-26

    Six highly enantiopure analogues of [2.2.2] were synthesized with five- or seven-membered rings in the (original) quinuclidine skeleton. Five of these compounds were prepared through epoxide opening by a secondary cyclic amine, providing the nor- and homoquinuclidine moieties through five- and six-membered ring formation. This method failed in the case of seven-membered ring formation, so for that particular ring size a different synthetic route starting from 3-quinuclidone was applied. The six novel analogues were examined as organocatalysts in four asymmetric conjugate addition reactions and the results compared with those of known cinchona alkaloid catalysts. This study shows that modification of the quinuclidine ring can have a substantial influence on catalyst activity and enantioselectivity. To acquire more insight into the characteristics of the new catalysts, the pKaH values were determined by means of fluorescence spectroscopy. Furthermore, relative reaction rates of conjugate thiol additions reactions catalyzed by these quinidine analogues were measured through polarimetry. PMID:27531315

  10. Structure-activity relationship studies on cholecystokinin: Analogues with partial agonist activity

    SciTech Connect

    Galas, M.C.; Lignon, M.F.; Rodriguez, M.; Mendre, C.; Fulcrand, P.; Laur, J.; Martinez, J. )

    1988-02-01

    In the present study, hepta- and octapeptide analogues of the C-terminal part of cholecystokinin, modified on the C-terminal phenylalanine residue, were synthesized. CCK analogues were prepared in which the peptide bond between aspartic acid and phenylalanine had or had not been modified and were lacking the C-terminal primary amide function. These CCK derivatives were able to cause full stimulation of amylase release from rat pancreatic acini but without a decrease in amylase release at supramaximal concentrations. There was a close relationship between the abilities of these derivatives to stimulate amylase release and their abilities to inhibit binding of {sup 125}I-BH-CCK-9 to CCK receptors on rat and guinea pig pancreatic acini. These CCK analogues were also able to recognize the guinea pig brain CCK receptors, some of them being particularly potent. The findings indicate that the aromatic ring of phenylalanine is important for the binding to brain and pancreatic CCK receptors, whereas the C-terminal primary amide function is not essential for the binding to pancreatic CCK receptors but is crucial for biological activity of rat pancreatic acini.

  11. Combined QM/MM study of thyroid and steroid hormone analogue interactions with αvβ3 integrin.

    PubMed

    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 αvβ3 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 (Ca(2+)) or magnesium (Mg(2+)) ions. These data reveal that 3,5'-triiodothyronine (T(3)) and 3,5,3',5'-tetraiodothyroacetic acid (T(4)ac) 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 T(3). PMID:22547930

  12. THE USE OF PANAX GINSENG AND ITS ANALOGUES AMONG PHARMACY CUSTOMERS IN ESTONIA: A CROSS-SECTIONAL STUDY.

    PubMed

    Volmer, Dasy; Raal, Ain; Kalle, Raivo; Sõukand, Renata

    2016-01-01

    The aim of the cross-sectional study was to evaluate the pattern of complementary self-treatment with P. ginseng and its analogues amongst pharmacy customers in Estonia. The study instrument consisted of multiple-choice items related to personal knowledge about and experience with the use of P. ginseng and its analogues. In total, 1233 customers participated in the study. Of study participants, 18.1% reported the use of P. ginseng and its analogues in their lives. P. ginseng preparations were used mostly according to the well- known indications (tiredness, weakness and decreased mental and physical capacity). Of P. ginseng users 44.3% reported positive treatment effects and 12.0% had experienced different side effects. With increase of age (p < 0.01) and at lower levels of education (p = 0.04), the use of ginseng or its analogues decreased. The better the users evaluated their health, the better they perceived the effect of P. ginseng preparations (p < 0.01). This study reported rather frequent use of P. ginseng and its analogues. P. ginseng could be seen in the treatment of conditions, where the use of local medicinal plants has not been established. Further research is needed to learn more about public knowledge and experiences about efficacy and safety of P. ginseng and its analogues. PMID:27476299

  13. THE USE OF PANAX GINSENG AND ITS ANALOGUES AMONG PHARMACY CUSTOMERS IN ESTONIA: A CROSS-SECTIONAL STUDY.

    PubMed

    Volmer, Dasy; Raal, Ain; Kalle, Raivo; Sõukand, Renata

    2016-01-01

    The aim of the cross-sectional study was to evaluate the pattern of complementary self-treatment with P. ginseng and its analogues amongst pharmacy customers in Estonia. The study instrument consisted of multiple-choice items related to personal knowledge about and experience with the use of P. ginseng and its analogues. In total, 1233 customers participated in the study. Of study participants, 18.1% reported the use of P. ginseng and its analogues in their lives. P. ginseng preparations were used mostly according to the well- known indications (tiredness, weakness and decreased mental and physical capacity). Of P. ginseng users 44.3% reported positive treatment effects and 12.0% had experienced different side effects. With increase of age (p < 0.01) and at lower levels of education (p = 0.04), the use of ginseng or its analogues decreased. The better the users evaluated their health, the better they perceived the effect of P. ginseng preparations (p < 0.01). This study reported rather frequent use of P. ginseng and its analogues. P. ginseng could be seen in the treatment of conditions, where the use of local medicinal plants has not been established. Further research is needed to learn more about public knowledge and experiences about efficacy and safety of P. ginseng and its analogues.

  14. Biological and chemical study of fused tri- and tetracyclic indazoles and analogues with important antiparasitic activity

    NASA Astrophysics Data System (ADS)

    Díaz-Urrutia, Christian A.; Olea-Azar, Claudio A.; Zapata, Gerald A.; Lapier, Michel; Mura, Francisco; Aguilera-Venegas, Benjamín; Arán, Vicente J.; López-Múñoz, Rodrigo A.; Maya, Juan D.

    A series of fused tri- and tetracyclic indazoles and analogues compounds (NID) with potential antiparasitic effects were studied using voltamperometric and spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry were characterized by electron spin resonance spectroscopy (ESR) and their spectral lines were explained and analyzed using simulated spectra. In addition, we examined the interaction between radical species generated from nitroindazole derivatives and glutathione (GSH). Biological assays such as activity against Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally, spin trapping and molecular modeling studies were also done in order to elucidate the potentials action mechanisms involved in the trypanocidal activity.

  15. Biological and chemical study of fused tri- and tetracyclic indazoles and analogues with important antiparasitic activity.

    PubMed

    Díaz-Urrutia, Christian A; Olea-Azar, Claudio A; Zapata, Gerald A; Lapier, Michel; Mura, Francisco; Aguilera-Venegas, Benjamín; Arán, Vicente J; López-Múñoz, Rodrigo A; Maya, Juan D

    2012-09-01

    A series of fused tri- and tetracyclic indazoles and analogues compounds (NID) with potential antiparasitic effects were studied using voltamperometric and spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry were characterized by electron spin resonance spectroscopy (ESR) and their spectral lines were explained and analyzed using simulated spectra. In addition, we examined the interaction between radical species generated from nitroindazole derivatives and glutathione (GSH). Biological assays such as activity against Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally, spin trapping and molecular modeling studies were also done in order to elucidate the potentials action mechanisms involved in the trypanocidal activity.

  16. [Efficacy of somatostatin and its analogues in the treatment of acute pancreatitis: clinical retrospective study].

    PubMed

    Citone, G; Perri, S; Nardi, M; Maira, E; Lotti, R; Gabbrielli, F; Antonellis, M; Orsini, S

    2001-04-01

    Acute pancreatitis is an acute inflammatory disease of the pancreas, with variable involvement of other regional tissues or remote organ systems. Acute pancreatitis is mild in 80% of cases; virtually all patients with this form of disease will survive, because it's associated with minimal organ dysfunction and uneventful recovery; the severe pancreatitis develops in 20% of cases and is associated with higher morbidity and mortality. It's most important to identify the severity of disease at the moment of hospital admission; many scoring systems have been developed to serve as early prognostic signs: Ranson's criteria, Imrie's criteria, Apache II score, Balthazar's TC score. Recently, new drugs have been proposed in the treatment of acute pancreatitis, as, for example, calcitonine, glucagon, systemic antioxidants, antagonists of the receptors of interleukines, antiproteases (aprotinin and gabexate-mesilate) and the inhibitors of pancreatic secretions (somatostatin and its analogues). However, many controversies still exist concerning the real efficacy of these drugs in the treatment of acute pancreatitis, particularly regarding the inhibitors of pancreatic secretions: recently, some studies showed that somatostatin is able to actually reduce the local complication of the disease and the development of severe forms of acute pancreatitis; on the other hand, other studies failed to show real advantages of somatostatin reducing morbidity and mortality for pancreatitis. The aim of present study is a retrospective analysis of patients affected by acute pancreatitis in order to evaluate efficacy of somatostatin and its analogues. All patients subdivided in two groups: group A, patients treated with conventional therapy plus somatostatin and/or octreotide (SS/LS), and group B, patients treated only with conventional therapy. Results seem to show that somatostatin does not positively affect morbidity and mortality in patients with acute pancreatitis. The Authors conclude

  17. The novel fluorescent CDP-analogue (Pbeta)MABA-CDP is a specific probe for the NMP binding site of UMP/CMP kinase.

    PubMed Central

    Rudolph, M. G.; Veit, T. J.; Reinstein, J.

    1999-01-01

    Direct thermodynamic and kinetic investigations of the binding of nucleotides to the nucleoside monophosphate (NMP) site of NMP kinases have not been possible so far because a spectroscopic probe was not available. By coupling a fluorescent N-methylanthraniloyl- (mant) group to the beta-phosphate of CDP via a butyl linker, a CDP analogue [(Pbeta)MABA-CDP] was obtained that still binds specifically to the NMP site of UmpKdicty, because the base and the ribose moieties, which are involved in specific interactions, are not modified. This allows the direct determination of binding constants for its substrates in competition experiments. PMID:10631985

  18. Muon spin relaxation study of the magnetism in unilluminated Prussian Blue analogue photomagnets

    NASA Astrophysics Data System (ADS)

    Salman, Z.; Parolin, T. J.; Chow, K. H.; Keeler, T. A.; Miller, R. I.; Wang, D.; Macfarlane, W. A.

    2006-05-01

    We present longitudinal field muon spin relaxation (μSR) measurements in the unilluminated state of the photosensitive molecular magnetic Co-Fe Prussian Blue analogues M1-2xCo1+x[Fe(CN)6]•zH2O , where M=K and Rb with x=0.4 and ≃0.17 , respectively. These results are compared to those obtained in the x=0.5 stoichiometric limit Co1.5[Fe(CN)6]•6H2O , which is not photosensitive. We find evidence for correlation between the range of magnetic ordering and the value of x in the unilluminated state, which can be explained using a site percolation model.

  19. Studies on the interaction of fluorescein isothiocyanate and its sugar analogues with cetyltrimethylammonium bromide

    NASA Astrophysics Data System (ADS)

    Ghosh, Sujit Kumar; Ali, Mohammed; Chatterjee, Hirak

    2013-03-01

    The interaction of fluorescein isothiocyanate (FITC) and its two sugar analogues (viz., FITC-Dextran 40S and FITC-Dextran 2000S) with cetyltrimethylammonium bromide has been elucidated by absorption, fluorescence, Fourier transform infrared spectroscopy and fluorescence microscopic studies. It is seen that the emission of the probe molecules is uniquely sensitive to the changes in surfactant concentrations at a particular regime due to the formation of dye-surfactant supramolecular assembly. The formation of supramolecular assembly becomes effective at a lower surfactant concentration with increasing dextran size as a consequence of definite dye-surfactant interaction and could pave a facile strategy for designing hierarchical superstructures.

  20. 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.

  1. Biological synthesis of a protein analogue of acetylcholinesterase: Monoclonal anti-idiotype antibody analogue of the esteratic site. Annual report, 15 May 1983-14 May 1984

    SciTech Connect

    August, J.T.

    1984-07-10

    The goal of this research during the first year of the contract was to develop a method for the purification of human erythrocyte acetylcholinesterase and to initiate the preparation and analysis of monoclonal antibodies. This was accomplished by the preparation of red blood cell membrane ghosts, enzyme solubilization with a non-ionic detergent, and enzyme purification by monoclonal antibody affinity chromatography. Sixty ml of packed red blood cells yielded a final fraction of 750 micrograms. approximately 20,000-fold purified. The purified fraction contained a single protein of about 75,000 daltons that was labeled with 3H-diisopropylfluorophosphate and gave a single peak during high-performance liquid chromatography on a TSK-SW3000 silica-enzyme for the preparation of monoclonal antibodies. anti-cholinesterase, anti-active site, and anti-idiotype monoclonal antibodies have been developed.

  2. 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.

  3. [Theoretical study on nuclear magnetic resonance spectra of the four kinds of curcumin analogues].

    PubMed

    Jia, Fei-yun; Ran, Ming; Su, Yu; Zhu, Jiang; Zhang, Bo

    2013-09-01

    Abstract The structure of four kinds of curcumin analogues was optimized at the level of B3LYP/6-31G(d, p), under which the stability was verified by means of vibration analysis. Moreover, NMR spectra of urcumin analogues compounds were studied at the level of B3LYP/6-311G(d,p) by GIAO method. The results show that the structure of four kinds of compounds, a larger conjugated system, has good planarity. Because of introducing hydroxyl and methoxy, the compound-B/C/D-C3, C4 and compoud-A and compound-D-Cs have greater 8 value. delta value of compound-A-C4. C4 is relatively smaller, and delta value of C3 is relatively larger. In the conjugated carbonyl compounds, compared with the acetaldehyde delta value (201 ppm), carbonyl C13 delta value (183 ppm) decreases relatively, C(11, 15) (alpha-carbon) delta value(122 ppm) decreases relatively, and C(9, 17) (beta-carbon) delta value(145 ppm) increases relatively. Finally, the correlation between experimental delta value and theoretical delta value of the 1H NMR was analyzed through the linear regression method. Results show that they have good correlation, and the experimental values coincide with the theoretical values.

  4. Probing the leucyl/phenylalanyl tRNA protein transferase active site with tRNA substrate analogues.

    PubMed

    Fung, Angela Wai Shan; Ebhardt, H Alexander; Krishnakumar, Kollappillil S; Moore, Jack; Xu, Zhizhong; Strazewski, Peter; Fahlman, Richard P

    2014-07-01

    Aminoacyl-tRNA protein transferases post-translationally conjugate an amino acid from an aminoacyl-tRNA onto the N-terminus of a target polypeptide. The eubacterial aminoacyl-tRNA protein transferase, L/F transferase, utilizes both leucyl-tRNA(Leu) and phenylalanyl-tRNA(Phe) as substrates. X-ray crystal structures with substrate analogues, the minimal substrate phenylalanyl adenosine (rA-Phe) and inhibitor puromycin, have been used to characterize tRNA recognition by L/F transferase. However analyses of these two X-ray crystal structures reveal significant differences in binding. Through structural analyses, mutagenesis, and enzymatic activity assays, we rationalize and demonstrate that the substrate analogues bind to L/F transferase with similar binding affinities using a series of different interactions by the various chemical groups of the analogues. Our data also demonstrates that enlarging the hydrophobic pocket of L/F transferase selectively enhances puromycin inhibition and may aid in the development of improved inhibitors for this class of enzymes.

  5. Social Studies. [SITE 2002 Section].

    ERIC Educational Resources Information Center

    2002

    This document contains the following papers on social studies from the SITE (Society for Information Technology & Teacher Education) 2002 conference: (1) "Technology Portfolios in Pre-Service Social Studies Teacher Education" (Marsha Alibrandi); (2) "North Carolina's Sixth Graders Go to Russia: A Global Education/Curriculum Integration Project…

  6. 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.

  7. 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

  8. Nonstationary analogue black holes

    NASA Astrophysics Data System (ADS)

    Eskin, Gregory

    2014-12-01

    We study the existence of analogue nonstationary spherically symmetric black holes. The prime example is the acoustic model see Unruh (1981 Phys. Rev. Lett. 46 1351). 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.

  9. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    PubMed Central

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-01-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents. PMID:27671769

  10. 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.

  11. A comparative study of two novel nanosized radiolabeled analogues of methionine for SPECT tumor imaging.

    PubMed

    Khosroshahi, A G; Amanlou, M; Sabzevari, O; Daha, F J; Aghasadeghi, M R; Ghorbani, M; Ardestani, M S; Alavidjeh, M S; Sadat, S M; Pouriayevali, M H; Mousavi, L; Ebrahimi, S E S

    2013-01-01

    It has been reported that most tumor cells show an increased uptake of variety of amino acids specially methionine when compared with normal cells and amino acid transport is generally increased in malignant transformation. Based on the evidences, two novel nanosized analogues of methionine (Anionic Linear Globular Dendrimer G(2), a biodigredabale anionic linear globular-Methionin, and DTPA-Methionine(1) conjugates) were synthesized and labeled with (99m)Tc and used in tumor imaging/ therapy in vitro and in vivo. The results showed marked tumor SPECT molecular imaging liabilities for both compounds but with a better performance by administration of (99m)Tc-Dendrimer G(2)-Methionin. The results also showed a good anticancer activity for 99mTc-DTPA-Methionine. Based on the present study (99m)Tc-Dendrimer G(2)-Methionin or 99mTc-DTPA-(Methionine)(1) have potentials to be used in tumor molecular imaging as well as cancer therapy in future.

  12. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    NASA Astrophysics Data System (ADS)

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-09-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

  13. Social Studies. [SITE 2001 Section].

    ERIC Educational Resources Information Center

    White, Cameron, Ed.

    This document contains the following papers on social studies from the SITE (Society for Information Technology & Teacher Education) 2001 conference: (1) "Teacher's Guide to the Holocaust: An Extensive Online Resource for Teachers" (Ann E. Barron and others); (2) "Preparing a Virtual Field Trip To Teach Value of Community and Sense of Place"…

  14. New Insights into Nisin's Antibacterial Mechanism Revealed by Binding Studies with Synthetic Lipid II Analogues.

    PubMed

    't Hart, Peter; Oppedijk, Sabine F; Breukink, Eefjan; Martin, Nathaniel I

    2016-01-12

    Nisin is the preeminent lantibiotic, and to date its antibacterial mechanism has been investigated using a variety of techniques. While nisin's lipid II-mediated mode of action is well-established, a detailed analysis of the thermodynamic parameters governing this interaction has not been previously reported. We here describe an approach employing isothermal titration calorimetry to directly measure the affinity of nisin for lipid II and a number of synthetic lipid II precursors and analogues. Our measurements confirm the pyrophosphate unit of lipid II as the primary site of nisin binding and also indicate that the complete MurNAc moiety is required for a high-affinity interaction. Additionally, we find that while the pentapeptide unit of the lipid II molecule is not required for strong binding by nisin, it does play an important role in stabilizing the subsequently formed nisin-lipid II pore complex, albeit at an entropic cost. The anchoring of lipid II in a membrane environment was also found to play a significant role in enhancing nisin binding and is required in order to achieve a high-affinity interaction. PMID:26653142

  15. Bioisosteric Exchange of Csp3 -Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues.

    PubMed

    Krautwald, Simon; Nilewski, Christian; Mori, Mihoko; Shiomi, Kazuro; Ōmura, Satoshi; Carreira, Erick M

    2016-03-14

    Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, atpenin A5, are described. These analogues were selected on the basis of Cl→CH3 or H3 C→Cl exchanges in the side-chain of atpenin A5. The interchange of chloro and methyl substituents led to complex II inhibitors with equal IC50 values. This suggests that Cl↔Me bioisosteric exchange can be realized in aliphatic settings. PMID:26891236

  16. Antifungal activity of eugenol analogues. Influence of different substituents and studies on mechanism of action.

    PubMed

    Carrasco, Héctor; Raimondi, Marcela; Svetaz, Laura; Di Liberto, Melina; Rodriguez, María V; Espinoza, Luis; Madrid, Alejandro; Zacchino, Susana

    2012-01-19

    Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH(3) at C-2 or the presence of one or two NO(2) groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL-1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.

  17. A theoretical study of medium effects on the structure of the glycine analogue aminomethylphosphonic acid.

    PubMed

    Benbrahim, Nasséra; Rahmouni, Ali; Ruiz-López, Manuel F

    2008-09-28

    alpha-Aminophosphonic acids are analogues of natural alpha-aminoacids and very promising agents for use in various pharmaceutical applications. However, in contrast to the numerous theoretical investigations on the structure of natural alpha-aminoacids, only very few studies on alpha-aminophosphonic acids have been performed. In the present work, we report a detailed investigation of the simplest compound, the glycine analogue aminomethylphosphonic acid (AMPA), by means of quantum mechanical calculations at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) and MP2/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) levels. We focus on the structure of the neutral species looking at the evolution of non-ionized and ionized forms from gas phase to non-polar solvents and aqueous media. Continuum and discrete-continuum solvent models have been employed to account for the effects of the environment. The discussion is centered on: (1) the geometry and relative stability of possible conformers in gas phase and aqueous solution, (2) the free energy of tautomerization in different media, (3) the role of hydrogen bonds in liquid water, and (4) the free energy of transfer from water to a hydrophobic solvent such as cyclohexane. Systematic comparison between AMPA and Gly is performed. Though both systems exhibit many similarities, some important differences have also been found that may be explained, at least in part, by the higher acidity of phosphonic acids compared to carboxylic acids. In particular, in solvents lacking hydrogen-bond formation capability, Gly derivatives should mainly exist as non-ionized molecules while the equivalent AMPA derivatives should adopt a zwitterionic structure in media with dielectric constant above 10. This might have significant environmental or biological consequences that will need to be addressed.

  18. 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

  19. 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.

  20. Study of a CCP RF Dusty Plasma for the Production of Titan's Aerosols Analogues

    SciTech Connect

    Alcouffe, G.; Cernogora, G.; Ouni, F.; Correia, J. J.; Cavarroc, M.; Boufendi, L.; Szopa, C.

    2008-09-07

    The CCP-RF discharge PAMPRE experiment produces analogues of Titan's aerosols. Here are presented the plasma characteristics as a function of gas mixtures and dust formation. Electronic density, optical emission spectroscopy, and self-bias voltage measurements are presented.

  1. Improved thrombin binding aptamer analogues containing inversion of polarity sites: structural effects of extra-residues at the ends.

    PubMed

    Virgilio, A; Amato, T; Petraccone, L; Filosa, R; Varra, M; Mayol, L; Esposito, V; Galeone, A

    2016-08-10

    In this paper, we report the investigations, based on NMR, molecular modelling, CD measurements and electrophoresis, of thrombin binding aptamer (TBA) analogues containing an extra-residue at the 3'-end or at both the ends of the original TBA sequence, linked through 3'-3' or 5'-5' phosphodiester bonds. The data indicate that most of the modified aptamers investigated adopt chair-like G-quadruplex structures very similar to that of the TBA and that stacking interactions occur between the 3'-3' or 5'-5' extra residues and the deoxyguanosines of the upper G-tetrad. A comparison of the thermodynamic data of TBA-A and TBA-T containing a 3'-3' extra residue and their canonical versions clearly indicates that the 3'-3' phosphodiester bond is fundamental in endowing the modified aptamers with remarkably higher thermal stabilities than the original TBA. PMID:27461474

  2. Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells.

    PubMed

    Kaschula, Catherine H; Hunter, Roger; Stellenboom, Nashia; Caira, Mino R; Winks, Susan; Ogunleye, Thozama; Richards, Philip; Cotton, Jonathan; Zilbeyaz, Kani; Wang, Yabing; Siyo, Vuyolwethu; Ngarande, Ellen; Parker, M Iqbal

    2012-04-01

    The organosulfur compound ajoene derived from the rearrangement of allicin found in crushed garlic can inhibit the proliferation of tumour cells by inducing G(2)/M cell cycle arrest and apoptosis. We report on the application of a concise four-step synthesis (Hunter et al., 2008 [1]) that allows access to ajoene analogues with the end allyl groups substituted. A library of twelve such derivatives tested for their anti-proliferation activity against WHCO1 oesophageal cancer cells has identified a derivative containing p-methoxybenzyl (PMB)-substituted end groups that is twelve times more active than Z-ajoene, with an IC(50) of 2.1μM (Kaschula et al., 2011 [2]). Structure-activity studies involving modification of the sulfoxide and vinyl disulfide groups of this lead have revealed that the disulfide is the ajoene pharmacophore responsible for inhibiting WHCO1 cell growth, inducing G(2)/M cell cycle arrest and apoptosis by caspase-3 activation, and that the vinyl group serves to enhance the anti-proliferation activity a further eightfold. Reaction of the lead with cysteine in refluxing THF as a model reaction for ajoene's mechanism of action based on a thiol/disulfide exchange reveals that the allylic sulfur of the vinyl disulfide is the site of thiol attack in the exchange. PMID:22381354

  3. Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells.

    PubMed

    Kaschula, Catherine H; Hunter, Roger; Stellenboom, Nashia; Caira, Mino R; Winks, Susan; Ogunleye, Thozama; Richards, Philip; Cotton, Jonathan; Zilbeyaz, Kani; Wang, Yabing; Siyo, Vuyolwethu; Ngarande, Ellen; Parker, M Iqbal

    2012-04-01

    The organosulfur compound ajoene derived from the rearrangement of allicin found in crushed garlic can inhibit the proliferation of tumour cells by inducing G(2)/M cell cycle arrest and apoptosis. We report on the application of a concise four-step synthesis (Hunter et al., 2008 [1]) that allows access to ajoene analogues with the end allyl groups substituted. A library of twelve such derivatives tested for their anti-proliferation activity against WHCO1 oesophageal cancer cells has identified a derivative containing p-methoxybenzyl (PMB)-substituted end groups that is twelve times more active than Z-ajoene, with an IC(50) of 2.1μM (Kaschula et al., 2011 [2]). Structure-activity studies involving modification of the sulfoxide and vinyl disulfide groups of this lead have revealed that the disulfide is the ajoene pharmacophore responsible for inhibiting WHCO1 cell growth, inducing G(2)/M cell cycle arrest and apoptosis by caspase-3 activation, and that the vinyl group serves to enhance the anti-proliferation activity a further eightfold. Reaction of the lead with cysteine in refluxing THF as a model reaction for ajoene's mechanism of action based on a thiol/disulfide exchange reveals that the allylic sulfur of the vinyl disulfide is the site of thiol attack in the exchange.

  4. The crystal structure of an isopenicillin N synthase complex with an ethereal substrate analogue reveals water in the oxygen binding site.

    PubMed

    Clifton, Ian J; Ge, Wei; Adlington, Robert M; Baldwin, Jack E; Rutledge, Peter J

    2013-08-19

    Isopenicillin N synthase (IPNS) is a non-heme iron oxidase central to the biosynthesis of β-lactam antibiotics. IPNS converts the tripeptide δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N while reducing molecular oxygen to water. The substrate analogue δ-(L-α-aminoadipoyl)-L-cysteinyl-O-methyl-D-threonine (ACmT) is not turned over by IPNS. Epimeric δ-(L-α-aminoadipoyl)-L-cysteinyl-O-methyl-D-allo-threonine (ACmaT) is converted to a bioactive penam product. ACmT and ACmaT differ from each other only in the stereochemistry at the β-carbon atom of their third residue. These substrates both contain a methyl ether in place of the isopropyl group of ACV. We report an X-ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. This structure reveals an additional water molecule bound to the active site metal, held by hydrogen-bonding to the ether oxygen atom of the substrate analogue.

  5. Synthesis of farnesyl diphosphate analogues containing ether-linked photoactive benzophenones and their application in studies of protein prenyltransferases.

    PubMed

    Turek, T C; Gaon, I; Distefano, M D; Strickland, C L

    2001-05-18

    Protein prenylation is a posttranslational lipid modification in which C(15) and C(20) isoprenoid units are linked to specific protein-derived cysteine residues through a thioether linkage. This process is catalyzed by a class of enzymes called prenyltransferases that are being intensively studied due to the finding that Ras protein is farnesylated coupled with the observation that mutant forms of Ras are implicated in a variety of human cancers. Inhibition of this posttranslational modification may serve as a possible cancer chemotherapy. Here, the syntheses of two new farnesyl diphosphate (FPP) analogues containing photoactive benzophenone groups are described. Each of these compounds was prepared in six steps from dimethylallyl alcohol. Substrate studies, inhibition kinetics, photoinactivation studies, and photolabeling experiments are also included; these experiments were performed with a number of protein prenyltransferases from different sources. A X-ray crystal structure of one of these analogues bound to rat farnesyltransferase illustrates that they are good substrate mimics. Of particular importance, these new analogues can be enzymatically incorporated into Ras-based peptide substrates allowing the preparation of molecules with photoactive isoprenoids that may serve as valuable probes for the study of prenylation function. Photoaffinity labeling of human protein geranylgeranyltransferase with (32)P-labeled forms of these analogues suggests that the C-10 locus of bound geranylgeranyl diphosphate (GGPP) is in close proximity to residues from the beta-subunit of this enzyme. These results clearly demonstrate the utility of these compounds as photoaffinity labeling analogues for the study of a variety of protein prenyltransferases and other enzymes that employ FPP or GGPP as their substrates.

  6. 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

  7. Deposition of latex colloids at rough mineral surfaces: an analogue study using nanopatterned surfaces.

    PubMed

    Krishna Darbha, Gopala; Fischer, Cornelius; Michler, Alex; Luetzenkirchen, Johannes; Schäfer, Thorsten; Heberling, Frank; Schild, Dieter

    2012-04-24

    Deposition of latex colloids on a structured silicon surface was investigated. The surface with well-defined roughness and topography pattern served as an analogue for rough mineral surfaces with half-pores in the submicrometer size. The silicon topography consists of a regular pit pattern (pit diameter = 400 nm, pit spacing = 400 nm, pit depth = 100 nm). Effects of hydrodynamics and colloidal interactions in transport and deposition dynamics of a colloidal suspension were investigated in a parallel plate flow chamber. The experiments were conducted at pH ∼ 5.5 under both favorable and unfavorable adsorption conditions using carboxylate functionalized colloids to study the impact of surface topography on particle retention. Vertical scanning interferometry (VSI) was applied for both surface topography characterization and the quantification of colloidal retention over large fields of view. The influence of particle diameter variation (d = 0.3-2 μm) on retention of monodisperse as well as polydisperse suspensions was studied as a function of flow velocity. Despite electrostatically unfavorable conditions, at all flow velocities, an increased retention of colloids was observed at the rough surface compared to a smooth surface without surface pattern. The impact of surface roughness on retention was found to be more significant for smaller colloids (d = 0.3, 0.43 vs. 1, 2 μm). From smooth to rough surfaces, the deposition rate of 0.3 and 0.43 μm colloids increased by a factor of ∼2.7 compared to a factor of 1.2 or 1.8 for 1 and 2 μm colloids, respectively. For a substrate herein, with constant surface topography, the ratio between substrate roughness and radius of colloid, Rq/rc, determined the deposition efficiency. As Rq/rc increased, particle-substrate overall DLVO interaction energy decreased. Larger colloids (1 and 2 μm) beyond a critical velocity (7 × 10(-5) and 3 × 10(-6) m/s) (when drag force exceeds adhesion force) tend to detach from the surface

  8. Deposition of latex colloids at rough mineral surfaces: an analogue study using nanopatterned surfaces.

    PubMed

    Krishna Darbha, Gopala; Fischer, Cornelius; Michler, Alex; Luetzenkirchen, Johannes; Schäfer, Thorsten; Heberling, Frank; Schild, Dieter

    2012-04-24

    Deposition of latex colloids on a structured silicon surface was investigated. The surface with well-defined roughness and topography pattern served as an analogue for rough mineral surfaces with half-pores in the submicrometer size. The silicon topography consists of a regular pit pattern (pit diameter = 400 nm, pit spacing = 400 nm, pit depth = 100 nm). Effects of hydrodynamics and colloidal interactions in transport and deposition dynamics of a colloidal suspension were investigated in a parallel plate flow chamber. The experiments were conducted at pH ∼ 5.5 under both favorable and unfavorable adsorption conditions using carboxylate functionalized colloids to study the impact of surface topography on particle retention. Vertical scanning interferometry (VSI) was applied for both surface topography characterization and the quantification of colloidal retention over large fields of view. The influence of particle diameter variation (d = 0.3-2 μm) on retention of monodisperse as well as polydisperse suspensions was studied as a function of flow velocity. Despite electrostatically unfavorable conditions, at all flow velocities, an increased retention of colloids was observed at the rough surface compared to a smooth surface without surface pattern. The impact of surface roughness on retention was found to be more significant for smaller colloids (d = 0.3, 0.43 vs. 1, 2 μm). From smooth to rough surfaces, the deposition rate of 0.3 and 0.43 μm colloids increased by a factor of ∼2.7 compared to a factor of 1.2 or 1.8 for 1 and 2 μm colloids, respectively. For a substrate herein, with constant surface topography, the ratio between substrate roughness and radius of colloid, Rq/rc, determined the deposition efficiency. As Rq/rc increased, particle-substrate overall DLVO interaction energy decreased. Larger colloids (1 and 2 μm) beyond a critical velocity (7 × 10(-5) and 3 × 10(-6) m/s) (when drag force exceeds adhesion force) tend to detach from the surface

  9. Interaction studies to evaluate 2- carboxyphenolate analogues as inhibitor of anti-apoptotic protein Bcl-2.

    PubMed

    Al-Karaawi, Mohammed A

    2013-01-01

    Apoptosis is a cellular process that leads to the death of damaged cells. Its malfunction can cause cancer and poor response to conventional chemotherapy. After being activated by cellular stress signals, pro-apoptotic proteins bind anti-apoptotic proteins, thus allowing apoptosis to go forward. An excess of anti-apoptotic proteins can prevent apoptosis. Designed molecules that imitate the roles of pro-apoptotic proteins can promote the death of cancer cells. In this work we have applied an insilico approach to study the binding of 2-carboxyphenolate analogues as potent inhibitors of anti-apoptotic protein Bcl-2. Molecular docking study was performed in order to find specific binding mode using AutoDock. From the docking results it was observed that zinc 2- carboxyphenolate showed strong inhibition with Bcl-2 with docking energy of -4.6 kcal/mol. The effects of the Zinc 2- hydroxybenzoate on apoptosis in HT-1080 cell lines were also analysed, which shows strong evidence for their apoptotic mode of action using flow cytometric analysis of Annexin-V. Our study gave valuable insights on inhibitor specificity of anti-apoptotic proteins and might be considered as potent chemopreventive agents. PMID:23847403

  10. Indenes and tetralenes analogues attenuates lipopolysaccharide-induced inflammation: An in-vitro and in-vivo study.

    PubMed

    Mohanty, Shilpa; Gautam, Yashveer; Maurya, Anil Kumar; Negi, Arvind S; Prakash, Om; Khan, Feroz; Bawankule, Dnyaneshwar Umrao

    2016-02-01

    In an effort to evaluate novel pharmacological activity of 1-chloro-2-formyl indene and tetralene analogues possessing potential antitubercular and antistaphylococcal agents, we explored its anti-inflammatory potential against lipopolysaccharide(LPS)-induced inflammation using in-vitro and in-vivo bioassay. Synthesized analogues significantly inhibited the production and expression of pro-inflammatory cytokines against LPS-induced inflammation in macrophages isolated from mice. Among all the analogues, TAF-5 (1-Chloro-2-formyl-1-tetralene) exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the therapeutic efficacy and safety of TAF-5 in in-vivo system using LPS-induced sepsis, a systemic inflammation model and acute oral toxicity respectively in mice. Oral administration of TAF-5 inhibited the pro-inflammatory cytokines in serum, attenuated the organs injuries and improved host survival in dose dependent manner. Acute oral toxicity study showed TAF-5 is non-toxic at higher dose in mice. These results suggest the suitability of indene and tetralene analogues as new chemical entities for further investigation towards the management of inflammation related diseases.

  11. Production and Study of Titan's Aerosols Analogues with A RF Low Pressure Plasma Discharge

    SciTech Connect

    Szopa, C.; Cernogora, G.; Correia, J.J.; Boufendi, L.; Jolly, A.

    2005-10-31

    The atmosphere of Titan, the biggest satellite of Saturn, contains aerosols produced by the organic chemistry induced by the photochemistry of N2 and CH4, the major gaseous atmospheric compounds. In spite of their importance for the properties of the Titan's atmosphere, and for organic chemistry, only few direct information are available about them because of the limitations of the observational techniques, and their processes of formation and growth are not understood. In order to bring answers to these questions, we developed a new type of laboratory simulation to produce analogues of Titan's aerosols (known as tholins) with a low pressure Radio Frequency plasma discharge. The main originality of this experiment (named PAMPRE) comes from its ability to produce particles in volume, as they are maintained in levitation by electrostatic forces compensating gravity, whereas the other experiments produce tholins on the reactors walls or a substrate. We initiated our investigations by a study of the properties of the produced particles as a function of the plasma operating conditions (i.e. amount of CH4 in N2, injected RF power, pressure, and gas flow). We here present the results of this study.

  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 β-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. A Numerical and Analogue Study of Dike Ascent in Asymmetric Continental Rift Zones

    NASA Astrophysics Data System (ADS)

    Schierjott, J.; Maccaferri, F.; Acocella, V.; Rivalta, E.

    2015-12-01

    In continental rift zones, tectonic extension generates deep topographic depressions, typically graben or half-graben structures, confined by large border faults. Volcanism may be distributed within, at the border and outside of the depressions, and the mechanisms controlling this distribution are debated. Recently, Maccaferri et al. (2014) proposed that the reorientation of the principal stresses linked to crustal thinning and overall crustal mass redistribution in rift zones modifies the expected trajectory of ascending magma pockets and plays a fundamental role in the distribution of volcanism at the surface. However, the model does not explain why volcanism is asymmetric in most continental rift zones. The goal of this study is to investigate the relation between the characteristic distribution of volcanism at the surface, the distribution and geometry of magma storage at depth, and the observed geometric asymmetry of the grabens at most rift zones. By using a boundary element model for dike propagation and analogue laboratory experiments we evaluate the ascent path of magmatic dikes in asymmetric continental rifts.We find that the position of the magma source along the cross section of the rift and its spatial extent and the asymmetry of the graben cross section are the most important factors controlling one-sided volcanic activity at surface. For dikes starting beneath the rift's center, the more asymmetric the rift structure the more likely is asymmetric volcanic activity. Dikes are deflected to the shallow rift side and no volcanism develops on the deep side or only focused in one spot. However, if the position of the magma ponding region is offset towards the deep side of the graben, the dikes tend to emerge on the rift shoulder adjacent to such deep side. To a minor extent, also the starting depth of the dikes, any topographic loading on the graben flanks due to flank uplift and the background tectonic stress impact the surface distribution of volcanism

  14. New Insights into the Design of Inhibitors of Human S-Adenosylmethionine Decarboxylase: Studies of Adenine C[superscript 8] Substitution in Structural Analogues of S-Adenosylmethionine

    SciTech Connect

    McCloskey, Diane E.; Bale, Shridhar; Secrist, III, John A.; Tiwari, Anita; Moss, III, Thomas H.; Valiyaveettil, Jacob; Brooks, Wesley H.; Guida, Wayne C.; Pegg, Anthony E.; Ealick, Steven E.

    2009-04-02

    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 C{sup 8}-substituted adenine analogues bound in the active site.

  15. 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

  16. Discrete and analogue quantity processing in the parietal lobe: a functional MRI study.

    PubMed

    Castelli, Fulvia; Glaser, Daniel E; Butterworth, Brian

    2006-03-21

    The human intraparietal sulcus (IPS) is implicated in processing symbolic number information and possibly in nonsymbolic number information. Specific IPS activity for discrete quantities (numerosities) as compared with continuous, analogue quantity has not been demonstrated. Here we use a stimulus-driven paradigm to distinguish automatic estimation of "how many things" from "how much" and "how long." The discrete analogue response task (DART) uses the perception of hues which can change either abruptly (discrete, numerous stimuli) or smoothly (analogue, nonnumerous stimuli) in space or in time. Subjects decide whether they saw more green or more blue. A conjunction analysis of spatial and temporal conditions revealed that bilateral IPS was significantly more active during the processing of discrete stimuli than during analogue stimuli, as was a parietal-occipital transition zone. We suggest that processing numerosity is a distinct process from processing analogue quantity, whether extended in space or time, and that an intraparietal network connects objects' segmentation to the estimation of their numerosity. PMID:16537401

  17. Synthesis and Structure–Activity Relationship Study of 5a-Carbasugar Analogues of SL0101

    PubMed Central

    2014-01-01

    The Ser/Thr protein kinase, RSK, is associated with oncogenesis, and therefore, there are ongoing efforts to develop RSK inhibitors that are suitable for use in vivo. SL0101 is a natural product that demonstrates selectivity for RSK inhibition. However, SL0101 has a short biological half-life in vivo. To address this issue we designed a set of eight cyclitol analogues, which should be resistant to acid catalyzed anomeric bond hydrolysis. The analogues were synthesized and evaluated for their ability to selectively inhibit RSK in vitro and in cell-based assays. All the analogues were prepared using a stereodivergent palladium-catalyzed glycosylation/cyclitolization for installing the aglycon. The l-cyclitol analogues were found to inhibit RSK2 in in vitro kinase activity with a similar efficacy to that of SL0101, however, the analogues were not specific for RSK in cell-based assays. In contrast, the d-isomers showed no RSK inhibitory activity in in vitro kinase assay. PMID:25589938

  18. An experimental analogue study into the role of abstract thinking in trauma-related rumination.

    PubMed

    Ehring, Thomas; Szeimies, Anna-Kristina; Schaffrick, Christina

    2009-04-01

    Trauma-related rumination has been shown to predict the maintenance of posttraumatic stress disorder (PTSD). However, it is still unclear how rumination can be distinguished from functional forms of thinking about traumatic events. The current study used an analogue design to experimentally test the hypothesis that the abstractness of thinking is responsible for the dysfunctional effects of trauma-related rumination. Eighty-three healthy university students first watched a distressing video and were then randomly assigned to abstract ruminative thinking, concrete thinking or distraction. Abstract thinking was found to lead to a significantly longer maintenance of negative mood and arousal than both concrete thinking and distraction. These results are in line with earlier findings in the context of excessive worry and depressive rumination and support the view that abstractness is a critical factor for the dysfunctional effects of trauma-related rumination. However, results regarding intrusive memories were not supportive of the hypotheses. Unexpectedly, the distraction group showed the highest number of intrusions, whereas the abstract and concrete conditions did not significantly differ. Implications for theoretical models of trauma-related rumination and possible clinical implications are discussed. PMID:19200947

  19. In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt(1)-DALDA Analogues.

    PubMed

    Ballet, Steven; Betti, Cecilia; Novoa, Alexandre; Tömböly, Csaba; Nielsen, Carsten Uhd; Helms, Hans Christian; Lesniak, Anna; Kleczkowska, Patrycja; Chung, Nga N; Lipkowski, Andrzej W; Brodin, Birger; Tourwé, Dirk; Schiller, Peter W

    2014-04-10

    In this study the μ opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH2) and Dmt(1)-DALDA (Dmt-d-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4-7) proved to possess high affinity and agonist potency at both MOR and DOR (δ opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood-brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these experiments were indicative of transcellular transport but not active transport. In vivo assays demonstrated that the peptides were capable of (i) crossing the blood-brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt(1)-DALDA 1, compounds 4-7 are mixed MOR/DOR agonists, expected to produce reduced opioid-related side effects.

