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1

Understanding Rubredoxin Redox Sites by Density Functional Theory Studies of Analogues  

PubMed Central

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

Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko

2012-01-01

2

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

PubMed

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

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

2007-04-19

3

Lessons from Natural CO2 Leakage Analogue Site Studies and their Application to Secure CO2 Storage and Monitoring  

NASA Astrophysics Data System (ADS)

At CO2 injection sites, CO2 leakage from the storage formation could be catastrophic. CO2 is a highly compressible fluid, typically injected at high pressure and temperature conditions. If this compressed CO2 reaches highly permeable conduits such as faults and fractures, CO2 could leak unabated to other formations (e.g. fresh water aquifers) and/or to the surface. Assuming a fast-flow path to the surface, CO2 escaping from the storage formation instantaneously reaches the surface while experiencing adiabatic expansion, which results in Joule-Thomson cooling. The addressed eruptive mechanisms are analogues to natural CO2 eruption mechanisms, which are found in CO2-driven cold-water geysers around the world. A notable example of a CO2-driven cold-water geyser is the Crystal Geyser in central Utah. The fluid mechanics of this regularly erupting geyser was investigated by instrumenting its conduit with pressure, temperature, pH, EC, and dissolved oxygen sensors, measuring every 1 minute during and between eruptions. Results of these measurements suggest that the time-scale of a single-eruption cycle is composed of four successive eruption types with two recharge periods ranging from 30 to 40 hours. Current eruption patterns exhibit a bimodal distribution although previous measurements and anecdotal evidence suggests that this pattern was different prior to recent seismic activity. This cold geyser's eruptions are regular and predictable, and reflect pressure, temperature, EC, pH, and dissolved oxygen changes resulting from Joule-Thomson cooling, endothermic CO2 exsolution, and exothermic CO2 dissolution. Specifically, the perturbation of pressure and temperature data observed at the Crystal Geyser suggested the possibility of using temperature sensing technology within the observation well at the engineered CO2 sequestration site. With the lessons learned from the Crystal Geyser studies, we established the theoretical framework of temperature changes caused by CO2 related chemical reactions in the observation wells and tested with numerical simulation tools, which predicted thermal processes caused by solid NaCl precipitation, buoyancy-driven supercritical CO2 migration, and potential non-isothermal effects. Simulation results suggest that these processes - solid NaCl precipitation, buoyancy effects, Joule-Thomson cooling, water vaporization, and exothermic CO2 reactions - are strongly coupled and dynamic (transient). Overall, a fundamental understanding of potential thermal processes investigated through this research will be beneficial in the collection and analysis of temperature signals collectively measured from monitoring wells.

Han, W.; McPherson, B. J.; Kim, K.; Chae, G.; Yum, B.

2011-12-01

4

Infrared study of synthetic peptide analogues of the calcium-binding site III of troponin C: The role of helix F of an EF-hand motif.  

PubMed

The EF-hand motif (helix-loop-helix) is a Ca(2+) -binding domain that is common among many intracellular Ca(2+) -binding proteins. We applied Fourier-transform infrared spectroscopy to study the synthetic peptide analogues of site III of rabbit skeletal muscle troponin C (helix E-loop-helix F). The 17-residue peptides corresponding to loop-helix F (DRDADGYIDAEELAEIF), where one residue is substituted by the D-type amino acid, were investigated to disturb the ?-helical conformation of helix F systematically. These D-type-substituted peptides showed no band at about 1555 cm(-1) even in the Ca(2+) -loaded state although the native peptide (L-type only) showed a band at about 1555 cm(-1) in the Ca(2+) -loaded state, which is assigned to the side-chain COO(-) group of Glu at the 12th position, serving as the ligand for Ca(2+) in the bidentate coordination mode. Therefore, helix F is vital to the interaction between the Ca(2+) and the side-chain COO(-) group of Glu at the 12th position. Implications of the COO(-) antisymmetric stretch and the amide-I' of the synthetic peptide analogues of the Ca(2+) -binding sites are discussed. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 342-347, 2013. PMID:23426577

Nara, Masayuki; Morii, Hisayuki; Tanokura, Masaru

2013-05-01

5

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

SciTech Connect

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

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

1988-06-28

6

The geology of Australian Mars analogue sites  

NASA Astrophysics Data System (ADS)

Australia has numerous landforms and features, some unique, that provide a useful reference for interpreting the results of spacecraft orbiting Mars and exploring the martian surface. Examples of desert landforms, impact structures, relief inversion, long-term landscape evolution and hydrothermal systems that are relevant to Mars are outlined and the relevant literature reviewed. The Mars analogue value of Australia's acid lakes, hypersaline embayments and mound spring complexes is highlighted along with the Pilbara region, where the oldest convincing evidence of life guides exploration for early life on Mars. The distinctive characteristics of the Arkaroola Mars Analogue Region are also assessed and opportunities for future work in Australia are outlined.

West, Michael D.; Clarke, Jonathan D. A.; Thomas, Matilda; Pain, Colin F.; Walter, Malcolm R.

2010-03-01

7

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

NASA Astrophysics Data System (ADS)

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

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

2004-06-01

8

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

NASA Astrophysics Data System (ADS)

Combined ?-XRF, ?-XAFS, and ?-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 ?-XRF/?-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.

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

2007-02-01

9

Space analogue studies in Antarctica  

NASA Astrophysics Data System (ADS)

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.

Lugg, D.; Shepanek, M.

1999-09-01

10

Probing the steric requirements of the ?-aminobutyric acid aminotransferase active site with fluorinated analogues of vigabatrin.  

PubMed

We have synthesized three analogues of 4-amino-5-fluorohexanoic acids as potential inactivators of ?-aminobutyric acid aminotransferase (GABA-AT), which were designed to combine the potency of their shorter chain analogue, 4-amino-5-fluoropentanoic acid (AFPA), with the greater enzyme selectivity of the antiepileptic vigabatrin (Sabril®). Unexpectedly, these compounds failed to inactivate or inhibit the enzyme, even at high concentrations. On the basis of molecular modeling studies, we propose that the GABA-AT active site has an accessory binding pocket that accommodates the vinyl group of vigabatrin and the fluoromethyl group of AFPA, but is too narrow to support the extra width of the distal methyl group in the synthesized analogues. PMID:23306054

Juncosa, Jose I; Groves, Andrew P; Xia, Guoyao; Silverman, Richard B

2012-12-20

11

Carbon storage at defect sites in mantle mineral analogues  

NASA Astrophysics Data System (ADS)

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

Wu, Jun; Buseck, Peter R.

2013-10-01

12

In vivo competition studies with analogues of 3-quinuclidinyl benzilate  

Microsoft Academic Search

Among ligands that bind to the ..cap alpha..- and ..beta..-adrenoceptors and to the muscarinic acetylcholine receptor (m-AChR), those that bind to the latter have the best properties for external detection of receptor sites by gamma-camera imaging. To develop the optimal radiotracer, nonradioactive analogues of 3-quinuclidinyl benzilate (I) were tested in vivo displacement studies with (-)-(³H)I to determine their ability to

William C. Eckelman; M. Grissom; J. Conklin; W. J. Rzeszotarski; R. E. Gibson; B. E. Francis; E. M. Jagoda; R. Eng; R. C. Reba

1984-01-01

13

Martian analogue test site - pilbara craton, western Australia  

NASA Astrophysics Data System (ADS)

All exploration for life elsewhere depends on extrapolation from our knowledge of Earth. If the target is former microbial life, for example on Mars, there is no better analogue on Earth than the 3.5 billion year old rocks of the Pilbara region, Western Australia. This area is home to signs of the earliest life on Earth in the form of microbe, many famous stromatolitic horizons and carbon isotope biosignatures. These occur in a volcanic terrain, with weathering and hydrothermal alteration, which also has some similarity to Mars. The geology of this region is known in detail after decades of mapping and other studies. Current work includes studies to resolve disputes about the biogenicity of the microfossils and stromatolites. On balance, biological origins are most likely. In any event, problems of demonstrating biogenicity on other planets will be far more severe, and the work on the Pilbara materials will illuminate those problems. Also underway is mineral mapping of the volcanic, hydrothermal and fossiliferous units using both airborne and hand-held short-wave infrared spectrometers, We are able to map the fossiliferous units using this technique and contend that it would be a powerful exploration technique on Mars and elsewhere. Using the Pilbara as an analogue for other bodies in the Solar System can extend to using it as a place to test instrument packages under realistic conditions. The region has good air and road access, and good supporting infrastructure.

Brown, A.; Allwood, A.; Walter, M. R.; van Kranendonk, M.

14

Analogue model studies of induction effects at auroral latitudes  

Microsoft Academic Search

In addition to field observations and numerical models, geomagnetic induction effects can be studied by scaled analogue model experiments. We present here results of analogue model studies of the auroral electrojet with an Earth model simulating the Arctic Ocean and inland conductivity structures in northern Fennoscandia. The main elements of the analogue model used were salt water simulating the host

A. Viljanen; L. Szarka

1995-01-01

15

Biological studies of martian soil analogues  

NASA Astrophysics Data System (ADS)

Results of the study of the influence of Martian soil analogues, both as described by American scientists and as prepared by us, and of hydrogen peroxide on the viability of microorganisms are presented. The experiments were carried out using mixtures of soil analogues with desert soil and black earth (chernozem) samples, and pure cultures of microorganism. Microorganisms capable of withstanding a concentration of hydrogen peroxide in the medium as high as 1.5-2.0% were isolated. None of the 40 strains of microorganisms studied, all belonging to different systematic and physiological groups, exhibited growth inhibition on solid media in the presence of Martian soil analogues. In view of the fact that Martian soil cannot contain microorganisms in great quantities, we suggest using electroadsorption for their concentration, to make detection reliable. A device was designed for this purpose, using the principle of electroadsorption on a polarisable carrier (sterile cotton wool or cheesecloth). The concentrated suspension of microorganisms thus obtained was then characterized by various physicochemical methods.

Imshenetsky, A. A.; Murzakov, B. G.; Evdokimova, M. D.; Dorofeyeva, I. K.

16

Origins, closed system formation and preservation of calcites in glaciated crystalline bedrock: evidence from the Palmottu natural analogue site, Finland  

Microsoft Academic Search

A study of the geochemistry of fracture filling calcite from the Palmottu research site, a U–Th deposit located about 100 km NW of Helsinki, Finland, was part of a comprehensive natural analogue research project considering the migration of U in the crystalline bedrock environment. Fracture filling minerals act as records of the paleohydrological and chemical conditions and therefore provide insight

Alexander Blyth; Shaun Frape; Timo Ruskeeniemi; Runar Blomqvist

2004-01-01

17

Site Specific Incorporation of Amino Acid Analogues into Proteins In Vivo.  

National Technical Information Service (NTIS)

The goal of this project is to develop methods for the site-specific insertion in vivo of one or more amino acid analogues into proteins in eubacteria and in eukaryotes. The amino acids to be used include those that are photoactivatable, those that are fl...

U. L. RajBhandary

2010-01-01

18

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

PubMed

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. PMID:21387054

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

2011-03-09

19

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

USGS Publications Warehouse

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

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

1992-01-01

20

Site-specific PEGylation of bone morphogenetic protein-2 cysteine analogues.  

PubMed

Three cysteine analogues of bone morphogenetic protein (BMP)-2, BMP2A2C, BMP2N56C, and BMP2E96C, were generated in order to enable the attachment of SH-reactive poly(ethylene glycol) (PEG) at specific sites. Three different approaches (Ap) were used for SH-specific PEGylation: (Ap1) reaction of glutathione activated proteins with thiol PEG; (Ap2) reaction of DTT reduced proteins with orthopyridyl disulfide PEG; (Ap3) reaction of DTT reduced proteins with maleimide PEG. Non-, mono-, and di-PEGylated BMP-2 analogues could be separated by RP-HPLC. Trypsin digestion of PEGylated proteins and Trypsin and GluC double-digestion of N-ethylmaleimide-labeled proteins confirmed that the modifications were site-specific. Surface plasmon resonance analysis of type I and type II receptor binding of the PEGylated BMP-2 analogues revealed that all three PEGylation approaches were equivalent. PEGylation at positions 2 and 96 caused a similar decrease in receptor affinity. PEGylation at position 56 resulted in a larger decrease in affinity for both types of receptors. Mono-PEGylated BMP-2 analogues exhibited intermediate affinities in comparison with unmodified and di-PEGylated proteins. However, the biological activity of the PEGylated BMP-2 analogues as measured in alkaline phosphatase assay was higher than BMP-2 wild-type for the PEGylated BMP2A2C, slightly reduced for the BMP2N56C, and strongly reduced for the BMP2E96C. These results taken together indicate that specific attachment of PEG at engineered sites of BMP-2 is possible and that the attachment site is critical for biological activity. Furthermore, the biological activity of PEGylated BMP-2 analogues in cell culture seems to be determined not only by receptor affinity, but also by other factors such as protein solubility and stability. It is also discussed that the attached PEG interferes with the binding of BMP-2 to modulator proteins, co-receptors, or heparinic sites of proteoglycans in the extracellular matrix. PMID:20886828

Hu, Junli; Duppatla, Viswanadham; Harth, Stefan; Schmitz, Werner; Sebald, Walter

2010-10-20

21

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

SciTech Connect

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.

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

2008-10-25

22

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

NASA Astrophysics Data System (ADS)

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

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

23

Thermodynamic and kinetic studies of competitive inhibition of adenosine deaminase by ring opened analogues of adenine nucleoside.  

PubMed

Ring opened analogues of adenine nucleosides substituted at the ninth adenine positions, with and without esterification (compounds I and II), have been studied kinetically and thermodynamically at various temperatures in order to determine the sites of ring opened analogues. These are deemed to be important for binding to the adenosine deaminase. Adenosine deaminase is found to bind more strongly to compound I than to compound II, therefore compound I is a stronger inhibitor than II, because the position of (5') OH on the ribose moiety decreases the inhibitory strength on the ring opened analogue. PMID:8485104

Moosavi-Movahedi, A A; Rahmani, Y; Hakimelahi, G H

1993-04-01

24

Preptin analogues: chemical synthesis, secondary structure and biological studies.  

PubMed

Peptide hormones that modulate insulin secretion have been recognized to have therapeutic potential, with peptides such as amylin (pramlintide acetate, Symlin) and exendin-4 (exenatide, Byetta) now commercially available. Preptin is a peptide that has been shown to increase insulin secretion in vitro and in vivo. Here, we describe the first chemical synthesis and analysis of a short series of preptin analogues based on the rat preptin sequence. Phe 21 in the preptin sequence was substituted with the non-protein amino acids D-Phe, D-Hphe, 3-aminobenzoic acid and 1-aminocyclooctane-1-carboxylic acid, which rendered the preptin analogues resistant to chymotryptic protease hydrolysis at this position. Substitution of Phe 21 with these non-protein amino acids did not abrogate the insulin secretory effect of preptin, with analogues showing a similar dose-dependent effect on insulin secretion from ?TC6-F7 mouse ?-cells in both the presence and absence of glucose as unmodified rat preptin. Further studies on the stability of the preptin analogues and their effect on insulin secretion are in progress. PMID:23745966

Buchanan, Christina M; Peng, Zhenzhen; Cefre, Aiko; Sarojini, Vijayalekshmi

2013-10-01

25

Geochemical assessment of an analogue site for an engineered landform at Ranger Uranium Mine, Northern Territory, Australia  

Microsoft Academic Search

An essential element in identifying sites as analogues for the long-term development of soils and vegetation on engineered\\u000a landforms of the rehabilitated Ranger Uranium Mine, Northern Territory, Australia, is the need to match rocks. Comparison\\u000a of the geochemistry of rocks from the waste rock dump of Ranger Uranium Mine and the potential analogue site of Tin Camp Creek\\u000a area, Western

S. J. Riley; J. F. Rich

1998-01-01

26

Interrelation between high and low affinity tentoxin binding sites in chloroplast F1-ATPase revealed by synthetic analogues.  

PubMed

Eight synthetic analogues of tentoxin (cyclo-(L-N-MeGlu1-L-Leu2-N-MeDeltaZPhe3-Gly4)) modified in residues 1, 2, and 3 were checked for their ability to inhibit and reactivate the ATPase activity of the activated soluble part of chloroplast ATP synthase. The data were consistent with a model involving two binding sites of different affinities for the toxins. The occupancy of the high affinity site (or tight site) gave rise to an inactive complex, whereas filling both sites (tight + loose) gave rise to a complex of variable activity, dependent on the toxin analogue. Competition experiments between tentoxin and nonreactivating analogues allowed discrimination between the absence of binding and a nonproductive binding to the site of lower affinity (or loose site). The affinity for the loose site was not affected significantly by the modifications of the tentoxin molecule, whereas the affinity for the tight site was found notably changed. Increasing the size of side chain 1 or 2 and introducing a net electrical charge both resulted in a decrease of affinity for the tight site, but the second change dominated the first one. The activity of different ternary complexes enzyme-tentoxin-analogue depended on the nature of the toxin bound on each site and not only on that bound on the loose site. This demonstrates that the reactivation process results from an interaction, direct or not, between these two binding sites. Possible molecular mechanisms are discussed. PMID:9452452

Santolini, J; Haraux, F; Sigalat, C; Munier, L; André, F

1998-02-01

27

Laboratory studies of cometary ice analogues  

NASA Astrophysics Data System (ADS)

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.

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

1989-12-01

28

Interaction of benzylidene-anabaseine analogues with agonist and allosteric sites on muscle nicotinic acetylcholine receptors  

PubMed Central

Background and purpose Benzylidene-anabaseines (BAs) are partial agonists of the ?7 nicotinic acetylcholine receptor (nAChR) but their mechanism(s) of action are unknown. Our study explores several possibilities, including direct interactions of BAs with the nAChR channel. Experimental approach Functional and radioligand-binding assays were used to examine the interaction of two BA analogues, 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) and its primary metabolite 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine (4OH-DMXBA) with both agonist and non-competitive antagonist (NCA)-binding sites on muscle-type nAChRs. Key results Both BAs non-competitively inhibited ACh activation of human fetal muscle nAChRs and sterically inhibited the specific binding of the NCAs [piperidyl-3,4-3H(N)]-(N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) and [3H]dizocilpine to Torpedo nAChRs in the desensitized state. These compounds modulated [3H]tetracaine, [14C]amobarbital and [3H]TCP binding to resting nAChRs by allosteric mechanisms. Both BAs enhanced [3H]TCP binding when the nAChR was initially in the resting but activatable state, suggesting that both compounds desensitized the Torpedo nAChR. Although DMXBA failed to activate human fetal muscle nAChRs, 4OH-DMXBA was found to be a partial agonist. [3H]Nicotine competition-binding experiments confirmed that 4OH-DMXBA has higher affinity than DMXBA for the agonist sites, and that DMXBA is also a competitive antagonist. Conclusions and implications 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine is a partial agonist for human fetal muscle nAChRs, whereas DMXBA only has competitive and NCA activities. The NCA-binding site for BAs overlaps both the phencyclidine-and dizocilpine-binding sites in the desensitized Torpedo nAChR ion channel. The desensitizing property of BAs suggests another possible mode of non-competitive inhibition in addition to direct channel-blocking mechanisms.

Arias, HR; Xing, H; MacDougall, K; Blanton, MP; Soti, F; Kem, WR

2009-01-01

29

Physical-property measurements on samples from an analogue Soviet Nuclear Test Site: Northern Maine. Technical report  

SciTech Connect

The Joint Verification Experiments (JVE) between the US and USSR were designed to improve yield estimates and verification methods for underground nuclear tests. Members of US team retrieved cores of underground rock samples from Semipalatinsk test site. The mechanical properties of these rocks are being measured in a number of US laboratories. DARPA has begun geological and geophysical characterization of a potential analogue test site here in the U.S. It was decided to first measure a number of mechanical properties of end member samples retrieved from the analogue site to compare with similar lithologies from USSR. A team of scientists from USGS, LDGO, and Smithsonian Institute traveled to No. Maine and studied the geology of the Mt. Katahdin region. Samples of rocks were selected for testing. The Lamont test compared strengths of end member samples under different confining pressures, strain rates, saturation conditions and pore pressures. The two selected end members were Katahdin granite and a tuffaceous sandstone. The same tests were conducted on Sierra White granite for comparison with a standard. (Katahdin granite is really a quartz monzonite).

Biegel, R.L.; Scholz, C.H.

1991-04-11

30

Interaction of pentylsarin analogues with human acetylcholinesterase: A kinetic study  

Microsoft Academic Search

Previous kinetic studies investigating the interactions between human acetylcholinesterase (AChE), structurally different organophosphorus compounds (OP) and oximes did not reveal a conclusive structure–activity relationship of the different reactions. The only exception was for a homologous series of methylphosphonofluoridates bearing C1–C4 O-n- or O-i-alkyl residues. Hence, it was tempting to investigate the kinetic interactions between different pentylsarin analogues, human AChE and

F. Worek; N. M. Herkert; M. Koller; N. Aurbek; H. Thiermann

2009-01-01

31

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

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

32

Metallic fluoride complexes as phosphate analogues for structural and mechanistic studies of phosphoryl group transfer enzymes.  

PubMed

There have been intensive efforts to try to understand the details of phosphoryl transfer reactions extending from nonenzymatic (or enzyme model) systems to the mechanisms of the enzyme catalysed reactions. As phosphate analogues, few metallic fluorides AlFx, BeFx and MgFx affect the activity of a variety of phosphoryl transfer enzymes, and it is accepted that these small inorganic complexes are useful chemical probes for structural and mechanistic studies in enzymology because they are able to mimic phosphoryl group in ground state (BeFx) as well as in transition state (AlFx,MgFx). Al3+ and Be2+ tend to form stable complexes with different fluoride anions (x = 1 to 4) spontaneously in aqueous solution but Mg2+ does not. BeFx geometry is strictly tetrahedral resembling the phosphate ground state when bound to an acyl group of protein active site (phosphorylated acyl groups are unstable otherwise), or the Michaelis complex when BeFx concominantly with nucleoside diphosphate replaces g-phosphate group in nucleoside triphosphate sites. AlFx and MgFx are identified as enzymatic analogues of phosphoryl transition state where both are able to form different coordination geometries within the enzyme active sites: trigonal bipyramidal (AlF3 and MgF3-) or octahedral (AlF4- or MgF42-). The geometry and charge of MgF3- are the best suited to mimicking the trigonal planar PO3- moiety of phosphoryl transfer transition state but MgF3- does not, unlike aluminum and beryllium fluoride complexes, exists in solution and can be assembled and stabilized in suitable active site only. Therefore it is particularly interesting to characterize as a potentially highly accurate transition state analogue and may be the best reagent of choice for studying phosphoryl transfer reactions in future. PMID:24061722

Goli?nik, Marko

2010-06-01

33

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

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 selective ligand is compound 23, which displayed a K(i) value of 0.06 nM and has essentially no activity at the DAT or NET. The present results have important implications for drug addiction as well as a number of psychiatric diseases. PMID:11960503

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

2002-04-25

34

Synthesis, characterization and biological studies of diosgenyl analogues.  

PubMed

A series of optical amino acid diosgenyl esters and diosgenyl salicylate conjugates were designed and synthesized to develop new anticancer and anti-inflammatory agents. The analogue 9c that contains an 6-aminohexanoic acid residue at C-3 of diosgenin exhibits higher potency against all three tumor cell lines with IC(50) values ranging from 4.7 ?M in C26 cells to 14.6 ?M in Hep G2 cells. In addition, seven of newly synthesized compounds significantly inhibit xylene-induced ear edema and exhibit comparable or better anti-inflammatory activities than those of diosgenin and aspirin. Furthermore, preliminary structure-activity relationship studies demonstrate that diosgenyl salicylate conjugates have stronger anti-inflammatory activities than amino acid diosgenyl esters. PMID:23153797

Huang, Baozhan; Du, Dan; Zhang, Rui; Wu, Xiaohua; Xing, Zhihua; He, Yang; Huang, Wen

2012-10-23

35

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

SciTech Connect

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.

McCarthy, J.F.

1994-10-01

36

Mutation of a conserved residue enhances the sensitivity of analogue-sensitised kinases to generate a novel approach to the study of mitosis in fission yeast.  

PubMed

The chemical genetic strategy in which mutational enlargement of the ATP-binding site sensitises of a protein kinase to bulky ATP analogues has proved to be an elegant tool for the generation of conditional analogue-sensitive kinase alleles in a variety of model organisms. Here, we describe a novel substitution mutation in the kinase domain that can enhance the sensitivity of analogue-sensitive kinases. Substitution of a methionine residue to phenylalanine in the +2 position after HRDLKxxN motif of the subdomain VIb within the kinase domain markedly increased the sensitivities of the analogue-sensitive kinases to ATP analogues in three out of five S. pombe kinases (i.e. Plo1, Orb5 and Wee1) that harbor this conserved methionine residue. Kinome alignment established that a methionine residue is found at this site in 5-9% of kinases in key model organisms, suggesting that a broader application of this structural modification may enhance ATP analogue sensitivity of analogue-sensitive kinases in future studies. We also show that the enhanced sensitivity of the wee1.as8 allele in a cdc25.22 background can be exploited to generate highly synchronised mitotic and S phase progression at 36°C. Proof-of-principle experiments show how this novel synchronisation technique will prove of great use in the interrogation of the mitotic or S-phase functions through temperature sensitivity mutation of molecules of interest in fission yeast. PMID:23986474

Tay, Ye-Dee; Patel, Avinash; Kaemena, Daniel F; Hagan, Iain M

2013-08-28

37

Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains.  

PubMed

Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains. PMID:12161147

Cheng, Yuan; Zhang, Fengqi; Rano, Thomas A; Lu, Zhijian; Schleif, William A; Gabryelski, Lori; Olsen, David B; Stahlhut, Mark; Rutkowski, Carrie A; Lin, Jiunn H; Jin, Lixia; Emini, Emilio A; Chapman, Kevin T; Tata, James R

2002-09-01

38

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

SciTech Connect

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.

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

1988-10-01

39

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

NASA Astrophysics Data System (ADS)

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.

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

2012-02-01

40

Conformational analyses and MO studies of f152A1 and its analogues as potent protein kinase inhibitors.  

PubMed

f152A1 was isolated from a fermentation broth of Curvularia verruculosa and characterized as a potent inhibitor of TNFalpha transcription, with anti-inflammatory activity. f152A1 and several analogues displayed inhibitory activity against the MAP kinases ERK2 and MEK1 in in vitro kinase assays. Through SAR studies on f152A1 and analogues prepared via total synthesis, we have identified structural features that contribute to inhibitory activity. To rationalize these results and to aid in the discovery process, a combination of high temperature molecular dynamics and MOPAC AM1 semiempirical molecular orbital method studies was used in studies that yielded a postulated active conformation, M1(8). This active conformation M1(8) reflects a high degree of conformational similarity among f152A1 and its more potent analogues. In view of the highly reactive cis-enone moiety in the flexible 14-membered resorcylic acid lactone ring of f152A1, the chemical reactivities of the enone moieties in various analogues were assessed by molecular orbital calculations. The enone reactivity analyses suggested that these inhibitors were prone to Michael addition at the alpha,beta-unsaturated ketone moiety and might chemically react with cysteine residues in the ATP-binding site of MAP kinases. Reactivity of the cis-enone moiety and the M1(8) conformation make important contributions to the inhibitory activity of MAP kinases. PMID:19995092

Ikemori-Kawada, Megumi; Kawai, Takatoshi; Goto, Masaki; Wang, Yuan John; Kawakami, Yoshiyuki

2009-12-01

41

Emotions and Habitability study in Moon Mars Analogue.  

NASA Astrophysics Data System (ADS)

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

Mertens, Alexandre; Lia Schlacht, Irene

42

Okinoshima site study  

NASA Astrophysics Data System (ADS)

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

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

2011-07-01

43

Lithic microbial communities from a Mars analogue site in Utah desert  

NASA Astrophysics Data System (ADS)

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

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

2012-09-01

44

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

NASA Astrophysics Data System (ADS)

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

Felix, C. V.; Gini, A.

45

COX-2 structural analysis and docking studies with gallic acid structural analogues.  

PubMed

Emblica officinalis is an ayurvedic herbal plant. The compounds isolated from this plant have good inhibitory effects against cyclooxygenase-2 (COX-2), among them gallic acid (GA) has the highest inhibitory effect. COX-2 (1.14.99.1) is an oxidoreductase having a role in prostaglandin biosynthesis, inflammatory responses and in cardiovascular events. COX-2 has gained special focus on research since past few decades. The sequence and structural studies reveals Mus musculus COX-2 shares the common conserved sequence and structural pattern with human COX-2. Molecular modeling and docking analysis with gallic acid and their structural analogues showed that 2-[(2E,4E)-hexa-2,4-dienyl]-3,4,5-trihydroxybenzoic acid, (3,4,5-trihydroxybenzoyl) 3,4,5-trihydroxybenzoate and 3-hydroxy-4-sulfooxybenzoic acid are more interactive and binding strongly than gallic acid at active site. Hence these three compounds should be considered as strong inhibitors for COX-2. PMID:23483789

Amaravani, M; Prasad, Nirmal K; Ramakrishna, Vadde

2012-12-10

46

Study of analogue states in 52 Cr through proton capture by 51 V  

Microsoft Academic Search

?-Ray yield function has been studied for the proton capture by vanadium in the proton energy range 720–1300 keV. Isobaric\\u000a analogues of low lying states in52V have been identified. At two resonances the?-decay and?-ray angular distributions have been obtained and the branching ratios and the multipole mixing ratios have been deduced.\\u000a The analogue-antianalogue M1 transition in52Cr is found to be

A Roy; K V K Iyengar; M L Jhingan; S K Bhattacherjee

1974-01-01

47

Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.  

PubMed

A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers. PMID:12213053

Houlihan, William J; Kelly, Lawrence; Pankuch, Jessica; Koletar, Judith; Brand, Leonard; Janowsky, Aaron; Kopajtic, Theresa A

2002-09-12

48

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

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

49

A novel kynurenic acid analogue: a comparison with kynurenic acid. An in vitro electrophysiological study.  

PubMed

Kynurenic acid is an endogenous product of the tryptophan metabolism, and as a broad-spectrum antagonist of excitatory amino acid receptors may serve as a protective agent in neurological disorders. The use of kynurenic acid as a neuroprotective agent is rather limited, however, because it has only restricted ability to cross the blood-brain barrier. Accordingly, new kynurenic acid analogues which can readily cross the blood-brain barrier and exert their complex anti-excitotoxic activity are greatly needed. Such a novel analogue, 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride, has been developed and tested. In an in vitro electrophysiological study, in which its properties were compared with those of kynurenic acid, the new analogue behaved quite similarly to kynurenic acid: in the micromolar range, its administration led to a decrease in the amplitudes of the field excitatory postsynaptic potentials in the CA1 region of the hippocampus, while in nanomolar concentrations it did not give rise to inhibition, but, in fact, facilitated the field excitatory postsynaptic potentials. Moreover, the new analogue demonstrated similar protective action against PTZ-induced facilitation to that observed after kynurenic acid administration. The findings strongly suggest that the neuroactive effects of the new analogue are comparable with those of kynurenic acid, but, in contrast with kynurenic acid, it readily crosses the blood-brain barrier. The new analogue may therefore be considered a promising candidate for clinical studies. PMID:19953278

Marosi, Máté; Nagy, Dávid; Farkas, Tamás; Kis, Zsolt; Rózsa, Eva; Robotka, Hermina; Fülöp, Ferenc; Vécsei, László; Toldi, József

2009-12-02

50

Structure-based design, synthesis, and A-site rRNA cocrystal complexes of functionally novel aminoglycoside antibiotics: C2" ether analogues of paromomycin.  

PubMed

A series of 2"-O-substituted ether analogues of paromomycin were prepared based on new site-selective functionalizations. X-ray cocrystal complexes of several such analogues revealed a new mode of binding in the A-site rRNA, whereby rings I and II adopted the familiar orientation and position previously observed with paromomycin, but rings III and IV were oriented differently. With few exceptions, all of the new analogues showed potent inhibitory activity equal or better than paromomycin against a sensitive strain of S. aureus. Single digit microM MIC values were obtained against E. coli, with some of the ether appendages containing polar or basic end groups. Two analogues showed excellent survival rate in a mouse septicemia protection assay. Preliminary histopathological analysis of the kidney showed no overt signs of toxicity, while controls with neomycin and kanamycin were toxic at lower doses. PMID:17458946

Hanessian, Stephen; Szychowski, Janek; Adhikari, Susanta Sekhar; Vasquez, Guillermo; Kandasamy, Pachamuthu; Swayze, Eric E; Migawa, Michael T; Ranken, Ray; François, Boris; Wirmer-Bartoschek, Julia; Kondo, Jiro; Westhof, Eric

2007-04-26

51

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

PubMed Central

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.

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

2008-01-01

52

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

PubMed Central

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

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

2011-01-01

53

Mechanistic studies of substrate-assisted inhibition of ubiquitin-activating enzyme by adenosine sulfamate analogues.  

PubMed

Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate intermediate and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2). MLN4924 is an adenosine sulfamate analogue that was identified as a selective, mechanism-based inhibitor of NEDD8-activating enzyme (NAE), another E1 enzyme, by forming a NEDD8-MLN4924 adduct that tightly binds at the active site of NAE, a novel mechanism termed substrate-assisted inhibition (Brownell, J. E., Sintchak, M. D., Gavin, J. M., Liao, H., Bruzzese, F. J., Bump, N. J., Soucy, T. A., Milhollen, M. A., Yang, X., Burkhardt, A. L., Ma, J., Loke, H. K., Lingaraj, T., Wu, D., Hamman, K. B., Spelman, J. J., Cullis, C. A., Langston, S. P., Vyskocil, S., Sells, T. B., Mallender, W. D., Visiers, I., Li, P., Claiborne, C. F., Rolfe, M., Bolen, J. B., and Dick, L. R. (2010) Mol. Cell 37, 102-111). In the present study, substrate-assisted inhibition of human UAE (Ube1) by another adenosine sulfamate analogue, 5'-O-sulfamoyl-N(6)-[(1S)-2,3-dihydro-1H-inden-1-yl]-adenosine (Compound I), a nonselective E1 inhibitor, was characterized. Compound I inhibited UAE-dependent ATP-PP(i) exchange activity, caused loss of UAE thioester, and inhibited E1-E2 transthiolation in a dose-dependent manner. Mechanistic studies on Compound I and its purified ubiquitin adduct demonstrate that the proposed substrate-assisted inhibition via covalent adduct formation is entirely consistent with the three-step ubiquitin activation process and that the adduct is formed via nucleophilic attack of UAE thioester by the sulfamate group of Compound I after completion of step 2. Kinetic and affinity analysis of Compound I, MLN4924, and their purified ubiquitin adducts suggest that both the rate of adduct formation and the affinity between the adduct and E1 contribute to the overall potency. Because all E1s are thought to use a similar mechanism to activate their cognate ubiquitin-like proteins, the substrate-assisted inhibition by adenosine sulfamate analogues represents a promising strategy to develop potent and selective E1 inhibitors that can modulate diverse biological pathways. PMID:21969368

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

2011-10-03

54

Studies on vitamin D (calciferol) and its analogues. 10. Side-chain analogues of 25-hydroxyvitamin D3.  

