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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. PMID:22881577

Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko



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

PubMed Central

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

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



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.



Space analogue studies in Antarctica  

NASA Technical Reports Server (NTRS)

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

Lugg, D.; Shepanek, M.



Synthesis and serotonin binding site studies of some conformationally restricted indolylethylamine analogues based on 2-amino-3-(3'-indolyl)bicyclo[2.2.2]octane.  


The bicycloannulation reaction between cyclohexenone and indolyl enamines yields trans-3-(cyclic amino)-2-(3'-indolyl)bicyclo[2.2.2]octan-5-ones, and these adducts are conformationally restricted analogues of indolylethylamine (tryptamine) which exhibit structure-dependent affinity for the serotonin 5HT2 and 5HT1a receptors. The stereochemistry of the isomeric endo and exo adducts obtained is assigned from the 1H NMR spectra of the specifically deuterated alkenes prepared from the ketones by the Bamford-Stevens reaction. Molecular mechanics calculations indicate that the conformational flexibility of the amino and indolyl groups is restricted through van der Waals interactions with the bridges of the bicyclic unit. These compounds inhibit the binding of [3H]ketanserin to 5HT2 sites in mouse cerebrocortical membranes, and the binding of [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) to 5HT1a sites in mouse hippocampal membranes. The endo compounds are the most potent, and molecular mechanics calculations indicate that these isomers have a less bulky bicyclo bridge proximate to the amine group and more conformational freedom about the C alpha-C beta-N(+)-H dihedral angle (tau 3). In the 5HT2 assay, endo-trans-3-(N-piperidinyl)-2-(3'-indolyl)bicyclo[2.2.2]octan-5-one (10a) is the most potent, and endo-trans-3-(N-pyrrolidinyl)-2-(3'-indolyl)bicyclo[2.2.2]oct-5-ene (12a) is the most potent in the 5HT1a assay. A phenyl-substituted adduct shows the least affinity in these two assays. These data provide insight into the structural differences between the 5HT1a and 5HT2 receptor sites. PMID:2136918

Schlecht, M F; Tsarouhtsis, D; Lipovac, M N; Debler, E A



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

PubMed Central

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 one distal methyl group in the synthesized analogues. PMID:23306054

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



A method to site-specifically incorporate methyl-lysine analogues into recombinant proteins.  


The site-specific and degree-specific methylation of histone lysine residues is important for the regulation of chromatin. To study the biochemical roles of lysine methylation, several approaches have been developed to reconstitute chromatin fibers in vitro with well-defined methylation patterns. Here, we describe the installation of methyl-lysine analogues (MLAs) as a simple and scalable method to introduce mono-, di-, or trimethylation at specific sites of recombinantly expressed histones. In this method, a histone is engineered to harbor a lysine-to-cysteine mutation at the desired site of modification. These mutant histones are treated with halo-ethylamines that react with the cysteine side chain, providing high yields of N-methylated aminoethylcysteines, analogues of N-methylated lysine residues. These MLA histones have been used to construct well-defined chromatin templates to study the direct biochemical consequences of histone lysine methylation in a variety of contexts. PMID:22910202

Simon, Matthew D; Shokat, Kevan M



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.



Upheaval Dome, An Analogue Site for Gale Center  

NASA Technical Reports Server (NTRS)

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

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



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

SciTech Connect

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

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



Novel imidazole-based combretastatin A-4 analogues: evaluation of their in vitro antitumor activity and molecular modeling study of their binding to the colchicine site of tubulin.  


The in vitro antitumor activity of novel combretastatin-like 1,5- and 1,2-diaryl-1H-imidazoles was evaluated against the NCI 60 human tumor cell lines panel. Compounds 2d and 2g proved to be more cytotoxic than CA-4 in tests involving their evaluation over a 10(-4)-10(-8) range. Docking experiments showed a good correlation between the MG_MID Log GI(50) values of all these compounds and their calculated interaction energies with the colchicine binding site of alphabeta-tubulin. PMID:16950621

Bellina, Fabio; Cauteruccio, Silvia; Monti, Susanna; Rossi, Renzo



NASA/ESMD Analogue Mission Plans  

NASA Technical Reports Server (NTRS)

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

Hoffman, Stephen J.



Stability and bioactivity studies on dipeptidyl peptidase IV resistant glucogan-like peptide-1 analogues.  


Glucagon-like peptide-1 (GLP-1) was once considered as an ideal anti-diabetic candidate for its important role in maintaining glucose homeostasis through the regulation of islet hormone secretion, as well as hepatic and gastric function. However, the major therapeutic obstacle for using native GLP-1 as a therapeutic agent is its very short half-life primarily due to their degradation by the enzyme dipeptidyl peptidase IV (DPP-IV). In this study, GLP-1 analogues with modifications in amino acid site 8, 22 and 23 were synthesized using solid phase peptide synthesis. Resistance of these analogues to DPP-IV cleavage was investigated in vitro by incubation of the peptides with DPP-IV or human plasma. Glucoregulating efficacy of the analogues was evaluated in normal Kunming mice using intraperitoneal glucose tolerance model. Glucose lowering effect of combination therapy (analogue plus Vildagliptin) has also been studied. In vitro studies showed that the modified analogues were much more stable than native GLP-1 (nearly 100% of the peptide keep intact after 4 h incubation). In vivo biological activity evaluation revealed that His8-EEE (the most potent GLP-1 analogues in this study) exhibited significantly improved glycemic control potency (approximately 4.1-fold over saline and 2.5-fold over GLP-1) and longer time of active duration (at least 5 h). Combination therapy also showed the trend of its superiority over mono-therapy. Modified analogues showed increased potency and biological half-time compared with the native GLP-1, which may help to understand the structure-activity relationship of GLP-1 analogues. PMID:21838700

Chen, Wei; Zhou, Yinghong; Zhang, Huibin; Qian, Hai; Huang, Wenlong; Yang, Baowei; Han, Jing; Zhou, Jingpei; Chi, Yushi; Ni, Shuaijian



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.



Synthesis of cross-linked DNA containing oxidized abasic site analogues.  


DNA interstrand cross-links are an important family of DNA damage that block replication and transcription. Recently, it was discovered that oxidized abasic sites react with the opposing strand of DNA to produce interstrand cross-links. Some of the cross-links between 2'-deoxyadenosine and the oxidized abasic sites, 5'-(2-phosphoryl-1,4-dioxobutane) (DOB) and the C4-hydroxylated abasic site (C4-AP), are formed reversibly. Chemical instability hinders biochemical, structural, and physicochemical characterization of these cross-linked duplexes. To overcome these limitations, we developed methods for preparing stabilized analogues of DOB and C4-AP cross-links via solid-phase oligonucleotide synthesis. Oligonucleotides of any sequence are attainable by synthesizing phosphoramidites in which the hydroxyl groups of the cross-linked product were orthogonally protected using photochemically labile and hydrazine labile groups. Selective unmasking of a single hydroxyl group precedes solid-phase synthesis of one arm of the cross-linked DNA. The method is compatible with commercially available phosphoramidites and other oligonucleotide synthesis reagents. Cross-linked duplexes containing as many as 54 nt were synthesized on solid-phase supports. Subsequent enzyme ligation of one cross-link product provided a 60 bp duplex, which is suitable for nucleotide excision repair studies. PMID:24949656

Ghosh, Souradyuti; Greenberg, Marc M



A Laboratory Analogue for the Study of Peer Sexual Harassment  

ERIC Educational Resources Information Center

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

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



Present-day serpentinization in the Tablelands, Gros Morne National Park, Newfoundland: a Mars Analogue Site  

NASA Astrophysics Data System (ADS)

Serpentinization - a reaction between water and ultramafic rock (derived from the mantle) - is suspected to be a source of hydrocarbons such as methane on Mars. Through the hydration of ultramafic rock, this reaction produces hydrogen (H2) gas and reducing conditions necessary for abiogenic hydrocarbon synthesis, while also producing conditions amendable for the production of methane through microbial chemoautotrophic pathways. Mars analogue sites of present-day serpentinization can be used to determine what geochemical measurements are required for determining the reactions responsible for the methane in the Martian atmosphere. On Earth few locations that are known to exhibit active serpentinization are easily accessible. One such location is found in the Tablelands at Gros Morne National Park, Newfoundland. Peridotite rocks similar to those found on Mars dominate the Tablelands thus making the Tablelands an important analogue site for potential ecosystems on Mars. Present-day serpentinization is evidenced by fluid seeps characterized by highly alkaline (pH 11 to 12) and highly reducing (as low as -820 mV) conditions, travertine and the presence of dissolved methane. These fluids contain high concentrations of Ca2+ (~5.00x104ppb) compared to freshwater inputs (~ 1.00x103) and react at the surface with atmospheric CO2 producing travertine deposits (as CaCO3 precipitate). Dissolved H2 gas produced abiogenically through the serpentinization reaction also provides copious geofuels, which can be used for chemosynthesis. Preliminary data has shown that microbial life lives in the high pH springs of the Tablelands. Ongoing studies of targeted compounds including phospholipid fatty acids and ether-linked lipids are being used to determine the microbial community compositions and verify the occurrence of Bacteria and Archaea in these fluids. An important question is also the source of the serpentinized fluid seeps. Hydrogen (?2H) and oxygen (?18O) isotopes of these fluids indicate meteoric water. The site also receives freshwater inputs (pH 7) creating strong redox gradients with reducing seeps. Isotopic and geochemical analysis of the fluids, associated gases and carbonates, and preliminary results on microbial communities will be discussed to help understand how methane is produced in these springs at the Tablelands and how the information can be useful to help identify the source of methane on Mars.

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



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


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  

Microsoft Academic Search

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

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



Compound Lava Flow Fields on Planetary Surfaces: Hawaiian Analogue Studies  

Microsoft Academic Search

Quantitative, process-oriented analyses of planetary volcanism have primarily been based on analogue studies of single-lobed lava flows emplaced as discrete units. Comparative analyses of compound lava flow fields on the Earth and terrestrial planets are being conducted in order to include volcanic styles characterized by complex distributary systems, stratigraphic relationships, and emplacement histories. Field observations, differential Global Positioning Systems (dGPS)

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



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.



Natural analogue study of radionuclide migration in clays  

SciTech Connect

The use of sediment laid down in a Scottish loch during the Flandrain marine transgression as a source term for a natural analogue study of elemental migration in clays over a timescale of 10/sup 3/ - 10/sup 4/ y has been investigated. Depth profiles of over 20 elements have been measured which illustrate varying post depositional behavior ranging from effectively total immobility to complete redistribution throughout the sediment profile. These results are contrasted with laboratory batch sorption data for a range of nuclides on samples of this sediment. 5 references, 1 figure, 1 table.

McKinley, I.G.; MacKenzie, A.B.; West, J.M.; Scott, R.D.



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

NASA Astrophysics Data System (ADS)

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

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



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

NASA Astrophysics Data System (ADS)

A numerical multicomponent reactive transport model described fully in Steefel and Lichtner (1998)[Steefel, C.I., Lichtner, P.C., 1998. Multicomponent reactive transport in discrete fractures, I. Controls on reaction front geometry. J. Hydrol. (in press)] is used to simulate the infiltration of hyperalkaline groundwater along discrete fractures at Maqarin, Jordan, a site considered as a natural analogue to cement-bearing nuclear waste repositories. In the Eastern Springs area at Maqarin, two prominent sets of sub-parallel fractures trending NW-SE are approximately perpendicular to the local water table contours, with the slope of the water table indicating north-westward flow. Extensive mineralogic investigations [Alexander W.R. (Ed.), 1992. A natural analogue study of cement-buffered, hyperalkaline groundwaters and their interaction with a sedimentary host rock. NAgrA Technical Report (NTB 91-10), Wettingen, Switzerland; Milodowski, A.E., Hyslop, E.K., Pearce, J.M., Wetton, P.D., Kemp, S.J., Longworth, G., Hodginson, E., and Hughes, C.R., 1998. Mineralogy and geochemistry of the western springs area. In: Smellie, J.A.T. (ed.), 1998: Maqarin Natural Analogue Study: Phase III. SKB Technical Report TR98-04, Stockholm, Sweden] indicate that the width of intense rock alteration zone bordering the fractures changes from about 4 mm at one locality (the M1 sampling site) to approximately 1 mm 100 m to the north-west in the flow direction (the M2 site), suggesting a lessening of alteration intensity in that direction. Using this information, the dimensionless parameter ? v/? D' (?=porosity, D'=effective diffusion coefficient in rock matrix, ?=fracture aperture, and v=fluid velocity in the fracture) and measurements of the local hydraulic head gradient and effective diffusion coefficient in the rock matrix, a mean fracture aperture of 0.194 mm is calculated assuming the cubic law applies. This information, in combination with measured groundwater compositions at the Maqarin site, is used as input for numerical simulations of the hyperalkaline groundwater infiltration along fractures. The width of the alteration zones in the rock matrix bordering fractures is also used to constrain mineral dissolution rates in the field. The simulations predict that ettringite [Ca 6Al 2(SO 4) 3(OH) 12·26H 2O] with lesser amounts of hillebrandite and tobermorite (hydrated calcium silicates or CSH phases) will be the dominant alteration products forming at the expense of the primary silicates in the rock matrix and fracture, in agreement with observations at the Maqarin site. The simulations also come close to matching the pH of water samples collected along fractures at the M1 and M2 sites, with a fracture aperture of 0.22 mm giving the closest match with the pH data (within 13% of the value indicated by the rock matrix alteration widths). The simulations suggest two possible scenarios for the time evolution of the fracture-rock matrix system. Where rate constants for secondary mineral precipitation reactions are the same in both the rock matrix and fracture, the rock matrix tends to become completely cemented before the fracture. This results in a downstream migration of the hyperalkaline plume. In contrast, if rates are as little as one order of magnitude higher in the fracture than in the rock matrix, it is possible to seal the fracture first, thus causing the mineral zones to collapse upstream as a result of the reduction in fracture permeability. Sealing of fractures is observed at Maqarin and the simulations predict a mineral paragenesis in the fracture resulting from this scenario which is broadly compatible with field observations.

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



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

PubMed Central

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

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



Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents  

PubMed Central

Toxoplasma gondii is an opportunistic pathogen responsible for toxoplasmosis. T. gondii is a purine auxotroph incapable of de novo purine biosynthesis and depends on salvage pathways for its purine requirements. Adenosine kinase (EC. is the major enzyme in the salvage of purines in these parasites. 6-Benzylthioinosine and analogues were established as “subversive substrates” for the T. gondii, but not for the human adenosine kinase. Therefore, these compounds act as selective anti-toxoplasma agents. In the present study, a series of N6-benzyladenosine analogues were synthesized from 6-chloropurine riboside with substituted benzylamines & ? solution phase parallel synthesis. These N6-benzyladenosine analogues were evaluated for their binding affinity to purified T. gondii adenosine kinase. Furthermore, the anti-toxoplasma efficacy and host toxicity of these compounds were tested in cell culture. Certain substituents on the aromatic ring improved binding affinity to T. gondii adenosine kinase when compared to the unsubstituted N6-benzyladenosine. Similarly, varying the type and position of the substituents on the aromatic ring led to different degrees of potency and selectivity as anti-toxoplasma agents. Among the synthesized analogues, N6-(2,4-dimethoxybenzyl)adenosine exhibited the most favorable anti-toxoplasma activity without host toxicity. The binding mode of the synthesized N6-benzyladenosine analogues were characterized to illustrate the role of additional hydrophobic effect and van der Waals interaction within an active site of T. gondii adenosine kinase by induced fit molecular modeling. PMID:17306769

Kim, Young Ah; Sharon, Ashoke; Chu, Chung K.; Rais, Reem H.; Al Safarjalani, Omar. N.; Naguib, Fardos N. M.; el Kouni, Mahmoud H.



Emotions and Habitability study in Moon Mars Analogue  

Microsoft Academic Search

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

Alexandre Mertens; Irene Lia Schlacht



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



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


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.


Natural analogue studies as supplements to biomineralization research  

SciTech Connect

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

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



Synthesis and study of new paramagnetic resveratrol analogues.  


New resveratrol analogues containing five- and six-membered nitroxides and isoindoline nitroxides were synthesized. These new compounds were compared to resveratrol based on their ABTS radical scavenging ability as well on their capacity to suppress inflammatory process in macrophages induced by lipopolysaccharides. The ABTS and ROS scavenging activities of new molecules were the same or weaker than that of resveratrol, but some of paramagnetic resveratrol derivatives suppressed nitrite and TNF? production more efficiently than resveratrol. Based on these results the new nitroxide and phenol containing hybrid molecules can be considered as new antioxidant and anti-inflammatory agents. PMID:22088309

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



Biological Studies of Radiolabeled Glucose Analogues Iodinated in Positions 3, Iodinated glucose analogues  

E-print Network

-insensitive GLUT1 transporter, adipocytes were also used as a model for the insulin-sensitive GLUT4 transporter. 2 erythrocytes have been widely used to study glucose uptake because glucose transporters are highly expressed within their cellular membranes [18]. However, as erythrocytes mainly express the insulin

Paris-Sud XI, Université de


Conformational studies of neurohypophyseal hormones analogues with glycoconjugates by NMR spectroscopy.  


Two glycosylated peptides have been studied using NMR spectroscopy supported by molecular modeling. Peptide I is an oxytocin (OT) analogue in which glutamine 4 was replaced by serine with attached ?-d-mannose through the oxygen ? atom, whereas peptide II is a lysine-vasopressin (LVP) analogue with lysine 8 side chain modified by the attachment of glucuronic acid through an amide bond. Both peptides exhibit very weak uterotonic effect and are less susceptible to proteolytic degradation than the mother hormones. Additionally, peptide II reveals very weak pressor and antidiuretic activities. Our results have shown that the conformational preferences of glycosylated analogues are highly similar to those of their respective mother hormones. OT glycosylated analogue (I) exhibits a 3,4 ?-turn characteristic of OT-like peptides, and vasopressin-glycosylated analogue (II) exhibits??-turns typical of vasopressin-like peptides. Therefore, the lack of binding of the glycosylated analogues to the receptors can be attributed to a steric interference between the carbohydrate moieties and the receptors. We also consider this to be the reason of the very low activity of the analyzed glycopeptides. We expect that results from these studies will be helpful in designing new OT-like and vasopressin-like drugs. PMID:24644276

Lubecka, Emilia A; Sikorska, Emilia; Marcinkowska, Alina; Ciarkowski, Jerzy



Scintigraphic studies in rats. Kinetics of insulin analogues covering wide range of receptor affinities  

SciTech Connect

Whole-body kinetics of {sup 123}I-labeled human insulin and five insulin analogues were investigated by scintigraphic studies in rats. The amino acid substitutions and the relative receptor affinities (RAs), determined by binding to HepG2 cells, were: GluB12, des-B30 insulin, RA 0.15%; AspB9, GluB27 insulin, RA 18%; AspB26 insulin, RA 80%; AspB18 insulin, RA 327%; and HisA8, HisB4, GluB10, HisB27 insulin, RA 687%. All analogues were compared with human insulin (RA 100%). The analogue with RA 0.15% showed a significantly slower disappearance in the heart window, no liver uptake, and the greatest kidney radioactivity, the latter probably caused by high plasma concentrations. The low-affinity analogue (RA 18%) reached a surprisingly high hepatic peak value, although significantly lower than insulin. Kidney radioactivity was higher than for insulin. The analogue with RA 80% showed liver and kidney radioactivities that were not significantly different from those of insulin. The two high-affinity analogues (RAs 327 and 687%) showed peak liver radioactivities not significantly different from insulin. However, liver radioactivity after the peaks declined significantly more slowly. Compared with insulin, the kidney radioactivity curves were not significantly different. We conclude that high-affinity insulin analogues will bind to any available receptor that, because of the large number of receptors in the periphery and the distribution of cardiac output, favors extrahepatic elimination. In contrast, low-affinity analogues bind to receptors several times before they are eliminated. This leads to recirculation and, thus, hepatic elimination due to the high receptor density there.

Jensen, I.; Kruse, V.; Larsen, U.D. (Novo Research Institute, Novo Nordisk, Bagsvaerd, (Denmark))



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



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


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



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. 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.



Characterization of the Taxol binding site on the microtubule. Identification of Arg(282) in beta-tubulin as the site of photoincorporation of a 7-benzophenone analogue of Taxol.  


Photoaffinity labeling methods have allowed a definition of the sites of interaction between Taxol and its cellular target, the microtubule, specifically beta-tubulin. Our previous studies have indicated that [(3)H]3'-(p-azidobenzamido)Taxol photolabels the N-terminal 31 amino acids of beta-tubulin (Rao, S., Krauss, N. E., Heerding, J. M., Swindell, C. S., Ringel, I., Orr, G. A., and Horwitz, S. B. (1994) J. Biol. Chem. 269, 3132-3134) and [(3)H]2-(m-azidobenzoyl)Taxol photolabels a peptide containing amino acid residues 217-233 of beta-tubulin (Rao, S., Orr, G. A., Chaudhary, A. G., Kingston, D. G. I., and Horwitz, S. B. (1995) J. Biol. Chem. 270, 20235-20238). The site of photoincorporation of a third photoaffinity analogue of Taxol, [(3)H]7-(benzoyldihydrocinnamoyl) Taxol, has been determined. This analogue stabilizes microtubules polymerized in the presence of GTP, but in contrast to Taxol, does not by itself enhance the polymerization of tubulin to its polymer form. CNBr digestion of [(3)H]7-(benzoyldihydrocinnamoyl)Taxol-labeled tubulin, with further arginine-specific cleavage by clostripain resulted in the isolation of a peptide containing amino acid residues 277-293. Amino acid sequence analysis indicated that the photoaffinity analogue cross-links to Arg(282) in beta-tubulin. Advances made by electron crystallography in understanding the structure of the tubulin dimer have allowed us to visualize the three sites of photoincorporation by molecular modeling. There is good agreement between the binding site of Taxol in beta-tubulin as determined by photoaffinity labeling and electron crystallography. PMID:10608867

Rao, S; He, L; Chakravarty, S; Ojima, I; Orr, G A; Horwitz, S B



Stabilization of a transition-state analogue at the active site of yeast cytosine deaminase: importance of proton transfers.  


It is believed that the binding of pyrimidin-2-one to cytosine deaminase (CD) leads to the formation of 4-[R]-hydroxyl-3,4-dihydropyrimidine (DHP). Here the formation of transition-state analogue (TSA) at the active site of yeast cytosine deaminase (yCD) is investigated by quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations. It is shown that DHP may in fact be unstable in the active site and a proton transfer from the Zn hydroxide group to Glu-64 may occur during the nucleophilic attack, leading to an alkoxide-like TSA complex instead. The free energy simulations for the nucleophilic attack process show that the proton transfer from the Zn hydroxide to Glu-64 may play an important role in stabilizing the TSA complex. PMID:17506543

Xu, Qin; Guo, Haobo; Gorin, Andrey; Guo, Hong



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

SciTech Connect

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

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



Discrete and analogue quantity processing in the parietal lobe: A functional MRI study  

E-print Network

Discrete and analogue quantity processing in the parietal lobe: A functional MRI study Fulvia representations might be closely linked (11). However, the few functional MRI (fMRI) studies investigat- ing, 13). For example, a recent study showed fMRI adaptation in the horizontal segment of IPS during

Butterworth, Brian


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

E-print Network

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

Paris-Sud XI, Université de


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. PMID:18274663

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



Molecular modeling studies of atorvastatin analogues as HMGR inhibitors using 3D-QSAR, molecular docking and molecular dynamics simulations.  


3-Hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) is generally regarded as targets for the treatment of hypercholesterolemia. HMGR inhibitors (more commonly known as statins) are discovered as plasma cholesterol lowering molecules. In this work, 120 atorvastatin analogues were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulation. The results show that the best CoMFA (comparative molecular field analysis) model has q(2)=0.558 and r(2)=0.977, and the best CoMSIA (comparative molecular similarity indices analysis) model has q(2)=0.582 and r(2)=0.919. Molecular docking and MD simulation explored the binding relationship of the ligand and the receptor protein. The calculation results indicated that the hydrophobic and electrostatic fields play key roles in QSAR model. After MD simulation, we found four vital residues (Lys735, Arg590, Asp690 and Asn686) and three hydrophobic regions in HMGR binding site. The calculation results show that atorvastatin analogues obtained by introduction of F atoms or gem-difluoro groups could obviously improve the inhibitory activity. The new HMGR inhibitor analogues design in this Letter had been submitted which is being currently synthesized by our laboratories. PMID:25022881

Wang, Zhi; Cheng, Liping; Kai, Zhenpeng; Wu, Fanhong; Liu, Zhuoyu; Cai, Minfeng



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

PubMed Central

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

Zakova, Lenka; Kletvikova, Emilia; Lepsik, Martin; Collinsova, Michaela; Watson, Christopher J.; Turkenburg, Johan P.; Jiracek, Jiri; Brzozowski, Andrzej M.



Socioeconomic Site Study Plan: Draft  

SciTech Connect

Social and economic issues and concerns of the Deak Smith County site area will be evaluated during site characterization. Effects that the area could experience from a repository project include demographic, economic, community service, fiscal, and social impacts. The Socioeconomic Site Study Plan is designed to provide a strategy to assess the potential for those impacts. The Socioeconomic Site Study Plan is structured to provide an overview of the socioeconomic program requirements, objectives, and activities to be conducted during site characterization. This report will describe the study design and its rationale; data collection, management, and reporting; program schedules and milestones; site study organization and management; and quality assurance issues. 43 refs.

Not Available



Chalcone based azacarboline analogues as novel antitubulin agents: Design, synthesis, biological evaluation and molecular modelling studies.  


The present study involves the design of a series of 3-aryl-9-acetyl-pyridazino[3,4-b]indoles as constrained chalcone analogues. A retrosynthetic route was proposed for the synthesis of target compounds. All the synthesized compounds were evaluated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and A-549 human cancer cell lines. The results indicated that 2a, 3a, 5a and 6a possessed significant cytotoxic potential with an IC50 value ranging from 1.13 to 5.76 ?M. Structure activity relationship revealed that the nature of both Ring A and Ring B influences the activity. Substitution of methoxy groups on the phenyl ring (Ring A) and unsubstituted phenyl ring (Ring B) were found to be the preferred structural features. The most potent compound 2a was further tested for tubulin inhibition. Compound 2a was found to significantly inhibit the tubulin polymerization (IC50 value - 2.41 ?M against THP-1). Compound 2a also caused disruption of microtubule assembly as evidenced by Immunoflourescence technique. The significant cytotoxicity and tubulin inhibition by 2a was rationalized by molecular modelling studies. The most potent structure was docked at colchicine binding site (PDB ID-1SA0) and was found to be stabilized in the cavity via various hydrophobic and hydrogen bonding interactions. PMID:25128667

Sharma, Sahil; Kaur, Charanjit; Budhiraja, Abhishek; Nepali, Kunal; Gupta, Manish K; Saxena, A K; Bedi, P M S



Pharmacokinetic studies of amino acid analogues of 2-nitroimidazole, new hypoxic cell radiosensitizers.  


A series of new analogues of 2-nitroimidazole has been synthesized by inserting various amino acids at 1-position through an amide bond. The ethyl esters of N-alpha-[(2-nitro-1-imidazolyl)acetyl]-L-phenylalanine and N-alpha-[2-nitro-1-imidazolyl)acetyl]-L-tyrosine were found to be the most effective radiosensitizers in vitro against hypoxic Chinese hamster (V-79) cells. The sensitizer enhancement ratios (SER) of these derivatives were 2.2 and 2.3 respectively at 1 mM concentration after 2 hr exposure under hypoxia. However, the free acid of phenylalanine analogue was less active as a radiosensitizer and required 5 mM concentration to produce SER of 1.9. In contrast, the free acid of tyrosine analogue was inactive in this test system. The pharmacokinetic studies with the esters revealed their rapid hydrolysis in serum to the corresponding acids within 5 minutes as detected by HPLC. The pharmacokinetic parameters were therefore determined by employing the free acid analogues and solubilizing them as their sodium salts. The drugs were administered intraperitoneally at 0.5 mg/g dose level to C-57 mice bearing B16 melanoma. These agents were cleared from the plasma rapidly with an apparent t 1/2 of 18.8 and 15.6 min respectively. Peak tumor concentration of approximately 217 micrograms/g was achieved within 15 min with phenylalanine analogue. The tumor to brain ratio was 10:1 suggesting that this agent is excluded from CNS and that the phenylalanine analogue should be considered a potentially less neurotoxic radiosensitizer than misonidazole. PMID:6469754

Agrawal, K C; Larroquette, C A; Garg, P K



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.