  20. 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.

  1. Ligand-dependent active-site closure revealed in the crystal structure of Mycobacterium tuberculosis MenB complexed with product analogues.

    PubMed

    Song, Haigang; Sung, Hoi Pang; Tse, Yuk Sing; Jiang, Ming; Guo, Zhihong

    2014-11-01

    1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase catalyzes an essential intramolecular Claisen condensation in menaquinone biosynthesis and is an important target for the development of new antibiotics. This enzyme in Mycobacterium tuberculosis is cofactor-free and is classified as a type II DHNA-CoA synthase, differing from type I enzymes, which rely on exogenous bicarbonate for catalysis. Its crystal structures in complex with product analogues have been determined at high resolution to reveal ligand-dependent structural changes, which include the ordering of a 27-residue active-site loop (amino acids 107-133) and the reorientation of the carboxy-terminal helix (amino acids 289-301) that forms part of the active site from the opposing subunit across the trimer-trimer interface. These structural changes result in closure of the active site to the bulk solution, which is likely to take place through an induced-fit mechanism, similar to that observed for type I DHNA-CoA synthases. These findings demonstrate that the ligand-dependent conformational changes are a conserved feature of all DHNA-CoA synthases, providing new insights into the catalytic mechanism of this essential tubercular enzyme.

  2. Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue

    SciTech Connect

    Ida, Tomoyo; Suzuki, Hideyuki; Fukuyama, Keiichi; Hiratake, Jun; Wada, Kei

    2014-02-01

    The binding modes of acivicin, a classical and an electrophilic active-site-directed glutamate analogue, to bacterial γ-glutamyltranspeptidases were found to be diverse. γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp{sup 2} hybridization to Thr403 O{sup γ}, the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs.

  3. Using and interpreting analogue designs.

    PubMed

    Cook, Bryan G; Rumrill, Phillip D

    2005-01-01

    Researchers in rehabilitation counseling and disability studies sometimes use analogue research, which involves materials that approximate or describe reality (e.g., written vignettes, videotaped exemplars) rather than investigating phenomena in real-world settings. Analogue research often utilizes experimental designs, and it thereby frequently possesses a high degree of internal validity. Analogue research allows investigators to exercise tight control over the implementation of the independent or treatment variable and over potentially confounding variables, which enables them to isolate the effects of those treatment variables on selected outcome measures. However, the simulated nature of analogue research presents an important threat to external validity. As such, the generalizability of analogue research to real-life settings and situations may be problematic. These and other issues germane to analogue research in vocational rehabilitation are discussed in this article, illustrated with examples from the contemporary literature.

  4. Des analogues naturels de sites de stockage de déchets nucléaires vieux de 2 milliards d'années : les réacteurs de fission nucléaire naturels du Gabon (Afrique)

    NASA Astrophysics Data System (ADS)

    Gauthier-Lafaye, François

    2002-10-01

    Two billion years ago, the increase of oxygen in atmosphere and the high 235U/ 238U uranium ratio (>3%) made possible the occurrence of natural nuclear reactors on Earth. These reactors are considered to be a good natural analogue for nuclear waste disposal. Their preservation during such a long period of time is mainly due to the geological stability of the site, the occurrence of clays surrounding the reactors and acting as an impermeable shield, and the occurrence of organic matter that maintained the environment in reducing conditions, favourable for the stability of uraninite. Hydrogeochemical studies and modelling have shown the complexity of the geochemical system at Oklo and Bangombé (Gabon) and the lack of precise data about uranium and fission products retention and migration mechanisms in geological environments. To cite this article: F. Gauthier-Lafaye, C. R. Physique 3 (2002) 839-849.

  5. NMR studies of multiple conformations in complexes of Lactobacillus casei dihydrofolate reductase with analogues of pyrimethamine

    SciTech Connect

    Birdsall, B.; Tendler, S.J.B.; Feeney, J.; Carr, M.D. ); Arnold, J.R.P.; Thomas, J.A.; Roberts, G.C.K. ); Griffin, R.J.; Stevens, M.F.G. )

    1990-10-01

    {sup 1}H and {sup 19}F NMR signals from bound ligands have been assigned in one- and two-dimensional NMR spectra of complexes of Lactobacillus casei dihydrofolate reductase with various pyrimethamine analogues. The signals were identified mainly by correlating signals from bound and free ligands by using 2D exchange experiments. Analogues with symmetrically substituted phenyl rings give rise to {sup 1}H signals from four nonequivalent aromatic protons, clearly indicating the presence of hindered rotation about the pyrimidine-phenyl bond. Analogues with symmetrically substituted phenyl rings give rise to {sup 1}H signals from four nonequivalent aromatic protons, clearly indicating the presence of hindered rotation about the pyrimidine-phenyl bond. Analogues containing asymmetrically substituted aromatic rings exist as mixtures of two rotational isomers (an enantiomeric pair) because of this hindered rotation and the NMR spectra revealed that both isomers (forms A and B) bind to the enzyme with comparable, though unequal, binding energies. In this case two complete sets of bound proton signals were observed. The relative orientations of the two forms have been determined from NOE through-space connections between protons on the ligand and protein. Ternary complexes with NADP{sup {plus}} were also examined.

  6. Laser-Raman and FT-IR spectroscopic studies of peptide-analogues of silkmoth chorion protein segments.

    PubMed

    Benaki, D C; Aggeli, A; Chryssikos, G D; Yiannopoulos, Y D; Kamitsos, E I; Brumley, E; Case, S T; Boden, N; Hamodrakas, S J

    1998-07-01

    Silkmoth chorion, the proteinaceous major component of the eggshell, with extraordinary mechanical and physiological properties, consists of a complex set of proteins, which have a tripartite structure: a central, evolutionarily conserved, domain and two more variable 'arms'. Peptide-analogues of silkmoth chorion protein central domain segments have been synthesized. Laser-Raman and infrared spectroscopic studies suggest the preponderance of antiparallel beta-pleated sheet structure for these peptides, both in solution and in the solid state. PMID:9644596

  7. A numerical and analogue study of dike ascent in asymmetric continental rift zones

    NASA Astrophysics Data System (ADS)

    Schierjott, Jana; Maccaferri, Francesco; Keir, Derek; Kemna, Andreas; Rivalta, Eleonora

    2015-04-01

    In continental rift zones, tectonic extension is responsible for the creation of deep topographic depressions bordered by large border faults. Volcanism may be distributed within, at the border and outside of the depressions, and the mechanisms controlling this distribution are debated. Recently, Maccaferri et al. (2014) proposed that the reorientation of the principal stresses linked to crustal thinning and overall crustal mass redistribution in rift zones modifies the expected trajectory of ascending magma pockets and plays a fundamental role in the distribution of volcanism at the surface. However, the model does not explain why volcanism is asymmetric in most continental rift zones. The goal of this study is to investigate the relation between the characteristic distribution of volcanism at the surface, the distribution and geometry of magma storage at depth, and the observed geometric asymmetry of the grabens at most rift zones. By using a boundary element model for dike propagation and analogue laboratory experiments we evaluate the ascent path of magmatic dikes in asymmetric continental rifts. We find that introducing asymmetry of various degrees into the models has a huge impact on the modeled location of the surface volcanic activity. In particular, varying model parameters such as the half-graben width and depth and the degree of asymmetry leads to numerous different scenarios, including one-sided volcanic activity when the degree of asymmetry is very high and the half-graben is not too deep. For wider or deeper half-grabens and moderate asymmetry a larger proportion of the magma tends to become arrested as horizontal intrusions at depth.

  8. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    PubMed

    Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  9. Exploring an active hydrothermal system - An analogue study from the Swiss Alps

    NASA Astrophysics Data System (ADS)

    Egli, Daniel; Herwegh, Marco; Berger, Alfons; Baron, Ludovic

    2016-04-01

    Understanding the detailed flow paths in hydrothermal reservoirs is crucial for successful exploration of naturally porous and permeable rock masses for energy production. However, due to the common inaccessibility of active hydrothermal systems of suitable depth, e.g. in the northern Alpine foreland of the European Alps, direct observations are normally impossible and the knowledge about such systems is still insufficient. For that reason, a known fault-bound hydrothermal system in the crystalline basement of the Aar Massif serves as an analogue for potential geothermal reservoirs in the deep crystalline subsurface of the northern Alpine foreland. During summer 2015, a 125 m hole has been drilled across this active hydrothermal zone on the Grimsel Pass for in-situ characterization of its structural, petrophysical, mechanical as well as geophysical parameters. With this information, this project aims at improving the knowledge of natural hydrothermal systems as a potentially exploitable energy source. The investigated system is characterized by a central breccia zone surrounded by different types of cataclasites and localized high strain zones. The surrounding includes different altered and deformed granitoid host rocks. In this study, we focus on the ductile and brittle deformation (shear zones, fractures, joints) that provides the main fluid pathways. Their spatial distribution around a central water-bearing breccia zone as well as their continuity and permeability provide constraints on the water flow paths in such structurally controlled hydrothermal systems. The aim will be the connection of detailed structural data with petrophysical parameters such as porosities and permeabilities. The drillcore shows the high variability of deformation structures and related fluid pathways at different scales (millimeter-decameter) demonstrating the urgent need for an improved understanding of the link between mechanical evolution, associated deformation structures as well

  10. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies

    PubMed Central

    Ashraf, Zaman; Bais, Abdul; Manir, Md. Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. PMID:26267242

  11. Al-toxicity studies in yeast using gallium as an aluminum analogue.

    PubMed

    Ritchie, Raymond J; Raghupathi, Shyam Sundar

    2008-08-01

    Aluminum (Al) is normally present in soils as the insoluble, harmless Al2O3. The highly toxic Al3+ and AlOH2+ monomeric cations are formed in acid soils but there is little consensus on the physiological basis of Al toxicity in plants. A major factor that has retarded progress in understanding aluminum toxicity in vascular plants is the lack of a convenient radioisotope for Al. Yeast and vascular plants share similar membrane transport mechanisms and so yeast (Saccharomyces cerevisiae) provides a convenient model system for studies of Al-toxicity. Al and gallium (Ga) have closely similar toxic effects on the yeast cells (Ki approximately 100 mmol m-3) and Ga3+ and Al3+, respond similarly to pH and are both reversible by a chelation agent (citric acid). We tested the feasibility of using 67Ga radioisotope as a tracer for Al transport with the view of using it to investigate the mechanism of Al uptake and toxicity in plants. The clinically available 67Ga citrate is unsuitable to use as an aluminum analogue because the chelated form is not toxic. Arrangements need to be made for it to be supplied as 67GaCl3. Large amounts of 67Ga rapidly bind to the cell wall of yeasts with a t 1/2 of approximately 1 s. There is a very slow net uptake of 67Ga into a second phase, presumably the cytoplasm. Uptake into the slow phase has a Vmax of only approximately 16 +/- 4 pmol m(-2) s(-1) (n = 16). The Km of 67Ga uptake could not be precisely determined but is below 100 mmol m(-3) (45 +/- 42 mmol m(-3), n = 16).

  12. 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

  13. CANTON CAFO FIELD SITE STUDY - SITE CHARACTERIZATION AND CONTAMINANT IMPACTS

    EPA Science Inventory

    This presentation of CAFO research concerning the Canton CAFO field site study, including its characterization and contaminant impacts, was given at a NRMRL program review discussion of the CAFO Research Program.

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

    PubMed

    Weidmann, Anke; Conradi, Ania; Groger, Kathrin; Fehm, Lydia; Fydrich, Thomas

    2009-10-01

    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 with regard to the comparability of results. The main goal of this study was to identify a film clip that (a) consistently provokes stress reactions and (b) provokes reactions that are as similar as possible to traumatic stress. We randomly exposed 105 male and female participants to one of four stressful films, differing, e.g., in content and origin. Intrusive memories of the film, reported immediately after the film and during a diary phase of three days, as well as distress, heart rate, and several mood states were measured. A film clip depicting rape elicited the most consistent reactions that were characterized by a higher heart rate, more distress and more intrusive memories, compared to the other three clips. Intrusive memories across all films were especially related to an increase in heart rate and disgust in response to the film.

  15. Biodegradable analogues of DDT*

    PubMed Central

    Metcalf, Robert L.; Kapoor, Inder P.; Hirwe, Asha S.

    1971-01-01

    Despite the immense utility of DDT for vector control its usefulness is prejudiced by its stability in the environment and by the low rate at which it can be degraded biologically. Metabolic studies in insects, in mice, and in a model ecosystem with several food chains have shown that DDT analogues with substituent groups readily attacked by multifunction oxidases undergo a substantial degree of biological degradation and do not appear to be stored readily in animal tissues or concentrated in food chains. Detailed metabolic pathways have been worked out and it is clear that comparative biochemistry can be used to develop DDT analogues that are adequately persistent yet biodegradable. A number of new DDT analogues have been evaluated for insecticidal activity against flies and mosquitos and for their potential usefulness as safe, persistent, and biodegradable insecticides. PMID:5315354

  16. Theoretical study on the influence of different para-substituents on 13C NMR of the single carbonyl curcumin analogues

    NASA Astrophysics Data System (ADS)

    Jia, Fei-yun; Ran, Ming; Zhang, Bo

    2015-12-01

    The structure of eight kinds of different para-substituents curcumin analogues has been optimized at the level of B3LYP/6-31G( d, p), under which the stability has been verified by means of vibration analysis. Moreover, NMR spectra of curcumin analogues compounds have been studied at the level of B3LYP/6-311G( d, p) by GIAO method. The results show that the structure of eight compounds, a larger conjugated system, has good planarity. The effect of ortho-substituents on bond lengths and bond angles is greater than para and meta. Different substituents and different positions of substituents all have different influence on NMR of the single carbonyl curcumin analogues. In general, after the hydrogen atom on the benzene ring is substituted by other groups, the δ value of α-C changes significantly, the δ value of ortho-carbon atom may also have great change, but the δ value change of meta-carbon atoms is not too obvious. The effect of substituent electronegativity on α-C atoms presents obvious regularity, while the influence of conjugate effect on carbon atoms of benzene ring is more complex. Finally, the bigger substituted alkyl is, the more the δ value of α-C increases.

  17. A comparative study on the crystal structure of bicycle analogues to the natural phytotoxin helminthosporins

    NASA Astrophysics Data System (ADS)

    Barbosa, Luiz Cláudio de Almeida; Teixeira, Robson Ricardo; Nogueira, Leonardo Brandão; Maltha, Celia Regina Alvares; Doriguetto, Antônio Carlos; Martins, Felipe Terra

    2016-02-01

    Herein we described structural insights of a series of analogues to helminthosporin phytotoxins. The key reaction used to prepare the compounds corresponded to the [3 + 4] cycloaddition between the oxyallyl cation generated from 2,4-dibromopentan-3-one and different furans. Their structures were confirmed upon IR, NMR and X-ray diffraction analyses. While bicycles 7, 8 and 9 crystallize in the centrosymmetric monoclinic space group P21/c, compound 10 was solved in the noncentrosymmetric orthorhombic space group P212121. The solid materials obtained were shown to be racemic crystals (7, 8, 9) or racemic conglomerate (10). In all compounds, there is formation of a bicycle featured by fused tetrahydropyranone and 2,5-dihydrofuran rings. They adopt chair and envelope conformations, respectively. Crystal packing of all compounds is stabilized through C-H•••O contacts. Conformational aspects as well as similarities and differences among the crystal structures of the synthesized analogues are discussed.

  18. Anomeric selectivity and influenza A virus inhibition study on methoxylated analogues of Pentagalloylglucose.

    PubMed

    Qurat-ul-ain, Shaikh; Wang, Wei; Yang, Meiting; Du, Na; Wan, Shengbiao; Zhang, Lijuan; Jiang, Tao

    2015-01-30

    Anomeric selectivity in galloylation of D-glucose and D-mannose with carboxylic acid was explored under steglich conditions. Base catalyst 4-dimethylaminopyridine favored the formation of alpha-anomers, while adding an acid and carbodiimide favored the formation of beta-anomers. Steric hindrance between α,β-unsaturated acid and C-2 OH stereochemistry (adjacent carbon to anomeric) influenced anomeric selectivity for both D-glucose and D-mannose. The influenza A virus inhibition activities of the synthesized compounds were evaluated in Madin-Darby canine kidney cell line using the cytopathic effect inhibition assay. All the synthetic methoxylated analogues showed more considerable activity against influenza A virus than their corresponding acids, which indicated the sugar core as key functionality for anti-viral activity. The activities of trimethoxy-cinnamic acid Pentagalloylglucose analogues, 3α, 3β, 4α, and 4β (IC50, 109.1 μM, 134.4 μM, 119.5 μM, 111.1 μM, respectively) were better than those of trimethoxy-benzoic acid Pentagalloylglucose analogues, 1-αβ and 2α, 2β (IC50, 209.8 μM, 132.9 μM, 161.2 μM, respectively), which suggested that the double bond in cinnamic acid Pentagalloylglucose analogues makes the major contribution for influenza A virus inhibitory activity. Notably, several anomeric mixtures showed better activities than pure alpha or beta anomer and were almost two times more effective than Ribavirin, a clinically used anti-viral drug. PMID:25498015

  19. Theoretical study of prebiotic precursors: the peptide bond and its silicon, sulphur and phosphorous analogues

    NASA Astrophysics Data System (ADS)

    Chiaramello, J. M.; Talbi, D.; Berthier, G.; Ellinger, Y.

    2005-04-01

    This paper looks at the possibility that the peptide bond may be more common than originally thought, leading to molecules of prebiotic interest containing heavier atoms of the second row of the periodic table. Ab initio Möller-Plesset (MP2) coupled-cluster molecular orbital methods and density functional theory have been used. A first investigation of the six-atom system [C,3H,O,N] showed that formamide, NH2[bond]CH[double bond]O, is the most stable system that can be formed. Systematic studies on this same system in which C, O and N were respectively replaced by Si, S and P were then carried out. It has been found that the peptide-like linkage is the most stable for [C,3H,S,N] and [Si,3H,O,N] where NH2[bond]CH[double bond]S and NH2[bond]SiH[double bond]O are about 10-14 kcal mol[minus sign]1 more favourable than the corresponding enol tautomers and well below other isomers on the energy scale. For [C,3H,O,P], the most stable species is CH3[bond]P[double bond]O, which is found 18 kcal mol[minus sign]1 below the PH2[bond]CH[double bond]O peptide analogue. By correcting the known inadequacies in the calculations with the average theoretical to experimental ratio from the benchmark molecules of the system, it is possible to obtain a best estimate of rotational constants and infrared frequencies that should be precise enough to initiate laboratory experiments and/or observations. The corrected values of B=6.0342 GHz and C=5.4921 GHz for NH2[bond]CH[double bond]S; B=9.2292 GHz and C=6.1164 GHz for NH2[bond]SiH[double bond]O; B=8.0275 GHz and C=6.4779 GHz for CH3[bond]P[double bond]O should be accurate to within a few tenths of a per cent. Theoretical infrared spectra are also provided to assist in identification of these exotic species.

  20. Osmium Bisterpyridine Complexes with Redox-Active Amine Substituents: A Comparison Study with Ruthenium Analogues.

    PubMed

    Sun, Meng-Jia; Shao, Jiang-Yang; Yao, Chang-Jiang; Zhong, Yu-Wu; Yao, Jiannian

    2015-08-17

    Five osmium complexes with redox-active amine substituents, [Os(ttpy)(Ntpy)](PF6)2 (1(PF6)2), [Os(Ntpy)2](PF6)2 (2(PF6)2), [Os(ttpy)(NPhtpy)](PF6)2 (3(PF6)2), [Os(Ntpy)(NPhtpy)](PF6)2 (4(PF6)2), and [Os(NPhtpy)2](PF6)2 (5(PF6)2), have been prepared, where ttpy is 4'-tolyl-2,2':6',2″-terpyridine, Ntpy is 4'-(di-p-anisylamino)-2,2':6',2″-terpyridine, and NPhtpy is 4'-(di-p-anisylaminophen-4-yl)-2,2':6',2″-terpyridine. X-ray crystallographic data of 2(PF6)2 and 4(PF6)2 are presented. These complexes show rich visible absorptions attributed to the singlet metal-to-ligand charge-transfer ((1)MLCT), triplet MLCT, and intraligand charge-transfer transitions. Complexes 3(PF6)2 and 5(PF6)2 show weak emissions around 720 nm at room temperature. All complexes show stepwise oxidations of the osmium ion and the amine segment. However, the redox potentials and the order of the Os(III/II) and N(•+/0) processes vary significantly, depending on the electronic nature of the amine substituents. In the singly oxidized state, either Os(II) → N(•+) MLCT or N → Os(III) ligand-to-metal charge-transfer transitions in the near-infrared region have been observed. For complexes 2(PF6)2, 4(PF6)2, and 5(PF6)2 with two amine substituents, no evidence has been observed for the presence of osmium-mediated amine-amine electronic coupling. Density functional theory (DFT) and time-dependent DFT calculations have been performed to complement these experimental results. The one-electron-oxidized forms 3(3+) and 5(3+) show distinct electron paramagnetic resonance (EPR) signals in CH3CN at room temperature. However, complexes 1(3+), 2(3+), and 4(3+) are EPR silent under similar conditions. In addition, a comparison study has been made between these osmium complexes and the previously reported ruthenium analogues. PMID:26237331

  1. 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

  2. Bisphenol A and Its Analogues Activate Human Pregnane X Receptor

    PubMed Central

    Sui, Yipeng; Ai, Ni; Park, Se-Hyung; Rios-Pilier, Jennifer; Perkins, Jordan T.; Welsh, William J.

    2012-01-01

    Background: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA and its analogues are present in environmental and human samples. Many endocrine-disrupting chemicals, including BPA, have been shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regulator of xenobiotic metabolism. However, the detailed mechanism by which these chemicals activate PXR remains unknown. Objective: We investigated the mechanism by which BPA interacts with and activates PXR and examined selected BPA analogues to determine whether they bind to and activate PXR. Methods: Cell-based reporter assays, in silico ligand–PXR docking studies, and site-directed mutagenesis were combined to study the interaction between BPA and PXR. We also investigated the influence of BPA and its analogues on the regulation of PXR target genes in human LS180 cells. Results: We found that BPA and several of its analogues are potent agonists for human PXR (hPXR) but do not affect mouse PXR activity. We identified key residues within hPXR’s ligand-binding pocket that constitute points of interaction with BPA. We also deduced the structural requirements of BPA analogues that activate hPXR. BPA and its analogues can also induce PXR target gene expression in human LS180 cells. Conclusions: The present study advances our understanding of the mechanism by which BPA interacts with and activates human PXR. Activation of PXR by BPA may explain some of the adverse effects of BPA in humans. PMID:22214767

  3. 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.

  4. 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…

  5. An analogue study of the initial carryover effects of meditation, hypnosis, and relaxation using native college students.

    PubMed

    Colby, F

    1991-06-01

    An analogue study involving two experiments was conducted to test the initial carryover effects of hypnosis, meditation, and relaxation upon self-reports of awareness. In the first experiment, concentrative meditators reported fewer nonsensorial events than controls. In the second experiment, concentrative meditators again reported fewer nonsensorial events, but covariate analysis and pretest/posttest comparisons revealed that it was the controls who had changed, increasing their nonsensorial reports. In addition, the relaxation group increased its reports of somatic awareness. Results were discussed in terms of the effects of performance demands and the possibility that meditation and hypnosis might be able to disinhibit awareness processes otherwise inhibited by normal daily routines.

  6. The project De Caldas International Project: An example of a large-scale radwaste isolation natural analogue study

    SciTech Connect

    Shea, M.

    1995-09-01

    The proper isolation of radioactive waste is one of today`s most pressing environmental issues. Research is being carried out by many countries around the world in order to answer critical and perplexing questions regarding the safe disposal of radioactive waste. Natural analogue studies are an increasingly important facet of this international research effort. The Pocos de Caldas Project represents a major effort of the international technical and scientific community towards addressing one of modern civilization`s most critical environmental issues - radioactive waste isolation.

  7. Distribution and geochemical characterization of coalbed gases at excavation fields at natural analogue site area Velenje Basin, Slovenia

    NASA Astrophysics Data System (ADS)

    Kanduč, Tjaša; Žigon, Stojan; Grassa, Fausto; Sedlar, Jerneja; Zadnik, Ivo; Zavšek, Simon

    2016-04-01

    Unconventional gas resources, including coal bed methane and shale gas, are a growing part of the global energy mix, which has changed the economic and strategic picture for gas consuming and producing countries, including the USA, China and Australia that, together are responsible for around half the currently recoverable unconventional gas resources. However, CBM production was often hindered by low permeability and mineralization in cleats and fractures, necessitating the development of cost effective horizontal drilling and completion techniques. Geochemical and isotopic monitoring of coalbed gases at excavation fields in Velenje Basin started in year 2000, with the aim to obtain better insights into the origin of coalbed gases. Results from active excavation fields in the mining areas Pesje and Preloge in the year period 2014-2015 are presented in this study. Composition and isotopic composition of coalbed gases were determined with mass - spectrometric methods. The chemical (methane, carbon dioxide, nitrogen) and isotopic composition of carbon in methane and carbon dioxide in the Velenje Basin vary and depend on the composition of the source of coalbed gas before excavation, advancement of the working face, depth of the longwall face, pre-mining activity and newly mined activity. The basic gas components determined in excavation fields are carbon dioxide and methane. Knowledge of the stable isotope geochemistry of coal bed and shale gas and the related production water is essential to determine not only gas origins but also the dominant methanogenic pathway in the case of microbial gas. Concentrations of methane at active excavation fields are changing from 1.8 to 63.9 %, concentrations of carbon dioxide are changing from 36.1 to 98.2% and CDMI (Carbon Dioxide Methane Index) index from 0.2 to 100 %. Isotopic composition of carbon dioxide is changing from -11.0 to -1.9‰ , isotopic composition of methane from -71.8 to -43.3‰ , isotopic composition of

  8. Studying Z-DNA and B- to Z-DNA transitions using a cytosine analogue FRET-pair

    PubMed Central

    Dumat, Blaise; Larsen, Anders Foller; Wilhelmsson, L. Marcus

    2016-01-01

    Herein, we report on the use of a tricyclic cytosine FRET pair, incorporated into DNA with different base pair separations, to study Z-DNA and B-Z DNA junctions. With its position inside the DNA structure, the FRET pair responds to a B- to Z-DNA transition with a distinct change in FRET efficiency for each donor/acceptor configuration allowing reliable structural probing. Moreover, we show how fluorescence spectroscopy and our cytosine analogues can be used to determine rate constants for the B- to Z-DNA transition mechanism. The modified cytosines have little influence on the transition and the FRET pair is thus an easily implemented and virtually non-perturbing fluorescence tool to study Z-DNA. This nucleobase analogue FRET pair represents a valuable addition to the limited number of fluorescence methods available to study Z-DNA and we suggest it will facilitate, for example, deciphering the B- to Z-DNA transition mechanism and investigating the interaction of DNA with Z-DNA binding proteins. PMID:26896804

  9. Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

    PubMed

    Luger, Peter; Dittrich, Birger; Tacke, Reinhold

    2015-09-14

    The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

  10. Synthesis and conformational studies of calixarene analogue chiral [3.3.1]metacyclophanes

    NASA Astrophysics Data System (ADS)

    Islam, Md Monarul; Hirotsugu, Tomiyasu; Thuery, Pierre; Matsumoto, Taisuke; Tanaka, Junji; Elsegood, Mark R. J.; Redshaw, Carl; Yamato, Takehiko

    2015-10-01

    Trihydroxy[3.3.1]metacyclophane, which can be regarded as an unsymmetrical or incomplete "homocalix[3]arene", has been prepared from trimethoxy[3.3.1]metacyclophane by demethylation with trimethylsilyl iodide in MeCN. Di-O-methylation at the lower rim of trihydroxy[3.3.1]metacyclophane in the presence of K2CO3 in acetone afforded a novel, inherently chiral calixarene-analogue, namely a macrocyclic [3.3.1]metacyclophane, possessing C1 symmetry. The inherent chirality of the two conformers was characterized by 1H NMR spectroscopy by addition of an excess of Pirkle's chiral shift reagent [(S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol], which caused a splitting of the OMe group and AB patterns corresponding to the methylene protons.

  11. Laboratory simulation and modeling of size, shape distributed interstellar graphite dust analogues: A comparative study

    NASA Astrophysics Data System (ADS)

    Boruah, Manash J.; Gogoi, Ankur; Ahmed, Gazi A.

    2016-06-01

    The computation of the light scattering properties of size and shape distributed interstellar graphite dust analogues using discrete dipole approximation (DDA) is presented. The light scattering properties of dust particles of arbitrary shapes having sizes ranging from 0.5 to 5.0 μm were computed using DDSCAT 7.3.0 software package and an indigenously developed post-processing tool for size and shape averaging. In order to model realistic samples of graphite dust and compute their light scattering properties using DDA, different target geometries were generated to represent the graphite particle composition in terms of surface smoothness, surface roughness and aggregation or their combination, for using as the target for DDSCAT calculations. A comparison of the theoretical volume scattering function at 543.5 nm and 632.8 nm incident wavelengths with laboratory simulation is also presented in this paper.

  12. Photophysical and nonlinear optical studies of tetraakynyl zincphthalocyanine and its "clicked" analogue

    NASA Astrophysics Data System (ADS)

    Bankole, Owolabi M.; Nyokong, Tebello

    2015-06-01

    We report here for the first time on the photophysical and nonlinear optical behavior of tetra-substituted alkynyl zinc phthalocyanine and its "clicked" analogue (4 and 5). The compounds exhibited high triplet quantum yields in dimethylsulphoxide (DMSO). Nonlinear optical (NLO) properties were also evaluated for the two compounds at 532 nm and 10 ns in DMSO. We observed two-photon absorption (2PA) and strong reverse saturable absorption (RSA) as the dominant mechanisms at nanosecond laser excitation. The presence of electron acceptor groups fused with triazole linkers in the peripheral positions of 4 provide excellent coexistent features, such as enhanced triplet quantum yields and lifetimes compared to 5. Large third-order susceptibility (2.09 × 10-11 and 3.53 × 10-9 esu) and hyperpolarizability (1.09 × 10-30 and 9.13 × 10-29 esu) were estimated for complexs 4 and 5, respectively.

  13. Evidence for Radical-Mediated Catalysis by HppE – A Study Using Cyclopropyl and Methylenecyclopropyl Substrate Analogues

    PubMed Central

    Huang, Hui; Chang, Wei-chen; Pai, Pei-Jing; Romo, Anthony; Mansoorabadi, Steven O.; Russell, David H.; Liu, Hung-wen

    2012-01-01

    (S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) is an unusual mononuclear iron enzyme that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonic acid ((S)-HPP) in the biosynthesis of the antibiotic fosfomycin. HppE also recognizes (R)-2-hydroxypropylphosphonic acid ((R)-HPP) as a substrate and converts it to 2-oxo-propylphosphonic acid. To probe the mechanisms of these HppE-catalyzed oxidations, cyclopropyl- and methylenecyclopropyl-containing compounds were synthesized and studied as radical clock substrate analogues. Enzymatic assays indicated that the (S)- and (R)-isomers of the cyclopropyl-containing analogues were efficiently converted to epoxide and ketone products by HppE, respectively. In contrast, the ultrafast methylenecyclopropyl-containing probe inactivated HppE, consistent with a rapid radical-triggered ring-opening process that leads to enzyme inactivation. Taken together, these findings provide, for the first time, experimental evidence for the involvement of a C2-centered radical intermediate with a lifetime on the order of nanoseconds in the HppE-catalyzed oxidation of (R)-HPP. PMID:23006053

  14. Aspartame and Its Analogues

    NASA Astrophysics Data System (ADS)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  15. Stadium Site Utilization Study. University of Cincinnati.

    ERIC Educational Resources Information Center

    Caudill, Rowlett, and Scott, New York, NY.

    An evaluative study of the University of Cincinnati stadium site shows its potential with relation to the existing campus. Conclusions and recommendations concerning its future utilization are presented, based upon consideration of the following--(1) basic university planning policies, (2) assets and liabilities of the site, (3) the decision to…

  16. Talking about depression: An analogue study of physician gender and communication style on patient disclosures

    PubMed Central

    Roter, Debra L.; Erby, Lori H.; Adams, Ann; Buckingham, Christopher D; Vail, Laura; Realpe, Alba; Larson, Susan; Hall, Judith A.

    2014-01-01

    Objectives To disentangle the effects of physician gender and patient-centered communication style on patients’ oral engagement in depression care. Methods Physician gender, physician race and communication style (high patient-centered (HPC) and low patient-centered (LPC)) were manipulated and presented as videotaped actors within a computer simulated medical visit to assess effects on analogue patient (AP) verbal responsiveness and care ratings. 307 APs (56% female; 70% African American) were randomly assigned to conditions and instructed to verbally respond to depression-related questions and indicate willingness to continue care. Disclosures were coded using Roter Interaction Analysis System (RIAS). Results Both male and female APs talked more overall and conveyed more psychosocial and emotional talk to HPC gender discordant doctors (all p <.05). APs were more willing to continue treatment with gender-discordant HPC physicians (p<.05). No effects were evident in the LPC condition. Conclusions Findings highlight a role for physician gender when considering active patient engagement in patient-centered depression care. This pattern suggests that there may be largely under-appreciated and consequential effects associated with patient expectations in regard to physician gender that these differ by patient gender. Practice Implications High patient-centeredness increases active patient engagement in depression care especially in gender discordant dyads. PMID:24882087

  17. Theoretical Study of the Photophysics of 8-Vinylguanine, an Isomorphic Fluorescent Analogue of Guanine.

    PubMed

    Kochman, Michał A; Pola, Martina; Miller, R J Dwayne

    2016-08-11

    Paving the way for the application of the algebraic-diagrammatic construction scheme of second-order (ADC(2)) to systems based on the guanine chromophore, we demonstrate the this excited-state electronic structure method provides a realistic description of the photochemistry of 9H-guanine, in close agreement with the benchmark provided by the CASPT2 method. We then proceed to apply the ADC(2) method to the photochemistry of 8-vinylguanine (8vG), a minimally modified analogue of guanine which, unlike the naturally occurring nucleobase, displays intense fluorescence, indicative of a much longer-lived excited electronic state. The emissive electronic state of 8vG is identified as an ππ*-type intramolecular charge transfer (ICT) state, in which a charge of roughly -0.2 e is transferred from the guanine moiety onto the vinyl substituent. The main radiationless deactivation pathway competing with fluorescence is predicted to involve the molecule leaving the minimum on the ICT ππ* state, and reaching a region of the S1 adiabatic state where it resembles the La ππ* state of unmodified 9H-guanine. The topology of the La ππ* region of the S1 state favors subsequent internal conversion at a crossing seam with the ground electronic state. The sensitivity of this process to environment polarity may explain the experimentally observed fluorescence quenching of 8vG upon incorporation in single- and double-stranded DNA. PMID:27427772

  18. Study the interactions between human serum albumin and two antifungal drugs: fluconazole and its analogue DTP.

    PubMed

    Zhang, Shao-Lin; Yao, Huankai; Wang, Chenyin; Tam, Kin Y

    2014-11-01

    Binding affinities of fluconazole and its analogue 2-(2,4-dichlorophenyl)-1,3-di(1H-1,2,4-triazol-yl)-2-propanol (DTP) to human serum albumin (HSA) were investigated under approximately human physiological conditions. The obtained result indicated that HSA could generate fluorescent quenching by fluconazole and DTP because of the formation of non-fluorescent ground-state complexes. Binding parameters calculated from the Stern-Volmer and the Scatchard equations showed that fluconazole and DTP bind to HSA with binding affinities of the order 10(4)L/mol. The thermodynamic parameters revealed that the binding was characterized by negative enthalpy and positive entropy changes, suggesting that the binding reaction was exothermic. Hydrogen bonds and hydrophobic interaction were found to be the predominant intermolecular forces stabilizing the drug-protein. The effect of metal ions on the binding constants of fluconazole-HSA complex suggested that the presence of Mg(2+) and Zn(2+) ions could decrease the free drug level and extend the half-life in the systematic circulation. Docking experiments revealed that fluconazole and DTP binds in HSA mainly by hydrophobic interaction with the possibility of hydrogen bonds formation between the drugs and the residues Arg 222, Lys 199 and Lys 195 in HSA.

  19. Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer.

    PubMed Central

    Macaulay, V. M.; Smith, I. E.; Everard, M. J.; Teale, J. D.; Reubi, J. C.; Millar, J. L.

    1991-01-01

    We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically. Images Figure 4 PMID:1654981

  20. Formation of DNA nanoparticles in the presence of novel polyamine analogues: a laser light scattering and atomic force microscopic study

    PubMed Central

    Vijayanathan, Veena; Thomas, Thresia; Antony, Thomas; Shirahata, Akira; Thomas, T. J.

    2004-01-01

    We synthesized a pentamine (3-3-3-3) and two hexamine (3-3-3-3-3 and 3-4-3-4-3) analogues of the natural polyamine, spermine (3-4-3) and studied their effectiveness in condensing pGL3 plasmid DNA, using light scattering and atomic force microscopic (AFM) techniques. The midpoint concentration of the polyamines on pGL3 condensation (EC50) was 11.3, 10.6, 1.5, 0.49 and 0.52 µM, respectively, for 3-4-3, norspermine (3-3-3), 3-3-3-3, 3-3-3-3-3 and 3-4-3-4-3 in 10 mM Na cacodylate buffer. Dynamic laser light scattering study showed a decrease in hydrodynamic radii of plasmid DNA particles as the number of positive charges on the polyamines increased. AFM data showed the presence of toroids with outer diameter of 117–191 nm for different polyamines, and a mean height of 2.61 ± 0.77 nm. AFM results also revealed the presence of intermediate structures, including those showing circumferential winding of DNA to toroids. The dependence of the EC50 on Na+ concentration suggests different modes of binding of spermine and its higher valent analogues with DNA. Our results show a 20-fold increase in the efficacy of hexamines for DNA condensation compared to spermine, and provide new insights into the mechanism(s) of DNA nanoparticle formation. These studies might help to develop novel nonviral gene delivery vehicles. PMID:14704349

  1. 3D-QSAR Studies on a Series of Dihydroorotate Dehydrogenase Inhibitors: Analogues of the Active Metabolite of Leflunomide

    PubMed Central

    Li, Shun-Lai; He, Mao-Yu; Du, Hong-Guang

    2011-01-01

    The active metabolite of the novel immunosuppressive agent leflunomide has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. Self-organizing molecular field analysis (SOMFA), a simple three-dimensional quantitative structure-activity relationship (3D-QSAR) method is used to study the correlation between the molecular properties and the biological activities of a series of analogues of the active metabolite. The statistical results, cross-validated rCV2 (0.664) and non cross-validated r2 (0.687), show a good predictive ability. The final SOMFA model provides a better understanding of DHODH inhibitor-enzyme interactions, and may be useful for further modification and improvement of inhibitors of this important enzyme. PMID:21686163

  2. Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents.

    PubMed

    Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L; Guzman, Monica L; Crooks, Peter A

    2015-03-01

    A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI50 values of <10 nM against 74% and 70%, respectively, of the human cancer cell lines in the 60-cell panel. Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine, and were stabilized by van der Waals' interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs.

  3. Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase.

    PubMed

    Ashraf, Zaman; Rafiq, Muhammad; Seo, Sung-Yum; Kwon, Kang Sung; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf

    2015-06-15

    The present studies reports the synthesis of hydoxylated thymol analogues (4a-e) and (6a-c) as mushroom tyrosinase inhibitors. The title compounds were obtained in good yield and characterized by FTIR, (1)H NMR, (13)C NMR, Mass spectral data and X-ray crystallography in case of compound (6a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 2-[5-methyl-2-(propan-2-yl)phenoxy]-2-oxoethyl (2E)-3-(4-hydroxyphenyl)prop-2-enoate (6b) showed tyrosinase inhibitory activity (IC50 15.20 μM) comparable to kojic acid (IC50 16.69 μM) while 2-[5-methyl-2-(propan-2-yl)phenoxy]-2-oxoethyl 3,4-dihydroxybenzoate (4d) exhibited higher antioxidant potential (IC50 11.30 μM) than standard ascorbic acid (IC50 24.20 μM). The docking studies of synthesized thymol analogues was also performed against tyrosinase protein (PDBID 2ZMX) to compare the binding affinities with IC50 values. The predicted binding affinities are in good agreement with the IC50 values as compound (6b) showed highest binding affinity -7.1 kcal/mol. The kinetic mechanism analyzed by Lineweaver-Burk plots exhibited that compound (4d) and (6b) inhibit the enzyme by two different pathways displayed mixed-type inhibition. The inhibition constants Ki calculated from Dixon plots for compounds (4d) and (6b) are 34 μM and 25 μM respectively. It was also found from kinetic analysis that derivative (6b) formed reversible enzyme inhibitor complex. It is propose on the basis of our investigation that title compound (6b) may serve as lead structure for the design of more potent tyrosinase inhibitors.

  4. Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase.

    PubMed

    Ashraf, Zaman; Rafiq, Muhammad; Seo, Sung-Yum; Kwon, Kang Sung; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf

    2015-06-15

    The present studies reports the synthesis of hydoxylated thymol analogues (4a-e) and (6a-c) as mushroom tyrosinase inhibitors. The title compounds were obtained in good yield and characterized by FTIR, (1)H NMR, (13)C NMR, Mass spectral data and X-ray crystallography in case of compound (6a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 2-[5-methyl-2-(propan-2-yl)phenoxy]-2-oxoethyl (2E)-3-(4-hydroxyphenyl)prop-2-enoate (6b) showed tyrosinase inhibitory activity (IC50 15.20 μM) comparable to kojic acid (IC50 16.69 μM) while 2-[5-methyl-2-(propan-2-yl)phenoxy]-2-oxoethyl 3,4-dihydroxybenzoate (4d) exhibited higher antioxidant potential (IC50 11.30 μM) than standard ascorbic acid (IC50 24.20 μM). The docking studies of synthesized thymol analogues was also performed against tyrosinase protein (PDBID 2ZMX) to compare the binding affinities with IC50 values. The predicted binding affinities are in good agreement with the IC50 values as compound (6b) showed highest binding affinity -7.1 kcal/mol. The kinetic mechanism analyzed by Lineweaver-Burk plots exhibited that compound (4d) and (6b) inhibit the enzyme by two different pathways displayed mixed-type inhibition. The inhibition constants Ki calculated from Dixon plots for compounds (4d) and (6b) are 34 μM and 25 μM respectively. It was also found from kinetic analysis that derivative (6b) formed reversible enzyme inhibitor complex. It is propose on the basis of our investigation that title compound (6b) may serve as lead structure for the design of more potent tyrosinase inhibitors. PMID:26025140

  5. Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents

    PubMed Central

    Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L.; Guzman, Monica L.; Crooks, Peter A.