PubMed

A homologous series of side-chain analogues of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol) in which the length of the side chain is modified while maintaining its characteristic tertiary hydroxyl moiety has been synthesized. The following five analogues have been prepared and characterized: pentanor-25-OH-D3 (2a), trinor-25-OH-D3 (2b), dinor-25-OH-D3 (2c), nor-25-OH-D3 (2d), and homo-25-OH-D3 T2e). Biological assays in vivo of intestinal calcium absorption and bone calcium mobilization in the chick of the five analogues revealed that the homo analogue 2e exhibited a significant biological response relative to the -D (vitamin D3) control. Compared to the natural vitamin D3, 2e is as active in its ability to mobilize bone calcium and is about half as effective in stimulating intestinal calcium transport. The remaining analogues (2a-d) exhibited no significant activity in either assay, although the nor analogue 2d was previously observed to exhibit antimetabolite activity. PMID:833826

Johnson, R L; Carey, S C; Norman, A W; Okamura, W H

1977-01-01

55

An analogue model study of EM induction in the Japan-Korea-China region  

NASA Astrophysics Data System (ADS)

Electromagnetic induction in the coastal region of Japan-Korea-China is studied using a scaled laboratory analogue model. The model includes a simulation of the known ocean bathymetry, the complex coastlines and the deep conductive Pacific trench. Model measurements of the electromagnetic field components are carried out for simulated periods of 15-180 min for two mutually perpendicular polarizations of a uniform horizontal inducing source field. In-phase and quadrature Bx, By, and Bz model measurements are examined in detail for a series of traverses over Japan, the Korean peninsula, and the coastal region of China and the U.S.S.R. Large anomalous in-phase model magnetic fields are observed over the Korea-Japan strait for E-polarization and over the Bohai, Tsugaru, and La Perouse straits for B-polarization owing to current channelling. The significant responses observed at short periods over the peninsulas in the shallow coastal areas decrease with increasing period. Large gradients in the in-phase B2 field are observed over Japan for E-polarization for both short and long periods owing to the effects of induced currents in the surrounding oceans. Thus induction arrow responses over all regions of Japan are expected to show the dominant effects of the ocean. A comparison of analogue model and field site induction arrows over the Kii peninsula of Japan indicates that, the ocean effects alone cannot fully account for the observed responses. The differences in the model and field results can be attributed to lateral inhomogeneities in the conductivity structure under Japan.

Meng, Z.; Dosso, H. W.

56

Phase I study of the mitomycin C analogue BMS-181174.  

PubMed Central

BMS-181174 is an aminodisulphide derivative of Mitomycin C (MMC) with activity against a range of tumour cell lines and xenografts, including MMC-resistant tumours. In a phase I study of 82 patients with confirmed malignancy, we administered BMS-181174 at doses of 0.8-75 mg m(-2) by intravenous injection every 28 days. At least three patients were evaluated at each dose level, and 174 courses were administered. The pharmacokinetics were dose linear at BMS-181174 doses of 11.5-75 mg m(-2) and the drug appeared to undergo wide distribution. The maximum-tolerated dose was 65 mg m(-2) in previously treated patients and 75 mg m(-2) in chemotherapy-naive cases. The dose-limiting toxicity was myelosuppression, particularly thrombocytopenia, which was prolonged and cumulative. Three patients treated at 65-75 mg m(-2) died suddenly with evidence of pneumonia/pneumonitis, thought to be drug-related. Other toxicities included thrombophlebitis, possible cardiotoxicity (asymptomatic, reversible decline in left ventricular function) and renal impairment. The partial response rate was 5% (4 out of 82) overall, and 9% (3 out of 32) in patients treated at 65-75 mg m(-2). Responses occurred in treated and previously-untreated patients, including cases of colorectal cancer, non-small-cell lung cancer, ovarian cancer and adenocarcinoma of unknown primary site. BMS-181174 has anti-cancer activity but, because of its toxicity, particularly pneumonitis and thrombophlebitis, no phase II studies are planned.

Macaulay, V. M.; O'Byrne, K. J.; Green, J. A.; Philip, P. A.; McKinley, L.; LaCreta, F. P.; Winograd, B.; Ganesan, T. S.; Harris, A. L.; Talbot, D. C.

1998-01-01

57

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

SciTech Connect

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.

Stockman, H.W.; Krumhansl, J.L.; Ho, C.K. [Sandia National Labs., Albuquerque, NM (United States); Kovach, L. [US Nuclear Regulatory Commission, Washington, DC (United States); McConnell, V.S. [Univ. of Alaska, Fairbanks, AK (United States)

1995-03-01

58

Characterization of yeast seryl-tRNA synthetase active site mutants with improved discrimination against substrate analogues.  

PubMed

The involvement of amino acids within the motif 2 loop of Saccharomyces cerevisiae seryl-tRNA synthetase (SerRS) in serine and ATP binding was demonstrated previously [B. Lenhard et al., J. Biol. Chem. 272 (1997) 1136-1141]. In our attempt to analyze the structural basis for the substrate specificity and to explore further the catalytic mechanism employed by S. cerevisiae SerRS, two new active site mutants, SerRS11 and SerRS12, were constructed. The catalytic effects of amino acid replacement at positions Lys287, Asp288 and Ala289 with purified wild-type and mutant seryl-tRNA synthetases were tested. The alteration of these semi-conserved amino acids interferes with tRNA-dependent optimization of serine recognition. Additionally, mutated enzymes SerRS11 (Lys287Thr, Asp288Tyr, Ala289Val) and SerRS12 (Lys287Arg) are less sensitive to inhibition by two competitive inhibitors: serine hydroxamate, an analogue of serine, and 5'-O-[N-(L-seryl)-sulfamoyl]adenosine, a stable analogue of aminoacyl adenylate, than the wild-type enzyme. SerRS mutants also display different activation kinetics for serine and serine hydroxamate, indicating that specificity toward the substrates is modulated by amino acid replacement in the motif 2 loop. PMID:11004561

Landeka, I; Filipic-Rocak, S; Zinic, B; Weygand-Durasevic, I

2000-07-14

59

Synthesis and Cytotoxicity Studies of Titanocene C Analogues  

PubMed Central

From the carbolithiation of 6-N,N-dimethylamino fulvene (3) and 2,4[bis(N,N-dimethylamino)methyl]-N-methylpyrrolyl lithium (2a), N-(N?,N?-dimethylaminomethyl)benzimidazolyl lithium (2b), or p-(N,N-dimethylamino)methylphenyl lithium (2c), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4' resulting in N,N-dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), the IC50 values obtained were of 23, and 52? ?M for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene in this paper, 5c with an IC50 value of 13??M, was found to be approximately two times less cytotoxic than its analogue Titanocene C (IC50=5.5??M) and almost four times less cytotoxic than cisplatin, which showed an IC50 value of 3.3??M when tested on the LLC-PK cell line.

Hogan, Megan; Claffey, James; Fitzpatrick, Eoin; Hickey, Thomas; Pampillon, Clara; Tacke, Matthias

2008-01-01

60

Natural Analogue Synthesis Report  

SciTech Connect

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 release on the biosphere, and potentially disruptive events. Results of these studies will be used to corroborate estimates of the magnitude and limitation of operative processes in order to build realism into conceptual and numerical process models used as a foundation for PA in the representative case of postclosure safety.

A. M. Simmons

2002-05-01

61

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

PubMed

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

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

2013-03-13

62

Mapping a Study Site  

NSDL National Science Digital Library

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

Science, Lawrence H.

1982-01-01

63

Secondary minerals and regolith profiles in basaltic rocks in northeastern US and in Svalbard, an Arctic Mars analogue site  

NASA Astrophysics Data System (ADS)

Data reported from the Mars Rovers, previous missions, and remote sensing have yielded a body of exciting evidence documenting that a Critical Zone nourished by water may also exist or have existed on Mars. However, the extent to which weathering is responsible for secondary mineral formation on Mars is not clear. We are investigating plagioclase and pyroxene weathering and precipitation of iron oxyhydroxides and clays in regolith profiles developed on rocks of basaltic composition from three different sites (Pennsylvania, Virginia, Svalbard), located in very different climatic conditions. Two of these sites were formed under a cool temperate climate, while the Svalbard profile is formed in a dry polar climate that has been identified as a Mars analogue. The two sites located in the northeastern US show similar rates of plagioclase dissolution, while slower rates were observed at Svalbard. Depth of weathering is also much greater in Pennsylvania and Virginia than in Svalbard, where weathering has only proceeded since the last glaciation. Nonetheless, weathering in Svalbard is accelerated by spalling of altered surfaces, presumably due to temperature cycling. We are using a variety of techniques including Fe isotope measurements to better understand secondary mineral precipitation in regolith. Knowledge of the climatic effects upon these processes on Earth can ultimately be applied to better understand weathering mechanisms on Mars.

Brantley, S. L.; Yesavage, T. A.; Bazilevskaya, E.

2011-12-01

64

Analogue Computer Representations of Synchronous Generators in Voltage-Regulation Studies  

Microsoft Academic Search

This paper develops a general block-diagram representation of the synchronous generator when applied to voltage-regulating system studies. This representation, which is suited particularly to analogue-type computation, includes saturation effects, variable-speed operation, variable-load power factor, and also the effects of saliency and damper circuits.

M. Riaz

1956-01-01

65

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...

66

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

ERIC Educational Resources Information Center

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

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

2004-01-01

67

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

PubMed

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

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

2012-11-09

68

XAFS And Molecular Dynamics Study of Natural Minerals, Analogues of Ceramics for Nuclear Waste Storage  

SciTech Connect

Natural actinides (U and Th) are harmful for the crystalline structure of natural minerals, due to their irradiation. Natural minerals can then become amorphous to x-ray diffraction ('metamict') after being irradiated throughout a long period of time (10{sup 8} years). Then, they are used as natural analogues of ceramics for nuclear waste storage. XAFS studies were performed in zircon, monazite and titanite to understand the effect of radiation damage on the local structure around Th, U, Zr and P and compared to available molecular dynamics (MD) simulations. In zircon, a local expansion around actinides (when substituting for Zr) is found. The radial expansion is a function of the metamictisation degree: up to {approx}4 {angstrom} in crystalline zircon and larger in the metamict counterparts. Ab-initio calculations (FEFF7) were performed around Zr ({approx}23000 sites) and around U (1000 to 3000 sites) in various crystalline and alpha-decay damaged zircon MD simulations. The calculated averaged EXAFS spectra confirms this expansion, which validates the use of the potentials used in the simulations as well as the alpha decay damage model considered in these MD simulations. Tetravalent actinides were found to be 8-coordinated in the undamaged structure, whereas their coordination drops to 7 in the damaged structures. In contrast to zircon, no local expansion around actinides in monazite was detected, despite some polymerization around P is measured (related to radiation damage). Finally, in some phases (such as titanite), actinides are found as oxyde-type clusters (ThO{sub 2}, UO{sub 2}). Consequently, actinides do not 'systematically' substitute for major actions in these structure, in contrast to the common belief in mineralogy.

Harfouche, M.; Farges, F.; Crocombette, J.P.; Flank, A.M.; /SLAC, SSRL

2006-10-27

69

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)

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 soils and groundwater.

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

70

Acidity of carboxyl group of tyrosine and its analogues and derivatives studied by steady-state fluorescence spectroscopy  

Microsoft Academic Search

The acidity of the carboxyl group of tyrosine and its derivatives and analogues was studied by means of fluorimetric titration using a steady-state fluorescence method. The pKa value of carboxyl group of tyrosine, its analogues and derivatives with blocked amino or hydroxyl group or both determined from the fluorimetric titration curve indicates that the methylation of hydroxyl group of phenolic

Mariusz Szabelski; Katarzyna Guzow; Alicja Rzeska; Joanna Malicka; Monika Przyborowska; Wies?aw Wiczk

2002-01-01

71

Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies.  

PubMed

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading to the biosynthesis of folate cofactors. Like other enzymes in the folate pathway, HPPK is an ideal target for the development of antimicrobial agents because the enzyme is essential for microorganisms but is absent from human and animals. Three bisubstrate analogues have been synthesized for HPPK and characterized by biochemical and X-ray crystallographic analyses. All three bisubstrate analogues consist of a pterin, an adenosine moiety, and a link composed of 2-4 phosphoryl groups. P(1)-(6-Hydroxymethylpterin)-P(2)-(5'-adenosyl)diphosphate (HP(2)A, 5) shows little affinity and inhibitory activity for E. coli HPPK. P(1)-(6-Hydroxymethylpterin)-P(3)-(5'-adenosyl)triphosphate (HP(3)A, 6) shows moderate affinity and inhibitory activity with K(d) = 4.25 microM in the presence of Mg(2+) and IC(50) = 1.27 microM. P(1)-(6-Hydroxymethylpterin)-P(4)-(5'-adenosyl)tetraphosphate (HP(4)A, 7) shows the highest affinity and inhibitory activity with K(d) = 0.47 microM in the presence of Mg(2+) and IC(50) = 0.44 microM. The affinity of MgHP(4)A for HPPK is approximately 116 and 76 times higher than that of MgADP and 6-hydroxymethylpterin, respectively. The crystal structure of HPPK in complex with 7 (HPPK.MgHP(4)A) has been determined at 1.85 A resolution with a crystallographic R factor of 0.185. The crystal structure shows that 7 occupies both HP- and ATP-binding sites and induces significant conformational changes in HPPK. The biochemical and structural studies of the bisubstrate analogues indicate that the bisubstrate analogue approach can produce more potent inhibitors for HPPK and the minimum length of the link for a bisubstrate analogue is approximately 7 A. PMID:11311059

Shi, G; Blaszczyk, J; Ji, X; Yan, H

2001-04-26

72

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

NASA Astrophysics Data System (ADS)

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.

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

73

Subacute administration of a TRH analogue (RX77368) in motorneuron disease: an open study.  

PubMed Central

Sixteen patients with motor neuron disease received RX77368, a TRH analogue, IV, repeatedly over 1-12 weeks (median 2 weeks). Slight to moderate improvement in bulbar function, particularly speech, was reproduced or persisted with repeated infusions in 8 of 12 responders over a median of 18 days (range 14-90) during the period of study. Cramps (5/9) and spasticity (5/8) improved for a median of 14 days (range 7-35) and 7 days (range 2-14) respectively. The highest benefit/side effect ratio was seen with 0.2 mg/kg (0.15 mg/kg in those with severe bulbar palsy) every 3-4 days. Long term studies with this analogue in MND are indicated. Images

Modarres-Sadeghi, H; Rogers, H; Emami, J; Guiloff, R J

1988-01-01

74

Novel hepatoselective insulin analogues: studies with covalently linked thyroxyl-insulin complexes.  

PubMed

To explore the possibility that insulin analogues designed to have restricted access to peripheral tissues may display relative hepatoselectivity in vivo, Nalphabeta1-thyroxyl-insulin (B1-T4-Ins) and Nalphabeta1-thyroxyl-aminohexanoyl insulin (B1-T4-AHA-Ins) were synthesized. These insulin analogues bind thyroid hormone binding proteins to form high molecular weight complexes. Effects of intravenous infusions of B1-T4-Ins; B1-T4-AHA-Ins; combined thyroxine binding globulin (TBG) and B1-T4-Ins and combined TBG and B1-T4-AHA-Ins were compared with those of insulin infusion in hyperinsulinaemic euglycaemic clamp protocols in anaesthetized beagles (n=4 and n=3 for combined TBG infusions). Glucose turnover rates were measured using D-[3-3H]glucose infusion. With all 5 protocols the rate of glucose disappearance (Rd) was increased and the rate of endogenous glucose production (Ra) decreased from basal level 13.53+/-0.60 micromol kg(-1) min(-1)(p<0.05). Insulin-like activity for Ra and Rd was calculated as the area between the basal values of each variable and the subsequent values plotted graphically against time (AUC). For insulin, B1-T4-Ins, B1-T4-AHA-Ins, combined infusions of TBG+B1-T4-Ins, and TBG+B1-T4-AHA-Ins, respectively, AUC for Rd values were 6.30+/-0.69, 3.35+/-0.53, 4.40+/-0.64, 2.82+/-0.40 and 3.46+/-0.95 (mmol kg(-1)), all analogue infusions being different from insulin (p<0.05). AUC for Rd was further reduced by addition of TBG to B1-T4-AHA-Ins (p<0.05). In contrast the effect of all analogues on AUC for Ra was similar to that of insulin. These observations are compatible with the suggestion that insulin analogues which bind to thyroid hormone binding proteins retain access to hepatic insulin receptors which primarily control Ra. The reduced peripheral insulin-like effect (Rd) could be due to reduced transcapillary access to peripheral insulin receptor sites. PMID:9827847

Shojaee-Moradie, F; Eckey, H; Jackson, N C; Schüttler, A; Brandenburg, D; Sönksen, P H; Jones, R H

1998-11-01

75

Theoretical studies on the interaction of guanine riboswitch with guanine and its closest analogues  

Microsoft Academic Search

Experimental studies (M. Mandal, B. Boese, J.E. Barrick, W.C. Winkler and R.R. Breaker, Riboswitches control fundamental biochemical pathways in bacillus subtilis and other bacteria, Cell 113 (2003), pp. 577–586) demonstrated that, besides recognising guanine with high specificity, guanine riboswitch could also bind guanine analogues, but the alteration of every functionalised position on the guanine heterocycle could cause a substantial loss

Baoping Ling; Rui Zhang; Zhiguo Wang; Lihua Dong; Yongjun Liu; Changqiao Zhang; Chengbu Liu

2010-01-01

76

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

Microsoft Academic Search

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

Thomas Ehring; Anna-Kristina Szeimies; Christina Schaffrick

2009-01-01

77

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

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.

2009-01-01

78

Study of the substrate-binding properties of bovine liver adenosine kinase and inhibition by fluorescent nucleoside analogues.  

PubMed

Adenosine kinase (AK) catalyzes the phosphorylation of adenosine to AMP with ATP as phosphate donor. Intrinsic fluorescence of bovine liver AK was shown previously to be a sensitive probe to quantify the binding of substrates to the enzyme [Elaloui, A., Divita, G., Maury, G., Imbach, J.-L. & Goody, R. S. (1994) Eur. J Biochem. 221, 839-846]. AK contains two catalytic, sites: a high-affinity site, which binds adenosine and AMP selectively; and a site for ATP and ADP. In the present work, these two sites were characterized by combining the quenching of protein fluorescence induced by the binding of the ligands and the fluorescence enhancement observed upon binding of the N-methylanthraniloyl-derivated nucleotides or adenosine. A new fluorescent analog of adenosine, 5'-N-methylanthraniloyl-adenosine, was synthesized and shown to bind selectively to the high-affinity adenosine-binding site with an affinity similar to that of adenosine (Kd 1 microM). In contrast, 2'(3')-N-methylanthraniloyl derivatives of ATP, adenosine (5')tetraphospho(5')adenosine (Ap4A), and adenosine (5')pentaphospho(5')adenosine (Ap5A), bind to the enzyme at the ATP site. Methylantraniloyl derivatives of ATP and adenosine were used as tools for selective characterization of a series of adenosine analogues. The bisubstrate inhibitors Ap4A and Ap5A bind to the ATP site with high affinity and apparently not to the adenosine site, thus acting more as ATP analogues than true bisubstrate ligands. The binding properties of a series of adenosine analogues were strongly dependent on the structural modifications on adenosine. The analogues modified at positions 2' or 3' show similar affinities for AK as that of adenosine, whereas adenosine analogues modified at the base present a relatively low affinity for the enzyme. PMID:9342249

Pelicano, H; Maury, G; Elalaoui, A; Shafiee, M; Imbach, J L; Goody, R S; Divita, G

1997-09-15

79

Intestinal absorption of riboflavin, studied by an in situ circulation system using radioactive analogues.  

PubMed

The intestinal absorption of riboflavin was studied using radioactive riboflavin and its analogues 8-demethylriboflavin, 3-methylriboflavin, 5'-deoxyriboflavin, 2'-deoxyriboflavin, 7,8-dimethyl-10-hydroxyethylisoalloxazine, lumiflavin, lumichrome, and riboflavin-5'-monosulfate, which were synthesized with high specific radioactivity. A specific absorption of riboflavin at dietary concentrations was confirmed using an in situ circulation system. The relation between the chemical structure of flavins and the absorption mechanism was studied using this system. The 8-demethylriboflavin, an analogue modified at benzene moiety of the isoalloxazine ring, was absorbed in a similar way to riboflavin, by dual kinetics: by a process specific for riboflavin at dietary concentrations and by simple diffusion (nonspecific absorption) predominating at higher concentrations (over 100 microM). However, 3-methylriboflavin and analogues modified at the ribityl group, including 5'-deoxyriboflavin, were absorbed only via simple diffusion even at dietary concentrations. Many flavins examined, except for 3-isobutylriboflavin, 3-carboxymethylriboflavin, lumichrome, and riboflavin-5'-monosulfate, interfered with the specific absorption of riboflavin. It was concluded from these results that one of the specific absorption processes for riboflavin is a phosphorylation-dephosphorylation process. Four water-soluble vitamins did not interfere with the specific absorption of riboflavin, indicating that these vitamins do not share a common specific absorption pathway with riboflavin. PMID:3183777

Kasai, S; Nakano, H; Kinoshita, T; Miyake, Y; Maeda, K; Matsui, K

1988-06-01

80

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

PubMed Central

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

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

2001-01-01

81

WebGIS Tools Applied to Science Traverse Planning and the Geospatial Analysis of Terrestrial Analogue Sites  

NASA Astrophysics Data System (ADS)

The Canadian space agency (CSA) is currently developing a geospatial architecture intended for planetary and terrestrial analogue databases and a WebGIS for traverses planning for extravehicular activities.

Phaneuf, M.; Germain, M.; Williamson, M.-C.; Hipkin, V.

2010-03-01

82

Copper Inhibits Activated Protein C: Protective Effect of Human Albumin and an Analogue of Its High-Affinity Copper-Binding Site, d-DAHK  

Microsoft Academic Search

Activated protein C (APC) is useful in the treatment of sepsis. Ischemia and acidosis, which often accompany sepsis, cause the release of copper from loosely bound sites. We investigated (i) whether physiological concentrations of copper inhibit APC anticoagulant activity and (ii) if any copper-induced APC inhibition is reversible by human serum albumin (HSA) or a high-affinity copper-binding analogue of the

David Bar-Or; Leonard T. Rael; James V. Winkler; Richard L. Yukl; Gregory W. Thomas; Richard P. Shimonkevitz

2002-01-01

83

Diversity and evolutionary relationship of nucleotide binding site-encoding disease-resistance gene analogues in sweet potato ( Ipomoea batatas Lam.)  

Microsoft Academic Search

Most plant disease-resistance genes (R-genes) isolated so far encode proteins with a nucleotide binding site (NBS) domain and belong to a superfamily. NBS domains\\u000a related to R-genes show a highly conserved backbone of an amino acid motif, which makes it possible to isolate resistance gene analogues\\u000a (RGAs) by degenerate primers. Degenerate primers based on the conserved motif (P-loop and GLPL)

Guanshui Chen; Daren Pan; Yifei Zhou; Sheng Lin; Xiangde Ke

2007-01-01

84

Neurosteroid Analogues. 17. Inverted Binding Orientations of Androsterone Enantiomers at the Steroid Potentiation Site on ?-Aminobutyric Acid Type A (GABAA) Receptors  

PubMed Central

The enantiomer pair androsterone and ent-androsterone are positive allosteric modulators of ?-aminobutyric acid type A (GABAA) receptors. Each enantiomer was shown to bind at the same receptor site. Binding orientations of the enantiomers at this site were deduced using enantiomer pairs containing OBn substituents at either C-7 or C-11. 11?-OBn substituted steroids and 7?-OBn substituted ent-steroids potently displace [35S]TBPS, augment GABA currents and anesthetize tadpoles. In contrast, 7?-OBn substituted steroids and 11?-OBn substituted ent-steroids have diminished actions. The results suggest that the binding orientations of the active analogues are inverted relative to each other with the 7? and 11? substituents similarly located on the edges of the molecules not in contact with the receptor surface. Analogue potentiation of GABA current was abrogated by an ?1 subunit Q241L mutation indicating that the active analogues act at the same sites in ?1?2?2L receptors previously associated with positive neurosteroid modulation.

Krishnan, Kathiresan; Manion, Brad D.; Taylor, Amanda; Bracamontes, John; Steinbach, Joseph H.; Reichert, David E.; Evers, Alex S.; Zorumski, Charles F.; Mennerick, Steven; Covey, Douglas F.

2012-01-01

85

4D-QSAR Analysis of a Set of Propofol Analogues: Mapping Binding Sites for an Anesthetic Phenol on the GABAA Receptor  

PubMed Central

A training set of 27 propofol (2,6-diisopropylphenol) analogues was used to construct four-dimensional (4D) quantitative structure–activity relationship (QSAR) models for three screens of biological activity: loss of righting reflex (LORR) in tadpoles, enhancement of agonist activity at the ?-aminobutyric acid type A (GABAA) receptor, and direct (agonist-independent) activation of the receptor. The three resulting 4D-QSAR models are almost identical in form, and all suggest three key ligand–receptor interaction sites. The formation of an intermolecular hydrogen bond involving the proton of the ligand–OH group is the most important binding interaction. A hydrophobic pocket binding interaction involving the six-substituent is the second most significant binding site, and a similar hydrophobic pocket binding interaction near the two-substituent is the third postulated binding site from the 4D-QSAR models. A test set of eight compounds was used to evaluate the tadpole LORR 4D-QSAR model. Those compounds highly congeneric to the training set compounds were accurately predicted. However, compounds exploring substituent sites and/or electronic structures different from the training set were less well-predicted. Overall, the results show a striking similarity between the models of the sites responsible for anesthesia and those mediating effects of the training set of propofol analogues on the GABAA receptor; it follows that the GABAA receptor is therefore the likely site of propofol’s anesthetic action.

Krasowski, Matthew D.; Hong, Xuan; Hopfinger, A. J.

2010-01-01

86

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

NASA Astrophysics Data System (ADS)

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.

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.

87

Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123).  

PubMed

Previous studies suggest that dephosphorylation of connexin43 (Cx43) is related to uncoupling of gap junction communication, which plays an important role in the genesis of ischemia-induced ventricular tachycardia. We studied changes in Cx43 phosphorylation during global ischemia in the absence and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass spectrometry. Thirteen different serine phosphorylation sites were identified in Cx43 during non-ischemic conditions, three of which had not previously been described. Within the first 7 min of ischemia, Ser306 became fully dephosphorylated whereas Ser330 became phosphorylated. Between 15 and 30 min of ischemia, the critical time interval where gap junction uncoupling occurs, Ser297 and Ser368 also became fully dephosphorylated. During the same time period, all untreated hearts developed asystole. Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed dephosphorylation of Ser297 and Ser368 at 30 min of ischemia. Our results suggest that phosphorylation of Ser297 and Ser368 may be involved in functional gating of Cx43 during ischemia and may be possible downstream targets for rotigaptide signaling. PMID:16678851

Axelsen, Lene N; Stahlhut, Martin; Mohammed, Shabaz; Larsen, Bjarne Due; Nielsen, Morten S; Holstein-Rathlou, Niels-Henrik; Andersen, Søren; Jensen, Ole N; Hennan, James K; Kjølbye, Anne Louise

2006-05-05

88

Use of a 'caged' analogue to study the traffic of choline within acetylcholinesterase by kinetic crystallography.  

PubMed

Acetylcholinesterase plays a crucial role in nerve-impulse transmission at cholinergic synapses. The apparent paradox that it displays high turnover despite its active site being buried raises cogent questions as to how the traffic of substrates and products to and from the active site can occur so rapidly in such circumstances. Here, a kinetic crystallography strategy aimed at structurally addressing the issue of product traffic in acetylcholinesterase is presented, in which UV-laser-induced cleavage of a photolabile precursor of the enzymatic product analogue arsenocholine, 'caged' arsenocholine, is performed in a temperature-controlled X-ray crystallography regime. The 'caged' arsenocholine was shown to bind at both the active and peripheral sites of acetylcholinesterase. UV irradiation of a complex with acetylcholinesterase during a brief temperature excursion from 100 K to room temperature is most likely to have resulted in a decrease in occupancy by the caged compound. Microspectrophotometric experiments showed that the caged compound had indeed been photocleaved. It is proposed that a fraction of the arsenocholine molecules released within the crystal had been expelled from both the active and the peripheral sites. Partial q-weighted difference refinement revealed a relative movement of the two domains in acetylcholinesterase after photolysis and the room-temperature excursion, resulting in an increase in the active-site gorge volume of 30% and 35% in monomers A and B of the asymmetric unit, respectively. Moreover, an alternative route to the active-site gorge of the enzyme appeared to open. This structural characterization of acetylcholinesterase 'at work' is consistent with the idea that choline exits from the enzyme after catalysis either via the gorge or via an alternative 'backdoor' trajectory. PMID:18007027

Colletier, Jacques-Philippe; Royant, Antoine; Specht, Alexandre; Sanson, Benoît; Nachon, Florian; Masson, Patrick; Zaccai, Giuseppe; Sussman, Joel L; Goeldner, Maurice; Silman, Israel; Bourgeois, Dominique; Weik, Martin

2007-10-17

89

Social Studies. [SITE 2001 Section].  

ERIC Educational Resources Information Center

|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"…

White, Cameron, Ed.

90

Mars Analog Site Study (MASS)  

NASA Astrophysics Data System (ADS)

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

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

1993-03-01

91

Isolation of nucleotide binding site-leucine rich repeat and kinase resistance gene analogues from sugarcane (Saccharum spp.)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Resistance gene analogues (RGAs) offer great potential to breeding for disease resistance through marker assisted selection, either as closely linked markers or through candidate gene approaches. Many R-gene sequences contain kinase domains and indeed kinase genes have been reported as being proxim...

92

Probing the ribosomal RNA A-site with functionally diverse analogues of paromomycin—synthesis of ring I mimetics  

Microsoft Academic Search

Methods were developed to selectively cleave the 2-amino-2-deoxy-?-d-glucopyranosyl ring in paromomycin. The preferentially N- and O-protected products were alkylated on the liberated C4 hydroxyl group of the deoxystreptamine subunit. Further manipulation furnished a series of aromatic, heteroaromatic, and aliphatic appendages as spatial mimics of ring I. Modest inhibitory activity was found against Staphylococcus aureus with two analogues (27 and 63),

Stephen Hanessian; Susanta Adhikari; Janek Szychowski; Kandasmy Pachamuthu; Xiaojing Wang; Michael T. Migawa; Richard H. Griffey; Eric E. Swayze

2007-01-01

93

Neuropharmacological study of hetero[2,1]benzothiazepine derivatives analogues of tianeptine.  

PubMed

Neuropharmacological studies were conducted in mice with a number of hetero[2,1]benzothiazepine derivatives, analogues of tianeptine. Seven of the 12 compounds under study potentiated the actions of 5-hydroxytryptophan (5-HTP, 50 mg/kg i.p.) and/or antagonised the hypothermia induced by high doses of apomorphine. Moreover, some of them inhibited the head twitches induced by 5-HTP (250 mg/kg i.p.) and the stereotyped behaviour and/or climbing behaviour of low doses of apomorphine. These compounds also produced a slight inhibition of exploratory behaviour in the holeboard test. On the other hand, no significant muscle relaxant, anticonvulsant and anxiolytic activities were observed at any dose employed. Together, these data suggest that some of the compounds under study exert antidepressant and neuroleptic effects in mice with no muscle relaxant, anxiolytic and anticonvulsant activities. PMID:12595031

Sánchez-Mateo, Candelaria C; Darias, Victoriano; Expósito-Orta, M Auxiliadora; Albertos, Luz M

2003-01-01

94

Evidence for the two phosphate binding sites of an analogue of the thioacyl intermediate for the Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase-catalyzed reaction, from its crystal structure.  

PubMed

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the reversible oxidative phosphorylation of d-glyceraldehyde 3-phosphate (GAP) into d-glycerate 1,3-bisphosphate (1,3-diPG) in the presence of NAD(+) and inorganic phosphate (P(i)). Within the active site, two anion-binding sites were ascribed to the binding of the C3 phosphate of GAP (P(s)) and to the binding of the attacking phosphate ion (P(i)). The role played by these two sites in the catalytic mechanism in connection with the functional role of coenzyme exchange (NADH-NAD(+) shuttle) has been investigated by several studies leading to the C3 phosphate flipping model proposed by Skarzynski et al. [Skarzynski, T., Moody, P. C., and Wonacott, A. J. (1987) J. Mol. Biol. 193, 171-187]. This model has not yet received direct confirmation. To gain further insight into the role of both sites, we synthesized irreversible inhibitors which form with the essential cysteine residue a thioacyl enzyme analogue of the catalytic intermediate. Here we report the refined glycosomal Trypanosoma cruzi GAPDH in complex with a covalently bound GAP analogue at an improved resolution of 2.0-2.5 A. For this holo-thioacyl enzyme complex, a flip-flop movement is clearly characterized, the change from the P(i) to the P(s) binding site being correlated with the coenzyme exchange step: the weaker interaction of the intermediate when bound at the P(s) site with the cofactor allows its release and also the binding of the inorganic phosphate for the next catalytic step. This result gives strong experimental support for the generally accepted flip-flop model of the catalytic mechanism in GAPDH. PMID:12795610

Castilho, Marcelo S; Pavão, Fernando; Oliva, Glaucius; Ladame, Sylvain; Willson, Michèle; Périé, Jacques

2003-06-17

95

Luminescence study of Eu(III) analogues of esterase-activated magnetic resonance contrast agents.  

PubMed

A model for an accumulation and enzyme-activation strategy of a magnetic resonance contrast agent was investigated via the luminescence of Eu(III) analogues. Neutral q = 2 Eu(III) ethyl and acetoxymethyl ester LnaDO3A-based complexes showed increased emission intensity in the presence of serum concentrations of carbonate because of inner-sphere water molecule displacement by the anion. The affinity for carbonate is suppressed by the introduction of negative charge to the complex following enzymatic hydrolysis of the ester groups, resulting in quenching of Eu(III) luminescence and changes in spectral form. The conversion of neutral, carboxylic ester-containing complexes into free acid forms by enzymatic hydrolysis using pig liver esterase was demonstrated by luminescence (Eu) and (1)H NMR spectroscopic investigations (Y). These studies demonstrated that the concept of inhibition of anion binding as a result of enzyme activation is feasible. PMID:19715374

Giardiello, Marco; Lowe, Mark P

2009-09-01

96

Differential furanose selection in the active sites of archaeal DNA polymerases probed by fixed-conformation nucleotide analogues.  

PubMed

DNA polymerases select for the incorporation of deoxyribonucleotide triphosphates (dNTPs) using amino acid side-chains that act as a "steric-gate" to bar improper incorporation of rNTPs. An additional factor in the selection of nucleotide substrates resides in the preferred geometry for the furanose moiety of the incoming nucleotide triphosphate. We have probed the role of sugar geometry during nucleotide selection by model DNA polymerases from Sulfolobus solfataricus using fixed conformation nucleotide analogues. North-methanocarba-dATP (N-MC-dATP) locks the central ring into a RNA-type (C2'-exo, North) conformation near a C3'-endo pucker, and South-methanocarba-dATP (S-MC-dATP) locks the central ring system into a (C3'-exo, South) conformation near a C2'-endo pucker. Dpo4 preferentially inserts N-MC-dATP and in the crystal structure of Dpo4 in complex with N-MC-dAMP, the nucleotide analogue superimposes almost perfectly with Dpo4 bound to unmodified dATP. Biochemical assays indicate that the S. solfataricus B-family DNA polymerase Dpo1 can insert and extend from both N-MC-dATP and S-MC-dATP. In this respect, Dpo1 is unexpectedly more tolerant of substrate conformation than Dpo4. The crystal structure of Dpo4 bound to S-MC-dADP shows that poor incorporation of the Southern pucker by the Y-family polymerase results from a hydrogen bond between the 3'-OH group of the nucleotide analogue and the OH group of the steric gate residue, Tyr12, shifting the S-MC-dADP molecule away from the dNTP binding pocket and distorting the base pair at the primer-template junction. These results provide insights into substrate specificity of DNA polymerases, as well as molecular mechanisms that act as a barrier against insertion of rNTPs. PMID:23050956

Ketkar, Amit; Zafar, Maroof K; Banerjee, Surajit; Marquez, Victor E; Egli, Martin; Eoff, Robert L

2012-10-30

97

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

NASA Astrophysics Data System (ADS)

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

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

2009-04-01

98

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

SciTech Connect

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.

Dale Spall; Robert Villarreal

1998-08-01

99

Mapping general anesthetic binding site(s) in human ?1?3 ?-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue.  