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


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



Oxo transfer reactions mediated by bis(dithiolene)tungsten analogues of the active sites of molybdoenzymes in the DMSO reductase family: comparative reactivity of tungsten and molybdenum.  


The discovery of tungsten enzymes and molybdenum/tungsten isoenzymes, in which the mononuclear catalytic sites contain a metal chelated by one or two pterin-dithiolene cofactor ligands, has lent new significance to tungsten-dithiolene chemistry. Reaction of [W(CO)(2)(S(2)C(2)Me(2))(2)] with RO(-) affords a series of square pyramidal desoxo complexes [W(IV)(OR')(S(2)C(2)Me(2))(2)](1)(-), including R' = Ph (1) and Pr(i)() (3). Reaction of 1 and 3 with Me(3)NO gives the cis-octahedral complexes [W(VI)O(OR')(S(2)C(2)Me(2))(2)](1)(-), including R' = Ph (6) and Pr(i)() (8). These W(IV,VI) complexes are considered unconstrained versions of protein-bound sites of DMSOR and TMAOR (DMSOR = dimethylsulfoxide reductase, TMAOR = trimethylamine N-oxide reductase) members of the title enzyme family. The structure of 6 and the catalytic center of one DMSO reductase isoenzyme have similar overall stereochemistry and comparable bond lengths. The minimal oxo transfer reaction paradigm thought to apply to enzymes, W(IV) + XO --> W(VI)O + X, has been investigated. Direct oxo transfer was demonstrated by isotope transfer from Ph(2)Se(18)O. Complex 1 reacts cleanly and completely with various substrates XO to afford 6 and product X in second-order reactions with associative transition states. The substrate reactivity order with 1 is Me(3)NO > Ph(3)AsO > pyO (pyridine N-oxide) > R(2)SO > Ph(3)PO. For reaction of 3 with Me(3)NO, k(2) = 0.93 M(-)(1) s(-)(1), and for 1 with Me(2)SO, k(2) = 3.9 x 10(-)(5) M(-)(1) s(-)(1); other rate constants and activation parameters are reported. These results demonstrate that bis(dithiolene)W(IV) complexes are competent to reduce both N-oxides and S-oxides; DMSORs reduce both substrate types, but TMAORs are reported to reduce only N-oxides. Comparison of k(cat)/K(M) data for isoenzymes and k(2) values for isostructural analogue complexes reveals that catalytic and stoichiometric oxo transfer, respectively, from substrate to metal is faster with tungsten and from metal to substrate is faster with molybdenum. These results constitute a kinetic metal effect in direct oxo transfer reactions for analogue complexes and for isoenzymes provided the catalytic sites are isostructural. The nature of the transition state in oxo transfer reactions of analogues is tentatively considered. This research presents the first kinetics study of substrate reduction via oxo transfer mediated by bis(dithiolene)tungsten complexes. PMID:11456814

Sung, K M; Holm, R H



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.



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.



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.



Circulation in Lake Vostok: A laboratory analogue study  

Microsoft Academic Search

The waters of sub-glacial Lake Vostok are thought to represent a unique biological habitat that has been out of contact with the atmosphere for millions of years. Although the water circulation within the lake will determine how nutrients are redistributed and hence where life may exist, the handful of existing studies conflict regarding whether the lake is stratified or well

Mathew G. Wells; J. S. Wettlaufer



Gale Crater Analogue Geology Studies at Multiple Scales  

NASA Astrophysics Data System (ADS)

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

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



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.


Structural and biochemical studies of actin in complex with synthetic macrolide tail analogues.  


The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine?C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13)?nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide?C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. Structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis. PMID:25047814

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



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

SciTech Connect

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

Galas, M.C.; Lignon, M.F.; Rodriguez, M.; Mendre, C.; Fulcrand, P.; Laur, J.; Martinez, J. (Centre de Pharmacologie-Endocrinologie, Montpellier (France))



Potent fluorinated agelastatin analogues for chronic lymphocytic leukemia: design, synthesis, and pharmacokinetic studies.  


Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro activity against primary cell lines of CLL and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of 1a in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds. PMID:24673739

Stout, E Paige; Choi, Michael Y; Castro, Januario E; Molinski, Tadeusz F



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

Microsoft Academic Search

Discrete explosive bursts are known from many volcanic eruptions. In maar–diatreme eruptions, they have occurred in debris-filled volcanic vents when magma interacted with groundwater, implying that material mobilized by such explosions passed through the overlying and enclosing debris to reach the surface. Although other studies have addressed the form and characteristics of craters formed by discrete explosions in unconsolidated material,

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



Interactions of taurine and structurally related analogues with the GABAergic system and taurine binding sites of rabbit brain  

PubMed Central

The aim of this study was to find taurinergic compounds that do not interact with brain GABA ergic systems. Washed synaptic membranes (SM) from whole rabbit brain were able to bind [3H]muscimol. Saturation experiments of the binding of [3H]GABA to GABAB receptors showed that SM possess two binding components; twice Triton X-100-treated SM contained 0.048 mmol endogenous taurine/kg protein and bound [3H]taurine in a saturable manner (Kd=249.0±6.3 nM and Bmax=3.4±1.0 pmol mg?1 prot). Among the 19 structural analogues of taurine, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide (TAG), 2-aminoethylarsonic (AEA), 2-hydroxyethanesulfonic (ISE) and (±)cis-2-aminocyclohexane sulfonic acids (CAHS) displaced [3H]taurine binding (Ki=0.13, 0.13, 13.5 and 4.0 ?M, respectively). These analogues did not interact with GABAA and GABAB receptors and did not affect taurine- and GABA-uptake systems and GABA-transaminase activity. 3-Aminopropanesulfonic acid (OMO), ?-alanine, pyridine-3-sulfonic acid, N,N,N-trimethyltaurine (TMT), 2-(guanidino)ethanesulfonic acid (GES), ethanolamine-O-sulphate, N,N-dimethyltaurine (DMT), taurine and (±)piperidine-3-sulfonic acid (PSA) inhibited [3H]muscimol binding to GABAA receptors with different affinities (Ki=0.013, 7.9, 24.6, 47.5, 52.0, 91.0, 47.5, 118.1 and 166.3 ?M, respectively). Taurine, 2-aminoethylphosphonic acid, DMT, TMT and OMO inhibited the binding of [3H]GABA to GABAB receptors with Ki's in the ?M range (0.8, 3.5, 4.4, 11.3 and 5.0, respectively). GES inhibited taurine uptake (IC50=3.72 ?M) and PSA GABA transaminase activity (IC50=103.0 ?M). In conclusion, AEA, TAG, ISE and CAHS fulfill the criteria for taurinergic agents. PMID:12684273

Frosini, Maria; Sesti, Casilde; Dragoni, Stefania; Valoti, Massimo; Palmi, Mitri; Dixon, Henry B F; Machetti, Fabrizio; Sgaragli, Giampietro



Study by electronic circular dichroism spectroscopy of the interaction between aminooxy analogues of biogenic polyamines and selected oligonucleotides  

NASA Astrophysics Data System (ADS)

The interaction between a series of aminooxy analogues of the biogenic polyamines spermine and spermidine and selected 15-mer oligodeoxyribonucleotides with alternating purine-pyrimidine base sequences, adenine-thymine (AT) and guanine-cytosine (GC), has been studied using electronic circular dichroism (CD) spectroscopy. These analogues resulted from the substitution of the two terminal aminomethylene groups of the polyamines, -CH 2NH 2+, by an aminooxy one, -ONH 2. Since spermidine has no centre of symmetry, it gives rise to two different isosteric molecules, which have been named AOEPUT and APAPA. On the contrary, spermine gives rise to a single aminooxy analogue, named as AOSPM. As the p Ka of an aminooxy group (about 5) is not high enough to be protonated at a neutral pH, these analogues have a positive charge less than the corresponding polyamine under physiological settings, which makes them suitable models to investigate the roles of the charge and the structure in the polyamine-DNA interaction. At low pH values, both the biogenic polyamine and their aminooxy analogues have a similar positive charge. The CD spectra of solutions containing different concentrations of the three aminooxy analogues and a 15-mer oligonucleotide, containing either the GC or the AT sequence, at a fixed concentration 60 ?M in phosphate, were recorded. Solutions at pH values 7.5 and 5.0 were studied in order to investigate the role of the molecular charge. The spectra demonstrated that the interaction of these oligonucleotides with the aminooxy analogues had a significant sequence-selectivity. Spectra of the oligonucleotides in the presence of AOSMP showed two isodicroic points, thus indicating the presence of different oligonucleotide conformations in solution. The CD spectra of AOEPUT and APAPA supported the non-equivalent role that the outer ammonium groups of spermidine, N1 and N8 positions, could have in the interaction of this biogenic polyamine with DNA.

Ruiz-Chica, A. J.; Medina, M. A.; Sánchez-Jiménez, F.; Ramírez, F. J.



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

SciTech Connect

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

August, J.T.



A study of tumour growth based on stoichiometric principles: a continuous model and its discrete analogue  

PubMed Central

In this paper, we consider a continuous mathematically tractable model and its discrete analogue for the tumour growth. The model formulation is based on stoichiometric principles considering tumour-immune cell interactions in potassium (K +)-limited environment. Our both continuous and discrete models illustrate ‘cancer immunoediting’ as a dynamic process having all three phases namely elimination, equilibrium and escape. The stoichiometric principles introduced into the model allow us to study its dynamics with the variation in the total potassium in the surrounding of the tumour region. It is found that an increase in the total potassium may help the patient fight the disease for a longer period of time. This result seems to be in line with the protective role of the potassium against the risk of pancreatic cancer as has been reported by Bravi et al. [Dietary intake of selected micronutrients and risk of pancreatic cancer: An Italian case-control study, Ann. Oncol. 22 (2011), pp. 202–206]. PMID:24963981

Saleem, M.; Agrawal, Tanuja; Anees, Afzal



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

PubMed Central

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

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



Analogue Gravity  

E-print Network

Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing) and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity).

Carlos Barcelo; Stefano Liberati; Matt Visser



Polarization studies of fluffy cometary analogues with the PROGRA2 experiment  

NASA Astrophysics Data System (ADS)

Various observation and modelling results (infrared spectroscopy, dynamics of the particles, linear polarization of the scattered light), suggest the presence of fluffy aggregates in cometary comae. The solar light scattered by the dust is partially linearly polarized. The phase curve has a positive branch at phase angles higher than 20 degrees (with a maximum value of 30 percent in the visible domain at about 90 degrees phase angle) and a negative branch for smaller phase angles. For the positive branch, the polarization increases with wavelength. Laboratory scattering measurements with the PROGRA2 experiment (in A300-CNES and ESA dedicated microgravity flights or in ground based configurations) offer an alternative to models for exploring the scattering properties of aggregates particularly for structures too large or too complex to be handled easily by computer simulations. High porosity aggregates have been previously studied in levitation on single materials (pyrogenic oxides or carbon blacks). Their constituent grains size range is 10-100 nm; these grains are linked in aggregates with sizes in the 10 microns range. The levitating particles studied in the experiment are agglomerates of these aggregates with sizes between 10 microns and 500 microns (the size distribution is determined during the experiment by the imaging polarization technique). Their polarization phase curves have shapes that are approximately similar to those obtained for comets between 20 and 160 degrees phase angles. For grains in the 100 nm size range, the maximum value of polarization is smaller than 40 percent. Cometary particles are made of various materials (silicates and carbonaceous compounds). Mixtures of oxides (silica) and carbon blacks are currently studied to better understand the physical properties of these particles, which can become good analogues for cometary comae. The polarization phase curves obtained in two wavelengths for some of these mixtures and for silicates cometary analogues will be presented and discussed. A negative branch at phase angles smaller than 20 degrees is observed. The PROGRA2 experiment results give a sensitive complementary diagnostic tool to cometary dust particles analogues.

Hadamcik, E.; Renard, J.-B.; Levasseur-Regourd, A.-C.; Worms, J.-C.


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

NASA Technical Reports Server (NTRS)

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

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



Synthesis, spectroscopy and computational studies of selected hydroxyquinolines and their analogues.  


Synthetic, spectroscopy and mechanistic aspects of preparation of selected hydroxyquinolines and their analogues or derivatives contained methoxy, fluoro, chloro, carboxylic, carbodithioic and phosphinate or dioxaphosphinane groups were elaborated. The multinuclear NMR and five single crystal X-ray characteristics of the series of quinolines have been determined. The molecular orbitals of the selected hydroxyquinolines have been calculated by density functional theory. The X-ray and NMR studies of 8-[(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)oxy]-5,7-dibromo-2-methylquinoline and 8-[(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)oxy]-5-fluoro-2-methylquinoline indicate the appearance of anomeric effect. PMID:24001976

Nycz, Jacek E; Szala, Marcin; Malecki, Grzegorz J; Nowak, Maria; Kusz, Joachim



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

PubMed Central

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.



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

SciTech Connect

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

Not Available



Structural insights into the interactions of xpt riboswitch with novel guanine analogues: a molecular dynamics simulation study.  


Ligand recognition in purine riboswitches is a complex process requiring different levels of conformational changes. Recent efforts in the area of purine riboswitch research have focused on ligand analogue binding studies. In the case of the guanine xanthine phosphoribosyl transferase (xpt) riboswitch, synthetic analogues that resemble guanine have the potential to tightly bind and subsequently influence the genetic expression of xpt mRNA in prokaryotes. We have carried out 25 ns Molecular Dynamics (MD) simulation studies of the aptamer domain of the xpt G-riboswitch in four different states: guanine riboswitch in free form, riboswitch bound with its cognate ligand guanine, and with two guanine analogues SJ1 and SJ2. Our work reveals novel interactions of SJ1 and SJ2 ligands with the binding core residues of the riboswitch. The ligands proposed in this work bind to the riboswitch with greater overall stability and lower root mean square deviations and fluctuations compared to guanine ligand. Reporter gene assay data demonstrate that the ligand analogues, upon binding to the RNA, lower the genetic expression of the guanine riboswitch. Our work has important implications for future ligand design and binding studies in the exciting field of riboswitches. PMID:24404773

Jain, Swapan S; Sonavane, Uddhavesh B; Uppuladinne, Mallikarjunachari V N; McLaughlin, Emily C; Wang, Weiqing; Black, Sheneil; Joshi, Rajendra R



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. PMID:22309909

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



Crystal Structures of HIV-1 gp120 Envelope Glycoprotein in Complex with NBD Analogues That Target the CD4-Binding Site  

PubMed Central

Efforts to develop therapeutic agents that inhibit HIV-1 entry have led to the identification of several small molecule leads. One of the most promising is the NBD series, which binds within a conserved gp120 cavity and possesses para-halogen substituted aromatic rings, a central oxalamide linker, and a tetramethylpiperidine moiety. In this study, we characterized structurally the interactions of four NBD analogues containing meta-fluoro substitution on the aromatic ring and various heterocyclic ring replacements of the tetramethylpiperidine group. The addition of a meta-fluorine to the aromatic ring improved surface complementarity and did not alter the position of the analogue relative to gp120. By contrast, heterocyclic ring replacements of the tetramethylpiperidine moiety exhibited diverse positioning and interactions with the vestibule of the gp120 cavity. Overall, the biological profile of NBD-congeners was modulated by ligand interactions with the gp120-cavity vestibule. Herein, six co-crystal structures of NBD-analogues with gp120 provide a structural framework for continued small molecule-entry inhibitor optimization. PMID:24489681

Kwon, Young Do; LaLonde, Judith M.; Yang, Yongping; Elban, Mark A.; Sugawara, Akihiro; Courter, Joel R.; Jones, David M.; Smith, Amos B.; Debnath, Asim K.; Kwong, Peter D.



Structureactivity studies of RFamide analogues on central neurones of Helix aspersa  

Microsoft Academic Search

The effects of FMRFamide were compared with those of FMRFamide analogues, FLRFamide, LFRFamide, FFRFamide, LLRFamide, D-FMRFamide, F-D-MRFamide and FM-D-RFamide, and the fragments, MRFamide and LRFamide, on identified central neurones, F1, F2, F5 and E16, of the snail Helix aspersa, using intracellular recording and two electrode voltage clamp techniques. All FMRFamide analogues showed an inhibitory effect on F1 neurones with an

M. L. Chen; R. Sharma; R. J. Walker



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


Deposition of latex colloids on a structured silicon surface was investigated. The surface with well-defined roughness and topography pattern served as an analogue for rough mineral surfaces with half-pores in the submicrometer size. The silicon topography consists of a regular pit pattern (pit diameter = 400 nm, pit spacing = 400 nm, pit depth = 100 nm). Effects of hydrodynamics and colloidal interactions in transport and deposition dynamics of a colloidal suspension were investigated in a parallel plate flow chamber. The experiments were conducted at pH ? 5.5 under both favorable and unfavorable adsorption conditions using carboxylate functionalized colloids to study the impact of surface topography on particle retention. Vertical scanning interferometry (VSI) was applied for both surface topography characterization and the quantification of colloidal retention over large fields of view. The influence of particle diameter variation (d = 0.3-2 ?m) on retention of monodisperse as well as polydisperse suspensions was studied as a function of flow velocity. Despite electrostatically unfavorable conditions, at all flow velocities, an increased retention of colloids was observed at the rough surface compared to a smooth surface without surface pattern. The impact of surface roughness on retention was found to be more significant for smaller colloids (d = 0.3, 0.43 vs. 1, 2 ?m). From smooth to rough surfaces, the deposition rate of 0.3 and 0.43 ?m colloids increased by a factor of ?2.7 compared to a factor of 1.2 or 1.8 for 1 and 2 ?m colloids, respectively. For a substrate herein, with constant surface topography, the ratio between substrate roughness and radius of colloid, Rq/rc, determined the deposition efficiency. As Rq/rc increased, particle-substrate overall DLVO interaction energy decreased. Larger colloids (1 and 2 ?m) beyond a critical velocity (7 × 10(-5) and 3 × 10(-6) m/s) (when drag force exceeds adhesion force) tend to detach from the surface irrespective of the impact of roughness. For polydisperse solutions, an increase in the polydispersity and flow velocity resulted in a reduction of colloid deposition efficiency due to the resulting enhanced double-layer repulsion. Quantification of surface topography variations of two endmembers of natural grain surfaces showed that half-pore depths and roughness of sedimentary quartz grains are mainly in the micrometer range. Grains with diagenetically formed quartz overgrowths, however, show surface roughness mainly in the submicrometer range. Thus, surface topography features applied in the here presented analogue study and resulting variation in particle retention can serve as quantitative analogue for particle reactions in diagenetically altered quartz sands and sandstones. The reported impact of particle polydispersity can have an important application for quantitative prediction of retention of varying types of minerals, such as different clay minerals in the environment under prevailing unfavorable conditions. PMID:22448713

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



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. PMID:19209891



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


Isopenicillin N synthase (IPNS) is a non-heme iron oxidase central to the biosynthesis of ?-lactam antibiotics. IPNS converts the tripeptide ?-(L-?-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N while reducing molecular oxygen to water. The substrate analogue ?-(L-?-aminoadipoyl)-L-cysteinyl-O-methyl-D-threonine (ACmT) is not turned over by IPNS. Epimeric ?-(L-?-aminoadipoyl)-L-cysteinyl-O-methyl-D-allo-threonine (ACmaT) is converted to a bioactive penam product. ACmT and ACmaT differ from each other only in the stereochemistry at the ?-carbon atom of their third residue. These substrates both contain a methyl ether in place of the isopropyl group of ACV. We report an X-ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. This structure reveals an additional water molecule bound to the active site metal, held by hydrogen-bonding to the ether oxygen atom of the substrate analogue. PMID:23860486

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



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. PMID:21674039

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



Women's Preference of Therapist Based on Sex of Therapist and Presenting Problem: An Analogue Study  

PubMed Central

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

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



In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt1-DALDA Analogues  

PubMed Central

In this study the ? opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH2) and Dmt1-DALDA (Dmt-d-Arg-Phe-Lys-NH2, Dmt = 2?,6?-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4–7) proved to possess high affinity and agonist potency at both MOR and DOR (? opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood–brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these experiments were indicative of transcellular transport but not active transport. In vivo assays demonstrated that the peptides were capable of (i) crossing the blood–brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt1-DALDA 1, compounds 4–7 are mixed MOR/DOR agonists, expected to produce reduced opioid-related side effects. PMID:24839540

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



A strategy for fusion expression and preparation of functional glucagon-like peptide-1 (GLP-1) analogue by introducing an enterokinase cleavage site.  


KGLP-1, a 31-amino acid glucagon-like peptide-1 (GLP-1) analogue, has a great therapeutic potential for anti-diabetes. In this work, a strategy for expression and purification of functional KGLP-1 peptide has been established. KGLP-1 cDNA was fused with glutathione S-transferase (GST), with an enterokinase cleavage site in the fusion junction. The recombinant fusion protein GST-KGLP-1 was affinity purified via the GST-tag, and then digested with enterokinase. The resulting GST part as well as the enzymes were eliminated by ultra-filtration followed by size exclusion chromatograph. The yield of purified KGLP-1 was approximately 12.1 mg/L, with purity of 96.18 %. The recombinant KGLP-1 was shown to have similar bioactivity as native GLP-1 when evaluated in a Chinese hamster ovary cell line expressing a GLP-1 receptor-egfp reporter gene. PMID:24737080

Liu, Yang; Ren, Limei; Ge, Lingmiao; Cui, Qingxin; Cao, Xiaofang; Hou, Yuanyuan; Bai, Fang; Bai, Gang




E-print Network

LS-61 April 28, 1986 SITE EXCAVATION STUDY A. N. Lowing #12;ARGONNE NATIONAL LABORATORY To: Y. Cho From: A. N. Lowing ~~Subject: Site Excavation Study INTRA-LABORATORY MEMO ARGONNE NAn HIGH £NE a site location for the GXS based upon least- excavation vs. zero percent fill material as a criteria

Kemner, Ken



EPA Science Inventory

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


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


1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase catalyzes an essential intramolecular Claisen condensation in menaquinone biosynthesis and is an important target for the development of new antibiotics. This enzyme in Mycobacterium tuberculosis is cofactor-free and is classified as a type II DHNA-CoA synthase, differing from type I enzymes, which rely on exogenous bicarbonate for catalysis. Its crystal structures in complex with product analogues have been determined at high resolution to reveal ligand-dependent structural changes, which include the ordering of a 27-residue active-site loop (amino acids 107-133) and the reorientation of the carboxy-terminal helix (amino acids 289-301) that forms part of the active site from the opposing subunit across the trimer-trimer interface. These structural changes result in closure of the active site to the bulk solution, which is likely to take place through an induced-fit mechanism, similar to that observed for type I DHNA-CoA synthases. These findings demonstrate that the ligand-dependent conformational changes are a conserved feature of all DHNA-CoA synthases, providing new insights into the catalytic mechanism of this essential tubercular enzyme. PMID:25372686

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



A combined gas-phase photoelectron spectroscopic and theoretical study of Zeise's anion and its bromine and iodine analogues.  


Shining light on Zeise: In a study of Zeise's anion, [PtCl(3)(C(2)H(4))](-), and its bromine and iodine analogues, electronic structure information for each species, derived from spectral features, is assigned through calculations at the coupled cluster level of theory. The calculations indicate that the electron binding energies decrease with halogen size and that there is a synergistic ?(2) interaction between C(2)H(4) and the PtX(3)(-) anions. PMID:22565588

Hou, Gao-Lei; Wen, Hui; Lopata, Kenneth; Zheng, Wei-Jun; Kowalski, Karol; Govind, Niranjan; Wang, Xue-Bin; Xantheas, Sotiris S



A comparative study of the cytotoxic and genotoxic effects of cisplatin and its analogue, TNO-6, in yeast.  


The antitumour drug cisplatin and its analogue, TNO-6, were studied for their cytotoxic, mutagenic and recombinagenic effects in a diploid strain (D7) of the yeast, Saccharomyces cerevisiae. It was observed that the structural change in TNO-6 resulted in reduced cytotoxicity and recombinagenicity (mitotic gene conversion) but increased mutagenic activity compared to the effects of cisplatin at equimolar concentrations. These results indicated that the mechanism through which TNO-6 damages cellular DNA is different from that of cisplatin. PMID:3280985

Hannan, M A



PRECLINICAL STUDIES A novel synthetic C-1 analogue of 7-deoxypancratistatin  

E-print Network

availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7 concentration JCTH-1 JC-TH-acid-1 JCTH-4 JC-TH-acetate-4 D. Ma :P. Tremblay :K. Mahngar :P. Akbari-Asl : S pore RFU relative fluorescence units ROS reactive oxygen species SDHA succinate dehydrogenase subunit

Hudlicky, Tomas


Conformational and inframolecular studies of the protonation of adenophostin analogues lacking the adenine moiety  

Microsoft Academic Search

Four adenophostin analogues lacking the adenine moiety were subjected to 31P- and 1H-NMR titrations in order to determine the acid–base behaviour of the individual ionisable groups of the molecules and the complex interplay of intramolecular interactions resulting from the protonation process. For the two trisphosphorylated compounds, the curve pattern of the phosphorus nuclei corresponds to the superimposition of the titration

Hélène Dozol; Clarisse Maechling; Roland Graff; Akira Matsuda; Satoshi Shuto; Bernard Spiess



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



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. PMID:22214767

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



Material and Methods -Study sites  

E-print Network

were always collected at the same lunar phase (after new moon-until full moon). The cellular changes us to study the gametogenic phases by examining sexual and nutritive cell in the tissues (Walker et

Hernández, José Carlos


Acknowledgments and References Study Sites  

E-print Network

) for their assistance on study design and techniques. We thank Dr Kelly Steele (ASU, Department of Applied Sciences transects along 3 reaches which vary in terms of urbanization and vegetation. 1. Compare herpetofauna community in terms of abundance, species richness, and diversity among the 3 reaches 2. Compare microhabitat

Hall, Sharon J.


A comparative study of cellular and molecular pharmacology of doxorubicin and MEN 10755, a disaccharide analogue.  


MEN 10755 is a disaccharide anthracycline endowed with a broader spectrum of antitumour activity than doxorubicin (DOX). To investigate the cellular and molecular basis of its action, cytotoxic activity, drug uptake, subcellular localisation, induction of DNA damage, and apoptosis were assessed in the human A2780 ovarian carcinoma cell line. Experiments with radiolabelled anthracyclines indicated that MEN 10755 exhibited reduced cellular accumulation and a different subcellular distribution (higher cytoplasmic/nuclear ratio) than DOX. In spite of the lower nuclear concentration, MEN 10755 was as potent as DOX in eliciting DNA single- and double-strand breaks, G2/M cell arrest, and apoptosis. Sequencing of drug-induced topoisomerase II cleavage sites showed a common DNA cleavage pattern for MEN 10755 and DOX. Cleavage sites were always characterised by the presence of adenine in -1 position. However, the extent of DNA cleavage stimulation induced by MEN 10755 was greater than that produced by DOX. Reversibility studies showed that MEN 10755-stimulated DNA cleavage sites were more persistent than those induced by DOX, thus suggesting a more stable interaction of the drug in the ternary complex. As a whole, the study indicated that the cellular pharmacokinetics of MEN 10755 substantially differs from that of DOX, showing a lower uptake and a different subcellular disposition. In spite of the apparently unfavourable cellular pharmacokinetics, MEN 10755 was still as potent as DOX in inducing topoisomerase-mediated DNA damage. Although the extent and persistence of protein-associated DNA breaks may contribute to the cytotoxic effects, the drug's efficacy as apoptosis inducer and antitumour agent could not be adequately explained on the basis of DNA damage mediated by the known target (i.e. topoisomerase II), thus supporting additional cellular effects that may be relevant in cellular response. PMID:11377397

Bigioni, M; Salvatore, C; Bullo, A; Bellarosa, D; Iafrate, E; Animati, F; Capranico, G; Goso, C; Maggi, C A; Pratesi, G; Zunino, F; Manzini, S



Antarctic analogues for Mars exploration: a Raman spectroscopic study of biogeological signatures  

NASA Astrophysics Data System (ADS)

There is now much interest in the construction of portable Raman systems for the analysis of cyanobacterial and lichen communities in the field; to this extent, Raman spectra obtained with laboratory-based systems operating at different wavelengths have been evaluated for potential fieldwork applications of miniaturized units. Selected test specimens of the cyanobacterial Nostoc commune, epilithic lichens Acarospora chlorophana, and Caloplaca saxicola and the endolithic Chroococcidiopsis from Antarctic sites have been examined in the present preliminary studies. Although some organisms gave useable Raman spectra with short-wavelength lasers, 1064 nm was the only excitation that was consistently excellent for all organisms. We conclude that a miniaturized Raman spectrometer, operating at layer wavelength excitation, is the optimal instrument for in situ studies of pigmented communities at the limits of life on Earth. This has practical potential for the quest for biomolecules residual from any former surface or subsurface life on Mars.