    2015-01-01

    A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI50 values of <10 nM against 74% and 70%, respectively, of the human cancer cell lines in the 60-cell panel. Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine, and were stablized by van der Waals’ interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. PMID:25557492

  6. Biochemical characterization of the novel rice kinesin K23 and its kinetic study using fluorescence resonance energy transfer between an intrinsic tryptophan residue and a fluorescent ATP analogue.

    PubMed

    Umezu, Nozomi; Hanzawa, Nobue; Yamada, Masafumi D; Kondo, Kazunori; Mitsui, Toshiaki; Maruta, Shinsaku

    2011-05-01

    We previously demonstrated that the rice kinesin K16, which belongs to the kinesin-7 subfamily, has unique enzymatic properties and atomic structure within key functional regions. In this study, we focused on a novel rice plant kinesin, K23, which also belongs to the kinesin-7 subfamily. The biochemical characterization of the K23 motor domain (K23MD) was studied and compared with the rice kinesin K16 and other related kinesins. K23 exhibits ∼45-fold (1.3 Pi mol(-1) site mol(-1) s(-1)) lower microtubule-dependent ATPase activity than conventional kinesins, whereas its affinity for microtubules is comparable with conventional kinesins. MgADP-free K23 is unstable compared with the unusually stable MgADP-free K16MD. The enzymatic properties of K23MD are somewhat different from those of K16. We used a fluorescent ATP analogue 2'(3')-O-(N'-methylanthraniloyl)-ATP (mant-ATP) for the kinetic characterization of K23. The fluorescence of mant-ATP was not significantly altered during its hydrolysis by K23. However, significant fluorescence resonance energy transfer (FRET) between mant-ATP and W21 in the motor domain was observed. The kinetic study using FRET revealed that K23 has unique kinetic characteristics when compared with other kinesins.

  7. 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.

  8. The role of GLP-1 mimetics and basal insulin analogues in type 2 diabetes mellitus: guidance from studies of liraglutide

    PubMed Central

    Barnett, A H

    2012-01-01

    In people with type 2 diabetes mellitus (T2DM), the incretin effect is reduced, but the recent advent of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide (GLP)-1 agonists/analogues has enabled restoration of at least some of the function of the incretin system, with accompanying improvements in glycaemic control. Two GLP-1 receptor agonists/analogues are currently approved for the treatment of T2DM—exenatide (Byetta®, Eli Lilly & Co., Indianapolis, IN, US) and liraglutide (Victoza®, Novo Nordisk, Bagsvaerd, Denmark); a once-weekly formulation of exenatide (Bydureon®, Eli Lilly & Co.) has also been approved by the European Medicines Agency. The National Institute for Health and Clinical Excellence (NICE) has recently published guidance on the use of liraglutide in T2DM, based on evidence from the Liraglutide Effect and Action in Diabetes (LEAD) Phase III trial programme, which compared liraglutide with existing glucose-lowering therapies, such as exenatide and insulin glargine. The LEAD programme reported HbA1c reductions from 0.8 to 1.5% with liraglutide (1.2 and 1.8 mg), accompanied by low rates of hypoglycaemia and some weight loss; side effects were primarily gastrointestinal in nature (e.g. nausea and diarrhoea). Based on the findings of the LEAD studies and the NICE recommendation, liraglutide now represents an important therapy widely available in the UK for certain patient groups, including those with a body mass index (BMI) ≥35.0 kg/m2, and patients with a BMI <35 kg/m2 who are considered unsuitable for insulin and are failing to meet targets for glycaemic control with oral agents. NICE guidelines still suggest that most patients without considerable obesity (BMI <35 kg/m2) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin. PMID:22051096

  9. Dose-finding study for the use of long-acting gonadotrophin-releasing hormone analogues prior to ovarian stimulation for IVF.

    PubMed

    Yim, S F; Lok, I H; Cheung, L P; Briton-Jones, C M; Chiu, T T; Haines, C J

    2001-03-01

    Gonadotrophin-releasing hormone (GnRH) analogues improve the outcome of treatment with IVF by increasing the number and quality of oocytes retrieved and by reducing cycle cancellation rates. Whilst short-acting GnRH analogues are most commonly used, depot preparations are now available that are more convenient for patient use. Some studies have reported that pregnancy rates with depot GnRH analogues are similar to those of short-acting preparations, but others have suggested that the more profound down-regulation seen with depot GnRH analogues results in inferior embryo quality. The purpose of this study was to determine whether a lower than conventional dose of a depot GnRH analogue may be more appropriate for use in ovarian stimulation prior to IVF. Sixty patients were randomized to receive either 3.75 mg (conventional dose) or 1.87 mg (low dose) triptorelin prior to ovarian stimulation for IVF. Suppression was measured using serum concentrations of LH measured 2 and 3 weeks after the administration of the GnRH analogues, the dose of gonadotrophin used and the time to resumption of menses. Mean concentrations of LH were 2.2 +/- 1.0 and 1.1 +/- 0.6 IU/l in the conventional dose group and 3.5 +/- 5.5 and 2.7 +/- 1.9 IU/l in the low dose group (P < 0.05 at 2 and 3 weeks). There were no significant differences between the doses of gonadotrophins used, the number of oocytes and embryos available and the time to resumption of menses, nor in the pregnancy rates. Although the degree of suppression as measured biochemically was more profound with the conventional dose, this did not affect the IVF outcome. The use of a lower dose therefore appears to be equally effective and could contribute to a reduction in the cost of treatment.

  10. 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

  11. Novel lavendamycin analogues as antitumor agents: synthesis, in vitro cytotoxicity, structure-metabolism, and computational molecular modeling studies with NAD(P)H:quinone oxidoreductase 1.

    PubMed

    Hassani, Mary; Cai, Wen; Holley, David C; Lineswala, Jayana P; Maharjan, Babu R; Ebrahimian, G Reza; Seradj, Hassan; Stocksdale, Mark G; Mohammadi, Farahnaz; Marvin, Christopher C; Gerdes, John M; Beall, Howard D; Behforouz, Mohammad

    2005-12-01

    Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet-Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2'-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2'-CH2OH-7-NH2 derivative) and 31 (2'-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 +/- 30 and 0.1 +/- 0.1 micromol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT cells with 37 as the most selective. Molecular docking supported a model in which the best substrates were capable of efficient hydrogen-bonding interactions with key residues of the active site along with hydride ion reception. PMID:16302813

  12. 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

  13. Comparative Study of Modern Stromatolites in Coastal Lagoa Salgada and Lagoa Vermehla, Brazil: Analogues for Precambrian Environmental Evolution

    NASA Astrophysics Data System (ADS)

    Vasconcelos, C.; Lundberg, R.; Bahniuk, A.; Och, L.; McKenzie, J. A.

    2009-12-01

    Ancient microbial processes continue to be active in isolated modern lacustrine environments. As these unique environments can serve as analogues for Precambrian systems, biogeochemical studies in modern lakes or lagoons can be used to develop a better understanding of microcosms thriving on the early Earth. We study the biogeochemical processes associated with modern stromatolite formation in two distinctly different lagoons (lagoas in Portuguese) located in a special semi-arid microclimate within the tropical region along the central Brazilian coast. Although the stromatolites in both lagoons are characterized by high-Mg calcite to dolomite precipitation, the aqueous geochemistry is very different. Lagoa Salgada, Brazil contains fresh to brackish water feed by meteoric ground waters and has low sulfate concentrations, whereas Lagoa Vermehla, Brazil is brackish to hypersaline as a result of recharge with altered marine water and has sulfate concentrations greater than normal sea water. The average oxygen isotope composition of the in situ stromatolites reflects the different hydrology of the lakes: δ18O values of Lagoa Salgada stromatolites average -1.5 ‰, while the δ18O values of Lagoa Vermehla stromatolites average 1.5 ‰. Furthermore, the average carbon isotope composition of the stromatolites mirrors the prominent microbial process active in the lakes: δ13C values of Lagoa Salgada stromatolites average 10 to 20 ‰, while the δ13C values of Lagoa Vermehla stromatolites average -2.5 ‰. These dissimilar δ13C values indicate the importance of different microbial processes as the main carbon source for the carbonate incorporated into the laminae, that is, methanogenesis vs. sulfate reduction, respectively. In fact, using microbiologic and genomic techniques, the molecular characterization of the microbial mats from which the discrete laminae develop is consistent with this geochemical observation. We propose that a comparative study of the Lagoa Salgada

  14. 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…

  15. Asymmetric Synthesis and Binding Study of New Long-Chain HPA-12 Analogues as Potent Ligands of the Ceramide Transfer Protein CERT.

    PubMed

    Ďuriš, Andrej; Daïch, Adam; Santos, Cécile; Fleury, Laurence; Ausseil, Frédéric; Rodriguez, Frédéric; Ballereau, Stéphanie; Génisson, Yves; Berkeš, Dušan

    2016-05-01

    A series of 12 analogues of the Cer transfer protein (CERT) antagonist HPA-12 with long aliphatic chains were prepared as their (1R,3S)-syn and (1R,3R)-anti stereoisomers from pivotal chiral oxoamino acids. The enantioselective access to these intermediates as well as their ensuing transformation relied on a practical crystallization-induced asymmetric transformation (CIAT) process. Sonogashira coupling followed by triple bond reduction and thiophene ring hydrodesulfurization (HDS) into the corresponding alkane moieties was then implemented to complete the synthetic routes delivering the targeted HPA-12 analogues in concise 4- to 6-step reaction sequences. Ten compounds were evaluated regarding their ability to bind to the CERT START domain by using the recently developed time-resolved FRET-based homogeneous (HTR-FRET) binding assay. The introduction of a lipophilic appendage on the phenyl moiety led to an overall 10- to 1000-fold enhancement of the protein binding, with the highest effect being observed for a n-hexyl residue in the meta position. The importance of the phenyl ring for the activity was indicated by the reduced potency of the 3-deoxyphytoceramide aliphatic analogues. The 1,3-syn stereoisomers were systematically more potent than their 1,3-anti analogues. In silico studies were used to rationalized these trends, leading to a model of protein recognition coherent with the stronger binding of (1R,3S)-syn HPAs.

  16. Bioluminescence of beetle luciferases with 6'-amino-D-luciferin analogues reveals excited keto-oxyluciferin as the emitter and phenolate/luciferin binding site interactions modulate bioluminescence colors.

    PubMed

    Viviani, Vadim R; Neves, Deimison Rodrigues; Amaral, Danilo Trabuco; Prado, Rogilene A; Matsuhashi, Takuto; Hirano, Takashi

    2014-08-19

    Beetle luciferases produce different bioluminescence colors from green to red using the same d-luciferin substrate. Despite many studies of the mechanisms and structural determinants of bioluminescence colors with firefly luciferases, the identity of the emitters and the specific active site interactions responsible for bioluminescence color modulation remain elusive. To address these questions, we analyzed the bioluminescence spectra with 6'-amino-D-luciferin (aminoluciferin) and its 5,5-dimethyl analogue using a set of recombinant beetle luciferases that naturally elicit different colors and different pH sensitivities (pH-sensitive, Amydetes vivianii λmax=538 nm, Macrolampis sp2 λmax=564 nm; pH-insensitive, Phrixotrix hirtus λmax=623 nm, Phrixotrix vivianii λmax=546 nm, and Pyrearinus termitilluminans λmax=534 nm), a luciferase-like enzyme (Tenebrionidae, Zophobas morio λmax=613 nm), and mutants of C311 (S314). The green-yellow-emitting luciferases display red-shifted bioluminescence spectra with aminoluciferin in relation to those with D-luciferin, whereas the red-emitting luciferases displayed blue-shifted spectra. Bioluminescence spectra with 5,5-dimethylaminoluciferin, in which enolization is blocked, were almost identical to those of aminoluciferin. Fluorescence probing using 2-(4-toluidino)naphthalene-6-sulfonate and inference with aminoluciferin confirm that the luciferin binding site of the red-shifted luciferases is more polar than in the case of the green-yellow-emitting luciferases. Altogether, the results show that the keto form of excited oxyluciferin is the emitter in beetle bioluminescence and that bioluminescence colors are essentially modulated by interactions of the 6'-hydroxy group of oxyluciferin and basic moieties under the influence of the microenvironment polarity of the active site: a strong interaction between a base moiety and oxyluciferin phenol in a hydrophobic microenvironment promotes green-yellow emission, whereas a more polar

  17. Astrobiology through the ages of Mars: the study of terrestrial analogues to understand the habitability of Mars.

    PubMed

    Fairén, Alberto G; Davila, Alfonso F; Lim, Darlene; Bramall, Nathan; Bonaccorsi, Rosalba; Zavaleta, Jhony; Uceda, Esther R; Stoker, Carol; Wierzchos, Jacek; Dohm, James M; Amils, Ricardo; Andersen, Dale; McKay, Christopher P

    2010-10-01

    Mars has undergone three main climatic stages throughout its geological history, beginning with a water-rich epoch, followed by a cold and semi-arid era, and transitioning into present-day arid and very cold desert conditions. These global climatic eras also represent three different stages of planetary habitability: an early, potentially habitable stage when the basic requisites for life as we know it were present (liquid water and energy); an intermediate extreme stage, when liquid solutions became scarce or very challenging for life; and the most recent stage during which conditions on the surface have been largely uninhabitable, except perhaps in some isolated niches. Our understanding of the evolution of Mars is now sufficient to assign specific terrestrial environments to each of these periods. Through the study of Mars terrestrial analogues, we have assessed and constrained the habitability conditions for each of these stages, the geochemistry of the surface, and the likelihood for the preservation of organic and inorganic biosignatures. The study of these analog environments provides important information to better understand past and current mission results as well as to support the design and selection of instruments and the planning for future exploratory missions to Mars.

  18. Structure Activity Relationship and Mechanism of Action Studies of Manzamine Analogues for the Control of Neuroinflammation and Cerebral Infections

    PubMed Central

    Peng, Jiangnan; Kudrimoti, Sucheta; Prasanna, Sivaprakasam; Odde, Srinivas; Doerksen, Robert J.; Pennaka, Hari K; Choo, Yeun-Mun; Rao, Karumanchi V.; Tekwani, Babu L.; Madgula, Vamsi; Khan, Shabana I.; Wang, Bin; Mayer, Alejandro M. S.; Jacob, Melissa R.; Tu, Lan Chun; Gertsch, Jürg; Hamann, Mark T.

    2010-01-01

    Structure-activity relationship studies were carried out by chemical modification of manzamine A (1), 8-hydroxymanzamine A (2), manzamine F (14), and ircinol isolated from the sponge Acanthostrongylophora. The derived analogues were evaluated for antimalarial, antimicrobial, and antineuroinflammatory activities. Several modified products exhibited potent and improved in vitro antineuroinflammatory, antimicrobial, and antimalarial activity. 1 showed improved activity against malaria compared to chloroquine in both multi- and single-dose in vivo experiments. The significant antimalarial potential was revealed by a 100% cure rate of malaria in mice with one administration of 100 mg/kg of 1. The potent antineuroinflammatory activity of the manzamines will provide great benefit for the prevention and treatment of cerebral infections (e.g. Cryptococcus and Plasmodium). In addition, 1 was shown to permeate across the blood-brain barrier (BBB) in an in vitro model using a MDR-MDCK monolayer. Docking studies support that 2 binds to the ATP-noncompetitive pocket of glycogen synthesis kinase-3β (GSK-3β), which is a putative target of manzamines. Based on the results presented here it will be possible to initiate rational drug design efforts around this natural product scaffold for the treatment of several different diseases. PMID:20017491

  19. Novel quinazoline-urea analogues as modulators for Aβ-induced mitochondrial dysfunction: design, synthesis, and molecular docking study.

    PubMed

    Elkamhawy, Ahmed; Lee, Jiyoun; Park, Beoung-Geon; Park, Insun; Pae, Ae Nim; Roh, Eun Joo

    2014-09-12

    A novel series of twenty-six quinazoline-urea derivatives was designed and synthesized. Their blocking activities against β-amyloid peptide (Aβ) induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measured the change of mitochondrial membrane potential. Seven compounds showed better inhibitory activities than the standard Cyclosporin A (CsA). The most active analogues were tested by MTT assay to evaluate their toxicity on the cellular survival; they revealed excellent cellular viability. To explain the difference in inhibitory activity, molecular docking study using (GOLD) program was performed for selected sets of the most active and inactive compounds on cyclophilin D (CypD) receptor as a major component of mPTP. Moreover, ADME profiling, in silico toxicity, drug-likeness, and drug-score studies were discussed. From these results, we report compound 31 as the most active nonpeptidyl mPTP blocker possessing quinazoline-urea scaffold; 2 folds of CsA activity, which would constitute a new direction for the design of novel mPTP modulators.

  20. Experimental and computational studies on the formation of three para-benzyne analogues in the gas phase.

    PubMed

    Kirkpatrick, Lindsey M; Vinueza, Nelson R; Jankiewicz, Bartłomiej J; Gallardo, Vanessa A; Archibold, Enada F; Nash, John J; Kenttämaa, Hilkka I

    2013-07-01

    Experimental and computational studies on the formation of three gaseous, positively-charged para-benzyne analogues in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer are reported. The structures of the cations were examined by isolating them and allowing them to react with various neutral reagents whose reactions with aromatic carbon-centered σ-type mono- and biradicals are well understood. Cleavage of two iodine-carbon bonds in N-deuterated 1,4-diiodoisoquinolinium cation by collision-activated dissociation (CAD) produced a long-lived cation that showed nonradical reactivity, which was unexpected for a para-benzyne. However, the reactivity closely resembles that of an isomeric enediyne, N-deuterated 2-ethynylbenzonitrilium cation. A theoretical study on possible rearrangement reactions occurring during CAD revealed that the cation formed upon the first iodine atom loss undergoes ring-opening before the second iodine atom loss to form an enediyne instead of a para-benzyne. Similar results were obtained for the 5,8-didehydroisoquinolinium cation and the 2,5-didehydropyridinium cation. The findings for the 5,8-didehydroisoquinolinium cation are in contradiction with an earlier report on this cation. The cation described in the literature was regenerated by using the literature method and demonstrated to be the isomeric 5,7-didehydro-isoquinolinium cation and not the expected 5,8-isomer.

  1. Astrobiology through the ages of Mars: the study of terrestrial analogues to understand the habitability of Mars.

    PubMed

    Fairén, Alberto G; Davila, Alfonso F; Lim, Darlene; Bramall, Nathan; Bonaccorsi, Rosalba; Zavaleta, Jhony; Uceda, Esther R; Stoker, Carol; Wierzchos, Jacek; Dohm, James M; Amils, Ricardo; Andersen, Dale; McKay, Christopher P

    2010-10-01

    Mars has undergone three main climatic stages throughout its geological history, beginning with a water-rich epoch, followed by a cold and semi-arid era, and transitioning into present-day arid and very cold desert conditions. These global climatic eras also represent three different stages of planetary habitability: an early, potentially habitable stage when the basic requisites for life as we know it were present (liquid water and energy); an intermediate extreme stage, when liquid solutions became scarce or very challenging for life; and the most recent stage during which conditions on the surface have been largely uninhabitable, except perhaps in some isolated niches. Our understanding of the evolution of Mars is now sufficient to assign specific terrestrial environments to each of these periods. Through the study of Mars terrestrial analogues, we have assessed and constrained the habitability conditions for each of these stages, the geochemistry of the surface, and the likelihood for the preservation of organic and inorganic biosignatures. The study of these analog environments provides important information to better understand past and current mission results as well as to support the design and selection of instruments and the planning for future exploratory missions to Mars. PMID:21087162

  2. Geothermal energy from the Main Karoo Basin (South Africa): An outcrop analogue study of Permian sandstone reservoir formations

    NASA Astrophysics Data System (ADS)

    Campbell, Stuart A.; Lenhardt, Nils; Dippenaar, Matthys A.; Götz, Annette E.

    2016-04-01

    The geothermal potential of the South African Main Karoo Basin has not been addressed in the past, although thick siliciclastic successions in geothermal prone depths are promising target reservoir formations. A first assessment of the geothermal potential of the Karoo Basin is based on petro- and thermophysical data gained from an outcrop analogue study of Permian sandstones in the Eastern Cape Province, and evaluation of groundwater temperature and heat flow values from literature. A volumetric approach of the sandstones' reservoir potential leads to a first estimation of 2240 TWh (8.0 EJ) of power generation within the central and southern part of the basin. Comparison with data from other sedimentary basins where deep geothermal reservoirs are identified shows the high potential of the Karoo for future geothermal resource exploration, development and production. The mainly low permeability lithotypes may be operated as stimulated systems, depending on the fracture porosity in the deeper subsurface. In some areas auto-convective thermal water circulation might be expected and direct heat use becomes reasonable. The data presented here serve to identify exploration areas and are valuable attributes for reservoir modeling, contributing to (1) a reliable reservoir prognosis, (2) the decision of potential reservoir stimulation, and (3) the planning of long-term efficient reservoir utilization.

  3. Vitamin E analogue Trolox C. E.s.r. and pulse-radiolysis studies of free-radical reactions.

    PubMed Central

    Davies, M J; Forni, L G; Willson, R L

    1988-01-01

    The reactions between Trolox C, a water-soluble vitamin E analogue, and several oxidizing free radicals including the hydroxyl radical and various peroxy radicals were examined by using the pulse-radiolysis technique. The results demonstrate that Trolox C may undergo rapid one-electron-transfer reactions as well as hydrogen-transfer processes; the resulting phenoxyl radical is shown to be relatively stable, in common with the phenoxyl radical derived from vitamin E. The reactions between the Trolox C phenoxyl radical and a variety of biologically relevant reducing compounds were examined by using both pulse radiolysis and e.s.r. The results demonstrate that the Trolox C phenoxyl radical is readily repaired by ascorbate (k = 8.3 x 10(6) dm3.mol-1.s-1) and certain thiols (k less than 10(5) dm3.mol-1.s-1) but not by urate, NADH or propyl gallate. Evidence from e.s.r. studies indicates that thiol-containing compounds may also enter into similar repair reactions with the alpha-tocopherol phenoxyl radical. Kinetic evidence is presented that suggests that Trolox C may 'repair' proteins that have been oxidized by free radicals. PMID:2849418

  4. Anion Recognition by Pyrylium Cations and Thio-, Seleno- and Telluro- Analogues: A Combined Theoretical and Cambridge Structural Database Study.

    PubMed

    Quiñonero, David

    2015-06-24

    Pyrylium salts are a very important class of organic molecules containing a trivalent oxygen atom in a six-membered aromatic ring. In this manuscript, we report a theoretical study of pyrylium salts and their thio-, seleno- and telluro- analogues by means of DFT calculations. For this purpose, unsubstituted 2,4,6-trimethyl and 2,4,6-triphenyl cations and anions with different morphologies were chosen (Cl-, NO3- and BF4-). The complexes were characterized by means of natural bond orbital and "atoms-in-molecules" theories, and the physical nature of the interactions has been analyzed by means of symmetry-adapted perturbation theory calculations. Our results indicate the presence of anion-π interactions and chalcogen bonds based on both σ- and π-hole interactions and the existence of very favorable σ-complexes, especially for unsubstituted cations. The electrostatic component is dominant in the interactions, although the induction contributions are important, particularly for chloride complexes. The geometrical features of the complexes have been compared with experimental data retrieved from the Cambridge Structural Database.

  5. Analysis of complex mixtures recovered from space missions statistical approach to the study of Titan atmosphere analogues (tholins).

    PubMed

    Pietrogrand, M C; Coll, P; Sternberg, R; Szopa, C; Navarro-Gonzalez, R; Vidal-Madjar, C; Dondi, F

    2001-12-21

    To study Titan, the largest moon of Saturn, laboratory simulation experiments have been performed to obtain analogues of Titan's aerosols (named tholins) using different energy sources. Tholins, which have been demonstrated to represent aerosols in Titan's haze layers, are a complex mixture, resulting from the chemical evolution of several hydrocarbons and nitriles. Their chromatographic analysis yields complex chromatograms, which require the use of mathematical procedures to extract from them all the information they contain. Two different chemometric approaches (the Fourier analysis approach and the statistical model of peak overlapping) have been successfully applied to pyrolysis-GC-MS chromatogram of a tholin sample. Fundamental information on the mixture's chemical composition (number of components, m) and on the separation system performance (separation efficiency, sigma) can be easily estimated: the excellent correspondence between the data calculated by the two independent procedures proves the reliability of the statistical approaches in characterizing a tholin chromatogram. Moreover, the plot of autocorrelation function contains, in a simplified form, all the information on the retention pattern: retention recursivities can be easily singled out and related to specific molecular structure variations. Therefore, the autocorrelation function (ACF) plot constitutes a simplified fingerprint of the pyrolysis products of tholins, which can be used as a powerful tool to characterize a tholin sample.

  6. Reducing unwanted trauma memories by imaginal exposure or autobiographical memory elaboration: An analogue study of memory processes

    PubMed Central

    Ehlers, Anke; Mauchnik, Jana; Handley, Rachel

    2012-01-01

    Unwanted memories of traumatic events are a core symptom of post-traumatic stress disorder. A range of interventions including imaginal exposure and elaboration of the trauma memory in its autobiographical context are effective in reducing such unwanted memories. This study explored whether priming for stimuli that occur in the context of trauma and evaluative conditioning may play a role in the therapeutic effects of these procedures. Healthy volunteers (N = 122) watched analogue traumatic and neutral picture stories. They were then randomly allocated to 20 min of either imaginal exposure, autobiographical memory elaboration, or a control condition designed to prevent further processing of the picture stories. A blurred picture identification task showed that neutral objects that preceded traumatic pictures in the stories were subsequently more readily identified than those that had preceded neutral stories, indicating enhanced priming. There was also an evaluative conditioning effect in that participants disliked neutral objects that had preceded traumatic pictures more. Autobiographical memory elaboration reduced the enhanced priming effect. Both interventions reduced the evaluative conditioning effect. Imaginal exposure and autobiographical memory elaboration both reduced the frequency of subsequent unwanted memories of the picture stories. PMID:21227404

  7. 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

  8. Phosphorous-containing analogues of aspartame.

    PubMed

    Nelson, V; Mastalerz, P

    1984-12-01

    Four analogues of aspartame (aspartylphenylalanine methyl ester) were prepared in which one of the carboxylate groups was replaced by a phosphonate group. None of the peptides so obtained was sweet, in contrast with the parent compound which is over 100 times sweeter than sucrose. These results contrast with several published reports of phosphonate analogues of amino acids and peptides which are potent inhibitors of enzymes containing acceptor sites for the parent compound.

  9. 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…

  10. 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.

  11. 3D-QSAR study and design of 4-hydroxyamino α-pyranone carboxamide analogues as potential anti-HCV agents

    NASA Astrophysics Data System (ADS)

    Li, Wenlian; Xiao, Faqi; Zhou, Mingming; Jiang, Xuejin; Liu, Jun; Si, Hongzong; Xie, Meng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-09-01

    The three dimensional-quantitative structure activity relationship (3D-QSAR) study was performed on a series of 4-hydroxyamino α-pyranone carboxamide analogues using comparative molecular similarity indices analysis (COMSIA). The purpose of the present study was to develop a satisfactory model providing a reliable prediction based on 4-hydroxyamino α-pyranone carboxamide analogues as anti-HCV (hepatitis C virus) inhibitors. The statistical results and the results of validation of this optimum COMSIA model were satisfactory. Furthermore, analysis of the contour maps helped to provide guidelines for finding structural requirement. Therefore, the satisfactory results from this study may provide useful guidelines for drug development of anti-HCV inhibitors.

  12. A Functionalized Sphingolipid Analogue for Studying Redistribution during Activation in Living T Cells.

    PubMed

    Collenburg, Lena; Walter, Tim; Burgert, Anne; Müller, Nora; Seibel, Jürgen; Japtok, Lukasz; Kleuser, Burkhard; Sauer, Markus; Schneider-Schaulies, Sibylle

    2016-05-01

    Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools to further study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions to fluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells. PMID:27036914

  13. 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.

  14. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    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. DNA interactions and cytotoxic studies of cis-platin analogues of substituted 2,2'-bipyridines

    NASA Astrophysics Data System (ADS)

    Patel, Mohan N.; Parmar, Pradhuman A.; Gandhi, Deepen S.; Patidar, Anshul P.

    2012-11-01

    Platinum(II) complexes [Pt(4″-fpbpy)Cl2] (1), [Pt(4″-mepbpy)Cl2] (2), [Pt(4″-mpbpy)Cl2] (3) and [Pt(4″-bopbpy)Cl2] (4) {where 4″-fpbpy = 4-(4″-fluorophenyl)-6-phenyl-2,2'-bipyridine, 4″-mepbpy = 4-(4″-methylphenyl)-6-phenyl-2,2'-bipyridine, 4″-mpbpy = 4-(4″-methoxyphenyl)-6-phenyl-2,2'-bipyridine, 4″-bopbpy = 4-(4″-benzyloxyphenyl)-6-phenyl-2,2'-bipyridine} have been synthesized and characterized. The binding strength and binding mode of the complexes with HS DNA (Herring Sperm) have been investigated by absorption titration and viscosity measurement studies. The results have been revealed that the complexes bind to DNA by covalent mode with intrinsic binding constant Kb ranging from 6.05 × 104 M-1 to 3.48 × 105 M-1. The unwinding angle of pUC19 DNA has been evaluated by gel electrophoresis assay. The brine shrimp bioassay has been performed to study the in vitro cytotoxic properties of the synthesized metal complexes.

  16. Stardust: Studies in microgravity of condensation and agglomeration of cosmic dust analogue

    NASA Technical Reports Server (NTRS)

    Ferguson, F.; Lilleleht, L. U.; Nuth, J.; Stephens, J. R.; Bussoletti, E.; Carotenuto, L.; Colangeli, L.; Dellaversana, P.; Mele, F.; Mennella, V.

    1992-01-01

    A short description of the program Stardust whose goal is to study the formation and properties of high temperature particles and gases, including silicate and carbonaceous materials, that are of interest in astrophysics and planetary science, is given. The international program was carried out in microgravity conditions in parabolic flight. A description of the laboratory equipment, conceived to perform experimental tests in reduced gravity conditions, and which is based on the gas evaporation technique, is given. The gas evaporation technique utilizes one or more heated crucible to vaporize solids materials (SiO, Mg) in a low pressure of inert or reactive gas inside of a vacuum bell jar. The vapor pressures of the materials are controlled by the temperature of the crucibles. The temperature and pressure of inert gas are also controlled. By varying the vapor pressure relative to the gas temperature and pressure, the conditions for substantial grain condensation can be controlled and grain formation measured using light scattering techniques. Thus the partial pressure for grain condensation, can be measured as a function of temperature. The gas evaporation technique has the advantage that complex chemical systems can be studied by using multiple crucibles each containing solid source material. Experimental results and future trends are addressed.

  17. 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 (θ) 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

  18. 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

  19. Biaryl analogues of conformationally constrained tricyclic tropanes as potent and selective norepinephrine reuptake inhibitors: synthesis and evaluation of their uptake inhibition at monoamine transporter sites.

    PubMed

    Zhou, Jia; Zhang, Ao; Kläss, Thomas; Johnson, Kenneth M; Wang, Cheng Z; Ye, Yan Ping; Kozikowski, Alan P

    2003-05-01

    A series of novel conformationally constrained tricyclic tropane derivatives containing a biaryl moiety, (Z)-9-(biarylylmethylene)-7-azatricyclo[4.3.1.0(3,7)]decanes, were synthesized and evaluated for their ability to inhibit reuptake of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) by the DA, 5-HT, and NE transporters. Most of the compounds containing a methoxycarbonyl substituent at C-10 exhibit moderate to high inhibitory activity at the NET but lower activity at the DAT and SERT. Among these new compounds, some potent, NET-selective ligands were identified. The p-methoxy derivative 11a has a K(i) value of 39 nM for uptake inhibition at the NET and moderate to high selectivity over the SERT (100-fold) and the DAT (20-fold). Compound 11f exhibits a remarkable potency (K(i) = 9.7 nM) at the NET and a 25-fold selectivity over both the SERT and the DAT. Analogue 23 containing a thiophene ring as a bioisosteric replacement of the phenyl ring Ar(1) displays a high activity (K(i) = 10.3 nM) for the NET and similar selectivity over the SERT (50-fold) and the DAT (37-fold). The selectivity profile of biaryl analogues differs from that of the monoaryl series, as most members of that series display excellent potency at and selectivity for the SERT (J. Med. Chem. 2002, 45, 1930). This finding suggests that the different shape and size of the lipophilic recognition pocket that encompasses the aryl ring(s) of these tropanes are major determinants of a ligand's transporter activity at either the NET or the SERT. Some of the compounds in this series may also be valuable in sorting out the contribution of the individual transporters to cocaine's reinforcing properties.

  20. Analogue method for the study of pivot irregularities in meridian instruments

    NASA Astrophysics Data System (ADS)

    de Concini, C.; Zanzu, T.

    1980-07-01

    After a brief review of the methods used so far in studying the shape of pivots in meridian instruments, a system of measurements based on a chain of fully automated instruments is described. It involves the use of a micrometric transducer, able to record 1/100 micron with a twin-channel graph-recorder and a digital voltmeter printer. A graph of the pivot shape and a digital output measuring the movement of the transducer stylus are obtained. After showing the advantages offered by this system and the problems which its use can solve, the theoretical background of the method is discussed and expressions for the true shape of the pivots and the consequent corrections to be made to astronomical observations are given. Finally, some results of pivot measurements on the Large Transit Instrument of the International Astronomical Station of Latitude at Cagliari are given.

  1. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion.

    PubMed

    Ito, Yohei; Ishibashi, Kenichiro; Masaki, Ayako; Fujii, Kana; Fujiyoshi, Yukio; Hattori, Hideo; Kawakita, Daisuke; Matsumoto, Manabu; Miyabe, Satoru; Shimozato, Kazuo; Nagao, Toshitaka; Inagaki, Hiroshi

    2015-05-01

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade carcinoma with morphologic and genetic similarity, including ETV6-NTRK3 fusion, to secretory carcinoma of the breast. ETV6 is frequently involved in other epithelial and nonepithelial tumors, and many fusion partners of ETV6 have been reported. In the present study, 14 Japanese MASC cases were clinicopathologically and molecularly analyzed. The median age of the patients was 39 years, and the male:female ratio was 6:8. All cases showed histopathologic findings compatible with those previously described for MASC and harbored an ETV6 split as visualized by fluorescence in situ hybridization. Two cases showed thick fibrous septa and invasive features including vascular or perineural tumor involvement, findings that are rare in MASC. In addition, in these 2 cases, non-NTRK3 genes appeared to fuse with ETV6 (ETV6-X fusion). NTRK1 and NTRK2, both members of the NTRK family, were not involved. Of the 14 MASC cases, the ETV6-NTRK3 fusion transcript was positive in 6 cases, and the relative expression level of the ETV6-NTRK3 fusion transcript was variable, ranging from 1 to 5.8. Results of the present study of MASC suggest that (1) ETV6 occasionally fuses with unknown non-NTRK3 genes, (2) ETV6-X cases might have an invasive histology, (3) for molecular diagnosis of MASC, fluorescence in situ hybridization to detect ETV6 splits is the method of choice, and (4) the expression level of the ETV6-NTRK3 fusion transcript is considerably variable. These findings provide a novel insight into the oncogenesis, histopathology, diagnosis, treatment, and prognosis of this newly recognized carcinoma. PMID:25651470

  2. A phase I study of the vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer.

    PubMed Central

    Gulliford, T.; English, J.; Colston, K. W.; Menday, P.; Moller, S.; Coombes, R. C.

    1998-01-01

    Preclinical studies have shown that the vitamin D analogue EB 1089 has significantly less calcaemic activity than its parent compound 1,25-dihydroxyvitamin D (1,25(OH)2D3) and significant anti-tumour activity. This phase I trial was designed to evaluate the calcaemic effect of the drug in patients with advanced cancer. EB 1089 was given to 36 patients with advanced breast and colorectal cancer in doses of between 0.15 and 17.0 microg m(-2) day(-1). Serial serum and urine calcium, urine creatinine and serum parathyroid hormone (PTH) were monitored. Hypercalcaemia was seen in all patients receiving 17.0 microg m(-2) day(-1). Hypercalcaemia attributable to EB 1089 was reversible by discontinuing or reducing EB 1089 therapy. During the first 5 days of treatment, urine calcium (P = 0.0001) and serum-corrected calcium (P = 0.027) were related to EB 1089 dose, whereas serum parathyroid hormone (P = 0.0001) showed an inverse relationship. Twenty-one patients received compassionate treatment for between 10 and 234 days. No complete or partial responses were seen. Six patients on treatment for more than 90 days showed stabilization of disease. EB 1089 was well tolerated and adverse events considered to be caused by EB 1089 were limited to dose-dependent effects on calcium metabolism. The dose estimated to be tolerable for most patients from this study is around 7 microg m(-2) day(1). These data support previous work that has demonstrated EB 1089 to be significantly less calcaemic than 1,25-dihydroxyvitamin D3. PMID:9662243

  3. 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…

  4. Structure activity relationship study of Mezzettiasides natural products and their four new disaccharide analogues for anticancer/antibacterial activity

    PubMed Central

    Bajaj, Sumit O.; Shi, Pei

    2014-01-01

    Ten members of the mezzettiaside family of natural products were synthesized and evaluated for anticancer and antibacterial activity. Complete anticancer (H460) and antibacterial (B. subtilis) activities for the ten natural products and four new analogues were found. Comparison to the cleistrioside and cleistetroside classes of natural products were made. PMID:25729554

  5. Molecular modeling studies, synthesis and biological evaluation of dabigatran analogues as thrombin inhibitors.

    PubMed

    Dong, Ming-Hui; Chen, Hai-Feng; Ren, Yu-Jie; Shao, Fang-Ming

    2016-01-15

    In this work, 48 thrombin inhibitors based on the structural scaffold of dabigatran were analyzed using a combination of molecular modeling techniques. We generated three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on three alignments for both comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to highlight the structural requirements for thrombin protein inhibition. In addition to the 3D-QSAR study, Topomer CoMFA model also was established with a higher leave-one-out cross-validation q(2) and a non-cross-validation r(2), which suggest that the three models have good predictive ability. The results indicated that the steric, hydrophobic and electrostatic fields play key roles in QSAR model. Furthermore, we employed molecular docking and re-docking simulation explored the binding relationship of the ligand and the receptor protein in detail. Molecular docking simulations identified several key interactions that were also indicated through 3D-QSAR analysis. On the basis of the obtained results, two compounds were designed and predicted by three models, the biological evaluation in vitro (IC50) demonstrated that these molecular models were effective for the development of novel potent thrombin inhibitors.

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

    SciTech Connect

    Leszczynski, Jerzy; Sponer, Judit; Sponer, Jiri; Sumpter, Bobby G; Fuentes-Cabrera, Miguel A; Vazquez-Mayagoitia, Alvaro

    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.

  7. Design, Synthesis, and Biological Evaluation of 1-Methyl-1,4-dihydroindeno[1,2-c]pyrazole Analogues as Potential Anticancer Agents Targeting Tubulin Colchicine Binding Site.

    PubMed

    Liu, Yan-Na; Wang, Jing-Jing; Ji, Ya-Ting; Zhao, Guo-Dong; Tang, Long-Qian; Zhang, Cheng-Mei; Guo, Xiu-Li; Liu, Zhao-Peng

    2016-06-01

    By targeting a new binding region at the interface between αβ-tubulin heterodimers at the colchicine binding site, we designed a series of 7-substituted 1-methyl-1,4-dihydroindeno[1,2-c]pyrazoles as potential tubulin polymerization inhibitors. Among the compounds synthesized, 2-(6-ethoxy-3-(3-ethoxyphenylamino)-1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy)acetamide 6a and 2-(6-ethoxy-3-(3-ethoxyphenylamino)-1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy)-N-hydroxyacetamide 6n showed noteworthy low nanomolar potency against HepG2, Hela, PC3, and MCF-7 cancer cell lines. In mechanism studies, 6a inhibited tubulin polymerization and disorganized microtubule in A549 cells by binding to tubulin colchicine binding site. 6a arrested A549 cells in G2/M phase that was related to the alterations in the expression of cyclin B1 and p-cdc2. 6a induced A549 cells apoptosis through the activation of caspase-3 and PARP. In addition, 6a inhibited capillary tube formation in a concentration-dependent manner. In nonsmall cell lung cancer xenografts mouse model, 6a suppressed tumor growth by 59.1% at a dose of 50 mg/kg (ip) without obvious toxicity, indicating its in vivo potential as anticancer agent. PMID:27172319

  8. 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.

  9. 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

  10. Studies on Labour Safety in Construction Sites

    PubMed Central

    Kanchana, S.; Sivaprakash, P.; Joseph, Sebastian

    2015-01-01

    Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites. PMID:26839916

  11. Studies on Labour Safety in Construction Sites.

    PubMed

    Kanchana, S; Sivaprakash, P; Joseph, Sebastian

    2015-01-01

    Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites.

  12. Studies on Labour Safety in Construction Sites.

    PubMed

    Kanchana, S; Sivaprakash, P; Joseph, Sebastian

    2015-01-01

    Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites. PMID:26839916

  13. QSAR analyses of DDT analogues and their in silico validation using molecular docking study against voltage-gated sodium channel of Anopheles funestus.

    PubMed

    Saini, V; Kumar, A

    2014-01-01

    DDT has enjoyed the reputation of a successful pesticide in disease control programme and agricultural practices along with the serious opposition and ban later on due to its biomagnification and toxic action against non-target organisms. The present work was carried out to develop QSAR models for analysing DDT analogues for their pesticidal activity and in silico validation of these models. A 2D-QSAR model was generated using stepwise with multiple regression, and the model with a value of r(2) = 0.7324; q(2) = 0.6215; pred r(2) = 0.7038, containing five descriptors, was selected for further study. The 3D QSAR with CoMFA analysis showed that steric contribution of 21% and electrostatic contribution of about 79% were required for larvicidal activity of DDT analogues. A set of 3430 molecules was generated using the basic DDT skeleton as template, and these were evaluated for their mosquito larvicidal activity using the generated QSAR models and DDT as standard. Eleven molecules were selected for in silico validation of these models. For this, a docking study of the selected molecules against the homology-modelled voltage-gated sodium channel of Anopheles funestus was conducted. The study showed that the activities of these analogues as predicted by 2D-QSAR, 3D-QSAR with CoMFA and dock score were observed to be well correlated.

  14. QSAR analyses of DDT analogues and their in silico validation using molecular docking study against voltage-gated sodium channel of Anopheles funestus.