PubMed

The ?-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 ?Met-236 and ?Met-286 in the ?M1 and ?M3 transmembrane helices identified an etomidate binding site in the GABA(A)R transmembrane domain at the interface between the ? and ? 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-?1?3 GABA(A)Rs and more extensively identify photolabeled GABA(A)R amino acids. [³H]TDBzl-etomidate photolabeled in an etomidate-inhibitable manner ?3Val-290, in the ?3M3 transmembrane helix, as well as ?1Met-236 in ?1M1, a residue photolabeled by [³H]azietomidate, while no photolabeling of amino acids in the ?M2 and ?M2 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 ?3Met-227 in ?M1 by [³H]TDBzl-etomidate and [³H]azietomidate also provides evidence of a homologous etomidate binding site at the ?3-?3 subunit interface in the ?1?3 GABA(A)R. PMID:22243422

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

2012-01-23

100

Effects of CO2-rich fluids on a redbed reservoir: outcrop analogue study from the Buntsandstein (Germany)  

Microsoft Academic Search

Carbon capture and storage (CCS) in saline aquifers will induce fluid-rock interactions, with effects on the mineralogy and physical properties of the reservoir. These effects are difficult to study in real reservoirs. Outcrop analogues provide access to relatively large rock volumes, but it may be difficult to prove that CO2 was involved in the mineral reactions observed. We present circumstantial

N. Kasch; J. Kley; J. Koester; R. van Geldern; M. Wehrer; J. Wendler

2010-01-01

101

Neurosteroid Analogues. 15. A Comparative Study of the Anesthetic and GABAergic Actions of Alphaxalone, ?16-Alphaxalone and Their Corresponding 17-Carbonitrile Analogues  

PubMed Central

Alphaxalone, a neuroactive steroid containing a 17?-acetyl group, has potent anesthetic activity in humans. This pharmacological activity is attributed to this steroid’s enhancement of ?-amino butyric acid-mediated chloride currents at ?-amino butyric acid type A receptors. The conversion of alphaxalone into ?16-alphaxalone produces an analogue that lacks anesthetic activity in humans and that has greatly diminished receptor actions. By contrast, the corresponding 17?-carbonitrile analogue of alphaxalone and the ?16-17-carbonitrile analogue both have potent anesthetic and receptor actions. The differential effect of the ?16-double bond on the actions of alphaxalone and the 17?-carbonitrile analogue is accounted for by a differential effect on the orientation of the 17-acetyl and 17-carbonitrile substituents.

Bandyopadhyaya, Achintya K.; Manion, Brad D.; Benz, Ann; Taylor, Amanda; Rath, Nigam P.; Evers, Alex S.; Zorumski, Charles F.; Mennerick, Steven; Covey, Douglas F.

2010-01-01

102

Neurosteroid analogues. 15. A comparative study of the anesthetic and GABAergic actions of alphaxalone, ?16-alphaxalone and their corresponding 17-carbonitrile analogues.  

PubMed

Alphaxalone, a neuroactive steroid containing a 17?-acetyl group, has potent anesthetic activity in humans. This pharmacological activity is attributed to this steroid's enhancement of ?-amino butyric acid-mediated chloride currents at ?-amino butyric acid type A receptors. The conversion of alphaxalone into ?(16)-alphaxalone produces an analogue that lacks anesthetic activity in humans and that has greatly diminished receptor actions. By contrast, the corresponding 17?-carbonitrile analogue of alphaxalone and the ?(16)-17-carbonitrile analogue both have potent anesthetic and receptor actions. The differential effect of the ?(16)-double bond on the actions of alphaxalone and the 17?-carbonitrile analogue is accounted for by a differential effect on the orientation of the 17-acetyl and 17-carbonitrile substituents. PMID:20875742

Bandyopadhyaya, Achintya K; Manion, Brad D; Benz, Ann; Taylor, Amanda; Rath, Nigam P; Evers, Alex S; Zorumski, Charles F; Mennerick, Steven; Covey, Douglas F

2010-09-15

103

RESERVOIR ARCHITECTURE IN A TERMINAL ALLUVIAL PLAIN: AN OUTCROP ANALOGUE STUDY (UPPER TRIASSIC, SOUTHERN GERMANY) PART II: CYCLICITY, CONTROLS AND MODELS  

Microsoft Academic Search

This outcrop analogue study investigates Triassic fluvial sandstones of the Stubensandstein Formation which were deposited on a terminal alluvial plain under semi- arid to sub-humid climatic conditions in the land-locked South German Keuper Basin. The Stubensandstein may serve as an analogue for reservoir units in comparable continental basins. Data came from studies of 13 large sandpits, together with a subsurface

J. Hornung; T. Aigner

2002-01-01

104

Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors  

PubMed Central

It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D-docking). The crystal structures of leucine transporter from Aquifex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators.

Jaronczyk, Malgorzata; Wolosewicz, Karol; Gabrielsen, Mari; Nowak, Gabriel; Kufareva, Irina; Mazurek, Aleksander P.; Ravna, Aina W.; Abagyan, Ruben; Bojarski, Andrzej J.; Sylte, Ingebrigt; Chilmonczyk, Zdzislaw

2012-01-01

105

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

PubMed Central

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.

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

2013-01-01

106

Measuring fast-temporal sediment fluxes with an analogue acoustic sensor: a wind tunnel study.  

PubMed

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

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

2013-09-18

107

Assessing the bioequivalence of analogues of endogenous substances ('endogenous drugs'): considerations to optimize study design  

PubMed Central

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

Dissanayake, Sanjeeva

2010-01-01

108

Synthesis, receptor binding, and activation studies of N(1)-alkyl-L-histidine containing thyrotropin-releasing hormone (TRH) analogues.  

PubMed

Thyrotropin-releasing hormone (TRH) analogues in which the N(1)-position of the imidazole ring of the centrally placed histidine residue is substituted with various alkyl groups were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). Analogue 3 (R=C2H5) exhibited binding affinity (Ki) of 0.012 microM to TRH-R1 that is about 1.1-fold higher than that of TRH. Several analogues were found to selectively activate TRH-R2 with greater potency than TRH-R1. The most selective agonist of the series 5 [R=CH(CH3)2] was found to activate TRH-R2 with a potency (EC50) of 0.018 microM but could only activate TRH-R1 at EC50 value of 1.6 microM; that is, exhibited 88-fold greater potency for TRH-R2 versus TRH-R1. The results of this study indicate that modulation of central histidine residue is important for designing analogues which were selective agonist at TRH receptor subtypes. PMID:16735122

Kaur, Navneet; Monga, Vikramdeep; Josan, Jatinder S; Lu, Xinping; Gershengorn, Marvin C; Jain, Rahul

2006-06-02

109

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

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.

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.; (USF); (Cornell); (Southern Research); (Penn)

2009-04-02

110

Analysis of a pentacoordinate iron dicarbonyl as synthetic analogue of the Hmd or mono-iron hydrogenase active site.  

PubMed

Pentacoordinate iron dicarbonyls, (NS)Fe(CO)(2)P (NS=2-amidothiophenylate, P=PCy(3) (4), PPh(3), (5), and P(OEt)(3) (6)) were prepared as potential biomimetics of the active site of the mono-iron hydrogenase, [Fe]-H(2)ase. Full characterization including X-ray diffraction, density functional theory (DFT) computations, and Mössbauer studies for complexes 5 and 6 find that, despite similar infrared v(CO) pattern and absorption frequencies as the active site of the [Fe]-H(2)ase, the geometrical distortions towards trigonal bipyramidal, the negative isomer shift parameters, and the differences in CO-uptake reactivity are due to the "non-innocence" of the NS ligand. Ligand-based protonation with a strong acid, HBF(4).Et(2)O, interrupted the extensive pi-delocalization over Fe and NS ligand of complex 4 and switched on CO uptake (1 bar) to form a CO adduct, mer-[(H-NS)Fe(CO)(3)(PCy(3))](+) or 4(CO)-H(+). The extrinsic CO is reversibly removed on deprotonation with Et(3)N to regenerate complex 4. In a (13)CO atmosphere, concomitant CO uptake by 4-H(+) and exchange with intrinsic CO groups provide a facile route to (13)C-labeled 4(CO)-H(+) and, upon deprotonation, (13)C-labeled complex 4. DFT calculations show substantial Fe character in the LUMO of 4-H(+) typical of the d(6) Fe(II) in a regular square-pyramidal geometry. Thus, the Lewis acidity of 4-H(+) makes it amenable for CO binding, whereas the dianionic NS ligand renders the iron center of 4 insufficiently electrophilic and largely of Fe(I) character. PMID:20119989

Liu, Tianbiao; Li, Bin; Popescu, Codrina V; Bilko, Andrey; Pérez, Lisa M; Hall, Michael B; Darensbourg, Marcetta Y

2010-03-01

111

XAFS and XEOL of tetramesityldigermene - An electronic structure study of a heavy group 14 ethylene analogue  

NASA Astrophysics Data System (ADS)

Digermene, the germanium analogue of ethylene, has a multiple bonding motif that differs greatly from that of alkenes and exhibits no pure ? or ? type bonds. The electronic structure of digermenes is difficult to study experimentally due to their reactivity, and is computationally challenging because of their shallow potential energy surfaces. Using X-ray absorption near edge structures at both the germanium K and L edges we have been able to directly probe the unoccupied electronic states, or the lowest unoccupied molecular orbital (LUMO), and LUMO+ etc. in the Ge=Ge bond of tetramesityldigermene. We have demonstrated that the LUMO, LUMO+, etc. are composed of hybrid Ge 4s and 4p orbitals. Additionally, our data suggest that the LUMO exhibits relatively more Ge 4s character, whereas the LUMO+ and LUMO+2 exhibit relatively more Ge 4p character. An X-ray excited optical luminescence study of Ge2Mes4 revealed one broad optical emission band at 620 nm, which is significantly red shifted compared to the known energy gap of this molecular germanium compound.

Ward, Matthew J.; Rupar, Paul A.; Murphy, Michael W.; Yiu, Yun-Mui; Baines, Kim M.; Sham, Tsun-Kong

2013-04-01

112

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

PubMed Central

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

Lopez-Munguia, Agustin; Hernandez-Romero, Yanet; Pedraza-Chaverri, Jose; Miranda-Molina, Alfonso; Regla, Ignacio; Martinez, Ana; Castillo, Edmundo

2011-01-01

113

A study of faulting patterns in the Pearl River Mouth Basin through analogue modeling  

NASA Astrophysics Data System (ADS)

The Pearl River Mouth Basin is one of the most favorable areas for gas exploration on the northern slope of the South China Sea. Differences of fault patterns between shelf and slope are obvious. In order to investigate the tectonic evolution, five series of analogue modeling experiments were compared. The aim of this study is to investigate how crustal thickness influences fault structures, and compare this to the observed present-day fault structures in the Pearl River Mouth Basin. The initial lithospheric rheological structure can be derived from the best fit between the modeled and observed faults. The results indicate. (1) Different initial crustal rheological structures can produce different rift structures in the Pearl River Mouth Basin. (2) We also model that the Baiyun Sag in the southern Pearl River Mouth Basin may have had a thinned crust before rifting compared to the rest of the basin. (3) The thickness ratio of brittle to ductile crust in southern Pearl River Mouth Basin is less than normal crust, suggesting an initially hot and weak lithosphere. (4) Slightly south of the divergent boundary magma may have taken part in the rifting process during the active rift stage.

Zhang, Yun Fan; Sun, Zhen

2013-08-01

114

Study on C8-substituent effects of synthetic bacteriochlorophyll-d/f analogues  

NASA Astrophysics Data System (ADS)

Bacteriochlorophyll(=BChl)s- c/d/e are known to be major pigments constructing the main light-harvesting antennae of photosynthetic green bacteria. In this study, methyl bacteriopheophorbide-d derivatives having a series of alkyl or alkenyl substituents at the 8-position and their zinc complexes were synthesized, and their visible absorption spectra and self-aggregation in a solution were examined. It was shown that the C8-substituents conjugating with the chlorin ?-system cause red-shifts of the Qx peaks in their monomeric forms, but do not strongly affect the supramolecular structure of the self-aggregates along the Qy axis. Furthermore, 31-epimerically pure Zn-MBPhe-f analogues possessing the C8-formyl group were also synthesized, and their spectral characteristics were compared to those of the C7-formyl compounds. It was found that the C8-formyl group cause drastic spectral changes both in monomeric and oligomeric forms compared to the spectra of Zn-MBPhe-f having the C7-formyl group. For example, self-aggregates of the former showed more red-shifted Qy peak in 6%THF-H2O than the latter, and larger diastereomeric control in the oligomeric Qy peaks was observed for C8-formyl derivatives than for C7-formyl compounds.

Sasaki, Shin-Ichi; Tamiaki, Hitoshi

2004-08-01

115

Toward libraries of biotinylated chondroitin sulfate analogues: from synthesis to in vivo studies.  

PubMed

Chondroitin sulfate-E (CS-E) oligosaccharidic analogues (di to hexa) were prepared from lactose. In these compounds, the 2-acetamido group was replaced by a hydroxyl group. This modification speeded up the synthesis, and large oligosaccharides were constructed in a few steps from a lactose-originated block. The protecting groups used were as follows; Fmoc for hydroxyl groups to be glycosylated, allyl group for anomeric position protection, and trichoroacetimidate leaving groups were used to prepare up to octasaccharides. We took advantage of the presence of allyl group to develop a click biotinylation, through its transformation into a 3-azido-2-hydroxyl propyl group in two steps (epoxidation and sodium azide epoxide opening). The biotinylating agent was a water-soluble propargylated and biotinylated triethylene glycol (PEG). By using surface plasmon resonance (SPR), it was shown that the di-, tetra-, and hexasaccharides display a binding affinity and selectivity toward HSF/GSF and CXCL12 similar to that of CS-E. A parallel study confirmed their mimicry of natural compounds, based on the hexasaccharide interaction with Otx2, a homeodomain protein involved in brain maturation, thus validating our simplification approach to synthesize bioactive GAG. PMID:23154924

Despras, Guillaume; Bernard, Clémence; Perrot, Anthony; Cattiaux, Laurent; Prochiantz, Alain; Lortat-Jacob, Hugues; Mallet, Jean-Maurice

2012-11-14

116

Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues  

SciTech Connect

Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (N?,N?-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), N?,N?-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and N?,N?-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex.

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

2008-10-01

117

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

PubMed

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

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

2009-01-14

118

A comparative study of web site performance  

Microsoft Academic Search

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

JungKook Lee; Alastair M. Morrison

2010-01-01

119

Fluorinated pseudopeptide analogues of the neuropeptide 26RFa: synthesis, biological, and structural studies.  

PubMed

A series of four fluorinated dipeptide analogues each containing a fluoro-olefin moiety as peptide bond surrogate has been designed and synthesized. These motifs have been successfully introduced into the bioactive C-terminal heptapeptide of the neuropeptide 26RFa by conventional SPPS. We then evaluated the ability of the generated pseudopeptides to increase [Ca²?](i) in GPR103-transfected cells. For these fluorinated analogues, greater stability in human serum was observed. Their conformations were also investigated, leading to the valuable identification of differences depending on the position of the fluoro-olefin moiety in the sequence. PMID:23940098

Pierry, Camille; Couve-Bonnaire, Samuel; Guilhaudis, Laure; Neveu, Cindy; Marotte, Amélie; Lefranc, Benjamin; Cahard, Dominique; Ségalas-Milazzo, Isabelle; Leprince, Jérôme; Pannecoucke, Xavier

2013-08-12

120

Sensing of hydrophobic cavity of serum albumin by an adenosine analogue: Fluorescence correlation and ensemble spectroscopic studies.  

PubMed

Adenosine is a naturally occurring purine nucleoside that plays important role in various biochemical processes. We have studied the binding of TNP-Ado (trinitrophenylated-adenosine), a fluorescent analogue of adenosine (which itself is a weak fluorophore), with a model transport protein, bovine serum albumin (BSA). The binding affinity was determined using Fluorescence correlation spectroscopy (FCS) and compared with its value obtained from macroscopic fluorescence spectroscopic studies. Fluorescence and circular dichroism (CD) spectroscopies were employed together with molecular docking study to locate the probable binding site of TNP-Ado on BSA and its effect on the conformation and stability of BSA. Fluorescence studies showed that TNP-Ado binds to BSA in 1:1 stoichiometry via an entropically favoured process. Induced CD spectra revealed that a chiro-optical switching of TNP-Ado occurs upon binding to BSA. Results on urea-induced denaturation of BSA and docking study suggested that the binding site for the ligand is in the hydrophobic subdomain IIA of BSA, consistent with the results of other measurements. This study establishes TNP-Ado as a sensor of hydrophobic regions in proteins like serum albumin, having the capability of detecting a minimum concentration of 140ng/ml protein. FCS measurement of binding interaction of rhodamine-labeled TNP-Ado (RTNP-Ado) with BSA yielded an association constant of KFCS=(1.03±0.06) × 10(4)M(-1). The association constants (Ka) obtained for binding of BSA with rhodamine-free (i.e. TNP-Ado) and rhodamine-labeled (RTNP-Ado) ligands, obtained using the ensemble spectroscopic technique, were (2.3±0.06) × 10(5)M(-1) and (3.4±0.03) × 10(4)M(-1), respectively. The difference between the values of Ka for the free and labeled ligands suggests that fluorescent labeling of small molecules perceptibly interferes with the binding process. On the other hand, the difference in Ka obtained by FCS and ensemble techniques is due to the fact that while the former measures the change in the diffusion constant (i.e. size) of RTNP-Ado upon binding to BSA, the latter focuses on the change of tryptophan emission properties of BSA due to the presence of bound RTNP-Ado. PMID:24061159

Nag, Moupriya; Bera, Kallol; Chakraborty, Sandipan; Basak, Soumen

2013-08-30

121

Hypnotic Enhancement of Cognitive-Behavioral Interventions for Pain: An Analogue Treatment Study  

Microsoft Academic Search

Recent meta-analyses have shown that adding hypnosis enhances the effectiveness of cognitive-behavioral psychotherapy. This hypnotic enhancement effect was evaluated in the analogue treatment of pain. Individuals scoring in the high (n = 135) and low (n = 150) ranges of hypnotic suggestibility were randomly assigned to 1 of 6 conditions: Stress Inoculation Training, the same treatment provided hypnotically, nonhypnotic analgesia

Leonard S. Milling; Michelle R. Levine; Suzanne A. Meunier

2003-01-01

122

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

SciTech Connect

{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.

Birdsall, B.; Tendler, S.J.B.; Feeney, J.; Carr, M.D. (National Institute for Medical Research, London (United Kingdom)); Arnold, J.R.P.; Thomas, J.A.; Roberts, G.C.K. (Univ. of Leicester (United Kingdom)); Griffin, R.J.; Stevens, M.F.G. (Aston Univ., Birmingham (United Kingdom))

1990-10-01

123

A new analogue scale for assessing children's pain: an initial validation study  

Microsoft Academic Search

A new instrument was designed to provide a practical clinical measure for assessing children's pain intensity and pain affect. The pocket size measure includes a Coloured Analogue Scale (CAS) to assess intensity and a facial affective scale to assess the aversive component of pain. Both scales have numerical ratings on the back, so that the person administering it can quickly

Patricia A. McGrath; Cheryl E. Seifert; Kathy N. Speechley; John C. Booth; Larry Stitt; Margaret C. Gibson

1996-01-01

124

Design, synthesis, and structure-activity relationship studies of ATP analogues as DNA gyrase inhibitors.  

PubMed

We report herein the design and synthesis of ATP-analogues, namely 4-amino-pyrazolo[3,4-d]pyrimidines and 4-amino-pyrazolo[1,5-a][1,3,5]triazines, with DNA gyrase inhibitory activity. Among these series, some compounds exhibited promising antibacterial activity. PMID:10782694

Lübbers, T; Angehrn, P; Gmünder, H; Herzig, S; Kulhanek, J

2000-04-17

125

Studies on the induction of petite mutants in yeast by analogues of berenil  

Microsoft Academic Search

Compound Hoe 15 030 is an analogue of berenil which is as effective as berenil in inducing petite mutants in Saccharomyces cerevisiae. Hoe 15 030 has greater stability than berenil in aqueous solution, and is less toxic to yeast at high drug concentrations. Mutants of S. cerevisia strain J69-1B have been isolated which are resistant to the petite inducing effects

Paul R. Vaughan; H. Loewe; Phillip Nagley

1979-01-01

126

Solid–liquid equilibrium and thermochemical studies of organic analogue of metal–nonmetal system: Succinonitrile–pentachloronitrobenzene  

Microsoft Academic Search

The phase diagram of an organic analogue of a metal–nonmetal system, involving succinonitrile–pentachloronitrobenzene, shows the formation of a eutectic and a monotectic. The two immiscible liquid phases are in equilibrium with a single liquid phase and the consolute temperature being 53.5°C above the monotectic horizontal. The phase equilibrium study confirms the alloy composition of monotectic and eutectic at 0.150 and

Shiva Kant; R. N. Rai

2011-01-01

127

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam  

Microsoft Academic Search

The experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the “photosensitivity model”, an early phaseII study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13–38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised

D. G. A. Kasteleijn-Nolst Trenité; C. Marescaux; S. Stodieck; P. M. Edelbroek; J. Oosting

1996-01-01

128

Studies of inositol analogues as inhibitors of the phosphoinositide pathway, and incorporation of 2-deoxy-2-fluoro-myo-inositol to give analogues of phosphatidylinositol intermediates.  

PubMed

The incorporation of [3H]Ins into PtdIns by exchange of free and lipid-bound inositol moieties occurs via the action of at least two types of Mg2+/Mn(2+)-dependent enzymes in turkey erythrocytes. One is a nucleotide-independent PtdIns/Ins exchange enzyme and its function is, as yet, unknown, whereas the other is CMP-dependent and appears to be an exchange reaction catalysed by PtdIns synthase. The effects of analogues with modifications of the substituent at the 1-, 2-, 3-, 4- and 5-positions on the incorporation of [3H]Ins into PtdIns under both synthase and exchange reaction conditions were investigated in turkey erythrocytes. Analogues causing substantial inhibition of [3H]Ins incorporation were then used in kinetic experiments to determine the type of inhibition involved. The analogues 1-deoxy-1-fluoro-scyllo-inositol and 5-O-methyl-myo-inositol exhibited the greatest effects on the incorporation of [3H]Ins via both the synthase and exchange reactions, and the kinetic analysis indicated that they were competitive inhibitors of Ins. Ki values of 0.37 mM and 2.87 mM were observed for 1-deoxy-1-fluoro-scyllo-inositol under exchange and synthase reaction conditions respectively; similar Ki values of 0.26 mM and 2.80 mM were observed for 5-O-methyl-myo-inositol in the exchange and synthase reactions respectively. The ability of 1-deoxy-1-fluoro-scyllo-inositol and its diastereoisomer, 2-deoxy-2-fluoro-myo-inositol, to act as substrates for the synthase and exchange reactions in turkey erythrocytes was investigated. The radiolabelled derivative of the former analogue was not incorporated into phospholipids, whereas the radiolabelled derivative of the latter analogue was a poor substrate for the synthase and exchange enzymes. In the presence of ATP, the labelled analogue of PtdIns, derived from 2-deoxy-2-fluoro-myo-[2-3H]inositol, appeared to be converted into phosphorylated PtdIns analogues, presumably by the enzymes of the phosphoinositide pathway. PMID:1650182

McPhee, F; Downes, C P; Lowe, G

1991-07-15

129

Developing Study Stations on Your School Site.  

ERIC Educational Resources Information Center

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…

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

130

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

PubMed Central

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

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

131

Physical-property measurements on samples from an analogue Soviet Nuclear Test Site: Northern Maine. Technical report  

Microsoft Academic Search

The Joint Verification Experiments (JVE) between the US and USSR were designed to improve yield estimates and verification methods for underground nuclear tests. Members of US team retrieved cores of underground rock samples from Semipalatinsk test site. The mechanical properties of these rocks are being measured in a number of US laboratories. DARPA has begun geological and geophysical characterization of

R. L. Biegel; C. H. Scholz

1991-01-01

132

Revisiting sesquiterpene biosynthetic pathways leading to santalene and its analogues: a comprehensive mechanistic study.  

PubMed

Santalene and bergamotene are the major olefinic sesquiterpenes responsible for the fragrance of sandalwood oil. Herein we report the details of density functional theory investigations on the biosynthetic pathway of this important class of terpenes. The mechanistic study has been found to be effective toward gaining significant new insight into different possibilities for the formation of the key intermediates involved in santalene and bergamotene biosynthesis. The stereoelectronic features of the transition states and intermediates for (i) ring closure of the initial bisabolyl cation, and (ii) skeletal rearrangements in the ensuing bicyclic carbocationic intermediates leading to (-)-epi-?-santalene, (-)-?-santalene, (-)-?-santalene, (+)-epi-?-santalene, exo-?-bergamotene, endo-?-bergamotene, exo-?-bergamotene, and endo-?-bergamotene are presented. Interesting structural features pertaining to certain new carbocationic intermediates (such as b) resulting from the ring closure of bisabolyl cation are discussed. Extensive conformational sampling of all key intermediates along the biosynthetic pathway offered new insight into the role of the isoprenyl side chain conformation in the formation of santalene and its analogues. Although the major bicyclic products in Santalum album appear to arise from the right or left handed helical form of farnesyl pyrophosphate (FPP), different alternatives for their formation are found to be energetically feasible. The interconversion of the exo and endo isomers of bisabolyl cation and a likely epimerization, both with interesting mechanistic implications, are presented. The exo to endo conversion is identified to be energetically more favorable than another pathway emanating from the left handed helical FPP. The role of pyrophosphate (OPP(-)) in the penultimate deprotonation step leading to olefinic sesquiterpenes is also examined. PMID:22951817

Jindal, Garima; Sunoj, Raghavan B

2012-10-21

133

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

NASA Astrophysics Data System (ADS)

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

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

2011-05-01

134

Structural, thermodynamic, and kinetic properties of Gramicidin analogue GS6 studied by molecular dynamics simulations and statistical mechanics.  

PubMed

Gramicidin S (GS) analogues belong to an important class of cyclic peptides, characterized by an antiparallel double-stranded beta-sheet structure with Type II' beta-turns. Such compounds can be used as model systems to understand the folding/unfolding process of beta-hairpins and more in general of beta-structures. In the present study, we specifically investigate the folding/unfolding behavior of the hexameric Gramicidin S analogue GS6 by using all-atoms molecular dynamics (MD) simulations at different temperatures, coupled to a statistical mechanical model based on the Quasi Gaussian Entropy theory. Such an approach permits to describe the structural, thermodynamic, and kinetic properties of the peptide and to quantitatively characterize its folding/unfolding transitions. PMID:19396809

Zanetti-Polzi, Laura; Anselmi, Massimiliano; D'Alessandro, Maira; Amadei, Andrea; Di Nola, Alfredo

2009-12-01

135

1,5-(Diethylamino)piperidine, a novel spermidine analogue that more specifically activates the N-methyl-D-aspartate receptor-associated polyamine site.  

PubMed

We have investigated the action of 1,5-(diethylamino)piperidine (DEAP), a novel spermidine analogue that activates the polyamine site associated with the N-methyl-D-aspartate receptor. DEAP increased [3H]dizocilpine ([3H]MK801) binding to rat brain membranes with a potency similar to that of spermine and spermidine, but with a somewhat greater efficacy. Unlike other polyamines, however, DEAP did not exhibit low affinity inhibition of [3H] dizocilpine binding, suggesting that it binds more selectively to the polyamine site. DEAP increased the equilibrium affinity of [3H]dizocilpine. The increase in affinity was due to slowed dissociation, as well as a small increase in the association rate of [3H]dizocilpine. All of these effects of DEAP could be reversed by arcaine. These data illustrate the utility of DEAP as a novel polyamine agonist at the N-methyl-D-aspartate receptor complex. However, these data fail to support the hypothesis that polyamines activate the N-methyl-D-aspartate receptor by a mechanism similar to that of glutamate and glycine. PMID:1535417

Reynolds, I J

1992-06-01

136

Neurosteroid analogues. 15. A comparative study of the anesthetic and GABAergic actions of alphaxalone, ? 16-alphaxalone and their corresponding 17-carbonitrile analogues  

Microsoft Academic Search

Alphaxalone, a neuroactive steroid containing a 17?-acetyl group, has potent anesthetic activity in humans. This pharmacological activity is attributed to this steroid’s enhancement of ?-amino butyric acid-mediated chloride currents at ?-amino butyric acid type A receptors. The conversion of alphaxalone into ?16-alphaxalone produces an analogue that lacks anesthetic activity in humans and that has greatly diminished receptor actions. By contrast,

Achintya K. Bandyopadhyaya; Brad D. Manion; Ann Benz; Amanda Taylor; Nigam P. Rath; Alex S. Evers; Charles F. Zorumski; Steven Mennerick; Douglas F. Covey

2010-01-01

137

A study of temperature regulation in the human body with the aid of an analogue computer  

Microsoft Academic Search

To be able to predict man's thermal response to any given environment it is essential to have a thorough understanding of man's thermo-regulatory mechanism. The mechanism is dependant on a number of highly non-linear variables. An analogue computer can be of great value with such a problem as non-linear control characteristics are easily incorporated into its programme. The computer is

A. R. Atkins; C. H. Wyndham

1969-01-01

138

Studies of Titan s aerosols analogues produced by radio frequency dischare  

NASA Astrophysics Data System (ADS)

Titan s organic aerosols play a significant role in the physico-chemical mechanisms of the Titan s atmosphere and heat transfer on the Titan s surface. As a matter of fact, the increase of surface temperature due to the methane green house effect is reduced by the solar flux absorption due to the haze layers of Titan s atmosphere. The presented laboratory experiment is developed to produce analogues of Titan s aerosols. The photo chemistry of the N2-CH4 mixture representative of Titan s atmosphere is simulated by a low pressure Radio Frequency plasma discharge. In this plasma, solid particles are produced in the gas. They are maintained in levitation by electrostatic force and they grow in the gas, away from the reactor walls. This phenomena was first observed in Argon Silane RF plasmas used for micro-electronic component production. The aim of this paper is to present new results obtained in N2-CH4 RF plasma. In this plasma the gas mixture is injected continuously and pumped with a mechanical vacuum pump, in order to maintain the plasma in low pressure conditions. In the studied pressure range, the plasma is not in thermal equilibrium, i.e neutral gas remains at room temperature, when electrons have a mean energy of about 1eV. Solid particles produced into the plasma are ejected when their weight is too high to be balanced by electrostatic force. The collected particles are observed and analysed. We observe that their colour changes from clear brown to dark brown following the plasma conditions. In order to change the composition of solid particles, total pressure is adjusted from 0.2 mbar to 3 mbar, and the CH4 percentage up to 10%. Solid particles are also observed by Scanning Electron Microscopy (SEM). They present a regular spherical shape and a size dispersion with a mean diameter of 0.8 mm. Their composition is investigated by pyrolysis-Gas-Chromatography-Mass Spectrometry (pyr-GC-MS) and elementary analysis. In order to correlate the solid particles composition to the plasma properties, plasma is studied by UV visible Optical Emission Spectroscopy (OES). Presence of reactive radicals like CN is observed. Moreover, from OES it is possible to point out an evolution of the electron mean energy with total pressure. From these data, it is possible to have information on the Electron Energy Distribution Function (EEDF) which is important for the modelling of the physico-chemical mechanisms of the plasma, and to compare these mechanisms to that of Titan s atmosphere.

Szopa, C.; Cernogora, G.; Boufendi, L.; Correia, J. J.; Ausset, P.

139

Comparison with Several Oxidation States of Ruthenium Binuclear Complexes; Ruthenium Analogue for Iron Protein Active Site Model  

Microsoft Academic Search

Alkoxo bridged ruthenium dinuclear complexes as a non-heme diiron protein active site model, [Ru(III)2(dhpta)(O2CR)2] (H5dhpta=1, 3-diamino-2- hydroxypropane-N,N,N?,N?-tetraacetic acid, R=CH3(1), C6H5(2), C6H4-p-OH(3), C6H4-p-NH2(4)) exhibited the strongly antiferromagnetically coupled magnetic behavior (H = ?2J*S1*S2, -J=310?470 cm). The magnetic interaction between Ru(III) ions varies depending on the bridged carboxylato ligand. The one- electron reduced Ru(II)Ru(III) mixed-valence states by electrolysis shows two absorption bands

Keiko Tanaka; Akio Ichimura; Isamu Kinoshita; Masa-Aki Haga; Wasuke Mori; Masako Kato; Shigenobu Yano

1996-01-01

140

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

NASA Astrophysics Data System (ADS)

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.

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

2005-04-01

141

Copper inhibits activated protein C: protective effect of human albumin and an analogue of its high-affinity copper-binding site, d-DAHK.  

PubMed

Activated protein C (APC) is useful in the treatment of sepsis. Ischemia and acidosis, which often accompany sepsis, cause the release of copper from loosely bound sites. We investigated (i) whether physiological concentrations of copper inhibit APC anticoagulant activity and (ii) if any copper-induced APC inhibition is reversible by human serum albumin (HSA) or a high-affinity copper-binding analogue of the human albumin N-terminus, d-Asp-d-Ala-d-His-d-Lys (d-DAHK). APC activity after 30 min of incubation with CuCl2 (10 microM) was decreased 26% below baseline. HSA, both alone and when combined with various ratios of CuCl2, increased APC activity significantly above baseline. d-DAHK alone and 2:1 and 4:1 ratios of d-DAHK:CuCl2 also increased APC activity. APC contained 1.4 microM copper, which helps explain the increased APC activity with HSA and d-DAHK alone. These in vitro results indicate that copper inhibits APC activity and that albumin and d-DAHK reverse the copper-induced APC deactivation. PMID:11820775

Bar-Or, David; Rael, Leonard T; Winkler, James V; Yukl, Richard L; Thomas, Gregory W; Shimonkevitz, Richard P

2002-02-01

142

Synthesis and SAR of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one as NMDA/glycine site antagonists.  

PubMed

A series of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one was synthesized and assayed as NMDA/glycine receptor antagonists. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [(3)H]5,7-dicholorokynurenic acid ([(3)H]DCKA) in rat brain cortical membranes. Selected compounds were also tested for functional antagonism using electrophysiological assays in Xenopus oocytes expressing cloned NMDA receptor (NR) 1A/2C subunits. Among the 5-, 6-, 7-, and 8-aza-3-aryl-4-hydroxyquinoline-2(1H)-ones investigated, 5-aza-7-chloro-4-hydroxy-3-(3-phenoxyphenyl)quinolin-2-(1H)-one (13i) is the most potent antagonist, having an IC(50) value of 110 nM in [(3)H]DCKA binding and a K(b) of 11 nM in the electrophysiology assay. Compound 13i is also an active anticonvulsant when administered systemically in the mouse maximum electroshock-induced seizure test (ED(50)=2.3mg/kg, IP). PMID:11504642

Zhou, Z L; Navratil, J M; Cai, S X; Whittemore, E R; Espitia, S A; Hawkinson, J E; Tran, M; Woodward, R M; Weber, E; Keana, J F

2001-08-01

143

Alternating-Site Mechanism of Kinesin-1 Characterized by Single-Molecule FRET Using Fluorescent ATP Analogues  

PubMed Central

Abstract Kinesin-1 motor proteins move along microtubules in repetitive steps of 8 nm at the expense of ATP. To determine nucleotide dwell times during these processive runs, we used a Förster resonance energy transfer method at the single-molecule level that detects nucleotide binding to kinesin motor heads. We show that the fluorescent ATP analog used produces processive motility with kinetic parameters altered <2.5-fold compared with normal ATP. Using our confocal fluorescence kinesin motility assay, we obtained fluorescence intensity time traces that we then analyzed using autocorrelation techniques, yielding a time resolution of ?1 ms for the intensity fluctuations due to fluorescent nucleotide binding and release. To compare these experimental autocorrelation curves with kinetic models, we used Monte-Carlo simulations. We find that the experimental data can only be described satisfactorily on the basis of models assuming an alternating-site mechanism, thus supporting the view that kinesin's two motor domains hydrolyze ATP and step in a sequential way.