Edwards, Howell G. M.; Moody, Caroline A.; Jorge Villar, Susana E.; Dickensheets, David L.; Wynn-Williams, David D.



WSSLinks: Women and Gender Studies Web Sites  

NSDL National Science Digital Library

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



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.



The Cheb Basin (Czech Republic) as a Potential Natural Analogue Site for Geological Carbon Storage - Past, Current and Planned Activities  

NASA Astrophysics Data System (ADS)

General difficulties for evaluating methods for the detection and monitoring of CO2 spreading and degassing to the atmosphere induced by CO2 sequestration are the time scale of transport processes and the desired situation of a non-release of sequestered CO2 from the subsurface. The unique structures of the Cheb Basin (western Eger rift / Czech Republic) provide excellent opportunities for further direct investigations of transport processes along migration paths caused by cap rock failures and the development and validation of adequate monitoring tools. The Eger rift belongs to the European Cenozoic rift system and represents an approximately 50 km wide and 300 km long ENE-WSW striking continental rift that formed during the Upper Cretaceous-Tertiary transition. This rift zone is one of the most active seismic regions in Central Europe. This rift zone is one of the most active seismic regions in Central Europe. There are a lot of gas emanations (cold vents) with high CO2 contents (> 99 vol% CO2). The CO2-fluxes vary in a wide range between smaller than 1 up to 4000 L/h per vent. The degassing activity is assumed to be generally connected to the seismic activity, which has mainly a swarm-like character, and is originated in the upper mantle. Comprehensive studies of CO2-rich fluids have been started 20 years ago and have in particular included two extended chemical and isotope monitoring studies lasting for several years. These studies result in the identification of the fluid component sources. The CO2 stems from the lithospheric mantle - a deeper source area as in the case of CO2 sequestration. A distinct relationship was found between the steadily magmatic CO2-degassing and the recurrence of swarm earthquakes in the Novy Kostel focal zone close to the Cheb basin. Such areas with permanent CO2 fluxes from a well-known characterized deep source are especially suitable to study and test methods and method combinations for CO2 degassing monitoring. Several past and ongoing geophysical investigations concerning the geodynamical activity and the structural settings have been carried out to characterize the active fault systems. The lateral distribution of swarm seismicity is limited to a small number of focal zones, which have been periodically reactivated during the last years. The migration of fluids, uprising in permeable channels, is assumed to be the trigger of these earthquake swarms. Tectonic setting and sedimentary layers in the area have a great influence on the degassing situation of CO2 at the surface. Due to their permeability, faults act as preferential pathways for the upward migration and deep gases can escape to the atmosphere. Furthermore, regional patterns of diffuse CO2 emissions have been intensely studied to obtain insights into spatial and temporal variations of soil gas fluxes and concentrations.

Schuetze, C.; Dietrich, P.; Strauch, G.; Braeuer, K.; Schloemer, S.; Faber, E.; Kaempf, H.; Flechsig, C.



Measuring satiety with pictures compared to visual analogue scales. An exploratory study.  


Visual analogue scales (VAS) are a standard tool used to measure subjective appetite. To explore a potentially more intuitive and precise alternative, we developed a method based on pictures and assessed its performance characteristics vs. VAS. The objective was to compare the capacity of the two methods to discriminate appetite ratings between interventions. Both methods were applied within a previously published trial in which 16 healthy adults received standardised meals followed by three different ileal infusions in a balanced crossover design. At regular intervals volunteers indicated how many units of individually pictured food portions (for 10 different items) they would like to eat, and also scored six VAS. Methods were compared over different timeframes and assessed for their sensitivity to intervention effects. Pictures were more sensitive than VAS in differentiating intervention effects; however, further refinement and validation would be needed for pictures to become a standardised and accepted alternative to VAS for this type of research. PMID:22086153

Sadoul, Bastien C; Schuring, Ewoud A H; Symersky, Tomas; Mela, David J; Masclee, Ad A M; Peters, Harry P F



Synthesis of a tritium-labeled indolidan analogue and its use as a radioligand for phosphodiesterase-inhibitor cardiotonic binding sites  

SciTech Connect

We have radiolabeled a structural analogue of indolidan, a potent phosphodiesterase-inhibitor cardiotonic, to permit biochemical studies regarding the interaction of this class of drugs with their pharmacological receptor. (/sup 3/H)-LY186126 (1,3-dihydro-3,3-dimethyl-1-(/sup 3/H3)methyl-5-(1,4,5,6-tetrahydro-4-me thyl-6- oxo-3-pyridazinyl)-2H-indol-2-one; (/sup 3/H)-3) was selected as a synthetic target because of its potency as a cardiotonic and the ability to readily incorporate three tritia via the indolone N-CH3 substituent. Alkylation of a desmethyl precursor with tritium-labeled iodomethane resulted in (/sup 3/H)-3 with a radiochemical purity of 98% and a specific activity of 79.2 Ci/mmol. This radioligand binds with high affinity to myocardial membrane vesicles. The binding was saturable, and Kd and Bmax values of 4.1 nM and 383 fmol/mg protein were obtained. A series of indolidan congeners displaced (/sup 3/H)-3 bound to myocardial vesicles, and Ki values for inhibition of binding were highly correlated with canine inotropic ED50 values, suggesting the specific binding of (/sup 3/H)-3 to cardiac vesicles is pharmacologically relevant.

Robertson, D.W.; Krushinski, J.H.; Utterback, B.G.; Kauffman, R.F.



Studies on the mechanisms of the radiosensitizing and cytotoxic properties of RSU-1069 and its analogues  

SciTech Connect

RSU 1069 is a substantially more efficient sensitizer than misonidazole when hypoxic Chinese hamster V79 cells are irradiated in vitro at room temperature; such that for 0.5 mmol dm-3 sensitizer an ER of 3.0 is obtained for RSU 1069 whereas an ER of only 1.6 is obtained for misonidazole. However, when irradiation is done at 4/sup 0/C, the radiosensitization caused by RSU 1069 is reduced to a level close to that obtained with misonidazole, the action remaining unaltered at the lower temperature. This temperature dependent component of sensitization for RSU 1069 suggests the involvement of a slow biochemical process that has an appreciable activation energy. The RSU 1069 analogue RB 7040 is a more efficient radiosensitizer than RSU 1069 particularly at lower concentrations. This compound has a pKa value of 8.45, in contrast to that of RSU 1069 which is 6.04. Weak bases with pKa values in excess of average intra-cellular pH can be taken up preferentially into cells from medium at pH 7.4. It is shown that RB 7040 has a 4 X higher intracellular concentration than RSU 1069 for a similar extracellular concentration. This will explain, at least in part, the greater sensitizing efficiency of this compound when compared to RSU 1069 in vitro.

Walling, J.M.; Stratford, I.J.; Adams, G.E.; Silver, A.R.; Ahmed, I.; Jenkins, T.C.; Fielden, E.M.



Aspartame and Its Analogues  

NASA Astrophysics Data System (ADS)

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

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



ADP induces desensitisation of equine platelet aggregation responses: studies using ADP beta S, a stable analogue of ADP.  


Pre-incubation of equine platelets in platelet-rich plasma with adenosine 5'-diphosphate (ADP) induced a reduction in aggregation responsiveness to subsequent additions of ADP. The desensitisation was shown to be homologous since the responsiveness to platelet-activating factor, thrombin, collagen, 5-hydroxytryptamine or ionomycin remained unchanged. Adenosine 5'-(beta-thio)-diphosphate (ADP beta S), a non-hydrolysable analogue of ADP, was shown to act as an agonist inducing aggregation by interaction with the ADP receptor. ADP beta S was then used in the desensitisation studies in which residual ADP was degraded by the addition of apyrase. The desensitisation to ADP beta S fully recovered by one hour after pre-treatment with ADP and was not induced by an extracellular mediator. The mechanism of desensitisation is therefore likely to involve the ADP receptor or proximal intermediates in the signal transduction pathway for ADP. PMID:8460266

Poole, A W; Heath, M F; Evans, R J



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. PMID:3691438

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



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


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



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.


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.



Pharmacokinetics of MEN-10755, a novel anthracycline disaccharide analogue, in two phase I studies in adults with advanced solid tumours.  


The doxorubicin analogue MEN-10755 has been identified as a compound with promising antitumour activity based on structure-activity studies of a new series of anthracycline disaccharides. The high antitumour activity of MEN-10755 in human tumour xenografts, including doxorubicin-resistant xenografts, and its unique pharmacological and biological properties made this novel disaccharide analogue an interesting candidate for clinical evaluation. Two pharmacokinetic phase I studies with different dosing schedules were performed in adults with solid refractory malignancies. The pharmacokinetics of MEN-10755 were studied after a 15-min i.v. infusion given once every 3 weeks or once every week for 3 weeks followed by 1 week rest. Plasma and urine levels of MEN-10755 were measured by HPLC with fluorescent detection. It was possible to combine the pharmacokinetic results of the two studies because there was no accumulation of MEN-10755 before the next infusion of MEN-10755 in the weekly study with 1 week rest. The administered dose levels on day 1 in this study were all in the lower range from the 3-weekly study. The postinfusion plasma kinetics of MEN-10755 were best described by a triexponential model. The plasma peak levels (Cmax) of MEN-10755 showed a linear relationship with the administered dose. Peak plasma MEN-10755 levels ranged between 474 and 21,587 microg/l. The mean elimination half-life (T(1/2gamma)) was 20.7+/-9.0 h. The AUC(0-infinity) was proportional to the administered dose. The mean plasma clearance of MEN-10755 was 6.0+/-2.2 l/h per m2 with a mean volume of distribution (Vss) of 95.6+/-43.4 l/m2. The mean renal excretion of unchanged drug within 24 h was 4.3+/-1.8%. Compared to epirubicin and doxorubicin, the pharmacokinetics of MEN-10755 were characterized by an approximately twofold shorter terminal half-life, a much lower total plasma clearance and a much smaller volume of distribution. PMID:11761453

Bos, A M; de Vries, E G; Dombernovsky, P; Aamdal, S; Uges, D R; Schrijvers, D; Wanders, J; Roelvink, M W; Hanauske, A R; Bortini, S; Capriati, A; Crea, A E; Vermorken, J B



Ab Initio Quantum Mechanical Study of the Structures and Energies for the Pseudorotation of 5-Dehydroxy Analogues of 2-Deoxyribose  

E-print Network

-(1-pyrollyl)tetrahydrofuran and 4-hydroxy-5-methyl-2-(1-pyrollyl)- tetrahydrofuran, close analogues of 2-4 In the case of tetrahydrofuran (THF) and the more complex 2-deoxyribose and ribose sugars, there are barriers

Goddard III, William A.


The fatty acid analogue 11-(dansylamino)undecanoic acid is a fluorescent probe for the bilirubin-binding sites of albumin and not for the high-affinity fatty acid-binding sites.  

PubMed Central

1. The fluorescent fatty acid probe 11-(dansylamino)undecanoic acid (DAUDA) binds with high affinity to bovine and human serum albumin (BSA and HSA) at three sites. 2. The Kd of the primary binding site could not be determined; however, the two secondary sites appeared to be equivalent, with an apparent Kd of 8 x 10(-7) M for both BSA and HSA. 3. The spectral characteristics of DAUDA when bound to the primary site of the two albumins were different, with HSA producing a greater fluorescence enhancement and emission maximum at a shorter wavelength (480 nm) than for BSA (495 nm). 4. Displacement studies indicated that the DAUDA-binding sites were not equivalent to the primary long-chain fatty acid-binding sites on albumin, but corresponded to the bilirubin sites. Fatty acyl-CoAs also bind to the bilirubin sites, as do medium-chain fatty acids. 5. The solubility, stability and spectral properties of DAUDA make it an excellent probe for investigating the bilirubin-binding sites of albumin, particularly HSA. PMID:2396975

Wilton, D C



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.



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



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


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



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



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


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



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

PubMed Central

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

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



[Studies on tissue schizonticide of malaria parasite: synthesis of 2-substituted benzyloxy (or methoxy)-5-substituted phenoxy analogues of primaquine].  


2-Chloro-6-methoxy-8-nitroquinoline was reacted with substituted benzyl alcohols (or sodium methanol) and then brominated to give 2-substituted benzyloxy-6-methoxy- and 2,6-dimethoxy-5-bromo-8-nitroquinolines (compounds 5-8 in Table 1). These products were condensed with substituted phenols to form corresponding 5-substituted phenoxy compounds (9-19 in Tables 1 and 2) which were subsequently reduced to afford 2-substituted benzyloxy-6-methoxy- and 2,6-dimethoxy-5-substituted phenoxy-8-aminoquinolines (20-28, 47 and 48 in Tables 3 and 6). Condensation with 4-bromophthalimidopentane yielded corresponding 8-(4-phthalimido-1-methylbutyl)aminoquinolines (29-37, 49 and 50 in Tables 4 and 6) which were subsequently treated with hydrazine hydrate to give 2-substituted benzyloxy-6-methoxy- and 2,6-dimethoxy-5-substituted phenoxy-8-(4-amino-1-methylbutyl)amino-quinolines, compounds III and IV (38-46, 51 and 52 in Tables 5 and 6), the analogues of primaquine. Compounds III and IV were tested against Plasmodium yoenii in mice infected with sporozoites. The parasitaemia of 80% and 90% of tested mice was negative at an oral single dose of 100 mg/kg of compounds 39 and 45, respectively. The results of further studies on compound 45 showed that the parasitaemia of 80% of mice was negative at a single dose of 20 mg/kg, and the acute toxicity in mice was less than that of primaquine. PMID:1823988

Zheng, X Y; Chen, C; Gao, F H



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. PMID:21227404

Ehlers, Anke; Mauchnik, Jana; Handley, Rachel



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


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

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



Toward the standardization of use-wear studies: constructing an analogue to prehistoric hide work  

E-print Network

This thesis is a use-wear study that deals with microwear on stone endscrapers used on one worked material: animal skins. The first part of the study defines and describes the process of rendering freshly skinned pelts into functional leather...

Wiederhold, James Edward




E-print Network

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

Cui, Yan


Synthesis and structure-activity relationship studies of N-terminal analogues of the antimicrobial peptide tridecaptin A(1).  


Chemical synthesis was used to increase the potency of the antimicrobial lipopeptide tridecaptin A1. Lipid tail modification proved to be an ideal platform for synthesizing structurally simpler analogues that are not readily accessible by isolation. The stereochemical elements of the tridecaptin A1 lipid tail are not essential for antimicrobial activity and could be replaced with hydrophobic aliphatic or aromatic groups. Some simpler analogues displayed potent antimicrobial activity against Gram-negative bacteria, including Campylobacter jejuni, Escherichia coli O157:H7, and multidrug resistant Klebsiella pneumoniae. PMID:24479847

Cochrane, Stephen A; Lohans, Christopher T; Brandelli, Jeremy R; Mulvey, George; Armstrong, Glen D; Vederas, John C



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

PubMed Central

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



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


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



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

NASA Technical Reports Server (NTRS)

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

Conrad, Pamela G.



A laboratory study of meteor smoke analogues: Composition, optical properties and growth kinetics  

Microsoft Academic Search

Meteoric smoke forms in the mesosphere from the recondensation of the metallic species and silica produced by meteoric ablation. A photochemical flow reactor was used to generate meteoric smoke mimics using appropriate photolytic precursors of Fe and Si atoms in an excess of oxidant. The following systems were studied: (i) Fe+O3\\/O2, (ii) Fe+O3\\/O2+H2O, (iii) Fe+Si\\/SiO+O3\\/O2 and (iv) Si\\/SiO+O3\\/O2. The resulting

Russell W. Saunders; John M. C. Plane



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

NASA Technical Reports Server (NTRS)

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.



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.



Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents.  


A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-?)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives. PMID:25302700

Leong, Sze Wei; Faudzi, Siti Munirah Mohd; Abas, Faridah; Aluwi, Mohd Fadhlizil Fasihi Mohd; Rullah, Kamal; Wai, Lam Kok; Bahari, Mohd Nazri Abdul; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H



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

NASA Astrophysics Data System (ADS)

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

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




E-print Network

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


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

Microsoft Academic Search

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

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



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

SciTech Connect

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

McKenzie, W.F.



Genetic processes behind calderas formation on Venus through a comparative study with Terrestrial analogues  

NASA Astrophysics Data System (ADS)

On the base of remote sensing and terrestrial geological data we have elaborated a hypothesis about the origin of calderas on Venus through a global and a local scale comparison with similar structures on Earth. For the global scale comparison, we categorized the Venusian and the terrestrial volcanic depressions. We extracted for comparison geometric data such as areal dimensions and eccentricity. For the local scale comparison we have selected two cases of study which are comparable in terms of size: Mezrina Patera, on Venus, and Vulsini Complex (Lazio, Italy) on Earth. A geological mapping of the main structural features and deposits has been conducted and a number of specific features, which are interpreted to be related to extrusion of lava and intrusion of magma have been identified in Mezrina Patera. These are: volcano-tectonic depressions, resurgences, lobate deposits, channelized flows (plausible lava flows) and concentric lava domes. The genetic processes behind the formation of the Venusian patera seem to have been influenced from both global and local scale stress fields. Vulsini Complex doesn't show the same evidence, so that the terrestrial volcanic complex appears to have been predominantly influenced by local scale stress fields. While Vulsini Complex is clearly related to explosive volcanism, Mezrina Patera could be connected with a hot spot or mantle plume activity. A deeper analysis of the most recent 1 micron thermal emissivity and surface temperature data, which will be reported in a further pubblication, will allow us to better constrain if Mezrina Patera might be related to recent volcanism.

D'Incecco, P.; Törmänen, T.; Helbert, J.; D'Amore, M.; Maturilli, A.



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


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

Saini, V; Kumar, A



Thermophysical properties of potential geothermal reservoir rocks: an outcrop analogue study of the sedimentary series of the Buda Mts., Hungary  

NASA Astrophysics Data System (ADS)

The detailed knowledge of sedimentary features from microscopic to regional scales is regarded as crucial in reservoir characterization and prediction of deep geothermal systems. Generally, in the early stages of reservoir exploration, characterization of the reservoir is accomplished by evaluation of drilling data and seismic surveys. However, for reservoir prognosis, the main geothermal parameters such as permeability, thermal conductivity, and reservoir heat flow have to be quantified with respect to a 3D structural model. Outcrop analogue studies serve to predict such subsurface thermophysical properties, and based on detailed facies analysis, the geothermal exploration concept becomes more precise and descriptive. Our data from the Meso- and Cenozoic sedimentary series of Budapest include carbonates and clastic sediments of Triassic, Eocene, and Oligo-Miocene age as well as Pleistocene travertine, exposed on the western side of the river Danube. Field and laboratory analyses reveal distinct horizons of different geothermal potential and thus, enable us to identify and interpret corresponding exploration target horizons in geothermal prone depths of the Pannonian Basin. Upper Triassic limestones (Main Dolomite, Budaörs Dolomite, Mátyáshegy Limestone) show values of thermal conductivity in the range of 2,0 to 3,5 W/(m·K). Matrix permeabilities measured with a gas mini-permeameter span in the range of 10-12 to 10-14 m2. Additionally, these limestones are highly fractured and show a different degree of karstification increasing the fluid migration. Thus, hydrothermal exploration of such limestone reservoirs in geothermal prone depths of about 5 km known from the Zala and Danube basins of W Hungary is seen very promising. Miocene bioclastic limestones (e.g, Tinnye Limestone) reveal lower values of thermal conductivity in the range of 1,0 to 1,5 W/(m·K). On the other hand, they are characterized by much higher permeabilities (10-11 to 10-12 m2). Depending on their occurrence in the deep subsurface, they might be considered as reservoir rocks. Marls and travertines show values of thermal conductivity in the range of 2,0 to 2,5 W/(m·K). Matrix permeabilities of marls are low (10-15 to 10-16 m2), whereas travertines are characterized by the highest permeabilities up to 10-11 m2. Both, marls and travertines are not considered as deep geothermal reservoir rocks: marls due to their low permeabilities, and travertines due to their occurrence mostly in surface outcrops. Clastic sediments of Palaeo- and Neogene age are grouped into low permeable and low heat conducting clays (e.g., Kiscell Clay), and high permeable, high heat conducting sandstones (e.g., Hárshegy Sandstone). Thus, hydrothermal exploration of high permeable sandstone reservoirs in geothermal prone depths known from different basins in Hungary (e.g., Central Great Plain) is also seen very promising. Based on these preliminary results, further outcrop analogue studies will serve as a powerful tool to predict such subsurface properties and thus, finally lead to a better understanding of deep geothermal reservoirs in the Pannonian Basin.

Götz, A. E.; Török, Á.; Tóth, M.; Hlavi?ka, V.; Sass, I.



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.



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.



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

PubMed Central

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

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



A model of antimycin A binding based on structure-activity studies of synthetic antimycin A analogues  

Microsoft Academic Search

The structural factors of antimycin A molecule required for inhibitory action were studied using newly synthesized antimycin A derivatives with bovine heart submitochondrial particles, in order to probe the interaction between antimycin A and its binding site. In particular, we focused upon the roles of the amide bond bridge, which connects the salicylic acid and dilactone ring moieties, and the

Hideto Miyoshi; Nobuya Tokutake; Yasuhiro Imaeda; Toshio Akagi; Hajime Iwamura



Chemoenzymatic preparation of germacrene analogues.  


A small library of novel germacrenes was generated using a combination of two plant enzymes, germacrene A synthase, and D synthase and modified farnesyl diphosphate (FDP) analogues. This chemoenzymatic approach allows the preparation of potentially valuable volatiles for biological studies. PMID:22914774

Cascón, Oscar; Touchet, Sabrina; Miller, David J; Gonzalez, Veronica; Faraldos, Juan A; Allemann, Rudolf K



Elwood Murray's Interdisciplinary Analogue Laboratory.  

ERIC Educational Resources Information Center

Describes Elwood Murray's Interdisciplinary Analogue Laboratory which was designed to identify analogous structures occurring in different fields of education. These basic structures could then serve as foundations of an integrated curriculum where students would be encouraged to view their subjects of study relationally. (JMF)

Brownell, Judith



Synthesis and anion binding studies of o-phenylenevinylene-bridged tetrapyrrolic macrocycle as an expanded analogue of calix[4]pyrrole.  


An o-phenylenevinylene-bridged tetrapyrrolic macrocycle (2) was synthesized by means of a Horner-Wadsworth-Emmons reaction between benzylbisphosphonate and SEM-protected diformylpyrrole, followed by deprotection of the SEM groups. This conformationally flexible tetrapyrrole can be considered as an expanded calix[4]pyrrole analogue, which acts as a receptor for the chloride and bromide anions in THF-d8, but undergoes deprotonation upon exposure to the fluoride anion. PMID:24584326

Ghosh, Sudip Kumar; Ishida, Masatoshi; Li, Jiazhu; Cha, Won-Young; Lynch, Vincent M; Kim, Dongho; Sessler, Jonathan L



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

SciTech Connect

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

Not Available



Survey of Analogue Spacetimes  

NASA Astrophysics Data System (ADS)

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

Visser, Matt


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



The action site of the synthetic kainoid (2S,3R,4R)-3-carboxymethyl-4-(4-methylphenylthio)pyrrolidine-2-carboxylic acid (PSPA-4), an analogue of Japanese mushroom poison acromelic acid, for allodynia (tactile pain).  


We previously demonstrated that intrathecal (i.t.) administration of acromelic acid A (Acro-A) induced allodynia in mice and that simultaneous administration of (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1), an Acro-A analogue, attenuated the Acro-A-induced allodynia. To clarify a mechanism of PSPA-1, we attached methyl radical to PSPA-1 and synthesized (2S,3R,4R)-3-carboxymethyl-4-(4-methylphenylthio) pyrrolidine-2-carboxylic acid (PSPA-4) and [(11)C]PSPA-4 for behavioral and autoradiography studies. Although PSPA-4 inhibited the Acro-A-induced allodynia in a dose-dependent manner from 1 to 10 fg/mouse, PSPA-4 itself induced allodynia at 10 to 100 pg/mouse. In vitro autoradiography, [(11)C]PSPA-4 was specifically bound to the rat brain and spinal cord, and the binding was significantly displaced by PSPA-1 and kainic acid, but not by AMPA and antagonists of NMDA, AMPA and kainate receptors. Conversely, [(3)H]kainate was specifically bound to the rat brain and the dorsal horn of spinal cord, and the binding was significantly displaced by PSPA-1 and PSPA-4. The PSPA-4-induced allodynia was blocked by the AMPA/kainate antagonist GYKI53655, but not by kainate antagonists NS102 and UBP296. PSPA-4 increased intracellular Ca(2+) concentration in 27.9% of cultured dorsal root ganglion neurons responding to glutamate, much higher than kainate in 10.9% of them. Taken together, these results suggest that PSPA-4 attenuated the Acro-A-induced allodynia at low doses and induced allodynia at high doses via a binding site different from known kainate antagonists. The development of a radio-labeled PSPA-4 will enable us to promote the understanding of the action mechanism not only of Acro-A, but also of pain transmission in the periphery and central nervous system. PMID:23124023

Miyazaki, Shinichiro; Minami, Toshiaki; Mizuma, Hiroshi; Kanazawa, Masakatsu; Doi, Hisashi; Matsumura, Shinji; Lu, Jingshan; Onoe, Hirotaka; Furuta, Kyoji; Suzuki, Masaaki; Ito, Seiji



School Counseling Site Supervisor Training: An Exploratory Study  

ERIC Educational Resources Information Center

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

DeKruyf, Lorraine; Pehrsson, Dale-Elizabeth



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 optimised using B3LYP with a double-? basis set with polarisation functions, and the energies of these geometries are calculated using B3LYP with additional diffuse functions added to the sulphurs. A comparison of our calculated energies for redox site analogues in the gas phase against electron detachment energies measured by a combination of electrospray ionisation and photoelectron spectroscopy (EI–PES) by Wang and co-workers has been essential because the comparison is for exactly the same molecule with no approximation for the environment. Overall, the correlation of our B3LYP/ 6-31(++)SG**//B3LYP/6-31G** detachment energies with EI–PES experiments is excellent for a wide variety of analogues. Moreover, our calculations at this level have provided insight into a wide variety of properties of iron–sulphur proteins.

Niu, Shuqiang; Ichiye, Toshiko



Plant Volatile Analogues Strengthen Attractiveness to Insect  

PubMed Central

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

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



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

NASA Technical Reports Server (NTRS)

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

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



Comparative Study of Chemical Approaches to the SolidPhase Synthesis of a Tumor-Seeking ?-MSH Analogue  

Microsoft Academic Search

The synthesis of a cyclic melanocortin analogue (H-pz-?Ala-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2), where the Boc-protected derivative of a metal-chelating pyrazolyl ligand (pz) was inserted as N-terminal residue, was addressed\\u000a by several different Fmoc\\/tBu and Boc\\/Bzl solid-phase strategies. On-resin cyclization was achieved immediately following\\u000a incorporation of Asp, by condensation of the Asp side chain carboxyl with the Lys side chain primary amine after selective\\u000a and

Magdalena Valldosera; Marta Monsò; Catarina Xavier; Paula Raposinho; João D. G. Correia; Isabel Santos; Paula Gomes



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


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.