    PubMed

    Saini, V; Kumar, A

    2014-01-01

    DDT has enjoyed the reputation of a successful pesticide in disease control programme and agricultural practices along with the serious opposition and ban later on due to its biomagnification and toxic action against non-target organisms. The present work was carried out to develop QSAR models for analysing DDT analogues for their pesticidal activity and in silico validation of these models. A 2D-QSAR model was generated using stepwise with multiple regression, and the model with a value of r(2) = 0.7324; q(2) = 0.6215; pred r(2) = 0.7038, containing five descriptors, was selected for further study. The 3D QSAR with CoMFA analysis showed that steric contribution of 21% and electrostatic contribution of about 79% were required for larvicidal activity of DDT analogues. A set of 3430 molecules was generated using the basic DDT skeleton as template, and these were evaluated for their mosquito larvicidal activity using the generated QSAR models and DDT as standard. Eleven molecules were selected for in silico validation of these models. For this, a docking study of the selected molecules against the homology-modelled voltage-gated sodium channel of Anopheles funestus was conducted. The study showed that the activities of these analogues as predicted by 2D-QSAR, 3D-QSAR with CoMFA and dock score were observed to be well correlated. PMID:25271473

  15. Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

    PubMed

    Maćczak, Aneta; Bukowska, Bożena; Michałowicz, Jaromir

    2015-01-01

    Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed its significant hemolytic and oxidative potential. Moreover, no study has been conducted to evaluate the effect of BPA analogues on red blood cells. The purpose of the present study was to compare the impact of BPA and its selected analogues such as bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on hemolytic and morphological changes and hemoglobin oxidation (methemoglobin formation) of human erythrocytes. The erythrocytes were incubated with different bisphenols concentrations ranging from 0.5 to 500μg/ml for 1, 4 and 24h. The compounds examined caused hemolysis in human erythrocytes with BPAF exhibiting the strongest effect. All bisphenols examined caused methemoglobin formation with BPA inducing the strongest oxidative potential. Flow cytometry analysis showed that all bisphenols (excluding BPS) induced significant changes in erythrocytes size. Changes in red blood cells shape were conducted using phase contrast microscopy. It was noticed that BPA and BPAF induced echinocytosis, BPF caused stomatocytosis, while BPS did not provoke significant changes in shape of red blood cells. Generally, the results showed that BPS, which is the main substituent of bisphenol A in polymers and thermal paper production, exhibited significantly lower disturbance of erythrocyte functions than BPA.

  16. 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.

  17. 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.

  18. Pena blanca natural analogue project: summary of activities

    SciTech Connect

    Levy, Schon S; Goldstein, Steven J; Abdel - Fattah, Amr I

    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.

  19. Global profiling and rapid matching of natural products using diagnostic product ion network and in silico analogue database: Gastrodia elata as a case study.

    PubMed

    Lai, Chang-Jiang-Sheng; Zha, Liangping; Liu, Da-Hui; Kang, Liping; Ma, Xiaojing; Zhan, Zhi-Lai; Nan, Tie-Gui; Yang, Jian; Li, Fajie; Yuan, Yuan; Huang, Lu-Qi

    2016-07-22

    Rapid discovery of novel compounds of a traditional herbal medicine is of vital significance for pharmaceutical industry and plant metabolic pathway analysis. However, discovery of unknown or trace natural products is an ongoing challenge. This study presents a universal targeted data-independent acquisition and mining strategy to globally profile and effectively match novel natural product analogues from an herbal extract. The famous medical plant Gastrodia elata was selected as an example. This strategy consists of three steps: (i) acquisition of accurate parent and adduct ions (PAIs) and the product ions data of all eluting compounds by untargeted full-scan MS(E) mode; (ii) rapid compound screening using diagnostic product ions (DPIs) network and in silico analogue database with SUMPRODUCT function to find novel candidates; and (iii) identification and isomerism discrimination of multiple types of compounds using ClogP and ions fragment behavior analyses. Using above data mining methods, a total of 152 compounds were characterized, and 70 were discovered for the first time, including series of phospholipids and novel gastroxyl derivatives. Furthermore, a number of gastronucleosides and phase II metabolites of gastrodin and parishins were discovered, including glutathionylated, cysteinylglycinated and cysteinated compounds, and phosphatidylserine analogues. This study extended the application of classical DPIs filter strategy and developed a structure-based screening approach with the potential for significant increase of efficiency for discovery and identification of trace novel natural products.

  20. Global profiling and rapid matching of natural products using diagnostic product ion network and in silico analogue database: Gastrodia elata as a case study.

    PubMed

    Lai, Chang-Jiang-Sheng; Zha, Liangping; Liu, Da-Hui; Kang, Liping; Ma, Xiaojing; Zhan, Zhi-Lai; Nan, Tie-Gui; Yang, Jian; Li, Fajie; Yuan, Yuan; Huang, Lu-Qi

    2016-07-22

    Rapid discovery of novel compounds of a traditional herbal medicine is of vital significance for pharmaceutical industry and plant metabolic pathway analysis. However, discovery of unknown or trace natural products is an ongoing challenge. This study presents a universal targeted data-independent acquisition and mining strategy to globally profile and effectively match novel natural product analogues from an herbal extract. The famous medical plant Gastrodia elata was selected as an example. This strategy consists of three steps: (i) acquisition of accurate parent and adduct ions (PAIs) and the product ions data of all eluting compounds by untargeted full-scan MS(E) mode; (ii) rapid compound screening using diagnostic product ions (DPIs) network and in silico analogue database with SUMPRODUCT function to find novel candidates; and (iii) identification and isomerism discrimination of multiple types of compounds using ClogP and ions fragment behavior analyses. Using above data mining methods, a total of 152 compounds were characterized, and 70 were discovered for the first time, including series of phospholipids and novel gastroxyl derivatives. Furthermore, a number of gastronucleosides and phase II metabolites of gastrodin and parishins were discovered, including glutathionylated, cysteinylglycinated and cysteinated compounds, and phosphatidylserine analogues. This study extended the application of classical DPIs filter strategy and developed a structure-based screening approach with the potential for significant increase of efficiency for discovery and identification of trace novel natural products. PMID:27318507

  1. Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2

    PubMed Central

    Lousuebsakul-Matthews, Vichuda; Thorpe, Donna L; Knutsen, Raymond; Beeson, W Larry; Fraser, Gary E; Knutsen, Synnove F

    2014-01-01

    Objective In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors. Design A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007. Setting Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members. Subjects Respondents (n 33 208) to a baseline and a follow-up questionnaire. Results In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio=0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio=0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49% reduced risk of hip fracture (hazard ratio=0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly. Conclusions Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture. PMID:24103482

  2. Antimicrobial Peptide from the Wild Bee Hylaeus signatus Venom and Its Analogues: Structure-Activity Study and Synergistic Effect with Antibiotics.

    PubMed

    Nešuta, Ondřej; Hexnerová, Rozálie; Buděšínský, Miloš; Slaninová, Jiřina; Bednárová, Lucie; Hadravová, Romana; Straka, Jakub; Veverka, Václav; Čeřovský, Václav

    2016-04-22

    Venoms of hymenopteran insects have attracted considerable interest as a source of cationic antimicrobial peptides (AMPs). In the venom of the solitary bee Hylaeus signatus (Hymenoptera: Colletidae), we identified a new hexadecapeptide of sequence Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Ala-Ala-His-Ile-Ala-Lys-NH2. Named HYL, it belongs to the category of α-helical amphipathic AMPs. HYL exhibited weak antimicrobial activity against several strains of pathogenic bacteria and moderate activity against Candida albicans, but its hemolytic activity against human red blood cells was low. We prepared a set of HYL analogues to evaluate the effects of structural modifications on its biological activity and to increase its potency against pathogenic bacteria. This produced several analogues exhibiting significantly greater activity compared to HYL against strains of both Staphylococcus aureus and Pseudomonas aeruginosa even as their hemolytic activity remained low. Studying synergism of HYL peptides and conventional antibiotics showed the peptides act synergistically and preferentially in combination with rifampicin. Fluorescent dye propidium iodide uptake showed the tested peptides were able to facilitate entrance of antibiotics into the cytoplasm by permeabilization of the outer and inner bacterial cell membrane of P. aeruginosa. Transmission electron microscopy revealed that treatment of P. aeruginosa with one of the HYL analogues caused total disintegration of bacterial cells. NMR spectroscopy was used to elucidate the structure-activity relationship for the effect of amino acid residue substitution in HYL. PMID:26998557

  3. Nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in olefin metathesis: a computational study.

    PubMed

    Pazio, A; Woźniak, K; Grela, K; Trzaskowski, B

    2015-12-14

    We used the density functional theory to evaluate the suitability of nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in ruthenium-based metathesis catalysts. We demonstrate that these analogues induce only minor structural changes in Hoveyda-Grubbs-like precatalysts, but have major impact on precatalyst initiation. Nitrenium ion-modified precatalysts are characterized by a weak Ru-N bond resulting in a relatively strong Ru-O bond and large free energy barriers for initiation, making them good candidates for efficient latent Ru-based catalysts. On the other hand the trivalent boron ligand, bearing a formal -1 charge, binds strongly to the ruthenium ion, weakening the Ru-O bond and facilitating its dissociation, to promote fast reaction initiation. We show that the calculated bond dissociation energy of the Ru-C/N/B bond may serve as an accurate indicator of the Ru-O bond strength and the rate of metathesis initiation.

  4. Structure-Activity Studies of Brassinosteroids and the Search for Novel Analogues and Mimetics with Improved Bioactivity.

    PubMed

    Back, Thomas G.; Pharis, Richard P.

    2003-12-01

    A number of novel brassinosteroid analogues were synthesized and subjected to the rice leaf lamina inclination bioassay. Modified B-ring analogues included lactam, thiolactone, cyclic ether, ketone, hydroxyl, and exocyclic methylene derivatives of brassinolide. Those derivatives containing polar functional groups retained considerable bioactivity, whereas the exocyclic methylene compounds were devoid of activity. Analogues containing normal alkyl and cycloalkyl substituents at C-24 (in place of the isopropyl group of brassinolide) showed an inverse relationship between activity and chain length or ring size, respectively. The corresponding cyclopropyl and cyclobutyl derivatives were significantly more active than brassinolide and appear to be the most potent brassinosteroids reported to date. When synergized with the auxin indole-3-acetic acid (IAA), their bioactivity can be further enhanced by 1-2 orders of magnitude. The cyclopropyl derivative, when coapplied with the auxin naphthaleneacetic acid, gave a significant increase in yield of wheat in a field trial. Certain 25- and 26-hydroxy derivatives are known metabolites of brassinosteroids. All of the C-25 stereoisomers of 25-hydroxy, 26-hydroxy, and 25,26-dihydroxy derivatives of brassinolide were prepared and shown to be much less active than brassinolide. This indicates that they are likely metabolic deactivation products of the parent phytohormone. A series of methyl ethers of brassinolide was synthesized to block deactivation by glucosylation of the free hydroxyl groups. The most significant finding was that the compound where three of the four hydroxyl groups (at C-3, C-22, and C-23) had been converted to methyl ethers retained substantial bioactivity. This type of modification could, in theory, allow brassinolide or 24-epibrassinolide to resist deactivation and thus offer greater persistence in field applications. A series of nonsteroidal mimetics of brassinolide was designed and synthesized. Two of the

  5. Bradykinin antagonists with dehydrophenylalanine analogues at position 5.

    PubMed

    Greiner, G; Dornberger, U; Paegelow, I; Schölkens, B A; Liebmann, C; Reissmann, S

    1998-04-01

    Continuing the studies on structural requirements of bradykinin antagonists, it has been found that analogues with dehydrophenylalanine (deltaPhe) or its ring-substituted analogues (deltaPhe(X)) at position 5 act as antagonists on guinea pig pulmonary artery, and on guinea pig ileum. Because both organs are considered to be bradykinin B2 receptor tissues, the analogues with deltaPhe or deltaPhe(X) at position 5, but without any replacement at position 7, seem to represent a new structural type of B2 receptor antagonist. All the analogues investigated act as partial antagonists; they inhibit the bradykinin-induced contraction at low concentrations and act as agonists at higher concentrations. Ring substitutions by methyl groups or iodine reduce both the agonistic and antagonistic activity. Only substitution by fluorine gives a high potency. Incorporation of deltaPhe into different representative antagonists with key modifications at position 7 does not enhance the antagonist activity of the basic structures, with one exception. Only the combination of deltaPhe at position 5 with DPhe at position 7 increases the antagonistic potency on guinea pig ileum by about one order of magnitude. Radioligand binding studies indicate the importance of position 5 for the discrimination of B2 receptor subtypes. The binding affinity to the low-affinity binding site (KL) was not significantly changed by replacement of Phe by deltaPhe. In contrast, ring-methylation of deltaPhe results in clearly reduced binding to KL. The affinity to the high-affinity binding site (KH) was almost unchanged by the replacement of Phe in position 5 by deltaPhe, whereas the analogue with 2-methyl-dehydrophenylalanine completely failed to detect the KH-site. The peptides were synthesized on the Wang-resin according to the Fmoc/Bu(t) strategy using Mtr protection for the side chain of Arg. The dehydrophenylalanine analogues were prepared by a strategy involving PyBop couplings of the dipeptide unit Fmoc

  6. Regression of endometrial hyperplasia after treatment with the gonadotrophin-releasing hormone analogue triptorelin: a prospective study.

    PubMed

    Grimbizis, G; Tsalikis, T; Tzioufa, V; Kasapis, M; Mantalenakis, S

    1999-02-01

    Endometrial hyperplasia is thought to be caused by the prolonged, unopposed oestrogenic stimulation of the endometrium. The regression of hyperplastic back to normal endometrium is the main purpose of any conservative treatment in order to prevent development of adenocarcinoma. The aim of this study was to evaluate the regression of hyperplastic to normal endometrium in patients with various forms of endometrial hyperplasia after treatment with the gonadotrophin-releasing hormone analogue (GnRHa) triptorelin for 6 months. Fifty-six patients with endometrial hyperplasia were enrolled in this trial; 39 patients (group I) presented simple hyperplasia, 14 (group II) complex hyperplasia and three (group III) atypical complex hyperplasia. All patients were treated with triptorelin for 6 months. Bleeding control during treatment was excellent. A post-treatment curettage for estimation of endometrial histology was performed on 54 out of 56 patients 100.1 +/- 44.7 days after the last triptorelin dose, following the restoration of pituitary function. Regression of hyperplastic to normal endometrium was observed in 32 (86.5%) out of 37 patients in group I and in 12 (85.7%) out of 14 in group II. Persistence of simple hyperplasia was found in five (14.5%) out of 37 patients in group I. Persistence of complex hyperplasia was found in 1 (7.1%) out of 14 patients and progression to atypical complex hyperplasia in another one (7.1%) woman in group II. In some of these cases, the presence of risk factors such as obesity, diabetes mellitus and ovulatory disturbances may contribute to the disease persistence despite therapy. On the other hand, in group III, none of the three patients had normal post-treatment endometrial histology. It seems, therefore, that in cases of endometrial hyperplasia without atypia, the administration of the GnRHa triptorelin is associated with high regression rates to normal endometrium. Conversely, the presence of atypia seems to be a poor prognostic

  7. A solid-state hybrid density functional theory study of Prussian blue analogues and related chlorides at pressure

    NASA Astrophysics Data System (ADS)

    Middlemiss, Derek S.; Lawton, Lorreta M.; Wilson, Chick C.

    2008-08-01

    The variations with pressure in the structural, electronic and magnetic properties of a series of Prussian blue analogues (PBAs) KIMII[CrIII(CN)6] (M = VII, MnII and NiII) and associated isomorphous chlorides KIMIICrIIICl6 are investigated within a series of solid-state hybrid density functional calculations. The sensitivity of the computed properties to the choice of Hamiltonian is tested by application of functionals containing 35%, 65% and 100% admixtures of Fock exchange. Magnetic coupling constants (J) are obtained at a range of cell volumes (V), with fits of the Bloch relationship (J \\propto V^{-\\varepsilon } , ɛ typically 3-4) yielding exponents ɛ in the ranges 5.16-6.34, 8.48-12.07 and 4.00-4.51 for the antiferromagnetic (AF) VIICrIII-, ferrimagnetic (FI) MnIICrIII- and ferromagnetic (FO) NiIICrIII PBAs, respectively; and 3.33-4.99, 1.86-3.09 and 1.65-3.28 for the AF VIICrIII-, FO MnIICrIII- and FO NiIICrIII chlorides, respectively. The MnIICrIII PBA range encloses the high values ɛ~9-10 obtained in a recent joint experimental and theoretical study, and it is suggested that this strong magnetostructural effect arises due to the presence of competing AF and FO interactions in this material. Estimates of the spin ordering temperatures derived from the combination of the 35%-functional couplings with a mean field approach are in good agreement with experiment in the VIICrIII and NiIICrIII PBAs, but are too low in the MnIICrIII system. The variations with pressure in the structural parameters, charges and spin moments are also detailed, the PBA and chloride energy-volume data yielding bulk moduli in the ranges 39-53 and 36-50 GPa, respectively. Finally, the energies governing CN- ligand isomerization are estimated and successfully interpreted in terms of a simple crystal field stabilization model.

  8. QM/MM study of catalytic methyl transfer by the N5-glutamine SAM-dependent methyltransferase and its inhibition by the nitrogen analogue of coenzyme.

    PubMed

    Wu, Ruibo; Cao, Zexing

    2008-02-01

    The combined density functional quantum mechanical/molecular mechanical (QM/MM) approach has been used to investigate methyl-transfer reactions catalyzed by the N(5)-glutamine S-adenosyl-L-methionine (SAM)-dependent methyltransferase (HemK) and the coenzyme-modified HemK with the replacement of SAM by a nitrogen analogue. Calculations reveal that the catalytic methyl transfer by HemK is an energy-favored process with an activation barrier of 15.7 kcal/mol and an exothermicity of 12.0 kcal/mol, while the coenzyme-modified HemK is unable to catalyze the methyl transfer because of a substantial barrier of 20.6 kcal/mol and instability of the product intermediate. The results lend support to the experimental proposal that the nitrogen analogue of the SAM coenzyme should be a practicable inhibitor for the catalytic methyl transfer by HemK. Comparative QM/MM calculations show that the protein environment, especially the residues Asn197 and Pro198 in the active site, plays a pivotal role in stabilizing the transition state and regulating the positioning of reactive groups.

  9. 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 β-ionone and benzaldehyde. The stabilities of β-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 β-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 β-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

  10. Assessment of CO2 discharge in a spring using time-variant stable carbon isotope data as a natural analogue study of CO2 leakage

    NASA Astrophysics Data System (ADS)

    Yu, Soonyoung; Chae, Gitak; Jo, Minki; Kim, Jeong-Chan; Yun, Seong-Taek

    2015-04-01

    CO2-rich springs have been studied as a natural analogue of CO2 leakage through shallow subsurface environment, as they provide information on the behaviors of CO2 during the leakage from geologic CO2 storage sites. For this study, we monitored the δ13C values as well as temperature, pH, EC, DO, and alkalinity for a CO2-rich spring for 48 hours. The water samples (N=47) were collected every hour in stopper bottles without headspace to avoid the interaction with air and the CO2 degassing. The δ13C values of total dissolved inorganic carbon (TDIC) in the water samples were analyzed using a cavity ring-down spectroscopy (CRDS) system (Picarro). The values of δ13CTDIC, temperature, pH, EC, DO, and alkalinity were in the range of -9.43 ~ -8.91 o 12.3 ~ 13.2oC, 4.86 ~ 5.02, 186 ~ 189 μS/cm, 1.8 ~ 3.4 mg/L, and 0.74 ~ 0.95 meq/L, respectively. The concentrations of TDIC calculated using pH and alkalinity values were between 22.5 and 34.8 mmol/L. The δ13CTDIC data imply that dissolved carbon in the spring was derived from a deep-seated source (i.e., magmatic) that was slightly intermixed with soil CO2. Careful examination of the time-series variation of measured parameters shows the following characteristics: 1) the δ13CTDIC values are negatively correlated with pH (r = -0.59) and positively correlated with TDIC (r = 0.58), and 2) delay times of the change of pH and alkalinity following the change of δ13CTDIC values are 0 and -3 hours, respectively; the pH change occurs simultaneously with the change of δ13CTDIC, while the alkalinity change happens before 3 hours. Our results indicate that the studied CO2-rich spring is influenced by the intermittent supply of deep-seated CO2. [Acknowledgment] This work was financially supported by the fundamental research project of KIGAM and partially by the "Geo-Advanced Innovative Action (GAIA) Project (2014000530003)" from Korea Ministry of Environment (MOE).

  11. Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue.

    PubMed

    Chiara, David C; Dostalova, Zuzana; Jayakar, Selwyn S; Zhou, Xiaojuan; Miller, Keith W; Cohen, Jonathan B

    2012-01-31

    The γ-aminobutyric acid type A receptor (GABA(A)R) is a target for general anesthetics of diverse chemical structures, which act as positive allosteric modulators at clinical doses. Previously, in a heterogeneous mixture of GABA(A)Rs purified from bovine brain, [³H]azietomidate photolabeling of αMet-236 and βMet-286 in the αM1 and βM3 transmembrane helices identified an etomidate binding site in the GABA(A)R transmembrane domain at the interface between the β and α subunits [Li, G. D., et.al. (2006) J. Neurosci. 26, 11599-11605]. To further define GABA(A)R etomidate binding sites, we now use [³H]TDBzl-etomidate, an aryl diazirine with broader amino acid side chain reactivity than azietomidate, to photolabel purified human FLAG-α1β3 GABA(A)Rs and more extensively identify photolabeled GABA(A)R amino acids. [³H]TDBzl-etomidate photolabeled in an etomidate-inhibitable manner β3Val-290, in the β3M3 transmembrane helix, as well as α1Met-236 in α1M1, a residue photolabeled by [³H]azietomidate, while no photolabeling of amino acids in the αM2 and βM2 helices that also border the etomidate binding site was detected. The location of these photolabeled amino acids in GABA(A)R homology models derived from the recently determined structures of prokaryote (GLIC) or invertebrate (GluCl) homologues and the results of computational docking studies predict the orientation of [³H]TDBzl-etomidate bound in that site and the other amino acids contributing to this GABA(A)R intersubunit etomidate binding site. Etomidate-inhibitable photolabeling of β3Met-227 in βM1 by [³H]TDBzl-etomidate and [³H]azietomidate also provides evidence of a homologous etomidate binding site at the β3-β3 subunit interface in the α1β3 GABA(A)R.

  12. 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.

  13. 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

  14. Alligator rivers analogue project an OECD/NEA international project

    SciTech Connect

    Duerden, P.; Airey, P.; Pescatore, C.

    1994-12-31

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained.

  15. Oxidation and reaction of trolox c, a tocopherol analogue, in aqueous solution. A pulse-radiolysis study

    SciTech Connect

    Thomas, M.J. ); Bielski, B.H.J. )

    1989-04-26

    Trolox c, 3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carboxylic acid, 1, a water-soluble {alpha}-tocopherol analogue, was oxidized with Br{sub 2}{sup {minus}} to give the phenoxyl radical 2. These radicals disproportionate by a second-order, pH-dependent process to give 1 and an unstable intermediate 3, identified as 4,5-dihydro-3,6,8,9-tetramethyl-2H-3,9a-epoxy-1-benzoxepin-2,7(3H)-dione, which has a strong UV absorption at 235 nm. The disproportionation rate constant decreases with increasing pH, the greatest change occurring between pH 2 and 9, where it decreased by 10{sup 4}. The rate constant versus pH plot is consistent with a scheme that involves three reactions of the protonated and the unprotonated forms of 2. Intermediate 3 undergoes slow pH-dependent decomposition to 2-hydroxy-2-methyl-4-(2,5,6-trimethyl-2,4-dioxo-2,5-cyclohexadienyl)butanoic acid, 4. The same first-order rate constant was found for the decay of 3 and the appearance of 4. Simultaneous intramolecular cyclization during disproportionation is unique to 2 and similar derivatives, but would not occur in analogues that have hydrocarbon chains instead of a carboxyl moiety.

  16. Theoretical Study of Pd11 Si6 Nanosheet Compounds Including Seven-Coordinated Si Species and Its Ge Analogues.

    PubMed

    Chen, Yue; Sunada, Yusuke; Nagashima, Hideo; Sakaki, Shigeyoshi

    2016-01-18

    Nanosheet compounds Pd11 (SiiPr)2 (SiiPr2 )4 (CNtBu)10 (1) and Pd11 (SiiPr)2 (SiiPr2 )4 (CNMes)10 (2), containing two Pd7 (SiiPr)(SiiPr2 )2 (CNR)4 plates (R=tBu or Mes) connected with three common Pd atoms, were investigated with DFT method. All Pd atoms are somewhat positively charged and the electron density is accumulated between the Pd and Si atoms, indicating that a charge transfer (CT) occurs from the Pd to the Si atoms of the SiMe2 and SiMe groups. Negative regions of the Laplacian of the electron density were found between the Pd and Si atoms. A model of a seven-coordinated Si species, that is, Pd5 (Pd-SiMe), is predicted to be a stable pentagonal bipyramidal molecule. Five Pd atoms in the equatorial plane form bonding overlaps with two 3p orbitals of the Si atom. This is a new type of hypervalency. The Ge analogues have geometry and an electronic structure similar to those of the Si compounds. But their formation energies are smaller than those of the Si analogues. The use of the element Si is crucial to synthesize these nanoplate compounds.

  17. Nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in olefin metathesis: a computational study.

    PubMed

    Pazio, A; Woźniak, K; Grela, K; Trzaskowski, B

    2015-12-14

    We used the density functional theory to evaluate the suitability of nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in ruthenium-based metathesis catalysts. We demonstrate that these analogues induce only minor structural changes in Hoveyda-Grubbs-like precatalysts, but have major impact on precatalyst initiation. Nitrenium ion-modified precatalysts are characterized by a weak Ru-N bond resulting in a relatively strong Ru-O bond and large free energy barriers for initiation, making them good candidates for efficient latent Ru-based catalysts. On the other hand the trivalent boron ligand, bearing a formal -1 charge, binds strongly to the ruthenium ion, weakening the Ru-O bond and facilitating its dissociation, to promote fast reaction initiation. We show that the calculated bond dissociation energy of the Ru-C/N/B bond may serve as an accurate indicator of the Ru-O bond strength and the rate of metathesis initiation. PMID:26525899

  18. Molecular Docking Evaluation of Imidazole Analogues as Potent Candida albicans 14α-Demethylase Inhibitors.

    PubMed

    Rani, Nidhi; Kumar, Praveen; Singh, Randhir; Sharma, Ajay

    2015-01-01

    Candida albicans is one of the most important causes of life-threating fungal infections. Lanosterol 14α-demethylase (Cytochrome P450DM) is the target enzyme of azole antifungal agents. The study involved selection and modeling of the target enzyme followed by refinement of the model using molecular dynamic simulation. The modeled structure of enzyme was validated using Ramachandran plot and Sequence determination technique. A series of chlorosubstituted imidazole analogues were evaluated for Cytochrome P450 inhibitory activity using molecular docking studies. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program. The docking study indicated that all the imidazole analogues (AN1-AN45) and standard drugs i.e., Ketoconazole, Clotrimazole and Miconazole have interaction with protein residue of 14α-demethylase, Heme cofactor and the water molecules present in the active site. PMID:26081558

  19. 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.

  20. Policy issues in space analogues

    NASA Astrophysics Data System (ADS)

    Auger, Robin N.; Facktor, Debra D.

    Space mission planning is increasingly focusing on destinations beyond Earth orbit. Advancements in technology will inevitably be required to enable long-duration human spaceflight missions, and breakthroughs in the policy arena will also be needed to achieve success in such missions. By exploring how policy issues have been addressed in analogous extreme environments, policymakers can develop a framework for addressing these issues as they apply to long-term human spaceflight. Policy issues that need to be addressed include: crew selection, training, organization, and activities, medical testing, illness, injury, and death; communication; legal accountability and liability; mission safety and risk management; and environmental contamination. This paper outlines the approach of a study underway by The George Washington University and ANSER to examine how these policy issues have been addressed in several analogues and how the experiences of these analogues can help formulate policies for long-duration human spaceflight missions. Analogues being studied include Antarctic bases, submarine voyages, undersea stations, Biosphere 2, and the U.S. Skylab and Russian Mir space stations.

  1. Pro Free Will Priming Enhances “Risk-Taking” Behavior in the Iowa Gambling Task, but Not in the Balloon Analogue Risk Task: Two Independent Priming Studies

    PubMed Central

    Schrag, Yann; Tremea, Alessandro; Lagger, Cyril; Ohana, Noé; Mohr, Christine

    2016-01-01

    Studies indicated that people behave less responsibly after exposure to information containing deterministic statements as compared to free will statements or neutral statements. Thus, deterministic primes should lead to enhanced risk-taking behavior. We tested this prediction in two studies with healthy participants. In experiment 1, we tested 144 students (24 men) in the laboratory using the Iowa Gambling Task. In experiment 2, we tested 274 participants (104 men) online using the Balloon Analogue Risk Task. In the Iowa Gambling Task, the free will priming condition resulted in more risky decisions than both the deterministic and neutral priming conditions. We observed no priming effects on risk-taking behavior in the Balloon Analogue Risk Task. To explain these unpredicted findings, we consider the somatic marker hypothesis, a gain frequency approach as well as attention to gains and / or inattention to losses. In addition, we highlight the necessity to consider both pro free will and deterministic priming conditions in future studies. Importantly, our and previous results indicate that the effects of pro free will and deterministic priming do not oppose each other on a frequently assumed continuum. PMID:27018854

  2. Pro Free Will Priming Enhances "Risk-Taking" Behavior in the Iowa Gambling Task, but Not in the Balloon Analogue Risk Task: Two Independent Priming Studies.

    PubMed

    Schrag, Yann; Tremea, Alessandro; Lagger, Cyril; Ohana, Noé; Mohr, Christine

    2016-01-01

    Studies indicated that people behave less responsibly after exposure to information containing deterministic statements as compared to free will statements or neutral statements. Thus, deterministic primes should lead to enhanced risk-taking behavior. We tested this prediction in two studies with healthy participants. In experiment 1, we tested 144 students (24 men) in the laboratory using the Iowa Gambling Task. In experiment 2, we tested 274 participants (104 men) online using the Balloon Analogue Risk Task. In the Iowa Gambling Task, the free will priming condition resulted in more risky decisions than both the deterministic and neutral priming conditions. We observed no priming effects on risk-taking behavior in the Balloon Analogue Risk Task. To explain these unpredicted findings, we consider the somatic marker hypothesis, a gain frequency approach as well as attention to gains and / or inattention to losses. In addition, we highlight the necessity to consider both pro free will and deterministic priming conditions in future studies. Importantly, our and previous results indicate that the effects of pro free will and deterministic priming do not oppose each other on a frequently assumed continuum. PMID:27018854

  3. Complex of Burkholderia cepacia lipase with transition state analogue of 1-phenoxy-2-acetoxybutane: biocatalytic, structural and modelling study.

    PubMed

    Luić, M; Tomić, S; Lescić, I; Ljubović, E; Sepac, D; Sunjić, V; Vitale, L; Saenger, W; Kojic-Prodić, B

    2001-07-01

    In a series of four racemic phenoxyalkyl-alkyl carbinols, 1-phenoxy-2-hydroxybutane (1) is enantioselectively acetylated by Burkholderia cepacia (formerly Pseudomonas cepacia) lipase with an E value > or = 200, whereas for the other three racemates E was found to be < or = 4. To explain the high preference of B. cepacia lipase for (R)-(+)-1, a precursor of its transition state analogue with a tetrahedral P-atom, (R(P),S(P))-O-(2R)-(1-phenoxybut-2-yl)methylphosphonic acid chloride was prepared and crystallized in complex with B. cepacia lipase. The X-ray structure of the complex was determined, allowing to compare the conformation of the inhibitor with results of molecular modelling.

  4. 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…

  5. Design, Synthesis, EPR-Studies and Conformational Bias of Novel Spin-Labeled DCC-Analogues for the Highly Regioselective Labeling of Aliphatic and Aromatic Carboxylic Acids.

    PubMed

    Gölz, Jan Philipp; NejatyJahromy, Yaser; Bauer, Mirko; Muhammad, Ashraf; Schnakenburg, Gregor; Grimme, Stefan; Schiemann, Olav; Menche, Dirk

    2016-07-01

    Novel types of spin-labeled N,N'-dicyclohexylcarbodiimides (DCC) are reported that bear a 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) residue on one side and different aromatic and aliphatic cyclohexyl analogues on the other side of the diimide core. These readily available novel reagents add efficiently to aliphatic and aromatic carboxylic acids, forming two possible spin-labeled amide derivatives with different radical distances of the resulting amide. The addition of aromatic DCC analogues proceeds with excellent selectivity, giving amides where the carboxylic acid is exclusively connected to the aromatic residue, while little or no selectivity was observed for the aliphatic congeners. The usefulness of these adducts in structural studies was demonstrated by EPR (electron paramagnetic resonance) measurements of biradical adducts of biphenyl-4,4'-dicarboxylic acids. These analyses also reveal high degrees of conformational bias for aromatic DCC derivatives, which further underlines the powerfulness of these novel reagents. This observation was further corroborated by quantum chemical calculations, giving a detailed understanding of the structural dynamics, while detailed information on the solid state structure of all novel reagents was obtained by X-ray structure analyses.

  6. Resolution and Determination of the Absolute Configuration of a Twisted Bis-Lactam Analogue of Tröger's Base: A Comparative Spectroscopic and Computational Study.

    PubMed

    Rúnarsson, Ögmundur Vidar; Benkhäuser, Christian; Christensen, Niels Johan; Ruiz, Josep Artacho; Ascic, Erhad; Harmata, Michael; Snieckus, Victor; Rissanen, Kari; Fristrup, Peter; Lützen, Arne; Wärnmark, Kenneth

    2015-08-21

    The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in a chiral space group P212121 using Cu-irradiation resulting in a very low Flack parameter of -0.06(3), despite the heaviest element being an oxygen atom, thus unambiguously confirming the results from the spectroscopic studies. We conclude that, for the Tröger's base (TB) analogue (2), we may rank the reliability of the individual methods for AC determination as AXRD ≫ VCD > ECD, while the synergy of all three methods provides very strong confidence in the assigned ACs of (+)-(R,R)-2 and (-)-(S,S)-2. PMID:26244379

  7. Design, Synthesis, EPR-Studies and Conformational Bias of Novel Spin-Labeled DCC-Analogues for the Highly Regioselective Labeling of Aliphatic and Aromatic Carboxylic Acids.

    PubMed

    Gölz, Jan Philipp; NejatyJahromy, Yaser; Bauer, Mirko; Muhammad, Ashraf; Schnakenburg, Gregor; Grimme, Stefan; Schiemann, Olav; Menche, Dirk

    2016-07-01

    Novel types of spin-labeled N,N'-dicyclohexylcarbodiimides (DCC) are reported that bear a 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) residue on one side and different aromatic and aliphatic cyclohexyl analogues on the other side of the diimide core. These readily available novel reagents add efficiently to aliphatic and aromatic carboxylic acids, forming two possible spin-labeled amide derivatives with different radical distances of the resulting amide. The addition of aromatic DCC analogues proceeds with excellent selectivity, giving amides where the carboxylic acid is exclusively connected to the aromatic residue, while little or no selectivity was observed for the aliphatic congeners. The usefulness of these adducts in structural studies was demonstrated by EPR (electron paramagnetic resonance) measurements of biradical adducts of biphenyl-4,4'-dicarboxylic acids. These analyses also reveal high degrees of conformational bias for aromatic DCC derivatives, which further underlines the powerfulness of these novel reagents. This observation was further corroborated by quantum chemical calculations, giving a detailed understanding of the structural dynamics, while detailed information on the solid state structure of all novel reagents was obtained by X-ray structure analyses. PMID:27272435

  8. Metabolic effects of the iodothyronine functional analogue TRC150094 on the liver and skeletal muscle of high-fat diet fed overweight rats: an integrated proteomic study.

    PubMed

    Silvestri, Elena; Glinni, Daniela; Cioffi, Federica; Moreno, Maria; Lombardi, Assunta; de Lange, Pieter; Senese, Rosalba; Ceccarelli, Michele; Salzano, Anna Maria; Scaloni, Andrea; Lanni, Antonia; Goglia, Fernando

    2012-07-01

    A novel functional iodothyronine analogue, TRC150094, which has a much lower potency toward thyroid hormone receptor (α1/β1) activation than triiodothyronine, has been shown to be effective at reducing adiposity in rats simultaneously receiving a high-fat diet (HFD). Here, by combining metabolic, functional and proteomic analysis, we studied how the hepatic and skeletal muscle phenotypes might respond to TRC150094 treatment in HFD-fed overweight rats. Drug treatment increased both the liver and skeletal muscle mitochondrial oxidative capacities without altering mitochondrial efficiency. Coherently, in terms of individual respiratory in-gel activity, blue-native analysis revealed an increased activity of complex V in the liver and of complexes II and V in tibialis muscle in TCR150094-treated animals. Subsequently, the identification of differentially expressed proteins and the analysis of their interrelations gave an integrated view of the phenotypic/metabolic adaptations occurring in the liver and muscle proteomes during drug treatment. TRC150094 significantly altered the expression of several proteins involved in key liver metabolic pathways, including amino acid and nitrogen metabolism, and fructose and mannose metabolism. The canonical pathways most strongly influenced by TRC150094 in tibialis muscle included glycolysis and gluconeogenesis, amino acid, fructose and mannose metabolism, and cell signaling. The phenotypic/metabolic influence of TRC150094 on the liver and skeletal muscle of HFD-fed overweight rats suggests the potential clinical application of this iodothyronine analogue in ameliorating metabolic risk parameters altered by diet regimens.

  9. One-site versus two-site phacotrabeculectomy: a prospective randomized study

    PubMed Central

    Moschos, Marilita M; Chatziralli, Irini P; Tsatsos, Michael

    2015-01-01

    Purpose The purpose of this study is to compare the efficacy and safety of one-site and two-site combined phacotrabeculectomy with foldable posterior chamber intraocular lens implantation. Methods Thirty-four patients (41 eyes) with glaucoma and cataract were randomly assigned to undergo either a one-site (22 eyes) or a two-site (19 eyes) combined procedure. One-site approach consisted of a standard superior phacotrabeculectomy with a limbus-based conjunctival flap, while two-site approach consisted of a clear cornea phacoemulsification and a separate superior trabeculectomy with a limbus-based conjunctival flap. Results Mean follow-up period was 54 months (standard deviation [SD] 2.3). Mean preoperative intraocular pressure (IOP) in the one-site group was 21.3 mmHg (SD 2.8) and in the two-site group was 21.8 mmHg (SD 3.0) (P>0.1). Mean postoperative IOP significantly decreased in both groups compared to the preoperative level and was 15.6 mmHg (SD 3.5) in the one-site group and 14.9 mmHg (SD 2.7) in the two-site group. Three months later, the difference between the two groups was not statistically significant (P=0.058). The one-site group required significantly more medications than the two-site group (P=0.03). Best-corrected visual acuity (BCVA) improved similarly in both groups, but there was less postoperative (induced) astigmatism in the two-site group in a marginal statistical level (P=0.058). Intra- and postoperative complications were comparable in the two groups. Conclusion Both techniques yielded similar results concerning final BCVA and IOP reduction. However, the two-site group had less induced astigmatism and a better postoperative IOP control with less required postoperative antiglaucoma medications compared to the one-site group. PMID:26347460

  10. Synthesis and evaluation of bioorthogonal pantetheine analogues for in vivo protein modification.

    PubMed

    Meier, Jordan L; Mercer, Andrew C; Rivera, Heriberto; Burkart, Michael D

    2006-09-20

    In vivo carrier protein tagging has recently become an attractive target for the site-specific modification of fusion systems and new approaches to natural product proteomics. A detailed study of pantetheine analogues was performed in order to identify suitable partners for covalent protein labeling inside living cells. A rapid synthesis of pantothenamide analogues was developed and used to produce a panel which was evaluated for in vitro and in vivo protein labeling. Kinetic comparisons allowed the construction of a structure-activity relationship to pinpoint the linker, dye, and bioorthogonal reporter of choice for carrier protein labeling. Finally bioorthogonal pantetheine analogues were shown to target carrier proteins with high specificity in vivo and undergo chemoselective ligation to reporters in crude cell lysate. The methods demonstrated here allow carrier proteins to be visualized and isolated for the first time without the need for antibody techniques and set the stage for the future use of carrier protein fusions in chemical biology.

  11. The Valles natural analogue project

    SciTech Connect

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    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.

  12. Combined nuclear magnetic resonance spectroscopy and molecular dynamics study of growth hormone releasing hexapeptide GHRP-6 and a cyclic analogue.

    PubMed

    Fernández-Oliva, Miguel; Santana, Héctor; Suardíaz, Reynier; Gavín, José A; Pérez, Carlos S

    2012-05-01

    The Growth Hormone Releasing Hexapeptide, GHRP-6 was the first of a family of synthetic peptides that enhance the release of the Growth Hormone by the pituitary gland in a dose-dependent manner. Since its discovery, it has been used as a benchmark and starting point in numerous researches aiming to obtain new drugs. Complete resonance assignment of GHRP-6 NMR spectra in both open and cyclic forms are reported, showing some differences to random coil chemical shifts. Connectivities observed in the ROESY spectra indicate spatial proximity between the aromatic residues side-chains in both molecules, as well as between residues DPhe5 and Lys6 sidechains. An ensemble of 10 structures was generated for each one of the molecules, showing RMSD values indicative of nonrandom structures. Molecular Dynamics simulations, both with and without explicit solvent, were carried out for GHRP-6 and its cyclic analogue. Conformational analysis performed on the trajectories showed a nonrandom structure with a well preserved backbone. The presence of geometrical patterns resembling those typical of π-π interactions in both peptides, suggest that this kind of interactions may be relevant for the biological activity of GHRP-6. Same conclusion can be drawn from the spatial proximity of residues DPhe5 and Lys6 sidechains.

  13. Electronic structure and vibrational spectra of cis-diammine(orotato)platinum(II), a potential cisplatin analogue: DFT and experimental study

    NASA Astrophysics Data System (ADS)

    Wysokiński, Rafał; Hernik, Katarzyna; Szostak, Roman; Michalska, Danuta

    2007-03-01

    Orotic acid (vitamin B 13) is a key intermediate in biosynthesis of the pyrimidine nucleotides in living organisms, moreover, it may serve as the biological carrier for some metal ions. cis-Diammine(orotato)platinum(II), cis-[Pt(C 5H 2N 2O 4)(NH 3) 2] can be considered as a new potential cisplatin analogue. The FT-Raman and FT-IR spectra of the title complex are reported, for the first time. The molecular structure, vibrational frequencies, and the theoretical infrared and Raman intensities have been calculated by the density functional mPW1PW91 method. The detailed vibrational assignment has been made on the basis of the calculated potential energy distribution. The theoretically predicted IR and Raman spectra show very good agreement with experiment. Natural bond orbital (NBO) analyses were performed for cisplatin, carboplatin and the title complex. The results provided new data on the nature of platinum-ligand bonding in these compounds. Strong intramolecular hydrogen bond between the orotate ligand and the coordinated ammonia group stabilizes the structure of the platinum(II) complex. Thus, it is suggested that the orotate ligand in the title complex is more inert to the substitution reactions than the chloride ligands in cisplatin.

  14. Programming of the macronucleus of Paramecium during asexual and sexual reproduction: A further study with cytidine analogues, dimethylsulfoxide, L-ethionine and N-butyric acid.