Verbrugge, Sander; Lechner, Bettina; Woehlke, Gunther; Peterman, Erwin J.G.

2009-01-01

144

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

Microsoft Academic Search

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

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

2009-01-01

145

Bisphenol A and Its Analogues Activate Human Pregnane X Receptor  

PubMed Central

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.

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

2012-01-01

146

Synergistic Inhibition of Growth of Breast and Colon Human Cancer Cell Lines by Site-selective Cyclic AMP Analogues  

Microsoft Academic Search

Our past studies on the mechanism of cyclic AMP (cAMP)-mediated control of tumor growth, using the experimental rat mammary tumor models as well as human breast cancer cell lines, indicated that the action of cAMP is mediated by the R\\

Pierosandro Tagliaferri; Dionyssios Katsaros; Timothy Clair; Giampaolo Tortora; Leonard Neckers; Yu-an Chang; Ganapathi R. Revankar; Gerald W. Crabtree; Roland K. Robins; Yoon Sang

1988-01-01

147

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

Microsoft Academic Search

We synthesized a pentamine (3-3-3-3) and two hex- amine (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 micro- scopic (AFM) techniques. The midpoint concentra- tion of the polyamines on pGL3 condensation (EC50) was 11.3, 10.6, 1.5, 0.49 and 0.52 mM, respectively, for 3-4-3,

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

2004-01-01

148

Synthesis of 13C- and 14C-labeled dinucleotide mRNA cap analogues for structural and biochemical studies  

PubMed Central

Herein we describe the first simple and short method for specific labeling of mono- and trimethylated dinucleotide mRNA cap analogues with 13C and 14C isotopes. The labels were introduced within the cap structures either at the N7 for monomethylguanosine cap or N7 and N2 position for trimethylguanosine cap. The compounds designed for structural and biochemical studies will be useful tools for better understanding the role of the mRNA cap structures in pre-mRNA splicing, nucleocytoplasmic transport, translation initiation and mRNA degradation.

Piecyk, Karolina; Davis, Richard E.; Jankowska-Anyszka, Marzena

2013-01-01

149

Phosphonate analogues of aminoacyl adenylates.  

PubMed Central

Phosphonomethyl analogues of glycyl phosphate and valyl phosphate, i.e. NH2-CHR-CO-CH2-PO(OH)2, were synthesized and esterified with adenosine to give analogues of aminoacyl adenylates. The interaction of these adenylate analogues with valyl-tRNA synthetase from Escherichia coli was studied by fluorescence titration. The analogue of valyl phosphate has an affinity for the enzyme comparable with that of valine, but that of valyl adenylate is bound much less tightly than either valyl adenylate or corresponding derivative of valinol. The affinity of the analogue of glycyl adenylate was too low to be measured. We conclude that this enzyme interacts specifically with both the side chain and the anhydride linkage of the adenylate intermediate.

Southgate, C C; Dixon, H B

1978-01-01

150

Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies.  

PubMed Central

A number of nucleoside analogues are active against the infectivity of human immunodeficiency virus (HIV); however, their use is limited by toxic side effects and by limited phosphorylation in the infected cells. In an attempt to overcome these problems, a drug delivery system has been developed. A prototype of these drugs in a form already phosphorylated (2',3'-dideoxycytidine 5'-triphosphate; ddCTP) was encapsulated into erythrocytes. Subsequently, by the addition of Zn, an arrangement of band 3 in clusters was induced (band 3 is the major transmembrane protein in erythrocytes). The immune system recognizes these clusters as nonself, promoting autologous IgG binding and phagocytosis by cells of the monocyte-macrophage lineage. In this way, ddCTP encapsulated into erythrocytes was delivered to macrophage cells, where concentrations greater than 2 microM were found. Addition of ddCTP-loaded erythrocytes to macrophages previously infected by HIV-1 results in almost complete inhibition of HIV production over 3 weeks in culture. Administration of ddCTP-loaded erythrocytes to LP-BM5-infected mice at 10-day intervals over a period of 3 months results in reduction of lymphoadenopathy, splenomegaly, and hypergammaglobulinemia. Thus, the delivery of nucleoside analogues in phosphorylated form is feasible, and selective targeting to virus reservoirs (macrophage cells) can be accomplished by the use of autologous erythrocytes. Images

Magnani, M; Rossi, L; Brandi, G; Schiavano, G F; Montroni, M; Piedimonte, G

1992-01-01

151

Study of the rat liver S-adenosylmethionine synthetase active site with 8-azido ATP.  

PubMed Central

The active site of rat liver S-adenosylmethionine synthetase was studied using 8-azido ATP, a photolabile analogue of ATP. Both forms of the enzyme, tetramer and dimer, could be labelled by using concentrations of the analogue similar to the KmATP values for each form, 350 microM and 1 mM respectively. Labelling of both S-adenosylmethionine synthetase forms with 8-azido [alpha-32P]ATP, followed by tryptic digestion and purification by HPLC, afforded one specifically labelled peptide in each case. Identification of the labelled peptide by amino acid analysis and peptide sequencing, and comparison with the enzyme sequence, indicated that the same peptide (267-286) was modified in both enzyme forms. The results are discussed on the basis of the high degree of similarity that this peptide shows in all the known S-adenosylmethionine synthetase sequences. Images Figure 3

Deigner, H P; Mato, J M; Pajares, M A

1995-01-01

152

Hanford Site lighting occupancy sensor study  

SciTech Connect

This study was designed to assess the potential energy savings from the use of lighting occupancy sensor control in the US Department of Energy (DOE) Hanford Site office facilities. The final results of the study provide useful information for assessing cost-effective use of occupancy sensor lighting control. The results also include specific application data for Hanford Site office building spaces that indicate where sensor technology could be applied for cost-effective energy savings.

Richman, E.E.; Dittmer, A.L.; Keller, J.M.

1993-09-01

153

Taxane analogues against breast cancer: a quantitative structure-activity relationship study.  

PubMed

Breast cancer is the second leading cause of cancer death among women in the United States. Two taxane analogues, taxol and taxotere, are the most important antimitotic drugs currently in clinical use for the treatment of breast cancers. However, recent reports have indicated that the use of these drugs often results in various undesired side effects as well as multi-drug resistance. These limitations have led to the development of new taxane derivatives with fewer side effects, superior pharmacological properties, and improved anticancer activity to maximize the induced benefits for breast cancer patients. Herein, four series of taxane derivatives were used to correlate their inhibitory activities against breast cancer cells with their hydrophobic and steric properties in order to understand their chemical-biological interactions. The resulting QSARs show that the inhibitory activities of taxane analogues against breast cancers are mainly dependent either on their hydrophobicity or the hydrophobic/molar refractivity descriptor of their substituents. A parabolic correlation with MR(Y) is the most encouraging example, in which the optimum value of this parameter is well defined. We believe this correlation may prove to be an adequate predictive model that can help provide guidance in design and synthesis and subsequently yield highly specific compounds that may have high anti-breast-cancer activity with fewer side effects and superior pharmacological properties. On the basis of this QSAR model, five compounds are suggested as potential synthetic targets. Internal (cross-validation (LOO-q(2) and LMO-q(2)), quality factor (Q), Fischer statistics (F), and Y-randomization) and external validation tests have validated all the QSAR models. PMID:18196507

Verma, Rajeshwar P; Hansch, Corwin

2008-04-01

154

The missing link in COS metabolism: a model study on the reactivation of carbonic anhydrase from its hydrosulfide analogue.  

PubMed

Carbonic anhydrase (CA) is known to react with carbonyl sulfide, an atmospheric trace gas, whereby H(2)S is formed. It has been shown that, in the course of this reaction, the active catalyst, the His(3)ZnOH structural motif, is converted to its hydrosulfide form: His(3)ZnOH+COS-->His(3)ZnSH+CO(2). In this study, we elucidate the mechanism of reactivation of carbonic anhydrase (CA) from its hydrosulfide analogue by using density functional calculations, a model reaction and in vivo experimental investigation. The desulfuration occurs according to the overall equation His(3)ZnSH+H(2)O right harpoon over left harpoon His(3)ZnOH+H(2)S. The initial step is a protonation equilibrium at the zinc-bound hydrosulfide. The hydrogen sulfide ligand thus formed is then replaced by a water molecule, which is subsequently deprotonated to yield the reactivated catalytic centre of CA. Such a mechanism is thought to enable a plant cell to expel H(2)S or rapidly metabolise it to cysteine via the cysteine synthase complex. The proposed mechanism of desulfuration of the hydrosulfide analogue of CA can thus be regarded as the missing link between COS consumption of plants and their sulfur metabolism. PMID:17304603

Notni, Johannes; Schenk, Stephan; Protoschill-Krebs, Gabi; Kesselmeier, Jürgen; Anders, Ernst

2007-03-26

155

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

PubMed Central

(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.

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

2012-01-01

156

A perfusion study of the handling of urea and urea analogues by the gills of the dogfish shark (Squalus acanthias)  

PubMed Central

The branchial mechanism of urea retention in elasmobranchs was investigated using an in vitro isolated-perfused head preparation, as well as in vivo samples, in the spiny dogfish shark. Both in vivo and in control saline perfusions containing 350 mmol L?1 urea, calculated intracellular urea concentrations in gill epithelial cells were close to extracellular concentrations. Urea efflux to the external water fell only non-significantly, and calculated gill intracellular urea concentration did not change when perfusate urea concentration was reduced from 350 to 175 mmol?L?1 with osmotic compensation by 175 mmol L?1 mannitol. However, when the urea analogues thiourea or acetamide were present in the perfusate at concentrations equimolar (175 mmol L?1) to those of urea (175 mmol L?1), urea efflux rates were increased 4-fold and 6.5-fold respectively, and calculated gill intracellular urea concentrations were depressed by about 55%. Analogue efflux rates were similar to urea efflux rates. Previous studies have argued that either the basolateral or apical membranes provided the limiting permeability barrier, and/or that a back-transporter on the basolateral membranes of gill cells is responsible for urea retention. The present results provide new evidence that the apical membrane is the limiting factor in maintaining gill urea impermeability, and raise the prospect that a urea back-transporter, which can be competitively inhibited by thiourea and acetamide, operates at the apical membrane.

Liew, Hon Jung; De Boeck, Gudrun; Walsh, Patrick J.

2013-01-01

157

Additional Media Studies for Site Suitability Criteria.  

National Technical Information Service (NTIS)

Site suitability studies have been made previously at LLL on bedded salt and shale. In the present study domed salt, basalt, and crystalline rock are compared with bedded salt and shale and with each other as possible repositories. The level of effort req...

T. R. Donich A. M. Kaufman G. D. Sauter T. L. Steinborn D. F. Towse

1978-01-01

158

Caffeine as base analogue of adenine or guanine: a theoretical study.  

PubMed

The results of quantum mechanical calculations, including binding energies and results of the population analysis show that the GC and AT base pair complexes are more stable than the CAF-X ones (where CAF is caffeine and X=adenine (A), thymine (T), cytosine (C) and guanine (G)). Structural similarity between the CAF molecule and purine bases (G and A) provides the possibility of incorporation of the CAF molecule into the DNA macromolecule. By comparing the CAF-A and CAF-T complexes with the AT base pair, and the CAF-G and CAF-C complexes with the GC base pair, it was found that the formation of the CAF-T complex is more probable than the other complexes. Thus, the CAF molecule acts as an analogue base of A and can be incorporated into the DNA macromolecule and paired with T and C in normal and rare state, respectively. Indeed, the results show that formation of the CAF-C complex is less probable than the CAF-T one and an AT to GC conversion is rarely occurred in the next DNA replication, so the CAF molecule may be considered as a weak mutagenic compound. To examine solvent effect, the binding energies have been calculated in solvent for the most important structures of the CAF-G, CAF-T, CAF-A and CAF-C complexes. The results in solvent are in agreement with those in the gas phase. PMID:23583737

Ebrahimi, Ali; Habibi-Khorassani, Mostafa; Akher, Farideh Badichi; Farrokhzadeh, Abdolkarim; Karimi, Pouya

2013-03-18

159

Upper Ottawa street landfill site health study.  

PubMed Central

This report describes the design and conduct of two sequential historical prospective morbidity surveys of workers and residents from the Upper Ottawa Street Landfill Site in Hamilton, Ontario. The workers study was carried out first and was a hypothesis-generating study. Workers and controls were administered a health questionnaire, which was followed by an assessment of recall bias through medical chart abstraction. Multiple criteria were used to identify health problems associated with landfill site exposure. Those problems with highest credibility included clusters of respiratory, skin, narcotic, and mood disorders. These formed the hypothesis base in the subsequent health study of residents living adjacent to the landfill site. In that study, the association between mood, narcotic, skin, and respiratory conditions with landfill site exposure was confirmed using the following criteria: strength of association; consistency with the workers study; risk gradient by duration of residence and proximity to the landfill; absence of evidence that less healthy people moved to the area; specificity; and the absence of recall bias. The validity of these associations were reduced by three principal problems: the high refusal rate among the control population; socioeconomic status differences between the study groups; and the fact that the conditions found in excess were imprecisely defined and potentially interchangeable with other conditions. Offsetting these problems were the multiple criteria used to assess each hypothesis, which were applied according to present rules. Evidence is presented that supports the hypothesis that vapors, fumes, or particulate matter emanating from the landfill site, as well as direct skin exposure, may have lead to the health problems found in excess. Evidence is also presented supporting the hypothesis that perception of exposure and, therefore, of risk, may explain the results of the study. However, based on the analyses performed, it is the conclusion of the authors that the adverse effects seen were more likely the result of chemical exposure than of perception of risk.

Hertzman, C; Hayes, M; Singer, J; Highland, J

1987-01-01

160

Comparative study of alkane dications (protonated alkyl cations, C(n)H(2n+2)2+) and their isoelectronic boron cation analogues.  

PubMed

Comparative study of the superelectrophilic alkane dications (C(n)H(2n+2)2+), n = 1-5) and their isoelectronic boron cation analogues was carried out using the ab initio method at the MP2/cc-pVTZ level. The structure, bonding, and relative stability of doubly charged alkane dications and monocharged boron cation analogues are discussed. These studies contribute to our general understanding of the superelectrophilic activation of alkyl cations as well as the electrophilic reactivity of C-H and C-C single bonds. PMID:22731108

Rasul, Golam; Prakash, G K Surya; Olah, George A

2012-07-03

161

Simulations & Case Studies. [SITE 2002 Section].  

ERIC Educational Resources Information Center

|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…

Seymour, Cathy R., Ed.

162

Kinetic studies of the predicted substrate-binding site of varicella-zoster virus thymidine kinase.  

PubMed

To investigate the mechanism of kinetic action and substrate recognition of varicella-zoster virus (VZV) thymidine kinase (TK), we designed and isolated a site-directed mutant VZV TK which has double amino acid substitutions, 136threonine to leucine and 137isoleucine to leucine (SDM TK). This mutant was designed to alter the substrate-binding site of the VZV TK to duplicate that of the herpes simplex virus type 2 enzyme. Kinetic studies of the activity of wild-type TK indicated that the binding order of ATP and thymidine is random and that wild-type VZV TK possessed high thymidylate kinase (TM-K) activity. The sensitivity of VZV TK to bisubstrate analogues, dinucleotides of adenosine and thymidine, showed that the optimum distance between the ATP- and substrate-binding sites is two phosphoryl groups greater than with the natural substrate for TK activity. SDM TK lost deoxycytidine kinase activity and had reduced TK and TM-K activities. Inhibition studies on both WT and SDM TK by 5-halogenovinyluridine analogues and their 5' monophosphate derivatives revealed that amino acids at positions 136 and 137 are involved in substrate binding, probably through a role in the formation of the binding pocket for bulky substrates. PMID:8389797

Suzutani, T; Davies, L C; Honess, R W

1993-06-01

163

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

PubMed Central

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.

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

2011-01-01

164

Study of the cytotoxicity and antioxidant capacity of N/OFQ(1-13)NH2 and its structural analogues.  

PubMed

The effect of side-chain shortening of N/OFQ(1-13)NH(2) at position 9 ([Orn(9)]N/OFQ(1-13)NH(2), [Dab(9)]N/OFQ(1-13)NH(2), [Dap(9)]N/OFQ(1-13)NH(2)) was studied regarding potential toxicity and antioxidant capacity. Staurosporine- and H2O2-induced damage of SH-SY5Y neuroblastoma cells was not changed in the presence of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2), but was strongly enhanced in the presence of [Dab(9)]N/OFQ(1-13)NH(2) and [Dap(9)]N/OFQ(1-13)NH(2). Moreover, treatment of cells with the latter two analogues alone led to cell injury. Neuropeptide-dependent differences in the viability of SH-SY5Y cells were also observed, i.e., a cytoprotective effect was observed only in the presence of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2). Compared to [Dab(9)]N/OFQ(1-13)NH(2) and [Dap(9)]N/OFQ(1-13)NH(2), the effects of N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2) were more beneficial in systems generating free oxygen radicals (O(2)(-) and .OH), as well as on the antioxidant status of rat brain and liver. Taken together, our findings show that N/OFQ(1-13)NH(2) and its structural analogue [Orn(9)]N/OFQ(1-13)NH(2) possess more favorable profiles than the other two nociceptin (N/OFQ) analogues. The present results suggest that shortening of the side-chain of N/OFQ(1-13)NH(2) might increase cell damage and reduce the viability of SH-SY5Y neuroblastoma cells. Moreover, such alterations may lead to changes in free-oxygen generating systems and in antioxidant status in animal tissues. PMID:20081252

Kirkova, Margarita; Zamfirova, Rositsa; Le?kiewicz, Monika; Kubera, Marta; Laso?, W?adys?aw; Todorov, Simeon

165

Bismuth-doped tin clusters: experimental and theoretical studies of neutral Zintl analogues.  

PubMed

The electron count of gas-phase clusters is increased gradually by element substitution in order to mimic the total number of electrons of known stable closo-clusters. A combination of elements from the fourth and fifth group of the periodic table such as Sn and Bi is well-suited for this approach. Hence, these small Sn-Bi clusters are investigated by employing the electric field deflection method. For clusters in the series Sn(M-N)Bi(N) (M = 5-13, N = 1-2), the beam profiles obtained in cryogenic experiments are dominated by beam broadening, indicating the presence of a permanent electric dipole moment that is sensitive to the (rigid) cluster structure. An intensive search for the global minimum structure employing a density functional theory/genetic algorithm method is performed. Dielectric properties for the identified low-energy isomers are computed. The structural and dielectric properties are used in beam profile simulations in order to discuss the experimental data. Comparison of theoretical and experimental results enables identification of the growing pattern of these small bimetallic clusters. For multiply doped clusters, it is concluded that the dopant atoms do not form direct Bi-Bi bonds, but more interestingly, a rearrangement of the cluster skeleton becomes apparent. The structural motifs are different from pure tin clusters but rather are rationalized using the corresponding structures of tin anions or are based on the Wade-Mingos concept. Further evidence for this idea is deduced from nuclear independent chemical shift calculations, which show nearly identical behavior for negatively charged pure and neutral bimetallic clusters. All of these findings are consistent with the idea of neutral Zintl analogues in the gas phase. PMID:22709275

Heiles, Sven; Johnston, Roy L; Schäfer, Rolf

2012-07-12

166

Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent.  

PubMed

A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1)H, (13)C) spectroscopy, and single-crystal X-ray diffraction. The in vitro inhibitory activity of 1 against 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51.17% of inhibition at 10 ?M), being more active than clofibrate and clofibric acid. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus rat model. The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration. Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11?-HSD1. In this model, compound 1 binds into the catalytic site of 11?-HSD1 in two different orientations. Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP(+). PMID:23597793

Navarrete-Vázquez, Gabriel; Alaniz-Palacios, Alfredo; Hidalgo-Figueroa, Sergio; González-Acevedo, Cristina; Ávila-Villarreal, Gabriela; Estrada-Soto, Samuel; Webster, Scott P; Medina-Franco, José L; López-Vallejo, Fabian; Guerrero-Álvarez, Jorge; Tlahuext, Hugo

2013-04-05

167

Base-base recognition of nonionic dinucleotide analogues in an apolar environment studied by low-temperature NMR spectroscopy.  

PubMed

Two self-complementary dinucleotide analogues T(Si)A and A(Si)T with a nonionic diisopropylsilyl-modified backbone were synthesized, and their association in a nonaqueous aprotic environment was studied by NMR spectroscopy. Using a CDClF(2)/CDF(3) solvent mixture, measurements at temperatures as low as 113 K allowed the observation and structural characterization of individual complexes in the slow exchange regime. The A(Si)T analogue associates to exclusively form a dinucleotide antiparallel duplex with regular Watson-Crick base pairing, but both A and T nucleosides exhibit a predominant C3'-endo sugar pucker reminiscent of an A-type conformation. In contrast to A(Si)T, the T(Si)A dinucleotide is found to exhibit significant variability and flexibility. Thus, different secondary structures with weaker hydrogen bonds for all T(Si)A structures are observed at low temperatures. Although a B-like Watson-Crick antiparallel dinucleotide duplex with a preferred C2'-endo sugar pucker largely predominates at temperatures above 153 K, two additional species, namely a dinucleotide Hoogsteen duplex with a syn glycosidic torsion angle of the adenosine nucleoside and a presumably intramolecularly folded structure, are increasingly populated upon further cooling. By adding typical DNA intercalators like anthracene or benz[c]acridine derivatives to the A(Si)T dinucleotide duplex in the aprotic solvent environment, no binding of the polycyclic aromatic molecules can be detected even at lower temperatures. Obviously, van der Waals and stacking interactions are insufficient to compensate for the other unfavorable contributions to the overall free energy of binding, and only in the presence of additional hydrophobic effects in an aqueous environment does binding occur. PMID:20180555

Xiao, Zhou; Weisz, Klaus

2010-03-24

168

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

PubMed

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/m(2) , and patients with a BMI <35 kg/m(2) 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/m(2) ) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin. PMID:22051096

Barnett, A H

2011-12-22

169

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

PubMed Central

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.

Barnett, A H

2012-01-01

170

Migrastatin analogues target fascin to block tumour metastasis  

SciTech Connect

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.

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

2010-04-15

171

Migrastatin Analogues Target Fascin to Block Tumor Metastasis  

PubMed Central

Tumor metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumor metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces 1,2, and synthesized migrastatin analogues are potent inhibitors of metastatic tumor cell migration, invasion and tumor metastasis 3–6. 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, similar to the microtubule protein tubulin.

Chen, Lin; Yang, Shengyu; Jakoncic, Jean; Zhang, J. Jillian; Huang, Xin-Yun

2010-01-01

172

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

NASA Astrophysics Data System (ADS)

High speed [5-30km/s] interstellar dust (ISD) analogues shot onto Stardust aerogel flight spares show morphology of impact tracks and structural & chemical modification of the projectiles. First results indicate a different ISD flux than previously assumed.

Postberg, F.; Allan, 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.; Grün, E.; Heck, P. R.; Hillier, J. K.; Hoppe, P.; Howard, L.; Huss, G. R.; Huth, J.; Kearsley, A.; King, A. J.; Lai, B.; Leitner, J.; Lemelle, L.; Leroux, H.; Nittler, L. R.; Ogliore, R. C.; Price, M. C.; Sandford, S. A.; Sans Tresseras, J. A.; Schmitz, S.; Schoonjans, T.; Silversmit, G.; Simionovici, A.; Srama, R.; Stadermann, F. J.; Stephan, T.; Sterken, V.; Stodolna, J.; Stroud, R. M.; Sutton, S. R.; Toucoulou, R.; Trieloff, M.; Tsou, P.; Tsuchiyama, A.; Tyliczszak, T.; Vekemans, B.; Vincze, L.; Westphal, A. J.; Zolensky, M. E.

2011-03-01

173

Design, conformational studies and analysis of structure-function relationships of PTH (1-11) analogues: the essential role of Val in position 2.  

PubMed

The N-terminal 1-34 segment of parathyroid hormone (PTH) is fully active in vitro and in vivo and it elicits all the biological responses characteristic of the native intact PTH. Recent studies reported potent helical analogues of the PTH (1-11) with helicity-enhancing substitutions. This work describes the synthesis, biological activity, and conformational studies of analogues obtained from the most active non-natural PTH (1-11) peptide H-Aib-Val-Aib-Glu-Ile-Gln-Leu-Nle-His-Gln-Har-NH2; specifically, the replacement of Val in position 2 with D-Val, L-(?Me)-Val and N-isopropyl-Gly was studied. The synthesized analogues were characterized functionally by in-cell assays and their structures were determined by CD and NMR spectroscopy. To clarify the relationship between the structure and activity, the structural data were used to generate a pharmacophoric model, obtained overlapping all the analogues. This model underlines the fundamental functional role of the side chain of Val2 and, at the same time, reveals that the introduction of conformationally constrained C?-tetrasubstituted ?-amino acids in the peptides increases their helical content, but does not necessarily ensure significant biological activity. PMID:21918876

Caporale, A; Gesiot, L; Sturlese, M; Wittelsberger, A; Mammi, S; Peggion, E

2011-09-15

174

The Media and Communications Studies Site  

NSDL National Science Digital Library

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

Chandler, Daniel.

1995-01-01

175

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

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

176

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

NASA Astrophysics Data System (ADS)

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: ?18O values of Lagoa Salgada stromatolites average -1.5 ‰, while the ?18O 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: ?13C values of Lagoa Salgada stromatolites average 10 to 20 ‰, while the ?13C values of Lagoa Vermehla stromatolites average -2.5 ‰. These dissimilar ?13C 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 and Lagoa Vermehla microbial systems can serve as an analogue to evaluate the impact of the gradual transition from anoxic methane-rich, sulfate-free to sulfate-dominant environments with the rise of atmospheric oxygen on the Precambrian evolution of the microcosm.

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

2009-12-01

177

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

PubMed Central

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

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

2012-01-01

178

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

SciTech Connect

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

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

2009-02-16

179

Defining reference conditions for acidified waters using a modern analogue approach  

Microsoft Academic Search

Analogue matching is a palaeolimnological technique that aims to find matches for fossil sediment samples from a set of modern surface sediment samples. Modern analogues were identified that closely matched the pre-disturbance conditions of eight of the UK Acid Waters Monitoring Network (AWMN) lakes using diatom- and cladoceran-based analogue matching. These analogue sites were assessed in terms of hydrochemistry, aquatic

Gavin L. Simpson; Ewan M. Shilland; Julie M. Winterbottom; Janey Keay

2005-01-01

180

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

PubMed

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

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

181

Hydrolysis of New Transplatin Analogue Containing One Aliphatic and One Planar Heterocyclic Amine Ligand: A Density Functional Theory Study  

NASA Astrophysics Data System (ADS)

Herein we give a theoretical study of the hydrolysis processes of a novel anticancer drug trans-[PtCl2(3-pico)(ipa)] (3-pico = 3-methylpyridine, ipa = isopropylamine). Two different models, model 1 relative to isolated reactant/product (R/P, wherein R = platinum complex+H2O, P = platinum complex+Cl-) and model 2 relative to reactant complex/product complex (RC/PC, wherein RC = (platinum complex)(H2O), PC = (platinum complex)(Cl-) are employed and the geometric structures are optimized at the B3LYP level of DFT method. It is found that the processes of the reactions follow the established theory for ligand substitution in square planar complexes; the geometries of the transition states (TS) agree with the previous related work and all of the reactions are endothermic. The effects originating from the inclusion of the attacking water/released chloride into the second coordination shell of platinum in RC/PC play an important role in the thermodynamic and kinetic profiles of the reactions, that is, the barrier heights of the reactions of model 2 are increased by ~26.3 and ~23.8 kJ/mol for step1 and step2 respectively, and the endothermicity is considerably decreased by ~420.5 and ~771.2 kJ/mol compared to model 1 in the gas phase. The consideration of the bulk solvation effects increase the barrier heights for both steps of model 1 by ~27.6 and ~6.7 kJ/mol respectively, whereas it reduces the barrier heights by ~7.9 and ~29.3 kJ/mol for model 2. The reaction energies are all decreased, especially for model 1, indicating more stable complexes solvated in the bulk aqueous solution than in the gas phase. Additionally, to get an accurate energy picture of the title complex, the relative free energies derived from the DFT-SCRF (density functional theory self-consistent field) calculations are compared with the relative total energies. The results are that activation energies rise for the first hydrolysis and fall for the second hydrolysis for all the systems, and for all the systems, the barrier height of the second hydrolysis is always higher than that of the first step. The rate constants indicate that transplatin analogue is kinetically comparable to cisplatin and its analogue in the hydrolysis process.

Gao, Yan; Zhou, Li-xin

2008-08-01

182

Further SAR studies of piperidine-based analogues of cocaine. 2. Potent dopamine and serotonin reuptake inhibitors.  

PubMed

The synthesis and monoamine transporter activity of additional members of a series of 3,4-disubstituted piperidines (truncated analogues of the WIN series) are described. All members of this series were prepared from arecoline hydrobromide in optically pure form and were evaluated for their ability to inhibit high affinity uptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) into rat brain nerve endings (synaptosomes). Most of the compounds prepared in this series are reasonably potent DAT inhibitors (K(i) values of 4-400 nM) and have selectivity for the 5-HT transporter relative to both the NE transporter (3-9-fold) and to the DAT ( approximately 25-fold). In the present series, (-)-methyl 1-methyl-4beta-(2-naphthyl)piperidine-3beta-carboxylate (6) was found to be the most potent piperidine-based ligand, exhibiting K(i)'s of 21 nM and 7.6 nM at the DAT and 5-HTT, respectively. While the 5-HTT activity of compound 6 is comparable to that of the antidepressant medication fluoxetine, it is less selective. As is apparent from the data presented, the naphthyl substituted piperidines 6-9, which differ in their stereochemistry, show different degrees of selectivity for the three transporters. Consistent with results reported in the literature for the tropane analogues, removal of the methyl group from the nitrogen atom of 9 leads to a further enhancement in 5-HTT activity. To examine the in vivo effects of these piperidines, preliminary behavioral screening was carried out on piperidine 14. Despite its 2.5-fold greater DAT activity compared to cocaine, piperidine 14 was found to be about 2. 5-fold less potent in increasing distance traveled in mice. However, consistent with its DAT activity, piperidine 14 was found to be about 2.5-fold more potent than cocaine in enhancing stereotypic movements. Further studies of these piperidine-based ligands may provide valuable insights into the pharmacological mechanisms underlying the enhancement in distance traveled versus stereotypic movements. The present results have important implications for better understanding the structural motifs required in the design of agents with specific potency and selectivity at monoamine transporters. PMID:10737754

Tamiz, A P; Zhang, J; Flippen-Anderson, J L; Zhang, M; Johnson, K M; Deschaux, O; Tella, S; Kozikowski, A P

2000-03-23

183

Probing the nucleotide binding sites of axonemal dynein with the fluorescent nucleotide analogue 2'(3')-O-(-N-Methylanthraniloyl)-adenosine 5'-triphosphate.  

PubMed

MantATP [2'(3')-O-(-N-methylanthraniloyl)-adenosine 5'-triphosphate] was employed as a fluorescence probe of the nucleotide-binding sites of dynein from sea urchin sperm flagella. MantATP binds specifically with enhanced fluorescence (approximately 2.2-fold), homogeneous lifetime (8.4 ns), and high anisotropy (r approximately 0.38) to dynein and can be displaced by ATP and ADP added to the medium. The association constants of mantATP complexed with dynein were determined from anisotropy titration data. Using a multiple stepwise equilibrium model, the average values of the first two association constants are K1 = 2.7 x 10(5) M-1 and K2 = 1.8 x 10(4) M-1. This value of K1 is 7-8 times higher than that found previously for unsubstituted ATP, whereas K2 is little changed [Mocz and Gibbons (1996) Biochemistry 35, 9204-9211]. The lower-affinity binding sites, K3 and K4, observed previously could not be studied with mantATP within the available protein concentrations. The alpha and beta heavy chain subfractions have binding parameters similar to those of intact dynein. Formation of the stable ternary complex of mantATP with dynein and monomeric vanadate is accompanied by only a moderate increase in the binding affinities. Oligomeric vanadate reduces the binding affinities by approximately 50%. Addition of TritonX-100, methanol, or various salts changes the binding affinities by up to 50%, suggesting that the microenvironment of the nucleotide-binding sites involves significant contributions from both polar and apolar interactions. The distinct affinities of the individual binding sites are consistent with a physiological role in regulating nucleotide binding. PMID:9657700

Mocz, G; Helms, M K; Jameson, D M; Gibbons, I R

1998-07-01

184

Cortical DC potential shifts accompanying the central processing of visually presented analogue and digital time displays.  

PubMed

According to studies in brain-lesioned patients, the cortical substrate subserving the reading of digitally presented time displays seems to differ from that of reading analogue displays. While the right hemisphere has been assumed to be important for reading analogue displays, reading digital displays is attributed to the left hemisphere. This study attempts to localize the cortical substrate of reading analogue versus digital time displays in the intact human brain using scalp-recorded event-related slow negative DC potential shifts. In the arithmetic tasks, subjects had to judge whether or not the time conveyed by the last out of three tachistoscopically presented (analogue or digital) slides was the exact difference between the time conveyed by the first and the second slide. In the control condition, subjects only had to attend to (analogue or digital) time displays. With analogue slides, frontolateral recording sites revealed a right hemispheric preponderance of DC shifts measured in the interval between the second and third slide. Anterior temporal recording sites revealed a right hemispheric preponderance only when calculations were performed. By contrast, there was no hemispheric lateralization with digital slides. The arithmetic versus control manipulation modulated waveforms, but did not influence hemispheric laterality. PMID:9051683

Ebenbichler, G; Uhl, F; Lang, W; Lindinger, G; Egkher, A; Deecke, L

1997-03-01

185

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

PubMed Central

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.

Ehlers, Anke; Mauchnik, Jana; Handley, Rachel

2012-01-01

186

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

PubMed Central

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.

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

1988-01-01

187

CROSS SITE TRANSFER SYSTEM DISPOSITION STUDY  

SciTech Connect

This document describes the cross-site transfer system and evaluates alternative regulatory process for closing the cross-site transfer system. The cross-site transfer system is a component of the single shell tank (SST) system. This document is intended to promote integration and coordination of removal and closure actions for the cross-site transfer system with U Plant closure activities and other facilities on the Central Plateau.

LEE, T.A.

2004-07-14

188

Molecular recognition of synthetic siderophore analogues: A study with receptor-deficient and fhu(AB) deletion mutants of Escherichia coli  

Microsoft Academic Search

The biological activity of six synthetic siderophore analogues (two dihydroxamates, two trihydroxamates, one tetrahydroxamate and one 3-hydroxy-4(1H)pyridinone) has been studied in Escherichia coli, Morganella morganii 13 and Proteus mirabilis 8993 strains by using growth promotion tests. Various transport-deficient mutants of E. coli were used to study the route of entry into gram-negative bacteria. The results indicated that the synthetic hydroxamate compounds

Margarida Gaspar; M. Amélia Santos; Katja Krauter; Günther Winkelmann

1999-01-01

189

Theoretical study of the stability of the DNA duplexes modified by a series of hydrophobic base analogues.  