What Makes a Good Site for Field Study? Abridged  

NSDL National Science Digital Library

This unit offers a hands-on approach to helping students learn what makes a good site for studying biodiversity. It's designed to be completed in three or more sessions and has information for teachers, including tips about how to select, map out, and measure team plots within the class site. The three lessons cover planning how to measure and mark the plots, completing a detailed site report, and data collection to create an accurate map of the site.


Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation.  


Metronidazole (MTZ) and other nitroimidazole derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. However, the need for new derivatives with similar therapeutic activity but lower toxicity to human beings prevails. On this purpose, three metronidazole analogues were synthesized, namely: 1-(p-methylphenacyl)-2-methyl-4-nitro imidazole (CPMe), 1-(p-methoxyphenacyl)-2-methyl-4-nitroimidazole (CPMeO), and 1-(p-fluorphenacyl)-2-methyl-4-nitroimidazole (CPF), which at low concentrations (0.5-2 microg/ml) showed a higher activity against Entamoeba histolytica than MTZ (3-6 microg/ml). The aim of this work was to investigate the cytogenetic effect of the three MTZ analogues on human lymphocyte cultures with and without metabolic activation in vitro, using the sister chromatid exchange test (SCE), comparatively with MTZ. The effect of the compounds on the cell proliferation kinetics (CPK) measured by the replication index (RI) and the cytotoxic effect in the mitotic index (MI) was evaluated as well. The SCE frequencies with and without S9 metabolic activation in treated and control lymphocytes showed no significant statistical differences. However when metabolic activation was involved a significant increase in the amount of third division metaphases provoked the CPK increased significantly with all the tested compounds. The RI showed similar behaviour, except for compound CPF. PMID:15046779

Gómez-Arroyo, Sandra; Melchor-Castro, Sara; Villalobos-Pietrini, Rafael; Camargo, Estela Meléndez; Salgado-Zamora, Héctor; Campos Aldrete, Maria Elena



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))



Cheese analogues: a review  

Microsoft Academic Search

Cheese analogues are usually defined as products made by blending individual constituents, including non-dairy fats or proteins, to produce a cheese-like product to meet specific requirements. They are being used increasingly due to their cost-effectiveness, attributable to the simplicity of their manufacture and the replacement of selected milk ingredients by cheaper vegetable products. Sales of cheese analogues are closely linked

Hans-Peter Bachmann



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.



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))



Raft River geothermal site: a reinjection study  

SciTech Connect

Analysis of transient pressure tests combined with spinner surveys and a knowledge of the geology of the area have allowed us to define the injectivity potential of the Raft River geothermal site. The present two injection wells will allow approximately two to four months of injection at the required rate of 2500 gpm without fracturing the formation. A numerical simulator has been used to model the injection portion of the reservoir to investigate options such as hydraulic fracturing or the drilling of an additional well to provide sufficient subsurface disposal.

Ahmed, U.; Wolgemuth, K.M.; Abou-Sayed, A.S.; Schatz, J.F.; Jones, A.H.



Prediction of high- and low-affinity quinol-analogue-binding sites in the aa3 and bo3 terminal oxidases from Bacillus subtilis and Escherichia coli1.  


Haem-copper oxidases are the terminal enzymes in both prokaryotic and eukaryotic respiratory chains. They catalyse the reduction of dioxygen to water and convert redox energy into a transmembrane electrochemical proton gradient during their catalytic activity. Haem-copper oxidases show substantial structure similarity, but spectroscopic and biochemical analyses indicate that these enzymes contain diverse prosthetic groups and use different substrates (i.e. cytochrome c or quinol). Owing to difficulties in membrane protein crystallization, there are no definitive structural data about the quinol oxidase physiological substrate-binding site(s). In the present paper, we propose an atomic structure model for the menaquinol:O2 oxidoreductase of Bacillus subtilis (QOx.aa3). Furthermore, a multistep computational approach is used to predict residues involved in the menaquinol/menaquinone binding within B. subtilis QOx.aa3 as well as those involved in quinol/quinone binding within Escherichia coli QOx.bo3. Two specific sequence motifs, R70GGXDX4RXQX3PX3FX[D/N/E/Q]X2HYNE97 and G159GSPX2GWX2Y169 (B. subtilis numbering), were highlighted within QOx from Bacillales. Specific residues within the first and the second sequence motif participate in the high- and low-affinity substrate-binding sites respectively. Using comparative analysis, two analogous motifs, R71GFXDX4RXQX8[Y/F]XPPHHYDQ101 and G163EFX3GWX2Y173 (E. coli numbering) were proposed to be involved in Enterobacteriales/Rhodobacterales/Rhodospirillales QOx high- and low-affinity quinol-derivative-binding sites. Results and models are discussed in the context of the literature. PMID:24779955

Bossis, Fabrizio; De Grassi, Anna; Palese, Luigi Leonardo; Pierri, Ciro Leonardo



Web Site Projects Evaluation: A Case Study of Romanian Faculties of Economics Web Sites  

ERIC Educational Resources Information Center

In this paper, an evaluation of web sites regarded like projects is discussed. We give an overview of the Web Assessment Index (WAI), by presenting a web sites of Romanian Faculties of Economics case study. The WAI contains five categories: accessibility, access speed, navigability, content and reliability. We analyzed and presented a detailed…

vultur, Sidonia Otilia; Marincas, Delia Adriana



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

SciTech Connect

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

Not Available



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. PMID:23766810

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



Radiological studies of the Baije nuclear power plant potential site  

Microsoft Academic Search

Radioecological studies were carried out of the Baiji nuclear power plant potential site. The annual effective dose equivalents for the highest exposed individual resulting from the atmospheric and aquatic releases of radionuclides from the WER nuclear power plant were estimated. The source term was furnished by Atomteploele Troproekt, USSR, in the site selection feasibility study for the nuclear power plant

B. A. Marouf; A. S. Mohamad; J. S. Taha; J. A. Mahmood



Nutrient and dissolved oxygen studies at OTEC sites  

SciTech Connect

In order to adequately assess the impact of artificial upwelling and other possible ecological impacts of OTEC operations on the chemistry of the water column at OTEC sites, studies were initiated at several potential sites. At most sites,hydrocasts were taken at approximately noon and midnight to a depth of about 100 m; samples were collected from about 15 depths to be analyzed for nitrates, nitrites, reactive phosphate, silicate and dissolved oxygen. At some sites, samples were analyzed for various other parameters including ammonia, total organic phosphorus and carbonate alkalinity. Preliminary data on nitrates, phosphates, silicates and dissolved oxygen from several potential sites - off Hawaii, Oahu, Peurto Rico, and the Virgin Islands - are presented and compared. Significant differences between nutrient concentrations have been found at the Caribbean and Hawaiian sites. There is also evidence of seasonal variation at the Oahu site. (LEW)

Quinby-Hunt, M.S.; Fanning, K.; Ziemann, D.; Walsh, T.W.; Knauer, G.A.



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.



Designing prostacyclin analogues.  


A series of prostacyclin analogues were synthesized and investigated for influence on blood pressure in rats, in vivo inhibition of platelet aggregation in rats, and in vitro inhibition of platelet aggregation in human platelet-rich plasma. The common feature of the analogues described is a replacement of C1-C4 of prostacyclin by a carboxyphenylene residue. The following structure-activity relationships were obtained. Only the meta-carboxyphenylene derivatives yield substantial prostacyclin activity. The 2,3,4-trinor-1,5-inter-m-phenylene prostacyclin analogues in contrast to the natural prototype are reasonably stable against hydrolysis of the enolether bond. The corresponding 2,3,4-trinor-1,5-inter-m-phenylene analogues of carbaprostacyclin have a somewhat lower specific activity but are superior in stability at acid pH values. With regard to the stereoisomerism at the delta 5 double bond, the Z-isomers of the oxa-cyclic prostacyclin series and the E-isomers of the carba-cyclic prostacyclin series are substantially more active than their counterparts. As with natural prostacyclin, the OH group at C15 has to be present in S-configuration. The "wrong" isomers do not inhibit prostacyclin-dependent effects. Resistance against 15-hydroxyprostaglandin dehydrogenase is achieved by substitutions at or near C15. Optimum specific activity combined with resistance against all known prostaglandin-activating enzymes is observed in prostacyclin and carbaprostacyclin analogues, in which the terminal n-pentyl residue is replaced by cyclohexyl. Duration of action, i.e. lowering of blood pressure in anaesthesized rats and inhibition of platelet aggregation in anaesthesized rats, was investigated with selected analogues in order to check the consequences of chemical and metabolic stabilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6315026

Flohé, L; Böhlke, H; Frankus, E; Kim, S M; Lintz, W; Loschen, G; Michel, G; Müller, B; Schneider, J; Seipp, U



In silico screening of the juvabione category of juvenile hormone analogues with juvenile hormone binding protein of Galleria mellonella--a docking study.  


Juvabione, dehydrojuvabione and their aromatic analogues act as juvenile hormone mimics against diverse strains of insect species. Large numbers of modified juvenoids containing the juvabione skeleton, with various structural variations, are synthesized. Some of these compounds exhibit a very high degree of juvenile hormone activity and are presently in use. In this paper we report a comparative molecular docking study of synthesized juvabione, natural juvenile hormone III and synthetic insect growth regulators (fenoxycarb, S-21149, Compound 1, pyriproxyfen) with the juvenile hormone binding protein of Galleria mellonella. The study clearly indicates a higher binding affinity of nitro-substituted juvabione over natural juvenile hormone III and synthetic insect growth regulators such as fenoxycarb and S-21149. PMID:22799597

Awasthi, P; Sharma, P



The Valles natural analogue project  

SciTech Connect

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

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



Synthesis studies of structural analogues of tagetitoxin: 4-O- acetyl-3-amino-1,6-anhydro-3-deoxy- d-gulose 2-phosphate  

Microsoft Academic Search

Synthetic approaches to structural analogues of tagetitoxin (1) are described. The successful route to analogue 3 (X?O) has, as a key step, protection of the cis-vicinal amino alcohol moiety of compound 7 as an N-benzylated cyclic carbamate (9). X-Ray crystallographic analyses of the hydrochloride of compound 7 and of the hydroxyacid 56 are reported.

Barry R. Dent; Richard H. Furneaux; Graeme J. Gainsford; Gregory P. Lynch



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



Development of a general quantum-chemical descriptor for steric effects: density functional theory based QSAR study of herbicidal sulfonylurea analogues.  


Quantitative structure-activity relationship (QSAR) analysis has become one of the most effective approaches for optimizing lead compounds and designing new drugs. Although large number of quantum-chemical descriptors were defined and applied successfully, it is still a big challenge to develop a general quantum-chemical descriptor describing the bulk effects more directly and effectively. In this article, we defined a general quantum-chemical descriptor by characterizing the volume of electron cloud for specific substituent using the method of density functional theory. The application of our defined steric descriptors in the QSAR analysis of sulfonylurea analogues resulted in four QSAR models with high quality (the best model: q2 = 0.881, r2 = 0.901, n = 35, s = 0.401, F = 68.44), which indicated that this descriptor may provide an effective way for solving the problem how to directly describe steric effect in quantum chemistry-based QSAR studies. PMID:16868987

Xi, Zhen; Yu, Zhihong; Niu, Congwei; Ban, Shurong; Yang, Guangfu




E-print Network

......................................................................................... xvii CHEMICAL SYMBOLS AND FORMULAS Study St. Louis North County Site ­ FUSRAP Final May 1, 2003 ii TABLE OF CONTENTS VOLUME I LIST..............................................................................................................viii LIST OF FIGURES

US Army Corps of Engineers


Off-Site Access Study for NOSR 1. Draft.  

National Technical Information Service (NTIS)

The Off-site Access Study addresses the routes available for access to NOSR 1, the use of a funicular railroad, potential staging areas, the need and availability of railroad spurs, utility corridors, new water supply, and construction methodologies (sche...



DFT and electrochemical studies on nortriptyline oxidation sites.  


A study on the possible sites of oxidation and epoxidation of nortriptyline was performed using electrochemical and quantum chemical methods; these sites are involved in the biological responses (for example, hepatotoxicity) of nortriptyline and other similar antidepressants. Quantum chemical studies and electrochemical experiments demonstrated that the oxidation and epoxidation sites are located on the apolar region of nortriptyline, which will useful for understanding the molecule's activity. Also, for the determination of the compound in biological fluids or in pharmaceutical formulations, we propose a useful analytical methodology using a graphite-polyurethane composite electrode, which exhibited the best performance when compared with boron-doped diamond or glassy carbon surfaces. PMID:19172315

de Toledo, Renata A; Santos, Mauro C; Suffredini, Hugo B; Homem-de-Mello, Paula; Honorio, Kathia M; Mazo, Luiz H



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. PMID:21207999

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



Utah Energy-Facility-Siting Study. Phase II: Colorado Plateau.  

National Technical Information Service (NTIS)

The general purposes of the Great Basin Study were: to understand the balance between social/economic/resource/environmental interests in the study areas; to facilitate the siting of energy facilities in the study areas; and to reduce planning/constructio...



Second Information Technology in Education Study: SITES 2006 Technical Report  

ERIC Educational Resources Information Center

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

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



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)



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



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

Microsoft Academic Search

Based on studies with chimeras between (non-)gastric H,K-ATPase and Na,K-ATPase, a model for the ouabain binding site has\\u000a recently been presented (Qiu et al. J.Biol.Chem. 280 (2005) 32349). In this model, hydrogen bonds between specific amino acid\\u000a residues of Na,K-ATPase and hydroxyl groups of ouabain play a crucial role. In the present study, a series of ouabain analogues\\u000a were tested

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



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

NASA Technical Reports Server (NTRS)

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

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



Site-specific magnetization reversal studies of magnetite  

SciTech Connect

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

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



Quantum Analogue Computing  

E-print Network

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

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



Orally active prostacyclin analogue for cardiovascular disease.  


Prostacyclin has vasoprotective effects such as vasodilation and antiplatelet aggregatory activity. A relative deficiency of prostacyclin contributes to the pathogenesis of cardiovascular disease including pulmonary artery disease (PAH). Inconvenient intravenous dosing of prostacyclin led to the development of more stable, an orally active analogue: beraprost. It is a chemically stable prostacyclin analogue owing to its cyclo-pentabenzofuranyl structure and produces strong vasodilation and inhibition of platelet aggregation. To date, beraprost has been used in the treatment of PAH and peripheral arterial disease (PAD). Recently, we have shown that beraprost induces neovascularization in ischemic myocardium by enhancement of bone marrow cell mobilization. Interestingly, meta-analysis of clinical studies for PAD has shown that repeated administration of beraprost decreases the number of cardiovascular events. These results suggest that oral administration of beraprost has beneficial effects on cardiovascular disease. Orally active prostacyclin analogues, are promising drugs for the treatment of cardiovascular disease. PMID:20357744

Nagaya, N



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. PMID:22691718



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



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.  


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




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...


Overview of the Ridge 2000 Integrated Studies Sites  

Microsoft Academic Search

The Ridge 2000 program is in its fourth year and fieldwork at each of the Integrated Studies Sites (ISS) is in full swing. Multidisciplinary monitoring continues at the EPR ISS with seismic, temperature, and current data being continuously recorded. Long-term fluid sampling programs aimed at furthering our understanding of temporal variations in the chemistry of high-temperature hydrothermal vents are continuing.

C. Fisher



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


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

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



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

ERIC Educational Resources Information Center

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

Gregory, Martin



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


The present preliminary study aimed to shed light on the mechanisms underlying the development of insomnia. An analogue stressor (i.e., trauma video) was used to prevent presleep cognitive de-arousal. Subsequent changes in nocturnal sleep and sleep-related attentional processing were examined. Thirty-four participants were randomly assigned to either a cognitive arousal (trauma video; age: M = 22.9, SD = 4.3, 6 male, 11 female) or control (pleasant video; age: M = 23.8, SD = 5.8, 7 male, 10 female) condition. Although no significant differences were found for presleep cognitive de-arousal (p = .39), the cognitive arousal group experienced a significant worsening in sleep latency (p = .048, partial ?(2) = .12) and an increase in sleep-related attentional bias (p = .032, d = 0.51) following the manipulation. However, changes in sleep and attentional bias were not maintained. Vulnerability to stress did not significantly account for any change in attentional bias, arousal, or sleep. These findings challenge current conceptualizations of the development of insomnia, yet also supporting the notion that good sleep is a default state that protects individuals from sleep disturbance. PMID:24628110

Richardson, Cele; Gradisar, Michael; Pulford, Amanda



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


For several decades, people have been in contact with bisphenol A (BPA) primarily through their diet. Nowadays it is gradually replaced by an analogue, bisphenol S (BPS). In this study, we compared the effects of these two bisphenols in parallel with the positive control diethylstilbestrol (DES) on different hepatocyte cell lines. Using a cellular impedance system we have shown that BPS is less cytotoxic than BPA in acute and chronic conditions. We have also demonstrated that, contrary to BPA, BPS is not able to induce an increase in intracellular lipid and does not activate the PXR receptor which is known to be involved in part, in this process. In parallel, it failed to modulate the expression of CYP3A4 and CYP2B6, the drug transporter ABCB1 and other lipid metabolism genes (FASN, PLIN). However, it appears to have a weak effect on GSTA4 protein expression and on the Erk1/2 pathway. In conclusion, in contrast to BPA, BPS does not appear to induce the metabolic syndrome that may lead to non-alcoholic fatty liver disease (NAFLD), in vitro. Although we have to pay special attention to BPS, its use could be less dangerous concerning this toxicological endpoint for human health. PMID:24793377

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



A pilot study of evaluation of the antioxidative activity of resveratrol and its analogue in a 6-month feeding test in young adult mice.  


Resveratrol, a polyphenolic phytoalexin, has free-radical scavenging activity and we found that it induces chromosomal aberrations, micronuclei, and sister chromatid exchanges in vitro. We synthesized its analogue 4-hydroxy-trans-stilbene (4-OH) and found that it has the same in vitro clastogenic activities as resveratrol, suggesting that the 4' hydroxy group of resveratrol is responsible for the effect. We fed resveratrol and 4-OH to young adult ICR mice at 0, 0.2, 2, or 20 ppm in their standard powder diet for 6 months and investigated the antioxidative effects. Half of each group was given 3000 ppm potassium bromate (KBrO(3)) in water for the last week to cause oxidative damage. Body weight gain tended to increase in males at 0.2 ppm resveratrol or 4-OH, and in females at 2 ppm 4-OH. Micronucleus (MN) analysis in bone marrow erythrocytes showed that the KBrO(3) tendency to induce MN was not prevented by the dietary resveratrol or 4-OH, which themselves did not induce MN under the present conditions. In this pilot study, resveratrol and 4-OH showed no obvious effect, either beneficial or adverse, at doses that are feasible in daily life for humans. PMID:18155340

Matsuoka, A; Kodama, Y; Fukuhara, K; Honda, S; Hayashi, M; Sai, K; Hasebe, M; Fujiwara, Y



Wildlife studies on the Hanford site: 1994 Highlights report  

SciTech Connect

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

Cadwell, L.L. [ed.



Chymotrypsin substrate analogues inhibit endocytosis of insulin and insulin receptors in adipocytes  

PubMed Central

To explore the possible role of proteolytic step(s) in receptor- mediated endocytosis of insulin, the effects of inhibitors of various classes of proteases on the internalization process were studied in isolated rat adipocytes. Intracellular accumulation of receptor-bound 125I-insulin at 37 degrees C was quantitated after rapidly dissociating surface-bound insulin with an acidic buffer (pH 3.0). Of the 23 protease inhibitors tested, only chymotrypsin substrate analogues inhibited insulin internalization. Internalization was decreased 62-90% by five different chymotrypsin substrate analogues: N-acetyl-Tyr ethyl ester, N-acetyl-Phe ethyl ester, N-acetyl-Trp ethyl ester, benzoyl-Tyr ethyl ester, and benzoyl-Tyr amide. The effect of the substrate analogues in inhibiting insulin internalization was dose-dependent, reversible, and required the full structural complement of a chymotrypsin substrate analogue. Cell surface receptor number was unaltered at 12 degrees C. However, concomitant with their inhibition of insulin internalization at 37 degrees C, the chymotrypsin substrate analogues caused a marked increase (160-380%) in surface-bound insulin, indicating trapping of insulin-receptor complexes on the cell surface. Additionally, 1 mM N-acetyl-Tyr ethyl ester decreased overall insulin degradation by 15-20% and also prevented the chloroquine-mediated increase in intracellular insulin, further indicating that surface- bound insulin was prevented from reaching intracellular chloroquine- sensitive degradation sites. The internalization of insulin receptors that were photoaffinity labeled on the cell surface with B2(2-nitro-4- azidophenylacetyl)-des-PheB1-insulin was also inhibited 70-90% by the five chymotrypsin substrate analogues, as determined by the effects of the analogues on the accumulation of trypsin-insensitive (intracellular) 440-kD intact labeled receptors. In summary, these results show that chymotrypsin substrate analogues efficiently inhibit the internalization of insulin and insulin receptors in adipocytes and implicate a possible role for endogenous chymotrypsin-like enzyme(s) or related substances in receptor-mediated endocytosis of insulin. PMID:2877995



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

NASA Astrophysics Data System (ADS)

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

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



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.



Characterization of the radioiodinated analogue of SCH 23390: in vitro and in vivo D-1 dopamine receptor binding studies  

SciTech Connect

A new radioiodinated molecule, /sup 125/I-SCH 38840 (previously referred to as /sup 125/I-SCH 23982), has been recently reported to be a D-1 dopamine receptor ligand. The current study confirms and expands the characterization of both the radiolabeled and unlabeled forms of this compound, as well as describing the development of an in vivo D-1 receptor binding assay utilizing the /sup 125/I-SCH 38840. The binding of /sup 125/I-SCH 38840 to rat striatal membranes, in vitro, was saturable and exhibited a K/sub D/ of 1.47 nM. Competition studies using /sup 125/I-SCH 38840 exhibited a pharmacological profile consistent with the proposal that /sup 125/I-SCH 38840 was binding to the D-1 receptor. Further studies with the unlabeled SCH 38840 demonstrated that it inhibited dopamine-stimulated adenylate cyclase with a K/sub I/ of 66.1 nM, indicating that SCH 38840 was acting as a D-1 antagonist. Behavioral studies demonstrated that SCH 38840, blocked conditioned avoidance responding in rats, a measurement considered predictive of anti-psychotic activity in man. In vivo binding of /sup 125/I-SCH 38840 to rat striatum following s.c. administration was specific.

McQuade, R.D.; Chipkin, R.; Amlaiky, N.; Caron, M.; Iorio, L.; Barnett, A.



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


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

Rai, Balwant; Kaur, Jasdeep



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.



Nevada Test Site tortoise population monitoring study. Final report  

SciTech Connect

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

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



[Study of the nucleation sites in collagen mineralization].  


By comparing IR spectra of collagen, collagen/CaCl2 and collagen/calcium phosphate, it was found that intensities of amide I, II and III bands were significantly decreased after mineralization. Band amide I shifted to wards lower wave number. This shift indicated chemical interaction between carboxyl groups and Ca ions formed in the mineralization. The result indicated that there was another nucleation site, i.e. carbonyl [structure: see text] on collagen, besides the previous reported nucleation site of carboxyl (-COOH) on collagen. The decrease of amide I peak intensity was mainly due to blockage of C=O stretch. Comparing the IR spectra of demineralized collagen and pure collagen, amide I, II and III peaks intensity and position were almost the same. When the mineral dissolved, amide peaks rebounded, which indicated that the crystals nucleated on these sites enwrapped the groups and blocked the groups vibration. The decreases of peak intensity of amide I, II and III were different due to their different vibration modes. The result confirmed that the carbonyl group was one kind of the nucleation site during collagen mineralization. The relationship between the process of collagen mineralization and variety of amide bonds was also studied. PMID:15769040

Huang, Zhao-long; Zhang, Wei; Cui, Fu-zhai



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


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



Off-site Access Study for NOSR 1. Draft  

SciTech Connect

The Off-site Access Study addresses the routes available for access to NOSR 1, the use of a funicular railroad, potential staging areas, the need and availability of railroad spurs, utility corridors, new water supply, and construction methodologies (schedule, manpower, locations for modular construction facilities, etc.) for optional development of the Reserves. Information on schedules and manpower (both construction and operation) is an important input to the socioeconomic study, and the location of modular construction facilities, railroads, staging areas, etc., identify potential demographic regions of population. Public access to the NOSR property is presently limited to two unimproved roadways, (Cow Creek and JQS Trail); however, several private roads provide access to the site. The NOSR is open to public use for recreation and hunting. Commercially, the property is used for grazing of cattle and sheep. Surface uses of the NOSR site are managed by the Bureau of Land Management. To develop an oil shale-producing facility on the Reserve, suitable access for a large work force must be constructed. This study of access roads includes definition of three methods of constructing a plant and identifies 10 potential routes suitable for the transportation requirements during construction and operation of the oil shale facilities. 50 figures, 1 table.

Not Available



Overview of the Ridge 2000 Integrated Studies Sites  

NASA Astrophysics Data System (ADS)

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

Fisher, C.



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


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



Comparative study of midtrimester termination of pregnancy using hypertonic saline, ethacridine lactate, prostaglandin analogue and iodine-saline.  


The study consisted of terminations of 200 cases of second trimester pregnancies ranging from 14 weeks to 20 weeks. Out of these 200 cases, in 50 cases intra-amniotic instillation of 20% hypertonic saline (200 ml) was done after withdrawing 35-200 ml of amniotic fluid. Ethacridine lactate was instilled in 50 cases extra-amniotically. Prostaglandin F2 alpha was injected intramuscularly at regular intervals in 50 cases. Fifty cases of pregnancies were terminated with extra-amniotic instillation of 5% povidone-iodine solution mixed with normal saline. Comparison was made among all the methods regarding instillation-abortion interval, completeness of abortion, failure of the procedure and postoperative complications. Solution of 5% povidone-iodine in normal saline was found to be comparable in all aspects to other methods and above all a much cheaper alternative for poor patients. Success rate was highest with iodine-saline solution (100%) followed by ethacridine lactate (98%), hypertonic saline (96%) and lowest with prostaglandin F2 alpha (90%). PMID:1460314

Allahbadia, G



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.



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


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

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



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


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

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



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.)



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. PMID:9337848

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



Radionuclide migration studies at the Nevada Test Site  

SciTech Connect

The United States government routinely tests nuclear devices at the Nevada Test Site (NTS) in southern Nevada. A significant amount of radioactive material exists underground at the NTS with no containers or engineered barriers to inhibit its subsequent migration. The Department of Energy has sponsored for many years a research program on radionuclide movement in the geologic media at this location. Goals of this research program are to measure the extent of movement of radionuclides away from underground explosion sites and to determine the mechanisms by which such movement occurs. This program has acquired significance in another aspect of nuclear waste management because of the Yucca Mountain Project. Yucca Mountain at the NTS is being intensively studied as the possible site for a mined repository for high level nuclear waste. The NTS provides a unique setting for field studies concerning radionuclide migration; there is the potential for greatly increasing our knowledge of the behavior of radioactive materials in volcanogenic media. This review summarizes some of the significant findings made under this research program at the NTS and identifies reports in which the details of the research may be found. 36 refs., 4 figs.

Thompson, J.L.



Choose study sites carefully |

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


[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.




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))



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. PMID:19342233

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



IAU Extended Case Studies of Key Astronomical Heritage Sites  

NASA Astrophysics Data System (ADS)

Following a directive from the IAU in 2010, members of the WG have been developing 11 ``extended case studies'' in order to explore and clarify some of the key general issues that can arise in the particular case of astronomical heritage sites. Specific extended case studies might well facilitate the eventual preparation of a full nomination dossier should a State Party decide to prepare one, but this is not the aim of our work. While dark sky areas cannot in themselves be recognized by UNESCO as specific types or categories of World Heritage cultural or natural property, the WG has a strong interest in how dark sky issues might best be represented within nomination dossiers for various types of astronomical heritage site. For this reason, more than half of the extended case studies relate in one way or another to such issues. These case studies will be presented to the General Assembly for formal approval at the second plenary session, as part of the General Secretary's report. This session will provide a more detailed presentation of the ECSs and a discussion forum where delegates can give their reactions and feedback and raise issues.