    PubMed

    Au, K Y; Yao, C M; Cowan, R; Ng, S F

    1990-08-31

    The control of the function of the macronucleus of Paramecium is studied, in connection with its role in the compensation for the asexual somatic function of the micronucleus. Following removal of the micronuclei, amicronucleate cell lines as a rule suffer a transient period of growth and developmental depression in the initial phase of asexual propagation. But they gradually recover to near-normal. Previous studies of treatment of amicronucleate cells with cytidine analogues have implicated the macronucleus in compensating for the somatic function of the micronucleus following the loss of the micronucleus, and the activation of this macronuclear function probably involves DNA-demethylation. The present study further tests this notion, by treating micronucleate cells with agents known to promote demethylation of 5-methylcytosine. After treatment, the cells were vegetatively propagated, and then enucleated to give rise to amicronucleate cell lines. Treatments with dimethylsulfoxide, L-ethionine, and 5-aza-2'-deoxycytidine promoted recovery in amicronucleate cell lines thus derived. Cells treated with 6-azacytidine did not produce such an effect. Hence, the compensatory mechanism, presumably residing in a repressed state in the macronucleus, can be activated or primed to activate by demethylating agents even before the loss of the micronucleus, and once established the new macronuclear programme perpetuates in succeeding asexual cell generations. This shows that during asexual propagation the macronuclear programme can be altered to 'pre-adapt' the cells for amicronuclearity. Treatment of micronucleate conjugants with 5-azacytidine, when the macronuclear anlagen develop, produced clones that had become similarly pre-adapted. There were also some indication of persistence of such effects of the analogue into the next clonal cycle following autogamy. The notion of macronuclear DNA-demethylation as a basis for the activation and maintenance of the compensatory mechanism

  15. Does Balloon Kyphoplasty Deliver More Cement Safely into Osteoporotic Vertebrae with Compression Fractures Compared with Vertebroplasty? A Study in Vertebral Analogues

    PubMed Central

    Abduljabbar, Fahad H.; Al-jurayyan, Abdulaziz; Alqahtani, Saad; Sardar, Zeeshan M.; Saluja, Rajeet Singh; Ouellet, Jean; Weber, Michael; Steffen, Thomas; Beckman, Lorne; Jarzem, Peter

    2015-01-01

    Study Design A biomechanical and radiographic study using vertebral analogues. Objectives Kyphoplasty and vertebroplasty are widely used techniques to alleviate pain in fractures secondary to osteoporosis. However, cement leakage toward vital structures like the spinal cord can be a major source of morbidity and even mortality. We define safe cement injection as the volume of the cement injected into a vertebra before the cement leakage occurs. Our objective is to compare the amount of cement that can be safely injected into an osteoporotic vertebra with simulated compression fracture using either vertebroplasty or balloon kyphoplasty techniques. Methods Forty artificial vertebral analogues made of polyurethane with osteoporotic cancellous matrix representing the L3 vertebrae were used for this study and were divided into four groups of 10 vertebrae each. The four groups tested were: low-viscosity cement injected using vertebroplasty, high-viscosity cement injected using vertebroplasty, low-viscosity cement injected using balloon kyphoplasty, and high-viscosity cement injected using balloon kyphoplasty. The procedures were performed under fluoroscopic guidance. The injection was stopped when the cement started protruding from the created vascular channel in the osteoporotic vertebral fracture model. The main outcome measured was the volume of the cement injected safely into a vertebra before leakage through the posterior vascular channel. Results The highest volume of the cement injected was in the vertebroplasty group using high-viscosity cement, which was almost twice the injected volume in the other three groups. One-way analysis of variance comparing the four groups showed a statistically significant difference (p < 0.005). Conclusions High-viscosity cement injected using vertebroplasty delivers more cement volume before cement leakage and fills the vertebral body more uniformly when compared with balloon kyphoplasty in osteoporotic vertebrae with

  16. Programming of the macronucleus of Paramecium during asexual and sexual reproduction: A further study with cytidine analogues, dimethylsulfoxide, L-ethionine and N-butyric acid.

    PubMed

    Au, K Y; Yao, C M; Cowan, R; Ng, S F

    1990-08-31

    The control of the function of the macronucleus of Paramecium is studied, in connection with its role in the compensation for the asexual somatic function of the micronucleus. Following removal of the micronuclei, amicronucleate cell lines as a rule suffer a transient period of growth and developmental depression in the initial phase of asexual propagation. But they gradually recover to near-normal. Previous studies of treatment of amicronucleate cells with cytidine analogues have implicated the macronucleus in compensating for the somatic function of the micronucleus following the loss of the micronucleus, and the activation of this macronuclear function probably involves DNA-demethylation. The present study further tests this notion, by treating micronucleate cells with agents known to promote demethylation of 5-methylcytosine. After treatment, the cells were vegetatively propagated, and then enucleated to give rise to amicronucleate cell lines. Treatments with dimethylsulfoxide, L-ethionine, and 5-aza-2'-deoxycytidine promoted recovery in amicronucleate cell lines thus derived. Cells treated with 6-azacytidine did not produce such an effect. Hence, the compensatory mechanism, presumably residing in a repressed state in the macronucleus, can be activated or primed to activate by demethylating agents even before the loss of the micronucleus, and once established the new macronuclear programme perpetuates in succeeding asexual cell generations. This shows that during asexual propagation the macronuclear programme can be altered to 'pre-adapt' the cells for amicronuclearity. Treatment of micronucleate conjugants with 5-azacytidine, when the macronuclear anlagen develop, produced clones that had become similarly pre-adapted. There were also some indication of persistence of such effects of the analogue into the next clonal cycle following autogamy. The notion of macronuclear DNA-demethylation as a basis for the activation and maintenance of the compensatory mechanism

  17. Effect of vitamin-D analogue on albuminuria in patients with non-dialysed chronic kidney disease stage 4–5: a retrospective single center study

    PubMed Central

    2012-01-01

    Background The vitamin D receptor activator paricalcitol has been shown to reduce albuminuria. Whether this is a unique property of paricalcitol, or common to all vitamin D analogues, is unknown. The primary aim of this study was to evaluate the effect of alfacalcidol on proteinuria, measured as 24 hour (24 h) albuminuria, in patients with chronic kidney disease (CKD) stage 4–5 being treated for secondary hyperparathyroidism (sHPT). Methods A retrospective single-center study including adult patients with CKD 4–5, undergoing treatment for sHPT with alfacalcidol, with macroalbuminuria in minimum one 24 h urine collection. Patients were identified in a prospectively collected database of all patients with S-creatinine > 300 μM or creatinine clearance < 30 ml/min. The observation period was from 1st of January 2005 to 31st of December 2009. Phosphate binders and alfacalcidol were provided to patients free of charge. Results A total of 146 macroalbuminuric patients were identified, and of these, 59 started alfacalcidol treatment during the observation period. A 12% reduction in 24 h albuminuria was seen after starting treatment. In 19 patients with no change in renin-angiotensin-aldosteron-system (RAAS) inhibition, the reduction in albuminuria was 16%. The reduction remained stable over time (9%) in a subgroup of patients (n = 20) with several urine collections before and after the start of alfacalcidol-treatment. Conclusion The present study supports experimental and clinical data on antiproteinuric actions of activated vitamin D analogues, and suggests that this may be a class-effect. PMID:22958603

  18. 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.

  19. An analogue study of the influence of solidification on the advance and surface thermal signature of lava flows

    NASA Astrophysics Data System (ADS)

    Garel, F.; Kaminski, E.; Tait, S.; Limare, A.

    2014-06-01

    The prediction of lava flow advance and velocity is crucial during an effusive volcanic crisis. The effusion rate is a key control of lava dynamics, and proxies have been developed to estimate it in near real-time. The thermal proxy in predominant use links the satellite-measured thermal radiated power to the effusion rate. It lacks however a robust physical basis to allow time-dependent modeling. We investigate here through analogue experiments the coupling between the spreading of a solidifying flow and its surface thermal signal. We extract a first order behavior from experimental results obtained using polyethylene glycol (PEG) wax, that solidifies abruptly during cooling. We find that the flow advance is discontinuous, with relatively low supply rates yielding long stagnation phases and compound flows. Flows with higher supply rates are less sensitive to solidification and display a spreading behavior closer to that of purely viscous currents. The total power radiated from the upper surface also grows by stages, but the signal radiated by the hottest and liquid part of the flow reaches a quasi-steady state after some time. This plateau value scales around half of the theoretical prediction of a model developed previously for the spreading and cooling of isoviscous gravity currents. The corrected scaling yields satisfying estimates of the effusion rate from the total radiated power measured on a range of basaltic lava flows. We conclude that a gross estimate of the supply rate of solidifying flows can be retrieved from thermal remote-sensing, but the predictions of lava advance as a function of effusion rate appears a more difficult task due to chaotic emplacement of solidifying flows.

  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. Accurate Characterization of the Peptide Linkage in the Gas Phase: A Joint Quantum-Chemical and Rotational Spectroscopy Study of the Glycine Dipeptide Analogue.

    PubMed

    Puzzarini, Cristina; Biczysko, Malgorzata; Barone, Vincenzo; Largo, Laura; Peña, Isabel; Cabezas, Carlos; Alonso, José Luis

    2014-02-01

    Accurate structures of aminoacids in the gas phase have been obtained by joint microwave and quantum-chemical investigations. However, the structure and conformational behavior of α-aminoacids once incorporated into peptide chains are completely different and have not yet been characterized with the same accuracy. To fill this gap, we present here an accurate characterization of the simplest dipeptide analogue (N-acetyl-glycinamide) involving peptidic bonds. State-of-the-art quantum-chemical computations are complemented by a comprehensive study of the rotational spectrum using a combination of Fourier transform microwave spectroscopy with laser ablation. The coexistence of the C7 and C5 conformers has been proved and energetically as well as spectroscopically characterized. This joint theoretical-experimental investigation demonstrated the feasibility of obtaining accurate structures for flexible small biomolecules, thus paving the route to the elucidation of the inherent behavior of peptides.

  2. Metal binding properties of fluorescent analogues of trichogin GA IV: a conformational study by time-resolved spectroscopy and molecular mechanics investigations.

    PubMed

    Venanzi, Mariano; Bocchinfuso, Gianfranco; Gatto, Emanuela; Palleschi, Antonio; Stella, Lorenzo; Formaggio, Fernando; Toniolo, Claudio

    2009-01-01

    The metal ion binding properties of two fluorescent analogues of trichogin GA IV, which is a natural undecapeptide showing significant antimicrobial activity, were studied by circular dichroism, time-resolved optical spectroscopy, and molecular mechanics calculations. Binding of Ca(II) and Gd(III) to the peptides investigated was shown to promote a structural transition from highly helical conformations to folded structures characterized by formation of a loop that embedded the metal ion. Time-resolved spectroscopy revealed that peptide dynamics is also remarkably affected by ion binding: peptide-backbone motions slowed down to the microsecond time scale. Finally, molecular mechanics calculations emphasized the role of the central Gly5-Gly6 motif, which allowed for the twisting of the peptide segment that gave rise to the formation of the binding cavity.

  3. A Transition State Analogue for an RNA-Editing Reaction

    PubMed Central

    Haudenschild, Brittany L.; Maydanovych, Olena; Véliz, Eduardo A.; Macbeth, Mark R.; Bass, Brenda L.; Beal, Peter A.

    2007-01-01

    Deamination at C6 of adenosine in RNA catalyzed by the ADAR enzymes generates inosine at the corresponding position. Because inosine is decoded as guanosine during translation, this modification can lead to codon changes in messenger RNA. Hydration of 8-azanebularine across the C6–N1 double bond generates an excellent mimic of the transition state proposed for the hydrolytic deamination reaction catalyzed by ADARs. Here, we report the synthesis of a phosphoramidite of 8-azanebularine and its use in the preparation of RNAs mimicking the secondary structure found at a known editing site in the glutamate receptor B subunit pre-mRNA. The binding properties of analogue-containing RNAs indicate that a tight binding ligand for an ADAR can be generated by incorporation of 8-azanebularine. The observed high-affinity binding is dependent on a functional active site, the presence of one, but not the other, of ADAR2’s two double-stranded RNA-binding motifs (dsRBMs), and the correct placement of the nucleoside analogue into the sequence/structural context of a known editing site. These results advance our understanding of substrate recognition during ADAR-catalyzed RNA editing and are important for structural studies of ADAR· RNA complexes. PMID:15355102

  4. 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.

  5. Presence of cobalamin analogues in animal tissues

    PubMed Central

    Kondo, Haruki; Kolhouse, Fred; Allen, Robert H.

    1980-01-01

    Cobalamin (Cbl, vitamin B-12) has been extracted and isolated from a number of animal tissues by using (i) reverse-affinity chromatography on R protein-Sepharose followed by adsorption to and elution from charcoal-coated agarose and (ii) paper chromatography. Radioisotope dilution assays showed that only 75-97% of the Cbl chromatographed in the position of crystalline Cbl. The remaining 3-25% was present in a number of slower and faster moving fractions. This suggested that Cbl analogues are present in animal tissues because appropriate controls ruled out the possibility that this material was artifactually derived from Cbl during the extraction and purification procedures. With a large-scale isolation from rabbit kidney, the material in five such fractions contained cobalt and had absorption spectra that were similar to but different from the spectrum of Cbl, indicating that they were Cbl analogues. Compared to Cbl, these Cbl analogues had decreased but definite affinities for Cbl-binding proteins with the following order of strength of binding: R protein > transcobalamin II > intrinsic factor. Compared to Cbl, they also had decreased but definite growth-promoting activity for two microorganisms, Euglena gracilis and Lactobacillus leichmannii, which require Cbl for growth. These Cbl analogues differed from each other and from 18 synthetic Cbl analogues, including the most common Cbl analogues synthesized by microorganisms, in at least one of the above features. These studies indicate that animal tissues contain a number of Cbl analogues whose origins, structures, and biologic activities remain to be determined. PMID:6928681

  6. Alternating sites reactivity is a common feature of thiamin diphosphate-dependent enzymes as evidenced by isothermal titration calorimetry studies of substrate binding.

    PubMed

    Schröder-Tittmann, Kathrin; Meyer, Danilo; Arens, Johannes; Wechsler, Cindy; Tietzel, Michael; Golbik, Ralph; Tittmann, Kai

    2013-04-16

    Thiamin diphosphate (ThDP)-dependent enzymes play vital roles in cellular metabolism in all kingdoms of life. In previous kinetic and structural studies, a communication between the active centers in terms of a negative cooperativity had been suggested for some but not all ThDP enzymes, which typically operate as functional dimers. To further underline this hypothesis and to test its universality, we investigated the binding of substrate analogue methyl acetylphosphonate (MAP) to three different ThDP-dependent enzymes acting on substrate pyruvate, namely, the Escherichia coli E1 component of the pyruvate dehydrogenase complex, E. coli acetohydroxyacid synthase isoenzyme I, and the Lactobacillus plantarum pyruvate oxidase using isothermal titration calorimetry. The results unambiguously show for all three enzymes studied that only one active center of the functional dimers accomplishes covalent binding of the substrate analogue, supporting the proposed alternating sites reactivity as a common feature of all ThDP enzymes and resolving the recent controversy in the field.

  7. An exploratory study on the peroxyl-radical-scavenging activity of 2,6-dimethyl-5-hepten-2-ol and its heterocyclic analogues

    NASA Astrophysics Data System (ADS)

    Stobiecka, Agnieszka; Sikora, Magdalena; Bonikowski, Radosław; Kula, Józef

    2016-03-01

    The structural properties and radical scavenging activity of 2,6-dimethyl-5-hepten-2-ol (1) and its new heterocyclic analogues, i.e. 2-methyl-4-(5-methylfuran-2-yl)-butan-2-ol (2) and 2-methyl-4-(5-methylthiophen-2-yl)-butan-2-ol (3) and have been studied by using the experimental and theoretical methods for the first time. Activity of title compounds against the peroxyl radical was determined by using standard fluorimetric test, i.e. the Oxygen Radical Absorbance Capacity assay (ORACFL). Furthermore, the electron-donating ability of odorants has been evaluated by using colorimetric ABTS assay. According to the experimental results obtained from the ORACFL test 2,6-dimethyl-5-hepten-2-ol was characterized by the highest activity in comparison with the novel counterparts. Nevertheless, all investigated compounds exhibited pronounced anti-peroxyl radical activity comparable to that exerted by the one of the most prominent antioxidant among the monoterpene alcohols, i.e. by linalool. On the other hand, the title compounds exerted relatively low capacity to quench the radical cation of ABTS. Theoretical calculations based on the Density Functional Theory (DFT) method with the hybrid functional B3LYP were carried out in order to investigate selected structural and electronic properties including the geometrical parameters as well as the energy of frontier molecular orbitals of parent molecules and the resulting radicals. Furthermore, the possible mechanism of peroxyl-radical-scavenging has been determined by using the thermodynamic descriptors such as the bond dissociation enthalpies (BDEs) and ionization potentials (IPs). These theoretical data pointed out the relevance of HAT mechanism in the peroxyl-radical-scavenging exhibited by 2,6-dimethyl-5-hepten-2-ol and its new heterocyclic analogues in polar and non-polar medium.

  8. Hanford tank initiative test facility site selection study

    SciTech Connect

    Staehr, T.W.

    1997-04-03

    The Hanford Tanks Initiative (HTI) project is developing equipment for the removal of hard heel waste from the Hanford Site underground single-shell waste storage tanks. The HTI equipment will initially be installed in the 241-C-106 tank where its operation will be demonstrated. This study evaluates existing Hanford Site facilities and other sites for functional testing of the HTI equipment before it is installed into the 241-C-106 tank.

  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

  10. 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.

  11. Universal Access in Heritage Sites: A Case Study on Historic Sites in Jaipur, India.

    PubMed

    Vardia, Shweta; Khare, Rachna; Khare, Ajay

    2016-01-01

    A nation is recognized by a range of its significant historical, cultural and natural properties. These properties are generally preserved and maintained either by national administration or by private owners and charitable trusts due to higher value of their cultural inheritance and termed globally as heritage or historic sites. Heritage sites are a significant asset, a unique and irreplaceable resource which reflects a rich and diverse expression of past societies and forms an integral part of local, regional and national cultural identity. Today, heritage sites also play an important role in communication and knowledge exchange. Thus the rapidly increasing heritage tourism industry faces several challenges too. One of the challenges is that there is a segment of society who is not yet able to equally enjoy the visit to historic structures/sites and attractions, facilities and services. This paper aims to study the experience and develop understanding regarding the heritage structures/sites approached and interacted by diverse users. This study is an outcome of a hands on workshop conducted with diverse users at various historic sites in the city of Jaipur viz. at The City Palace Complex, Jaipur, Jaigarh Fort and the Haveli at Kanota near to Jaipur India. PMID:27534337

  12. Universal Access in Heritage Sites: A Case Study on Historic Sites in Jaipur, India.

    PubMed

    Vardia, Shweta; Khare, Rachna; Khare, Ajay

    2016-01-01

    A nation is recognized by a range of its significant historical, cultural and natural properties. These properties are generally preserved and maintained either by national administration or by private owners and charitable trusts due to higher value of their cultural inheritance and termed globally as heritage or historic sites. Heritage sites are a significant asset, a unique and irreplaceable resource which reflects a rich and diverse expression of past societies and forms an integral part of local, regional and national cultural identity. Today, heritage sites also play an important role in communication and knowledge exchange. Thus the rapidly increasing heritage tourism industry faces several challenges too. One of the challenges is that there is a segment of society who is not yet able to equally enjoy the visit to historic structures/sites and attractions, facilities and services. This paper aims to study the experience and develop understanding regarding the heritage structures/sites approached and interacted by diverse users. This study is an outcome of a hands on workshop conducted with diverse users at various historic sites in the city of Jaipur viz. at The City Palace Complex, Jaipur, Jaigarh Fort and the Haveli at Kanota near to Jaipur India.

  13. 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.

  14. 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.

  15. 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

  16. Electromagnetic induction in New Zealand: analogue model and field results

    NASA Astrophysics Data System (ADS)

    Chen, J.; Dosso, H. W.; Ingham, M.

    The behaviour of electric and magnetic variations over North Island (New Zealand) is studied with the aid of a laboratory analogue model. The source field frequencies used in the analogue modelling simulate naturally occurring geomagnetic variations of 5-120 min periods. In-phase and quadrature magnetic and electric fields for a selection of traverses for the modelled region of North Island are presented. Since North Island is of a relatively narrow cross-section, the field responses, even for inland locations, are expected to show strongly the effects of the surrounding ocean. The irregular coastlines, as well as the strait between North and South Islands, lead to coastal and inland field anomalies due to induced currents being deflected and channelled to produce localized current densities. The comparison of model results with field station measurements obtained earlier individually by Ingham and by Midha for sites in the northeastern, central, and southern (near Cook Strait) regions of North Island demonstrates the large role the ocean has in the observed field responses. Differences in the model and field results at some sites are expected and should reflect the effects of the local geology and the conductive substructure related to the complex tectonics of the region not simulated in the model.

  17. Cyclic cholecystokinin analogues with high selectivity for central receptors

    SciTech Connect

    Charpentier, B.; Pelaprat, D.; Durieux, C.; Dor, A.; Roques, B.P. ); Reibaud, M.; Blanchard, J.C. )

    1988-03-01

    Taking as a model the N-terminal folding of the cholecystokinin tyrosine-sulfated octapeptide deduced from conformational studies, two cyclic cholecystokinin (CCK) analogues were synthesized by conventional peptide synthesis. The binding characteristics of these peptides were investigated on brain cortex membranes and pancreatic acini of guinea pig. Compounds I and II were competitive inhibitors of ({sup 3}H)Boc(Ahx{sup 28,31})CCK-(27-33) binding to central CCK receptors and showed a high degree of selectivity for these binding sites. This high selectivity was associated with a high affinity for central CCK receptors. Similar affinities and selectivities were found when {sup 125}I Bolton-Hunter-labeled CCK-8 was used as a ligand. Moreover, these compounds were only weakly active in the stimulation of amylase release from guinea pig pancreatic acini and were unable to induce contractions in the guinea pig ileum. The two cyclic CCK analogues, therefore, appear to be synthetic ligands exhibiting both high affinity and high selectivity for central CCK binding sites. These compounds could help clarify the respective role of central and peripheral receptors for various CCK-8-induced pharmacological effects.

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

    SciTech Connect

    Siegrist, R.L.; Korte, N.E.; Pickering, D.A. ); Phelps, T.J. )

    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.

  19. 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.

  20. 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)

  1. Self-assembly mechanism of nanoparticles of Ni-based Prussian Blue analogues at the air/liquid interface: a synchrotron X-ray reflectivity study.

    PubMed

    Giner-Casares, Juan J; Clemente-León, Miguel; Coronado, Eugenio; Brezesinski, Gerald

    2015-08-24

    Prussian Blue analogue (PBA) nanoparticles can be self-assembled at air/liquid interfaces to build novel materials with interesting magnetic features. Herein, we study the influence of the size of PBA Cs0.4 Ni[Cr(CN)6 ]0.9 and K0.25 Ni[Fe(CN)6 ]0.75 nanoparticles on the self-assembly behavior by synchrotron X-ray reflectivity. Both nanoparticles show similar Z-potential values. The phospholipid dipalmitoylphosphatidylcholine and the amino surfactant dimethyldioctadecylammonium have been used as Langmuir monolayers to anchor the PBA nanoparticles and study the interplay of forces directing the self-assembly of the nanoparticles at the surfactant/liquid interface. Whereas Cs0.4 Ni[Cr(CN)6 ]0.9 nanoparticles with a diameter of 8 nm form an incomplete layer at the surfactant/water interface, the larger K0.25 Ni[Fe(CN)6 ]0.75 nanoparticles with a diameter of 20 nm generate complete layers that can be stacked to one another. The size of the PBA nanoparticles is the main parameter determining the final arrangement at the air/liquid interface, due to the different extent of interparticle interaction. This study aims at the rationale design of PBA nanoparticles for an effective interfacial self-assembly, ultimately leading to functional materials.

  2. 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.

  3. Pyridopyrimidine analogues as novel adenosine kinase inhibitors.

    PubMed

    Zheng, G Z; Lee, C; Pratt, J K; Perner, R J; Jiang, M Q; Gomtsyan, A; Matulenko, M A; Mao, Y; Koenig, J R; Kim, K H; Muchmore, S; Yu, H; Kohlhaas, K; Alexander, K M; McGaraughty, S; Chu, K L; Wismer, C T; Mikusa, J; Jarvis, M F; Marsh, K; Kowaluk, E A; Bhagwat, S S; Stewart, A O

    2001-08-20

    A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.

  4. Studies on yeast nucleoside triphosphate-nucleoside diphosphate transphosphorylase (nucleoside diphosphokinase). IV. Steady-state kinetic properties with thymidine nucleotides (including 3'-azido-3'-deoxythymidine analogues).

    PubMed

    Kuby, S A; Fleming, G; Alber, T; Richardson, D; Takenaka, H; Hamada, M

    1991-01-01

    A study of the steady-state kinetics of the crystalline brewer's yeast (Saccharomyces carlsbergensis) nucleoside diphosphokinase, with the magnesium complexes of the adenine and thymidine nucleotides as reactants, has led to a postulated kinetic mechanism which proceeds through a substituted enzyme. This agrees with the earlier conclusions of Garces and Cleland [Biochemistry 1969; 8:633-640] who characterized a reaction between the magnesium complexes of the adenine and uridine nucleotides. An advantage of using thymidine nucleotides as reactants is that they permit accurate, rapid and continuous assays of the enzymatic activity in coupled-enzymatic tests. Through measurements of the initial velocities and product inhibition studies, the Michaelis constants, maximum velocities, and inhibition constants could be evaluated for the individual substrates. Competitive substrate inhibition was encountered at relatively high substrate concentrations, which also permitted an evaluation of their ability to act as 'dead-end' inhibitors. The Michaelis constants for the 3'-azido-3'-deoxythymidine (AzT) analogues were also evaluated and, although these values were only somewhat higher than those of their natural substrates, the Km's for the adenine nucleotides as paired substrates were lower and the Vmax's were drastically reduced. The pharmacological implications of these observations are touched upon and extrapolated to the cases where therapeutic doses of AzT may be employed.

  5. Monochromatic excimer light versus combination of topical steroid with vitamin D3 analogue in the treatment of nonsegmental vitiligo: a randomized blinded comparative study.

    PubMed

    Abdel Latif, Azmy Ahmed; Ibrahim, Shady Mahmoud Attia

    2015-01-01

    Vitiligo is a difficult disease to treat, socially stigmatizing its patients. Monochromatic excimer light (MEL) was developed for use in dermatology and adapted for the treatment of vitiligo. Comparing the efficacy of MEL versus topical combination therapy of vitamin D3 analogue and steroid in the treatment of nonsegmental vitiligo. Forty-four patients with localized and stable nonsegmental vitiligo participated in the present study. In each patient, two lesions were selected and divided randomly into two groups, group A was treated with daily topical combination of calcipotriol and betamethasone and group B was treated with biweekly sessions of MEL for 3 months. Efficacy based on repigmentation percentages were blindly evaluated by two independent physicians and patient's satisfaction. There was significant improvement in both treatment modalities at the end of the study, but without significant differences in both groups. There was a significant difference between both groups regarding the onset of repigmentation (p-value < 0.05), whereas group B showed early sign of repigmentation in first 4 weeks of treatment in 16 patients versus 7 patients in group A. Both treatment modalities offered encouraging results and both are promising lines for the treatment of vitiligo.

  6. Conformational and membrane interaction studies of the antimicrobial peptide alyteserin-1c and its analogue [E4K]alyteserin-1c.

    PubMed

    Subasinghage, Anusha P; O'Flynn, Donal; Conlon, J Michael; Hewage, Chandralal M

    2011-08-01

    Alyteserin-1c (GLKEIFKAGLGSLVKGIAAHVAS.NH(2)), first isolated from skin secretions of the midwife toad Alytes obstetricans, shows selective growth-inhibitory activity against Gram-negative bacteria. The structures of alyteserin-1c and its more potent and less haemolytic analogue [E4K]alyteserin-1c were investigated in various solution and membrane mimicking environments by proton NMR spectroscopy and molecular modelling. In aqueous solution, the peptide displays a lack of secondary structure but, in a 2,2,2-trifluoroethanol (TFE-d(3))-H(2)O solvent mixture, the structure is characterised by an extended alpha helix between residues Leu(2) and Val(21). Solution structural studies in the membrane mimicking environments, sodium dodecyl sulphate (SDS), dodecylphosphocholine (DPC), and 1,2-dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC) micelles, indicate that these peptides display an alpha helical structure between residues Lys(3) and Val(21). Positional studies of the peptides in SDS, DPC and DHPC media show that the N-terminal and central residues lie inside the micelle while C-terminal residues beyond Ala(19) do not interact with the micelles.

  7. 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.

  8. Site study plan for ecology, Deaf Smith County Site, Texas: Environmental Field Program: Preliminary Draft

    SciTech Connect

    Not Available

    1987-06-01

    The Ecology Site Study Plan describes a field program consisting of studies which include surveys for endangered, threatened, and candidate species; vegetation characterization, including mapping and cover typing, plant succession, wetlands description, and preexisting stresses; and wildlife community characterization, including availability and quality of habitats and descriptions of mammal, bird, reptile, amphibian, and invertebrate populations. The plan for each study describes the need for the study, study design, data management and use, schedule and personnel requirements, and quality assurance. These studies will provide data needed to satisfy requirements contained in, or derived from, the Salt Repository Project Requirements Document (SRP-RD). 83 refs., 3 tabs.

  9. Feasibility study for the United Heckathorn Superfund Site, Richmond, California

    SciTech Connect

    Lincoff, A.H.; Costan, G.P.; Montgomery, M.S.; White, P.J.

    1994-07-01

    The United Heckathom Superfund Site in Richmond, California, was used to formulate pesticides from approximately 1947 to 1966. Soils at the site and sediments in the harbor were contaminated with various chlorinated pesticides, primarily DDT, as a result of these activities. The US Environmental Protection Agency listed the site on the Superfund National Priorities List in 1990. This document is part of the Remedial Investigation and Feasibility Study phase of the Superfund response, which will provide the basis for selection of a final remedy that will protect human health and the environment and achieve compliance with federal and state envirorunental laws.

  10. Phosphonate analogues of dinucleotides as substrates for DNA-dependent RNA polymerase from Escherichia coli in primed abortive initiation reaction.

    PubMed

    Cvekl, A; Horská, K; Sebesta, K; Rosenberg, I; Holý, A

    1989-02-01

    Dinucleotides (3'-5')-ApU and UpA and their 3'-O-phosphonylmethyl and 5'-O-phosphonylmethyl analogues were studied as substrates in the primed abortive synthesis catalysed by Escherichia coli DNA-dependent RNA polymerase on poly[d(A-T)] template. All phosphonate analogues of dinucleotides containing the anomalous sugar-phosphate backbone are substrates for the holoenzyme as verified by RNase A and RNase T2 digestion of the trinucleotide analogues obtained. The finding that phosphonate dinucleotides act as primers for transcription indicates that steric requirements at the initiation site are not as specific as previously supposed. Analysis of kinetic constants of ordered bibi reaction Kia, KmA, KmB and Vmax suggests that the instability of short RNA-DNA hybrids contributes to the abortive release of trinucleotides formed.

  11. 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.

  12. 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),…

  13. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined. PMID:27575269

  14. 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.

  15. A new approach for ovarian stimulation in IVF using Corifollitropin Alfa in combination with GnRH analogues to trigger final oocyte maturation. A pilot study

    PubMed Central

    Decleer, W.; Osmanagaoglu, K.; Meganck, G.; Devroey, P.

    2014-01-01

    A pilot study of 10 patients undergoing IVF stimulation, using the new combination of Corifollitropin Alfa with highly purified hMG and GnRH antagonists has been performed, whereas final oocyte maturation was induced by GnRH analogues. The hormonal profiles were analyzed, as well as the clinical outcome. All patients were recruited between March 1st 2013 and June 30th 2013. They were all younger than 38 years, had a normal BMI (between 18,0 and 32,0) and did not have more than three previous IVF stimulations. The combination of long acting FSH with hphMG, and under protection of GnRH antagonists against spontaneous LH-surge, provided a normal hormonal profile for estradiol, progesterone, LH, and FSH. The average oocyte quality and embryo quality were excellent, which resulted in four pregnancies out of ten. We conclude that the described combination is a safe, efficient, and patient friendly alternative for the classical IVF stimulation. PMID:25374659

  16. The impact of genetic testing for Crohn's disease, risk magnitude and graphical format on motivation to stop smoking: an experimental analogue study.

    PubMed

    Wright, A J; Takeichi, C; Whitwell, S C L; Hankins, M; Marteau, T M

    2008-04-01

    Genetic tests may motivate risk-reducing behaviour more than other types of tests because they generate higher risk magnitudes and because their results have high personal relevance. To date, trial designs have not allowed the disentangling of the effects of these two factors. This analogue study examines the independent impacts of risk magnitude and provenance, and of risk display type, on motivation to quit smoking. A total of 180 smokers were randomly allocated to one of the 18 Crohn's disease risk vignettes in a 3 (risk provenance: family history. genetic test mutation positive. genetic test mutation negative) x 3 (risk magnitude: 3%, 6%, 50%) x 2 (display: grouped or dispersed icons) design. The 50% group had significantly higher intentions to quit than the 3% group. A significant risk provenance x magnitude interaction showed that participants in 50% or 6% groups were equally motivated, regardless of risk provenance, while participants in the 3% group had higher intentions associated with a mutation negative result than with a result based on family history alone. Grouped icon displays were more motivating than the dispersed icons. Using genetic tests to estimate risks of common complex conditions may not motivate behaviour change beyond the impact of the numerical risk estimates derived from such tests.

  17. The development of insomnia or the plasticity of good sleep? A preliminary study of acute changes in sleep and insomnia resulting from an analogue trauma.

    PubMed

    Richardson, Cele; Gradisar, Michael; Pulford, Amanda

    2015-01-01

    The present preliminary study aimed to shed light on the mechanisms underlying the development of insomnia. An analogue stressor (i.e., trauma video) was used to prevent presleep cognitive de-arousal. Subsequent changes in nocturnal sleep and sleep-related attentional processing were examined. Thirty-four participants were randomly assigned to either a cognitive arousal (trauma video; age: M = 22.9, SD = 4.3, 6 male, 11 female) or control (pleasant video; age: M = 23.8, SD = 5.8, 7 male, 10 female) condition. Although no significant differences were found for presleep cognitive de-arousal (p = .39), the cognitive arousal group experienced a significant worsening in sleep latency (p = .048, partial η(2) = .12) and an increase in sleep-related attentional bias (p = .032, d = 0.51) following the manipulation. However, changes in sleep and attentional bias were not maintained. Vulnerability to stress did not significantly account for any change in attentional bias, arousal, or sleep. These findings challenge current conceptualizations of the development of insomnia, yet also supporting the notion that good sleep is a default state that protects individuals from sleep disturbance.

  18. Ce(IV)- and light-driven water oxidation by [Ru(terpy)(pic)3]2+ analogues: catalytic and mechanistic studies.

    PubMed

    Duan, Lele; Xu, Yunhua; Tong, Lianpeng; Sun, Licheng

    2011-02-18

    A series of mononuclear ruthenium polypyridyl complexes [Ru(Mebimpy)(pic)(3)](PF(6))(2) (2; Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; pic = 4-picoline), Ru(bimpy)(pic)(3) (3; H(2)bimpy = 2,6-bis(benzimidazol-2-yl)pyridine), trans-[Ru(terpy)(pic)(2)Cl](PF(6)) (4; terpy = 2,2';6',2"-terpyridine), and trans-[Ru(terpy)(pic)(2)(OH(2))](ClO(4))(2) (5) are synthesized and characterized as analogues of the known Ru complex, [Ru(terpy)(pic)(3)](PF(6))(2) (1). The effect of the ligands on electronic and catalytic properties is studied and discussed. The negatively charged ligand, bimpy(2-), has a remarkable influence on the electrochemical events due to its strong electron-donating ability. The performance in light- and Ce(IV)-driven (Ce(IV) = Ce(NH(4))(2)(NO(3))(6)) water oxidation is successfully demonstrated. We propose that ligand exchange between pic and H(2)O occurs to form the real catalyst, a Ru-aqua complex. The synthesis and testing of trans-[Ru(terpy)(pic)(2)(OH(2))](ClO(4))(2) (5) confirmed our proposal. In addition, complex 5 possesses the best catalytic activity among these five complexes.

  19. Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease.

    PubMed

    Peyre, Ludovic; Rouimi, Patrick; de Sousa, Georges; Héliès-Toussaint, Cécile; Carré, Benjamin; Barcellini, Sylvie; Chagnon, Marie-Christine; Rahmani, Roger

    2014-08-01

    For several decades, people have been in contact with bisphenol A (BPA) primarily through their diet. Nowadays it is gradually replaced by an analogue, bisphenol S (BPS). In this study, we compared the effects of these two bisphenols in parallel with the positive control diethylstilbestrol (DES) on different hepatocyte cell lines. Using a cellular impedance system we have shown that BPS is less cytotoxic than BPA in acute and chronic conditions. We have also demonstrated that, contrary to BPA, BPS is not able to induce an increase in intracellular lipid and does not activate the PXR receptor which is known to be involved in part, in this process. In parallel, it failed to modulate the expression of CYP3A4 and CYP2B6, the drug transporter ABCB1 and other lipid metabolism genes (FASN, PLIN). However, it appears to have a weak effect on GSTA4 protein expression and on the Erk1/2 pathway. In conclusion, in contrast to BPA, BPS does not appear to induce the metabolic syndrome that may lead to non-alcoholic fatty liver disease (NAFLD), in vitro. Although we have to pay special attention to BPS, its use could be less dangerous concerning this toxicological endpoint for human health.

  20. Comparison of neural correlates of risk decision making between genders: an exploratory fNIRS study of the Balloon Analogue Risk Task (BART).

    PubMed

    Cazzell, Mary; Li, Lin; Lin, Zi-Jing; Patel, Sonal J; Liu, Hanli

    2012-09-01

    Functional magnetic resonance imaging (fMRI) research rarely reports gender differences in the neural correlates of risk decision making due to small sample sizes. In this functional near-infrared spectroscopy (fNIRS)-based imaging study of active and passive risk decision making, gender differences in oxygenated hemoglobin (HbO) concentration changes were investigated in the prefrontal cortex (PFC) of healthy adults. Forty adult participants (25-44 years; males=23) completed two sets of 15 balloon trials in active and passive decision making modes of the Balloon Analogue Risk Task (BART). In active mode, participants chose the number of balloon inflations, decided when to collect money, or risked accrued money if balloons exploded. BART is psychometrically well established and has predictive validity to real-world risk taking. The blocked experimental design and modification of BART for fNIRS were guided by a previous fMRI study that examined the neural correlates of risk decision making in young adults [Rao, H., Korczykowski, M., Pluta, J., Hoang, A., Detre, J.A., 2008. Neural correlates of voluntary and involuntary risk taking in the human brain: An fMRI study of the Balloon Analog Risk Task (BART). NeuroImage 42, 902-910]. Our findings were consistent with the previous fMRI study: no or little PFC activation during passive mode but strong PFC activation during active wins and losses among total sample. Active losses in females were associated with more significant bilateral activation in dorsal lateral prefrontal cortex (DLPFC) than males; no significant gender differences were found in DLPFC activation during active wins. Gender differences existed in direction and strength of correlations between BART behavioral and hemodynamic data. This study shows that use of fNIRS is a feasible, accessible, and less costly way to achieve adequate study power and investigate gender differences in neural correlates of risk decision making. PMID:22634214

  1. S-homoadenosyl-L-cysteine and S-homoadenosyl-L-homocysteine. Synthesis and binding studies of hon-hydrolyzed substrate analogues with S-adenosyl-L-homocysteine hydrolase.

    PubMed

    Miles, Robert W; Nielsen, Lars P C; Ewing, Gregory J; Yin, Daniel; Borchardt, Ronald T; Robins, Morris J

    2002-11-15

    Treatment of homoadenosine [9-(5-deoxy-beta-D-ribo-hexofuranosyl)adenine] with thionyl chloride and pyridine in acetonitrile gave 6'-chloro-6'-deoxyhomoadenosine, which underwent nucleophilic displacement with L-cysteine or L-homocysteine to give homologated analogues of S-adenosyl-L-homocysteine. Each amino acid in aqueous sodium hydroxide at 60 degrees C gave excellent conversion from the chloronucleoside, and adsorption on Amberlite XAD-4 resin provided more convenient isolation than prior methods. Weak binding of these non-hydrolyzed analogues to S-adenosyl-L-homocysteine hydrolase was observed.

  2. Design, Synthesis and Structure-Activity Relationship Studies of Novel 4 (1-adamantyl) Phenyl Analogues as HIF-1α Inhibitors.

    PubMed

    Xia, Yan; Duan, Qiong; Zhao, Bao-Hua; Li, Dong-Feng; Hou, Rui-Bin

    2016-01-01

    Hypoxia inducible factor-1 (HIF-1) is a key mediator during cancer cells to adapt tumor hypoxic condition. In this study, a series of adamantane-based compounds were synthesized and evaluated as potential inhibitors of HIF-1α. Examination of their structure-activity relationship (SAR) identified the adamantane-containing indole derivative 20a as a potent inhibitor of HIF-1α in Hep3B cell lines under tumor hypoxia (IC50 = 0.02 µM). The study herein may provide valuable information for the development of novel therapeutics against cancer and tumor angiogenesis. PMID:26548744

  3. EPR study of thermally treated Archean microbial mats analogues and comparison with Archean cherts: towards a possible marker of oxygenic photosynthesis?

    NASA Astrophysics Data System (ADS)

    Bourbin, M.; Derenne, S.; Westall, F.; Gourier, D.; Gautret, P.; Rouzaud, J.-N.; Robert, F.

    2012-04-01

    The datation of photosynthesis apparition remains an open question nowadays: did oxygenic photosynthesis appear just before the Great Oxidation Event (GOE) of the atmosphere, 2.3 to 2.4 Gyr ago, or does it originate much earlier? It is therefore of uttermost interest to find markers of oxygenic photosynthesis, applicable to samples of archean age. In order to handle this problem, Microcoleus Chtonoplastes cyanobacteria and Chloroflexus-like non-oxygenic photosynthetic bacteria, were studied using Electron Paramagnetic Resonance (EPR) spectroscopy, a high sensitivity technique for the study of organic radicals in mature geological samples (coals, cherts, meteorites...). M. chtonoplastes and Chloroflexus-like bacteria were sampled in mats from the hypersaline lake "La Salada de Chiprana" (Spain), an analogue to an Archean environment, and were submitted to accelerated ageing through cumulative thermal treatments. For thermal treatment temperatures higher than 620° C, a drastic increase in the EPR linewidth of the oxygenic photosynthetic bacteria (M. chtonoplastes) occurred, as compared with the anoxygenic photosynthetic one (Chloroflexus-like). The EPR study of a thermally treated mixture of the two bacteria evidences that this linewidth increase is driven by catalytic reaction at high temperatures on an element selectively fixed by M. chtonoplastes. Based on comparative EDS analyses, Mg is a potential candidate for this catalytic activity but its precise role and the nature of the reaction are still to be determined. The EPR study of organic radicals in chert rocks of ages ranging from 0.42 to 3.5 Gyr, from various localities and that underwent various metamorphisms, revealed a dispersion of the signal width for the most mature samples. This comparative approach between modern bacterial samples and Precambrian cherts leads to propose the EPR linewidth of mature organic matter in cherts as a potential marker of oxygenic photosynthesis. If confirmed, this marker

  4. Overview of Ground-Water Recharge Study Sites

    USGS Publications Warehouse

    Constantz, Jim; Adams, Kelsey S.; Stonestrom, David A.