PubMed

The geometries of a 13 mer of a DNA double helix (5'-GCGTACACATGCG-3') were determined by molecular dynamics simulations using a Cornell et al. empirical force field. The bases in the central base pair (shown in bold) were replaced (one or both) by a series of hydrophobic base analogues (phenyl, biphenyl, phenylnaphathalene, phenylanthracene and phenylphenanthrene). Due to the large fluctuations of the systems, an average geometry could not be determined. The interaction energies of the Model A, which consisted of three central steps of a duplex without a sugar phosphate backbone, taken from molecular dynamics simulations (geometry sampled every 1 ps), were calculated by the self-consistent charge density functional based tight-binding (SCC-DFTB-D) method and were subsequently averaged. The higher the stability of the systems the higher the aromaticity of the base analogues. To estimate the desolvation energy of the duplex, the COSMO continuum solvent model was used and the calculations were provided on a larger model, Model B (the three central steps of the duplex with a sugar phosphate backbone neutralised by H atoms), taken from molecular dynamics simulations (geometry sampled every 200 ps) and subsequently averaged. The selectivity of the base analogue pairs was ascertained (Model B) by including the desolvation energy and the interaction energy of both strands, as determined by the SCC-DFTB-D method. The highest selectivity was found for a phenylphenanthrene. Replacing the nucleic acid bases with a base analogue leads to structural changes of the central pair. Only with the smallest base analogues (phenyl) does the central base pair stay planar. When passing to larger base analogues the central base pair is usually stacked. PMID:19569131

Zendlová, Lucie; Reha, David; Hocek, Michal; Hobza, Pavel

2009-08-01

190

Western Maryland Power Plant Siting Study: discussion of licensing issues and site boundary considerations at three candidate sites. Final report  

SciTech Connect

This document is one of a series of technical reports prepared for the Western Maryland Power Plant Siting Study. Selected licensing issues for the three remaining candidate sites are discussed and related to site boundary considerations. None of the four licensing issues evaluated (noise, fugitive dust, solid waste disposal, point source water discharges) would eliminate any of the three candidate sites from the comparison study. All three sites could likely comply with the air quality standards applicable to fugitive dust emissions. Compliance could be periodically complicated by levels of airborne coal dust at WP-26 during high wind episodes. Noise and fugitive dust level predictions suggested that the original site boundaries could be further refined. Final site boundaries will not be established until after the preferred site is selected.

Klauda, R.J.; Portner, E.M.

1984-10-01

191

Synthesis and biological activity of oxytocin analogues containing unnatural amino acids in position 9: structure activity study  

Microsoft Academic Search

We report the solid phase synthesis and some pharmacological properties of 24 oxytocin (OT) analogues. Basic modifications\\u000a at position 9 (introduction of l- or d-?-(2-thienyl)-alanine [L- or D-Thi], or l- or d-3-Pyridylalanine [l- or d-3-Pal]) were combined with d-tyrosine(OEthyl) [d-Tyr(Et)] or d-1-naphthylalanine [d-1-Nal] in position 2 and ?-mercaptopropionic acid (Mpa) in position 1 modifications in altogether 14 analogues. Additionally, 8

Vassiliki Magafa; Lenka Borovi?ková; Ji?ina Slaninová; Paul Cordopatis

2010-01-01

192

Improved mealtime treatment of diabetes mellitus using an insulin analogue  

Microsoft Academic Search

The absorption of regular human insulin from subcutaneous injection sites is delayed due to the self-association of insulin to multimeric forms. The insulin analogue insulin lispro has a weak self-association and a fast absorption rate. We examined the safety and efficacy of insulin lispro in the premeal treatment of patients with diabetes mellitus. A 12-month study was performed in 336

James H. Anderson; Rocco L. Brunelle; Veikko A. Koivisto; Michael E. Trautmann; Louis Vignati; Richard DiMarchi

1997-01-01

193

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

Microsoft Academic Search

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

R. Navarro-González

2010-01-01

194

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

ERIC Educational Resources Information Center

|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…

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

2010-01-01

195

Under What Conditions Is Individual Psychotherapy Distressing to Clients' Romantic Partners? An Empirical Analogue Study  

Microsoft Academic Search

In this study, undergraduates (n = 473) were asked to envision that their romantic partner was seeing a psychotherapist individually, and were then asked to rate their distress in response to 16 different descriptions of the context of the psychotherapy. Results indicated that overall, participants felt slightly distressed about their partners being in therapy. All contextual variables examined significantly influenced

Andrew M. Pomerantz; Elizabeth A. Seely

2000-01-01

196

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

PubMed

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

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

2011-02-02

197

Applied relaxation: an experimental analogue study of therapist vs. computer administration  

Microsoft Academic Search

This experimental analog component study compared two ways of administrating relaxation, either via a computer or by a therapist. The second phase of applied relaxation was used, which is called “release-only relaxation”. Sixty participants from a student population were randomized to one of three groups: computer-administered relaxation, therapist-administered relaxation, or a control group in which participants surfed on the Internet.

Per Carlbring; Eva Björnstjerna; Anna F. Bergström; Johan Waara; Gerhard Andersson

2007-01-01

198

In Vitro Studies of Antiglaucomatous Prostaglandin Analogues: Travoprost with and without Benzalkonium Chloride and Preserved Latanoprost  

Microsoft Academic Search

PURPOSE. With use of the Wong-Kilbourne derivative Chang conjunctival cell line, this study compared in vitro the ocular toxicity of three topical intraocular pressure (IOP)-lowering agents: travoprost 0.004% containing 0.015% benzalkonium chloride (BAK), travoprost Z 0.004%, a new formulation with- out BAK, and latanoprost 0.005% containing 0.02% BAK. METHODS. Neutral red, Alamar blue, YOPRO-1, and annexin V\\/7-AAD assays were used

Christophe Baudouin; Luisa Riancho; Jean-Michel Warnet; Francoise Brignole

2007-01-01

199

Mineral-chemical and isotopic studies of Namaqualand granulites, South Africa: A grenville analogue  

Microsoft Academic Search

The northwestern part of South Africa and southern South-West Africa\\/Namibia is amongst the most extensive granulite terranes in Africa. This work reports the results of electron microprobe studies of minerals from two-pyroxene, cordieriteorthopyroxene (-gedrite) (-sapphirine) and garnet and\\/or cordierite parageneses from Namaqualand, in the N.W. Cape Province of South Africa. Determined PT conditions of prograde metamorphism based on thermodynamic calculations

Tom N. Clifford; Eugen F. Stumpfl; Alwyn J. Burger; Terence S. McCarthy; David C. Rex

1981-01-01

200

Mineral-chemical and isotopic studies of Namaqualand granulites, South Africa: A grenville analogue  

Microsoft Academic Search

The northwestern part of South Africa and southern South-West Africa\\/Namibia is amongst the most extensive granulite terranes\\u000a in Africa. This work reports the results of electron microprobe studies of minerals from two-pyroxene, cordieriteorthopyroxene\\u000a (-gedrite) (-sapphirine) and garnet and\\/or cordierite parageneses from Namaqualand, in the N.W. Cape Province of South Africa.\\u000a Determined PT conditions of prograde metamorphism based on thermodynamic calculations

Tom N. Clifford; Eugen F. Stumpfl; Alwyn J. Burger; Terence S. McCarthy; David C. Rex

1981-01-01

201

Docking studies on novel alkaloid tryptanthrin and its analogues against enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis.  

PubMed

Isoniazid resistance is a serious threat in the battle against the treatment of multi-drug resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB). Isoniazid is an inhibitor of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis, which is an important and functional enzyme of the type II fatty acid synthesis system and important therapeutic target. Natural alkaloid tryptanthrin and its analogues have shown anti-tubercular activity against MDR-TB, but their cellular target is unknown. In this work, in silico molecular docking was performed using docking server in order to see the interaction of tryptanthrin and its 15 analogues with InhA of M. tuberculosis. Results showed that among tryptanthrin and its 15 analogues, tryptanthrin and its two analogues exhibited good affinity to the binding site of InhA with free binding energy of -7.94 kcal/mol and inhibition constant (Ki) of 1.50 microm. Active site residues of InhA interacting with tryptanthrin were Ser13, Thr39, Phe41, Leu63, Asp64, Val65, Ile95, Phe97 and Ile122. In binding mode, polar bond were found between O1 (1) with Asp64 of bond length (3.34 A) and hydrophobic bonds were found between Leu63 with C15 and C12, Val65 with C7, Val65 with C12 and C4, Ile95 with C6 and C7, Ile95 with C10, C12 and C14. Important pi-pi bonds were found between Phe41 with C2, C5, C7, C12, C4, C6, C8, C9, C13 and Phe97 with C9. These interactions indicated stability of tryptanthrin in active residue and suggested it as a potential drug candidate. Thus, good affinity of tryptanthrin to binding site of InhA may lead to synthesis of anti-tubercular drug capable of combating MDR strains of M. tuberculosis. PMID:23350278

Tripathi, Ankit; Wadia, Nupur; Bindal, Deepak; Jana, Tarakanta

2012-12-01

202

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

PubMed

Platinum(II) complexes [Pt(4?-fpbpy)Cl(2)] (1), [Pt(4?-mepbpy)Cl(2)] (2), [Pt(4?-mpbpy)Cl(2)] (3) and [Pt(4?-bopbpy)Cl(2)] (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 K(b) ranging from 6.05×10(4)M(-1) to 3.48×10(5)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. PMID:22750337

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

2012-05-26

203

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

NASA Astrophysics Data System (ADS)

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.

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

2012-11-01

204

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

NASA Astrophysics Data System (ADS)

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.

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

1992-07-01

205

Dynamics and Conformational Studies of TOAC Spin Labeled Analogues of Ctx(Ile21)-Ha Peptide from Hypsiboas albopunctatus  

PubMed Central

Antimicrobial peptides (AMPs) isolated from several organisms have been receiving much attention due to some specific features that allow them to interact with, bind to, and disrupt cell membranes. The aim of this paper was to study the interactions between a membrane mimetic and the cationic AMP Ctx(Ile21)-Ha as well as analogues containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) incorporated at residue positions n?=?0, 2, and 13. Circular dichroism studies showed that the peptides, except for [TOAC13]Ctx(Ile21)-Ha, are unstructured in aqueous solution but acquire different amounts of ?-helical secondary structure in the presence of trifluorethanol and lysophosphocholine micelles. Fluorescence experiments indicated that all peptides were able to interact with LPC micelles. In addition, Ctx(Ile21)-Ha and [TOAC13]Ctx(Ile21)-Ha peptides presented similar water accessibility for the Trp residue located near the N-terminal sequence. Electron spin resonance experiments showed two spectral components for [TOAC0]Ctx(Ile21)-Ha, which are most likely due to two membrane-bound peptide conformations. In contrast, TOAC2 and TOAC13 derivatives presented a single spectral component corresponding to a strong immobilization of the probe. Thus, our findings allowed the description of the peptide topology in the membrane mimetic, where the N-terminal region is in dynamic equilibrium between an ordered, membrane-bound conformation and a disordered, mobile conformation; position 2 is most likely situated in the lipid polar head group region, and residue 13 is fully inserted into the hydrophobic core of the membrane.

Vicente, Eduardo F.; Basso, Luis Guilherme M.; Cespedes, Graziely F.; Lorenzon, Esteban N.; Castro, Mariana S.; Mendes-Giannini, Maria Jose S.; Costa-Filho, Antonio Jose; Cilli, Eduardo M.

2013-01-01

206

The use of swept-charge devices in planetary analogue X-ray fluorescence studies  

NASA Astrophysics Data System (ADS)

The Chandrayaan-1 X-ray Spectrometer (C1XS) was launched onboard the Indian Space Research Organisation (ISRO) Chandrayaan-1 lunar mission in October 2008. The instrument consisted of 24 swept-charge device (SCD) silicon X-ray detectors providing a total collecting area of ~ 24 cm2, corresponding to a 14° field of view (FWHM), with the ability to measure X-rays from 0.8-10 keV. One algorithm used to analyse the C1XS flight data was developed at Rutherford Appleton Laboratory (RAL) to convert the raw X-ray flux data into elemental ratios and abundances to make geological interpretations about the lunar surface. Laboratory X-ray fluorescence (XRF) data were used to validate the RAL algorithm, with previous studies investigating how the measured XRF flux varies with target surface characteristics including grain size and roughness. Evidence for a grain-size effect was observed in the data, the XRF line intensity generally decreasing with increasing sample grain size, dependent on the relative abundance of elemental components. This paper presents a subsequent study using more homogeneous samples made from mixtures of MgO, Al2O3 and SiO2 powders, all of grain size < 44 ?m, across a broader range of mixture ratios and at a higher level of X-ray flux data in order to further validate the RAL algorithm. For the majority of the C1XS flight data analysed so far with the RAL algorithm, the corresponding lunar ground tracks have been generally basaltic, laboratory verification of the algorithm having been primarily conducted using basaltic lunar regolith simulant (JSC-1A) XRF data. This paper also presents results from tests on a terrestrial anorthosite sample, more relevant to the anorthositic lunar highlands, from where the remaining C1XS lunar dataset derives. The operation of the SCD, the XRF test facility, sample preparation and collected XRF spectra are discussed in this paper.

Walker, T. E.; Smith, D. R.

2012-07-01

207

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

SciTech Connect

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.

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

2010-01-01

208

Analogue Experimental Study of Debris Entrainment by Ice Growing into Supercooled Water  

NASA Astrophysics Data System (ADS)

Field studies have identified several processes by which glaciers and ice sheets can accumulate debris-rich basal ice. Although significant effort has gone into modeling these processes and the inferred effects on glacier dynamics, there is a dearth of laboratory investigations. In particular, in several field settings debris entrainment by frazil ice growing in glaciohydraulically supercooled water channels has been suggested as the source of the dirty basal ice. However, the physical mechanisms by which frazil ice actually traps the sediment and then incorporates it into the basal ice remain unclear. In order to clarify this process, we have frozen solutions of 140 nm-diameter silica spheres dispersed in water in a 400 micron-thick cell supercooled to between -2 and -6 C. The thinness of the cell results in an essentially two-dimensional ice fabric, thus allowing us to observe the particle distribution and movement during freezing and subsequent coarsening. During the nucleation and unstable growth of the ice we find that many particles segregate to the liquid interstices between ice dendrites. Over the next 10 seconds the inter-dendrite liquid freezes and some particles become trapped between dendrites while some are pushed ahead of the ice front. As the ice coarsens over several days, particles migrate through the ice due to temperature gradient regelation and move with the grain boundaries/veins/nodes, which evolve to accommodate the coarsening. While the physical conditions in our experiment do not correspond exactly to those of subglacial conduits, our observations of the microscopic dynamics of particles during the freezing and evolution of supercooled, sediment-laden water can help guide future experiments and provide insight into the ice and sediment textures observed in glacier basal ice.

Spannuth, M.; Wettlaufer, J. S.

2007-12-01

209

Conformational preference of fused carbohydrate-templated proline analogues--a computational study.  

PubMed

The structure of fused C-glucosylproline hybrid (GlcProH) has been studied in detail computationally. A systematic molecular mechanics/Monte Carlo search has been performed in order to cover the entire conformational space of GlcProH. This has been followed by density-functional (DFT B3LYP) calculations in the gas phase and in aqueous solution, using the polarizable continuum model (PCM). In the gas phase, a large excess of the cis conformation with respect to the prolyl amide bond is found. This is reversed in aqueous solution where the calculations show 80% trans conformers, which is in accordance with experimental data. Thus, the PCM model is capable of accurately predicting cis-trans ratios. The free energy of solvation is not correlated with the dipole moment. Hence, a model (such as PCM) is required that takes into account the complete charge distribution. The reversal of the cis-trans ratio between gas phase and solution also emphasizes the effects of different free energies of solvation for the distinct conformers. Nevertheless, the energy difference between the cis and trans conformers is very small in solution (0.18 kcal/mol). Intramolecular hydrogen bonding is found to stabilize the cis conformers exclusively, which is a result of the rigid geometry of the fused rings. This can be contrasted to related more flexible molecules that show hydrogen bonding for both cis and trans isomers. The hydrogen bonding is at least partially responsible for the preferential stabilization of the cis conformers in the gas phase and a very small cis-trans energy difference in solution. PMID:23227822

Teklebrhan, Robel B; Owens, Neil W; Xidos, James D; Schreckenbach, Georg; Wetmore, Stacey D; Schweizer, Frank

2012-12-27

210

A Mossbauer spectroscopic study of iron-rich deposits of hydrothermal springs as Martian analogues  

NASA Astrophysics Data System (ADS)

In this work, results are reported of Mössbauer analysis focused on a suite of samples collected systematically along the outflow channel from an iron- rich hydrothermal vent mound in the Chocolate Pots area of Yellowstone National Park in the context of Mars exploration. Similar hydrothermal spring systems may well have been present on an early Mars and could have harbored primitive life. Mössbauer spectroscopy was chosen as the primary investigative technique in this study because of its ability to discriminate among the iron-bearing minerals in these samples. Those on the surface and near the vent are identified as predominantly ferrihydrite, Fe5HO8 ? 4H2O or 5Fe2O3 ? 9H2O. Subsurface samples, which seem to have been altered by either inorganic and/or biological processes, exhibit spectral signatures that include nontronite [(Ca,Na) 0.66Fe3+S4i7.34 Al0.66O20(OH) 4,nH2O], in the smectite clay mineral group, hematite (?-Fe 3+2O3), small- particle/nanophase goethite (?-Fe 3+OOH), and siderite (Fe2+CO3) . Evidence is presented that all these minerals, including those with the nanophase property, can have multi-billion year residence times and thus survive from their possible production in a putative early Martian hydrothermal environment to present day. Mössbauer spectroscopy will be a planned component of the instrument suite included on the 2001 Mars Surveyor Athena Rover mission. It is hoped that this work will aid in the use of this instrument, in the service of exobiology, and in helping to identify hydrothermal sediments and samples suitable for subsequent return to Earth.

Wade, Manson Lashawn

1999-09-01

211

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

NASA Astrophysics Data System (ADS)

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

Navarro-González, R.

2010-03-01

212

Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues.  

PubMed

Through an effort to develop novel ligands that have subtype selectivity for the estrogen receptors alpha (ERalpha) and beta (ERbeta), we have found that 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) acts as an agonist on both ER subtypes, but has a 70-fold higher relative binding affinity and 170-fold higher relative potency in transcription assays with ERbeta than with ERalpha. To investigate the ERbeta affinity- and potency-selective character of this DPN further, we prepared a series of DPN analogues in which both the ligand core and the aromatic rings were modified by the repositioning of phenolic hydroxy groups and by the addition of alkyl substituents and nitrile groups. We also prepared other series of DPN analogues in which the nitrile functionality was replaced with acetylene groups or polar functions, to mimic the linear geometry or polarity of the nitrile, respectively. To varying degrees, all of the analogues show preferential binding affinity for ERbeta (i.e., they are ERbeta affinity-selective), and many, but not all of them, are also more potent in activating transcription through ERbeta than through ERalpha (i.e., they are ERbeta potency-selective). meso-2,3-Bis(4-hydroxyphenyl)succinonitrile and dl-2,3-bis(4-hydroxyphenyl)succinonitrile are among the highest ERbeta affinity-selective ligands, and they have an ERbeta potency selectivity that is equivalent to that of DPN. The acetylene analogues have higher binding affinities but somewhat lower selectivities than their nitrile counterparts. The polar analogues have lower affinities, and only the fluorinated polar analogues have substantial affinity selectivities. This study suggests that, in this series of ligands, the nitrile functionality is critical to ERbeta selectivity because it provides the optimal combination of linear geometry and polarity. Furthermore, the addition of a second nitrile group beta to the nitrile in DPN or the addition of a methyl substitutent at an ortho position on the beta-aromatic ring increases the affinity and selectivity of these compounds for ERbeta. These ERbeta-selective compounds may prove to be valuable tools in understanding the differences in structure and biological function of ERalpha and ERbeta. PMID:11708925

Meyers, M J; Sun, J; Carlson, K E; Marriner, G A; Katzenellenbogen, B S; Katzenellenbogen, J A

2001-11-22

213

Rational design of renin inhibitors: x-ray studies of aspartic proteinases complexed with transition-state analogues  

SciTech Connect

The acceleration of the rates of specific reactions by enzymes is attributed to the stabilization of the transition state at the catalytic center. As a consequence, inhibitors that partially mimic the transition state bind more tightly than the equivalent substrate(s), and such transition-state analogues are being designed and tested for clinical use. Renin, an aspartic proteinase produced in the juxtaglomerula cells of the kidneys, catalyzes removal of the decapeptide angiotensin I (AI) from the N-terminus of angiotensinogen. The conversion of AI to the octapeptide angiotensin II (AII) is catalyzed by a carboxydipeptidase, angiotensin converting enzyme (ACE). Renin is a highly specific enzyme: it cleaves only the 10-11 bond in angiotensinogen. The minimum sequence of substrate still hydrolyzed by renin at a measurable rate is the 6-13 octapeptide. However, this cleavage is sufficiently slow to enable the octapeptide to act as a weak competitive inhibitor of the enzyme in vitro, with an IC/sub 50/ of 0.2 mM. The crystal structures of several aspartic proteinases have been solved by X-ray diffraction, revealing a common bilobal structure with a large cleft between the N- and C-terminal domains. The two essential carboxylates of Asp-32 and Asp-215 are within hydrogen-bonding distance and are approximately coplanar due to the restraints of a hydrogen-bonding network involving residues of the two highly conserved loops that contain the two essential aspartates. Modeling studies based on the homology of renin with other aspartic proteinases have shown that renins may assume tertiary structures that are similar to those of other aspartic proteinases.

Blundell, T.L.; Cooper, J.; Foundling, S.I.; Jones, D.M.; Atrash, B.; Szelke, M.

1987-09-08

214

A DFT study of the regeneration process of zinc porphyrin analogues in dye-sensitized solar cells.  

PubMed

The regeneration reaction of sensitizers in dye-sensitized solar cells is one of the critical steps in photonic chemical circuits. In this report, the two-step regeneration reaction of a series of zinc porphyrin sensitizers with a variety of substituent groups, i.e., CN-, F-, Cl-, H-, PhCH3-, OH- and NH2- groups, has been studied using density functional theory (DFT). The effects of the substituent groups on the structures of zinc porphyrin sensitizers, the regeneration intermediates and the reaction thermodynamics and kinetics have been explored. It is found that substituent groups at meso-position of zinc porphyrins strongly influenced the mode of two-step regeneration. For Por-CN, Por-F and Por-Cl, the formation of DyeI(Zn) and DyeI(Zn)-I intermediates are dominant, whereas for Por-H, Por-PhCH3 and Por-OH, the formation of DyeI(Py) and DyeI(Py)-I intermediates predominate. Due to the stronger electron-withdrawing effect of CN- and F-, the corresponding Por-CN and Por-F have no energy barrier in reaction. This suggests that their regeneration should be faster than the others. Besides two-step regeneration, alternative regenerations including one-step regeneration and reductive quenching reaction of excited dye and the influences of substituent groups on the electron injection efficiency are also estimated. These results provide valuable information for the design of novel zinc porphyrin analogues for DSCs. PMID:23913241

Yang, Fan; Zhang, Zidan; He, Xuehao

2013-08-02

215

Effects of sphingosine and sphingosine analogues on the free radical production by stimulated neutrophils: ESR and chemiluminescence studies  

PubMed Central

Sphingolipids inhibit the activation of the neutrophil (PMN) NADPH oxidase by protein kinase C pathway. By electron spin resonance spectroscopy (ESR) and chemiluminescence (CL), we studied the effects of sphingosine (SPN) and ceramide analogues on phorbol 12-myristate 13-acetate (PMA, 5 × 10-7M) stimulated PMN (6 × 106 cells). By ESR with spin trapping (100 mM DMPO: 5,5-dimethyl-1-pyrroline-Noxide), we showed that SPN (5 to 8 × 10-6M), C2-ceramide (N-acetyl SPN) and C6-ceramide (N-hexanoyl SPN) at the final concentration of 2 × 10-5 and 2 × 10-4M inhibit the production of free radicals by stimulated PMN. The ESR spectrum of stimulated PMN was that of DMPO-superoxide anion spin adduct. Inhibition by 5 × 10-6M SPN was equivalent to that of 30 U/ml SOD. SPN (5 to 8 × 10-6M) has no effect on in vitro systems generating superoxide anion (xanthine 50 mM/xanthine oxidase 110 mU/ml) or hydroxyl radical (Fenton reaction: 88 mM H2O2, 0.01 mM Fe2+ and 0.01 mM EDTA). SPN and N-acetyl SPN also inhibited the CL of PMA stimulated PMN in a dose dependent manner (from 2 × 10-6 to 10-5M), but N-hexanoyl SPN was less active (from 2 × 10-5 to 2 × 10-4M). These effects were compared with those of known PMN inhibitors, superoxide dismutase, catalase and azide. SPN was a better inhibitor compared with these agents. The complete inhibition by SPN of ESR signal and CL of stimulated PMN confirms that this compound or one of its metabolites act at the level of NADPH-oxidase, the key enzyme responsible for production of oxygen-derived free radicals.

Mouithys-Mickalad, A.; Deby-Dupont, G.; Hoebeke, M.; Mathy-Hartert, M.; Lamy, M.; Deby, C.

1997-01-01

216

First-principles study of energetic complexes (II): (5-cyanotetrazolato-N2) pentaammine cobalt (III) perchlorate (CP) and Ni, Fe and Zn analogues.  

PubMed

First-principles methods using the TPSS density functional level of theory with the basis set 6-31G** were applied to study (5-cyanotetrazolato-N(2)) pentaammine cobalt (III) perchlorate (CP) and Ni, Fe and Zn analogues in the gas phase. The optimized lowest-energy geometry of CP was calculated from reported experimental structural data using the TPSS method. The calculated values are in good agreement with those measured by X-ray diffraction. Ni, Fe and Zn analogues were constructed and calculated on the same basis. NBO results showed that the metal-ligand interactions have covalent character. Donor-acceptor analyses predicted that the delocalization energy E(2) decreases from Co to Zn, so the covalent nature of the complexes increases in the order Co>Fe>Ni>Zn. In addition, HOMO-LUMO composition was investigated to determine the stability of the title compounds. PMID:22127608

Shang, Jing; Zhang, Jian-Guo; Zhang, Tong-Lai; Huang, Hui-Sheng; Zhang, Shao-Wen; Zhou, Zun-Ning

2011-11-30

217

Pena Blanca Natural Analogue Project: Summary of activities  

SciTech Connect

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.

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

218

Binding to ? and ? opioid receptors by deltorphin I\\/II analogues modified at the Phe 3 and Asp 4\\/Glu 4 side chains: a report of 32 new analogues and a QSAR study  

Microsoft Academic Search

The synthesis and binding affinities of 32 X3Gly4 dual-substitution analogues of the natural opioid heptapeptides deltorphin I and II are reported. A multiple regression QSAR analysis was performed using those results along with literature data for the X3Asp4 and Phe3X4 side chain analogues. Fitting to a three-term potential well model with hydrophobic and van der Waals attraction terms and a

Stephen E. Schullery; Tasneem Mohammedshah; Hafida Makhlouf; Eleanor L. Marks; Benjamin S. Wilenkin; Sharleen Escobar; Carol Mousigian; Deborah L. Heyl

1997-01-01

219

Nuclear Power Plant Siting Study. Volume I.  

National Technical Information Service (NTIS)

The report presents the criteria and methodology for evaluating the siting of a nuclear power plant at Radford Army Ammunition Plant (RAAP) near Radford, VA. A detailed plant design is described utilizing the Process Energy Consolidated Nuclear Steam Gene...

1976-01-01

220

Site characterization studies in high plateau of Tibet  

NASA Astrophysics Data System (ADS)

The site survey in western China has been carried out since 2003. Remote studies and local surveys are performed, and Oma site, Ali area in southwest Tibet, has been selected in 2005 to make site testing measurements. The monitoring results show that Ali area can be the best choice for astronomical observations over the East Asian regions. A new site in Ali has been identified and begun construction in 2010 for small telescopes and detailed site characterization. This paper reviews the long term site survey, presents site characteristics in Tibet, and introduces current status of the new Ali observatory.

Yao, Yongqiang; Wang, Hongshuai; Liu, Liyong; Wang, Yiping; Qian, Xuan; Yin, Jia

2012-09-01

221

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

Microsoft Academic Search

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

A Flint; A Raben; JE Blundell; A Astrup

2000-01-01

222

Mechanisms on electrical breakdown strength increment of polyethylene by acetophenone and its analogues addition: a theoretical study.  

PubMed

A theoretical investigation is completed on the mechanism of electrical breakdown strength increment of polyethylene. It is shown that it is one of the most important factors for increasing electrical breakdown strength of polyethylene through keto-enol isomerization of acetophenone and its analogues at the ground state S0 and the lowest triplet state T1. The minimum structures and transition states of the keto- and the enol-tautomer of acetophenone and its analogues at the S0 and T1 states are obtained at the B3LYP/6-311+G(d,p) level, as well as the harmonic vibration frequencies of the equilibrium geometries and the minimum energy path (MEP) by the intrinsic reaction coordinate (IRC) theory at the same level. The two C-C bond cleavage reaction channels have been identified in acetophenone. The calculated results show that the energy barriers of keto-enol isomerization of acetophenone and its analogues at S0 and T1 states are much smaller than the average C-C bond energy of polyethylene, and the acetophenone doping or bond linked into polyethylene can increase the electrical breakdown strength and inhibit polyethylene electrical tree initiation and aging. PMID:23934300

Zhang, Hui; Shang, Yan; Zhao, Hong; Han, Baozhong; Li, Zesheng

2013-08-11

223

Blue copper proteins: Synthesis, spectra, and structures of CuIN3(SR) and CuIIN3(SR) active site analogues  

PubMed Central

The reaction of Cu(SR) or [Cu(SR)][ClO4] derivatives (SR = p-nitrobenzenethiolate or O-ethylcysteinate) with potassium hydrotris(3,5-dimethyl-1-pyrazolyl)borate produces redox pairs of the stoichiometry CuIN3(SR) and CuIIN3(SR). These complexes are well-defined synthetic approximations to the proposed N3S binding sites of blue (type 1) copper electron transfer proteins. The compounds were investigated by a variety of chemical and spectral (optical, resonance Raman, and electron paramagnetic resonance) techniques; the complex K[Cu(hydrotris(3,5-dimethyl-1-pyrazolyl)borate)(p- NO2C6H4S]-2 acetone was also studied by single-crystal x-ray diffraction methods. The spectrochemical characteristics of the CuIIN3(SR) species are in large part similar to the native system and thus provide some perspective regarding the origin of the unique type 1 spectral parameters and electron transfer properties.

Thompson, Jeffery S.; Marks, Tobin J.; Ibers, James A.

1977-01-01

224

Effect of gambierol and its tetracyclic and heptacyclic analogues in cultured cerebellar neurons: a structure-activity relationships study.  

PubMed

The polycyclic ether class of marine natural products has attracted the attention of researchers due to their complex and large chemical structures and diverse biological activities. Gambierol is a marine polycyclic ether toxin, first isolated along with ciguatoxin congeners from the dinoflagellate Gambierdiscus toxicus. The parent compound gambierol and the analogues evaluated in this work share the main crucial elements for biological activity, previously described to be the C28=C29 double bond within the H ring and the unsaturated side chain [Fuwa, H., Kainuma, N., Tachibana, K., Tsukano, C., Satake, M., and Sasaki, M. (2004) Diverted total synthesis and biological evaluation of gambierol analogues: Elucidation of crucial structural elements for potent toxicity. Chem. Eur. J. 10, 4894-4909]. With the aim to gain a deeper understanding of the cellular mechanisms involved in the biological activity of these compounds, we compared its activity in primary cultured neurons. The three compounds inhibited voltage-gated potassium channels (Kv) in a concentration-dependent manner and with similar potency, caused a small inhibition of voltage-gated sodium channels (Nav), and evoked cytosolic calcium oscillations. Moreover, the three compounds elicited a "loss of function" effect on Kv channels at concentrations of 0.1 nM. Additionally, both the tetracyclic and the heptacyclic derivatives of gambierol elicited synchronous calcium oscillations similar to those previously described for gambierol in cultured cerebellar neurons. Neither gambierol nor its tetracyclic derivative elicited cell toxicity, while the heptacyclic analogue caused a time-dependent decrease in cell viability. Neither the tetracyclic nor the heptacyclic analogues of gambierol exhibited lethality in mice after ip injection of 50 or 80 ?g/kg of each compound. Altogether, the results presented in this work support an identical mechanism of action for gambierol and its tetracyclic and heptacyclic analogues and indicate a "loss of function" effect on potassium channels even after administration of the three compounds at subnanomolar concentrations. In addition, because gambierol is known to stabilize the closed state of Kv3 channels, the results presented in this paper may have implications for understanding of channel functions and for future development of therapies against ciguatera poisoning and potassium channel-related diseases. PMID:22894724

Pérez, Sheila; Vale, Carmen; Alonso, Eva; Fuwa, Haruhiko; Sasaki, Makoto; Konno, Yu; Goto, Tomomi; Suga, Yuto; Vieytes, Mercedes R; Botana, Luis M

2012-08-29

225

SUPERFUND TREATABILITY CLEARINGHOUSE: LEETOWN PESTICIDE SITE TREATABILITY STUDY  

EPA Science Inventory

This is a site assessment and feasibility study of incineration alternatives at the ACME Solvents Site at Rockford, Illinois. The document contains laboratory results that are reported to simulate incineration conditions but no details on test methods were provided....

226

The ?,?-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase Dependent Signal Transduction  

Microsoft Academic Search

This overview focuses on the (a,a-difluoromethylene)phosphonate mimic of phosphoserine (pCF2Ser) and its application to the study of kinase-mediated signal transduction—pathways of great interest to drug develop- ment. The most versatile modes of access to these chemical biological tools are discussed, organized by method of PCF2-C bond formation. The pCF2-Ser mimic may be site-specifically incorporated into peptides (SPPS) and proteins (expressed

Kaushik Panigrahi; MariJean Eggen; Jun-Ho Maeng; Quanrong Shen; David B. Berkowitz

2009-01-01

227

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

SciTech Connect

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

Niu, Shuqiang; Ichiye, Toshiko

2011-06-08

228

Web Site Case Study #1: Blog  

Microsoft Academic Search

\\u000a Fireworks is a powerful end-to-end web design tool. It is as useful for rapid prototyping and wireframing as it is for creation\\u000a of vector art, logos, and pixel-perfect design detail and nuance. This example is going to walk through designing a blog site,\\u000a a relatively simple and standard format on the modern Web. Over the last several years, blogs have

Grant Hinkson; Craig Erskine; Matt Heerema; Chuck Mallott; Matthew Keefe; Hugh Griffith

229

Evaluation of stereoisomers of 4-fluoroalkyl analogues of 3-quinuclidinyl benzilate in in vivo competition studies for the M1, M2, and M3 muscarinic receptor subtypes in brain  

Microsoft Academic Search

To develop a subtype selective muscarinic acetylcholine receptor (mAChR) antagonist for PET, fluorine-19 labeled alkyl analogues of quinuclidinyl benzilate (QNB) were synthesized by stereoselective reactions. To investigate these analogues for tissue subtype specificity, in vivo competitive binding studies were performed in rat brain using (R)-3-quinuclidinyl (R)-4-[125I]Iodobenzilate (IQNB). Five, fifty, or five-hundred nmol of the non-radioactive ligands were coinjected intravenously with

Jaetae Lee; Chang H. Paik; Dale O. Kiesewetter; Seok G. Park; William C. Eckelman

1995-01-01

230

A Cross-National Study of Computer News Sites: Global News, Local Sites  

Microsoft Academic Search

The Internet is not only an object of and a tool for study; it is also both simultaneously global and local. In order to address how global and how local it is, this study compares the news content of 1 week from four different computer news web sites in four different countries (using four different languages). These sites use the

Nathaniel D. Poor

2007-01-01

231

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

PubMed Central

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

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

2012-01-01

232

Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study.  