Ruggles, Clive



Results and implications of eleven site specific biomass feasibility studies  

SciTech Connect

Beginning in 1993, the U.S. Department of Energy (DOE) through the National Renewable Energy Laboratory (NREL) and in partnership with the Electric Power Research Institute (EPRI) sponsored eleven site-specific feasibility studies that examined integrated systems for producing energy from biomass. Feedstocks included in these studies ranged from bagasse to alfalfa to wood chips and switchgrass. Biomass combustion, gasification, and pyrolysis technology was examined in systems ranging from biomass co-firing with coal in existing boilers to advanced integrated gasification combined cycle systems. These studies not only brought together entities that have, in several cases, formed on-going project teams, but helped reduce the uncertainty in cost estimates for a variety of promising biomass technologies. This paper will summarize the significant results of these eleven studies and discuss their implications for biomass power generation technologies domestically and in the international market.

Craig, K.R. [National Renewable Energy Lab., Golden, CO (United States); Reed, M. [Dept. of Energy, Washington, DC (United States)



Analogues of 3-hydroxyisoxazole-containing glutamate receptor ligands based on the 3-hydroxypyrazole-moiety: design, synthesis and pharmacological characterization.  


A series of analogues of the glutamate receptor ligands (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) and AMOA were synthesized in which the 3-hydroxyisoxazole moiety was exchanged for a 3-hydroxypyrazole moiety. This exchange enables further substitution at the additional nitrogen atom in the heterocyclic core. Several of the analogues have activity at AMPA receptors equipotent to the antagonist ATPO, demonstrating that additional substitution can be accommodated in the antagonist binding site. Modelling studies offer an explanation for the pharmacological pattern observed for the compounds and suggest that this scaffold may be developed further to obtain subtype selective antagonists. PMID:24848194

Jørgensen, Lars; Nielsen, Birgitte; Pickering, Darryl S; Kristensen, Anders S; Frydenvang, Karla; Madsen, Ulf; Clausen, Rasmus P



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. 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.



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

SciTech Connect

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

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



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. PMID:22989235

Subramanian, Thangaiah; Pais, June E.; Liu, Suxia; Troutman, Jerry M.; Suzuki, Yuta; Subramanian, Karunai Leela; Fierke, Carol; Andres, Douglas A.; Spielmann, H. Peter



Substrate Overlap between Mrp4 and Abcg2/Bcrp Affects Purine Analogue Drug Cytotoxicity and Tissue Distribution  

E-print Network

studies have indicated that Mrp4 transports substrates in common with Abcg2, most recently camptothecin analogues (6, 7). Because Abcg2 also transports and confers resistance to camptothecin analogues (8, 9

Hrycyna, Christine A.


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


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

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



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

Microsoft Academic Search

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

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



Two types of urate binding sites on hemocyanin from the crayfish Astacus leptodactylus: an ITC study.  


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




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...


An electrical analogue of the entire human circulatory system  

Microsoft Academic Search

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

L. de Pater; Jw. van den Berg



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



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. In another event, 248 thousand curies of tritium was disposed of in an overpack emplaced 6 m 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, ending in 1990, was found. In a third study, upward tritium migration in the soil, resulting in releases in the atmosphere were observed in a greater confinement disposal test. 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. Emanation of tritium from the buried containers has been increasing since disposal, but no significant migration was found four years following backfilling of the disposal hole.

Schulz, R.K.; Weaver, M.O.



Cardiac specific effects of thyroid hormone analogues.  


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

Danzi, S; Klein, I



Hydrological studies of a tropical reservoir site, Nigeria  

NASA Astrophysics Data System (ADS)

The study area, a potential reservoir site, is situated in the tropical belt and was chosen by an earlier worker after geophysical and geotechnical investigations. The area is underlain by the Precambrian Basement Complex. The aim of the present study is to determine whether the site could provide adequate water for a proposed reservoir. The climate of the area is of marked wet and dry seasons, with a tropical rainforest-type of vegetation. The catchment area is about 744.40 km 2. The population of the communities is presently about 528,169 (1963 census), and it is estimated to be approximately 600,000 by the year 2005. This paper provides an estimation of the water need of the expected population. Owing to scanty hydrological data for the Owena River, its expected discharge was extrapolated by comparison with the neighbouring Shasha River. From calculations, the following results were obtained: (1) expected available water within the catchment area, 256.75 × 10 6 m 3 per year; (2) expected reservoir capacity, 13.73 × 10 6 m 3; (3) average discharge of the Owena River at the investigation point, 2.91 m 3 s -1 over a period of one year; (4) expected water need of the communities (of 600,000 persons), 4.38 × 10 6 m 3 per year, about 0.5 m 3 s -1. On the basis of the expected excess water over demand, losses through evapo-transpiration and seepage, as well as the possible availability of building materials within the area, it is recommended that the creation of an earth dam reservoir is feasible.

Alabo, E. H.


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

NASA Astrophysics Data System (ADS)

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

Lebeuf, Martin


Site characterization for field radionuclide migration studies in Climax granite  

SciTech Connect

Radionuclide migration experiments in fractured granite at the Climax Stock, Nevada Test Site, are needed to compare field and laboratory measured retardation factors to determine whether laboratory studies accurately reflect in situ conditions. Initial field activities have concentrated on hydrological investigations to determine whether the fractures in Climax granite are suitable for migration experiments. A critical question was whether we could isolate a single vertical fracture between two boreholes and establish flow along that fracture from an upper to a lower borehole. Of the ten fractures tested, one fracture would not take water at pressures up to 200 psig for 24 hours. Several fractures were so permeable they accepted water at a rate which exceeded the pumping capacity of the equipment. Other fractures failed to show a connection between the two boreholes. In two fractures, we were able to establish a circulating system with up to 90 percent of the injected water being recovered. Constant pressure injection tests were conducted. Intrinsic permeabilities of 33 and 75 ({mu}m){sup 2} were estimated using a radial nonsteady flow model. These values correspond to effective fracture apertures of 20 and 30 {mu}m respectively. Concurrent with the hydraulic testing activities is a study of the Climax ground-water chemistry. Our analyses show the natural water to be very different in composition from the granite equilibrated water used in laboratory sorption studies. This paper includes the results of the hydrogeological and geochemical investigations, and describes the overall experimental design plans for the radionuclide migration experiments.

Isherwood, D.; Raber, E.; Stone, R.



Ecosystem dynamics at six contrasting sites: a generic modelling study  

NASA Astrophysics Data System (ADS)

A pelagic marine ecosystem simulation model ERSEM-2004, developed from the European Regional Seas Ecosystem Model (ERSEM II), is presented along with a parameter set applicable to six highly contrasting sites, ranging from a temperate mixed shelf station to a permanently stratified tropical deep-ocean station. The physical characteristics are simulated by direct coupling to a 1D vertically resolved turbulence model, parameterised for each site. A mathematical description of the pelagic ecosystem model is presented. Additions to ERSEM II's well resolved community and decoupling of gross production and ambient nutrient concentration include variable carbon to chlorophyll ratios, coupling of bacterial production to nutrient availability, improved resolution of the organic particulate and dissolved fractions and developments to the mesozooplankton description. Comparison of seasonally depth resolved and integrated properties illustrates that the model produces a wide range of community dynamics and structures that can be plausibly related to variations in mixing, temperature, irradiance and nutrient supply. The spatial-temporal variability in key environmental indicators only partially correlates with the spatial-temporal variability in community structure ( ?<0.5). Thus we infer that the complexity of the model's trophic structure and hence that of the marine system is important in defining the ecological response to the environment. A physical description of a marine domain may not be an adequate indicator of marine community structure or function. Particularly, lysis and grazer response are identified as important processes that define ecosystem dynamics and community structure. There is a closer correlation ( ?>0.75) between spatial-temporal variability in community structure (biomass) and function (production). ERSEM-2004 is shown to be a robust model that is capable of representing a range of systems commonly described in the marine system. Consequently, the model is proposed as a potential basis for an ecosystem-based management tool that may, with appropriate physical representation, be applied over large geographic and temporal scales with utility to both heuristic and predictive studies of the marine lower trophic levels.

Blackford, J. C.; Allen, J. I.; Gilbert, F. J.



A Virtual Collaborative Environment for Mars Surveyor Landing Site Studies  

NASA Technical Reports Server (NTRS)

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

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



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

NASA Astrophysics Data System (ADS)

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

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



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

NASA Astrophysics Data System (ADS)

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

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



A Virtual Web Environment for Mars Landing Site Studies  

NASA Technical Reports Server (NTRS)

A collection of web tools is available for both the landing site and broader Mars science communities to better utilize, visualize, and analyze Mars Global Surveyor data. These tools have grown out of a two year effort between the Center for Mars Exploration (CMEX), and the NAS data visualization group at NASA Ames Research Center (ARC), to promote interactions among the planetary community and to coordinate landing site activities. The web site will continue to evolve over the next several years as new tools and features are added to support the ongoing Mars missions.

Gulick, V. C.; Deardorff, D. G.; Briggs, G. A.



Causal structure of analogue spacetimes  

NASA Astrophysics Data System (ADS)

The so-called 'analogue models of general relativity' provide a number of specific physical systems, well outside the traditional realm of general relativity, that nevertheless are well-described by the differential geometry of curved spacetime. Specifically, the propagation of perturbations in these condensed matter systems is described by 'effective metrics' that carry with them notions of 'causal structure' as determined by an exchange of quasi-particles. These quasi-particle-induced causal structures serve as specific examples of what can be done in the presence of a Lorentzian metric without having recourse to the Einstein equations of general relativity. (After all, the underlying analogue model is governed by its own specific physics, not necessarily by the Einstein equations.) In this paper we take a careful look at what can be said about the causal structure of analogue spacetimes, focusing on those containing quasi-particle horizons, both with a view to seeing what is different from standard general relativity, and what the similarities might be. For definiteness, and because the physics is particularly simple to understand, we will phrase much of the discussion in terms of acoustic disturbances in moving fluids, where the underlying physics is ordinary fluid mechanics, governed by the equations of traditional hydrodynamics, and the relevant quasi-particles are the phonons. It must however be emphasized that this choice of example is only for the sake of pedagogical simplicity and that our considerations apply generically to wide classes of analogue spacetimes.

Barceló, Carlos; Liberati, Stefano; Sonego, Sebastiano; Visser, Matt



New routes towards reutericyclin analogues.  


A range of N-acylpyrrolo[3,4-c]isoxazoles and derived N-acyltetramides has been prepared via a nitrile oxide dipolar cycloaddition approach, as analogues of the acyltetramic acid metabolite reutericyclin, of interest for its antibiotic potential against Gram-positive bacteria including hospital-acquired infections of resistant Clostridium difficile. PMID:24382380

Jones, Raymond C F; Bullous, James P; Law, Carole C M; Elsegood, Mark R J



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

SciTech Connect

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

Not Available



Nitroimidazolyl hydrazones are better amoebicides than their cyclized 1,3,4-oxadiazoline analogues: In vitro studies and Lipophilic efficiency analysis.  


Two series of compounds with hydrazone derivatives (HZ1-HZl2, series 1) and oxadiazoline derivatives (OZ1-OZ12, series 2) of the 2-methyl-5-nitro-1H-imidazole scaffold were designed and synthesized. Physicochemical properties and Lipophilic efficiency (LipE) analysis predicted higher intrinsic quality of the acylhydrazone derivatives (series 1) than their corresponding oxadiazoline analogues (series 2). In vitro antiamoebic results supported the above findings and validated that the acylhydrazone derivatives (HZ1-HZl2) show better activity than the oxadiazoline derivatives (OZ1-OZ12). MTT assay, using HepG2 cell line, revealed noncytotoxic nature of the compounds. The most promising results were observed for compounds HZ5 (IC50 = 0.96 ?M) and HZ9 (IC50 = 0.81 ?M) both in silico and in vitro. Analysis of the Lipophilic efficiency (LipE) of the compounds provided new insight for the design of potent and selective amoebicides. PMID:23644202

Wani, Mohmmad Younus; Bhat, Abdul R; Azam, Amir; Athar, Fareeda



Biodegradation of bisphenol A and its halogenated analogues by Cunninghamella elegans ATCC36112  

Microsoft Academic Search

Bisphenol A and its halogenated analogues are commonly used industrial chemicals with strong toxicological effects over many\\u000a organisms. In this study, metabolic fate of bisphenol A and its halogenated analogues were evaluated with Cunninghamella elegans ATCC36112. Bisphenol A and related analogues were rapidly transformed into several metabolites by C. elegans within 2–4 days. Detailed analysis of metabolites reveals that both phase

Young Soo Keum; Hye Ri Lee; Hee Won Park; Jeong-Han Kim



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

E-print Network

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


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

NASA Technical Reports Server (NTRS)

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

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



The voluntary siting process, a case study in New Jersey.  


The Low-Level Radioactive Waste Policy Act of 1980 and its 1985 Amendments has not provided new disposal capacity within the United States; however, sufficient disposal capacity currently exists to handle today's disposal needs. Politics, opposition groups, and public mistrust in government have combined to limit the possibilities for establishing new disposal facilities. In 2000, New Jersey (NJ and Connecticut (CT), as members of the Northeast Compact for the disposal of low-level radioactive waste, admitted South Carolina (SC) to their compact, renaming it as the "Atlantic Compact." The advantage to SC is that they are able to prevent disposal of waste from outside the Compact. The advantage to NJ and CT is that they are guaranteed waste disposal for approximately the next 50 years, or until all currently operating nuclear power plants in the states are decommissioned. This paper details the process, much of it not following the scientific method, to try to site a low-level waste facility in NJ. With the formation of the NJ Siting Board in 1987, an effort was made to locate a site using deterministic criteria; however, in 1992, the Board shifted to a voluntary process. In 1998, the Board made the determination that there was adequate capacity for waste disposal and ended active siting. In 2000, the opportunity to form the Atlantic Compact ended siting through an out-of-state solution. While it is not clear that the voluntary process would have ultimately worked in NJ, it has worked in Canada and the process may be one of the few mechanisms for the siting of any type of hazardous material disposal facility. Also, other states still have to decide what they will do after 2008 when Barnwell is no longer open to them. PMID:14744073

Stencel, Joseph R; Lee, Kenneth Y



Overview of analogue science activities at the McGill Arctic Research Station, Axel Heiberg Island, Canadian High Arctic  

Microsoft Academic Search

The Canadian High Arctic contains several of the highest fidelity Mars analogue sites in the world. Situated at nearly 80° north, Expedition Fjord on Axel Heiberg Island is located within a polar desert climate, with the surrounding landscape and conditions providing an invaluable opportunity to examine terrestrial processes in a cold, dry environment. Through the Canadian Space Agency's Analogue Research

Wayne Pollard; Tim Haltigin; Lyle Whyte; Thomas Niederberger; Dale Andersen; Christopher Omelon; Jay Nadeau; Miles Ecclestone; Martin Lebeuf



In Vitro Structure-Activity Relationship of Re-cyclized Octreotide Analogues  

PubMed Central

Introduction Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods Various octreotide analogue sequences and coordination systems (e.g., S2N2 and S3N) were synthesized and cyclized with non-radioactive Re. In vitro competitive binding assays with 111In-DOTA-Tyr3-octreotide in AR42J rat pancreatic tumor cells yielded IC50 values as a measure of somatostatin receptor affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr3-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue’s pharmacophore. Results Only two of the eleven Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr3-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal-cyclization of octreotide analogues via NS3 and N2S2 coordination forming 5- and 6- membered chelate rings. In vivo biodistribution studies are underway of 99m Tc- cyclized analogue 4. PMID:20610157

Dannoon, Shorouk F.; Bigott-Hennkens, Heather M.; Ma, Lixin; Gallazzi, Fabio; Lewis, Michael R.; Jurisson, Silvia S.



Triple-helical transition state analogues: a new class of selective matrix metalloproteinase inhibitors.  


Alterations in activities of one family of proteases, the matrix metalloproteinases (MMPs), have been implicated in primary and metastatic tumor growth, angiogenesis, and pathological degradation of extracellular matrix (ECM) components, such as collagen and laminin. Since hydrolysis of the collagen triple-helix is one of the committed steps in ECM turnover, we envisioned modulation of collagenolytic activity as a strategy for creating selective MMP inhibitors. In the present study, a phosphinate transition state analogue has been incorporated within a triple-helical peptide template. The template sequence was based on the alpha1(V)436-450 collagen region, which is hydrolyzed at the Gly(439)-Val(440) bond selectively by MMP-2 and MMP-9. The phosphinate acts as a tetrahedral transition state analogue, which mimics the water-bound peptide bond of a protein substrate during hydrolysis. The phosphinate replaced the amide bond between Gly-Val in the P1-P1' subsites of the triple-helical peptide. Inhibition studies revealed Ki values in the low nanomolar range for MMP-2 and MMP-9 and low to middle micromolar range for MMP-8 and MMP-13. MMP-1, MMP-3, and MT1-MMP/MMP-14 were not inhibited effectively. Melting of the triple-helix resulted in a decrease in inhibitor affinity for MMP-2. The phosphinate triple-helical transition state analogue has high affinity and selectivity for the gelatinases (MMP-2 and MMP-9) and represents a new class of protease inhibitors that maximizes potential selectivity via interactions with both prime and nonprime active site subsites as well as with secondary binding sites (exosites). PMID:17672455

Lauer-Fields, Janelle; Brew, Keith; Whitehead, John K; Li, Shunzi; Hammer, Robert P; Fields, Gregg B




EPA Science Inventory

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



EPA Science Inventory

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


Ecosystem dynamics at six contrasting sites: a generic modelling study  

Microsoft Academic Search

A pelagic marine ecosystem simulation model ERSEM-2004, developed from the European Regional Seas Ecosystem Model (ERSEM II), is presented along with a parameter set applicable to six highly contrasting sites, ranging from a temperate mixed shelf station to a permanently stratified tropical deep-ocean station. The physical characteristics are simulated by direct coupling to a 1D vertically resolved turbulence model, parameterised

J. C. Blackford; J. I. Allen; F. J. Gilbert



Probing human red cone opsin activity with retinal analogues.  


Retinal analogues have been used to probe the chromophore binding pocket and function of the rod visual pigment rhodopsin. Despite the high homology between rod and cone visual pigment proteins, conclusions drawn from rhodopsin studies should not necessarily be extrapolated to cone visual pigment proteins. In this study, the effects of full-length and truncated retinal analogues on the human red cone opsin's ability to activate transducin, the G protein in visual transduction, were assessed. The result with beta-ionone (6) confirms that a covalent bond is not necessary to deactivate the red cone opsin. In addition, several small compounds were found able to deactivate this opsin. However, as the polyene chain is extended in a trans configuration beyond the 9-carbon position, the analogues became agonists up to all-trans-retinal (3). The 22-carbon analogue (2) appeared to be neither an agonist nor an inverse agonist. Although the all-trans-C17 (5) analogue was an agonist, the 9-cis-C17 (11) compound was an inverse agonist, a result that differs from that with rhodopsin. These results suggest that the red cone opsin has a more open structure in the chromophore binding region than rhodopsin and its activation or deactivation as a G-protein receptor may be less selective than rhodopsin. PMID:21314100

Kono, Masahiro; Crouch, Rosalie K



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

PubMed Central

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

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



Optical Properties of Titan's Aerosol Analogues  

NASA Astrophysics Data System (ADS)

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

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



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

Microsoft Academic Search

One issue that public librarians must consider when planning Web site design is accessibility for patrons with disabilities. This article reports a study of Web site accessibility of public libraries in Georgia. The focus of the report is whether public libraries use accessible guidelines and standards in making their Web sites accessible. An e-mail survey asked each of the 58

Emma Ingle; Ravonne A. Green; Julia Huprich



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

ERIC Educational Resources Information Center

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

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



Assessment of Reliability of Multi-site Neuroimaging Via Traveling Phantom Study  

E-print Network

analysis of neu- roimaging data of traveling human phantoms used for cross-site validation. We focus on the analysis of magnetic resonance image data including intra- and inter- site comparison. Locations and power analysis in new multi-site clinical studies. 1 Introduction Image data from patient populations

Prastawa, Marcel


Classification and mapping forest sites using geographic information system (GIS): a case study in Artvin Province.  


The productivity of forest sites has been indirectly determined with solo wood production objective in forest management. Forest site productivity should, however, be determined directly in order to implement ecosystem based multipurpose forest management philosophy. This article tackles the problem in distinguishing and mapping forest sites using both direct method and indirect method in Genya Mountain located in central of Artvin State Forest Enterprise. About 112 sample plots were designed and distributed over the area. In each sample plot, soil samples were collected and the classical timber inventory measurements were taken. According to direct method, Soil Moisture Regime (SMR) method is preferred due to a water deficiency in the study area. Water holding capacity was used as an essential criterion for the classification of the forest site. Forest site classifications were assigned regarding the physiographic factors such as landform, aspect, and slope. Five different forest sites classes; dry, moderate fresh, fresh, humid and hygric were determined. According to direct method, the guiding curve was used to generate anamorphic site index (SI) equations and three site index classes; good (SI=I-II), medium (SI=III) and low (SI=IV-V) were determined. Some important differences between the methods were realized. The forest sites determined with site index estimation method indicate that site index I and II is 505.99 ha, III 1095.79 ha and IV and V 992.95 ha, whereas forest sites determined with direct method related to dry site of 937.58 ha, moderate fresh site of 931.90 ha, fresh site of 1,797.71 ha, humid site of 80.48 ha and hygric site of 356.55 ha. The forest site maps of both methods were created using GIS functions. The forest sites of open and degraded areas should be determined according to direct method. PMID:17564804

Altun, Lokman; Baskent, Emin Zeki; Gunlu, Alkan; Kadiogullari, Ali Ihsan



Studies of Current Circulation at Ocean Waste Disposal Sites  

NASA Technical Reports Server (NTRS)

The author has identified the following significant results. Acid waste plume was observed in LANDSAT imagery fourteen times ranging from during dump up to 54 hours after dump. Circulation processes at the waste disposal site are highly storm-dominated, with the majority of the water transport occurring during strong northeasterlies. There is a mean flow to the south along shore. This appears to be due to the fact that northeasterly winds produce stronger currents than those driven by southeasterly winds and by the thermohaline circulation. During the warm months (May through October), the ocean at the dump site stratifies with a distinct thermocline observed during all summer cruising at depths ranging from 10 to 21 m. During stratified conditions, the near-bottom currents were small. Surface currents responded to wind conditions resulting in rapid movement of surface drogues on windy days. Mid-depth drogues showed an intermediate behavior, moving more rapidly as wind velocities increased.

Klemas, V. (principal investigator); Davis, G.; Henry, R.



Wildlife studies on the Hanford Site: 1993 Highlights report  

SciTech Connect

The Pacific Northwest Laboratory (PNL) Wildlife Resources Monitoring Project was initiated by DOE to track the status of wildlife populations to determine whether Hanford operations affected them. The project continues to conduct a census of wildlife populations that are highly visible, economically or aesthetically important, and rare or otherwise considered sensitive. Examples of long-term data collected and maintained through the Wildlife Resources Monitoring Project include annual goose nesting surveys conducted on islands in the Hanford Reach, wintering bald eagle surveys, and fall Chinook salmon redd (nest) surveys. The report highlights activities related to salmon and mollusks on the Hanford Reach of the Columbia River; describes efforts to map vegetation on the Site and efforts to survey species of concern; provides descriptions of shrub-steppe bird surveys, including bald eagles, Canada geese, and hawks; outlines efforts to monitor mule deer and elk populations on the Site; and describes development of a biological database management system.

Cadwell, L.L. [ed.



UV disinfection pilot plant study at the Savannah River Site  

SciTech Connect

An ultraviolet light disinfection system pilot plant was operated at the Savannah River Site Central Shops sanitary wastewater treatment package plant July 14, 1992 through August 13, 1992. The purpose was to determine the effectiveness of ultraviolet light disinfection on the effluent from the small package-type wastewater treatment plants currently used on-site. This pilot plant consisted of a rack of UV lights suspended in a stainless steel channel through which a sidestream of effluent from the treatment plant clarifier was pumped. Fecal coliform analyses were performed on the influent to and effluent from the pilot unit to verify the disinfection process. UV disinfection was highly effective in reducing fecal coliform colonies within NPDES permit limitations even under process upset conditions. The average fecal coliform reduction exceeded 99.7% using ultraviolet light disinfection under normal operating conditions at the package treatment plants.

Huffines, R.L.; Beavers, B.A.



UV disinfection pilot plant study at the Savannah River Site  

SciTech Connect

An ultraviolet light disinfection system pilot plant was operated at the Savannah River Site Central Shops sanitary wastewater treatment package plant July 14, 1992 through August 13, 1992. The purpose was to determine the effectiveness of ultraviolet light disinfection on the effluent from the small package-type wastewater treatment plants currently used on-site. This pilot plant consisted of a rack of UV lights suspended in a stainless steel channel through which a sidestream of effluent from the treatment plant clarifier was pumped. Fecal coliform analyses were performed on the influent to and effluent from the pilot unit to verify the disinfection process. UV disinfection was highly effective in reducing fecal coliform colonies within NPDES permit limitations even under process upset conditions. The average fecal coliform reduction exceeded 99.7% using ultraviolet light disinfection under normal operating conditions at the package treatment plants.

Huffines, R.L.; Beavers, B.A.



Chemical tailoring of teicoplanin with site-selective reactions.  


Semisynthesis of natural product derivatives combines the power of fermentation with orthogonal chemical reactions. Yet, chemical modification of complex structures represents an unmet challenge, as poor selectivity often undermines efficiency. The complex antibiotic teicoplanin eradicates bacterial infections. However, as resistance emerges, the demand for improved analogues grows. We have discovered chemical reactions that achieve site-selective alteration of teicoplanin. Utilizing peptide-based additives that alter reaction selectivities, certain bromo-teicoplanins are accessible. These new compounds are also scaffolds for selective cross-coupling reactions, enabling further molecular diversification. These studies enable two-step access to glycopeptide analogues not available through either biosynthesis or rapid total chemical synthesis alone. The new compounds exhibit a spectrum of activities, revealing that selective chemical alteration of teicoplanin may lead to analogues with attenuated or enhanced antibacterial properties, in particular against vancomycin- and teicoplanin-resistant strains. PMID:23692563

Pathak, Tejas P; Miller, Scott J



Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12.  


A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed substituents, indicating that the alpha-face of the lactone ring is in close contact with the binding site when the inhibitor is bound to the enzyme. PMID:7830270

Nielsen, S F; Thastrup, O; Pedersen, R; Olsen, C E; Christensen, S B



Inhibition of glutamate racemase by substrate-product analogues.  


D-Glutamate is an essential biosynthetic building block of the peptidoglycans that encapsulate the bacterial cell wall. Glutamate racemase catalyzes the reversible formation of D-glutamate from L-glutamate and, hence, the enzyme is a potential therapeutic target. We show that the novel cyclic substrate-product analogue (R,S)-1-hydroxy-1-oxo-4-amino-4-carboxyphosphorinane is a modest, partial noncompetitive inhibitor of glutamate racemase from Fusobacterium nucleatum (FnGR), a pathogen responsible, in part, for periodontal disease and colorectal cancer (Ki=3.1±0.6 mM, cf. Km=1.41±0.06 mM). The cyclic substrate-product analogue (R,S)-4-amino-4-carboxy-1,1-dioxotetrahydro-thiopyran was a weak inhibitor, giving only ?30% inhibition at a concentration of 40 mM. The related cyclic substrate-product analogue 1,1-dioxo-tetrahydrothiopyran-4-one was a cooperative mixed-type inhibitor of FnGR (Ki=18.4±1.2 mM), while linear analogues were only weak inhibitors of the enzyme. For glutamate racemase, mimicking the structure of both enantiomeric substrates (substrate-product analogues) serves as a useful design strategy for developing inhibitors. The new cyclic compounds developed in the present study may serve as potential lead compounds for further development. PMID:24507924

Pal, Mohan; Bearne, Stephen L




SciTech Connect

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

G.J. Saulnier Jr; W. Statham



Conducting Remedial Investigations/Feasibility studies for CERCLA municipal landfill sites  

SciTech Connect

The study aids in the development of methodologies and tools to assist in streamlining the Remedial Investigations/Feasibility Studies (RI/FS) and selection of remedy process for landfills. The study: (1) develops tools to assist in scoping the RI/FS for municipal landfill sites, (2) defines strategies for characterizing municipal landfill sites that are on the NPL, and (3) identifying practicable remedial action alternatives for addressing these types of sites.