    2007-01-01

    Multiyear studies were done to examine meteorologic and hydrogeologic controls on ephemeral streamflow and focused ground-water recharge at eight sites across the arid and semiarid southwestern United States. Campaigns of intensive data collection were conducted in the Great Basin, Mojave Desert, Sonoran Desert, Rio Grande Rift, and Colorado Plateau physiographic areas. During the study period (1997 to 2002), the southwestern region went from wetter than normal conditions associated with a strong El Ni?o climatic pattern (1997?1998) to drier than normal conditions associated with a La Ni?a climatic pattern marked by unprecedented warmth in the western tropical Pacific and Indian Oceans (1998?2002). The strong El Ni?o conditions roughly doubled precipitation at the Great Basin, Mojave Desert, and Colorado Plateau study sites. Precipitation at all sites trended generally lower, producing moderate- to severe-drought conditions by the end of the study. Streamflow in regional rivers indicated diminishing ground-water recharge conditions, with annual-flow volumes declining to 10?46 percent of their respective long-term averages by 2002. Local streamflows showed higher variability, reflecting smaller scales of integration (in time and space) of the study-site watersheds. By the end of the study, extended periods (9?15 months) of zero or negligible flow were observed at half the sites. Summer monsoonal rains generated the majority of streamflow and associated recharge in the Sonoran Desert sites and the more southerly Rio Grande Rift site, whereas winter storms and spring snowmelt dominated the northern and westernmost sites. Proximity to moisture sources (primarily the Pacific Ocean and Gulf of California) and meteorologic fluctuations, in concert with orography, largely control the generation of focused ground-water recharge from ephemeral streamflow, although other factors (geology, soil, and vegetation) also are important. Watershed area correlated weakly with focused

  5. A theoretical study of a ZnO graphene analogue: adsorption on Ag(111) and hydrogen transport.

    PubMed

    Demiroglu, Ilker; Stradi, Daniele; Illas, Francesc; Bromley, Stefan T

    2011-08-24

    A single sheet of zinc oxide (ZnO) based on the same flat two-dimensional (2D) hexagonal topology as graphene, but with alternating neighbouring Zn and O atoms in place of carbon atoms, is studied theoretically. Following experimental studies, the adsorption of 2D-ZnO with the Ag(111) surface is investigated using density functional theory, with and without a semi-empirical correction for dispersive interactions, and with classical interatomic potentials. The interaction of H atoms with the hexagonal Zn(3)O(3) rings of 2D-ZnO is given special attention where multi-centre bond formation is observed to significantly assist the transport of H atoms through the 2D-ZnO sheet.

  6. Pesticides in roof runoff: study of a rural site and a suburban site.

    PubMed

    Vialle, C; Sablayrolles, C; Silvestre, J; Monier, L; Jacob, S; Huau, M-C; Montrejaud-Vignoles, M

    2013-05-15

    The quality of stored roof runoff in terms of pesticide pollution was assessed over a one-year period. Two tanks, located at a rural and suburban site, respectively, were sampled monthly. The two studied collection surface were respectively a tile slope roof and a bituminous flat roof. Four hundred and five compounds and metabolites were screened using liquid and gas chromatography coupled with various detection systems. Principal Component Analysis was applied to the data sets to elucidate patterns. At the rural site, two groups of compounds associated with two different types of agriculture, vineyard and crops, were distinguished. The most frequently detected compound was glyphosate (83%) which is the most commonly used herbicide in French vineyards. At the suburban site, quantified compounds were linked to agriculture rather than urban practices. In addition, all samples were contaminated with mecoprop which is a roof-protecting agent. Its presence was attributed to the nature of roofing material used for rainwater collection. For both sites, the highest number and concentrations of compounds and metabolites were recorded at the end of spring and through summer. These results are consistent with treatment periods and higher temperatures.

  7. Interflavin electron transfer in human cytochrome P450 reductase is enhanced by coenzyme binding. Relaxation kinetic studies with coenzyme analogues.

    PubMed

    Gutierrez, Aldo; Munro, Andrew W; Grunau, Alex; Wolf, C Roland; Scrutton, Nigel S; Roberts, Gordon C K

    2003-06-01

    The role of coenzyme binding in regulating interflavin electron transfer in human cytochrome P450 reductase (CPR) has been studied using temperature-jump spectroscopy. Previous studies [Gutierrez, A., Paine, M., Wolf, C.R., Scrutton, N.S., & Roberts, G.C.K. Biochemistry (2002) 41, 4626-4637] have shown that the observed rate, 1/tau, of interflavin electron transfer (FADsq - FMNsq-->FADox - FMNhq) in CPR reduced at the two-electron level with NADPH is 55 +/- 2 s-1, whereas with dithionite-reduced enzyme the observed rate is 11 +/- 0.5 s-1, suggesting that NADPH (or NADP+) binding has an important role in controlling the rate of internal electron transfer. In relaxation experiments performed with CPR reduced at the two-electron level with NADH, the observed rate of internal electron transfer (1/tau = 18 +/- 0.7 s-1) is intermediate in value between those seen with dithionite-reduced and NADPH-reduced enzyme, indicating that the presence of the 2'-phosphate is important for enhancing internal electron transfer. To investigate this further, temperature jump experiments were performed with dithionite-reduced enzyme in the presence of 2',5'-ADP and 2'-AMP. These two ligands increase the observed rate of interflavin electron transfer in two-electron reduced CPR from 1/tau = 11 s-1 to 35 +/- 0.2 s-1 and 32 +/- 0.6 s-1, respectively. Reduction of CPR at the two-electron level by NADPH, NADH or dithionite generates the same spectral species, consistent with an electron distribution that is equivalent regardless of reductant at the initiation of the temperature jump. Spectroelectrochemical experiments establish that the redox potentials of the flavins of CPR are unchanged on binding 2',5'-ADP, supporting the view that enhanced rates of interdomain electron transfer have their origin in a conformational change produced by binding NADPH or its fragments. Addition of 2',5'-ADP either to the isolated FAD-domain or to full-length CPR (in their oxidized and reduced forms) leads to

  8. 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.

  9. 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

  10. 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

  11. Effects of gender-related domain violations and sexual orientation on perceptions of male and female targets: an analogue study.

    PubMed

    Blashill, Aaron J; Powlishta, Kimberly K

    2012-10-01

    The current study examined factors that influenced heterosexual male and female raters' evaluations of male and female targets who were gay or heterosexual, and who displayed varying gender roles (i.e., typical vs. atypical) in multiple domains (i.e., activities, traits, and appearance). Participants were 305 undergraduate students from a private, midwestern Jesuit institution who read vignettes describing one of 24 target types and then rated the target on possession of positive and negative characteristics, psychological adjustment, and on measures reflecting the participants' anticipated behavior toward or comfort with the target. Results showed that gender atypical appearance and activity attributes (but not traits) were viewed more negatively than their gender typical counterparts. It was also found that male participants in particular viewed gay male targets as less desirable than lesbian and heterosexual male targets. These findings suggest a nuanced approach for understanding sexual prejudice, which incorporates a complex relationship among sex, gender, sexual orientation, and domain of gendered attributes. PMID:22722956

  12. Effects of gender-related domain violations and sexual orientation on perceptions of male and female targets: an analogue study.

    PubMed

    Blashill, Aaron J; Powlishta, Kimberly K

    2012-10-01

    The current study examined factors that influenced heterosexual male and female raters' evaluations of male and female targets who were gay or heterosexual, and who displayed varying gender roles (i.e., typical vs. atypical) in multiple domains (i.e., activities, traits, and appearance). Participants were 305 undergraduate students from a private, midwestern Jesuit institution who read vignettes describing one of 24 target types and then rated the target on possession of positive and negative characteristics, psychological adjustment, and on measures reflecting the participants' anticipated behavior toward or comfort with the target. Results showed that gender atypical appearance and activity attributes (but not traits) were viewed more negatively than their gender typical counterparts. It was also found that male participants in particular viewed gay male targets as less desirable than lesbian and heterosexual male targets. These findings suggest a nuanced approach for understanding sexual prejudice, which incorporates a complex relationship among sex, gender, sexual orientation, and domain of gendered attributes.

  13. Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in patients with chronic hepatitis B: a prospective cohort study in China.

    PubMed

    Qi, X; Wang, J-Y; Mao, R-C; Zhang, J-M

    2015-01-01

    Chronic hepatitis B therapy with nucleos(t)ide analogues, particularly tenofovir or adefovir, may affect renal function. To date, there has not been a head-to-head controlled study to assess estimated glomerular filtration rate (eGFR) fluctuations in nucleos(t)ide-treated CHB patients. We aimed to evaluate the long-term effects of nucleos(t)ide on eGFR in Chinese patients with chronic hepatitis B. This prospective cohort study included 275 patients. Patient subgroups included those treated with lamivudine (n = 50), adefovir (n = 60), telbivudine (n = 68) and entecavir (n = 61); untreated patients (n = 36) served as control. After an average follow-up duration of 23 months, eGFR calculated by Cockcroft-Gault and Modification of Diet in Renal Disease formulas increased by 18.35 mL/min and 19.34 mL/min (P < 0.0001) in the telbivudine group, respectively, and decreased by 10.95 mL/min and 12.17 mL/min (P = 0.0001) in the adefovir group, respectively. Even if renal function was normal or mildly impaired at baseline, eGFR increased significantly more in the telbivudine group than in the other groups (P < 0.001). More patients in the adefovir group (23%) had a ≥20% decrease in eGFR than the other groups (P < 0.0001). More patients in the telbivudine group (31%) had a ≥20% increase in eGFR than the other groups (P < 0.0001). In conclusion, prolonged telbivudine therapy resulted in improved eGFR, while adefovir therapy was associated with decreased eGFR. Lamivudine and entecavir therapy did not significantly influence eGFR.

  14. The effect of long-term fluid-rock interactions on the mechanical properties of reservoir rock - a case study of the Werkendam natural CO2 analogue field

    NASA Astrophysics Data System (ADS)

    Hangx, Suzanne; Bertier, Pieter; Bakker, Elisenda; Nover, Georg; Busch, Andreas

    2015-04-01

    Geological storage of CO2 is one of the most promising technologies to rapidly reduce anthropogenic emissions of carbon dioxide. During long-term geological storage of CO2, fluid-rock interactions, induced by the formation of carbonic acid, may affect the mineralogical composition of the reservoir rock. Commonly expected reactions include the dissolution of carbonate and/or sulphate cements, as well as the reaction of primary minerals (feldspars, clays, micas) to form new, secondary phases. In order to ensure storage integrity, it is important to understand the effect of such fluid-rock interactions on the mechanical behaviour of a CO2 storage complex. However, most of these reactions are very slow, which limits the ability to study coupled chemical-mechanical processes in the lab. A possible way to circumvent long reaction times is to investigate natural CO2 analogue fields, which experienced CO2-exposure for thousands of years. In this study, we looked at the Dutch Werkendam natural CO2 field and its unreacted counterpart (Röt Fringe Sandstone, Werkendam, the Netherlands). We focussed on CO2-induced mineralogical and porosity-permeability changes, and their effect on mechanical behaviour of intact rock. Overall, CO2-exposure did not lead to drastic mineralogical changes, though markedly different porosity-permeability relationships were found for the unreacted and exposed material. The limited extent of reaction was in part the result of bitumen coatings protecting specific mineral phases from reaction. In local, mm-sized zones displaying significant anhydrite dissolution, enhanced porosity was observed. For most of the reservoir the long-term mechanical behaviour after CO2-exposure could be described by the behaviour of the unreacted sandstone, while these more 'porous' zones were significantly weaker. Simple stress path calculations predict that reservoir failure due to depletion and injection is unlikely.

  15. Itraconazole Side Chain Analogues: Structure–Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling

    PubMed Central

    Shi, Wei; Nacev, Benjamin A.; Aftab, Blake T.; Head, Sarah; Rudin, Charles M.; Liu, Jun O.

    2012-01-01

    Itraconazole is an antifungal drug that was recently found to possess potent antiangiogenic activity and anti-hedgehog (Hh) pathway activity. To search for analogues of itraconazole with greater potency and to understand the structure–activity relationship in both antiangiogenic and Hh targeting activity, 25 itraconazole side chain analogues were synthesized and assayed for inhibition of endothelial cell proliferation and Gli1 transcription in a medulloblastoma (MB) culture. Through this analysis, we have identified analogues with increased potency for inhibiting endothelial cell proliferation and the Hh pathway, as well as VEGFR2 glycosylation that was recently found to be inhibited by itraconazole. An SAR analysis of these activities revealed that potent activity of the analogues against VEGFR2 glycosylation was generally driven by side chains of at least four carbons in composition with branching at the α or β position. SAR trends for targeting the Hh pathway were divergent from those related to HUVEC proliferation or VEGFR2 glycosylation. These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole. PMID:21936514

  16. A Patient Specific Biomechanical Analysis of Custom Root Analogue Implant Designs on Alveolar Bone Stress: A Finite Element Study.

    PubMed

    Anssari Moin, David; Hassan, Bassam; Wismeijer, Daniel

    2016-01-01

    Objectives. The aim of this study was to analyse by means of FEA the influence of 5 custom RAI designs on stress distribution of peri-implant bone and to evaluate the impact on microdisplacement for a specific patient case. Materials and Methods. A 3D surface model of a RAI for the upper right canine was constructed from the cone beam computed tomography data of one patient. Subsequently, five (targeted) press-fit design modification FE models with five congruent bone models were designed: "Standard," "Prism," "Fins," "Plug," and "Bulbs," respectively. Preprocessor software was applied to mesh the models. Two loads were applied: an oblique force (300 N) and a vertical force (150 N). Analysis was performed to evaluate stress distributions and deformed contact separation at the peri-implant region. Results. The lowest von Mises stress levels were numerically observed for the Plug design. The lowest levels of contact separation were measured in the Fins model followed by the Bulbs design. Conclusions. Within the limitations of the applied methodology, adding targeted press-fit geometry to the RAI standard design will have a positive effect on stress distribution, lower concentration of bone stress, and will provide a better primary stability for this patient specific case. PMID:27274727

  17. 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 η2 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.

  18. Synthetic, structural and biological studies of the ubiquitin system: synthesis and crystal structure of an analogue containing unnatural amino acids.

    PubMed Central

    Love, S G; Muir, T W; Ramage, R; Shaw, K T; Alexeev, D; Sawyer, L; Kelly, S M; Price, N C; Arnold, J E; Mee, M P; Mayer, R J

    1997-01-01

    Ubiquitin is a 76-amino acid protein involved in the targeting for destruction of proteins in the cell. The protein can readily be synthesized chemically affording an extra dimension to studies of protein stability. Ubiquitin with various modifications to the hydrophobic core has been synthesized. In particular, two core amino acids have been replaced by aminobutyric acid (Val-26) and norvaline (for Ile-30) and the product crystallized. The refined crystal structure shows an overall contraction of the molecule and the side chain of Nva-30 rotates relative to Ile-30. However, the side chain rotation is not sufficient to compensate for the effect of the loss of the methyl group and hence a small cavity is introduced into the structure, which decreases the stability of the protein. The biological behaviour of the modified protein is unaltered. The observed changes in stability are of the magnitude expected for the removal of methyl groups from the hydrophobic core of a protein. Interestingly, the effect appears to be independent of the position of the removed methyl group. The intact structure, but not its stability, is important for recognition by the biological conjugating system. PMID:9169606

  19. A Patient Specific Biomechanical Analysis of Custom Root Analogue Implant Designs on Alveolar Bone Stress: A Finite Element Study

    PubMed Central

    2016-01-01

    Objectives. The aim of this study was to analyse by means of FEA the influence of 5 custom RAI designs on stress distribution of peri-implant bone and to evaluate the impact on microdisplacement for a specific patient case. Materials and Methods. A 3D surface model of a RAI for the upper right canine was constructed from the cone beam computed tomography data of one patient. Subsequently, five (targeted) press-fit design modification FE models with five congruent bone models were designed: “Standard,” “Prism,” “Fins,” “Plug,” and “Bulbs,” respectively. Preprocessor software was applied to mesh the models. Two loads were applied: an oblique force (300 N) and a vertical force (150 N). Analysis was performed to evaluate stress distributions and deformed contact separation at the peri-implant region. Results. The lowest von Mises stress levels were numerically observed for the Plug design. The lowest levels of contact separation were measured in the Fins model followed by the Bulbs design. Conclusions. Within the limitations of the applied methodology, adding targeted press-fit geometry to the RAI standard design will have a positive effect on stress distribution, lower concentration of bone stress, and will provide a better primary stability for this patient specific case. PMID:27274727

  20. Studies in vitro to discern the structural requirements for carcinogenicity in analogues of the carcinogen 4-dimethylaminoazobenzene (butter yellow).

    PubMed

    Ashby, J; Styles, J A; Paton, D

    1980-01-01

    4-Dimethylaminoazobenzene (butter yellow, DAB), is the parent member of a large family of 'azo-carcinogens'. Experiments have been conducted in vitro to determine the key structural requirements for carcinogenic activity in this chemical class, and it is suggested, based on the activity observed for 4-cyano-N,N-dimethylaniline, that the 4-phenylazo group of DAB is not an essential structural feature per se. The N-oxide derivative of DAB has been evaluated in vitro and the positive response observed related to its metabolic activation. It is concluded that cyclic amines, such as pyrrolidine, can replace the N-dimethyl group of DAB with a retention of biological activity. The confusion that exists in the literature concerning the chemical identity and carcinogenic status of 2-dimethylaminobenzo[c]cinnoline has been investigated, and it is concluded that it is a potential animal carcinogen. This observation also indicates that the phenylazo group of DAB can be incorporated within an aromatic ring system with a retention of biological activity. As observed earlier with a mixture of azobenzene and DAB, azobenzene also potentiates the cell transforming properties of the above cinnoline derivative in vitro. Two charts are presented. The first attempts to integrate DAB within a much larger family of carcinogens, and the second illustrates the usefulness of structure-activity studies in general.

  1. Synthesis, pharmacological screening and in silico studies of new class of Diclofenac analogues as a promising anti-inflammatory agents.

    PubMed

    Palkar, Mahesh B; Singhai, Anuj S; Ronad, Pradeepkumar M; Vishwanathswamy, A H M; Boreddy, Thippeswamy S; Veerapur, Veeresh P; Shaikh, Mahamadhanif S; Rane, Rajesh A; Karpoormath, Rajshekhar

    2014-05-15

    A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1,3,4-oxadiazol-2(3H)-thione (4a-k) derivatives have been synthesized by the Mannich reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)-thione (3) with an appropriately substituted primary/secondary amines, in the presence of formaldehyde and absolute ethanol. Structures of these novel compounds were characterized on the basis of physicochemical, spectral and elemental analysis. The title compounds (4a-k) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 10mg/kg b.w. Compound 4k exhibited the most promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e, 4i, and 4j showed moderate to good inhibitory activity at 2nd and 4thh, respectively. These compounds were also found to have considerable analgesic activity (acetic acid induced writhing model) and antipyretic activity (yeast induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. Compounds that displayed promising anti-inflammatory profile were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of the binding affinity, docking studies were performed using Molegro Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti-inflammatory activity. It was observed that the binding affinities calculated were in agreement with the IC50 values. PMID:24751552

  2. Synthesis and structure-activity relationship study of antidiabetic penta-O-galloyl-D-glucopyranose and its analogues.

    PubMed

    Ren, Yulin; Himmeldirk, Klaus; Chen, Xiaozhuo

    2006-05-01

    The rapid increase of obesity-associated diabetes has created urgent demands for more effective antidiabetic therapies and pharmaceuticals that are able to address the problems of hyperglycemia and weight gain simultaneously. Our previous studies indicated that the alpha- and beta-anomers of penta-O-galloyl-D-glucopyranose (PGG), 2 and 3, act as insulin mimetics that bind to and activate the insulin receptor, stimulate glucose transport in adipocytes, and reduce blood glucose and insulin levels in diabetic and obese animals. In addition, they inhibit differentiation of preadipocytes into adipocytes. These activities suggest that 2 and 3 may reduce blood glucose without increasing adiposity. To investigate the structure-activity relationship of 2 and 3, four series of novel compounds were prepared and their glucose transport stimulatory activities were measured using a radioactive glucose uptake bioassay. The assay results indicate that both the glucose and the galloyl groups are critical to the activity of 2 and 3. It appears that the glucose core provides an optimal scaffold to present the galloyl groups with the correct spatial orientation to induce activity. Moreover, the galloyl groups linked to the 1, 2, 3, and 4 positions of glucose are essential, while the galloyl group connected to the 6 position of 2 is unnecessary for the induction of activity. The discovery that two related novel compounds, 6-deoxytetra-O-galloyl-alpha-D-glucopyranose (43) and tetra-O-galloyl-alpha-D-xylopyranose (59), also possess glucose transport stimulatory activity suggests that 2 may be further modified around position 6 to modulate and enhance its efficacy. To test this hypothesis, we developed a new synthetic method that allows for the stereoselective preparation of derivatives of 2 that are modified on C-6. We found that 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-alpha-D-glucopyranose (80) exhibits a significantly higher glucose transport stimulatory activity than 2. Its activity

  3. Study on the Antifibrotic Effects of Recombinant Shark Hepatical Stimulator Analogue (r-sHSA) in Vitro and in Vivo.

    PubMed

    Wang, Ying; Zhang, Xiaoyuan; Yang, Yang; Yang, Xiaohong; Ye, Boping

    2015-08-18

    Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hence, in this article, the antifibrotic effects and possible mechanisms of r-sHSA, a recombinant protein with hepatoprotection potential, were investigated. Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type I collagen (Col1A1) and α-smooth muscle actin (α-SMA). It turned out those fibrosis indicators were typically inhibited by r-sHSA, suggesting its capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further investigated in vivo on CCl4-induced hepatic fibrosis, in view of significant improvement of the biochemical and histological indicators. More specifically, CCl4-intoxication induced a significant increase in serological biomarkers, e.g., transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed hepatic antioxidative status; most of the parameters were spontaneously ameliorated to a large extent by withdrawal of CCl4, although the fibrotic lesion was observed histologically. In contrast, r-sHSA treatment markedly eliminated fibrous deposits and restored architecture of the liver in a dose dependent manner, concomitantly with the phenomena of inflammation relief and HSCs deactivation. To sum up, these findings suggest a therapeutic potential for r-sHSA in hepatic fibrosis, though further studies are required.

  4. 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)

  5. 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.

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

    PubMed

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

    2006-11-01

    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 found that reduce soluble selenate (SeO (4) (2-) ) to insoluble elemental Se. Microcosm experiments were conducted for molecular genetic analysis of this microbial community by rRNA gene profiling. An acetone pretreatment step was developed to remove interfering pre-petroleum hydrocarbons from the samples prior to extraction. PCR was used to amplify 16S and 18S rRNA genes present in the microbial community DNA. The amplified products were subjected to denaturing gradient gel electrophoresis (DGGE). Isolates and excised DGGE bands were amplified and sequenced for identification to determine the relative importance of culturable isolates to the total microbial population. Analysis of samples from different sites at the mine showed how Se contamination and previous remediation treatments changed the microbial populations across the site. Members of the family Enterobacteriaceae were dominant among the selenate reducing isolates from the site containing high Se levels. In particular, Serratia fonticola was isolated repeatedly from contaminated Smoky Canyon Mine site samples. Packed column studies were performed with seleniferous waste rock fractions from Smoky Canyon Mine. Column amendments consisted of combinations of iron, compost, and whey. Eh, pH, and extractable Se measurements were taken. Tests with infiltrated water showed columns containing an organic amendment combined with iron metal were the most resistant to Se leaching. Iron-based compounds from the corroding metal are thought to strongly bind the Se reduced by microbial activity, thereby stabilizing the Se in an insoluble form

  7. Theoretical Study of 1,2-Hydride Shift Associated with the Isomerization of Glyceraldehyde to Dihydroxy Acetone by Lewis Acid Active Site Models

    SciTech Connect

    Assary, Rajeev S.; Curtiss, Larry A.

    2011-08-11

    The isomerization of glyceraldehyde to dihydroxy acetone catalyzed by the active site of Sn-beta zeolite is investigated using the B3LYP density functional and MP2 levels of theory. Structural studies were aimed to understanding the binding modes of glyceraldehyde with the active site, and the detailed free energy landscape was computed for the isomerization process. The rate-limiting step for the isomerization is the 1,2-hydride shift, which is enhanced by the active participation of the hydroxyl group in the hydrolyzed Sn-beta active site analogues to the one seen in the xylose isomerase. On the basis of the assessment of the activation barriers for isomerization by the Sn, Zr, Ti, and Si zeolite models, the activity of the catalysts are in the order of Sn > Zr > Ti > Si in aqueous dielectric media.

  8. Theoretical study of 1,2-hydride shift associated with the isomerization of glyceraldehyde to dihydroxy acetone by Lewis acid active site models.

    SciTech Connect

    Assary, R. S.; Curtiss, L. A.

    2011-08-01

    The isomerization of glyceraldehyde to dihydroxy acetone catalyzed by the active site of Sn-beta zeolite is investigated using the B3LYP density functional and MP2 levels of theory. Structural studies were aimed to understanding the binding modes of glyceraldehyde with the active site, and the detailed free energy landscape was computed for the isomerization process. The rate-limiting step for the isomerization is the 1,2-hydride shift, which is enhanced by the active participation of the hydroxyl group in the hydrolyzed Sn-beta active site analogues to the one seen in the xylose isomerase. On the basis of the assessment of the activation barriers for isomerization by the Sn, Zr, Ti, and Si zeolite models, the activity of the catalysts are in the order of Sn > Zr > Ti > Si in aqueous dielectric media.

  9. Isothermal titration calorimetric studies on the binding of deoxytrimannoside derivatives with artocarpin: implications for a deep-seated combining site in lectins.

    PubMed

    Rani, P G; Bachhawat, K; Reddy, G B; Oscarson, S; Surolia, A

    2000-09-01

    The carbohydrate binding specificity of the seed lectin from Artocarpus integrifolia, artocarpin, has been elucidated by the enzyme-linked lectin absorbent assay [Misquith, S., et al (1994) J. Biol. Chem. 269, 30393-30401], wherein it was demonstrated to be a Man/Glc specific lectin with high affinity for the trisaccharide present in the core of all N-linked oligosaccharide chains of glycoproteins. As a consequence of this characterization, the binding epitopes of this trisaccharide, 3, 6-di(alpha-D-mannopyranosyl)-D-mannose, for artocarpin were investigated by isothermal titration calorimetry using its monodeoxy as well as Glc and Gal analogues. The thermodynamic data presented here implicate 2-, 3-, 4-, and 6-hydroxyl groups of the alpha(1-3) Man and alpha(1-6) Man residues, and the 2- and 4-OH groups of the central Man residue, in binding to artocarpin. Nevertheless, alpha(1-3) Man is the primary contributor to the binding affinity, unlike other Man/Glc binding lectins which exhibit a preference for alpha(1-6) Man. In addition, unlike the binding reactions of most lectins reported so far, the interaction of mannotriose involves all of its hydroxyl groups with the combining site of the lectin. Moreover, the free energy and enthalpy contributions to binding of individual hydroxyl groups of the trimannoside estimated from the corresponding monodeoxy analogues show nonlinearity, suggesting differential contributions of the solvent and protein to the thermodynamics of binding of the analogues. Thus, this study not only provides evidence for the extended site recognition of artocarpin for the trimannoside epitope but also suggests that its combining site is best described as a deep cleft as opposed to shallow indentations implicated in other lectins.

  10. A CASE STUDY ILLUSTRATING THE IMPORTANCE OF ACCURATE SITE CHARACTERIZATION

    EPA Science Inventory

    Too frequently, researchers rely on incomplete site characterization data to determine the placement of the sampling wells. They forget that it is these sampling wells that will be used to evaluate the effectiveness of their research efforts. This case study illustrates the eff...

  11. RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model.

    PubMed

    Ferreira, Adilson Kleber; Tavares, Maurício Temotheo; Pasqualoto, Kerly Fernanda Mesquita; de Azevedo, Ricardo Alexandre; Teixeira, Sarah Fernandes; Ferreira-Junior, Wilson Alves; Bertin, Ariane Matiello; de-Sá-Junior, Paulo Luiz; Barbuto, José Alexandre Marzagão; Figueiredo, Carlos Rogério; Cury, Yara; Damião, Mariana Celestina Frojuello Costa Bernstorff; Parise-Filho, Roberto

    2015-09-01

    Capsaicin, the primary pungent component of the chili pepper, has antitumor activity. Herein, we describe the activity of RPF151, an alkyl sulfonamide analogue of capsaicin, against MDA-MB-231 breast cancer cells. RPF151 was synthetized, and molecular modeling was used to compare capsaicin and RPF151. Cytotoxicity of RPF151 on MDA-MB-231 was also evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis, by flow cytometry, and Western blot analysis of cycle-related proteins were used to evaluate the antiproliferative mechanisms. Apoptosis was evaluated by phosphatidyl-serine externalization, cleavage of Ac-YVAD-AMC, and Bcl-2 expression. The production of reactive oxygen species was evaluated by flow cytometry. RPF151 in vivo antitumor effects were investigated in murine MDA-MB-231 model. This study shows that RPF151 downregulated p21 and cyclins A, D1, and D3, leading to S-phase arrest and apoptosis. Although RPF151 has induced the activation of TRPV-1 and TRAIL-R1/DR4 and TRAIL-2/DR5 on the surface of MDA-MB-231 cells, its in vivo antitumor activity was TRPV-1-independent, thus suggesting that RPF151 should not have the same pungency-based limitation of capsaicin. In silico analysis corroborated the biological findings, showing that RPF151 has physicochemical improvements over capsaicin. Overall, the activity of RPF151 against MDA-MB-231 and its lower pungency suggest that it may have a relevant role in cancer therapy. PMID:25894379

  12. RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model.

    PubMed

    Ferreira, Adilson Kleber; Tavares, Maurício Temotheo; Pasqualoto, Kerly Fernanda Mesquita; de Azevedo, Ricardo Alexandre; Teixeira, Sarah Fernandes; Ferreira-Junior, Wilson Alves; Bertin, Ariane Matiello; de-Sá-Junior, Paulo Luiz; Barbuto, José Alexandre Marzagão; Figueiredo, Carlos Rogério; Cury, Yara; Damião, Mariana Celestina Frojuello Costa Bernstorff; Parise-Filho, Roberto

    2015-09-01

    Capsaicin, the primary pungent component of the chili pepper, has antitumor activity. Herein, we describe the activity of RPF151, an alkyl sulfonamide analogue of capsaicin, against MDA-MB-231 breast cancer cells. RPF151 was synthetized, and molecular modeling was used to compare capsaicin and RPF151. Cytotoxicity of RPF151 on MDA-MB-231 was also evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis, by flow cytometry, and Western blot analysis of cycle-related proteins were used to evaluate the antiproliferative mechanisms. Apoptosis was evaluated by phosphatidyl-serine externalization, cleavage of Ac-YVAD-AMC, and Bcl-2 expression. The production of reactive oxygen species was evaluated by flow cytometry. RPF151 in vivo antitumor effects were investigated in murine MDA-MB-231 model. This study shows that RPF151 downregulated p21 and cyclins A, D1, and D3, leading to S-phase arrest and apoptosis. Although RPF151 has induced the activation of TRPV-1 and TRAIL-R1/DR4 and TRAIL-2/DR5 on the surface of MDA-MB-231 cells, its in vivo antitumor activity was TRPV-1-independent, thus suggesting that RPF151 should not have the same pungency-based limitation of capsaicin. In silico analysis corroborated the biological findings, showing that RPF151 has physicochemical improvements over capsaicin. Overall, the activity of RPF151 against MDA-MB-231 and its lower pungency suggest that it may have a relevant role in cancer therapy.

  13. Chemical-mechanical coupling observed for depleted oil reservoirs subjected to long-term CO2-exposure - A case study of the Werkendam natural CO2 analogue field

    NASA Astrophysics Data System (ADS)

    Hangx, Suzanne; Bakker, Elisenda; Bertier, Pieter; Nover, Georg; Busch, Andreas

    2015-10-01

    Geological storage of CO2 is one of the most promising technologies to rapidly reduce anthropogenic emissions of carbon dioxide. In order to ensure storage integrity, it is important to understand the effect of long-term CO2/brine/rock interactions on the mechanical behaviour of a storage complex. As most of these reactions are too slow to reproduce on laboratory timescales, we studied a natural CO2 analogue reservoir (the Röt Fringe Sandstone, Werkendam field, the Netherlands; 125-135 Ma of CO2-exposure) and its unreacted counterpart. We focused on CO2-induced mineralogical and porosity-permeability changes, and their effect on mechanical behaviour of both intact rock and simulated fault gouge. Overall, CO2-exposure did not lead to drastic mineralogical changes. The CO2-exposed material shows a stronger dependence of permeability on porosity, which is attributed to differences in diagenesis (closed-system diagenesis and hydrocarbon emplacement) taking place before CO2 charging. The limited extent of reaction was in part the result of bitumen coatings protecting specific mineral phases from reaction. In local, mm-sized zones displaying significant anhydrite cement dissolution, enhanced porosity was observed. For most of the reservoir the long-term mechanical behaviour after CO2-exposure could be described by the behaviour of the unreacted sandstone, while these more 'porous' zones had a lower rock strength. In addition, CO2-exposure did not affect the fault friction behaviour, and slip is expected to result in stable sliding. Simple stress path calculations predict that reservoir failure due to depletion and injection is unlikely, even for the 'porous' zones, nor will fault reactivation occur for realistic injection scenarios.

  14. Risk perception in context: the Savannah River Site Stakeholder Study.

    PubMed

    Williams, B L; Brown, S; Greenberg, M; Kahn, M A

    1999-12-01

    Environmental managers are increasingly charged with involving the public in the development and modification of policies regarding risks to human health and the environment. Involving the public in environmental decision making first requires a broad understanding of how and why the public perceives various risks. The Savannah River Stakeholder Study was conducted with the purpose of investigating individual, economic, and social characteristics of risk perceptions among those living near the Savannah River Nuclear Weapons Site. A number of factors were found to impact risk perceptions among those living near the site. One's estimated proximity to the site and relative river location surfaced as strong determinants of risk perceptions among SRS residents. Additionally, living in a quality neighborhood and demonstrating a willingness to accept health risks for economic gain strongly abated heightened risk perceptions.

  15. Mars sample return: Site selection and sample acquisition study

    NASA Technical Reports Server (NTRS)

    Nickle, N. (Editor)

    1980-01-01

    Various vehicle and mission options were investigated for the continued exploration of Mars; the cost of a minimum sample return mission was estimated; options and concepts were synthesized into program possibilities; and recommendations for the next Mars mission were made to the Planetary Program office. Specific sites and all relevant spacecraft and ground-based data were studied in order to determine: (1) the adequacy of presently available data for identifying landing sities for a sample return mission that would assure the acquisition of material from the most important geologic provinces of Mars; (2) the degree of surface mobility required to assure sample acquisition for these sites; (3) techniques to be used in the selection and drilling of rock a samples; and (4) the degree of mobility required at the two Viking sites to acquire these samples.

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

    SciTech Connect

    Cadwell, L.L.

    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.

  17. Hydroxamate-based iron chelators: combinatorial syntheses of desferrioxamine B analogues and evaluation of binding affinities.

    PubMed

    Poreddy, Amruta R; Schall, Otto F; Osiek, Todd A; Wheatley, James R; Beusen, Denise D; Marshall, Garland R; Slomczynska, Urszula

    2004-01-01

    This article describes the solid-phase combinatorial methods developed for the synthesis of polyhydroxamate-based siderophores. This strategy was applied to generate several libraries of structural DFO (1a) analogues that include DFO variants, non-amide analogues, C-terminal modified analogues, reverse-amide analogues, and hybrid analogues. To assess the relative iron-binding affinities of these compounds, a high-throughput spectrophotometric screening method based on competition with 8-hydroxyquinoline-5-sulfonic acid was developed. Some of the promising candidates containing various terminal functional groups were identified and prepared on large scale to enable future studies in animal models for iron-overload diseases.

  18. Artificial extracellular matrix proteins containing phenylalanine analogues biosynthesized in bacteria using T7 expression system and the PEGylation.

    PubMed

    Takasu, Akinori; Kondo, Shiori; Ito, Akihiro; Furukawa, Yuya; Higuchi, Masahiro; Kinoshita, Takatoshi; Kwon, Inchan

    2011-10-10

    In vivo incorporation of phenylalanine (Phe) analogues into an artificial extracellular matrix protein (aECM-CS5-ELF) was accomplished using a bacterial expression host that harbors the mutant phenylalanyl-tRNA synthetase (PheRS) with an enlarged binding pocket. Although the Ala294Gly/Thr251Gly mutant PheRS (PheRS**) under the control of T5 promoter allows incorporation of some Phe analogues into a protein, the T5 system is not suitable for material science studies because the amount of materials produced is not sufficient due to the moderate strength of the T5 promoter. This limitation can be overcome by using a pair of T7 promoter and T7 RNA polymerase instead. In the T7 expression system, it is difficult, however, to achieve a high incorporation level of Phe analogues, due to competition of Phe analogues for incorporation with the residual Phe that is required for synthesis of active T7 RNA polymerase. In this study, we prepared the PheRS** under T7 promoter and optimized culture condition to improve both the incorporation level of recombinant aECM protein and the incorporation level of Phe analogues. Incorporation and expression levels tend to increase in the case of p-azidophenylalanine, p-iodophenylalanine, and p-acetylphenylalanine. We evaluated the lower critical transition temperature, which is dependent on the incorporation ratio and the turbidity decreased when the incorporation level increased. Circular dichromism measurement indicated that this tendency is based on conformational change from random coil to β-turn structure. We demonstrated that polyethylene glycol (PEG) can be conjugated at reaction site of Phe analogues incorporated. We also demonstrated that the increased hydrophilicity of elastin-like sequences in the aECM-CS5-ELF made by PEG conjugation could suppress nonspecific adhesion of human umbilical vein endothelial cells (HUVEC).

  19. A photoaffinity analogue of discodermolide specifically labels a peptide in beta-tubulin.

    PubMed

    Xia, Shujun; Kenesky, Craig S; Rucker, Paul V; Smith, Amos B; Orr, George A; Horwitz, Susan Band

    2006-10-01

    Discodermolide is a potentially important antitumor agent that stabilizes microtubules and blocks cells at the G2/M phase of the cell cycle in a manner similar to that of Taxol. Discodermolide also has unique properties that distinguish it from Taxol. In the present study, photoaffinity-labeled discodermolide analogues are used to investigate their binding site in tubulin. Three photoaffinity-labeled discodermolide analogues were synthesized, all of which promoted microtubule polymerization in the absence of GTP. The analogue, C19-[4-(4-(3)H-benzoyl-phenyl)-carbamate]-discodermolide (C19-[3H]BPC-discodermolide), was selected for photolabeling studies because it had the highest extent of photoincorporation, approximately 1%, of the three radiolabeled discodermolide analogues explored. Although compared to discodermolide, C19-BPC-discodermolide revealed no hypernucleation effect in the in vitro microtubule polymerization assay, it was more cytotoxic than discodermolide, and, like discodermolide, demonstrated synergism with Taxol. These results suggest that the hypernucleation effect of discodermolide is not involved in its cytotoxic activity. Similar to discodermolide, C19-BPC-discodermolide can effectively displace [3H]Taxol from microtubules, but Taxol cannot effectively displace C19-[3H]BPC-discodermolide binding. Discodermolide can effectively displace C19-[3H]BPC-discodermolide binding. Formic acid hydrolysis, immunoprecipitation experiments, and subtilisin digestion indicate that C19-BPC-discodermolide labels amino acid residues 305-433 in beta-tubulin. Further digestion with Asp-N and Arg-C enzymes suggested that C19-BPC-discodermolide binds to amino acid residues, 355-359, in beta-tubulin, which is in close proximity to the Taxol binding site. Molecular modeling guided by the above evidence led to a putative binding model for C19-BPC-discodermolide in tubulin.

  20. Total syntheses of (+)- and (-)-cacospongionolide B, cacospongionolide e, and related analogues. Preliminary study of structural features required for phospholipase a2 inhibition.

    PubMed

    Cheung, Atwood K; Murelli, Ryan; Snapper, Marc L

    2004-08-20

    The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide B and E are described. The pivotal steps in the synthetic route include a three-step sequence that couples the two main regions of the natural product, as well as generates the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A2 suggests that the cacospongionolides have enantiospecific interactions with the enzyme that may be independent of the gamma-hydroxybutenolide moiety.

  1. Ortho-hydroxyl effect and proton transfer via ion-neutral complex: the fragmentation study of protonated imine resveratrol analogues in mass spectrometry.

    PubMed

    Yue, Lei; Li, Jing; Xie, Xiaodong; Guo, Cheng; Yin, Xinchi; Yin, Qi; Chen, Yinjuan; Pan, Yuanjiang; Ding, Chuanfan

    2016-07-01

    The fragmentation pathways of protonated imine resveratrol analogues in the gas-phase were investigated by electrospray ionization-tandem mass spectrometry. Benzyl cations were formed in the imine resveratrol analogues that had an ortho-hydroxyl group on the benzene ring A. The specific elimination of the quinomethane neutral, CH2  = C6 H4  = O, from the two isomeric ions [M1 + H](+) and [M3 + H](+) via the corresponding ion-neutral complexes was observed. The fragmentation pathway for the related meta-isomer, ion [M2 + H](+) and the other congeners was not observed. Accurate mass measurements and additional experiments carried out with a chlorinated analogue and the trideuterated isotopolog of M1 supported the overall interpretation of the fragmentation phenomena observed. It is very helpful for understanding the intriguing roles of ortho-hydroxyl effect and ion-neutral complexes in fragmentation reactions and enriching the knowledge of the gas-phase chemistry of the benzyl cation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27434810

  2. 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

  3. 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

  4. Studies on the active site of pig plasma amine oxidase.

    PubMed Central

    Collison, D; Knowles, P F; Mabbs, F E; Rius, F X; Singh, I; Dooley, D M; Cote, C E; McGuirl, M

    1989-01-01

    Amine oxidase from pig plasma (PPAO) has two bound Cu2+ ions and at least one pyrroloquinoline quinone (PQQ) moiety as cofactors. It is shown that recovery of activity by copper-depleted PPAO is linear with respect to added Cu2+ ions. Recovery of e.s.r. and optical spectral characteristics of active-site copper parallel the recovery of catalytic activity. These results are consistent with both Cu2+ ions contributing to catalysis. Further e.s.r. studies indicate that the two copper sites in PPAO, unlike those in amine oxidases from other sources, are chemically distinct. These comparative studies establish that non-identity of the Cu2+ ions in PPAO is not a requirement for amine oxidase activity. It is shown through the use of a new assay procedure that there are two molecules of PQQ bound per molecule of protein in PPAO; only the more reactive of these PQQ moieties is required for activity. PMID:2559715

  5. 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.