PubMed

Background? Diabetes and obesity are more prevalent amongst psoriasis patients as is disturbance of the innate immune system. GLP-1 analogue therapy considerably improves weight and glycaemic control in people with type 2 diabetes and its receptor is present on innate immune cells. Objective? We aimed to determine the effect of liraglutide, a GLP-1 analogue, on psoriasis severity. Methods? Before and after 10?weeks of liraglutide therapy (1.2?mg subcutaneously daily) we determined the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) in seven people with both psoriasis and diabetes (median age 48?years, median body mass index 48.2?kg/m(2) ). We also evaluated the immunomodulatory properties of liraglutide by measuring circulating lymphocyte subset numbers and monocyte cytokine production. Results? Liraglutide therapy decreased the median PASI from 4.8 to 3.0 (P?=?0.03) and the median DLQI from 6.0 to 2.0 (P?=?0.03). Weight and glycaemic control improved significantly. Circulating invariant natural killer T (iNKT) cells increased from 0.13% of T lymphocytes to 0.40% (P?=?0.03). Liraglutide therapy also effected a non-significant 54% decrease in the proportion of circulating monocytes that produced tumour necrosis factor alpha (P?=?0.07). Conclusion? GLP-1 analogue therapy improves psoriasis severity, increases circulating iNKT cell number and modulates monocyte cytokine secretion. These effects may result from improvements in weight and glycaemic control as well as from direct immune effects of GLP-1 receptor activation. Prospective controlled trials of GLP-1 therapies are warranted, across all weight groups, in psoriasis patients with and without type 2 diabetes. PMID:22691169

Ahern, T; Tobin, A-M; Corrigan, M; Hogan, A; Sweeney, C; Kirby, B; O'Shea, D

2012-06-13

233

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)

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

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

2012-08-01

234

Microcalorimetric study on the transcription start site mutagenesis  

Microsoft Academic Search

The microcalorimetric method and DNA site-directed mutagenesis technique were used together to study the effect of transcription start site mutagenesis on RM07 promoter activity and gene transcription efficiency in Escherichia coli. The results revealed that once the putative transcription start site G was mutated to T, the promoter activity of RM07 promoter fragment was decreased and the transcription strength of

Y. Yang; Y. Liu; J. Zhu; P. Shen

2004-01-01

235

Inhibition of the complete set of mammalian secreted phospholipases A(2) by indole analogues: a structure-guided study.  

PubMed

Structure-guided design was employed in a search for potent and selective inhibitors of mammalian secreted phospholipases A(2) (sPLA(2)s). Using the X-ray structures of human groups IIA and X sPLA(2)s (hGIIA and hGX) as templates, homology structural models were made for the other human and mouse sPLA(2)s (hGIB, mGIB, mGIIA, mGIIC, hGIID, mGIID, hGIIE, mGIIE, hGIIF, mGIIF, hGV, mGV, and mGX). Me-Indoxam is a previously discovered indole analogue that binds tightly to many sPLA(2)s, and the X-ray structure of the hGX-Me-Indoxam complex was determined at a resolution of 2.0 A. Modeling suggests that the residues near the N(1)-substituent of Me-Indoxam vary significantly among the mammalian sPLA(2)s, and therefore a library of 83N(1)-variants was prepared by parallel synthesis. Several Me-Indoxam analogues bearing a 4-(2-oxy-ethanoic acid) side chain were potent inhibitors (IC(50) <0.05 microM) of hGIIA, mGIIA, mGIIC, hGIIE, mGIIE, hGV, and mGV, while they displayed intermediate potency (0.05-5 microM) against hGIB, mGIB, hGX, and mGX, and poorly inhibited (>5 microM) hGIID, mGIID, hGIIF, and mGIIF. Me-Indoxam analogues bearing a 5-(4-oxy-butanoic acid) side chain were generally less potent inhibitors. Although no compounds were found to be highly specific for a single human or mouse sPLA(2), combinations of Me-Indoxam analogues were discovered that could be used to distinguish the action of various sPLA(2)s in cellular events. For example, Me-Indoxam and compound 5 are approximately 5-fold more potent on hGIIA than on hGV, and compound 21 is 10-fold more potent on hGV versus hGIIA. PMID:15028265

Smart, Brian P; Pan, Ying H; Weeks, Amanda K; Bollinger, James G; Bahnson, Brian J; Gelb, Michael H

2004-04-01

236

Alligator rivers analogue project an OECD/NEA international project  

SciTech Connect

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.

Duerden, P.; Airey, P. [ANSTO, Menai (Australia); Pescatore, C. [OECD/NEA Issy-les-Moulineaux (France)

1994-12-31

237

Landfill siting in New York: Case studies confirming the importance of site-specific hydrogeologic investigations  

SciTech Connect

Landfill siting is one of the most problematic environmental issues facing society today for a variety of both technical and political reasons. New York State has approached many of these issues by requiring both generalized siting studies and detailed hydrogeologic evaluation of any proposed landfill site. Geographic Information Systems (GIS) have emerged as an appropriate tool for accumulating information for preliminary decision making. Recently, Goodman and others have suggested the use of a terrain suitability map (land use map) as a mechanism for simplifying landfill siting. They propose the use of existing geologic and morphologic information to eliminate large areas of New York from consideration as potential landfill locations. The study concludes that the Appalachian Plateau region (the Southern Tier), and the Erie-Ontario Plain are the most suitable areas for landfill development in the state. An evaluation of the geology at existing landfills and the impacts that relate to the facilities has shown that suitable sites do indeed exist in areas deemed unacceptable by Goodman and others. Conversely, a number of landfills located in suitable terranes have proven to be developed on less than suitable sites. While evaluation of existing information plays an obvious role in preliminary siting studies, it is not a substitute for detailed hydrogeologic investigation. It is local hydrogeological conditions that are most important in determining the suitability of a site for landfill development rather than the regional geologic context of the site.

Cloyd, K.C.; Concannon, P.W. (New York State Dept. of Environmental Conservation, Avon, NY (United States))

1993-03-01

238

Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors  

Microsoft Academic Search

PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin\\u000a analogue that possesses greater lactone stability in plasma compared with\\u000a other topoisomerase I inhibitors, a potential advantage for antitumor\\u000a activity. As with other camptothecins, oral administration has\\u000a pharmacological and clinical advantages. This Phase I study was performed\\u000a to assess the feasibility of the administration of oral diflomotecan, to\\u000a determine the maximum-tolerated, dose

A. J. Gelderblom; J. Prunonosa; C. Twelves; P. Principe; R. Salazar; J. Verweij; G. Pentheroudakis; M. Devlin; Hooije van C; F. Seguy; R. Obach; Jonge de M. J. A

2003-01-01

239

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

SciTech Connect

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.

Thomas, M.J. (Bowman Gray School of Medicine, Winston-Salem, NC (USA)); Bielski, B.H.J. (Brookhaven National Lab., Upton, NY (USA))

1989-04-26

240

Cross-bridge conformation as revealed by x-ray diffraction studies on insect flight muscles with ATP analogues.  

PubMed Central

The effects of three ATP analogues, alpha,beta-methylene-ATP [ATP(alpha,beta-CH1)], adenosine 5'-0-(3-thiotrophosphate) [ATP(gamma-S)], and beta,gamma-amino-ATP [ATP(beta,gamma-NH)] at various concentrations and temperatures on the X-ray fiber diagrams of glycerinated flight muscles from a water bug (Lethocerus maximus) have been investigated. It is shown that the "relaxed" state can be obtained with all three analogues at high concentrations, the result being particularly clear with ATP(gamma-S). It is inferred that the binding of an ATP-like molecule suffices to produce the relaxed state. At low concentrations ATP(beta,gamma-NH) produces state intermediate between rigor and relaxed which is not simply a mixture of the two. The possible nature of the intermediate is discussed. Images FIGURE 2a FIGURE 2b FIGURE 4a FIGURE 4b FIGURE 5 FIGURE 6a FIGURE 6b FIGURE 6c FIGURE 6d FIGURE 6e

Goody, R S; Holmes, K C; Mannherz, H G; Leigh, J B; Rosenbaum, G

1975-01-01

241

Cyclic chalcone analogue KRP6 as a potent modulator of cell proliferation: an in vitro study in HUVECs.  

PubMed

In the present investigation a novel series of chalcone analogues were synthesized and evaluated for their anti-proliferative activity in human umbilical vein endothelial cells (HUVECs). Among 14 tested compounds, chalcone analogue (E)-3-(2'-methoxybenzylidene)-4-chromanone (KRP6) exhibited the most potent activity with IC50 19 ?M. Moreover, HUVECs exhibited divergent, even opposing concentration-dependent responses to KRP6. This compound was the most potent inhibitor of cell proliferation and extracellular matrix formation (fibronectin and type IV collagen) at higher concentrations (20-50 ?M). In contrast, KRP6 stimulated the compensatory increase in proliferative activity including extracellular matrix formation at low concentrations (1, 10 ?M). KRP6 concentration-dependently modulated phosphorylation of Akt and mitogen-activated protein kinases such as extracellular signal-regulated kinase-1/-2 and p38 kinase, suggesting that these pathways play a role in the effect mediated by this compound. In addition, we found a selective effect on activated endothelial cells, in particular with resting endothelial cells. In conclusion, KRP6 is a potent modulator of selected steps of the angiogenic process in vitro. Accordingly, further in vivo research should be performed to facilitate its use in clinical practice. PMID:23666054

Ivanova, Lenka; Varinska, Lenka; Pilatova, Martina; Gal, Peter; Solar, Peter; Perjesi, Pal; Smetana, Karel; Ostro, Alexander; Mojzis, Jan

2013-05-11

242

Effects of CO2-rich fluids on a redbed reservoir: outcrop analogue study from the Buntsandstein (Germany)  

NASA Astrophysics Data System (ADS)

Carbon capture and storage (CCS) in saline aquifers will induce fluid-rock interactions, with effects on the mineralogy and physical properties of the reservoir. These effects are difficult to study in real reservoirs. Outcrop analogues provide access to relatively large rock volumes, but it may be difficult to prove that CO2 was involved in the mineral reactions observed. We present circumstantial evidence for the presence of CO2-rich fluids during the alteration of Triassic Buntsandstein redbeds from Germany. Fluid-rock interaction there is evidenced by localized bleaching of the red sandstones in fringes of a few mm to a few cm width along joints and fine cracks. The fringes can be traced along individual joints for a few dm to m. 3D geometric analysis on a cm scale shows that the bleached cracks form a complex interconnected network. On the outcrop scale, bleaching is essentially restricted to one north-trending joint set which is parallel to Miocene basalt dikes in the area. In underground salt mines, the dikes have caused bleaching of potassium salt minerals along their contacts. In the same mines CO2 is found trapped within rock salt along north-trending fractures, sometimes causing violent gas eruptions during mining operations. Together, these observations suggest that bleaching along north-trending joints in the Buntsandstein is causally related to the migration of CO2-rich fluids associated with the basalt volcanism. Today, CO2 ascends in CO2-enriched waters. We analyzed 12 samples of such waters. Their ?18O values correspond to meteoric waters. The ?13C (DIC) values of four water samples show signatures typical of volcanogenic CO2. Five samples contain mixed signals of volcanogenic and carbonatic CO2 or biogenic CO2 from soil. Volcanogenic and carbonatic CO2 are restricted to waters interpreted to rise along NW-SE striking basement faults. The switch of preferential fluid channeling from N-trending fractures in Tertiary time to NW-trending fractures today is compatible with a coeval rotation of the largest horizontal stress from N to NW, corroborating the control of fluid pathways by the contemporary stress field. Geochemical analyses of the bleached fringes show that bleaching causes a decrease in Fe and Mn due to hematite dissolution. Using cathodoluminescence microscopy and -spectroscopy combined with electron microprobe analysis and stable carbon isotopes, we detected two major fluid-mineral interactions probably involving CO2: (1) precipitation of zoned, joint-filling calcites and pore-filling calcite cements, the latter replacing an earlier dolomite, and (2) alkali feldspar alteration. We interpret Fe-rich calcite crystal cores to reflect incorporation of iron released by coeval bleaching during the dolomite-calcite transformation. This recrystallisation was associated with a volume increase, possibly suggesting some degree of sealing and enhanced retention of CO2. On the other hand, feldspar alteration has a destructing effect on the feldspar grains, implying that bleaching creates pore space.

Kasch, N.; Kley, J.; Koester, J.; van Geldern, R.; Wehrer, M.; Wendler, J.

2010-12-01

243

Site Characterization of Vehicle Signature Study Sites, General Motors Proving Grounds, Milford, Michigan.  

National Technical Information Service (NTIS)

An environmental characterization of two test sites to be used by TACOM for vehicle signature studies was conducted at the General Motors Proving Grounds, Milford, Michigan, during July and August 1972. Each test site consisted of a roadway (paved or unpa...

J. R. Curro

1973-01-01

244

A click-and-release pyrrolysine analogue.  

PubMed

What's the catch? A pyrrolysine analogue bearing a terminal alkyne and an ester functionality can be incorporated into recombinant proteins and render them amenable to capture by the click reaction and subsequent release through ester hydrolysis. The utility of this pyrrolysine-inspired technology is demonstrated for the identification of SUMOylation sites. PMID:23589397

Lee, Marianne M; Fekner, Tomasz; Tang, Tsz-Ho; Wang, Lin; Chan, Aurora Ho-Yin; Hsu, Pang-Hung; Au, Shannon W; Chan, Michael K

2013-04-15

245

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

PubMed

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

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

2013-03-15

246

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

SciTech Connect

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.

Not Available

1987-06-01

247

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

Microsoft Academic Search

Trolox c, 3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-carboxylic acid, 1, a water-soluble α-tocopherol analogue, was oxidized with Brâ⁻ 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

Michael J. Thomas; Benon H. J. Bielski

1989-01-01

248

Neutron thresholds to resonant analogue states  

Microsoft Academic Search

The anomalous energy behaviour of the neutron threshold to a resonant analogue state is investigated in detail. The analysis is applied to recently studied reactions of the type A(d, np)A but can equally well be applied to reactions involving other projectiles. To avoid all three-body effects, the reaction is assumed to be a sequential process, i.e. the resonant intermediate analogue

R. O. Stephen

1967-01-01

249

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

PubMed Central

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

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

2013-01-01

250

Social networking sites in the Czech Republic: an empirical study  

Microsoft Academic Search

Social Networking Sites are a phenomenon of the times. For example, the largest of them, Facebook, has more than 798 million users worldwide. Unfortunately, not much is known about the usage of Social Networking Sites in the European context. This study tries to reduce the gap. The study explores some of the most important questions regarding usage of Social Networking

Miroslav KARLÍ?EK; Ivan TOMEK; Mária HASPROVÁ; Marcela ZAMAZALOVÁ

2012-01-01

251

Studies on the biotin-binding site of avidin. Minimized fragments that bind biotin.  

PubMed Central

The object of this study was to define minimized biotin-binding fragments, or 'prorecognition sites', of either the egg-white glycoprotein avidin or its bacterial analogue streptavidin. Because of the extreme stability to enzymic hydrolysis, fragments of avidin were prepared by chemical means and examined for their individual biotin-binding capacity. Treatment of avidin with hydroxylamine was shown to result in new cleavage sites in addition to the known Asn-Gly cleavage site (position 88-89 in avidin). Notably, the Asn-Glu and Asp-Lys peptide bonds (positions 42-43 and 57-58 respectively) were readily cleaved; in addition, lesser levels of hydrolysis of the Gln-Pro (61-62) and Asn-Asp (12-13 and 104-105) bonds could be detected. The smallest biotin-binding peptide fragment, derived from hydroxylamine cleavage of either native or non-glycosylated avidin, was identified to comprise residues 1-42. CNBr cleavage resulted in a 78-amino acid-residue fragment (residues 19-96) that still retained activity. The data ascribe an important biotin-binding function to the overlapping region (residues 19-42) of avidin, which bears the single tyrosine moiety. This contention was corroborated by synthesizing a tridecapeptide corresponding to residues 26-38 of avidin; this peptide was shown to recognize biotin. Streptavidin was not susceptible to either enzymic or chemical cleavage methods used in this work. The approach taken in this study enabled the experimental distinction between the chemical and structural elements of the binding site. The capacity to assign biotin-binding activity to the tyrosine-containing domain of avidin underscores its primary chemical contribution to the binding of biotin by avidin. Images Fig. 1. Fig. 2. Fig. 3. Fig. 6. Fig. 7. Fig. 9.

Hiller, Y; Bayer, E A; Wilchek, M

1991-01-01

252

Hanford tank initiative test facility site selection study  

SciTech Connect

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.

Staehr, T.W.

1997-04-03

253

Differential inhibition of class I and class II 5-enolpyruvylshikimate-3-phosphate synthases by tetrahedral reaction intermediate analogues.  

PubMed

The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase or EPSPS) is best known as the target of the herbicide glyphosate. EPSPS is also considered an attractive target for the development of novel antibiotics since the pathogenicity of many microorganisms depends on the functionality of the shikimate pathway. Here, we have investigated the inhibitory potency of stable fluorinated or phosphonate-based analogues of the tetrahedral reaction intermediate (TI) in a parallel study utilizing class I (glyphosate-sensitive) and class II (glyphosate-tolerant) EPSPS. The (R)-difluoromethyl and (R)-phosphonate analogues of the TI are the most potent inhibitors of EPSPS described to date. However, we found that class II EPSPS are up to 400 times less sensitive to inhibition by these TI analogues. X-ray crystallographic data revealed that the conformational changes of active site residues observed upon inhibitor binding to the representative class I EPSPS from Escherichia coli do not occur in the prototypical class II enzyme from Agrobacterium sp. strain CP4. It appears that because the active sites of class II EPSPS do not possess the flexibility to accommodate these TI analogues, the analogues themselves undergo conformational changes, resulting in less favorable inhibitory properties. Since pathogenic microorganisms such as Staphylococcus aureus utilize class II EPSPS, we conclude that the rational design of novel EPSPS inhibitors with potential as broad-spectrum antibiotics should be based on the active site structures of class II EPSP synthases. PMID:17958399

Funke, Todd; Healy-Fried, Martha L; Han, Huijong; Alberg, David G; Bartlett, Paul A; Schönbrunn, Ernst

2007-10-25

254

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

SciTech Connect

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.

Not Available

1987-06-01

255

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

NASA Astrophysics Data System (ADS)

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.

Wysoki?ski, Rafa?; Hernik, Katarzyna; Szostak, Roman; Michalska, Danuta

2007-03-01

256

[13C]NMR studies of the effect of the somatostatin analogue octreotide on hepatic glycogenesis and glycogenolysis.  

PubMed

NMR spectroscopy is a useful tool for monitoring multiple intermediate metabolic pathways in different organs in intact animals and humans. We report the effect of the somatostatin analogue octreotide on the fate of 13C-labeled glucose administered to fasted and well-fed rats as determined by NMR spectroscopy. The production of 13C-labeled glycogen and its subsequent breakdown after the end of infusion was identified with a time resolution of 7 min. Hepatic glycogen synthesis was not different between control and octreotide-treated animals but persisted for 15 min after the end of the infusion only in control animals. Glycogenolysis, however, was initiated immediately after the end of infusion in octreotide-treated animals where the half-life of glycogen was 40 min compared with 68 min in control animals. However, once initiated, the rate of glycogenolysis was not significantly altered by octreotide. Although octreotide had no effect on glucose signal intensities in fasted animals, 13C glucose signals were more intense in octreotide compared with control well-fed animals. In conclusion, octreotide alters rat hepatic metabolism by accelerating the onset of glycogenolysis and stimulating glucose accumulation without significantly interfering with glycogen synthesis. PMID:7854973

Ezzat, S; Pahl-Wostl, C; Rudin, M; Harris, A G

1994-01-01

257

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

SciTech Connect

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.

Not Available

1987-12-22

258

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

SciTech Connect

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.

Not Available

1987-12-01

259

The Impact of Pretrauma Analogue GAD and Posttraumatic Emotional Reactivity Following Exposure to the September 11 Terrorist Attacks: A Longitudinal Study  

Microsoft Academic Search

The relation between analogue generalized anxiety disorder (GAD) assessed the day before the events of September 11, 2001 (9\\/11) and long-term outcome was examined in 44 young adults who were directly exposed the following day to the terrorist attacks in New York City. After controlling for high exposure to the attacks, preattack analogue GAD was associated with greater social and

Frank J. Farach; Douglas S. Mennin; Rita L. Smith; Matthew Mandelbaum

2008-01-01

260

Determination of the Substrate Binding Mode to the Active Site Iron of (S)-2-Hydroxypropylphosphonic Acid Epoxidase Using 17O-Enriched Substrates and Substrate Analogues†  

PubMed Central

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

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

2009-01-01

261

Hydrolysis Study and Exposure Data on Trimethyl Phosphate Site.  

National Technical Information Service (NTIS)

As requested in Mr. F. D. Kovar's letter of September 23, 1981, we are enclosing information on trimethyl phosphite hydrolysis and on levels of trimethyl phosphate measured at our production site. Attachment No. 1 summarizes the hydrolysis studies. The da...

1981-01-01

262

High Plains Regional Ground-water Study web site  

USGS Publications Warehouse

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.

Qi, Sharon L.

2000-01-01

263

Readability of menopause web sites: a cross-sectional study.  

PubMed

More women are frequently referring to the Internet for health information, yet the readability of information about menopause on the Internet has not been widely studied. To address this gap, this study examined the readability of information about menopause on 25 Internet Web sites. Findings included that information on the Web sites had a reading level higher than the recommended sixth-grade level, and culturally appropriate health information was lacking. Health educators and practitioners are in a pivotal role to help women understand information useful for healthcare decisions. Several criteria are discussed to help practitioners evaluate Web sites. PMID:23098043

Charbonneau, Deborah H

2012-01-01

264

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

SciTech Connect

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

Not Available

1987-06-01

265

Influence of Thiolate Ligands on Reductive N-O Bond Activation. Probing the O2? Binding Site of a Biomimetic SOR Analogue, and Examining the Proton-Dependent Reduction of Nitrite  

PubMed Central

Nitric oxide (NO) is frequently used to probe the substrate–binding site of “spectroscopically silent” non-heme Fe2+ sites of metalloenzymes, such as superoxide reductase (SOR). Herein we use NO to probe the superoxide binding site of our thiolate–ligated biomimetic SOR model [FeII(SMe2N4(tren))]+ (1). Like NO–bound trans cysteinate-ligated SOR (SOR-NO), the rhombic S= 3/2 EPR signal of NO–bound cis thiolate-ligated [Fe(SMe2N4(tren)(NO)]+ (2; g = 4.44, 3.54, 1.97), isotopically sensitive ?NO(?15NO) stretching frequency (1685(1640) cm?1), and 0.05 Å decrease in Fe–S bond length are shown to be consistent with the oxidative addition of NO to Fe(II) to afford an Fe(III)–NO? {FeNO}7 species containing high–spin (S= 5/2) Fe(III) antiferromagnetically coupled to NO? (S= 1). The cis versus trans positioning of the thiolate does not appear to influence these properties. Although it has yet to be crystallographically characterized, SOR-NO is presumed to possess a bent Fe-NO similar to that of 2 (Fe–N–O= 151.7(4)°). The N–O bond is shown to be more activated in 2 relative to N– and O–ligated {FeNO}7 complexes, and this is attributed to the electron donating properties of the thiolate ligand. Hydrogen bonding to the cysteinate sulfur attenuates N–O bond activation in SOR as shown by its higher ?NO frequency (1721 cm?1). In contrast, the ?O–O frequency of SOR peroxo intermediate and its analogues is not affected by H-bonds to the cysteinate sulfur, or other factors influencing the Fe–SR bond strength. These only influence the ?Fe–O frequency. Reactions between 1 and NO2? are shown to result in the proton–dependent heterolytic cleavage of an N–O bond. The mechanism of this reaction is proposed to involve both FeII–NO2? and {FeNO}6 intermediates similar to those implicated in the mechanism of NiR–promoted NO2? reduction.

Villar-Acevedo, Gloria; Nam, Elaine; Fitch, Sarah; Benedict, Jason; Freudenthal, John; Kaminsky, Werner; Kovacs, Julie A.

2011-01-01

266

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

SciTech Connect

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.

Not Available

1987-12-01

267

Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors.  

PubMed

A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3'OH and block intasome activity. PMID:24084160

Yu, Shenghui; Sanchez, Tino Wilson; Liu, Yang; Yin, Yanzhen; Neamati, Nouri; Zhao, Guisen

2013-09-13

268

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

Microsoft Academic Search

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

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

2006-01-01

269

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

SciTech Connect

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.

Not Available

1987-06-01

270

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

SciTech Connect

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.

Lincoff, A.H. [US Environmental Protection Agency, San Francisco, CA (United States). Region IX; Costan, G.P.; Montgomery, M.S.; White, P.J. [Pacific Northwest Lab., Richland, WA (United States)

1994-07-01

271

TWRS privatization phase I site development engineering study  

SciTech Connect

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.

Shord, A.L.

1996-09-30

272

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

SciTech Connect

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.

Not Available

1987-06-01

273

Which dressing do donor site wounds need?: study protocol for a randomized controlled trial  

PubMed Central

Background Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds. Methods A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale). Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009. Discussion This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s) that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such patients. Thus, we aim to contribute a well-designed trial, relevant to all clinicians involved in the care for donor site wounds, which will help enhance uniformity and quality of care for these patients. Trial registration http://www.trialregister.nl, NTR1849. Date registered: June 9, 2009

2011-01-01

274

Function of the ribosomal E-site: a mutagenesis study  

PubMed Central

Ribosomes synthesize proteins according to the information encoded in mRNA. During this process, both the incoming amino acid and the nascent peptide are bound to tRNA molecules. Three binding sites for tRNA in the ribosome are known: the A-site for aminoacyl-tRNA, the P-site for peptidyl-tRNA and the E-site for the deacylated tRNA leaving the ribosome. Here, we present a study of Escherichia coli ribosomes with the E-site binding destabilized by mutation C2394G of the 23S rRNA. Expression of the mutant 23S rRNA in vivo caused increased frameshifting and stop codon readthrough. The progression of these ribosomes through the ribosomal elongation cycle in vitro reveals ejection of deacylated tRNA during the translocation step or shortly after. E-site compromised ribosomes can undergo translocation, although in some cases it is less efficient and results in a frameshift. The mutation affects formation of the P/E hybrid site and leads to a loss of stimulation of the multiple turnover GTPase activity of EF-G by deacylated tRNA bound to the ribosome.

Sergiev, Petr V.; Lesnyak, Dmitry V.; Kiparisov, Sergey V.; Burakovsky, Dmitry E.; Leonov, Andrei A.; Bogdanov, Alexey A.; Brimacombe, Richard; Dontsova, Olga A.

2005-01-01

275

Function of the ribosomal E-site: a mutagenesis study.  

PubMed

Ribosomes synthesize proteins according to the information encoded in mRNA. During this process, both the incoming amino acid and the nascent peptide are bound to tRNA molecules. Three binding sites for tRNA in the ribosome are known: the A-site for aminoacyl-tRNA, the P-site for peptidyl-tRNA and the E-site for the deacylated tRNA leaving the ribosome. Here, we present a study of Escherichia coli ribosomes with the E-site binding destabilized by mutation C2394G of the 23S rRNA. Expression of the mutant 23S rRNA in vivo caused increased frameshifting and stop codon readthrough. The progression of these ribosomes through the ribosomal elongation cycle in vitro reveals ejection of deacylated tRNA during the translocation step or shortly after. E-site compromised ribosomes can undergo translocation, although in some cases it is less efficient and results in a frameshift. The mutation affects formation of the P/E hybrid site and leads to a loss of stimulation of the multiple turnover GTPase activity of EF-G by deacylated tRNA bound to the ribosome. PMID:16243787

Sergiev, Petr V; Lesnyak, Dmitry V; Kiparisov, Sergey V; Burakovsky, Dmitry E; Leonov, Andrei A; Bogdanov, Alexey A; Brimacombe, Richard; Dontsova, Olga A

2005-10-20

276

Proglumide analogues: potent cholecystokinin receptor antagonists.  

PubMed

Proglumide [N-(benzoyl)-L-glutamic acid-1-di-n-propylamide] is a specific cholecystokinin receptor antagonist. In the present study we synthesized various analogues of proglumide and used pancreatic acini from guinea pig pancreas to examine the abilities of these analogues to function as cholecystokinin receptor antagonists. Each analogue inhibited cholecystokinin octapeptide-stimulated amylase secretion but did not stimulate amylase secretion when present alone. There was a close correlation between the ability of a particular analogue to inhibit the action of cholecystokinin on acinar cell function and its ability to inhibit binding of 125I-cholecystokinin. Structure-function studies demonstrated that neither the dipropylamide nor the benzoyl moieties are essential for inhibiting the action of cholecystokinin but that both groups are important in determining the inhibitory potency. Replacing the dipropylamide group with a hydroxyl group caused a 13-fold decrease in potency. Replacing the benzoyl moiety by an acetyl group caused a 30- to 40-fold decrease in inhibitory potency, whereas replacing the benzoyl moiety by a p-chlorophenoxyacetyl or phenoxyacetyl moiety caused a 75-fold increase in potency. Replacing both the dipropylamide moiety with a hydroxyl group and the benzoyl moiety with a phenoxyacetyl group resulted in a 5-fold decrease in inhibitory potency. Inhibition of cholecystokinin-stimulated amylase release by both the phenoxyacetyl and p-chlorophenoxyacetyl analogues was competitive in nature, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2411147

Jensen, R T; Murphy, R B; Trampota, M; Schneider, L H; Jones, S W; Howard, J M; Gardner, J D

1985-08-01

277

Quantum analogue computing.  

PubMed

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

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

2010-08-13

278

Microbially mediated redox processes in natural analogues for radioactive waste  

Microsoft Academic Search

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.

Shelley A Haveman; Karsten Pedersen

2002-01-01

279

Analogue Downscaling of Seasonal Rainfall Forecasts  

NASA Astrophysics Data System (ADS)

We have taken an existing statistical downscaling model (SDM), based on meteorological analogues that was developed for downscaling climate change projections (Timbal et al 2009), and applied it in the seasonal forecasting context to produce downscaled rainfall hindcasts from a coupled model seasonal forecast system (POAMA). Downscaling of POAMA forecasts is required to provide seasonal climate information at local scales of interest. Analogue downscaling is a simple technique to generate rainfall forecasts appropriate to the local scale by conditioning on the large scale predicted GCM circulation and the local topography and climate. Analogue methods are flexible and have been shown to produce good results when downscaling 20th century South Eastern Australian rainfall output from climate models. A set of re-forecasts for three month rainfall at 170 observing stations in the South Murray Darling region of Australia were generated using predictors from the POAMA re-forecasts as input for the analogue SDM. The predictors were optimised over a number of different GCMS in previous climate change downscaling studies. Downscaling with the analogue SDM results in predicted rainfall with realistic variance while maintaining the modest predictive skill of the dynamical model. Evaluation of the consistency between the large scale mean of downscaled and direct GCM output precipitation is encouraging.

Charles, A. N.; Timbal, B.; Hendon, H.

2010-12-01

280

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

PubMed

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. PMID:23500648

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

2013-03-15

281

Substrate-binding recognition and specificity of trehalose phosphorylase from Schizophyllum commune examined in steady-state kinetic studies with deoxy and deoxyfluoro substrate analogues and inhibitors.  

PubMed Central

Trehalose phosphorylase is a component of the alpha-D-glucopyranosyl alpha-D-glucopyranoside (alpha,alpha-trehalose)-degrading enzyme system in fungi and it catalyses glucosyl transfer from alpha,alpha-trehalose to phosphate with net retention of the anomeric configuration. The enzyme active site has no detectable affinity for alpha,alpha-trehalose in the absence of bound phosphate and catalysis occurs from the ternary complex. To examine the role of non-covalent enzyme-substrate interactions for trehalose phosphorylase recognition, we used the purified enzyme from Schizophyllum commune and tested a series of incompetent structural analogues of the natural substrates and products as inhibitors of the enzyme. Equilibrium-binding constants (K(i)) for deoxy- and deoxyfluoro derivatives of D-glucose show that loss of interactions with the 3-, 4- or 6-OH, but not the reactive 1- and the 2-OH, results in considerably (> or =100-fold) weaker affinity for sugar-binding subsite +1, revealing the requirement for hydrogen bonding with hydroxyls, away from the site of chemical transformation to position precisely the D-glucose-leaving group/nucleophile for catalysis. The high specificity of trehalose phosphorylase for the sugar aglycon during binding and conversion of O-glycosides is in contrast with the observed alpha-retaining phosphorolysis of alpha-D-glucose-1-fluoride (alpha-D-Glc-1-F) since the productive bonding capability of the fluoride-leaving group with subsite +1 is minimal. The specificity constant (19 M(-1).s(-1)) and catalytic-centre activity (0.1 s(-1)) for the reaction with alpha-D-Glc-1-F are 0.10- and 0.008-fold the corresponding kinetic parameters for the enzymic reaction with alpha,alpha-trehalose. The non-selective-inhibition profile for a series of inactive alpha-D-glycopyranosyl phosphates shows that the driving force for the binary-complex formation lies mainly in interactions of the enzyme with the phosphate group and suggests that hydrogen bonding with hydroxyl groups at the catalytic site (subsite -1) contributes to catalysis by providing stabilization, which is specific to the transition state. Vanadate, a tight-binding phosphate mimic, inhibits the phosphorolysis of alpha-D-Glc-1-F by forming a ternary complex whose apparent dissociation constant of 120 microM is approx. 160-fold greater than the dissociation constant of the same inhibitor complex with alpha,alpha-trehalose.

Eis, Christian; Nidetzky, Bernd

2002-01-01

282

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

SciTech Connect

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

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

283

Seismic site selection at high frequencies: A case study  

SciTech Connect

A viable in-country seismic network for monitoring test ban treaties depends upon our ability to select suitable sites for seismic stations. Effective high frequency stations (greater than 10 Hz) rely on the premise that quiet sites with very low seismic noise and excellent signal-to-noise can be found throughout the Soviet Union. In this report the author outlines a case study of site selection within the Midwestern United States. These are not quiet sites, but are representative of agricultural regions and indicate the sensitivity of high frequencies to cultural noise. Based on this study, site selection procedures designed for short-periods are inadequate for high frequencies. Above 10 Hz strong spectral lines from mechanical sources and diurnal variations dominate the seismic noise; this cultural noise might obscure narrow-band spectral reinforcements which often characterize P/sub n/ signals for large chemical explosions. Thus, interference from narrow-band spectral noise would reduce the promise of high frequencies as a discriminant for decoupled explosions - our inability to discriminate numerous large mining blasts would give many unidentified events. To eliminate the offending noise sources requires a large increase in their distance from a prospective seismic station. For example, the minimum distance from an active quarry must increase to between 40 and 90 kilometers; the previous recommendation for RSTN stations is 5 kilometers. A borehole will not necessarily lower the high-frequency cultural noise. Only by emphasizing remote stations sites can the prerequisite quiet sites be located and exploited for seismic verification using high frequencies.

Smith, A.T.

1987-04-22

284

Cyclic cholecystokinin analogues with high selectivity for central receptors  

SciTech Connect

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.

Charpentier, B.; Pelaprat, D.; Durieux, C.; Dor, A.; Roques, B.P. (Institut National de la Sante et de la Recherche Medicale, Paris (France)); Reibaud, M.; Blanchard, J.C. (Rhone-Poulenc Sante, Vitry-sur-Seine (France))

1988-03-01

285

Molecular dynamics study of the ribosomal A-site.  

PubMed

Many aminoglycosidic antibiotics target the A-site of 16S RNA in the small ribosomal subunit and affect the fidelity of protein translation in bacteria. Upon binding, aminoglycosides displace two adenines (A1492 and A1493 for E. coli numbering) that are involved in tRNA anticodon loop recognition. The major difference in the aminoglycosidic binding site between the prokaryota and eukaryota is an adenine into guanine substitution in the position 1408. This mutation likely affects the dynamics of near A1492 and A1493 and hinders the binding of aminoglycosides to eukaryotic ribosomes. With multiple 20 ns long all-atom molecular dynamics simulations, we study the flexibility of a 22 nucleotide RNA fragment which mimics the aminoglycosidic binding site. Simulations are carried out for both native and A1408G mutated RNA as well as for their complexes with aminoglycosidic representative paromomycin. We observe intra- and extrahelical configurations of A1492 and A1493, which differ between the prokaryotic and the mutated structure. We obtain configurations of the A-site that are also observed in the NMR and crystal structures. Our studies show the differences in the internal mobility of the A-site, as well as that in ion and water density distributions inside of the binding cleft, between the prokaryotic and mutated RNA. We also compare the performance of two force field parameters for RNA, Amber and Charmm. PMID:18973356

Romanowska, Julia; Setny, Piotr; Trylska, Joanna

2008-11-27

286

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

SciTech Connect

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)

Not Available

1980-01-01

287

Synthesis and biological evaluation of phosphonate analogues of nevirapine.  