Not Available



Application of studies on the overboard placement of dredged sediments to the management of disposal sites  

USGS Publications Warehouse

From the mid 1960's until 1991, dredging and disposal occurred in the northern Chesapeake Bay without guidelines to maximize the capacity and to minimize the spread of the deposits beyond the disposal sites, particularly toward the navigation channel. Planning for future dredging projects is dependant upon the remaining site capacity and the behavior of the disposed sediment. Recent studies have shown that the fate of the deposited sediments is determined primarily by the water depth and bathymetry in the vicinity of the disposal site, and the method of dredging and disposal utilized. Currently used open-water disposal sites in the northern Chesapeake Bay are reaching their maximum capacity. This makes the application of the information from these studies critical, both for the optimal use of current sites and for the evaluation of new sites. Management scenarios utilizing these studies are applied to a disposal site in the northern Chesapeake Bay.

Panageotou, William; Halka, Jeffrey



Membrane transport and the antineoplastic action of nucleoside analogues  

Microsoft Academic Search

This article summarizes recent studies characterizing nucleoside transport in mammalian cells and discusses evidence for a role of membrane transport in the pharmacologic action of nucleoside analogues. Some of these studies have also addressed the controversy concerning the multiplicity in transport routes. It seems clear that erythrocytes and, perhaps, some other mammalian cells possess a single, broadly specific system for

F. M. Sirotnak; J. R. Barrueco



Groundwater hydrology study of the Ames Chemical Disposal Site  

SciTech Connect

The Ames Laboratory Chemical Disposal Site is located in northwestern Ames, Iowa west of Squaw Creek. From 1957 to 1966, Ames Laboratory conducted research to develop processes to separate uranium and thorium from nuclear power fuel and to separate yttrium from neutron shielding sources. The wastes from these processes, which contained both hazardous and radiological components, were placed into nine burial pits. Metal drums, plywood boxes, and steel pails were used to store the wastes. Uranium was also burned on the ground surface of the site. Monitoring wells were placed around the waste burial pits. Groundwater testing in 1993 revealed elevated levels of Uranium 234, Uranium 238, beta and alpha radiation. The north side of the burial pit had elevated levels of volatile organic compounds. Samples in the East Ravine showed no volatile organics; however, they did contain elevated levels of radionuclides. These analytical results seem to indicate that the groundwater from the burial pit is flowing down hill and causing contamination in the East Ravine. Although there are many avenues for the contamination to spread, the focus of this project is to understand the hydrogeology of the East Ravine and to determine the path of groundwater flow down the East Ravine. The groundwater flow data along with other existing information will be used to assess the threat of chemical migration down the East Ravine and eventually off-site. The primary objectives of the project were as follows: define the geology of the East Ravine; conduct slug tests to determine the hydraulic conductivity of both oxidized and unoxidized till; develop a three-dimensional mathematical model using ModIME and MODFLOW to simulate groundwater flow in the East Ravine.

Stickel, T.



Refinement of parameters of weak nuclear explosions conducted at the Semipalatinsk test site on the basis of historical seismograms study  

NASA Astrophysics Data System (ADS)

Many researchers working in the field of monitoring and discriminating of nuclear tests encounter the problem of lacking in seismic catalogues the information about source parameters for weak nuclear explosions. As usual, the information about origin time, coordinates and magnitude is absent, there is information about date, approximate coordinates and information about explosion yield. Huge work conducted on recovery of parameters of small underground nuclear explosions conducted at the Semipalatinsk Test Site using records of analogue seismic stations of the USSR located at regional distances was conducted by V. Khalturin, T. Rayutian, P. Richards (Pure and Applied Geophysics, 2001). However, if underground nuclear explosions are studied and described in literature quite well, then air and contact explosions were small and were not recorded by standard permanent seismic stations. In 1961-1962 maximum number of air and contact explosions was conducted at Opytnoye polye site of the STS. We managed to find and analyze additional seismic data from some temporary and permanent stations. That time IPE AS USSR installed a network of high-sensitive stations along Pamir-Baykal profile to study earth crust structure and upper mantle, the profile length was 3500 km. Epicentral distance from some stations of the profile to Opytnoye polye was 300-400 km. In addition, a permanent seismic station Semipalatinsk (SEM) located 175 km away from the site started its operation. The seismograms from this station became available recently. The digitized historical seismograms allowed to recover and add parameters for more than 36 air and surface explosions. Origin time, coordinates, magnitudes mpv, MLV and energy class K were determined for explosions. A regional travel-time curve for Central Kazakhstan constructed using records of calibration chemical explosions conducted at the STS in 1997-2000 and ground-truth underground nuclear explosions was used to determine kinematic parameters of explosions. MLV, mpv, and energy class K were determined for all underground nuclear explosions conducted at the STS using historical seismograms from Central Asia stations. Dependencies of regional magnitudes on yield were received for air and underground nuclear explosions. Thus, application of historical seismograms at regional distances allows to recover and replenish the seismic catalogues of past nuclear explosions for further use in scientific investigations and monitoring tasks.

Sokolova, Inna



Evolving a polymerase for hydrophobic base analogues  

PubMed Central

Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favourable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically-enhanced ability to utilize HBAs after five rounds of CSR selection. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, the selected polymerase 5D4 was also to extend HBA pairs such as Pyrene: ? (abasic site), d5NI: ?, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity. PMID:19778048

Loakes, David; Gallego, Jose; Pinheiro, Vitor B.; Kool, Eric T.; Holliger, Philipp



Non-natural Acetogenin Analogues as Potent Trypanosoma brucei Inhibitors.  


Neglected tropical diseases remain a serious global health concern. Here, a series of novel bis-tetrahydropyran 1,4-triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure-activity relationship studies. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti-HAT agents. PMID:25145275

Florence, Gordon J; Fraser, Andrew L; Gould, Eoin R; King, Elizabeth F B; Menzies, Stefanie K; Morris, Joanne C; Tulloch, Lindsay B; Smith, Terry K



In vivo antitumor activity of sparsomycin and its analogues in eight murine tumor models  

Microsoft Academic Search

Sparsomycin (Sm) is a known inhibitor of ribosomal protein synthesis with an attractive anticancer potential. Recently, several analogues of Sm which are more active than the parent drug were selected for further study on the basis of in vitro investigations. Six analogues as well as the parent drug were tested for their antitumor activity in eight in vivo murine tumor

Zbigniew Zylicz; D. J. Theo Wagener; Helga Rennes; Eppo Kleijn; Peter Lelieveld; Leon A. G. M. Broek; Harry C. J. Ottenheijm



Relationship between structure and histamine releasing action of polymyxin B and its analogues  

Microsoft Academic Search

The relationship between the structures of polymyxins and their histamine releasing action on rat mast cells was studied. Analogues of polymyxin B (PB) had different hydrophobic properties, positive charge and peptide chains (deca-, nona- and heptapeptides). The biologic activities of cyclic and decyclic heptapeptides (analogues of PB), and polymyxin M and its decyclic form were investigated. Removal of some amino

V. G. Voitenko; D. I. Bayramashvili; A. I. Zebrev; A. A. Zinchenko



Ab initio quantum mechanical study of the structures and energies for the pseudorotation of 5{prime}-dehydroxy analogues of 2{prime}-deoxyribose and ribose sugars  

SciTech Connect

The authors have used ab initio quantum mechanical (QM) methods to determine the potential energy of pseudorotation for 3,4-dihydroxy-5-methyl-2-(1-pyrollyl)tetrahydrofuran and 4-hydroxy-5-methyl-2-(1-pyrollyl)-tetrahydrofuran, close analogues of 2{prime}-deoxyribose and ribose sugars. The pyrrole is a substitute for the naturally occurring nucleic acid bases: adenine, thymine, guanine, cytosine, and uracil. At the highest calculation level (LMP2/cc-pVTZ(-f)//HF/6-31G**) for 2{prime}-deoxyribose, they find the C2{prime}-endo conformation is the global minimum. The C3{prime}-endo conformation is a local minimum 0.6 kcal/mol higher in energy, and an eastern barrier of 1.6 kcal/mol separates the two minima. Pseudorotation energies of ribose are quite complex and are strongly affected by local orientations of the 2{prime} and 3{prime} hydroxyl groups. When the hydroxyl groups are allowed to assume any conformation, the global minimum remains the C2{prime}-endo conformation. The eastern barrier increases slightly to 1.8 kcal/mol, and the C3{prime}-endo local minimum lies 0.6 kcal/mol above the global minimum. Constraining the torsion angle of the C3{prime} hydroxyl group to {minus}146{degree}, as is found in RNA polymers, results in the C3{prime}-endo conformation becoming the only energy minimum with a C2{prime}-endo conformation 1.9 kcal/mol higher in energy. Bond angles within the pentofuranose ring are correlated to the pseudorotational phase, as is observed by X-ray crystallography and is predicted by pseudorotation theory. Finally, a force field for use in molecular mechanics and dynamics simulations is presented which reproduces the QM potential energies for the 2{prime}-deoxyribose and ribose sugars.

Brameld, K.A.; Goddard, W.A. III



Correlations Between Electrically Quantified Pain Degree, Subjectively Assessed Visual Analogue Scale, and the McGill Pain Questionnaire: A Pilot Study  

PubMed Central

Objective To evaluate the clinical utility of the electrically calculated quantitative pain degree (QPD) and to correlate it with subjective assessments of pain degree including a visual analogue scale (VAS) and the McGill Pain Questionnaire (MPQ). Methods We recruited 25 patients with low back pain. Of them, 21 patients suffered from low back pain for more than 3 months. The QPD was calculated using the PainVision (PV, PS-2100; Nipro Co., Osaka, Japan). We applied electrodes to the medial forearm of the subjects and the electrical stimulus was amplified sequentially. Minimum perceived current (MPC) and pain equivalent current (PEC) were defined as minimum electrical stimulation that could be sensed by the subject and electrical stimulation that could trigger actual pain itself. To eliminate individual differences, we defined QPD as the following: QPD=PEC-MPC/MPC. We scored pre-treatment QPD three times at admission and post-treatment QPD once at discharge. The VAS, MPQ, and QPD were evaluated and correlations between the scales were analyzed. Results Result showed significant test-retest reliability (ICC=0.967, p<0.001) and the correlation between QDP and MPQ was significant (at admission SRCC=0.619 and p=0.001; at discharge SRCC=0.628, p=0.001). However, the correlation between QPD and VAS was not significant (at admission SRCC=0.240, p=0.248; at discharge SRCC=0.289, p=0.161). Conclusion Numerical values measured with PV showed consistent results with repeated calculations. Electrically measured QPD showed an excellent correlation with MPQ but not with VAS. These results demonstrate that PV is a significantly reliable device for quantifying the intensity of low back pain. PMID:25379496

Kim, Junho; Lee, Kyung Soo; Kong, Sang Won; Kim, Taikon; Kim, Mi Jung; Park, Si-Bog



High resolution 1H NMR-based metabonomic study of the auditory cortex analogue of developing chick (Gallus gallus domesticus) following prenatal chronic loud music and noise exposure.  


Proper functional development of the auditory cortex (ACx) critically depends on early relevant sensory experiences. Exposure to high intensity noise (industrial/traffic) and music, a current public health concern, may disrupt the proper development of the ACx and associated behavior. The biochemical mechanisms associated with such activity dependent changes during development are poorly understood. Here we report the effects of prenatal chronic (last 10 days of incubation), 110dB sound pressure level (SPL) music and noise exposure on metabolic profile of the auditory cortex analogue/field L (AuL) in domestic chicks. Perchloric acid extracts of AuL of post hatch day 1 chicks from control, music and noise groups were subjected to high resolution (700MHz) (1)H NMR spectroscopy. Multivariate regression analysis of the concentration data of 18 metabolites revealed a significant class separation between control and loud sound exposed groups, indicating a metabolic perturbation. Comparison of absolute concentration of metabolites showed that overstimulation with loud sound, independent of spectral characteristics (music or noise) led to extensive usage of major energy metabolites, e.g., glucose, ?-hydroxybutyrate and ATP. On the other hand, high glutamine levels and sustained levels of neuromodulators and alternate energy sources, e.g., creatine, ascorbate and lactate indicated a systems restorative measure in a condition of neuronal hyperactivity. At the same time, decreased aspartate and taurine levels in the noise group suggested a differential impact of prenatal chronic loud noise over music exposure. Thus prenatal exposure to loud sound especially noise alters the metabolic activity in the AuL which in turn can affect the functional development and later auditory associated behaviour. PMID:25049174

Kumar, Vivek; Nag, Tapas Chandra; Sharma, Uma; Mewar, Sujeet; Jagannathan, Naranamangalam R; Wadhwa, Shashi



Site-specific isotopic labeling of proteins for NMR studies  

SciTech Connect

NMR spectroscopy is a sensitive, site-specific probe of biomolecular structure. For relatively small proteins and peptides, the H resonances can be assigned using the sequential method. However, there are many cases, especially larger proteins, in which the spectra are too complex for complete, systematic resonance assignments. In some cases, assignments can be made by selective isotopic labeling (e.g., uniform incorporation of a {sup 13}C-labeled amino acid) in conjunction with site-directed mutagenesis or {sup 13}C, {sup 15}N double labeling of adjacent amino acids. However, in many large proteins, protein complexes, and unfolded proteins, resonance overlap and broadening prevents assignments. The ability to synthesize proteins with unnatural amono acids, beyond those specified by the genetic code, makes it possible to isotopically label a single amino acid residue in a protein. We report here the use of this approach to generate a T4 lysozyme (T4L) mutant containing a unique {sup 13}C-labeled alanine, for which {sup 13}C-filtered proton spectra were obtained in both the native and denatured states. This general methodology should be applicable to a variety of NMR measurements in large proteins and protein complexes. 14 refs., 1 fig.

Ellman, J.A.; Volkman, B.F.; Mendel, D. [Univ. of California, Berkeley, CA (United States)] [and others



Characterize and explore potential sites and prepare research and development plan (site investigation study). Final draft. Task 2. Milestone report  

SciTech Connect

A specific research and development plan to investigate the behavior and suitability of aquifers as compressed air energy storage (CAES) sites is presented. The proposed effort will evaluate present uncertainties in the performance of the underground energy storage subsystem and its impact on above ground plant design and cost. The project is planned to provide the utility industry with a quantitative basis for confidence that financial commitment to a demonstration plant and subsequent expansion is justified and poses acceptable risks. Activities in Phase II of a 5-phase overall CAES development program are reported. Information is included on the development of field testing specifications and schedules; selection of specific site for the conceptual design; development plan and schedule for the media site; development of analytical models of aquifer airflow; and well drilling requirements. As a result of these studies 14 sites in Illinois and Indiana were evaluated, 7 were ranked for suitability for CAES, and 4 were selected for possible use in the field testing program. Test procedures, the mathematical models and drilling requirments were developed. (LCL)




Thermal and biological treatability studies on explosives-contaminated soil from a DOD site  

SciTech Connect

Laboratory- and bench-scale treatability studies were conducted on explosives-contaminated soil from the former Nebraska Ordnance Plant (NOP) Site by RUST Environment and Infrastructure (RUST) for the U.S. Army Corps of Engineers (USACE) in order to obtain site-specific information for technologies evaluated in the Feasibility Study for the site. Both thermal and biological treatment were identified in the Feasibility Study as technologies that could potentially be used to remediate the explosives-contaminated soil at the site. However, additional information specific to the chemical concentrations and soil properties of the site was required to fully evaluate these technologies. Therefore, these studies were initiated in order to gain more information. The studies summarized in this paper include a rotary kiln incineration and geotechnical study conducted by RUST, Cross/Tessitore and Associates (C/TA) under subcontract to RUST, and a biological treatment study conducted by Radian Corporation (Radian) under subcontract to RUST.

Shultz, S.R.; Taylor, C.; Shultz, D.W.R. [RUST Environment and Infrastructure, Inc., Sheboygan, WI (United States); Cichelli, J. [Army Corps of Engineers, Kansas City, MO (United States); Pinion, J. [Harding Lawson Associates/Cross/Tessitore and Associates, Orlando, FL (United States); Oolman, T. [Radian Corp., Austin, TX (United States)



Radionuclide disequilibria studies for investigating the integrity of potential nuclear waste disposal sites: subseabed studies.  

SciTech Connect

This study of subseabed sediments indicates that natural radionuclides can be employed to define past long-term migration rates and thereby evaluate the integrity of potential disposal sites in ocean sediments. The study revealed the following conclusions: (1) the sedimentation rate of both the long and short cores collected in the North Pacific is 2.5 mm/1000 yr or 2.5 m/m.yr in the upper 3 meters; (2) the sedimentation rate has been rather constant over the last one million years; and (3) slow diffusive processes dominate within the sediment. Reworking of the sediment by physical processes or organisms is not observed.

Laul, J.C.; Thomas, C.W.; Petersen, M.R.; Perkins, R.W.



Studies of Current Circulation at Ocean Waste Disposal Sites. [Delaware  

NASA Technical Reports Server (NTRS)

The author has identified the following significant results. Circulation processes at the acid waste disposal site are highly event-dominated, with the majority of the water transport occurring during strong northeasters. There is a mean flow to the south alongshore. This appears to be due to the fact that northeasterly winds produce stronger currents than those driven by southeasterly winds and by the thermohaline circulation. During the warm months, the ocean stratifies with warm water over cold water. A distinct thermocline was observed with expendable bathythermographs during all summer cruises at depths ranging from 10 to 21 meters. During stratified conditions, the near-bottom drogues showed very little movements. The duPont waste plume was observed in LANDSAT satellite imagery during dump up to 54 hours after dump.

Klemas, V. (principal investigator); Davis, G.; Henry, R.



Case study of landfill reclamation at a Florida landfill site.  


A landfill reclamation project was considered to recover landfill airspace and soil, reduce future groundwater impacts by removing the waste buried in the unlined area, and optimize airspace use at the site. A phased approach was utilized to evaluate the technical and economic feasibility of the reclamation project; based on the results of these evaluations, approximately 6.8 ha of the unlined cells were reclaimed. Approximately 371,000 in-place cubic meters of waste was mined from 6.8 ha in this project. Approximately 230,600 cubic meters of net airspace was recovered due to beneficial use of the recovered final cover soil and reclaimed soil as intermediate and daily cover soil, respectively, for the current landfill operations. This paper presents the researchers' landfill reclamation project experience, including a summary of activities pertaining to reclamation operations, an estimation of reclamation rates achieved during the project, project costs and benefits, and estimated composition of the reclaimed materials. PMID:23089299

Jain, Pradeep; Townsend, Timothy G; Johnson, Patrick



Antimicrobial Evaluation of Mangiferin Analogues  

PubMed Central

The naturally occurring xanthone glycoside mangiferin has been isolated by column chromatography from the ethanol extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylaminomethyleno)mangiferin, 5-(N-p-chlorophenylaminomethyleno) mangiferin, 5-(N-2-methylphenylaminomethyleno) mangiferin, 5-(N-p-methoxyphenylaminomethyleno) mangiferin, 5-(N, N-diphenylaminomethyleno) mangiferin, 5-(N--napthylaminomethyleno) mangiferin and 5-(N-4-methylphenylaminomethyleno) mangiferin. Mangiferin and its analogues were characterized by melting point and Rf value determination and through spectral technique like UV, IR, and NMR spectral analysis. The synthesized compounds were screened for antimicrobial activity. PMID:20490307

Singh, S. K.; Kumar, Y.; Kumar, S. Sadish; Sharma, V. K.; Dua, K.; Samad, A.



Space Analogue Environments: Are the Populations Comparable?  

NASA Astrophysics Data System (ADS)

Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that were assessed. Most of the polar expeditionners had the combination of high scores on positive expressivity and high achievement motivation- a profile which has sometimes been characterized as "the right stuff" for coping in confined and isolated settings. Conclusion: The findings from this study suggest that populations in various space-analogue environments differ in personality traits which might impact on the comparability of psychological findings obtained in different setting. Gender differences in personality also represent a potential source of variance that need to be addressed when generalizing results across space analogue environments.

Sandal, G. M.


Site selection study for Sandia National Laboratories/New Mexico as an alternative site for the National Ignition Facility  

SciTech Connect

The Department of Energy (DOE) proposes to construct and operate the National Ignition Facility (NIF) in support of the Stockpile Stewardship and Management (SSM) Programmatic Environmental impact Statement (PEIS). The National Environmental Policy Act requires the DOE to look at alternative sites for the NIF. The SSM PEIS will evaluate four alternative locations for the NIF. This study documents the process and results of a site selection study for a preferred site for the NIF at SNL/NM. The NIF research objectives are to provide the world`s most powerful laser systems to be used in ignition of fusion fuel and energy gain to perform high energy density and radiation effects experiments in support of the DOE`s national security, energy, and basic science research mission. The most immediate application of the NIF will be to provide nuclear-weapon-related physics data, since many phenomena occurring on the laboratory scale are similar to those that occur in weapons. The NIF may also provide an important capability for weapons effects simulation. The NIF is designed to achieve propagating fusion bum and modest energy gain for development as a source of civilian energy.

Miller, D.; Wheeler, T.; McClellan, Y.



Planetary Analogues of Volcanic Systems  

NASA Astrophysics Data System (ADS)

Terrestrial volcanoes studies are being used to develop techniques for interpretation of the styles of volcanic processes and the evolution of volcanic systems on Mars. Detailed characterizations of terrestrial flow fields provide critical evaluation of flow field emplacement on planetary surfaces, namely at vent fissure type features associated to volcanic shields eruptions that help to develop techniques for analyses of planetary flow fields origin and emplacement. For the purpose of this work, field observations, using differential Global Positioning System (dGPS) measurements, and remote sensing analyses, using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) of some satellitic low shields on the east rift zone of Kilauea Volcano, Hawaii, were collected to allow detailed characterization of the textural and morphologic variability of flow field surfaces as well as provide a means to generate surface unit maps that represent local flow emplacement processes and constrain flow field development. The field characteristics were compared with remote sensing data, including visible and near-infrared spectra. These characteristics were then compared to what is observed on satellitic shield volcanoes on Mars, at the same wavelengths. On Mars, the emplacement of extensive lava flows associated to eruptive vent features in the surroundings of low shield volcanoes occur in two particular regions on Mars; in Syria Planum and at the Tharsis Montes. Their studies have been recently carried out (e.g. Baptista et al., 2008, 2009; Bleacher et al., 2007) using datasets with high spatial and/or spectral resolution, such as with HRSC or HiRISE, namely in what concerns the rheological properties of the flows, the relation and duration of several eruptive periods, and also the depth of the magma chambers. Satellitic shield eruptions on Kilauea contribute significantly to the growth of the volcano and they are closely associated with lava tube systems and long duration eruptions (Rowland and Munro, 1992). Of the 15 satellitic shields on Kilauea (Holcomb, 1987) three formed in post-contact times: Mauna Iki in 1919-1920; Mauna Ulu in 1969-1974; and Kupanaiaba in 1986-1992. The relationship between activity at the summit of Kilauea and downrift provides important support for the connections (hydraulic or not) between the summit and rift zones of Kilauea, as well as information concerning the depth of the magma chambers. This work investigates the textures of surface emplaced lavas to be used to examine flow field growth, development and local flow stratigraphy on Mauna Iki, establishing relations with the other Kilauea satellitic shield volcanoes. Also, in order to characterize regions within flow fields dominated by networks of lava toes and lobes, measurements of toe length, width, thickness, and orientation were done for both Martian and terrestrial analogues. We concluded that the volcanic systems in Syria Planum, Mars and the Kilauea and its satellitic system are analogous concerning their development. Their relation with the regional faulting pattern and morphological features distribution help us to interpret the origin and longstanding evolution of these volcanic provinces.

Baptista, A. R.; Craddock, R. A.; Zimbelman, J. R.



Ab initio study of the binding of Trichostatin A (TSA) in the active site of histone deacetylase like protein (HDLP).  


Histone deacetylase (HDAC) inhibitors have recently attracted considerable interest because of their therapeutic potential for the treatment of cell proliferative diseases. An X-ray structure of a very potent inhibitor, Trichostatin A (TSA), bound to HDLP (an HDAC analogue isolated from Aquifex aeolicus), is available. From this structure, an active site model (322 atoms), relevant for the binding of TSA and structural analogues, has been derived, and TSA has been minimized in this active site at HF 3-21G* level. The resulting conformation is in excellent accordance with the X-ray structure, and indicates a deprotonation of the hydroxamic acid in TSA by His 131. Also, a water molecule was minimized in the active site. In addition to a similar deprotonation, in accordance with a possible catalytic mechanism of HDAC as proposed by Finnin et al. (M. S. Finnin, J. R. Donigian, A. Cohen, V. M. Richon, R. A. Rifkind and P. A. Marks, Nature, 1999, 401, 188-193), a displacement of the resulting OH- ion in the active site was observed. Based on these results, the difference in energy of binding between TSA and water was calculated. The resulting value is realistic in respect to experimental binding affinities. Furthermore, the mechanism of action of the His 131-Asp 166 charge relay system was investigated. Although the Asp residue in this motif is known to substantially increase the basicity of the His residue, no proton transfer from His 131 to Asp 166 was observed on binding of TSA or water. However, in the empty protonated active site, this proton transfer does occur. PMID:12968347

Vanommeslaeghe, Kenno; Van Alsenoy, Christian; De Proft, Frank; Martins, José C; Tourwé, Dirk; Geerlings, Paul



Comment on ``Can One Predict DNA Transcription Start Sites by Studying Bubbles?''  

E-print Network

Comment on ``Can One Predict DNA Transcription Start Sites by Studying Bubbles?'' In a recent question: ``Can one predict DNA transcription start sites by studying bubbles?'' The purpose, the PBD model looks at spontaneous bubble for- mation as a strictly thermal process, in the absence of any

Benham, Craig J.


User preferences for web site attributes: A study of the Hong Kong Disneyland  

Microsoft Academic Search

The Hong Kong Disneyland will be open in 2005 and the theme park is very likely to have an official web site. In order to determine the nature of a model\\/ideal official web site that would serve the promotional purpose, this study is conducted with two objectives. First, the study makes an attempt to understand the information types that the

Lily Yip; Rob Law



Long term decontamination at the Hanford Site: A case study  

SciTech Connect

This paper describes an engineering study that evaluates decontamination requirements at Hanford and the potential reutilization of the first plutonium processing production facility as a decontamination facility. The logic used to develop the study, the options available for a long-term decontamination mission, and the resultant strategy recommended in the study are presented. The paper provides a starting point for other similar study efforts. The process flowsheets, regulatory restrictions, and preconceptual designs developed in this study are common throughout the nuclear waste industry.

Geuther, W.J. [Westinghouse Hanford Co., Richland, WA (United States); Hansen, G.E. [Parsons Engineering Science, Richland, WA (United States)



Norcantharidin analogues with nematocidal activity in Haemonchus contortus  

Microsoft Academic Search

With the major problems with resistance in parasitic nematodes of livestock to anthelmintic drugs, there is an urgent need to develop new nematocides. In the present study, we employed a targeted approach for the design of a series of norcantharidin analogues (n=54) for activity testing against the barber’s pole worm (Haemonchus contortus) of small ruminants in a larval development assay

Bronwyn E. Campbell; Mark Tarleton; Christopher P. Gordon; Jennette A. Sakoff; Jayne Gilbert; Adam McCluskey; Robin B. Gasser



Mechanism of LHRH Analogue Action in Uterine Fibroids  

Microsoft Academic Search

Luteinising hormone-releasing hormone analogues have been found to reduce the size of uterine fibroids. Further studies are required to determine their exact mechanism of action. However, they are known to induce hypo-oestrogenism, which leads to reduction in uterine arterial blood flow, one mechanism by which reduction of fibroid size is thought to occur.Copyright © 1989 S. Karger AG, Basel

Robert W. Shaw



Synthesis, biological evaluation and molecular modeling of GW 501516 analogues.  