  6. Cell-Cycle Analyses Using Thymidine Analogues in Fission Yeast

    PubMed Central

    Anda, Silje; Boye, Erik; Grallert, Beata

    2014-01-01

    Thymidine analogues are powerful tools when studying DNA synthesis including DNA replication, repair and recombination. However, these analogues have been reported to have severe effects on cell-cycle progression and growth, the very processes being investigated in most of these studies. Here, we have analyzed the effects of 5-ethynyl-2′-deoxyuridine (EdU) and 5-Chloro-2′-deoxyuridine (CldU) using fission yeast cells and optimized the labelling procedure. We find that both analogues affect the cell cycle, but that the effects can be mitigated by using the appropriate analogue, short pulses of labelling and low concentrations. In addition, we report sequential labelling of two consecutive S phases using EdU and 5-bromo-2′-deoxyuridine (BrdU). Furthermore, we show that detection of replicative DNA synthesis is much more sensitive than DNA-measurements by flow cytometry. PMID:24551125

  7. 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.

  8. Monometallic osmium(II) complexes with bis(N-methylbenzimidazolyl)benzene or -pyridine: a comparison study with ruthenium(II) analogues.

    PubMed

    Shao, Jiang-Yang; Zhong, Yu-Wu

    2013-06-01

    Seven bis-tridentate osmium complexes with Mebib or Mebip (Mebib is the 2-deprotonated form of 1,3-bis(N-methylbenzimidazolyl)benzene and Mebip is bis(N-methylbenzimidazolyl)pyridine) have been prepared, and their electrochemical and spectroscopic properties are compared with ruthenium structural analogues. Among them, four complexes have the [Os(NCN)(NNN)]-type coordination, including [Os(Mebib)(Mebip)](PF6)2 (1(PF6)2), [Os(dpb)(Mebip)](PF6) (2(PF6), dpb is the 2-deprotonated form of 1,3-di(pyrid-2-yl)benzene), [Os(Mebib)(ttpy)](PF6) (3(PF6), ttpy = 4'-tolyl-2,2':6',2"-terpyridine), and [Os(dpb)(ttpy)](PF6) (4(PF6)). The other three complexes are [Os(Mebip)2](PF6)2 (5(PF6)2), [Os(Mebip)(tpy)](PF6)2 (6(PF6)2, tpy = 2,2':6',2"-terpyridine), and [Os(ttpy)2](PF6)2 (7(PF6)2) with the [Os(NNN)(NNN)]-type coordination. Single crystals of 2(PF6) and 6(PF6)2 have been obtained, and their structures are studied by X-ray crystallographic analysis. The Os(II/III) redox potentials of 1(PF6)2 to 7(PF6)2 progressively increase from +0.04, +0.23, +0.24, +0.36, +0.56, +0.79 to +0.94 V vs Ag/AgCl, which are 200-300 mV less positive relative to the Ru(II/III) potentials of their ruthenium counterparts. The highest occupied molecular orbital energy levels of 1(+)-7(2+) are calculated to vary in a descending order. The ruthenium and osmium complexes have singlet metal-to-ligand charge-transfer (MLCT) transitions of similar energies and band shapes, while the osmium complexes display additional (3)MLCT transitions in the lower-energy region. Complexes 6(PF6)2 and 7(PF6)2 emit weakly at 780 and 740 nm, respectively. Complex 1(PF6)2 was synthesized as the oxidized Os(III) salt because of the low Os(II/III) potential. The transformation of 1(2+) to 1(+) by chemical reduction or electrolysis led to the emergence of the (1)MLCT transitions in the visible region.

  9. Formation of ophiolite-bearing tectono-sedimentary mélanges in accretionary wedges by gravity driven submarine erosion: Insights from analogue models and case studies

    NASA Astrophysics Data System (ADS)

    Malavieille, Jacques; Molli, Giancarlo; Genti, Manon; Dominguez, Stephane; Beyssac, Olivier; Taboada, Alfredo; Vitale-Brovarone, Alberto; Lu, Chia-Yu; Chen, Chih-Tung

    2016-10-01

    Orogenic wedges locally present chaotic tectonostratigraphic units that contain exotic blocks of various size, origin, age and lithology, embedded in a sedimentary matrix. The occurrence of ophiolitic blocks, sometimes huge, in such "mélanges" raises questions on (i) the mechanisms responsible for the incorporation of oceanic basement rocks into an accretionary wedge and (ii) the mechanisms allowing exhumation and redeposition of these exotic elements in "mélanges" during wedge growth. To address these questions, we present the results of a series of analogue experiments performed to characterize the processes and parameters responsible for accretion, exhumation and tectonosedimentary reworking of oceanic basement lithospheric fragments in an accretionary wedge. The experimental setup is designed to simulate the interaction between tectonics, erosion and sedimentation. Different configurations are applied to study the impact of various parameters, such as irregular oceanic floor due to structural inheritance, or the presence of layers with contrasted rheology that can affect deformation partitioning in the wedge (frontal accretion vs basal accretion) influencing its growth. Image correlation technique allows extracting instantaneous velocity field, and tracking of passive particles. By retrieving the particle paths determined from models, the pressure-temperature path of mélange units or elementary blocks can be discussed. The experimental results are then compared with observations from ophiolite-bearing mélanges in Taiwan (Lichi and Kenting mélanges) and Raman spectroscopy of carbonaceous material (RSCM) Thermometry data on rocks from the northern Apennines (Casanova mélange). A geological scenario is proposed following basic observations. The tectonic evolution of the retroside of doubly vergent accretionary wedges is mainly controlled by backthrusting and backfolding. The retro wedge is characterized by steep slopes that are prone to gravitational

  10. Substrate-induced conformational transition in human phenylalanine hydroxylase as studied by surface plasmon resonance analyses: the effect of terminal deletions, substrate analogues and phosphorylation.

    PubMed Central

    Stokka, Anne J; Flatmark, Torgeir

    2003-01-01

    The optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, was used for real-time measurements of the slow conformational transition (isomerization) which occurs in human phenylalanine hydroxylase (hPAH) on the binding/dissociation of L-phenylalanine (L-Phe). The binding to immobilized tetrameric wt-hPAH resulted in a time-dependent increase in the refractive index (up to approx. 3 min at 25 degrees C) with an end point of approx. 75 RU (resonance units)/(pmol subunit/mm(2)). By contrast, the contribution of binding the substrate (165 Da) to its catalytic core enzyme [DeltaN(1-102)/DeltaC(428-452)-hPAH] was only approx. 2 RU/(pmol subunit/mm(2)). The binding isotherm for tetrameric and dimeric wt-hPAH revealed a [S](0.5)-value of 98+/-7 microM (h =1.0) and 158+/-11 microM, respectively, i.e. for the tetramer it is slightly lower than the value (145+/-5 microM) obtained for the co-operative binding (h =1.6+/-0.4) of L-Phe as measured by the change in intrinsic tryptophan fluorescence. The responses obtained by SPR and intrinsic tryptophan fluorescence are both considered to be related to the slow reversible conformational transition which occurs in the enzyme upon L-Phe binding, i.e. by the transition from a low-activity state ('T-state') to a relaxed high-activity state ('R-state') characteristic of this hysteretic enzyme, however, the two methods reflect different elements of the transition. Studies on the N- and C-terminal truncated forms revealed that the N-terminal regulatory domain (residues 1-117) plus catalytic domain (residues 118-411) were required for the full signal amplitude of the SPR response. Both the on- and off-rates for the conformational transition were biphasic, which is interpreted in terms of a difference in the energy barrier and the rate by which the two domains (catalytic and regulatory) undergo a conformational change. The substrate analogue 3-(2-thienyl)-L-alanine revealed an SPR response comparable with

  11. 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

  12. Antimicrobial activity of resveratrol analogues.

    PubMed

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

    2014-06-10

    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.

  13. Similarity in drugs: reflections on analogue design.

    PubMed

    Wermuth, Camille G

    2006-04-01

    A survey of novel small-molecule therapeutics reveals that the majority of them result from analogue design and that their market value represents two-thirds of all small-molecule sales. In natural science, the term analogue, derived from the Latin and Greek analogia, has always been used to describe structural and functional similarity. Extended to drugs, this definition implies that the analogue of an existing drug molecule shares structural and pharmacological similarities with the original compound. Formally, this definition allows the establishment of three categories of drug analogues: analogues possessing chemical and pharmacological similarities (direct analogues); analogues possessing structural similarities only (structural analogues); and chemically different compounds displaying similar pharmacological properties (functional analogues). PMID:16580977

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

    SciTech Connect

    Gaylord, D.R.; Stetler, L.D.; Smith, G.D.; Mars, R.W.

    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.

  15. Computational studies of Bronsted acid sites in zeolites

    SciTech Connect

    Curtiss, L.A.; Iton, L.E.; Zygmunt, S.A.

    1995-01-01

    The authors have performed high-level ab initio calculations using both Hartree-Fock (HF) and Moller-Plesset perturbation theory (MP2) to study the geometry and energetics of the adsorption complex involving H{sub 2}O and the Bronsted acid site in the zeolite H-ZSM-5. In these calculations, which use aluminosilicate cluster models for the zeolite framework with as many a 28 T atoms (T = Si, Al), we included geometry optimization in the local vicinity of the acid site at the HF/6-31G(d) level of theory, and have calculated corrections for zero-point energies, extensions for zero-point energies, extensions to higher basis sets, and the influence of electron correlation. Results for the adsorption energy and geometry of this complex are reported and compared with previous theoretical and experimental values.

  16. From BPA to its analogues: Is it a safe journey?

    PubMed

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful?

  17. From BPA to its analogues: Is it a safe journey?

    PubMed

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID:27262103

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

    SciTech Connect

    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.

  19. Βasalts from Santorini Volcano: A New Candidate Martian Analogue

    NASA Astrophysics Data System (ADS)

    Pantazidis, A.; Baziotis, I.; Manoutsoglou, E.; Solomonidou, A.; Schwander, F.; Palles, D.; Kamitsos, E.; Koukouzas, N.; Keklikoglou, N.; Arvanitidis, C.; Martinez-Frias, J.; Asimow, P. D.

    2016-08-01

    We compared volcanic rocks from Santorini Volcano and ISAR basalts from Iceland, South Africa and Norway, which are considered as strong candidates for martian analogues. We conclude that Santorini expands the list of terrestrial Mars-like sites.

  20. Ecosystem studies at the Los Medanos site, Eddy County, New Mexico. Volume I

    SciTech Connect

    Hart, J.S.

    1981-05-01

    This report summarizes the results of biological studies conducted during 1980 at the Los Medanos site in southeastern New Mexico. The studies include: (1) densities and species composition of the avifauna of the Los Medanos site; (2) aquatic ecosystems of the lower Pecos drainage; (3) floristic studies at the Los Medanos site; (4) plant successional, grazing, trampling, and salt studies on the Los Medanos site; (5) soil and vegetation studies at the Los Medanos site; (6) arthropod and decomposition studies at the WIPP site; (7) amphibians, reptiles and mammals at the Los Medanos site; (8) vertebrate ecology at the Los Medanos site; and (9) statistical analysis and data management. 7 refs. (ACR)

  1. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss. PMID:27626017

  2. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss.

  3. 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.

  4. Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis-constrained analogues of combretastatin A-4.

    PubMed

    Madadi, Nikhil R; Penthala, Narsimha R; Howk, Kevin; Ketkar, Amit; Eoff, Robert L; Borrelli, Michael J; Crooks, Peter A

    2015-10-20

    A series of combretastatin A-4 (CA-4) analogues have been prepared from (Z)-substituted diarylacrylonitriles (1a-1p) obtained in a two-step synthesis from appropriate arylaldehydes and acrylonitriles. The resulting 4,5-disubstituted 2H-1,2,3-triazoles were evaluated for their anti-cancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogue 2l exhibited the most potent anti-cancer activity in the screening studies, with GI₅₀ values of <10 nM against almost all the cell lines in the human cancer cell panel and TGI values of <10 nM against cancer cell lines SF-539, MDA-MB-435, OVCAR-3 and A498. Furthermore, in silico docking studies of compounds 2l, 2e and 2h within the active site of tubulin were carried out in order to rationalize the mechanism of the anti-cancer properties of these compounds. From the in silico studies, compound 2e was predicted to have better affinity for the colchicine binding site on tubulin compared to compounds 2l and 2h. Analogue 2e was also evaluated for its anti-cancer activity by colony formation assay against 9LSF rat gliosarcoma cells and afforded an LD₅₀ of 7.5 nM. A cell cycle redistribution assay using analogue 2e was conducted to further understand the mechanism of action of these CA-4 analogues. From this study, analogues 2e and 2l were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs. PMID:26352674

  5. Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis-constrained analogues of combretastatin A-4.

    PubMed

    Madadi, Nikhil R; Penthala, Narsimha R; Howk, Kevin; Ketkar, Amit; Eoff, Robert L; Borrelli, Michael J; Crooks, Peter A

    2015-10-20

    A series of combretastatin A-4 (CA-4) analogues have been prepared from (Z)-substituted diarylacrylonitriles (1a-1p) obtained in a two-step synthesis from appropriate arylaldehydes and acrylonitriles. The resulting 4,5-disubstituted 2H-1,2,3-triazoles were evaluated for their anti-cancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogue 2l exhibited the most potent anti-cancer activity in the screening studies, with GI₅₀ values of <10 nM against almost all the cell lines in the human cancer cell panel and TGI values of <10 nM against cancer cell lines SF-539, MDA-MB-435, OVCAR-3 and A498. Furthermore, in silico docking studies of compounds 2l, 2e and 2h within the active site of tubulin were carried out in order to rationalize the mechanism of the anti-cancer properties of these compounds. From the in silico studies, compound 2e was predicted to have better affinity for the colchicine binding site on tubulin compared to compounds 2l and 2h. Analogue 2e was also evaluated for its anti-cancer activity by colony formation assay against 9LSF rat gliosarcoma cells and afforded an LD₅₀ of 7.5 nM. A cell cycle redistribution assay using analogue 2e was conducted to further understand the mechanism of action of these CA-4 analogues. From this study, analogues 2e and 2l were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs.

  6. Condensed matter analogues of cosmology

    NASA Astrophysics Data System (ADS)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    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

  7. Yucca Mountain Site Characterization Project exploratory studies facilities construction status

    SciTech Connect

    Allan, J.N.; Leonard, T.M.

    1993-12-31

    This paper discusses the progress to date on the construction planning and development of the Yucca Mountain Site Characterization Project (YMP) Exploratory Studies Facilities (ESF). The purpose of the ESF is to determine early site suitability and to characterize the subsurface of the Yucca Mountain site to assess its suitability for a potential high level nuclear waste repository. The present ESF configuration concept is for two main ramps to be excavated by tunnel boring machines (TBM) from the surface to the Topopah Spring Member of the Paintbrush Tuff Formation. From the main ramps, slightly above Topopah Spring level, supplemental ramps will be penetrated to the Calico Hills formation below the potential repository. There will be exploratory development drifts driven on both levels with the Main Test Area being located on the Topopah Spring level, which is the level of the proposed repository. The Calico Hills formation lies below the Topopah Spring member and is expected to provide the main geo-hydrologic barrier between the potential repository and the underlying saturated zones in the Crater Flat Tuff.

  8. Analogues of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, As Anti-Cancer Agents

    PubMed Central

    2013-01-01

    The rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its use as either a chemical probe or potential therapeutic. We report the synthesis and characterization of MKT-077 analogues designed for greater stability. The most potent molecules, such as 30 (JG-98), were at least 3-fold more active than MKT-077 against the breast cancer cell lines MDA-MB-231 and MCF-7 (EC50 values of 0.4 ± 0.03 and 0.7 ± 0.2 μM, respectively). The analogues modestly destabilized the chaperone clients, Akt1 and Raf1, and induced apoptosis in these cells. Further, the microsomal half-life of JG-98 was improved at least 7-fold (t1/2 = 37 min) compared to MKT-077 (t1/2 < 5 min). Finally, NMR titration experiments suggested that these analogues bind an allosteric site that is known to accommodate MKT-077. These studies advance MKT-077 analogues as chemical probes for studying Hsp70s roles in cancer. PMID:24312699

  9. 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

  10. The Violence Prevention Community Meeting: A Multi-Site Study

    PubMed Central

    Lanza, Marilyn; Ridenour, Marilyn; Hendricks, Scott; Rierdan, Jill; Zeiss, Robert; Schmidt, Satu; Lovelace, Jeff; Amandus, Harlan

    2016-01-01

    Objective The Violence Prevention Community Meeting (VPCM) is a specialized form of community meeting in which avoiding violence and promoting non-violent problem solving and interpersonal civility are focal points. A nationwide study to assess the VPCM as an effective intervention to reduce workplace violence was undertaken. Participants Seven acute locked psychiatric units of the Veterans Health Administration (VHA) throughout the United States participated in the study. Methods All patients and all staff on the seven in-patient locked psychiatry units participated in the intervention (VPCM) or as a control (treatment as usual). The study was 21 weeks at each site. The three time periods were pre-treatment weeks 1 – 3, treatment weeks 4 – 18, and post-treatment weeks 19 – 21. The VPCM was conducted during the treatment weeks. Results Overall rates of aggression declined by 0.6% (95%CI: −5.6%, 6.5%; nonsignificant) per week in the intervention hospitals and by 5.1% (95%CI: 0.4%, 9.6%; significant) per week for the control hospitals. Conclusions Aggression decreased for both the intervention and control hospitals which could be due to enrollment in a research study and thus being more aware of their ability to address workplace violence at their site. PMID:27256945

  11. 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.

  12. GC base sequence recognition by oligo(imidazolecarboxamide) and C-terminus-modified analogues of distamycin deduced from circular dichroism, proton nuclear magnetic resonance, and methidiumpropylethylenediaminetetraacetate-iron(II) footprinting studies.

    PubMed

    Lee, M; Rhodes, A L; Wyatt, M D; Forrow, S; Hartley, J A

    1993-04-27

    The DNA binding properties of a series of imidazole-containing and C-terminus-modified analogues 4-7 of distamycin are described. These analogues contain one to four imidazole units, respectively. Data from the ethidium displacement assay showed that these compounds bind in the minor groove of DNA, with the relative order of binding constants of 6 (Im3) > 7 (Im4) > 5 (Im2) > 4 (Im1). The reduced binding constants of these compounds for poly(dA-dT) relative to distamycin, while they still interact strongly with poly(dG-dC), provided evidence of GC sequence acceptance. The preferences for GC-rich sequences by these compounds were established from a combination of circular dichroism (CD) titration, proton nuclear magnetic resonance (1H-NMR), and methidiumpropylethylenediaminetetraacetate-iron(II) [MPE.Fe-(II)] footprinting studies. In the CD studies, these compounds produced significantly larger DNA-induced ligand bands with poly(dG-dC) than poly(dA-dT) at comparable ligand concentrations. 1H-NMR studies of the binding of 5 to d-[CATGGCCATG]2 provided further evidence of the recognition of GC sequences by these compounds, and suggested that the ligand was located on the underlined sequence in the minor groove with the C-terminus oriented over the T residue. MPE footprinting studies on a GC-rich BamHI/SalI fragment of pBR322 provided unambiguous evidence for the GC sequence selectivity for some of these compounds. Compounds 4 and 7 produced poor footprints on the gels; however, analogues 5 and 6 gave strong footprints.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

    NASA Astrophysics Data System (ADS)

    Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

    2015-08-01

    The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

  14. Numerical studies of a 36-site [ital kagome] antiferromagnet

    SciTech Connect

    Leung, P.W. Physics Department, The Hong Kong University of Science and Technology, Clear Water Bay ); Elser, V. )

    1993-03-01

    The ground-state wave function for the spin-1/2 quantum antiferromagnet on a 36-site [ital kagome]$[ital iaa]--- structure is found by numerical diagonalization. Spin-spin correlations and spin gaps indicate that the ground state of this system does not possess magnetic order. The spin-Peierls order is studied using a four-spin correlation function. The short-range structure in this correlation function is found to be consistent with a simple dimer-liquid model. The spin-Peierls order, if it exists, must be quite small.

  15. Outcrop analogue study of Permocarboniferous geothermal sandstone reservoir formations (northern Upper Rhine Graben, Germany): impact of mineral content, depositional environment and diagenesis on petrophysical properties

    NASA Astrophysics Data System (ADS)

    Aretz, Achim; Bär, Kristian; Götz, Annette E.; Sass, Ingo

    2016-07-01

    The Permocarboniferous siliciclastic formations represent the largest hydrothermal reservoir in the northern Upper Rhine Graben in SW Germany and have so far been investigated in large-scale studies only. The Cenozoic Upper Rhine Graben crosses the Permocarboniferous Saar-Nahe Basin, a Variscan intramontane molasse basin. Due to the subsidence in this graben structure, the top of the up to 2-km-thick Permocarboniferous is located at a depth of 600-2900 m and is overlain by Tertiary and Quaternary sediments. At this depth, the reservoir temperatures exceed 150 °C, which are sufficient for geothermal electricity generation with binary power plants. To further assess the potential of this geothermal reservoir, detailed information on thermophysical and hydraulic properties of the different lithostratigraphical units and their depositional environment is essential. Here, we present an integrated study of outcrop analogues and drill core material. In total, 850 outcrop samples were analyzed, measuring porosity, permeability, thermal conductivity and thermal diffusivity. Furthermore, 62 plugs were taken from drillings that encountered or intersected the Permocarboniferous at depths between 1800 and 2900 m. Petrographic analysis of 155 thin sections of outcrop samples and samples taken from reservoir depth was conducted to quantify the mineral composition, sorting and rounding of grains and the kind of cementation. Its influence on porosity, permeability, the degree of compaction and illitization was quantified. Three parameters influencing the reservoir properties of the Permocarboniferous were detected. The strongest and most destructive influence on reservoir quality is related to late diagenetic processes. An illitic and kaolinitic cementation and impregnation of bitumina document CO2- and CH4-rich acidic pore water conditions, which are interpreted as fluids that migrated along a hydraulic contact from an underlying Carboniferous hydrocarbon source rock. Migrating

  16. Microwave-assisted synthesis and biological evaluation of 3,4-diaryl maleic anhydride/N-substituted maleimide derivatives as combretastatin A-4 analogues.

    PubMed

    Guan, Qi; Zuo, Daiying; Jiang, Nan; Qi, Huan; Zhai, Yanpeng; Bai, Zhaoshi; Feng, Dongjie; Yang, Lei; Jiang, Mingyang; Bao, Kai; Li, Chang; Wu, Yingliang; Zhang, Weige

    2015-02-01

    A series of new CA-4 analogues bearing maleic anhydride/N-substituted maleimide moiety were synthesized via a microwave-assisted process. They were evaluated for the anti-proliferative activities against three tumor cell lines (SGC-7901, HT-1080 and KB). Most compounds showed moderate potencies in micromolar range, with the most promising analogue 6f showing active at submicromolar concentration against HT-1080 cancer cells which was selected to investigate the antitumor mechanisms. In addition, molecular docking studies within the colchicine binding site of tubulin were also in good agreement with the tubulin polymerization inhibitory data and provided a basis for further structure-guided design of novel CA-4 analogues. PMID:25529737

  17. Microwave-assisted synthesis and biological evaluation of 3,4-diaryl maleic anhydride/N-substituted maleimide derivatives as combretastatin A-4 analogues.

    PubMed

    Guan, Qi; Zuo, Daiying; Jiang, Nan; Qi, Huan; Zhai, Yanpeng; Bai, Zhaoshi; Feng, Dongjie; Yang, Lei; Jiang, Mingyang; Bao, Kai; Li, Chang; Wu, Yingliang; Zhang, Weige

    2015-02-01

    A series of new CA-4 analogues bearing maleic anhydride/N-substituted maleimide moiety were synthesized via a microwave-assisted process. They were evaluated for the anti-proliferative activities against three tumor cell lines (SGC-7901, HT-1080 and KB). Most compounds showed moderate potencies in micromolar range, with the most promising analogue 6f showing active at submicromolar concentration against HT-1080 cancer cells which was selected to investigate the antitumor mechanisms. In addition, molecular docking studies within the colchicine binding site of tubulin were also in good agreement with the tubulin polymerization inhibitory data and provided a basis for further structure-guided design of novel CA-4 analogues.

  18. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    NASA Astrophysics Data System (ADS)

    Foing, Bernard

    2014-05-01

    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

  19. Fluorescence histochemical study of the localisation and distribution of beta-adrenergic receptor sites in the spinal cord and cerebellum of the chicken.

    PubMed

    Bondok, A A; Botros, K G; el-Mohandes, E A

    1988-10-01

    The distribution of beta-adrenergic receptor sites has been studied in chicken spinal cord and cerebellum using a fluorescent analogue of propranolol, 9-amino-acridin-propranolol (9-AAP). In the cervical and lumbar regions of the spinal cord, beta-adrenoceptor sites were concentrated on cell bodies of alpha-motor neurons of the dorsolateral and ventrolateral nuclear groups of the ventral horn. In the thoracic region, they were present on cell bodies of the preganglionic sympathetic nucleus (dorsal commissural nucleus). In the dorsal horn, the receptor sites were present mainly on cell bodies of columna dorsalis magnocellularis. Sparse distribution of fluorescence was present in other regions of the gray matter. In the cerebellum, a dense distribution of beta-adrenergic receptor sites was observed on Purkinje cell bodies and their apical dendrites. Sparse distribution of receptor sites was present on fine ramifications of Purkinje cell dendrites in the molecular layer. Receptor sites were absent in the granule cell layer and the white matter. These observations indicate that alpha-motor neurons, preganglionic sympathetic neurons, neurons of columna dorsalis magnocellularis, and Purkinje cells are adrenoceptive, while granule cells are non-adrenoceptive.

  20. 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

  1. 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.

  2. 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

  3. Microbially mediated redox processes in natural analogues for radioactive waste

    NASA Astrophysics Data System (ADS)

    Haveman, Shelley A.; Pedersen, Karsten

    2002-03-01

    Natural analogues allow scientists to investigate biogeochemical processes relevant to radioactive waste disposal that occur on time scales longer than those that may be studied by time-limited laboratory experiments. The Palmottu U-Th deposit in Finland and the Bangombé natural nuclear reactor in Gabon involve the study of natural uranium, and are both considered natural analogues for subsurface radioactive waste disposal. The microbial population naturally present in groundwater may affect the redox conditions, and hence, the radionuclide solubility and migration. Therefore, groundwater samples from the two sites were investigated for microbial populations. The total numbers of cells ranged from 10 4 to 10 6 cells ml -1. Iron-reducing bacteria (IRB) were the largest culturable microbial population in the Palmottu groundwater and were present at up to 1.3×10 5 cells ml -1. Sulfate-reducing bacteria (SRB) and acetogens could also be cultured from the Palmottu groundwater. The numbers of IRB and SRB were largest in groundwater with the lowest uranium concentrations. Removal of dissolved U(VI) from solution was concomitant with the growth of IRB enrichment cultures and the reduction of iron. The redox buffer in the Palmottu groundwater consists of iron and uranium species, both of which are affected by IRB. IRB and aerobic heterotrophs were cultured from the Bangombé groundwater, where redox potentials are buffered by iron and organic carbon species. Microbial populations similar to those found at Palmottu and Bangombé are found throughout the Fennoscandian Shield, a potential host rock for subsurface radioactive waste disposal. These results confirm that microorganisms can be expected to play a role in stabilizing radioactive waste disposed of in the subsurface by lowering redox potential and immobilizing radionuclides.

  4. Geomorphological and Spectrophotometric Study of Philae Landing Site A

    NASA Astrophysics Data System (ADS)

    Pajola, M.; La Forgia, F.; Giacomini, L.; Oklay, N.; Massironi, M.; Bertini, I.; Simioni, E.; Marzari, F.; Barbieri, C.; Naletto, G.; Groussin, O.; Lazzarin, M.; Scholten, F.; Preusker, F.; Fornasier, S.; Vincent, J. B.; Sierks, H.

    2015-10-01

    On August 6, 2014, the European Space Agency's Rosetta spacecraft started orbiting the Jupiter family comet 67P/Churyumov-Gerasimenko (hereafter 67P). Afterwards, the OSIRIS instrument (Optical, Spectroscopic and Infrared Remote Imaging System [1]), got the highest-resolution-ever images of a cometary nucleus, reaching the unprecedented scale of 50 cm/px. A brief description of OSIRIS early analysis on the nucleus structure and activity of 67P is available in [2]. Despite its small dimensions, #4 km diameter, 67P shows a morphological diversity that is still puzzling the cometary community: boulders [3], highreflectivity particle clusters [4], local fracturing [5], pits [6], as well as dust covered terrains [7], are only few examples that can be found on 67P. Since the Rosetta arrival, an extremely detailed analysis of 67P surface has been performed to select five different landing sites candidates for the lander Philae. By using the OSIRIS images the comet shape model [8] has been produced to study the slope constraints, as well as the identification and measurements of boulders and production of hazard maps of the landing spots [3]. A final landing site, called Agilkia and located on the smaller lobe of the comet, was announced on October 15, 2014. Here, Philae, on November 12, 2014, made its historic comet touchdown [9]. Despite its unique scientific potential, one of the five finalists, called "site A", was avoided due to higher risks with respect to Agilkia, during both the landing phase and the surface operations. This area is located on the bigger lobe of the comet, on the Seth region [10] facing the Hathor cliff. Site A (Fig. 1) is close to the 'neck' region, i.e. the connecting bridge between the two lobes, where the main dust jet activity has been observed since the Rosetta arrival. This area is the biggest terrace of Seth region, delimited in the upper part by a steep wall showing multiple niches, strata heads and smaller terraces. Moreover, between the

  5. Adsorption on molecularly imprinted polymers of structural analogues of a template. Single-component adsorption isotherm data

    SciTech Connect

    Kim, Hyunjung; Guiochon, Georges A

    2005-10-01

    The equilibrium adsorption isotherms on two otherwise identical polymers, one imprinted with Fmoc-L-tryptophan (Fmoc-L-Trp) (MIP), the other nonimprinted (NIP), of compounds that are structural analogues of the template were acquired by frontal analysis (FA) in an acetonitrile/acetic acid (99/1 v/v) mobile phase, over a wide concentration range (from 0.005 to 50 mM). These analogues were Fmoc-L-tyrosine, Fmoc-L-serine, Fmoc-L-phenyalanine, Fmoc-glycine (Fmoc-Gly), Fmoc-L-tryptophan pentafluorophenyl ester (Fmoc-L-Trp(OPfp)), and their antipodes. These substrates have different numbers of functional groups able to interact with the 4-vinylpyridine groups of the polymer. For a given number of the functional groups, these substrates have different hydrophobicities of their side groups (as indicated by their partition coefficients (log P{sub ow}) in the octanol-water system (e.g., from 4.74 for Fmoc-Trp to 2.53 for Fmoc-Gly)). Statistical results from the fitting of the FA data to Langmuirian isotherm models, the calculation of the affinity energy distribution, and the comparison of calculated and experimental band profiles show that all these sets of FA data are best accounted for by a tri-Langmuir isotherm model, except for the data of Fmoc-L-Trp(OPfp) that are best modeled by a simple Langmuir isotherm. So, all compounds but Fmoc-L-Trp(OPfp) find three different types of adsorption sites on both the MIP and the NIP. The properties of these different types of sites were studied systematically. The results show that the affinity of the structural analogues for the NIP is controlled mostly by the number of the functional groups on the substrates and somewhat by the hydrophobicity of their side groups. These two factors control also the MIP affinity toward the enantiomers of the structural analogues that have a stereochemistry different from that of the template. In contrast, the affinity of the highest affinity sites of the MIP toward the enantiomers of these

  6. 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...

  7. Digitoxin Analogues with Improved Anticytomegalovirus Activity

    PubMed Central

    2014-01-01

    Cardiac glycosides are potent inhibitors of cancer cell growth and possess antiviral activities at nanomolar concentrations. In this study we evaluated the anticytomegalovirus (CMV) activity of digitoxin and several of its analogues. We show that sugar type and sugar length attached to the steroid core structure affects its anticytomegalovirus activity. Structure–activity relationship (SAR) studies identified the l-sugar containing cardiac glycosides as having improved anti-CMV activity and may lead to better understanding of how these compounds inhibit CMV replication. PMID:24900847

  8. Western Maryland power plant siting study: biological characterization of candidate sites. Final assessment. Final report

    SciTech Connect

    Jacobs, F.; Himel, J.; Cummins, R.; Weisberg, S.

    1984-10-01

    Three locations in western Maryland are being considered as potential candidate sites for future construction of a 1200-1800 MWe coal-fired power plant. This report provides a detailed biological characterization of each site and assesses potential terrestrial and aquatic impacts associated with plant construction and operation. This assessment considers possible impacts on geomorphology, vegetation, wildlife, water quality, and nearby aquatic biota. Relevant information contained in a Phase I document produced earlier under this contract, was incorporated into this final report.

  9. 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.

  10. 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

    (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

  11. 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.

  12. 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.

  13. Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART-CHF, COMPARE, MOMENTUM, thyroid hormone analogue study, HF-ACTION, I-PRESERVE, β-interferon study, BACH, and ATHENA

    PubMed Central

    Coletta, Alison P.; Clark, Andrew L.; Cleland, John G.F.

    2009-01-01

    This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the Heart Failure Society of America and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART-CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF-ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo. PMID:19168521

  14. Spectral analysis of lunar analogue samples

    NASA Astrophysics Data System (ADS)

    Offringa, Marloes; Foing, Bernard

    2016-04-01

    Analyses of samples derived from terrestrial analogue sites are used to study lunar processes in their geological context (Foing, Stoker, Ehrenfreund, 2011). For this study samples from the volcanic region of the Eifel, Germany collected during field campaigns (Foing et al., 2010), are analyzed with a variety of spectrometers. The aim is to obtain a database of analyzed samples that could be used as a reference for future in situ measurements. Equipment used in the laboratory consists of a Fourier Transform Infrared (FTIR) spectrometer, an X-Ray Fluorescence (XRF) spectrometer, a Raman laser spectrometer, as well as UV-VIS and NIR reflectance spectrometers. The Raman, UV-VIS and NIR are also used in combination with the EXoGeoLab mock-up lander during field campaigns (Foing, Stoker, Ehrenfreund, 2011). Calibration of the UV-VIS and NIR reflectance spectrometers is the main focus of this research in order to obtain the clearest spectra. The calibration of the UV-VIS and NIR reflectance spectrometers requires the use of a good light source as well as suitable optical fibers to create a signal that covers the widest range in wavelengths available. To eliminate noise towards the edges of this range, multiple measurements are averaged and data is processed by dividing the signal by reference spectra. Calibration of the devices by creating a new dark and reference spectra has to take place after every sample measurement. In this way we take into account changes that occur in the signal due to the eating of the devices during the measurements. Moreover, the integration time is adjusted to obtain a clear signal without leading to oversaturation in the reflectance spectrum. The typical integration times for the UV-VIS reflectance spectrometer vary between 1 - 18 s, depending on the amount of daylight during experiments. For the NIR reflectance spectrometer the integration time resulting in the best signals is approximately 150 ms in combination with a broad spectrum light

  15. Radiation inactivation study of aminopeptidase: probing the active site

    NASA Astrophysics Data System (ADS)

    Jamadar, V. K.; Jamdar, S. N.; Mohan, Hari; Dandekar, S. P.; Harikumar, P.

    2004-04-01

    Ionizing radiation inactivated purified chicken intestinal aminopeptidase in media saturated with gases in the order N 2O>N 2>air. The D 37 values in the above conditions were 281, 210 and 198 Gy, respectively. OH radical scavengers such as t-butanol and isopropanol effectively nullified the radiation-induced damage in N 2O. The radicals (SCN) 2•-, Br 2•- and I 2•- inactivated the enzyme, pointing to the involvement of aromatic amino acids and cysteine in its catalytic activity. The enzyme exhibited fluorescence emission at 340 nm which is characteristic of tryptophan. The radiation-induced loss of activity was accompanied by a decrease in the fluorescence of the enzyme suggesting a predominant influence on tryptophan residues. The enzyme inhibition was associated with a marked increase in the Km and a decrease in the Vmax and kcat values, suggesting an irreversible alteration in the catalytic site. The above observations were confirmed by pulse radiolysis studies.

  16. The action of structural analogues of ethidium bromide on the mitochondrial genome of yeast.

    PubMed

    Hall, R M; Mattick, J S; Nagley, P; Cobon, G S; Eastwood, F W; Linnane, A W

    1977-12-01

    We have studied the effects on the yeast mitochondrial genome of four analogues of ethidium bromide, in which the phenyl moieyt has been replaced by linear alkyl chains of lengths varying from seven to fifteen carbon atoms. These analogues are more efficient than ethidium bromide in inducing petite mutants in Saccharomyces cervisiae. The drugs also cause a loss of mtDNA from the cells in vivo; however these analogues are in fact less effective inhibitors of mitochondrial DNA replication per se, as shown by direct in vitro studies. It is concluded that these analogues are more efficient than ethidium bromide in causing the fragmentation of mitochondrial DNA in S. cervisiae. PMID:339057

  17. Structure-activity studies with ring E analogues of methyllycaconitine. Synthesis and evaluation of enantiopure isomers of selective antagonist at the alpha3 nicotinic receptor.

    PubMed

    Ismail, K A; Bergmeier, S C

    2002-06-01

    The four diastereomers 4a-d of methyllycaconitine (MLA) analogue 3 ( R =(CH(2))(3)Ph, R'=CH(3)) have been synthesized in enantiomerically pure form by coupling both (S)- and (R)-2-(methylsuccinimido)benzoic acid (5a and 5b) with both (S)- and (R)-3-hydroxymethyl-N-(3-phenyl) propylpiperidine (6a and 6b) using TBTU. These compounds were assayed for potency as nicotinic acetylcholine receptor (nAChRs) antagonist. All the four diastereomers showed the same potency at both the alpha3 and alpha7 receptors as racemic compound 3. This indicates that the binding at nicotine acetylcholine receptors (nAchRs) is probably non-stereospecific. PMID:12204473

  18. The α,α-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase-Dependent Signal Transduction in Vitro, and In Living Cells

    PubMed Central

    Panigrahi, Kaushik; Eggen, MariJean; Maeng, Jun-Ho; Shen, Quanrong; Berkowitz, David B.

    2009-01-01

    SUMMARY This overview focuses on the (α,α-difluoromethylene)phosphonate mimic of phosphoserine (pCF2Ser) and its application to the study of kinase-mediated signal transduction – pathways of great interest to drug development. The most versatile modes of access to these chemical biological tools are discussed, organized by method of PCF2-C bond. The pCF2-Ser mimic may be site-specifically incorporated into peptides (SPPS) and proteins (expressed protein ligation). This isopolar, dianionic pSer mimic results in a “constitutive phosphorylation” phenotype, and is seen to support native protein-protein interactions that depend upon serine phosphorylation. Signal transduction pathways studied with this chemical biological approach include the regulation of p53 tumor suppressor protein activity, and of melatonin production. Given these successes, the future is bright for the use of such “teflon phospho-amino acid mimics” to map kinase-based signaling pathways. PMID:19778720

  19. Site contamination health risk assessment case study involving tenant relocation from a former gasworks site.

    PubMed

    Turczynowicz, Len; Fitzgerald, D James; Nitschke, Monika; Mangas, Sam; McLean, Angela

    2007-10-01

    An Adelaide suburban public-housing residential site with 16 apartments was investigated after complaints of odor in some yard areas. A distinct 0.5-m layer of dark, odorous (tarry), contaminant material, which in some areas had been covered with plastic sheeting, was subsequently found beneath the topsoil across most of the site. This material appeared to extend beneath the apartments. Analysis indicated high levels of cyanide and polycyclic aromatic hydrocarbons (PAHs), consistent with gasworks waste. Historical investigation revealed that the site was originally owned by a gas company and that a large gasometer (gas-storage tank) existed in one corner of the site. This finding of significant soil contamination precipitated a decision by the health and housing authorities to notify tenants immediately and to plan for their relocation. In addition to tending to the consequent personal disruption and logistical difficulties this posed, a detailed risk assessment process was developed. Urine samples were collected before and after relocation and analyzed for 1-hydroxypyrene (1-OHP), a biomarker for polycyclic aromatic hydrocarbon (PAH) exposure. In addition, samples of tap water, indoor and outdoor air, indoor and ceiling dust, carpets, and soil from tillage areas were analyzed for PAHs. Data indicated a low health risk associated with tenancy on the site. This report presents details of the health risk assessment process undertaken and discusses vindicative reasons for tenant relocation. PMID:17763082

  20. Hydrological studies of a tropical reservoir site, Nigeria

    NASA Astrophysics Data System (ADS)

    Alabo, E. H.

    The study area, a potential reservoir site, is situated in the tropical belt and was chosen by an earlier worker after geophysical and geotechnical investigations. The area is underlain by the Precambrian Basement Complex. The aim of the present study is to determine whether the site could provide adequate water for a proposed reservoir. The climate of the area is of marked wet and dry seasons, with a tropical rainforest-type of vegetation. The catchment area is about 744.40 km 2. The population of the communities is presently about 528,169 (1963 census), and it is estimated to be approximately 600,000 by the year 2005. This paper provides an estimation of the water need of the expected population. Owing to scanty hydrological data for the Owena River, its expected discharge was extrapolated by comparison with the neighbouring Shasha River. From calculations, the following results were obtained: (1) expected available water within the catchment area, 256.75 × 10 6 m 3 per year; (2) expected reservoir capacity, 13.73 × 10 6 m 3; (3) average discharge of the Owena River at the investigation point, 2.91 m 3 s -1 over a period of one year; (4) expected water need of the communities (of 600,000 persons), 4.38 × 10 6 m 3 per year, about 0.5 m 3 s -1. On the basis of the expected excess water over demand, losses through evapo-transpiration and seepage, as well as the possible availability of building materials within the area, it is recommended that the creation of an earth dam reservoir is feasible.

  1. Incorporation of tryptophan analogues into the lantibiotic nisin.

    PubMed

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  2. Photoaffinity analogues of methotrexate as folate antagonist binding probes. 2. Transport studies, photoaffinity labeling, and identification of the membrane carrier protein for methotrexate from murine L1210 cells

    SciTech Connect

    Price, E.M.; Freisheim, J.H.