PubMed

A series of nevirapine-based analogues containing the phosphonate functionality were prepared and evaluated in vitro against HIV RT. The effect of the phosphonate was evaluated against the wild type and Y181C HIV replication. An in vivo PK study was performed on a select analogue. PMID:23375792

Parrish, Jay; Tong, Leah; Wang, Michael; Chen, Xiaowu; Lansdon, Eric B; Cannizzaro, Carina; Zheng, Xubin; Desai, Manoj C; Xu, Lianhong

2012-12-21

288

2D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetanilides analogues as potent HIV-1 non-nucleoside reverse transcriptase inhibitors  

PubMed Central

Background The discovery of clinically relevant inhibitors of HIV-RT for antiviral therapy has proven to be a challenging task. To identify novel and potent HIV-RT inhibitors, the quantitative structure–activity relationship (QSAR) approach became very useful and largely widespread technique forligand-based drug design. Methods We perform the two- and three-dimensional (2D and 3D) QSAR studies of a series of 1,2,3-thiadiazole thioacetanilides analogues to elucidate the structural properties required for HIV-RT inhibitory activity. Results The 2D-QSAR studies were performed using multiple linear regression method, giving r2?=?0.97 and q2?=?0.94. The 3D-QSAR studies were performed using the stepwise variable selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q2?=?0.89 and a non-cross-validated correlation coefficient r2?=?0.97 were obtained. Docking analysis suggests that the new series have comparable binding affinity with the standard compounds. Conclusions This approach showed that hydrophobic and electrostatic effects dominantly determine binding affinities which will further useful for development of new NNRTIs.

2012-01-01

289

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

SciTech Connect

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.

Not Available

1987-06-01

290

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...

291

Coordinated Seismic Study of the Multi-Well Experiment Site.  

National Technical Information Service (NTIS)

A series of seismic studies was performed at the Department of Energy Multi-Well Experiment site to delineate the character of the beds within the Mesaverde group in western Colorado. The experiment consisted of a three-dimensional seismic survey of the a...

1983-01-01

292

Surgical site infections in Italian Hospitals: a prospective multicenter study  

Microsoft Academic Search

BACKGROUND: Surgical site infections (SSI) remain a major clinical problem in terms of morbidity, mortality, and hospital costs. Nearly 60% of SSI diagnosis occur in the postdischarge period. However, literature provides little information on risk factors associated to in-hospital and postdischarge SSI occurrence. A national prospective multicenter study was conducted with the aim of assessing the incidence of both in-hospital

Nicola Petrosillo; Cecilia MJ Drapeau; Emanuele Nicastri; Lorena Martini; Giuseppe Ippolito; Maria Luisa Moro

2008-01-01

293

Study of extreme wind speed for Italian wind farm sites  

Microsoft Academic Search

Summary This study assesses the validity of three different codes used to estimate extreme wind speed for Italian wind farm sites. Extreme wind speeds are often the driving parameter for the selection of turbine models. This is particularly so in Italy, where conditions are characterised by relatively modest annual average wind speeds combined with relatively high extremes. The problem is

M. Boccolini; F. Magni; C. Stork

294

The Ethnoarchaeology of Reptile Remains at a Lake Turkana Occupation Site, Kenya  

Microsoft Academic Search

The role of reptiles in hominid hunter–gatherer subsistence in Pleistocene Africa has been largely overlooked. This study examines the reptile component of a modern lake shore camp (site 20) assemblage of low archaeological visibility. Site 20, located on the eastern shore of Lake Turkana, has been observed from its creation to burial. The site is an ideal modern analogue for

Natalia Rybczynski; Diane Gifford-Gonzalez; Kathlyn M. Stewart

1996-01-01

295

Site matching of wind turbine generators: A case study  

SciTech Connect

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

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

1999-12-01

296

2-methiopropamine, a thiophene analogue of methamphetamine: studies on its metabolism and detectability in the rat and human using GC-MS and LC-(HR)-MS techniques.  

PubMed

2-Methiopropamine [1-(thiophen-2-yl)-2-methylaminopropane, 2-MPA], a thiophene analogue of methamphetamine, is available from online vendors selling "research chemicals." The first samples were seized by the German police in 2011. As it is a recreational stimulant, its inclusion in routine drug screening protocols should be required. The aims of this study were to identify the phase I and II metabolites of 2-MPA in rat and human urine and to identify the human cytochrome-P450 (CYP) isoenzymes involved in its phase I metabolism. In addition, the detectability of 2-MPA in urine samples using the authors' well-established gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-linear ion trap-mass spectrometry (LC-MS(n)) screening protocols was also evaluated. The metabolites were isolated from rat and human urine samples by solid-phase extraction without or following enzymatic cleavage of conjugates. The phase I metabolites, following acetylation, were separated and identified by GC-MS and/or liquid chromatography-high-resolution linear ion trap mass spectrometry (LC-HR-MS(n)) and the phase II metabolites by LC-HR-MS(n). The following major metabolic pathways were proposed: N-demethylation, hydroxylation at the side chain and at the thiophene ring, and combination of these transformations followed by glucuronidation and/or sulfation. CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were identified as the major phase I metabolizing enzymes. They were also involved in the N-demethylation of the analogue methamphetamine and CYP2C19, CYP2D6, and CYP3A4 in its ring hydroxylation. Following the administration of a typical user's dose, 2-MPA and its metabolites were identified in rat urine using the authors' GC-MS and the LC-MS(n) screening approaches. Ingestion of 2-MPA could also be detected by both protocols in an authentic human urine sample. PMID:23361230

Welter, Jessica; Meyer, Markus R; Wolf, Ehud Udi; Weinmann, Wolfgang; Kavanagh, Pierce; Maurer, Hans H

2013-01-30

297

Site qualification studies of the UCG\\/SDB site, North Knobs, Wyoming  

Microsoft Academic Search

The site qualification program for the North Knobs UCG site near Rawlins, Wyoming has been completed. This site will be the location for the field tests of Underground Coal Gasification of Steeply Dipping Beds undertaken by Gulf Research and Development Company for DOE in a cost shared contract. Site characterization included a comprehensive geotechnical analysis along with vegetation, historical, and

B. E. Davis; S. A. Krajewski; P. F. Ahner; J. M. Avasthi; M. E. Dolde; C. A. Greenman; J. E. Miranda

1979-01-01

298

Improvement in chronic pelvic pain after gonadotropin releasing hormone analogue (GnRH-a) administration in premenopausal women suffering from adenomyosis or endometriosis: a retrospective study.  

PubMed

The aim of this study was to evaluate the improvement in catamenial chronic pelvic pain (CPP) after Gonadotropin Releasing Hormone analogue (GnRH-a) administration in women affected by adenomyosis or endometriosis. We retrospectively analysed clinical data of 63 premenopausal women with clinical suspect of adenomyosis (15 women, Group A) or endometriosis (48 women, Group B), which received GnRH-a in order to reduce CPP intensity during the time on surgery waiting list. Main outcome measures were variation of CPP intensity, numbers of days requiring analgesics and lost work productivity before and three months after GnRH-a administration. Compared to baseline, a significant decrease in CPP intensity (p < 0.05) was observed in both groups, even if this reduction was significantly higher in Group A than in Group B (p < 0.001). In both groups, moreover, a significant reduction in number of days requiring analgesics (p < 0.05) and lost work productivity (p < 0.05) was detected. In conclusion, GnRH-a administration in women with clinical suspect of adenomyosis induces a greater reduction in CPP when compared to women with endometriosis, thus representing a potential ex adiuvantibus criteria, helping TV-US in the clinical diagnosis of adenomyosis. PMID:23323768

Morelli, Michele; Rocca, Morena Luigia; Venturella, Roberta; Mocciaro, Rita; Zullo, Fulvio

2013-01-17

299

Coronary Calcification and Coronary Atherosclerosis: Site by Site Comparative Morphologic Study of Electron Beam Computed Tomography and Coronary Angiography  

Microsoft Academic Search

Objectives. We compared, on a site by site basis, the morphologic features of coronary calcifications determined by electron beam computed tomography (EBCT) and angiographically defined coronary atherosclerosis.Background. Quantification of coronary calcification using EBCT is clinically useful for the prediction of coronary stenosis. However, the relation between calcification and angiographic findings has not been evaluated by site.Methods. We studied 251 consecutive

Kouji Kajinami; Hiroyasu Seki; Noboru Takekoshi; Hiroshi Mabuchi

1997-01-01

300

Hanford Site Annual Treatability Studies Report Calendar Year 2001  

SciTech Connect

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

Grohs, Eugene L.

2002-02-20

301

Hanford Site Annual Treatability Studies Report, Calendar Year 2002  

SciTech Connect

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.

Grohs, Eugene L.

2003-02-28

302

A spectroscopy and isotope study of sediments from the Antarctic Dry Valleys as analogues for potential paleolakes on Mars  

Microsoft Academic Search

A spectroscopy and isotope study has been performed on igneous sediments from Lake Hoare, a nearly isolated ecosystem in the Dry Valleys region of Antarctica. The mineralogy and chemistry of these sediments were studied in order to gain insights into the biogeochemical processes occurring in a permanently ice-covered lake and to assist in characterizing potential habitats for life in paleolakes

Janice L. Bishop; Brandy L. Anglen; Lisa M. Pratt; Howell G. M. Edwards; David J. Des Marais; Peter T. Doran

2003-01-01

303

Photoaffinity analogues of farnesyl pyrophosphate transferable by protein farnesyl transferase.  

PubMed

Farnesylation is a posttranslational lipid modification in which a 15-carbon farnesyl isoprenoid is linked via a thioether bond to specific cysteine residues of proteins in a reaction catalyzed by protein farnesyltransferase (FTase). We synthesized analogues (3-6) of farnesyl pyrophosphate (FPP) to probe the range of modifications possible to the FPP skeleton which allow for efficient transfer by FTase. Photoaffinity analogues of FPP (5, 6) were prepared by substituting perfluorophenyl azide functional groups for the omega-terminal isoprene of FPP. Substituted anilines replace the omega-terminal isoprene in analogues 3 and 4. Compounds 3-5 were prepared by reductive amination of the appropriate anilines with 8-oxo-geranyl acetate, followed by ester hydrolysis, chlorination, and pyrophosphorylation. Additional substitution of three methylenes for the beta-isoprene of FPP gave photoprobe 6 in nine steps. Preparation of the analogues required TiCl(4)-mediated imine formation prior to NaBH(OAc)(3) reduction for anilines with a pK(a) < 1. The azide moiety was not affected by Ph(3)PCl(2) conversion of allylic alcohols 13-16 into corresponding chlorides 17-20. Analogues 3-6 are efficiently transferred to target N-dansyl-GCVLS peptide substrate by mammalian FTase. Comparison of analogue structures and kinetics of transfer to those of FPP reveals that ring fluorination and para substituents have little effect on the affinity of the analogue pyrophosphate for FTase and its transfer efficiency. These results are also supported with models of the analogue binding modes in the active site of FTase. The transferable azide photoprobe 5 photoinactivates FTase. Transferable analogues 5 and 6 allow the formation of appropriately posttranslationally modified photoreactive peptide probes of isoprene function. PMID:12105898

Chehade, Kareem A H; Kiegiel, Katarzyna; Isaacs, Richard J; Pickett, Jennifer S; Bowers, Katherine E; Fierke, Carol A; Andres, Douglas A; Spielmann, H Peter

2002-07-17

304

An experimental strategy towards optimising directed biosynthesis of communesin analogues by Penicillium marinum in submerged fermentation  

Microsoft Academic Search

It was previously demonstrated that a fungus producing communesin alkaloids, subsequently identified as Penicillium marinum, could also accept 6-fluoro analogues of tryptophan or tryptamine to form mono-fluoro-communesin analogues in addition to communesins. A strategy to increase the relative yield of analogues by mutation to impair decarboxylation of tryptophan has been studied. Four mutants with much reduced activity of tryptophan decarboxylase,

Lucy J. Wigley; David A. Perry; Peter G. Mantle

2008-01-01

305

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)

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 would support the hypothesis of oxygenic photosynthesis apparition at least 3.5 Gyr ago, long before the GOE.

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

2012-04-01

306

Benzodiazepine binding sites in the human hypothalamus. Autoradiographic study.  

PubMed

Using in vitro labelling and autoradiographic techniques, we have analyzed the fine and the detailed distribution of benzodiazepine binding sites in the post-mortem human hypothalamus. Binding sites were labelled in mounted tissue sections from adult brains, using the selective high affinity ligand [3H]-Flunitrazepam. A heterogeneous distribution of benzodiazepine binding sites was found throughout the rostrocaudal extent of human hypothalamus. The autoradiographic labelling was shown in the three hypothalamic parts, i.e., anterior, mediobasal and posterior levels. At the anterior level, the highest densities were present in the diagonal band of Broca, the preoptic area (medial and lateral parts) and the septohypothalamic nucleus. At the mediobasal hypothalamic level, the highest densities were mainly localized in the ventromedial nucleus, whereas the other structures were moderately labelled with [3H]-Flunitrazepam. The mammillary complex as well as the posterior hypothalamic area represented the most heavily labelled structures in the posterior hypothalamus. The results obtained in this study, indicate the presence of a large and heterogeneous distribution of benzodiazepine binding sites in human adult hypothalamus. This could support their implication in the control of distinct neural functions (like neuroendocrine role). PMID:10841448

Najimi, M; Bennis, M; Chigr, F; Kopp, N; Moyse, E; Miachon, S

1999-01-01

307

Risk assessment study of the Dickerson site. Volume 1. Text  

Microsoft Academic Search

A comprehensive, multipathway health-based risk assessment study was performed for routine air emissions from three combustion sources collocated at a rural site. The sources included a proposed 2250 ton\\/day municipal waste resource recovery facility, an existing 558 MW coal-fired power plant, and a proposed 750 MW oil\\/gas-fired combustion turbine power plant. State-of-the-art methods were developed to determine human exposure through

R. Brower; J. Gerritsen; K. Zankel; A. Huggins; N. Peters

1990-01-01

308

Clinical evaluation of three different gonadotrophin-releasing hormone analogues in an IVF programme: a prospective study  

Microsoft Academic Search

The efficacy and safety of short acting buserelin and nafarelin intranasal spray were compared to long acting leuprorelin depot intramuscular or subcutaneous injection in this prospective study of 157 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation (IVF). Patients were allocated to three groups to receive buserelin 150?g nasal spray three times daily (Group B), nafarelin nasal spray 400?g

A. El-Nemr; M. Bhide; Y. Khalifa; E. Al-Mizyen; C. Gillott; A. M. Lower; T. Al-Shawaf; J. G. Grudzinskas

2002-01-01

309

Towards adaptive Web sites: Conceptual framework and case study  

Microsoft Academic Search

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

Mike Perkowitz; Oren Etzioni

2000-01-01

310

Nuclear Energy Center study. Phase II. Site suitability analysis. Final report  

Microsoft Academic Search

A site screening study was conducted to identify a site or sites for detailed, site-specific study as a nuclear energy center. Using technical criteria of water requirements, geotechnical constraints, and projected load center and transmission considerations as well as environmental and institutional considerations, five potential study sites in the State of South Carolina were identified, evaluated against established criteria, and

W. S. Fellows; J. M. Sharp; B. I. Benator

1978-01-01

311

A Comparative Study of the Iron-Clearing Properties of Desferrithiocin Analogues With Desferrioxamine B in a Cebus Monkey Model  

Microsoft Academic Search

A comparative study of the iron-clearing properties of sub- cutaneously administered desferrioxamine B (DFO) with those of orally administered desferrithiocin sodium salt (1 ), desmethyl desferrithiocin (2). desazadesmethyl desferri- thiocin sodium salt (3), desazadesmethyl desferrithiocin pi- valoyloxymethyl ester (4). and desazadesmethyl-5.5-di- methyl desferrithiocin (5) in an iron-loaded Cebus monkey model and a non-iron overloaded bile duct-cannulated rat model is presented.

Raymond J. Bergeron; Richard R. Streiff; Elizabeth A. Creary; Richard D. Daniels Jr; Walter King; Gabriel Luchetta

1993-01-01

312

Phase I Study of JM216 (an Oral Platinum Analogue) in Combination with Paclitaxel in Patients with Advanced Malignancies  

Microsoft Academic Search

This phase I study wasconducted to determine the dose limitingtoxicity, maximum tolerated doses, andrecommended phase II doses of thecombination of JM-216 and paclitaxel. Patients received paclitaxel intravenouslyover one hour on day 1 of each cycle. OralJM-216 was administered on days 1–5starting after the paclitaxel infusion. Cycles were repeated every 21 days. Patients were accrued at nine differentdosing combinations. JM-216 doses

Suzanne Jones; John Hainsworth; Howard A. Burris; Dana Thompson; Eric Raefsky; Valerie Johnson; Sharon Calvert; Cecile Bulanhagui; David Lebwohl; F. Anthony Greco

2002-01-01

313

Reactions of trimethylphosphine analogues of auranofin with bovine serum albumin  

SciTech Connect

The reactions of bovine serum albumin (BSA) with (trimethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I), Me/sub 3/PAuSAtg, and its chloro analogue, Me/sub 3/PAuCl, were studied to develop insights into the role of the phosphine ligand in the serum chemistry of the related antiarthritic drug auranofin (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-thio-..beta..-D-glucopyranosato-S)gold(I). /sup 31/P NMR spectroscopy, protein modification, and gel-exclusion chromatography methods were employed. Comparison of the reactions of the methyl derivatives to the previously reported reactions of auranofin and Et/sub 3/PAuCl with BSA demonstrated that similar chemical species are formed but revealed three major differences. Despite these differences, the results for the methyl analogues provide important confirmation for previously developed chemical models of auranofin reactions in serum. Me/sub 3/PO was not observed in reaction mixtures lacking tetraacetylthioglucose (AtgSH); this result affirms the role of AtgSH, displaced by the reaction of Me/sub 3/PAuSAtg at Cys-34, in the generation of the phosphine oxide (an important metabolite in vivo). The weak binding sites on albumin react with Me/sub 3/PAuCl, but not Me/sub 3/PAuSAtg, demonstrating the importance of the strength and reactivity of the anionic ligand-gold bond on the reactions of auranofin analogues. The gold binding capacity of albumin is enhanced after Me/sub 3/PO is formed, consistent with reductive cleavage of albumin disulfide bonds by trimethylphosphine. 24 references, 2 figures, 3 tables.

Isab, A.A.; Shaw, C.F. III; Hoeschele, J.D.; Locke, J.

1988-10-05

314

A comparison of visual analogue and numerical rating scale formats for the Lung Cancer Symptom Scale (LCSS): Does format affect patient ratings of symptoms and quality of life?  

Microsoft Academic Search

Problem and Purpose: The Lung Cancer Symptom Scale (LCSS), a site-specific health-related quality of life measure for patients with lung cancer, was originally developed using a Visual Analogue Scale (VAS) format. However, the VAS format is not readily compatible with data management and software programs using scanning. The primary aim of this study was to evaluate the convergence of ratings

P. J. Hollen; R. J. Gralla; M. G. Kris; S. McCoy; G. W. Donaldson; C. M. Moinpour

2005-01-01

315

SITE: A methodology for assessment of energy facility siting patterns. Regional studies program  

Microsoft Academic Search

A documentation is presented of the computerized SITE methodology that was developed for evaluating health, environmental, and socioeconomic impacts related to utilization of alternate sites for energy production within a region of interest. The cost, impact, and attribute vectors, which are generated and displayed on density maps, can be used in a multiparameter overlay process to identify preferable siting areas.

N. A. Frigerio; L. J. Habegger; R. F. King; L. J. Hoover; N. A. Clark; J. M. Cobian

1975-01-01

316

Cafestol to Tricalysiolide B and Oxidized Analogues: Biosynthetic and Derivatization Studies Using Non-heme Iron Catalyst Fe(PDP)  

PubMed Central

The tricalysiolides are a recently isolated class of diterpene natural products featuring the carbon backbone of the well-known coffee extract, cafestol. Herein we validate the use of our non-heme iron complex, Fe(PDP), as an oxidative tailoring enzyme mimic to test the proposal that this class of natural products derives from cafestol via cytochrome P-450-mediated furan oxidation. Thereafter, as predicted by computational analysis, C–H oxidation derivatization studies provided a novel 2° alcohol product as a single diastereomer.

Bigi, Marinus A.; Liu, Peng; Zou, Lufeng

2013-01-01

317

Two and three-dimensional QSAR studies on benzyl amide-ketoacid inhibitors of HIV integrase and their reduced analogues  

Microsoft Academic Search

The discovery of clinically relevant inhibitors of HIV-integrase for antiviral therapy has proven to be a challenging task.\\u000a Ketoacid-derived inhibitors selectively inhibit the strand transfer reaction of HIV-integrase. To elucidate the structural\\u000a properties required for HIV-integrase inhibitory activity, we present here the results of two- and three-dimensional (2D and\\u000a 3D) QSAR studies of a series of 24 benzyl amide derivatives.

Sudha Vengurlekar; Rajesh Sharma; Piyush Trivedi

2010-01-01

318

Isothermal Titration Calorimetry Studies of the Binding of a Rationally Designed Analogue of the Antimicrobial Peptide Gramicidin S to Phospholipid Bilayer Membranes†  

PubMed Central

The binding of the positively charged antimicrobial peptide cyclo[VKLdKVdYPLKVKLdYP] (GS14dK4) to various lipid bilayer model membranes was investigated using isothermal titration calorimetry. GS14dK4 is a diastereomeric lysine ring-size analogue of the naturally occurring antimicrobial peptide gramicidin S which exhibits enhanced antimicrobial and markedly reduced hemolytic activities compared with GS itself. Large unilamellar vesicles composed of various zwitterionic (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphorylcholine [POPC]) and anionic phospholipids {1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(glycerol)] [POPG] and 1-palmitoyl-2-oleoyl-sn-glycero-3-[phosphoserine] [POPS]}, with or without cholesterol, were used as model membrane systems. Dynamic light scattering results indicate the absence of any peptide-induced major alteration in vesicle size or vesicle fusion under our experimental conditions. The binding of GS14dK4 is significantly influenced by the surface charge density of the phospholipid bilayer and by the presence of cholesterol. Specifically, a significant reduction in the degree of binding occurs when three-fourths of the anionic lipid molecules are replaced with zwitterionic POPC molecules. No measurable binding occurs to cholesterol-containing zwitterionic vesicles, and a dramatic drop in binding is observed in the cholesterol-containing anionic POPG and POPS membranes, indicating that the presence of cholesterol markedly reduces the affinity of this peptide for phospholipid bilayers. The binding isotherms can be described quantitatively by a one-site binding model. The measured endothermic binding enthalpy (?H) varies dramatically (+6.3 to +26.5 kcal/mol) and appears to be inversely related to the order of the phospholipid bilayer system. However, the negative free energy (?G) of binding remains relatively constant (?8.5 to ?11.5 kcal/mol) for all lipid membranes examined. The relatively small variation of negative free energy of peptide binding together with a pronounced variation of positive enthalpy produces an equally strong variation of T?S (+16.2 to +35.0 kcal/mol), indicating that GS14dK4 binding to phospholipids bilayers is primarily entropy driven.

Abraham, Thomas; Lewis, Ruthven N. A. H.; Hodges, Robert S.; McElhaney, Ronald N.

2011-01-01

319

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

SciTech Connect

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.

Not Available

1988-01-01

320

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

PubMed

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

Blashill, Aaron J; Powlishta, Kimberly K

2012-06-22

321

Computational studies of Bronsted acid sites in zeolites  

SciTech Connect

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.

Curtiss, L.A.; Iton, L.E. [Argonne National Lab., IL (United States); Zygmunt, S.A. [Valparaiso Univ., IN (United States). Dept. of Physics and Astronomy

1995-01-01

322

Computational studies of Bronsted acid sites in zeolites  

NASA Astrophysics Data System (ADS)

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 H2O 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.

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

1995-01-01

323

Summary of 1990 eolian characterization studies, Hanford Site, Washington  

SciTech Connect

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.

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

1993-12-01

324

Structure?Activity Relationship (SAR) Studies of Benzoxazinones, Their Degradation Products, and Analogues. Phytotoxicity on Problematic Weeds Avena fatua L. and Lolium rigidum Gaud  

Microsoft Academic Search

Avena fatua L. (wild oat) and Lolium rigidum Gaud. (rigid ryegrass) are highly problematic weeds affecting a wide variety of cereal crops worldwide. The fact that both of these weeds have developed resistance to several herbicide groups made them optimal candidates as target organisms for ongoing research about the potential application of allelochemicals and analogue compounds as natural herbicide models.

Francisco A. Macías; David Marín; Alberto Oliveros-Bastidas; Diego Castellano; Ana M. Simonet; José M. G. Molinillo

2006-01-01

325

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

326

Vitamin B12 Analogues, Homocysteine, Methylmalonic Acid, and Transcobalamins in the Study of Vitamin B12 Deficiency in Primary Degenerative Dementia  

Microsoft Academic Search

B12 analogues, homocysteine, methylmalonic acid (MMA), and unsaturated transcobalamins, all potential markers of vitamin B12 status, were analyzed in blood and cerebrospinal fluid (CSF) from 22 patients with primary degenerative dementia of Alzheimer type. The level of active vitamin B12 in serum correlated significantly with serum homocysteine, serum MMA, and CSF homocysteine. CSF B12 correlated significantly with serum homocysteine and

B. Regland; L. Abrahamsson; C. G. Gottfries; E. Magnus

1990-01-01

327

A Descriptive Study of the Use of Visual Analogue Scales and Verbal Rating Scales for the Assessment of Postoperative Pain in Orthopedic Patients  

Microsoft Academic Search

Visual analogue scales (VAS) and verbal rating scales (VRS) are widely used to assess pain. This paper presents a secondary analysis of a subsection of data collected as part of an evaluation of an intervention to improve nighttime pain. The aims were to describe the relationship between the VAS and VRS; to compare characteristics of the noncompliant groups in terms

Michelle Briggs; José S Closs

1999-01-01

328

Solid-phase synthesis and DNA binding studies of dichloroplatinum(ii) conjugates of dicarba analogues of octreotide as new anticancer drugs.  

PubMed

The first dichloroplatinum(ii) conjugates of dicarba analogues of octreotide, which is expected to act as a 'tumour-targeting device', have been efficiently synthesized following a stepwise solid-phase approach; these compounds emulate the mechanism of cisplatin since they form a 1,2-intrastrand cross-link with two consecutive guanines of an oligonucleotide. PMID:19641816

Barragán, Flavia; Moreno, Virtudes; Marchán, Vicente

2009-06-22

329

Structureactivity relationship of a series of C-terminus modified aminoalkyl, diaminoalkyl- and anilino-containing analogues of the benzoic acid mustard distamycin derivative tallimustine: Synthesis, DNA binding and cytotoxicity studies  

Microsoft Academic Search

As part of our investigations into the design of more cytotoxic analogues of the experimental anticancer drug tallimustine, 1, C-terminus modified aminoalkyl-, 2a–c, diaminoalkyl-, 3, and anilino-containing, 4, derivatives have been synthesized. Compounds 2a–c differ by 2, 3, or 4 methylene units in the C-terminus, respectively. Results from an ethidium displacement study on poly(dA-dT), poly(dG-dC), calf thymus DNA and T4

Natalie Brooks; John A Hartley; Jacob E Simpson; Stephen R Wright; Shirley Woo; Sara Centioni; Michael D Fontaine; Terry E McIntyre; Moses Lee

1997-01-01

330

Methysergide decreases prolactin release after FK 33-824 [Tyr-D-Ala-Gly-MePhe-Met(o)-ol], a potent analogue of methionine enkephalin. A study in man  

Microsoft Academic Search

This study investigated the mechanisms which may underly the prolactin (PRL) stimulating effects of FK 33-824, a potent enkephalin analogue. FK 33-824 (1 mg) was infused in healthy volunteers before and after pretreatment with 3 mg methysergide, a serotonin receptor blocker. All subjects showed a release of PRL after FK 33-824, which was significantly diminished after pretreatment with methysergide.

G. Jungkunz; N. Nedopil; E. Riither

1984-01-01

331

An Open-Label, Parallel Group Study Investigating the Effects of Age and Gender on the Pharmacokinetics of the Once-Daily Glucagon-Like Peptide1 Analogue Liraglutide  

Microsoft Academic Search

Liraglutide is a once-daily glucagon-like peptide-1 analogue being developed for the treatment of type 2 diabetes. The aim of this study was to investigate the effect of age and gender on the pharmacokinetics of liraglutide. Eight male and 8 female subjects were recruited from an 18- to 45-year-old group and an over-65-year-old group, respectively. All subjects received a single subcutaneous

Birgitte Damholt; Georg Golor; Werner Wierich; Poul Pedersen; Marianne Ekblom; Milan Zdravkovic

2006-01-01

332

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

SciTech Connect

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

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

2012-06-25

333

X-ray powder diffractometry and liquid chromatography studies of sibutramine and its analogues content in herbal dietary supplements.  

PubMed

The contemporary societies of the developed countries are prone to use traditional far-east medicines as remedies for all diseases. Some of them, such as obesity, might be classified as civilization diseases. Combating the problem, people try not only several miraculous diets but also herbal infusions (teas) and variety of "herbal" preparations. All these believing that such treatment is healthy and harmless as far as it is "natural". Leaving out of the way the question if herbal medicines can be taken safely without doctors' control the query arises if the common preparations are strictly natural and herbal. Here we report examples of quality studies of such medicines using both X-ray powder diffraction (XRPD) and liquid chromatography (LC) with various types of detection: ultraviolet (UV), coulometric electrode array (CEAD) and time-of-flight mass spectrometry (TOF-MS). Especially the XRPD assisted with an optical microscopy seems to be useful as a fast screening method of general sample composition of such preparations. First of all it can discriminate between capsules containing pure herbal materials and those with some chemical. PMID:21899974

Stypu?kowska, K; B?a?ewicz, A; Maurin, J; Sarna, K; Fija?ek, Z

2011-08-24

334

Tritium migration studies at the Nevada Test Site  

SciTech Connect

Emanation of tritium from waste containers is a commonly known phenomenon. Release of tritium from buried waste packages was anticipated, therefore a research program was developed to study both the rate of tritium release from buried containers and subsequent migration of tritium through soil. Migration of tritium away from low level radioactive wastes buried in Area 5 of the Nevada Test Site was studied. Four distinct disposal events were investigated. The oldest burial event studied was a 1976 emplacement of 3.5 million curies of tritium in a shallow land burial trench. Tritium transport to the atmosphere by plant transpiration was determined to have risen sharply with the passage of time, and is now occurring at the rate of about 6 curies per year. The tritium being released from this waste has not resulted in elevated tritium levels in the urine of people working directly on the trench cap. Air samplers placed around the perimeter of the Area 5 site show no higher tritium levels than the Nevada Test Site in general. In another event, 248 thousand curies of tritium was disposed of in an overpack emplaced 6 meters below the floor of a low-level waste disposal pit. Measurement of the emanation rate of tritium out of 55 gallon drums to the overpack was studied, and an annual doubling of the emanation rate over a seven year period was found. No evidence of significant migration of tritium away from the overpack was found. In a third study, upward tritium migration in the soil was observed in a greater confinement disposal test. The movement was suspected largely to be the result of experimental anomalies and heat generated by other radionuclides present in the waste. Releases of tritium to the atmosphere were found to be insignificant. The fourth event consisted of burial of 2.2 million curies of tritium in a greater confinement disposal operation. No significant migration was found. 4 refs., 4 figs., 6 tabs.

Schulz, R.K.; Romney, E.M.; Fujii, L.M.; Greger, P.D. (California Univ., Berkeley, CA (United States)); Kendall, E.W.; Hunter, R.B. (Reynolds Electrical and Engineering Co., Inc., Las Vegas, NV (United States))

1991-08-01

335

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

SciTech Connect

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.

NONE

1996-05-03

336

Clinical evaluation of three different gonadotrophin-releasing hormone analogues in an IVF programme: a prospective study.  

PubMed

The efficacy and safety of short acting buserelin and nafarelin intranasal spray were compared to long acting leuprorelin depot intramuscular or subcutaneous injection in this prospective study of 157 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation (IVF). Patients were allocated to three groups to receive buserelin 150 microg nasal spray three times daily (Group B), nafarelin nasal spray 400 microg twice daily (Group N), or leuprorelin depot 3.75 mg once by intramuscular or subcutaneous injection (Group L) for pituitary desensitisation prior to commencing COH with human menopausal gonadotrophins (hMG) according to the Centre's protocol. The mean (+/-S.D.) age (years) (32.6+/-3.8: Group B, 32.1+/-3.3: Group N versus 32.1+/-3.3: Group L); mean (+/-S.D.) total dosage of hMG (ampoules) (37.5+/-16.1: Group B, 39.8+/-14.2: Group N versus 41.9+/-12.6: Group L) and mean daily dosage of hMG (ampoules) (3.1: Group B, 2.8: Group N versus 3.0: Group L) seen were not statistically significantly different. The duration between starting the different gonadotrophin-releasing hormone (GnRHa) and the beginning of the next menstrual period was also not seen to be statistically significantly different between the three groups (Group B: 10+/-5.5, Group N: 9.1+/-4.1 versus Group L: 8.2+/-3, days). The number of abandoned cycles was higher in Group L (17% versus 11.8%: Group B and 11.3%: Group N) but this difference did not reach statistical significance. The clinical pregnancy rates per oocyte retrieval and per embryo transfer procedure were respectively, 31.1, 35% in Group B, 12.8, 14% in Group N versus 20.5, 23.7 in Group L and were not seen to be statistically significantly different even when ongoing pregnancy rates were compared. Apart from a statistically significantly greater incidence of allergic nasal reactions in the nafarelin group (P=0.001), all other side-effects were not shown to be statistically significantly different between the three groups. We conclude that a single dose of leuprorelin depot can be considered to be as an equally effective alternative to multiple doses of buserelin or nafarelin for pituitary desensitisation in women undergoing COH for IVF. PMID:12069736

El-Nemr, A; Bhide, M; Khalifa, Y; Al-Mizyen, E; Gillott, C; Lower, A M; Al-Shawaf, T; Grudzinskas, J G

2002-07-10

337

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

SciTech Connect

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)

Hart, J.S. (ed.)

1981-05-01

338

The silkmoth eggshell as a natural amyloid shield for the safe development of insect oocyte and embryo: insights from studies of silkmoth chorion protein peptide-analogues of the B family.  

PubMed

Silkmoth chorion is the major component of the silkmoth eggshell. The proteins that constitute more than 95% of its dry mass have remarkable mechanical and physicochemical properties forming a protective natural shield for the oocyte and the developing embryo from a wide range of environmental hazards. Peptide-analogues of the central conservative domain of the two major families of silkmoth chorion proteins, the A's and the B's, form amyloid fibrils under a variety of conditions, which prompted us to propose, 10 years ago, that silkmoth chorion is an amyloid with protective properties. Following our finding, a number of studies verified the existence of several functional amyloids. In this study, we designed, synthesized and studied two peptide-analogues of the central conservative domain of the B family of silkmoth chorion proteins, and we present experimental results, which show: (a) that the amyloidogenic properties of silkmoth chorion peptides are encoded into the tandemly repeating hexapeptides comprising the central domain of silkmoth chorion proteins, confirming our previous findings from peptide analogues of the A family of chorion proteins, and, (b) they suggest how silkmoth chorion proteins of the B family self-assemble in vivo, for the formation of the helicoidal architecture of silkmoth chorion. PMID:22252423

Iconomidou, Vassiliki A; Cordopatis, Paul; Hoenger, Andreas; Hamodrakas, Stavros J

2011-02-18

339

Synthesis and antitumor activity of cyclophosphamide analogues. 4. Preparation, kinetic studies, and anticancer screening of "phenylketophosphamide" and similar compounds related to the cyclophosphamide metabolite aldophosphamide.  