Eleven analogues of GW 501516 (1) were prepared and subjected to biological testing in a semi-high throughput human skeletal muscle cell assay. The assay testing indicated that all analogues elicited oxidation of oleic acid. Among the most potent agonists, 2e (2-{2-ethyl-4-[(4-methyl-2-(4-trifluoromethylphenyl)thiazol-5-yl)methylthio]phenoxy}-2-methylpropanoic acid), was also subjected to a luciferase-based transfection assay, which showed that this compound is a potent agonist against PPAR? and a moderate agonist against PPAR?. Docking of compound 2e into PPAR? revealed that it occupied the agonist binding site and exhibited key hydrogen bonding interactions with His323, His449, and Tyr473. PMID:21113965

Ciocoiu, Calin C; Ravna, Aina W; Sylte, Ingebrigt; Hansen, Trond Vidar



Analogue gravity in hyperbolic metamaterials  

E-print Network

Sub-wavelength confinement of light in nonlinear hyperbolic metamaterials due to formation of spatial solitons has attracted much recent attention because of its seemingly counter-intuitive behavior. In order to achieve self-focusing in a hyperbolic wire medium, a nonlinear self-defocusing Kerr medium must be used as a dielectric host. Here we demonstrate that this behavior finds natural explanation in terms of analogue gravity. Wave equation describing propagation of extraordinary light inside hyperbolic metamaterials exhibits 2+1 dimensional Lorentz symmetry. The role of time in the corresponding effective 3D Minkowski spacetime is played by the spatial coordinate aligned with the optical axis of the metamaterial. Nonlinear optical Kerr effect bends this spacetime resulting in effective gravitational force between extraordinary photons. In order for the effective gravitational constant to be positive, negative self-defocusing Kerr medium must be used as a host. If gravitational self-interaction is strong enough, spatial soliton may collapse into a black hole analogue.

Igor I. Smolyaninov



Railroad Lines as Study Sites in Plant Biology.  

ERIC Educational Resources Information Center

Presents reasons for utilizing abandoned railroad tracks in ecology field trip studies. Explanations are given for the factors influencing railroad vegetation. Activities for students are suggested. (SA)

Arnold, Robert M.



Synthesis and evaluation of heterocyclic analogues of bromoxynil.  


One attractive strategy to discover more active and/or crop-selective herbicides is to make structural changes to currently registered compounds. This strategy is especially appealing for those compounds with limited herbicide resistance and whose chemistry is accompanied with transgenic tools to enable herbicide tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor registered for control of broadleaf weeds in several agronomic and specialty crops. Recently at the University of Tennessee-Knoxville several analogues of bromoxynil were synthesized including a previously synthesized pyridine (2,6-dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6-dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N-oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of bromoxynil were also evaluated for their herbicidal activity on soybean ( Glycine max ), cotton ( Gossypium hirsutum ), redroot pigweed ( Amaranthus retroflexus ), velvetleaf ( Abutilon theophrasti ), large crabgrass ( Digitaria sanguinalis ), and pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second study was conducted on a glyphosate-resistant weed ( Amaranthus palmeri ) with the compounds being applied at 0.56 kg ha(-1). Although all compounds were believed to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus retroflexus. However, application of the pyrimidine herbicide resulted in the least injury to all species tested. These variations in efficacy were investigated using molecular docking simulations, which indicate that the pyridine analogue may form a stronger hydrogen bond in the pocket of the D1 protein than the original bromoxynil. A pyridine analogue was able to control the glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine analogues of bromoxynil showed potential to have a different weed control spectrum compared to bromoxynil. A pyridine analogue of bromoxynil synthesized in this research controlled several weed species greater than bromoxynil itself, potentially due to enhanced binding within the PSII binding pocket. Future research should compare this analogue to bromoxynil using optimized formulations at higher application rates. PMID:24354444

Cutulle, Matthew A; Armel, Gregory R; Brosnan, James T; Best, Michael D; Kopsell, Dean A; Bruce, Barry D; Bostic, Heidi E; Layton, Donovan S




SciTech Connect

An issue of concern at the Savannah River Site (SRS) over the past 20 years is whether tritiated groundwater originating at SRS might be the cause of low levels of tritium measured in certain domestic wells in Georgia. Tritium activity levels in several domestic wells have been observed to occur at levels comparable to what is measured in rainfall in areas surrounding SRS. Since 1988, there has been speculation that tritiated groundwater from SRS could flow under the river and find its way into Georgia wells. A considerable effort was directed at assessing the likelihood of trans-river flow, and 44 wells have been drilled by the USGS and the Georgia Department of Natural Resources. Also, as part of the data collection and analysis, the USGS developed a numerical model during 1997-98 (Ref. 1) to assess the possibility for such trans-river flow to occur. The model represented the regional groundwater flow system surrounding the Savannah River Site (SRS) in seven layers corresponding to the underlying hydrostratigraphic units, which was regarded as sufficiently detailed to evaluate whether groundwater originating at SRS could possibly flow beneath the Savannah River into Georgia. The model was calibrated against a large database of water-level measurements obtained from wells on both sides of the Savannah River and screened in each of the hydrostratigraphic units represented within the model. The model results verified that the groundwater movement in all hydrostratigraphic units proceeds laterally toward the Savannah River from both South Carolina and Georgia, and discharges into the river. Once the model was calibrated, a particle-track analysis was conducted to delineate areas of potential trans-river flow. Trans-river flow can occur in either an eastward or westward direction. The model indicated that all locations of trans-river flow are restricted to the Savannah River's floodplain, where groundwater passes immediately prior to discharging into the river. Whether the trans-river flow is eastward or westward depends primarily on the position of the Savannah River as it meanders back and forth within the floodplain and is limited to narrow sections of land adjacent to the river. With respect to ''westward'' trans-river flow, the model indicates that it primarily occurs in locations south of SRS and within the deeper aquifers (Crouch Branch and McQueen Branch). Particle-tracking analysis of westward trans-river flow in these aquifers indicates that the groundwater crossing from South Carolina into Georgia originates as recharge in upland areas well to the east and south of SRS. The model identified one location (an area of less than one square mile) where westward trans-river flow originating as recharge within the boundaries of SRS and which could conceivably receive tritium or other contaminants from SRS as a result. The one-square-mile area occurs immediately adjacent to the Savannah River, where groundwater within the Gordon Aquifer flows immediately prior to discharging into the river and is indicated in Figure 1. Reverse particle tracking indicates that recharge zones associated with the one square mile are located in the upland areas between D-Area and K-Area. There is no known subsurface contamination at these recharge zones. The travel times associated with the particles were calculated to range from 90 to 820 years, although these estimates are shorter than actual travel times since no accounting of groundwater transit time across the uppermost aquifer was included in the model. It is important to note that the range of travel times represents seven to 66 half-lives of tritium (12.33 years), suggesting that even if tritium contamination existed at the recharge areas, it likely would decay away prior to discharging into the Savannah River.

Hiergesell, R; Daniel Kaplan,D



Natural analogues of nuclear waste glass corrosion.  

SciTech Connect

This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.



Fusion of Geophysical Images in the Study of Archaeological Sites  

NASA Astrophysics Data System (ADS)

This paper presents results from different fusion techniques between geophysical images from different modalities in order to combine them into one image with higher information content than the two original images independently. The resultant image will be useful for the detection and mapping of buried archaeological relics. The examined archaeological area is situated in Kampana site (NE Greece) near the ancient theater of Maronia city. Archaeological excavations revealed an ancient theater, an aristocratic house and the temple of the ancient Greek God Dionysus. Numerous ceramic objects found in the broader area indicated the probability of the existence of buried urban structure. In order to accurately locate and map the latter, geophysical measurements performed with the use of the magnetic method (vertical gradient of the magnetic field) and of the electrical method (apparent resistivity). We performed a semi-stochastic pixel based registration method between the geophysical images in order to fine register them by correcting their local spatial offsets produced by the use of hand held devices. After this procedure we applied to the registered images three different fusion approaches. Image fusion is a relatively new technique that not only allows integration of different information sources, but also takes advantage of the spatial and spectral resolution as well as the orientation characteristics of each image. We have used three different fusion techniques, fusion with mean values, with wavelets by enhancing selected frequency bands and curvelets giving emphasis at specific bands and angles (according the expecting orientation of the relics). In all three cases the fused images gave significantly better results than each of the original geophysical images separately. The comparison of the results of the three different approaches showed that the fusion with the use of curvelets, giving emphasis at the features' orientation, seems to give the best fused image. In the resultant image appear clear linear and ellipsoid features corresponding to potential archaeological relics.

Karamitrou, A. A.; Petrou, M.; Tsokas, G. N.



Chromone studies. Part 13. Synthesis and electron-impact mass spectrometric studies of 5-hydroxy-2-isopropyl-7-methoxychromone, a constituent of the medicinal plant Baeckea frutescens, and side-chain analogues.  


5-Hydroxy-2-isopropyl-7-methoxychromone (1d), a chromone constituent isolated from the aerial parts of Baeckea frutescens, and four analogues (1a-c and 1e), all of which exhibit toxicity to the brine shrimp Artemia salina, have been prepared from 2',4',6'-trihydroxyacetophenone. High-resolution mass spectrometric analysis has permitted elucidation of the fragmentation patterns exhibited by these systems following electron-impact ionization. PMID:12932146

Gray, Christopher A; Kaye, Perry T; Nchinda, Aloysius T



Discrete analogue computing with rotor-routers  

E-print Network

Discrete analogue computing with rotor-routers James Propp August 18, 2010 Abstract: Rotor a certificate that can itself be computed by the rotor-router network. Rotor- router networks can be viewed processes. Rotor-router networks are discrete analogues of continuous linear systems such as electrical

Propp, James


Topical Prostaglandin Analogue Drugs Inhibit Adipocyte Differentiation  

PubMed Central

Purpose To investigate the effects of topical prostaglandin analogue drugs on the differentiation of adipocytes. Methods Differentiation of 3T3-L1 preadipocytes was induced with isobutylmethylxanthine, dexamethasone, and insulin. 3T3-L1 cells were exposed to 0.008, 0.08, 0.2 µM of latanoprost and travoprost. Reverse transcription polymerase chain reaction for mRNA expression of lipoprotein lipase and peroxisome proliferator-activated receptor ? 2 (PPAR?2), and glycerol-3-phosphate dehydrogenase (G3PDH) assays were performed to examine the effects on early and late differentiation, respectively. Also, glycerol assays were done to evaluate the effect of prostaglandin analogues on lipolysis after differentiation. Results Both prostaglandin analogues inhibited differentiation of preadipocytes. Topical prostaglandin analogues significantly decreased G3PDH activity, a marker of late differentiation. However, topical prostaglandin analogues did not change mRNA expressions of lipoprotein lipase and PPAR?2, markers of early differentiation. The activities of the early markers of differentiation were not changed significantly before and after growth arrest. Compared to latanoprost, travoprost decreased G3PDH activity more significantly (p < 0.05). Both prostaglandin analogues did not affect the lipolysis of differentiated adipocytes (p > 0.05). Conclusions Prostaglandin analogues display an inhibitory effect on the differentiation of adipocytes when the cells start to differentiate especially in the late stage of differentiation. Thus, commercial topical prostaglandin analogues may decrease the fat contents of eyelids. PMID:24882960



Analogues of estradiol as potential breast tumor imaging agents  

SciTech Connect

The radioiodinated analogue of estradiol, 11..beta..-methoxy-17..cap alpha..-(/sup 125/I)iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11..beta..-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11..beta..-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study.

Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.



Lactam-stabilized helical analogues of the analgesic ?-conotoxin KIIIA  

PubMed Central

?-Conotoxin KIIIA (?-KIIIA) blocks mammalian voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. Previous structure-activity studies of ?-KIIIA identified a helical pharmacophore for VGSC blockade. This suggested a route for designing truncated analogues of ?-KIIIA by incorporating the key residues into an ?-helical scaffold. As (i, i+4) lactam bridges constitute a proven approach for stabilizing ?-helices, we designed and synthesized six truncated analogues of ?-KIIIA containing single lactam bridges at various locations. The helicity of these lactam analogues was analysed by NMR spectroscopy, and their activities were tested against mammalian VGSC subtypes NaV1.1 through 1.7. Two of the analogues, Ac-cyclo9/13[Asp9,Lys13]KIIIA7–14 and Ac-cyclo9/13[Lys9,Asp13]KIIIA7–14, displayed µM activity against VGSC subtypes NaV1.2 and NaV1.6; importantly, the subtype selectivity profile for these peptides matched that of ?-KIIIA. Our study highlights structure-activity relationships within these helical mimetics and provides a basis for the design of additional truncated peptides as potential analgesics. PMID:21962108

Khoo, Keith K.; Wilson, Michael J.; Smith, Brian J.; Zhang, Min-Min; Gulyas, Joszef; Yoshikami, Doju; Rivier, Jean E.; Bulaj, Grzegorz; Norton, Raymond S.



Programs of Study: What "Mature" Sites Tell Us  

ERIC Educational Resources Information Center

Although career and technical education (CTE) Programs of Study (POS) were introduced in the Perkins IV legislation, neither the spirit nor the elements of POS are new in the history of CTE as a vehicle for high school reform. POS have evolved over several decades of efforts to create effective transition programs from secondary to postsecondary…

Alfeld, Corinne; Bhattacharya, Sharika



Developing Music Teacher Identities: An International Multi-Site Study  

ERIC Educational Resources Information Center

This study investigates pre-service music teacher's (PSMT) perceptions of their professional identities. University-level education students in the United States America (USA), Spain and Australia were all asked interview questions based on general themes relevant to teacher identity development, and their responses were subjected to content…

Ballantyne, Julie; Kerchner, Jody L.; Arostegui, Jose Luis



Sequence Specific Molecular Recognition and Binding by a GC Recognizing Hoechst 33258 Analogue to the Decadeoxyribonucleotide d-[CATGGCCATG]2: Structural and Dynamic Aspects Deduced from High Field H-NMR Studies  

Microsoft Academic Search

The non-exchangeable and imino proton NMR resonances have been assigned of the 1:1 complex of an analogue 2 of Hoechst 33258 1 bound to the decadeoxyribonuycleotide d- [CATGGCCATG]2 by a combination of NOE difference, COSY and NOESYPH techniques. In contrast to Hoechst 33258 which recognizes 5?-AATT sequences exclusively, analogue 2 possesses structural features designed to permit the recognition of GC

Surat Kumar; Bathini Yadagiri; Jurg Zimmermann; Richard T. Pon; J. William Lown



Ionization state of the catalytic dyad Asp25/25' in the HIV-1 protease: NMR studies of site-specifically 13C labelled HIV-1 protease prepared by total chemical synthesis.  


Total chemical synthesis was used to site-specifically (13)C-label active site Asp25 and Asp25' residues in HIV-1 protease and in several chemically synthesized analogues of the enzyme molecule. (13)C NMR measurements were consistent with a monoprotonated state for the catalytic dyad formed by the interacting Asp25, Asp25' side chain carboxyls. PMID:22659831

Torbeev, Vladimir Yu; Kent, Stephen B H



Febrifugine analogue compounds: synthesis and antimalarial evaluation.  


Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum, but exhibits toxic side effects. In this study novel febrifugine analogues were designed and efficiently synthesized. New compounds underwent efficacy and toxicity evaluation. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drugs and are expected to possess wide therapeutic windows. In Aotus monkeys infected with the chloroquine resistant FVO strain of P. falciparum, one interesting compound possesses a 50% curative dose of 2mg/kg/day and a 100% curative dose of 8 mg/kg/day. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs. PMID:22182577

Zhu, Shuren; Chandrashekar, Gudise; Meng, Li; Robinson, Katie; Chatterji, Dipsanker



Receptor binding and adenylate cyclase activities of glucagon analogues modified in the N-terminal region  

SciTech Connect

In this study, we determined the ability of four N-terminally modified derivatives of glucagon, (3-Me-His1,Arg12)-, (Phe1,Arg12)-, (D-Ala4,Arg12)-, and (D-Phe4)glucagon, to compete with 125I-glucagon for binding sites specific for glucagon in hepatic plasma membranes and to activate the hepatic adenylate cyclase system, the second step involved in producing many of the physiological effects of glucagon. Relative to the native hormone, (3-Me-His1,Arg12)glucagon binds approximately twofold greater to hepatic plasma membranes but is fivefold less potent in the adenylate cyclase assay. (Phe1,Arg12)glucagon binds threefold weaker and is also approximately fivefold less potent in adenylate cyclase activity. In addition, both analogues are partial agonists with respect to adenylate cyclase. These results support the critical role of the N-terminal histidine residue in eliciting maximal transduction of the hormonal message. (D-Ala4,Arg12)glucagon and (D-Phe4)glucagon, analogues designed to examine the possible importance of a beta-bend conformation in the N-terminal region of glucagon for binding and biological activities, have binding potencies relative to glucagon of 31% and 69%, respectively. (D-Ala4,Arg12)glucagon is a partial agonist in the adenylate cyclase assay system having a fourfold reduction in potency, while the (D-Phe4) derivative is a full agonist essentially equipotent with the native hormone. These results do not necessarily support the role of an N-terminal beta-bend in glucagon receptor recognition. With respect to in vivo glycogenolysis activities, all of the analogues have previously been reported to be full agonists.

McKee, R.L.; Pelton, J.T.; Trivedi, D.; Johnson, D.G.; Coy, D.H.; Sueiras-Diaz, J.; Hruby, V.J.



Pilot study of dredging and disposal alternatives for the New Bedford Harbor, Massachusetts, Superfund site  

Microsoft Academic Search

Bottom sediments in New Bedford Harbor are contaminated with polychlorinated biphenyls (PCB) and heavy metals to the extent that the site is considered one of the Nation's worst hazardous waste sites and is being studied by the US Environmental Protection Agency (EPA) under the Federal Superfund program. At the request of EPA, the Corps of Engineers has evaluated the feasibility





EPA Science Inventory

Bench-scale solvent extraction and soil washing studies were performed on soil samples obtained from three abandoned wood preserving sites that included in the NPL. The soil samples from these sites were contaminated with high levels of polyaromatic hydrocarbons (PAHs), pentachlo...


Study of New Youth Initiatives in Apprenticeship. Interim Report. Volume 2: Site Visit Reports.  

ERIC Educational Resources Information Center

This second volume of the interim report provides detailed case study reports on each of the eight Youth Apprenticeship Projects. (Volume 1, an overview of data from the site visits, is available separately as CE 032 791.) Discussion areas covered in each site visit report are local context/operational environment, administrative information,…

CSR, Inc., Washington, DC.


Revegetation Studies at Three Strip-Mine Sites in North-Central Pennsylvania.  

National Technical Information Service (NTIS)

As part of an experiment in the restoration of lands strip-mined for coal, revegetation studies were conducted at three backfilled strip-mine sites in north-central Pennsylvania. The sites were subdivided into plots that were given varying amounts of lime...

M. O. Magnuson, R. L. Kimball



Numerical Study of Spatial Surface Temperature and Nucleation Site Density At High Heat Flux Pool Boiling  

E-print Network

Numerical Study of Spatial Surface Temperature and Nucleation Site Density At High Heat Flux Pool method was developed to explore spatial and temporal variations on surface temperature. The results show Boiling, Surface Temperature, Nucleation Site Density INTRODUCTION The macrolayer is widely used

Maruyama, Shigeo


Discovering How Students Search a Library Web Site: A Usability Case Study.  

ERIC Educational Resources Information Center

Discusses results of a usability study at the University of Illinois Chicago that investigated whether Internet search engines have influenced the way students search library Web sites. Results show students use the Web site's internal search engine rather than navigating through the pages; have difficulty interpreting library terminology; and…

Augustine, Susan; Greene, Courtney



Ord River arboviruses--the study site and mosquitoes.  


The Ord Valey of tropical Western Australia has been studied for arbovirus activity following the development of a man-made lake of considerable size, a diversion dam and an irrigation scheme. Kununurra, the largest town in the valley, is the focus for very large populations of birds and mosquitoes. The irrigation areas have not been important as mosquito breeding areas because of the excessive use of insecticides. Lake Argyle does not support high mosquito a bird population at present. However, this may change as the ecosystem stabilizes. The mosquito fauna of the Ord Valley is dominated by Culex annulirostris. PMID:14612

Liehne, P F; Stanley, N F; Alpers, M P; Liehne, C G



Stabilization of microtubules by inorganic phosphate and its structural analogues, the fluoride complexes of aluminum and beryllium  

SciTech Connect

In order to elucidate how the elementary reactions of GTP cleavage and subsequent inorganic phosphate (P/sub i/) release, which accompany microtubule assembly, regulate microtubule dynamics, the effect of P/sub i/ and of its structural analogues AlF/sub 4//sup -/ and BeF/sub 3//sup -/ on the stability of GDP-microtubules has been investigated. Inorganic phosphate binds to microtubules with a low affinity (K/sub D/ = 25 mM) and slows down the rate of GDP-subunit dissociation by about 2 orders of magnitude. AlF/sub 4//sup -/ and BeF/sub 3//sup -/ exhibit phosphate-like effects with 1000-fold higher affinity. Evidence has been obtained for direct binding of BeF/sub 3//sup -/ to microtubules with a stoichiometry of 1 mol of BeF/sub 3//sup -/ per mole of GDP-subunit and an equilibrium dissociation constant of 12-15 AlF/sub 4//sup -/ and P/sub i/ compete for this site. Phosphate analogues abolish oscillatory polymerization kinetics and slow down microtubule turnover at steady state. In view of these results, the authors propose that P/sub i/ and its structural analogues bind to the site of the ..gamma..-phosphate of GTP in the E site and reconstitute a GDP-P/sub i/-microtubule, from which tubulin subunits dissociate very slowly. They therefore understand that, following GTP cleavage on microtubules, P/sub i/ release in the medium is accompanied by a structural change resulting in a large destabilization of the polymer. A cap of slowly dissociating GDP-P/sub i/-subunits prevents depolymerization of the microtubule GDP-core at steady state. The similarity with the actin system is studied.

Carlier, M.F.; Didry, D.; Melki, R.; Chabre, M.; Pantaloni, D.



Paleoseismological study on stone cultural sites in Gyeongju, SE Korea  

NASA Astrophysics Data System (ADS)

The Korean peninsular, located within the Eurasian intracontinental region, is presently considered to be tectonically safe compared with neighboring countries such as Japan and Taiwan. However, historical records for the Gyeongju area, which is an old capital city with many ancient stone buildings, demonstrate that seismic events have significantly affected lives and properties in this town. For example, one reported earthquake in 779 AD had an inferred magnitude of M=6.7 and resulted in the deaths of over a hundred people and the destruction of many buildings. This study examines the affects of paleoseismological events recorded by stone constructions in Gyeongju. The study area contains mostly granite and is located near the junction between the Yangsan and Ulsan faults, which represent two of the major faults in SE Korea. In May of 2007, a statue of Buddha that was previously attached to and carved from a vertical granite cliff was discovered resting on the 45° slope of the Yeolam valley. Based on the artistic style of the granite statue, it was estimated to be during the late 8th century; it has a weight of about 70 tons and dimensions of 250x190x620 cm. Four main joint directions exist in the statue and in granite exposed in the cliff at its original location. These joint sets match if the statue were rotated 15° clockwise back from present position. Another evidence for damages also occurs at ChumSungDae astronomical observatory. One possible cause for these destructions and damages is paleoseismicity in this area.

Lee, M.; Jin, K.; Kim, Y.



Siderophore receptor-mediated uptake of lactivicin analogues in gram-negative bacteria.  


Multidrug-resistant Gram-negative pathogens are an emerging threat to human health, and addressing this challenge will require development of new antibacterial agents. This can be achieved through an improved molecular understanding of drug-target interactions combined with enhanced delivery of these agents to the site of action. Herein we describe the first application of siderophore receptor-mediated drug uptake of lactivicin analogues as a strategy that enables the development of novel antibacterial agents against clinically relevant Gram-negative bacteria. We report the first crystal structures of several sideromimic conjugated compounds bound to penicillin binding proteins PBP3 and PBP1a from Pseudomonas aeruginosa and characterize the reactivity of lactivicin and ?-lactam core structures. Results from drug sensitivity studies with ?-lactamase enzymes are presented, as well as a structure-based hypothesis to reduce susceptibility to this enzyme class. Finally, mechanistic studies demonstrating that sideromimic modification alters the drug uptake process are discussed. PMID:24694215

Starr, Jeremy; Brown, Matthew F; Aschenbrenner, Lisa; Caspers, Nicole; Che, Ye; Gerstenberger, Brian S; Huband, Michael; Knafels, John D; Lemmon, M Megan; Li, Chao; McCurdy, Sandra P; McElroy, Eric; Rauckhorst, Mark R; Tomaras, Andrew P; Young, Jennifer A; Zaniewski, Richard P; Shanmugasundaram, Veerabahu; Han, Seungil



Site-Specific Proteomics Approach for Study Protein S-Nitrosylation  

SciTech Connect

Here we present a novel and robust method for the identification of protein S-nitrosylation sites in complex protein mixtures. The approach utilizes the cysteinyl affinity resin to selectively enrich S-nitrosylated peptides reduced by ascorbate followed by nanoscale liquid chromatography tandem mass spectrometry. Two alkylation agents with different added masses were employed to differentiate the S-nitrosylation sites from the non-Snitrosylation sites. We applied this approach to MDA-MB-231 cells treated with Angeli’s salt, a nitric oxide donor that has been shown to inhibit breast tumor growth and angiogenesis. A total of 162 S-nitrosylation sites were identified and an S-nitrosylation motif was revealed in our study. The 162 sites are significantly more than the number reported by previous methods, demonstrating the efficiency of our approach. Our approach will further facilitate the functional study of protein S-nitrosylation in cellular processes and may reveal new therapeutic targets.

Liu, Miao; Hou, Jinxuan; Huang, Lin; Huang, Xin; Heibeck, Tyler H.; Zhao, Rui; Pasa-Tolic, Ljiljana; Smith, Richard D.; Li, Yan; Fu, Kai; Zhang, Zhixin; Hinrichs, Steven; Ding, Shi-Jian



Herpesvirus proteinase: site-directed mutagenesis used to study maturational, release, and inactivation cleavage sites of precursor and to identify a possible catalytic site serine and histidine.  

PubMed Central

The cytomegalovirus maturational proteinase is synthesized as a precursor that undergoes at least three processing cleavages. Two of these were predicted to be at highly conserved consensus sequences--one near the carboxyl end of the precursor, called the maturational (M) site, and the other near the middle of the precursor, called the release (R) site. A third less-well-conserved cleavage site, called the inactivation (I) site, was also identified near the middle of the human cytomegalovirus 28-kDa assemblin homolog. We have used site-directed mutagenesis to verify all three predicted sequences in the simian cytomegalovirus proteinase, and have shown that the proteinase precursor is active without cleavage at these sites. We have also shown that the P4 tyrosine and the P2 lysine of the R site were more sensitive to substitution than the other R- and M-site residues tested: substitution of alanine for P4 tyrosine at the R site severely reduced cleavage at that site but not at the M site, and substitution of asparagine for lysine at P2 of the R site reduced M-site cleavage and nearly eliminated I-site cleavage but had little effect on R-site cleavage. With the exception of P1' serine, all R-site mutations hindered I-site cleavage, suggesting a role for the carboxyl end of assemblin in I-site cleavage. Pulse-chase radiolabeling and site-directed mutagenesis indicated that assemblin is metabolically unstable and is degraded by cleavage at its I site. Fourteen amino acid substitutions were also made in assemblin, the enzymatic amino half of the proteinase precursor. Among those tested, only 2 amino acids were identified as essential for activity: the single absolutely conserved serine and one of the two absolutely conserved histidines. When the highly conserved glutamic acid (Glu22) was substituted, the proteinase was able to cleave at the M and I sites but not at the R site, suggesting either a direct (e.g., substrate recognition) or indirect (e.g., protein conformation) role for this residue in determining substrate specificity. Images PMID:8230459

Welch, A R; McNally, L M; Hall, M R; Gibson, W



Study of the Nevada Test Site using Landsat satellite imagery  

SciTech Connect

In the period covered by the purchase order CSIS has obtained one Landsat image and determined that two images previously supplied to the principal investigator under a subcontract with George Washington University were inherently defective. We have negotiated with EOSAT over the reprocessing of those scenes and anticipate final delivery within the next few weeks. A critical early purchase during the subcontract period was of an EXABYTE tape drive, Adaptec SCSI interface, and the appropriate software with which to read Landsat images at CSIS. This gives us the capability of reading and manipulating imagery in house without reliance on outside services which have not proven satisfactory. In addition to obtaining imagery for the study, we have also performed considerable analytic work on the newly and previously purchased images. A technique developed under an earlier subcontract for identifying underground nuclear tests at Pahute Mesa has been significantly refined, and similar techniques were applied to the summit of Rainier Mesa and to the Yucca Flats area. An entirely new technique for enhancing the spectral signatures of different regions of NTS was recently developed, and appears to have great promise of success.