    1987-07-28

    A membrane-derived component of the methotrexate/one-carbon-reduced folate transport system in murine L1210 cells has been identified by using a photoaffinity analogue of methotrexate. The compound, a radioiodinated 4-azidosalicylyl derivative of the lysine analogue of methotrexate, is transported into murine L1210 cells in a temperature-dependent, sulfhydryl reagent inhibitable manner with a K/sub t/ of 506 +/- 79 nM and a V/sub max/ of 17.9 +/- 4.2 pmol min/sup -1/ (mg of total cellular protein)/sup -1/. Uptake of the iodinated compound at 200 nM is inhibited by low amounts of methotrexate. The parent compounds of the iodinated photoprobe inhibit (/sup 3/H)methotrexate uptake, with the uniodinated 4-azidosalicylyl derivative exhibiting a K/sub i/ of 66 +/- 21 nM. UV irradiation, at 4 /sup 0/C, of a cell suspension that had been incubated with the probe results in the covalent modification of a 46K-48K protein. This can be demonstrated when the plasma membranes from the labeled cells are analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Labeling of this protein occurs half-maximally at a reagent concentration that correlates with the K/sub t/ for transport of the iodinated compound. Protection against labeling of this protein by increasing amounts of methotrexate parallels the concentration dependence of inhibition of photoprobe uptake by methotrexate. Evidence that, in the absence of irradiation and at 37/sup 0/C, the iodinated probe is actually internalized is demonstrated by the labeling of two soluble proteins (M/sub r/ 38K and 21K) derived from the cell homogenate supernatant.

  3. 11-TRIFLUOROMETHYL-PHENYLDIAZIRINYL NEUROSTEROID ANALOGUES: POTENT GENERAL ANESTHETICS AND PHOTOLABELING REAGENTS FOR GABAA RECEPTORS

    PubMed Central

    Chen, Zi-Wei; Wang, Cunde; Krishnan, Kathiresan; Manion, Brad D.; Hastings, Randy; Bracamontes, John; Taylor, Amanda; Eaton, Megan M.; Zorumski, Charles F.; Steinbach, Joseph H.; Akk, Gustav; Mennerick, Steven; Covey, Douglas F.; Evers, Alex S.

    2014-01-01

    Rationale While neurosteroids are well-described positive allosteric modulators of GABAA receptors, the binding sites that mediate these actions have not been definitively identified. Objectives To synthesize neurosteroid analogue photolabeling reagents that closely mimic the biological effects of endogenous neurosteroids and have photochemical properties that will facilitate their use as tools for identifying the binding sites for neurosteroids on GABAA receptors. Results Two neurosteroid analogues containing a trifluromethyl-phenyldiazirine group linked to the steroid C11 position were synthesized. These reagents, CW12 and CW14, are analogues of allopregnanolone (5α-reduced steroid) and pregnanolone (5β-reduced steroid), respectively. Both reagents were shown to have favorable photochemical properties with efficient insertion into the C–H bonds of cyclohexane. They also effectively replicated the actions of allopregnanolone and pregnanolone on GABAA receptor functions: they potentiated GABA-induced currents in Xenopus laevis oocytes transfected with α1β2γ2L subunits, modulated [35S]t-butylbicyclophosphorothionate binding in rat brain membranes and were effective anesthetics in Xenopus tadpoles. Studies using [3H]CW12 and [3H]CW14 showed that these reagents covalently label GABAA receptors in both rat brain membranes and in TSA cells expressing either α1 and β2 subunits or β3 subunits of the GABAA receptor. Photolabeling of rat brain GABAA receptors was shown to be both concentration-dependent and stereospecific. Conclusions CW12 and CW14 have the appropriate photochemical and pharmacological properties for use as photolabeling reagents to identify specific neurosteroid binding sites on GABAA receptors. PMID:24756762

  4. 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.

  5. Emerald Lake Watershed study: Introduction and site description

    SciTech Connect

    Tonnessen, K.A. )

    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.

  6. Phosphonate analogue substrates for enolase.

    PubMed

    Anderson, V E; Cleland, W W

    1990-11-20

    Phosphonate analogues in which the bridge between C-2 and phosphorus is a CH2 group are slow substrates for yeast enolase. The pH variation of the kinetic parameters for the methylene analogue of 2-phosphoglycerate suggests that the substrate binds as a dianion and that Mg2+ can bind subsequently only if a metal ligand and the catalytic base are unprotonated. Primary deuterium isotope effects of 4-8 on V/KMg, but ones of only 1.15-1.32 on V for dehydration, show that proton removal to give the carbanion intermediate largely limits V/KMg and that a slow step follows which largely limits V (presumably carbanion breakdown). Since there is a D2O solvent isotope effect on V for the reverse reaction of 5, but not an appreciable one on the forward reaction, it appears that the slow rates with phosphonate analogues result from the fact that the carbanion intermediate is more stable than that formed from the normal substrates, and its reaction in both directions limits V. Increased stability as a result of replacement of oxygen by carbon at C-2 of the carbanion is the expected chemical behavior. PMID:2271661

  7. 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.

  8. Improved selectivity for Pb(II) by sulfur, selenium and tellurium analogues of 1,8-anthraquinone-18-crown-5: synthesis, spectroscopy, X-ray crystallography and computational studies.

    PubMed

    Mariappan, Kadarkaraisamy; Alaparthi, Madhubabu; Hoffman, Mariah; Rama, Myriam Alcantar; Balasubramanian, Vinothini; John, Danielle M; Sykes, Andrew G

    2015-07-14

    We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene-9,10-dione in a 1 : 1 ratio. The optical properties of the new compounds are examined and the sulfur and selenium analogues produce an intense green emission enhancement upon association with Pb(II) in acetonitrile. Selectivity for Pb(II) is markedly improved as compared to the oxygen analogue 1 which was also competitive for Ca(II) ion. UV-Visible and luminescence titrations reveal that 2 and 3 form 1 : 1 complexes with Pb(II), confirmed by single-crystal X-ray studies where Pb(II) is complexed within the macrocycle through coordinate covalent bonds to neighboring carbonyl, ether and heteroether donor atoms. Cyclic voltammetry of 2-8 showed classical, irreversible oxidation potentials for sulfur, selenium and tellurium heteroethers in addition to two one-electron reductions for the anthraquinone carbonyl groups. DFT calculations were also conducted on 1, 2, 3, 6, 6 + Pb(II) and 6 + Mg(II) to determine the trend in energies of the HOMO and the LUMO levels along the series. PMID:26051600

  9. Improved selectivity for Pb(II) by sulfur, selenium and tellurium analogues of 1,8-anthraquinone-18-crown-5: synthesis, spectroscopy, X-ray crystallography and computational studies.

    PubMed

    Mariappan, Kadarkaraisamy; Alaparthi, Madhubabu; Hoffman, Mariah; Rama, Myriam Alcantar; Balasubramanian, Vinothini; John, Danielle M; Sykes, Andrew G

    2015-07-14

    We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene-9,10-dione in a 1 : 1 ratio. The optical properties of the new compounds are examined and the sulfur and selenium analogues produce an intense green emission enhancement upon association with Pb(II) in acetonitrile. Selectivity for Pb(II) is markedly improved as compared to the oxygen analogue 1 which was also competitive for Ca(II) ion. UV-Visible and luminescence titrations reveal that 2 and 3 form 1 : 1 complexes with Pb(II), confirmed by single-crystal X-ray studies where Pb(II) is complexed within the macrocycle through coordinate covalent bonds to neighboring carbonyl, ether and heteroether donor atoms. Cyclic voltammetry of 2-8 showed classical, irreversible oxidation potentials for sulfur, selenium and tellurium heteroethers in addition to two one-electron reductions for the anthraquinone carbonyl groups. DFT calculations were also conducted on 1, 2, 3, 6, 6 + Pb(II) and 6 + Mg(II) to determine the trend in energies of the HOMO and the LUMO levels along the series.

  10. Comparison of the inhibitory action of synthetic capsaicin analogues with various NADH-ubiquinone oxidoreductases.

    PubMed

    Satoh, T; Miyoshi, H; Sakamoto, K; Iwamura, H

    1996-01-11

    Capsaicin is a new naturally occurring inhibitor of proton-pumping NADH-ubiquinone oxidoreductase (NDH-1), that competitively acts against ubiquinone. A series of capsaicin analogues was synthesized to examine the structural factors required for the inhibitory action and to probe the structural property of the ubiquinone catalytic site of various NADH-ubiquinone reductases, including non-proton-pumping enzyme (NDH-2), from bovine heart mitochondria, potato tuber (Solanum tuberosum, L) mitochondria and Escherichia coli (GR 19N) plasma membranes. Some synthetic capsaicins were fairly potent inhibitors of each of the three NDH-1 compared with the potent rotenone and piericidin A. Synthetic capsaicin analogues inhibited all three NDH-1 activities in a competitive manner against an exogenous quinone. The modification both of the substitution pattern and of the number of methoxy groups on the benzene ring, which may be superimposable on the quinone ring of ubiquinone, did not drastically affect the inhibitory potency. In addition, alteration of the position of dipolar amide bond unit in the molecule and chemical modifications of this unit did not change the inhibitory potency, particularly with bovine heart and potato tuber NDH-1. These results might be explained assuming that the ubiquinone catalytic site of NDH-1 is spacious enough to accommodate a variety of structurally different capsaicin analogues in a dissimilar manner. Regarding the moiety corresponding to the alkyl side chain, a rigid diphenyl ether structure was more inhibitory than a flexible alkyl chain. Structure-activity studies and molecular orbital calculations suggested that a bent form is the active conformation of capsaicin analogues. On the other hand, poor correlations between the inhibitory potencies determined with the three NDH-1 suggested that the structural similarity of the ubiquinone catalytic sites of these enzymes is rather poor. The sensitivity to the inhibition by synthetic capsaicins

  11. Active site directed irreversible inactivation of brewers' yeast pyruvate decarboxylase by the conjugated substrate analogue (E)-4-(4-chlorophenyl)-2-oxo-3-butenoic acid: development of a suicide substrate.

    PubMed

    Kuo, D J; Jordan, F

    1983-08-01

    (E)-4-(4-Chlorophenyl)-2-oxo-3-butenoic acid (CPB) was found to irreversibly inactivate brewers' yeast pyruvate decarboxylase (PDC, EC 4.1.1.1) in a biphasic, sigmoidal manner, as is found for the kinetic behavior of substrate. An expression was derived for two-site irreversible inhibition of allosteric enzymes, and the kinetic behavior of CPB fit the expression for two-site binding. The calculated Ki's of 0.7 mM and 0.3 mM for CPB were assigned to the catalytic site and the regulatory site, respectively. The presence of pyruvic acid at high concentrations protected PDC from inactivation, whereas low concentrations of pyruvic acid accelerated inactivation by CPB. Pyruvamide, a known allosteric activator of PDC, was found to enhance inactivation by CPB. The results can be explained if pyruvamide binds only to a regulatory site, but CPB and pyruvic acid compete for both the regulatory and the catalytic centers. [1-14C]CPB was found to lose 14CO2 concurrently with the inactivation of the enzyme. Therefore, CPB was being turned over by PDC, in addition to inactivating it. CPB can be labeled a suicide-type inactivator for PDC.

  12. Observational study of contracts processing at 29 CTSA sites.

    PubMed

    Kiriakis, James; Gaich, Nicholas; Johnston, S Claiborne; Kitterman, Darlene; Rosenblum, Daniel; Salberg, Libby; Rifkind, Adam

    2013-08-01

    We measured contracts final negotiation (FN) and full execution (FE) times using shared definitions in a prospective observational study of management of contracts for clinical trials at 29 CTSA institutions. Median FN and FE times were reached in 39 and 91 days, respectively; mean times for FN and FE were 55 and 103 days, respectively. Individual site medians ranged from 3 to 116 days for FN and 34 to 197 days for FE. The use of master agreements (MAs) and previously negotiated terms (PNTs) was associated with significant reduction of FN times by a mean of 33 days (p < 0) and 22 days (p < 0.001), respectively. PNTs, but not MAs, were associated with significantly reduced FE time (22 days, p < 0.007). Gap analysis revealed a gap of 22 days between contracts negotiation and Institutional Review Board (IRB) review and intervals of 33 days (contracts) and 48 days (IRB review) during which the process steps were being conducted alone, suggesting a potential benefit with parallel processing. These baseline data support a plan to investigate root causes of prolonged study start-up time by examining causes of variation and outliers.

  13. Enhanced Television Strategy Models: A Study of TV Web Sites.

    ERIC Educational Resources Information Center

    Ha, Louisa

    2002-01-01

    Compares the use of enhanced television features and television commerce features on the Web sites of cable and broadcast television networks. Shows differences in strategies and site usability; proposes three enhanced television strategy models; and discusses implications on television revenue and viewership. (Author/LRW)

  14. 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.

  15. A solution NMR study showing that active site ligands and nucleotides directly perturb the allosteric equilibrium in aspartate transcarbamoylase.

    PubMed

    Velyvis, Algirdas; Yang, Ying R; Schachman, Howard K; Kay, Lewis E

    2007-05-22

    The 306-kDa aspartate transcarbamoylase is a well studied regulatory enzyme, and it has emerged as a paradigm for understanding allostery and cooperative binding processes. Although there is a consensus that the cooperative binding of active site ligands follows the Monod-Wyman-Changeux (MWC) model of allostery, there is some debate about the binding of effectors such as ATP and CTP and how they influence the allosteric equilibrium between R and T states of the enzyme. In this article, the binding of substrates, substrate analogues, and nucleotides is studied, along with their effect on the R-T equilibrium by using highly deuterated, (1)H,(13)C-methyl-labeled protein in concert with methyl-transverse relaxation optimized spectroscopy (TROSY) NMR. Although only the T state of the enzyme can be observed in spectra of wild-type unliganded aspartate transcarbamoylase, binding of active-site substrates shift the equilibrium so that correlations from the R state become visible, allowing the equilibrium constant (L') between ligand-saturated R and T forms of the enzyme to be measured quantitatively. The equilibrium constant between unliganded R and T forms (L) also is obtained, despite the fact that the R state is "invisible" in spectra, by means of an indirect process that makes use of relations that emerge from the fact that ligand binding and the R-T equilibrium are linked. Titrations with MgATP unequivocally establish that its binding directly perturbs the R-T equilibrium, consistent with the Monod-Wyman-Changeux model. This study emphasizes the utility of modern solution NMR spectroscopy in understanding protein function, even for systems with aggregate molecular masses in the hundreds of kilodaltons.

  16. 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

  17. Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core

    PubMed Central

    2015-01-01

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues. PMID:25207434

  18. Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

    PubMed

    Kraft, Matthew B; Poudel, Yam B; Kedei, Noemi; Lewin, Nancy E; Peach, Megan L; Blumberg, Peter M; Keck, Gary E

    2014-09-24

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues.

  19. Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

    PubMed

    Kraft, Matthew B; Poudel, Yam B; Kedei, Noemi; Lewin, Nancy E; Peach, Megan L; Blumberg, Peter M; Keck, Gary E

    2014-09-24

    A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues. PMID:25207434

  20. How Analogue Research Can Advance Descriptive Evaluation Theory: Understanding (and Improving) Stakeholder Dialogue

    ERIC Educational Resources Information Center

    Campbell, Bernadette; Mark, Melvin M.

    2015-01-01

    Evaluation theories can be tested in various ways. One approach, the experimental analogue study, is described and illustrated in this article. The approach is presented as a method worthy to use in the pursuit of what Alkin and others have called descriptive evaluation theory. Drawing on analogue studies conducted by the first author, we…

  1. Binding of adenosine and receptor-specific analogues to lymphocytes from control subjects and patients with common variable immunodeficiency.

    PubMed Central

    Shah, T; Simpson, R J; Webster, A D; Peters, T J

    1987-01-01

    Studies were performed on the binding of tritiated adenosine and its analogues, 5'-N-ethylcarboxamide adenosine (NECA) and N6-phenylisopropyladenosine (PIA), to human peripheral blood lymphocytes. These revealed binding only of adenosine (Kd, 1-10 microM, 14,000 binding sites/cell), which was abolished by dipyridamole, a specific adenosine transport inhibitor, suggesting that the binding is to the nucleoside transporter. The absence of high affinity (Kd less than or equal to 1 microM) binding of adenosine or of the two analogues. NECA and PIA suggests that the previously reported effects of adenosine on cAMP formation are not mediated by cell surface specific nucleoside receptors. Binding of adenosine to the carrier in lymphocytes from patients with common variable immunodeficiency was similar to those from control subjects. PMID:2958197

  2. 76 FR 81959 - Notice of Proposed Information Collection: Comment Request; Homelessness Prevention Study Site...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... URBAN DEVELOPMENT Notice of Proposed Information Collection: Comment Request; Homelessness Prevention... following information: Title of Proposal: Homelessness Prevention Study Site Visits. OMB Control Number, if... requirements associated with HUD's Homelessness Prevention Study Site Visits. This information...

  3. Mammalian folylpoly-. gamma. -glutamate synthetase. 3. Specificity for folate analogues

    SciTech Connect

    George, S.; Cichowicz, D.J.; Shane, B.

    1987-01-27

    A variety of folate analogues were synthesized to explore the specificity of the folate binding site of hog liver folypolyglutamate synthetase and the requirements for catalysis. Modifications of the internal and terminal glutamate moieties of folate cause large drops in on rates and/or affinity for the protein. The only exceptions are glutamine, homocysteate, and ornithine analogues, indicating a less stringent specificity around the delta-carbon of glutamate. It is proposed that initial folate binding to the enzyme involves low-affinity interactions at a pterin and a glutamate site and that the first glutamate bound is the internal residue adjacent to the benzoyl group. Processive movement of the polyglutamate chain through the glutamate site and a possible conformational change in the protein when the terminal residue is bound would result in tight binding and would position the ..gamma..-carboxyl of the terminal glutamate in the correct position for catalysis. The 4-amino substitution of folate increases the on rate for monoglutamate derivatives but severely impairs catalysis with diglutamate derivatives. Pteroylornithine derivatives are the first potent and specific inhibitors of folylpolyglutamate synthetase to be identified and may act as analogues of reaction intermediates. Other folate derivatives with tetrahedral chemistry replacing the peptide bond, such as pteroyl-..gamma..-glutamyl-(psi,CH/sub 2/-NH)-glutamate, retain affinity for the protein but are considerably less effective inhibitors than the ornithine derivatives. Enzyme activity was assayed using (/sup 14/C)glutamate.

  4. Central effects of angiotensin II, its fragment and analogues.

    PubMed

    Georgiev, V P; Klousha, V E; Petkov, V D; Markovska, V L; Svirskis, S V; Mountsinietse, R K; Anouans, Z E

    1984-01-01

    The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

  5. A Virtual Web Environment for Mars Landing Site Studies

    NASA Technical Reports Server (NTRS)

    Gulick, V. C.; Deardorff, D. G.; Briggs, G. A.

    2001-01-01

    A collection of web tools is available for both the landing site and broader Mars science communities to better utilize, visualize, and analyze Mars Global Surveyor data. These tools have grown out of a two year effort between the Center for Mars Exploration (CMEX), and the NAS data visualization group at NASA Ames Research Center (ARC), to promote interactions among the planetary community and to coordinate landing site activities. The web site will continue to evolve over the next several years as new tools and features are added to support the ongoing Mars missions.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. a New Framework for Geospatial Site Selection Using Artificial Neural Networks as Decision Rules: a Case Study on Landfill Sites

    NASA Astrophysics Data System (ADS)

    Abujayyab, S. K. M.; Ahamad, M. A. S.; Yahya, A. S.; Saad, A.-M. H. Y.

    2015-10-01

    This paper briefly introduced the theory and framework of geospatial site selection (GSS) and discussed the application and framework of artificial neural networks (ANNs). The related literature on the use of ANNs as decision rules in GSS is scarce from 2000 till 2015. As this study found, ANNs are not only adaptable to dynamic changes but also capable of improving the objectivity of acquisition in GSS, reducing time consumption, and providing high validation. ANNs make for a powerful tool for solving geospatial decision-making problems by enabling geospatial decision makers to implement their constraints and imprecise concepts. This tool offers a way to represent and handle uncertainty. Specifically, ANNs are decision rules implemented to enhance conventional GSS frameworks. The main assumption in implementing ANNs in GSS is that the current characteristics of existing sites are indicative of the degree of suitability of new locations with similar characteristics. GSS requires several input criteria that embody specific requirements and the desired site characteristics, which could contribute to geospatial sites. In this study, the proposed framework consists of four stages for implementing ANNs in GSS. A multilayer feed-forward network with a backpropagation algorithm was used to train the networks from prior sites to assess, generalize, and evaluate the outputs on the basis of the inputs for the new sites. Two metrics, namely, confusion matrix and receiver operating characteristic tests, were utilized to achieve high accuracy and validation. Results proved that ANNs provide reasonable and efficient results as an accurate and inexpensive quantitative technique for GSS.

  11. A 1H NMR Study of Host/Guest Supramolecular Complexes of a Curcumin Analogue with β-Cyclodextrin and a β-Cyclodextrin-Conjugated Gemini Surfactant.

    PubMed

    Poorghorban, Masoomeh; Karoyo, Abdalla H; Grochulski, Pawel; Verrall, Ronald E; Wilson, Lee D; Badea, Ildiko

    2015-08-01

    Host systems based on β-cyclodextrin (βCD) were employed as pharmaceutical carriers to encapsulate a poorly soluble drug, curcumin analogue (NC 2067), in order to increase its water solubility. βCD was chemically conjugated with an amphiphilic gemini surfactant with the ability to self-assemble and to form nanoscale supramolecular structures. The conjugated molecule, βCDgemini surfactant (βCDg), was shown to be a promising drug delivery agent. In this report, its physicochemical properties were assessed in aqueous solution using 1D and 2D 1H NMR spectroscopy. The results showed that the apolar hydrocarbon domain of the gemini surfactant was self-included within the βCD internal cavity. The host/guest complexes composed of native βCD or βCDg with NC 2067 were examined using 1D/2D ROESY NMR methods. The stoichiometry of βCD/NC 2067 complex was estimated using Job's method via 1H NMR spectroscopy. The binding geometry of NC 2067 within βCD was proposed using molecular docking and further supported by 1D and 2D ROESY NMR results. Addition of NC 2067 to βCDg revealed minimal changes to the overall structure of the βCDg system, in agreement with the formation of a βCDg/NC 2067 ternary complex. PMID:26083126

  12. 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 π 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 1nπ* 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

  13. Studies on the cardiovascular effects produced by the spinal action of two substance P analogues in the rat: evidence for a central catecholaminergic mechanism.

    PubMed

    Couture, R; Gupta, A; Kérouac, R; Regoli, D

    1987-03-31

    The effects of two substance P (SP) analogues, [D-Trp7,9,10]SP (ana1) and [D-Pro4,Lys6,D-Trp7,9,10,Phe11]SP-(4-11) (ana2) on mean arterial pressure (MAP) and heart rate (HR) were measured following intrathecal administration at one of three spinal cord levels in rats anaesthetized with sodium pentobarbital. Following an initial increase, a profound and long-lasting fall in MAP and HR occurred when 6.5 nmol of either ana1 or ana2 was injected at T1-T3 or T8-T10. Only transient changes in MAP and a slight increase in HR was observed after injection of either peptide at L2-L4. The profound and long-lasting hypotension and bradycardia induced by ana1 were not significantly altered after intravenous injection of hexamethonium, phentolamine, propranolol, atropine, diphenhydramine, cimetidine, methysergide, naloxone or morphine. However, the biphasic effect of ana1 on MAP was prevented by the intrathecal administration of prazosin and yohimbine, suggesting that a central catecholaminergic mechanism including alpha 1- and alpha 2-adrenergic receptors is involved. The latter treatment did not prevent the tachycardia which occurred when the bradycardia was blocked, indicating that different mechanisms mediate the spinal action of ana1 on MAP and HR. Finally, cervical transection of the spinal cord eliminated the profound and long-lasting depressor effect of ana2, suggesting that a supraspinal mechanism is involved in this cardiovascular response.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    PubMed

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.

  1. Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors.

    PubMed

    Florence, Gordon J; Fraser, Andrew L; Gould, Eoin R; King, Elizabeth F B; Menzies, Stefanie K; Morris, Joanne C; Tulloch, Lindsay B; Smith, Terry K

    2014-11-01

    Neglected tropical diseases remain a serious global health concern. Here, a series of novel bis-tetrahydropyran 1,4-triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). 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. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti-HAT agents.

  2. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    DOEpatents

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  3. Magnetohydrodynamical Analogue of a Black Hole

    NASA Astrophysics Data System (ADS)

    Zamorano, Nelson; Asenjo, Felipe

    2014-03-01

    We study the conditions that a plasma fluid and its container should meet to generate a magneto-acoustic horizon. This effect becomes an alternative to the analogue black hole found in a transonic fluid flow setting. In this context we use the magnetohydrodynamic formalism (MHD) to analyze the evolution of an irrotational plasma fluid interacting with an external constant magnetic field. Under certain plausible approximations, the dynamic of the field perturbations is described by a scalar field potential that follows a second order differential equation. As we prove here, this equation corresponds to the wave equation associated to a scalar field in a curved space-time. This horizon emerges when the local speed of the medium grows larger than the sound velocity. The magnetic field generates an effective pressure which contributes to the magneto-acoustic speed. We compare these results with the known physics of analogue black holes. We will also refer to our ongoing experiment that, in its first stage, attempts to reproduce the wave horizons found in an open channel with an obstacle: PRL 106, 021302 (2011).

  4. Distribution and binding of 18F-labeled and 125I-labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: a whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients.

    PubMed

    Gulyás, Balázs; Spenger, Christian; Beliczai, Zsuzsa; Gulya, Károly; Kása, Péter; Jahan, Mahabuba; Jia, Zhisheng; Weber, Urs; Pfeifer, Andrea; Muhs, Andreas; Willbold, Dieter; Halldin, Christer

    2012-01-01

    AD patients and age matched control subjects, support the visualization capacity of the radiolabeled ACI-80 analogues of amyloid deposits in the human brain. Further studies are warranted to explore the usefulness of the (18)F-labeled analogues as in vivo molecular imaging biomarkers in diagnostic PET studies. PMID:22100791

  5. Memory amplification for trauma: Investigating the role of analogue PTSD symptoms in the laboratory.

    PubMed

    Oulton, Jacinta M; Takarangi, Melanie K T; Strange, Deryn

    2016-08-01

    Victims of trauma often remember their experience as being more traumatic later, compared to immediately after, the event took place. This finding-the "memory amplification effect"-is associated with increased re-experiencing symptoms. However, the effect has been found almost exclusively in field-based studies. We examined whether the effect could be replicated in the laboratory. In two studies, we exposed participants to negative photographs and assessed their memory for the photographs and analogue PTSD symptoms on two occasions. In Study 1, analogue symptoms at follow-up were positively associated with remembering more negative photos over time. In Study 2, we focused on "memory amplifiers": people whose memory of the photos amplified over time. Consistent with field research, analogue re-experiencing symptoms were associated with memory amplification. Overall, our findings confirm that analogue PTSD symptoms are also associated with an amplified memory for a trauma analogue. PMID:27328014

  6. The Object-analogue approach for probabilistic forecasting

    NASA Astrophysics Data System (ADS)

    Frediani, M. E.; Hopson, T. M.; Anagnostou, E. N.; Hacker, J.

    2015-12-01

    The object-analogue is a new method to estimate forecast uncertainty and to derive probabilistic predictions of gridded forecast fields over larger regions rather than point locations. The method has been developed for improving the forecast of 10-meter wind speed over the northeast US, and it can be extended to other forecast variables, vertical levels, and other regions. The object-analogue approach combines the analog post-processing technique (Hopson 2005; Hamill 2006; Delle Monache 2011) with the Method for Object-based Diagnostic Evaluation (MODE) for forecast verification (Davis et al 2006a, b). Originally, MODE is used to verify mainly precipitation forecasts using features of a forecast region represented by an object. The analog technique is used to reduce the NWP systematic and random errors of a gridded forecast field. In this study we use MODE-derived objects to characterize the wind fields forecasts into attributes such as object area, centroid location, and intensity percentiles, and apply the analogue concept to these objects. The object-analogue method uses a database of objects derived from reforecasts and their respective reanalysis. Given a real-time forecast field, it searches the database and selects the top-ranked objects with the most similar set of attributes using the MODE fuzzy logic algorithm for object matching. The attribute probabilities obtained with the set of selected object-analogues are used to derive a multi-layer probabilistic prediction. The attribute probabilities are combined into three uncertainty layers that address the main concerns of most applications: location, area, and magnitude. The multi-layer uncertainty can be weighted and combined or used independently in such that it provides a more accurate prediction, adjusted according to the application interest. In this study we present preliminary results of the object-analogue method. Using a database with one hundred storms we perform a leave-one-out cross-validation to

  7. 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…

  8. Remediating low permeability sites with 2-phase extraction -- Case studies

    SciTech Connect

    Tornatore, P.M.

    1994-12-31

    2-Phase Extraction is an innovative remedial process developed and patented by Xerox Corporation that combines the attributes of soil vapor extraction and groundwater recovery under high vacuum (>25 inches Hg at the source) in a way that synergistically increases the performance of the collective remedy. Haley and Aldrich has applied 2-Phase Extraction on a number of low permeability sites with a wide range of geologic conditions. The paper focuses on an overview of results achieved at 4 of the sites under pilot and full scale operations. Contaminants successfully extracted have ranged from petroleum products to blends of chlorinated solvents and mineral oils. In each case, mass removal has been accelerated by as much as 2 orders of magnitude compared to conventional remedies. This paper presents an overview of the results of 2-Phase Extraction application at four project locations. The sites include the following: Webster, New York; Blauvelt, New York; Clinton, Illinois; and Lee, New Hampshire.

  9. Scandium(III) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with (44)Sc from cyclotron and from a (44)Ti/(44)Sc generator.

    PubMed

    Kerdjoudj, R; Pniok, M; Alliot, C; Kubíček, V; Havlíčková, J; Rösch, F; Hermann, P; Huclier-Markai, S

    2016-01-28

    The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3AP(PrA) and DO3AP(ABn)) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with (45)Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc-DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free-ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with (44)Sc was performed using the radioisotope from two sources, a (44)Ti/(44)Sc generator and (44m)Sc/(44)Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 °C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of (44)Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the (44)Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine.

  10. Scandium(III) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with (44)Sc from cyclotron and from a (44)Ti/(44)Sc generator.

    PubMed

    Kerdjoudj, R; Pniok, M; Alliot, C; Kubíček, V; Havlíčková, J; Rösch, F; Hermann, P; Huclier-Markai, S

    2016-01-28

    The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3AP(PrA) and DO3AP(ABn)) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with (45)Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc-DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free-ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with (44)Sc was performed using the radioisotope from two sources, a (44)Ti/(44)Sc generator and (44m)Sc/(44)Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 °C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of (44)Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the (44)Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine. PMID:26675416

  11. Ab initio quantum mechanical study of the structures and energies for the pseudorotation of 5{prime}-dehydroxy analogues of 2{prime}-deoxyribose and ribose sugars

    SciTech Connect

    Brameld, K.A.; Goddard, W.A. III

    1999-02-10

    The authors have used ab initio quantum mechanical (QM) methods to determine the potential energy of pseudorotation for 3,4-dihydroxy-5-methyl-2-(1-pyrollyl)tetrahydrofuran and 4-hydroxy-5-methyl-2-(1-pyrollyl)-tetrahydrofuran, close analogues of 2{prime}-deoxyribose and ribose sugars. The pyrrole is a substitute for the naturally occurring nucleic acid bases: adenine, thymine, guanine, cytosine, and uracil. At the highest calculation level (LMP2/cc-pVTZ(-f)//HF/6-31G**) for 2{prime}-deoxyribose, they find the C2{prime}-endo conformation is the global minimum. The C3{prime}-endo conformation is a local minimum 0.6 kcal/mol higher in energy, and an eastern barrier of 1.6 kcal/mol separates the two minima. Pseudorotation energies of ribose are quite complex and are strongly affected by local orientations of the 2{prime} and 3{prime} hydroxyl groups. When the hydroxyl groups are allowed to assume any conformation, the global minimum remains the C2{prime}-endo conformation. The eastern barrier increases slightly to 1.8 kcal/mol, and the C3{prime}-endo local minimum lies 0.6 kcal/mol above the global minimum. Constraining the torsion angle of the C3{prime} hydroxyl group to {minus}146{degree}, as is found in RNA polymers, results in the C3{prime}-endo conformation becoming the only energy minimum with a C2{prime}-endo conformation 1.9 kcal/mol higher in energy. Bond angles within the pentofuranose ring are correlated to the pseudorotational phase, as is observed by X-ray crystallography and is predicted by pseudorotation theory. Finally, a force field for use in molecular mechanics and dynamics simulations is presented which reproduces the QM potential energies for the 2{prime}-deoxyribose and ribose sugars.

  12. β Sheets Not Required: Combined Experimental and Computational Studies of Self-Assembly and Gelation of the Ester-Containing Analogue of an Fmoc-Dipeptide Hydrogelator

    PubMed Central

    2015-01-01

    In our work toward developing ester-containing self-assembling peptides as soft biomaterials, we have found that a fluorenylmethoxycarbonyl (Fmoc)-conjugated alanine-lactic acid (Ala-Lac) sequence self-assembles into nanostructures that gel in water. This process occurs despite Fmoc-Ala-Lac’s inability to interact with other Fmoc-Ala-Lac molecules via β-sheet-like amide–amide hydrogen bonding, a condition previously thought to be crucial to the self-assembly of Fmoc-conjugated peptides. Experimental comparisons of Fmoc-Ala-Lac to its self-assembling peptide sequence analogue Fmoc-Ala-Ala using a variety of microscopic, spectroscopic, and bulk characterization techniques demonstrate distinct features of the two systems and show that while angstrom-scale self-assembled structures are similar, their nanometer-scale size and morphological properties diverge and give rise to different bulk mechanical properties. Molecular dynamics simulations were performed to gain more insight into the differences between the two systems. An analysis of the hydrogen-bonding and solvent-surface interface properties of the simulated fibrils revealed that Fmoc-Ala-Lac fibrils are stronger and less hydrophilic than Fmoc-Ala-Ala fibrils. We propose that this difference in fibril amphiphilicity gives rise to differences in the higher-order assembly of fibrils into nanostructures seen in TEM. Importantly, we confirm experimentally that β-sheet-type hydrogen bonding is not crucial to the self-assembly of short, conjugated peptides, and we demonstrate computationally that the amide bond in such systems may act mainly to mediate the solvation of the self-assembled single fibrils and therefore regulate a more extensive higher-order aggregation of fibrils. This work provides a basic understanding for future research in designing highly degradable self-assembling materials with peptide-like bioactivity for biomedical applications. PMID:24786493

  13. High resolution 1H NMR-based metabonomic study of the auditory cortex analogue of developing chick (Gallus gallus domesticus) following prenatal chronic loud music and noise exposure.

    PubMed

    Kumar, Vivek; Nag, Tapas Chandra; Sharma, Uma; Mewar, Sujeet; Jagannathan, Naranamangalam R; Wadhwa, Shashi

    2014-10-01

    Proper functional development of the auditory cortex (ACx) critically depends on early relevant sensory experiences. Exposure to high intensity noise (industrial/traffic) and music, a current public health concern, may disrupt the proper development of the ACx and associated behavior. The biochemical mechanisms associated with such activity dependent changes during development are poorly understood. Here we report the effects of prenatal chronic (last 10 days of incubation), 110dB sound pressure level (SPL) music and noise exposure on metabolic profile of the auditory cortex analogue/field L (AuL) in domestic chicks. Perchloric acid extracts of AuL of post hatch day 1 chicks from control, music and noise groups were subjected to high resolution (700MHz) (1)H NMR spectroscopy. Multivariate regression analysis of the concentration data of 18 metabolites revealed a significant class separation between control and loud sound exposed groups, indicating a metabolic perturbation. Comparison of absolute concentration of metabolites showed that overstimulation with loud sound, independent of spectral characteristics (music or noise) led to extensive usage of major energy metabolites, e.g., glucose, β-hydroxybutyrate and ATP. On the other hand, high glutamine levels and sustained levels of neuromodulators and alternate energy sources, e.g., creatine, ascorbate and lactate indicated a systems restorative measure in a condition of neuronal hyperactivity. At the same time, decreased aspartate and taurine levels in the noise group suggested a differential impact of prenatal chronic loud noise over music exposure. Thus prenatal exposure to loud sound especially noise alters the metabolic activity in the AuL which in turn can affect the functional development and later auditory associated behaviour.

  14. Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor).

    PubMed

    Takeuchi, Y; Noguchi, S; Satow, Y; Kojima, S; Kumagai, I; Miura, K; Nakamura, K T; Mitsui, Y

    1991-06-01

    Unlike trypsin-like serine proteases having only one conspicuous binding pocket in the active site, subtilisin BPN' has two such pockets, the S1 and S4 pockets, which accommodate the P1 and P4 residues of ligands (after Schechter and Berger notation) respectively. Using computer graphics, the geometrical nature of the two pockets was carefully examined and strategies for site-directed mutagenesis studies were set up against a protein SSI (Streptomyces subtilisin inhibitor), which is a strong proteinaceous inhibitor (or a substrate analogue) of subtilisin BPN'. It was decided to convert the P1 residue, methionine 73, into lysine (M73K) with or without additional conversion of the P4 residue, methionine 70, into glycine (M70G). The crystal structures of the two complexes of subtilisin BPN', one with the single mutant SSI (M73K) and the other with the double mutant SSI (M73K, M70G) were solved showing that (i) small 'electrostatic induced-fit movement' occurs in the S1 pocket upon introducing the terminal plus charge of the lysine side chain, and (ii) large 'mechanical induced-fit movement' occurs in the S4 pocket upon reducing the size of the P4 side chain from methionine to glycine. In both (i) and (ii), the induced-fit movement occurred in a concerted fashion involving both the enzyme and 'substrate' amino acid residues. The term 'substrate-assisted stabilization' was coined to stress the cooperative nature of the induced-fit movements. PMID:1891457

  15. Preliminary study on brominated dioxins/furans and hydroxylated/methoxylated PBDEs in Baltic cod (Gadus morhua) liver. Comparison to the levels of analogue chlorinated co-occurring pollutants.

    PubMed

    Roszko, Marek; Szymczyk, Krystyna; Rzepkowska, Małgorzata; Jędrzejczak, Renata

    2015-07-15

    Low pg levels of PBDD/Fs in 0.8-38.9 pg g(-1) (fat) range (mean 14.2 pg g(-1)) observed in the tested cod liver samples were significantly lower than levels of their chlorinated analogues (25.1-95.9 range, 37.7 mean pg g(-1) fat). Brominated furans dominated the congener profile. Elevated levels of OH-/MeO-BDE were however observed with mean concentrations at 2769±1319 and 5441±2918 pg g(-1) (fat) respectively. The observed congener profiles with the predominance of 6-OH-BDE 47 and the relatively high proportion between the native and hydroxylated compounds indicate on natural origin of those compounds or at least presence of various exposure sources. A large fraction of studied samples did not comply with the currently standing EU regulations concerning PCBs and chlorinated dioxins (11%), especially as regards non-dioxin like PCBs (88%).

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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...

  1. 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...

  2. 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.

  3. 3D-QSAR and 3D-QSSR studies of thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as CDK4 inhibitors by CoMFA analysis

    PubMed Central

    Cai, Bao-qin; Jin, Hai-xiao; Yan, Xiao-jun; Zhu, Peng; Hu, Gui-xiang

    2014-01-01

    Aim: To investigate the structural basis underlying potency and selectivity of a series of novel analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones as cyclin-dependent kinase 4 (CDK4) inhibitors and to use this information for drug design strategies. Methods: Three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models using comparative molecular field analysis (CoMFA) were conducted on a training set of 48 compounds. Partial least squares (PLS) analysis was employed. External validation was performed with a test set of 9 compounds. Results: The obtained 3D-QSAR model (q2=0.724, r2=0.965, r2pred=0.945) and 3D-QSSR model (q2=0.742, r2=0.923, r2pred=0.863) were robust and predictive. Contour maps with good compatibility to active binding sites provided insight into the potentially important structural features required to enhance activity and selectivity. The contour maps indicated that bulky groups at R1 position could potentially enhance CDK4 inhibitory activity, whereas bulky groups at R3 position have the opposite effect. Appropriate incorporation of bulky electropositive groups at R4 position is favorable and could improve both potency and selectivity to CDK4. Conclusion: These two models provide useful information to guide drug design strategies aimed at obtaining potent and selective CDK4 inhibitors. PMID:24122012

  4. 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…

  5. 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

  6. Variability in ultraplankton at the Porcupine Abyssal Plain study site

    NASA Astrophysics Data System (ADS)

    Martin, Adrian P.; Zubkov, Mikhail V.; Holland, Ross J.; Tarran, Glen; Burkill, Peter

    2010-08-01

    Observations of the ultraplankton (<5 μm) are presented from a 4 day mesoscale survey centred on the Porcupine Abyssal Plain (PAP) study site (49°00'N 16°30'W), in July 2006. The organisms enumerated include two groups of phytoplankton, Synechococcus cyanobacteria, heterotrophic bacteria, large viruses, and two size classes of heterotrophic protist. The dataset comprises over 400 samples from the mixed layer taken over a 100 × 100 km 2 area at a spatial resolution of typically 2-3 km. For phytoplankton and heterotrophic bacteria there is a clear bimodal structure to the histograms of abundance indicative of two distinct communities in the region. Using the strong bimodality of one of the phytoplankton groups' histogram as a basis, the dataset is split into two subsets, with roughly 200 points in each, corresponding to the two histogram peaks. Doing so provides evidence that Synechococcus and viruses may also have a bimodal structure. Correlations between all pairings of these five organisms (both phytoplankton groups, Synechococcus, heterotrophic bacteria and viruses) are positive and quite high (r>0.7). The two communities can therefore be characterised as high and low abundance. Although there is a coincidence of low abundances with high temperatures in the southwest corner of the region, where there was known to be an eddy present, the spatial distributions of these organisms over the whole region is poorly predicted by temperature (or salinity or density). Furthermore, the spatial distributions of heterotrophic protists are found to differ strongly from those of the other organisms, having a unimodal structure and no obvious large scale structure. The more random structure of the heterotrophs' spatial distribution compared to their prey is consistent with previous results from the continental shelf, but is demonstrated for the open ocean here for the first time. Spatial variability is a large potential source of error in point samples, such as those

  7. 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.

  8. 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

  9. [Study on Tritium Content in Soil at Sites of Nuclear Explosions on the Territory of Semipalatinsk Test Site].

    PubMed

    Timonova, L V; Lyakhova, O N; Lukashenko, S N; Aidarkhanov, A O

    2015-01-01

    As a result of investigations carried out on the territory of Semipalatinsk Test Site, tritium was found in different environmental objects--surface and ground waters, vegetation, air environment, and snow cover. The analysis of the data obtained has shown that contamination of environmental objects at the Semipalatinsk Test Site with tritium is associated with the places where underground nuclear tests were performed. Since tritium can originate from an activation reaction and be trapped by pock particles during a test, it was decided to examine the soil in the sites where surface and excavation tests took place. It was found that the concentration of tritium in soil correlates with the concentration of europium. Probably, the concentration of tritium in the soil depends on the character and yield of the tests performed. Findings of the study have revealed that tritium can be found in soil in significant amounts not only in sites where underground nuclear tests took place but also in sites where surface and excavation nuclear tests were carried out. PMID:26964352

  10. 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 line