PubMed

Phenyl ketone phosphorodiamidates [C6H5C(O)CH2CH2OP(O)NHR1NR2R3] were synthesized in conjunction with an ongoing investigation into the effects of substituents on the dynamical solution chemistry of the metabolites of cyclophosphamide (1a). In contrast to aldophosphamide (3a), which readily interconverts with its cyclic isomer 4-hydroxycyclophosphamide (2a), phenylketophosphamide (14a: R1 = H, R2 = R3 = CH2CH2Cl) exhibited an apparent "resistance" toward an intramolecular addition reaction such that 4-hydroxy-4-phenylcyclophosphamide (13a) could not be detected either spectroscopically (31P or 13C NMR) or chemically (NaCN trapping experiment). Control studies that compared the relative reactivities of 14a and methylketophosphamide [20: CH3C(O)CH2CH2OP(O)NH2N-(CH2CH2Cl)2] revealed that the factors that modulate the ring closure/opening reactions were not peculiar to the phenyl group; however, differences between phenyl and methyl profoundly influenced the rates of fragmentation of 14a and 20. 31P NMR spectroscopy was used to determine the rates at which each compound generated a cytotoxic alkylating agent. Under a standard set of reaction conditions [1 M lutidine buffer with added Me2SO (8:2), pH 7.4, 37 degrees C], the half-lives of 2a/3a, 14a, phenylketoifosfamide (14b: R1 = R2 = CH2CH2Cl, R3 = H), phenylketotrofosfamide (14c: R1 = R2 = R3 = CH2CH2Cl), and 20 were 72, 66, 63, 56, and 173 min, respectively. Analogues 14a and 14b exhibited good anticancer activity against a variety of test systems. PMID:3701785

Ludeman, S M; Boyd, V L; Regan, J B; Gallo, K A; Zon, G; Ishii, K

1986-05-01

340

Synthetic histatin analogues with broad-spectrum antimicrobial activity.  

PubMed Central

Histatins are salivary histidine-rich cationic peptides, ranging from 7 to 38 amino acid residues in length, that exert a potent killing effect in vitro on Candida albicans. Starting from the C-terminal fungicidal domain of histatin 5 (residues 11-24, called dh-5) a number of substitution analogues were chemically synthesized to study the effect of amphipathicity of the peptide in helix conformation on candidacidal activity. Single substitutions in dh-5 at several positions did not have any effect on fungicidal activity. However, multi-site substituted analogues (dhvar1 and dhvar2) exhibited a 6-fold increased activity over dh-5. In addition, dhvar1 and dhvar2 inhibited the growth of the second most common yeast found in clinical isolates, Torulopsis glabrata, of oral- and non-oral pathogens such as Prevotella intermedia and Streptococcus mutans, and of a methicillin-resistant Staphylococcus aureus. In their broad-spectrum activity, dhvar1 and dhvar2 were comparable to magainins (PGLa and magainin 2), antimicrobial peptides of amphibian origin. Both the fungicidal and the haemolytic activities of dhvar1, dhvar2 and magainins increased at decreasing ionic strength.

Helmerhorst, E J; Van't Hof, W; Veerman, E C; Simoons-Smit, I; Nieuw Amerongen, A V

1997-01-01

341

Adenosine analogues decrease myocardial. beta. -adrenergic receptor affinity for isoproterenol  

SciTech Connect

Adenosine and its analogues have been shown to attenuate catecholamine-induced activation of adenylate cyclase in rat myocardial membranes via adenosine R/sub i/ (inhibitory) receptors. The effects of adenosine analogues on binding characteristics of ..beta..-adrenergic receptors (BAR) in rat heart ventricular membranes were examined in the present study. Neither phenylisopropyladenosine (PIA, 1..mu..M) nor 2-chloroadenosine (CADO, 10..mu..M) significantly influenced /sup 125/I-cyanopinodolol (ICYP) binding to membranes as assessed by BAR affinity (Kd, 20 pM) or concentration (B/sub max/, 35 fmol/mg protein). However, in isoproterenol (ISO)-ICYP competition experiments, PIA, an R/sub i/ agonist, significantly shifted the ISO competition curve to the right 3.6 fold. The IC/sub 50/s of control and PIA treated membranes were 5.04 x 10/sup -8/M, and 1.81 X 10/sup -7/M respectively. The slope of the control curve (-0.58) was also increased in the PIA treated membranes (-0.94). CADO, a less specific adenosine R/sub i/ receptor agonist, shifted the curve to the right only 2 fold and increased the slope from -0.5 to -0.75. 2',5'-dideoxyadenosine, an adenosine P-site agonist, had no significant effect on ISO binding. These data suggest that adenosine R/sub i/ agonists may attenuate catecholamine-induced activation of adenylate cyclase by decreasing the affinity of BAR for agonists.

Romano, F.D.; Fenton, R.A.; Dobson, J.G. Jr.

1986-03-05

342

Inhibition of monoamine oxidase by (E)-styrylisatin analogues  

PubMed Central

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

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

2009-01-01

343

Testing technologies and strategies for exploration in Australian Mars analogues: A review  

Microsoft Academic Search

Australia is an ideal testing ground in preparation for the robotic and human exploration of Mars. Numerous sites with landforms or processes analogous to those on Mars are present and the deserts of central Australia provide a range of locations for free-ranging Mars analogue mission simulations. The latest developments in testing technologies and strategies for exploration in Australian Mars analogues

Michael D. West; Jonathan D. A. Clarke; Jennifer H. Laing; David Willson; James M. A. Waldie; Guy M. Murphy; Matilda Thomas; Graham A. Mann

2010-01-01

344

Design of Analogue Synapse Circuits using Non-Volatile aSi:H Memory Devices  

Microsoft Academic Search

Analogue hardware implementations of neural networks have hitherto been hampered by the lack of a straightforward analogue memory capability. The synaptic weights which are developed by the network learning process must be stored (preferably at each synapse site) in order that a network can adequately perform any recall or classification tasks. Ideally, the storage mechanism should be compact, non-volatile, easily

A. J. Holmes; Stephen Churcher; J. Hajto; Alan F. Murray; M. J. Rose

1994-01-01

345

Studies on fascioliasis in four selected sites in Ethiopia.  

PubMed

The incidence of fascioliasis was studied in Asela, Awasa, Debre Zeit and Debre Berhan by using 153 experimental sheep divided up into 4 groups designated tracer sheep, Controls I, II and III. Fasciola hepatica was encountered in Debre Berhan, Asela and Awasa, but it was not detected at Debre Zeit. In all areas, it was most frequently recovered after heavy rains. Altitude, soil type, salt content and local crowding of animals in watering sites appear to have influenced the varying degrees of incidence and intensity of infection. PMID:4049725

Lemma, B; Gabre-ab, F; Tedla, S

1985-06-01

346

Novobiocin Analogues as Anticancer Agents.  

National Technical Information Service (NTIS)

Novel analogues and derivatives of novobiocin are provided, including compounds having modifications to the amide side chain, coumarin ring, and sugar moieties. The compounds of the present invention are useful as heat shock protein 90 inhibitors, and may...

B. S. Blagg L. Neckers X. M. Yu

2005-01-01

347

Polarization Near Isobaric Analogue Resonances.  

National Technical Information Service (NTIS)

For the purpose of analysing isobaric analogue resonances, a single-level resonance formula has been incorporated into nuclear scattering amplitudes found with an optical-model potential. The inclusion of the resonance term leads to polarization magnitude...

J. L. Adams W. J. Thompson D. Robson

1966-01-01

348

Testing technologies and strategies for exploration in Australian Mars analogues: A review  

NASA Astrophysics Data System (ADS)

Australia is an ideal testing ground in preparation for the robotic and human exploration of Mars. Numerous sites with landforms or processes analogous to those on Mars are present and the deserts of central Australia provide a range of locations for free-ranging Mars analogue mission simulations. The latest developments in testing technologies and strategies for exploration in Australian Mars analogues are reviewed. These include trials of analogue space suits based on mechanical counter pressure technology and the development of an analogue, crewed, pressurized rover for long-range exploration. Field science activities and instrumentation testing relevant to robotic and future crewed missions are discussed. Australian-led human factors research undertaken during expeditions to Mars analogue research stations and expeditions to Antarctica are also reviewed. Education and public outreach activities related to Mars analogue research in Australia are also detailed.

West, Michael D.; D. A. Clarke, Jonathan; Laing, Jennifer H.; Willson, David; Waldie, James M. A.; Murphy, Guy M.; Thomas, Matilda; Mann, Graham A.

2010-03-01

349

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

PubMed

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 ?-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). PMID:21823658

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

2011-09-26

350

SHRINE: Enabling Nationally Scalable Multi-Site Disease Studies  

PubMed Central

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

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

2013-01-01

351

SHRINE: enabling nationally scalable multi-site disease studies.  

PubMed

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

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

2013-03-07

352

Regioselective bromination tactics in the de novo synthesis of chlorophyll b analogues.  

PubMed

The ability to introduce substituents at designated sites about the perimeter of the chlorin or 13(1)-oxophorbine macrocycle is essential for fundamental studies related to chlorophylls. A chlorin is a dihydroporphyrin, whereas a 13(1)-oxophorbine is a chlorin containing an annulated oxopentano ring spanning positions 13 and 15. 13(1)-Oxophorbines bearing auxochromes at the 7-position of the macrocycle are valuable targets given their resemblance to chlorophyll a or b, which contains the 13(1)-oxophorbine skeleton and bears a 7-methyl or 7-formyl group, respectively. A rational route to 7-substituted 13(1)-oxophorbines was developed that relies on a new method for regioselective bromination. Under neutral conditions, a 13-acetyl-10-mesitylchlorin (FbC-M(10)A(13)) undergoes bromination (with 1 molar equiv of NBS in THF) both in ring B (7-position) and at the 15-position (42% versus 28% isolated yield), thereby thwarting installation of the isocyclic ring (ring E, spanning the 13-15 positions). Under acidic conditions (10% TFA in CH(2)Cl(2)), ring B is deactivated, and bromination occurs preferentially at the 15-position (87% yield). The capability for preferential 15-bromination is essential to install the isocyclic ring, after which bromination can be directed to the 7-position of ring B (neutral conditions, 86% yield). The ability to suppress bromination in ring B (under acidic media) has been exploited in syntheses of sparsely substituted analogues of chlorophyll b. The analogues contain a 7-substituent (acetyl, formyl, or TIPS-ethynyl), a 10-mesityl group, and the 18,18-dimethyl group as the only substituents in the 13(1)-oxophorbine skeleton. The three analogues exhibit absorption spectral features that closely resemble those of free base analogues of chlorophyll b. Taken together, the facile access to chlorins and 13(1)-oxophorbines bearing substituents at distinct sites should enable fundamental spectroscopic studies and diverse applications. PMID:19388711

Muthiah, Chinnasamy; Lahaye, Dorothée; Taniguchi, Masahiko; Ptaszek, Marcin; Lindsey, Jonathan S

2009-05-01

353

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

PubMed

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

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

2013-01-02

354

Synthesis and solution conformation studies of the modified nucleoside N(4),2'-O-dimethylcytidine (m(4)Cm) and its analogues.  

PubMed

The dimethylated ribosomal nucleoside m(4)Cm and its monomethylated analogues Cm and m(4)C were synthesized. The conformations (syn vs anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O vs N methylation) was found to have an effect on the sugar pucker of cytidine. PMID:18805697

Mahto, Santosh K; Chow, Christine S

2008-09-09

355

A study on CYP1A inhibitory action of E-2-(4?-methoxybenzylidene)-1-benzosuberone and some related chalcones and cyclic chalcone analogues  

Microsoft Academic Search

In vivo investigation of E-2-(4?-methoxybenzylidene)-1-benzosuberone (4a) on the 7,12-dimethylbenz[a]anthracene (DMBA)-induced onco\\/tumor suppressor gene expressions suggested that inhibition of metabolic activation of DMBA might play a role in the observed activity of the compound. In order to explore this possible biological action we have investigated whether 4a and some of its structurally related analogues had inhibitory effects on the CYP1A enzymes.

Katalin Monostory; Viola Tamási; László Vereczkey; Pál Perjési

2003-01-01

356

Synthesis and solution conformation studies of the modified nucleoside N4, 2?-O-dimethylcytidine (m4Cm) and its analogues  

PubMed Central

The dimethylated ribosomal nucleoside m4Cm and its monomethylated analogues Cm and m4C were synthesized. The conformations (syn versus anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O versus N methylation) was found to have an effect on the sugar pucker of cytidine.

Mahto, Santosh K.; Chow, Christine S.

2008-01-01

357

Historic Resource Study Friendship Hill Historic Site Pennsylvania.  

National Technical Information Service (NTIS)

Friendship Hill National Historic Site was authorized by Congress in the National Parks and Recreation Act of 1978. The site includes the home of Albert Gallatin, known as Friendship Hill, and various other structures and farm buildings. The historic reso...

H. D. Unrau K. W. Fiero S. Jacobs

1981-01-01

358

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...

359

Two types of urate binding sites on hemocyanin from the crayfish Astacus leptodactylus: an ITC study.  

PubMed

The oxygen binding behaviour of hemocyanins from Crustacea is regulated by small organic compounds such as urate and L-lactate. We investigated the binding characteristics of urate and the related compound caffeine to the 2 x 6-meric hemocyanin of A. leptodactylus under fully oxygenated conditions employing isothermal titration calorimetry (ITC). An analysis of urate and caffeine binding based on a model of n identical binding sites resulted in approximately four binding sites for caffeine and eight for urate. This result suggests that the binding process for these effectors is more complex than this most simple model. Therefore, we introduced a number of alternative models. Displacement experiments helped to select the appropriate model. Based on these experiments, at least two different types of binding sites for urate and caffeine exist on the 2 x 6-meric hemocyanin of A. leptodactylus. The two binding sites differ strongly in their specificity towards the two analogues. It can be hypothesized that two different subunit types (beta and gamma) are responsible for the two types of binding sites. PMID:11407645

Hellmann, N; Jaenicke, E; Decker, H

2001-05-18

360

Cladribine: not just another purine analogue?  

PubMed

Cladribine was synthesized as a purine analogue drug that inhibited adenosine deaminase. It received FDA approval in the 1980s for treatment of hairy cell leukemia. Given its toxicity towards lymphocytes and its corresponding immunosuppressive effects, it has been studied and found efficacious in a variety of hematologic malignancies and autoimmune conditions, most recently multiple sclerosis. This review highlights pharmacological, toxicological and clinical data for the use of cladribine. It also discusses existing and new mechanisms that may contribute to its unique clinical activity. Emerging data show that in addition to its known purine nucleoside analogue activity, cladribine possesses epigenetic properties, inhibiting S-adenosylhomocysteine hydrolase and DNA methylation. This may contribute to its efficacy and highlights the importance of studying combination therapy with other epigenetic or targeted agents. Clinical trials are underway in a variety of malignant and nonmalignant conditions. PMID:19604118

Spurgeon, Stephen; Yu, Margaret; Phillips, John D; Epner, Elliot M

2009-08-01

361

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

SciTech Connect

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.

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

2007-11-01

362

A Cross-site Qualitative Study of Physician Order Entry  

PubMed Central

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

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

2003-01-01

363

Compositional characteristics of rennet caseins and hydration characteristics of the caseins in a model system as indicators of performance in Mozzarella cheese analogue manufacture  

Microsoft Academic Search

Rennet casein is widely used in the manufacture of Mozzarella cheese analogues. Wide variation in the functional performance of different rennet caseins during the manufacture of such cheese analogues is encountered, resulting in considerable variability in the functional properties of the cheese analogue. Samples of 44 batches of edible rennet caseins were studied for performance in Mozzarella cheese analogue manufacture

M. P. Ennis; D. M. Mulvihill

1999-01-01

364

Lead optimization of antimalarial propafenone analogues.  

PubMed

Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges. PMID:22708838

Lowes, David; Pradhan, Anupam; Iyer, Lalitha V; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W Armand; Sigal, Martina; Clark, Julie A; Wilson, Emily; Tang, Liang; Connelly, Michele C; Derisi, Joseph L; Kyle, Dennis E; Mirsalis, Jon; Guy, R Kiplin

2012-06-29

365

Isomer-shift analogue in neutron resonances  

Microsoft Academic Search

For the first time, the recently predicted chemical shift of neutron resonances, to be regarded as an analogue to the Mössbauer isomer shift, has been experimentally observed studying the 6.67 eV resonance of 238U. The experimental shifts were determined by a chi-square fitting technique from the time-of-flight transmission spectra of metallic uranium and four uranium compounds measured at the Dubna

A. Meister; D. Pabst; L. B. Pikelner; K. Seidel

1981-01-01

366

Farnesyl Diphosphate Analogues with Aryl Moieties are Efficient Alternate Substrates for Protein Farnesyltransferase  

PubMed Central

Farnesylation is an important post-translational modification essential for proper localization and function of many proteins. Transfer of the farnesyl group from farnesyl diphosphate (FPP) to proteins is catalyzed by protein farnesyltransferase (FTase). We employed a library of FPP analogues with a range of aryl groups substituting for individual isoprene moieties to examine some of the structural and electronic properties of analogue transfer to peptide catalyzed by FTase. Analysis of steady-state kinetics for modification of peptide substrates revealed that the multiple turnover activity depends on the analogue structure. Analogues where the first isoprene is replaced by a benzyl group and an analogue where each isoprene is replaced by an aryl group are good substrates. In sharp contrast with the steady-state reaction, the single turnover rate constant for dansyl-GCVLS alkylation was found to be the same for all analogues, despite the increased chemical reactivity of the benzyl analogues and the increased steric bulk of other analogues. However, the single turnover rate constant for alkylation does depend on the Ca1a2X peptide sequence. These results suggest that the isoprenoid transition state conformation is preferred over the inactive E•FPP• Ca1a2X ternary complex conformation. Furthermore, these data suggest that the farnesyl binding site in the exit groove may be significantly more selective for the farnesyl diphosphate substrate than the active site binding pocket and therefore might be a useful site for design of novel inhibitors.

Subramanian, Thangaiah; Pais, June E.; Liu, Suxia; Troutman, Jerry M.; Suzuki, Yuta; Subramanian, Karunai Leela; Fierke, Carol; Andres, Douglas A.; Spielmann, H. Peter

2012-01-01

367

Isobaric Analogue States in Heavy Nuclei. I. Molybdenum Isotopes  

Microsoft Academic Search

Isobaric analogue states observed as compound-nucleus resonances in proton elastic scattering and (p, n) reactions have been studied using the target isotopes Mo92, Mo94, Mo95, Mo96, Mo97, Mo98, and Mo100. The observed resonances which occur at high excitations in the target-plus-proton system have been analyzed using a Coulomb-plus-single-level formula. The spectroscopic information for these resonances is compared with the analogue

C. F. Moore; P. Richard; C. E. Watson; D. Robson; J. D. Fox

1966-01-01

368

Chemi- and bioluminescence of coelenterazine analogues possessing an adamantylmethyl group  

Microsoft Academic Search

Coelenterazine analogues possessing the adamantylmethyl group at the C2 or C8 position were prepared to study their effects on chemi- and bioluminescence. Stability of the excited state coelenteramide analogues was significantly affected by the substitutions, resulting in a neutral amide emission of chemiluminescence in diglyme-acetate buffer and in a blue-shifted emission of bioluminescence in Tris-HCI buffer. Substitution of the adamantylmethyl

Takashi Hirano; Ryo Negishi; Mihoko Yamaguchi; Feng Qi Chen; Yoshihiro Ohmiya; Frederick I. Tsuji; Mamoru Ohashi

1997-01-01

369

Holographic fluids with vorticity and analogue gravity  

NASA Astrophysics Data System (ADS)

We study holographic three-dimensional fluids with vorticity in local equilibrium and discuss their relevance to analogue gravity systems. The Fefferman-Graham expansion leads to the fluid's description in terms of a comoving and rotating Papapetrou- Randers frame. A suitable Lorentz transformation brings the fluid to the non-inertial Zermelo frame, which clarifies its interpretation as moving media for light/sound propagation. We apply our general results to the Lorentzian Kerr-AdS4 and Taub-NUT-AdS4 geometries that describe fluids in cyclonic and vortex flows respectively. In the latter case we associate the appearance of closed timelike curves to analogue optical horizons. In addition, we derive the classical rotational Hall viscosity of three-dimensional fluids with vorticity. Our formula remarkably resembles the corresponding result in magnetized plasmas.

Leigh, Robert G.; Petkou, Anastasios C.; Petropoulos, P. Marios

2012-11-01

370

A workload characterization study of the 1998 World Cup Web site  

Microsoft Academic Search

This article presents a detailed workload characterization study of the 1998 World Cup Web site. Measurements from this site were collected over a three-month period. During this time the site received 1.35 billion requests, making this the largest Web workload analyzed to date. By examining this extremely busy site and through comparison with existing characterization studies, we are able to

Martin Arlitt; Tai Jin

2000-01-01

371

Site sampling and treatability studies for demonstration of WasteChem's asphalt encapsulation technology under EPA's SITE program  

SciTech Connect

This paper presents a sampling approach that was used to determine whether there were adequate quantities and concentrations of wastes at the Woodland Township Route 532 Site for demonstration of the asphalt encapsulation technology. This paper also presents the result of a bench-scale treatability study on wastes from this site. The preliminary sampling and analysis confirmed most of the types of organic and inorganic contaminants found at the Woodland Township Route 532 site during the remedial investigation (RI). However, the contamination levels varied over relatively short distances across the site from some contaminants. The bench-scale treatability study indicated that, when compared with concentrations in the untreated waste, WasteChem's asphalt encapsulation technology reduced semivolatile organic compound concentrations in the toxicity characteristic leaching procedure extracts of treated wastes. The study also indicated that metals concentrations in the TCLP extracts were lower in the treated wastes than the untreated wastes in some samples and higher in others.

Hubbard, J.; Tsadwa, S.; Wills, N.; Evans, M.

1990-10-01

372

Analogue modelling of syntectonic leucosomes in migmatitic schists  

NASA Astrophysics Data System (ADS)

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.

Druguet, Elena; Carreras, Jordi

2006-10-01

373

Enhanced Television Strategy Models: A Study of TV Web Sites.  

ERIC Educational Resources Information Center

|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)|

Ha, Louisa

2002-01-01

374

Thymidine analogues for tracking DNA synthesis.  

PubMed

Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in "tagging DNA synthesis" is the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using 'Huisgen's reaction' (1,3-dipolar cycloaddition or 'click chemistry'). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other "unnatural bases". These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored. PMID:21921870

Cavanagh, Brenton L; Walker, Tom; Norazit, Anwar; Meedeniya, Adrian C B

2011-09-15

375

A hydraulic tomography approach coupling travel time inversion with steady shape analysis based on aquifer analogue study in coarsely clastic fluvial glacial deposit  

NASA Astrophysics Data System (ADS)

Rarely is it possible to draw a significant conclusion about the geometry and the properties of geological structures of the underground using the information which is typically obtained from boreholes, since soil exploration is only representative of the position where the soil sample is taken from. Conventional aquifer investigation methods like pumping tests can provide hydraulic properties of a larger area; however, they lead to integral information. This information is insufficient to develop groundwater models, especially contaminant transport models, which require information about the spatial distribution of the hydraulic properties of the subsurface. Hydraulic tomography is an innovative method which has the potential to spatially resolve three dimensional structures of natural aquifer bodies. The method employs hydraulic short term tests performed between two or more wells, whereby the pumped intervals (sources) and the observation points (receivers) are separated by double packer systems. In order to optimize the computationally intensive tomographic inversion of transient hydraulic data we have decided to couple two inversion approaches (a) hydraulic travel time inversion and (b) steady shape inversion. (a) Hydraulic travel time inversion is based on the solution of the travel time integral, which describes the relationship between travel time of maximum signal variation of a transient hydraulic signal and the diffusivity between source and receiver. The travel time inversion is computationally extremely effective and robust, however, it is limited to the determination of diffusivity. In order to overcome this shortcoming we use the estimated diffusivity distribution as starting model for the steady shape inversion with the goal to separate the estimated diffusivity distribution into its components, hydraulic conductivity and specific storage. (b) The steady shape inversion utilizes the fact that at steady shape conditions, drawdown varies with time but the hydraulic gradient does not. By this trick, transient data can be analyzed with the computational efficiency of a steady state model, which proceeds hundreds of times faster than transient models. Finally, a specific storage distribution can be calculated from the diffusivity and hydraulic conductivity reconstructions derived from travel time and steady shape inversion. The groundwork of this study is the aquifer-analogue study from BAYER (1999), in which six parallel profiles of a natural sedimentary body with a size of 16m x 10m x 7m were mapped in high resolution with respect to structural and hydraulic parameters. Based on these results and using geostatistical interpolation methods, MAJI (2005) designed a three dimensional hydraulic model with a resolution of 5cm x 5cm x 5cm. This hydraulic model was used to simulate a large number of short term pumping tests in a tomographical array. The high resolution parameter reconstructions gained from the inversion of simulated pumping test data demonstrate that the proposed inversion scheme allows reconstructing the individual architectural elements and their hydraulic properties with a higher resolution compared to conventional hydraulic and geological investigation methods. Bayer P (1999) Aquifer-Analog-Studium in grobklastischen braided river Ablagerungen: Sedimentäre/hydrogeologische Wandkartierung und Kalibrierung von Georadarmessungen, Diplomkartierung am Lehrstuhl für Angewandte Geologie, Universität Tübingen, 25 pp. Maji, R. (2005) Conditional Stochastic Modelling of DNAPL Migration and Dissolution in a High-resolution Aquifer Analog, Ph.D. thesis at the University of Waterloo, 187 pp.

Hu, R.; Brauchler, R.; Herold, M.; Bayer, P.; Sauter, M.

2009-04-01

376

Condensed matter analogues of cosmology  

NASA Astrophysics Data System (ADS)

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

Kibble, Tom; Srivastava, Ajit

2013-10-01

377

Condensed matter analogues of cosmology.  

PubMed

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

Kibble, Tom; Srivastava, Ajit

2013-09-11

378

Compressed-air energy storage preliminary design and site development program in an aquifer. Volume 3, part 1: Site Selection study  

NASA Astrophysics Data System (ADS)

The site selection study aspects of an aquifer based compressed air energy storage facility. Aquifer sites in the Illinois and Indiana portions of the Illinois Basin were identified and ranked. A site was selected from the four top ranked sites and was then utilized in other project work as the host site for the preliminary design of a compressed air energy storage facility.

1982-09-01

379

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

EPA Science Inventory

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

380

Ecosystem Studies at the Los Medanos Site, Eddy County, New Mexico. Volume I.  

National Technical Information Service (NTIS)

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 o...

J. S. Hart

1981-01-01

381

Comparative study of the affinity and metabolism of type I and type II binding quinoline carboxamide analogues by cytochrome P450 3A4.  

PubMed

Compounds that coordinate to the heme-iron of cytochrome P450 (CYP) enzymes are assumed to increase metabolic stability. However, recently we observed that the type II binding quinoline carboxamide (QCA) compounds were metabolically less stable. To test if the higher intrinsic clearance of type II binding compounds relative to type I binding compounds is general for other metabolic transformations, we synthesized a library of QCA compounds that could undergo N-dealkylation, O-dealkylation, benzylic hydroxylation, and aromatic hydroxylation. The results demonstrated that type II binding QCA analogues were metabolically less stable (2- to 12-fold) at subsaturating concentration compared to type I binding counterparts for all the transformations. When the rates of different metabolic transformations between type I and type II binding compounds were compared, they were found to be in the order of N-demethylation > benzylic hydroxylation> O-demethylation > aromatic hydroxylation. Finally, for the QCA analogues with aza-heteroaromatic rings, we did not detect metabolism in aza-aromatic rings (pyridine, pyrazine, pyrimidine), indicating that electronegativity of the nitrogen can change regioselectivity in CYP metabolism. PMID:22087535

Dahal, Upendra P; Joswig-Jones, Carolyn; Jones, Jeffrey P

2011-12-01

382

Structure-activity relationship (SAR) studies of benzoxazinones, their degradation products, and analogues. Phytotoxicity on problematic weeds Avena fatua L. and Lolium rigidum Gaud.  

PubMed

Avena fatua L. (wild oat) and Lolium rigidum Gaud. (rigid ryegrass) are highly problematic weeds affecting a wide variety of cereal crops worldwide. The fact that both of these weeds have developed resistance to several herbicide groups made them optimal candidates as target organisms for ongoing research about the potential application of allelochemicals and analogue compounds as natural herbicide models. Benzoxazinones, a family of natural allelochemicals present in corn, wheat, and rye, including 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, together with some degradation products, found in crop soils as well as in other systems, and some synthetic analogues of them were tested on wild oat and rigid ryegrass seeds; the results were statistically treated, and some structure-activity relationships, useful in further development of natural herbicide models, were elucidated. The most active compounds were the synthetic benzoxazinone 2-acetoxy-(2H)-1,4-benzoxazin-3(4H)-one and the degradation product 2-aminophenoxazin-3-one, with highly significant inhibition on the development of both weeds. The ecological role of these compounds is discussed by considering both degradability and phytotoxicity. The bioactivity of aminophenoxazines has been correlated by their aqueous solubility-lipophilicity predicted by means of computational methods. PMID:16478215

Macías, Francisco A; Marín, David; Oliveros-Bastidas, Alberto; Castellano, Diego; Simonet, Ana M; Molinillo, José M G

2006-02-22

383

Structural studies of [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond.  

PubMed

Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i mu=0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta=28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC(50)=0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu=13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2)=7.05). 1H NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. PMID:12670649

Okada, Yoshio; Fujita, Yoshio; Motoyama, Takashi; Tsuda, Yuko; Yokoi, Toshio; Li, Tingyou; Sasaki, Yusuke; Ambo, Akihiro; Jinsmaa, Yunden; Bryant, Sharon D; Lazarus, Lawrence H

2003-05-01

384

Report of the Fermilab Committee for Site Studies  

SciTech Connect

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.

Steve Holmes, Vic Kuchler et. al.

2001-09-10

385

Savannah River Site reactor hardware design modification study  

SciTech Connect

A study was undertaken to assess the merits of proposed design modifications to the Savannah River Site (SRS) reactors. The evaluation was based on the responses calculated by the RELAP5 systems code to double-ended guillotine break loss-of-coolant-accidents (DEGB LOCAs). The three concepts evaluated were (a) elevated plenum inlet piping with a guard vessel and clamshell enclosures, (b) closure of both rotovalves in the affected loop, and (c) closure of the pump suction valve in the affected loop. Each concept included a fast reactor shutdown (to 65% power in 100 ms) and a 2-s ac pump trip. System recovery potential was evaluated for break locations at the pump suction, the pump discharge, and the plenum inlet. The code version used was RELAP5/MOD2.5 version 3d3, a preliminary version of RELAP5/MOD3. The model was a three-dimensional representation of the K-Reactor water plenum and moderator tank. It included explicit representations of all six loops, which were based on the configuration of L-Reactor. A combination of features is recommended to ensure liquid inventory recovery for all break locations. Valve closure design performance for a break location in the short section of piping between the reactor concrete shield and the pump suction valve would benefit from the clamshell enclosing that section of piping. 7 refs., 10 figs., 2 tabs.

Fisher, J.E.

1990-01-01

386

Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells  

Microsoft Academic Search

Background Insulin analogues are widely used in the treatment of diabetes mellitus. Some insulin analogues were reported to display atypical activities in vitro that resemble those of insulin-like growth factor-I (IGF-I). The aim of this study was to investigate whether two long-acting insulin analogues (glargine (Lantus, Sanofi Aventis, Germany) and detemir (Levemir, Novo Nordisk, Denmark)) and two short-acting analogues (lispro

Doron Weinstein; Meital Simon; Einat Yehezkel; Zvi Laron; Haim Werner

2009-01-01

387

Adsorption on molecularly imprinted polymers of structural analogues of a template. Single-component adsorption isotherm data  

SciTech Connect

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 structural analogues that have the same stereochemistry as the template is highest for the imprinted molecule (Fmoc-L-Trp). The separation of the template from the substrates with the same stereochemistry is influenced by the number of the functional groups on the substrates that can interact with the highest affinity sites on the MIP. The separation of the enantiomers of the analogues of the substrates was also achieved on the MIP, and these enantiomeric separations are influenced by the hydrophobicity of the substrates.

Kim, Hyunjung [University of Tennessee, Knoxville (UTK); Guiochon, Georges A [ORNL

2005-10-01

388

The EPSILON study: aims outcome measures, study sites and patient sample [ch 1  

Microsoft Academic Search

The development and translation of assessment instruments in mental health is a complex process, which becomes increasingly important in a uniting Europe. The major aim of the European Commission BIOMED-funded multi-site study, the European Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) Study, was to produce standardised versions in several European languages of instruments measuring five key concepts

Thomas Becker; Martin Knapp; Helle Charlotte Knudsen; Aart H. Schene; Michele Tansella; Graham Thornicroft; José Luis Vázquez-Barquero; stgr EPSILON

2006-01-01

389

Site Preparation Studies for a Peritoneal Dialysis Access Plug.  

National Technical Information Service (NTIS)

Site preparations for peritoneal dialysis in dogs, cats, minipigs and rabbits were investigated. The experiments used various surgical concepts and access plugs. These included direct puncture into the peritoneal cavity, anastomosing the peritoneum to the...

M. A. Bianchi A. T. Gelman

1968-01-01

390

UV disinfection pilot plant study at the Savannah River Site.  

National Technical Information Service (NTIS)

An ultraviolet light disinfection system pilot plant was operated at the Savannah River Site Central Shops sanitary wastewater treatment package plant July 14, 1992 through August 13, 1992. The purpose was to determine the effectiveness of ultraviolet lig...

R. L. Huffines B. A. Beavers

1993-01-01

391

Siting a radioactive waste facility; A pathways analysis case study  

Microsoft Academic Search

A radioactive waste disposal facility was proposed to be sited in Oregon. The waste being considered contained 250 pCi\\/g of uranium consisting of U-234, U-235, U-236 and U-238 isotopes. No Ra-226 or Th-230 were specified to be present in the waste. As part of the siting effort, the proposed facility had to be qualified with regard to meeting requirements for

G. A. Holton; K. R. Meyer; H. R. Meyer

1987-01-01

392

Pena Blanca Natural Analogue Performance Assessment Model.  

National Technical Information Service (NTIS)

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 th...

G. J. Saulnier W. Statham

2006-01-01

393

Concentration dependent Electrospray Ionisation Mass Spectrometry and Tandem Mass Spectrometry (MS/MS ) studies on (E,E)-1-[5-(1,3-benzodioxol-5yl)-1-oxo-2,4-pentadienyl]- piperidine (Piperine) and its analogues.  

PubMed

Studies on piperine ((M 1 )) and its synthetic analogues (M 2-18 ) by positive electrospray ionisation mass spectrometry were carried out in the flow injection mode of analysis in methanol. The MS experiments on these compounds at concentration 5 ng/?L or above yielded dimeric ionic species [2 M + Na](+) which revealed that piperine and its analogues exhibit clustering of ions when the solutions of these compounds at concentrations 5 ng/?L or above were allowed to move through the electrospray interface of the mass spectrometer. The same clustering of the ions was not observed when the solutions of the same compounds at concentrations below 5 ng/?L were used for similar studies. The formation of the clusters was further confirmed by tandem mass spectrometry (MS/MS) studies wherein the fragmentation of dimeric ionic species [2 M + Na](+) led to the formation of sodium adducted monomeric ionic species [M + Na](+). The MS measurements of these compounds by Atmospheric Pressure Chemical Ionisation (APCI) were on expected lines as there was no clustering of the ions in case of APCI-MS measurements. PMID:24046811

Khajuria, Ravi K; Sharma, Neha; Koul, Jawahar L; Verma, Mahendra K

2013-08-31

394

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

SciTech Connect

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.

Not Available

1987-05-01

395

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

SciTech Connect

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.

Not Available

1987-06-01

396

Parametric Studies for Scenario Earthquakes: Site Effects and Differential Motion  

NASA Astrophysics Data System (ADS)

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

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

2001-12-01