Zimmerman, P.D. [Georgetown Univ., Washington, DC (United States). Center for Strategic and International Studies



Photoaffinity studies of the tubulin-colchicine binding site  

SciTech Connect

A variety of colchicine derivatives were synthesized and coupled with 3,3,3-trifluoro-2-diazapropionyl chloride (TFDP-Cl) to produce colchicine photoaffinity analogs for use in tubulin labelling studies. Photoaffinity analogs of allocolchicine and podophylotoxin were also made using the same photoreactive moiety. Several labels were found to be effective inhibitors of tubulin polymerization. The approximate tubulin binding constants of the labels, calculated from polymerization inhibition data, varied between 2.2 x 10/sup 5/ to 2.5 x 10/sup 3/ M/sup -1/. The labels chosen for use in tubulin labelling experiments were (N-TFDP) deacetyl-thiocolchicine 1, (O-TFDP)thiocolchifoline 2, and (O-TFDP)-2-demethylthiocolchicine 3. Compound 1 was found to bind tubulin reversibly and to competitively inhibit colchicine binding. Methods for the incorporation of tritium and /sup 14/C in these labels were developed. Conditions were found which caused labels to insert into solvent without photorearrangement of the colchicine skeleton. Catalytic base caused the ..cap alpha..-diazo amide of 1 to rearrange to a triazole.

Hahn, K.M.



Design, synthesis and biological evaluation of novel 1?,25-dihydroxyvitamin D 3 analogues possessing aromatic ring on 2?-position  

Microsoft Academic Search

In the present study, we describe the synthesis of new analogues of 1?,25-dihydroxyvitamin D3 (1), which possess hydrophobic aromatic ring on the 2? position. Among these analogues, 2?-benzyl analogue showed the highest potency in the affinity for the wild type vitamin D receptor (VDR) and induction of HL-60 cell differentiation as well as transcriptional activity. Affinity for the mutant VDR

Shinobu Honzawa; Koshiro Hirasaka; Yasuhiro Yamamoto; Sara Peleg; Toshie Fujishima; Masaaki Kurihara; Nozomi Saito; Seishi Kishimoto; Takayuki Sugiura; Keizo Waku; Hiroaki Takayama; Atsushi Kittaka



Marine biomass: New York state site and species study compositional analysis and systems studies. Final report Mar-Dec 81  

SciTech Connect

The primary objective of the Marine Biomass Programs is to provide an optimized, integrated process for producing methane from seaweeds cultivated in the open ocean and to do so at a price which is competitive with that of methane from other sources. The New York State Site and Species Study represents the first evaluation of a site outside of Southern California.

Makinen, R.W.; Farley, K.M.; Kugler, W.R.



Synthesis, characterization and biological evaluation of paeonol thiosemicarbazone analogues as mushroom tyrosinase inhibitors.  


A series of hydroxy- and methoxy-substituted paeonol thiosemicarbazone analogues were synthesized as potential tyrosinase inhibitors and their inhibitory effects on mushroom tyrosinase and inhibitory mechanism were evaluated. Paeonol thiosemicarbazone analogues have been found exhibiting more remarkable inhibition than their indexcompounds on mushroom tyrosinase. Among them, compound 2,4-dihydroxy acetophenone-4-phenyl-3-thiosemicarbazone (d1) had the most potent inhibition activity with the IC50 value of 0.006 ± 0.001 mM, displayed as a reversible competitive inhibitor. The inhibitory ability of o- or p-substituted acetophenone thiosemicarbazones was: di-substituted acetophenone thiosemicarbazones>mono-substituted acetophenone thiosemicarbazones>non-substituted acetophenone thiosemicarbazones. Copper ions chelation assay explained that compound d1 exhibited competitive inhibition by forming a chelate with the copper ions at the catalytic domain of tyrosinase as well as indicate a 1.5:1 binding ratio of compound d1 with copper ions. In the fluorescence spectrum study, compound d1 behaved stronger fluorescence quenching on tyrosinase towards d1-Cu(2+) complex, inhibiting tyrosinase mainly by means of chelating the two copper ions in the active site. The newly synthesized compounds may serve as structural templates for designing and developing novel tyrosinase inhibitors. PMID:24120880

Zhu, Tian-Hua; Cao, Shu-Wen; Yu, Yan-Ying



Inactivation of lipoxygenase and cyclooxygenase by natural betalains and semi-synthetic analogues.  


Betalains are natural pigments characteristic of plants of the order Caryophyllales. In this work, the role of betalains in the anti-inflammatory activity described for plant extracts is analysed in terms of the inactivation of the enzymes involved in the biochemical response (lipoxygenase and cyclooxygenase). Pure natural betalains and semi-synthetic analogues are demonstrated to promote a significant reduction of the enzymes activity. Reactions were followed spectrophotometrically and by HPLC-DAD. Phenethylamine-betaxanthin was the most potent in the inactivation of cyclooxygenase, with a reduction of 32% of the control activity at 125?M, while the natural pigment betanidin and a betalain analogue derived from indoline resulted as the most potent inactivators of lipoxygenase, with IC50 values of 41.4 and 40.1?M, respectively. Molecular docking studies revealed that betalains interact with the lipoxygenase amino acids involved in substrate binding and with Tyr-385 and Ser-530 close to the cyclooxygenase active site, interfering in enzyme catalysis. PMID:24518339

Vidal, Pedro J; López-Nicolás, José M; Gandía-Herrero, Fernando; García-Carmona, Francisco




EPA Science Inventory

NRMRL-ADA-01110 Lin**, Z., and Puls*, R.W. Studies of Interfacial Reactions Between Arsenic and Minerals and its Significance to Site Characterization. Environmental Geology 40 (11/12):1433-1439 (2001). ...


Ecological studies related to construction of the Defense Waste Processing Facility on the Savannah River Site  

SciTech Connect

The Savannah River Ecology Laboratory has completed 10 years of ecological studies related to the construction of the Defense Waste Processing Facility (DWPF) on the Savannah River Site. This progress report examines water quality studies on streams peripheral to the DWPF construction site and examines the effectiveness of refuge ponds'' in ameliorating the effects of construction on local amphibians. Individual papers on these topics are indexed separately. 93 refs., 15 figs., 15 tabs. (MHB)

Scott, D.E.; Pechmann, J.H.K.; Knox, J.N.; Estes, R.A.; McGregor, J.H.; Bailey, K. (ed.)



Rational Design of ?-Conotoxin Analogues Targeting ?7 Nicotinic Acetylcholine Receptors  

PubMed Central

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that belong to the superfamily of Cys loop receptors. Valuable insight into the orthosteric ligand binding to nAChRs in recent years has been obtained from the crystal structures of acetylcholine-binding proteins (AChBPs) that share significant sequence homology with the amino-terminal domains of the nAChRs. ?-Conotoxins, which are isolated from the venom of carnivorous marine snails, selectively inhibit the signaling of neuronal nAChR subtypes. Co-crystal structures of ?-conotoxins in complex with AChBP show that the side chain of a highly conserved proline residue in these toxins is oriented toward the hydrophobic binding pocket in the AChBP but does not have direct interactions with this pocket. In this study, we have designed and synthesized analogues of ?-conotoxins ImI and PnIA[A10L], by introducing a range of substituents on the Pro6 residue in these toxins to probe the importance of this residue for their binding to the nAChRs. Pharmacological characterization of the toxin analogues at the ?7 nAChR shows that although polar and charged groups on Pro6 result in analogues with significantly reduced antagonistic activities, analogues with aromatic and hydrophobic substituents in the Pro6 position exhibit moderate activity at the receptor. Interestingly, introduction of a 5-(R)-phenyl substituent at Pro6 in ?-conotoxin ImI gives rise to a conotoxin analogue with a significantly higher binding affinity and antagonistic activity at the ?7 nAChR than those exhibited by the native conotoxin. PMID:19131337

Armishaw, Christopher; Jensen, Anders A.; Balle, Thomas; Clark, Richard J.; Harps?e, Kasper; Skonberg, Christian; Liljefors, Tommy; Str?mgaard, Kristian



Synthesis and crystal structure of new temephos analogues as cholinesterase inhibitor: molecular docking, QSAR study, and hydrogen bonding analysis of solid state.  


A series of temephos (Tem) derivatives were synthesized and characterized by 31P, 13C, and 1H NMR and FT-IR spectral techniques. Also, the crystal structure of compound 9 was investigated. The hydrogen bonding energies (E2) were calculated by NBO analysis of the crystal cluster. The activities and the mixed-type mechanism of Tem derivatives were evaluated using the modified Ellman's and Lineweaver-Burk's methods on cholinesterase (ChE) enzymes. The inhibitory activities of Tem derivatives with a P?S moiety were higher than those with a P?O moiety. Docking analysis disclosed that the hydrogen bonds occurred between the OR (R=CH3 and C2H5) oxygen and N-H nitrogen atoms of the selected compounds and the receptor site (GLN and GLU) of ChEs. PCA-QSAR indicated that the correlation coefficients of the electronic variables were dominant compared to the structural descriptors. MLR-QSAR models clarified that the net charges of nitrogen and phosphorus atoms contribute important electronic function in the inhibition of ChEs. The validity of the QSAR model was confirmed by a LOO cross-validation method with q2=0.965 between the training and testing sets. PMID:24893121

Gholivand, Khodayar; Ebrahimi Valmoozi, Ali Asghar; Bonsaii, Mahyar



Astrobiology Field Research in Moon/Mars Analogue Environments: Preface  

NASA Technical Reports Server (NTRS)

Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on Astrobiology field research in Moon/Mars analogue environments relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

Foing, B. H.; Stoker, C.; Ehrenfreund, P.



Modulation of amyloid precursor protein processing by synthetic ceramide analogues  

Microsoft Academic Search

Previous studies suggest that membrane lipids may regulate proteolytic processing of the amyloid precursor protein (APP) to generate amyloid-beta peptide (Abeta). In the present study, we have assessed the capacity for a series of structurally related synthetic ceramide analogues to modulate APP processing in vitro. The compounds tested are established glucosylceramide synthase (GS) inhibitors based on the d-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) structure.

Hongyun Li; Woojin S. Kim; Gilles J. Guillemin; Andrew F. Hill; Genevieve Evin; Brett Garner



The use of silver coated dressings on donor site wounds: a prospective, controlled matched pair study.  


Acticoat, a new silver-coated dressing, produces a moist healing environment along with the sustained release of ionic silver for improved microbial control. These properties suggest that Acticoat might be a useful donor site dressing. However, there are no human studies which assess Acticoat for this use. The purpose of this study was to compare the healing of human skin graft donor sites dressed with Acticoat, to the healing of those dressed with Allevyn, an occlusive moist-healing environment material, which is our standard donor site dressing. In burn patients who had undergone burn excision and grafting, identical side-by-side split thickness donor site wound pairs were dressed with Allevyn and Acticoat. Re-epithelialization was directly assessed daily by a single observer from post-operative day 6 onward, and by four independent observers who rated the extent of re-epithelialization by viewing standardized digital images of the wounds that had been obtained on post-operative days 6, 8, 10,and 12. Donor sites were swabbed for bacterial culture on days 3, 6, and 9. Subsequently, each study donor site scar was rated by a blinded observer using the Vancouver Scar Scale at 1, 2, and 3 months. Sixteen paired sites in 15 patients (3 female, 12 male) were studied. Donor sites dressed with Allevyn were >90% re-epithelialized at a mean of 9.1+/-1.6 days while donor sites dressed with Acticoat required a mean of 14.5+/-6.7 days to achieve >90% re-epithelialization (P=0.004). The Allevyn sites had significantly greater estimated re-epithelialization at days 6, 8, 10 and 12 than the Acticoat sites based on the observations of the digital images. There were no significant differences in the incidence of positive bacterial cultures with either dressing at days 3, 6, and 9. Donor sites dressed with Acticoat had significantly worse scars at 1 and 2 months but this difference resolved by 3 months. Our findings do not support the use of Acticoat as a skin graft donor site dressing. PMID:11525858

Innes, M E; Umraw, N; Fish, J S; Gomez, M; Cartotto, R C



Site specific metals criteria as determined by Water Effect Ratio studies  

SciTech Connect

Water Effect Ratios (WER) are being used to implement site-specific water quality criteria to address the variability of physical and chemical characteristics of site water and metals that may influence toxicity. A case in point, Coors Brewing Company in Golden, Colorado, has been granted site-specific criteria for the discharge of copper and zinc based on results of WER studies. Acute bioassays were conducted to determine seasonal WER values for copper, zinc and silver. The tests exposed Ceriodaphnia dubia and Pimephales promelas to graduated levels of metals in Clear Creek site water (below discharge mixing zone), reconstituted laboratory water and effluent. Final WER values, calculated by the ratio of LC50`s determined in site water and laboratory water, were multiplied by the standard metals criteria to develop the site specific values incorporated into the Coors Brewing Company permit to discharge. It is suggested that the high LC50 values for metals in site water is a factor of the effluent`s binding capacity that may reduce the bioavailability of metals in site water.

Castle, C.J.; Neserke, G. [Commercial Testing and Engineering Co., Denver, CO (United States)



Lewis acid sites and surface aluminum in aluminas and zeolites. A high-resolution NMR study  

SciTech Connect

It was the main purpose of this work to study the nature of Lewis acidity in various catalysts (aluminas and zeolites) pretreated under controlled atmosphere at different temperatures. Isotopically enriched ammonia [sup 15]NH[sub 3] chemisorption was employed to probe the surface active sites and to allow for magnetization transfer to surface and close-to-surface Al nuclei. A special deconvolution procedure was applied to obtain [sup 27]Al spectral parameters for different Al sites in partially resolved spectra. The procedure accounted for the normal distribution of electric field gradient tensor components at a particular site. It is shown that there are two kinds of Lewis sites on aluminas: namely, a tetrahedral site with isotropic shift of about 58 ppm and quadrupolar coupling constant QCC [approx equal] 6 MHz and a pentagonal site with a isotropic shift of about 40 ppm and a slightly smaller QCC. In zeolites the same kinds of sites exist in the nonframework aluminum debris, and in addition, the Broensted sites are associated with framework aluminum. 32 refs., 8 figs., 5 tabs.

Coster, D.; Blumenfeld, A.L.; Fripiat, J.J. (Univ. of Wisconsin, Milwaukee, WI (United States))



Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid  

PubMed Central

Summary Tropodithietic acid (TDA) is a structurally unique sulfur-containing antibiotic from the Roseobacter clade bacterium Phaeobacter inhibens DSM 17395 and a few other related species. We have synthesised several structural analogues of TDA and used them in bioactivity tests against Staphylococcus aureus and Vibrio anguillarum for a structure–activity relationship (SAR) study, revealing that the sulfur-free analogue of TDA, tropone-2-carboxylic acid, has an antibiotic activity that is even stronger than the bioactivity of the natural product. The synthesis of this compound and of several analogues is presented and the bioactivity of the synthetic compounds is discussed. PMID:25161739

Rabe, Patrick; Klapschinski, Tim A; Brock, Nelson L; Citron, Christian A; D'Alvise, Paul; Gram, Lone



Metabolism of Biotin and Analogues of Biotin by Microorganisms. Ii. Further Studies on the Conversion of D-Biotin to Biotin Vitamers by Lactobaccillus Plantarum.  

National Technical Information Service (NTIS)

Lactobacillus plantarum growing in excess biotin converts a portion to two vitamers (combinable and uncombinable with avidin) not utilizable for growth. These were detected by differential yeast-lactobacillus assay. In the present study, suspensions of 12...

J. Birnbaum, H. C. Lichstein



Cantharimides: A new class of modified cantharidin analogues inhibiting protein phosphatases 1 and 2A  

Microsoft Academic Search

Cantharidin and its analogues have been of considerable interest as potent inhibitors of the serine\\/threonine protein phosphatases 1 and 2A (PP1 and PP2A). However, limited modifications to the parent compounds is tolerated. As part of an on-going study we have developed a new series of cantharidin analogues, the cantharimides. Inhibition studies indicate that cantharimides possessing a d- or l-histidine, are

Adam McCluskey; Cecilia Walkom; Michael C Bowyer; Stephen P Ackland; Emma Gardiner; Jennette A Sakoff



Synthesis of a tetraazulene porphodimethene analogue.  


Substituted calix[4]azulenes were prepared by reacting 6-alkylazulenes with paraformaldehyde in the presence of florisil. Hydride abstraction of a calix[4]azulene with Ph(3)CPF(6) afforded a tetraazulene analogue of the porphodimethenes. PMID:19908914

Lash, Timothy D; El-Beck, Jessica A; Colby, Denise A



Investigating the hydrogen-bond acceptor site of the nicotinic pharmacophore model: a computational and experimental study using epibatidine-related molecular probes.  


The binding mode of nicotinic agonists has been thoroughly investigated in the last decades. It is now accepted that the charged amino group is bound by a cation-? interaction to a conserved tryptophan residue, and that the aromatic moiety is projected into a hydrophobic pocket deeply located inside the binding cleft. A hydrogen bond donor/acceptor, maybe a water molecule solvating this receptor subsite, contributes to further stabilize the nicotinic ligands. The position of this water molecule has been established by several X-ray structures of the acetylcholine-binding protein. In this study, we computationally analyzed the role of this water molecule as a putative hydrogen bond donor/acceptor moiety in the agonist binding site of the three most relevant heteromeric (?4?2, ?3?4) and homomeric (?7) neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Our theoretical investigation made use of epibatidine 1 and deschloroepibatidine 2 as molecular probes, and was then extended to their analogues 3 and 4, which were subsequently synthesized and tested at the three target receptor subtypes. Although the pharmacological data for the new ligands 3 and 4 indicated a reduction of the affinity at the studied nAChRs with respect to reference agonists, a variation of the selectivity profile was clearly evidenced. PMID:24276616

Dallanoce, Clelia; Grazioso, Giovanni; Pomè, Diego Yuri; Sciaccaluga, Miriam; Matera, Carlo; Gotti, Cecilia; Fucile, Sergio; De Amici, Marco



Presence and formation of cobalamin analogues in multivitamin-mineral pills.  


Because the origin of cobalamin (vitamin B12) analogues in animal chows and animal and human blood and tissues is unknown, we investigated the possibility that multivitamin interactions might convert cobalamin to cobalamin analogues. We homogenized three popular multivitamin-mineral pills in water, incubated them at 37 degrees C for 2 h, and isolated the cobalamin. Using paper chromatography we observed that 20-90% of the cobalamin was present as cobalamin analogues. Studies using CN-[57Co]cobalamin showed that these analogues were formed due to the concerted action of vitamin C, thiamine, and copper on CN-cobalamin. These cobalamin analogues are absorbed from the gastrointestinal tract of mice and either fail to stimulate or actually inhibit cobalamin-dependent enzymes when injected parenterally. We conclude that CN-cobalamin can be converted to potentially harmful cobalamin analogues by multivitamin-mineral interactions and that these interactions may be responsible for the presence of cobalamin analogues in animal chows and animal and human blood and tissues. PMID:6126492

Kondo, H; Binder, M J; Kolhouse, J F; Smythe, W R; Podell, E R; Allen, R H



Ecological studies related to construction of the Defense Waste Processing Facility on the Savannah River Site  

SciTech Connect

The Defense Waste Processing Facility (DWPF) was built on the Savannah River Site (SRS) during the mid-1980's. The Savannah River Ecology Laboratory (SREL) has completed 12 years of ecological studies related to the construction of the DWPF complex. Prior to construction, the 600-acre site (S-Area) contained a Carolina bay and the headwaters of a stream. Research conducted by the SREL has focused primarily on four questions related to these wetlands: (1) Prior to construction, what fauna and flora were present at the DWPF site and at similar, yet undisturbed, alternative sites (2) By comparing the Carolina bay at the DWPF site (Sun Bay) with an undisturbed control Carolina bay (Rainbow Bay), what effect is construction having on the organisms that inhabited the DWPF site (3) By comparing control streams with streams on the periphery of the DWPF site, what effect is construction having on the peripheral streams (4) How effective have efforts been to lessen the impacts of construction, both with respect to erosion control measures and the construction of refuge ponds'' as alternative breeding sites for amphibians that formerly bred at Sun Bay Through the long-term census-taking of biota at the DWPF site and Rainbow Bay, SREL has begun to evaluate the impact of construction on the biota and the effectiveness of mitigation efforts. Similarly, the effects of erosion from the DWPF site on the water quality of S-Area peripheral streams are being assessed. This research provides supporting data relevant to the National Environmental Policy Act (NEPA) of 1969, the Endangered Species Act of 1973, Executive Orders 11988 (Floodplain Management) and 11990 (Protection of Wetlands), and United States Department of Energy (DOE) Guidelines for Compliance with Floodplain/Wetland Environmental Review Requirements (10CFR1022).

Pechmann, J.H.K.; Scott, D.E.; McGregor, J.H.; Estes, R.A.; Chazal, A.C.



Introduction of shared electronic records: multi-site case study using diffusion of innovation theory  

Microsoft Academic Search

Objective To explore the introduction of a centrally stored, shared electronic patient record (the summary care record (SCR)) in England and draw wider lessons about the implementation of large scale information technology projects in health care.Design Multi-site, mixed method case study applying utilisation focused evaluation.Setting Four early adopter sites for the SCR in England—three in urban areas of relative socioeconomic

Trisha Greenhalgh; Katja Stramer; Tanja Bratan; Emma Byrne; Yara Mohammad; Jill Russell



Antitrypanosomal and Antileishmanial Activities of Flavonoids and Their Analogues: In Vitro, In Vivo, StructureActivity Relationship, and Quantitative StructureActivity Relationship Studies  

Microsoft Academic Search

Trypanosomiasis and leishmaniasis are important parasitic diseases affecting millions of people in Africa, Asia, and South America. In a previous study, we identified several flavonoid glycosides as antiprotozoal principles from a Turkish plant. Here we surveyed a large set of flavonoid aglycones and glycosides, as well as a panel of other related compounds of phenolic and phenylpropanoid nature, for their

Deniz Tasdemir; Marcel Kaiser; Reto Brun; Vanessa Yardley; Thomas J. Schmidt; Fatma Tosun; Peter Ruedi



Technical procedures for the implementation of cultural resource site studies, Deaf Smith County, Texas: Preliminary draft  

SciTech Connect

Cultural resources at the Deaf Smith County site will be identified, evaluated and managed through the implementation of studies detailed in the Site Study Plan for Cultural Resources. This technical procedure outlines the conduct of pedestrian survey and the documentation of identified cultural resources. The purpose of the field surveys is to identify and document cultural resources in the areas that will be affected by site characterization activities and to record the environmental setting of identified cultural resources. Three pedestrian surveys will cover 100 percent of the on-site and off-site project areas. Survey 1 will provide coverage of the Repository Surface Facility (RSF) area, which includes the Exploratory Shaft Facility (ESF) and two linear engineering design borehole (EDBH) seismic survey corridors. Survey 2 will provide coverage of a 39 km/sup 2/ (15 mi/sup 2/) area that includes the 23 km/sup 2/ (9 mi/sup 2/) Deaf Smith County site plus a 0.4 to 0.8 kM (1/4 to 1/2 mi) border area but excludes the area covered by Survey 1. Survey 3 will cover offsite geotechnical test areas, such as the locations of playa boreholes, deep playa wells, hydrologic tests, site foundation borings, and their access routes. The purpose of site documentation or recording is to address the project information needs for land use permits and approvals, engineering design support, and cultural resource evaluation for National Register of Historic Places eligibility. Site documentation will consist of gathering sufficient data on identified resources to complete Texas Natural Resource Information System (TNRIS). 7 refs., 3 figs.

Not Available



Second-Sphere Contributions to Substrate-Analogue Binding in Iron(III) Superoxide Dismutase  

E-print Network

incoming substrate for reaction with the FeSOD active site. 1. Introduction Superoxide dismutases (SODsSecond-Sphere Contributions to Substrate-Analogue Binding in Iron(III) Superoxide Dismutase Juan adducts of iron(III) superoxide dismutase (N3-FeSOD), which have been known for more than two decades

Miller, Anne-Frances


Synthetic Analogues of Cysteinate-Ligated Non-Heme Iron and Non-Corrinoid Cobalt Enzymes  

E-print Network

Synthetic Analogues of Cysteinate-Ligated Non-Heme Iron and Non-Corrinoid Cobalt Enzymes Julie A June 24, 2003 Contents 1. Introduction to Non-Heme Iron Enzymes 825 2. Nitrile Hydratase (NHase) 826 2.1. Enzyme Function 826 2.2. Enzyme Active Site Structure 826 2.3. Spectroscopic Properties 827 2

Kovacs, Julie


Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D 3 analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies  

Microsoft Academic Search

The aim of this review with meta-analysis was to determine if there is a rationale to use activated forms of vitamin D 3 to treat or prevent glucocorticoid-induced osteoporosis, and to compare the effect of active vitamin D 3 metabolites with that of other anti-osteoporosis therapies. We performed a systemic search using MEDLINE\\/PubMed (1966–2003). Animal studies and clinical trials involving

R. N. J. de Nijs; J. W. G. Jacobs; A. Algra; W. F. Lems; J. W. J. Bijlsma



More than the Sum of Its Parts: A Multiple Case Study on the Implementation of RTI in Five Sites  

ERIC Educational Resources Information Center

Using a multiple-gating procedure, 5 research sites (3 elementary and 2 middle schools) were identified as implementing a Response to Intervention (RTI) framework. This study uses a multiple case study design to describe the RTI implementation in reading at these 5 sites. Findings suggest that the sites studied are utilizing a hybrid model (a…

Tackett, Kathryn Klingler



The use of prostaglandins and their analogues for abortion.  


In general, termination of second trimester pregnancy is associated with three to five times higher morbidity and mortality risks than termination during the first trimester. The procedures mainly used are extra- or intra-amniotic administration of solutions such as hypertonic saline, ethacridine lactate, PGF2 alpha and PGE2. In comparison with these procedures, the use of prostaglandin analogues may offer important advantages, the most important one being the possibility of using non-invasive routes of administration. The continuous development of new analogues has now resulted in compounds that are highly effective in stimulating uterine contractility and are associated with a low frequency of side-effects; these compounds are suitable for both vaginal and intramuscular administration and are applicable for termination of pregnancy during both the early and late parts of the second trimester. The most widely used method for termination of first trimester pregnancy is vacuum aspiration. It is a highly effective procedure and the overall complication rate is low. One problem with vacuum aspiration is the mechanical dilatation of the cervical canal which is necessary from at least the 8th week and onwards. Pretreatment with laminaria tents or with prostaglandin analogues eliminates or reduces the need for mechanical dilatation and significantly facilitates the procedure. Pretreatment with prostaglandin analogues also reduces the risk of both operative and postoperative complications. The prostaglandins also offer a possibility as a non-surgical procedure for termination of very early pregnancy. Both vaginal and intramuscular administration of the latest generation of PG analogues have been shown in several studies to be equally as effective as vacuum aspiration if the treatment is restricted to the first three weeks following the first missed menstrual period. Gastrointestinal side-effects are still a problem although of significantly less importance than if natural prostaglandins are used. Preliminary studies in which one of these PGE analogues was administered by the vaginal route indicate that self-administration at home starts to be a reality in selected patients. PMID:6391777

Bygdeman, M



A continuous-time hierarchical field programmable analogue array for rapid prototyping and hierarchical approach to analogue systems design  

Microsoft Academic Search

This paper presents our continuous-time Hierarchical Field Programmable Analogue Array (HFPAA) designed as a result of our research efforts to enable rapid prototyping for analogue system design. Here, we present our continuous-time configurable analogue block (CAB) used for our HFPAA, with increased flexibility in facilitating a hierarchical approach to analogue design and also in configuring target applications. This is achieved

David Varghese; J. N. Ross



Chlorophenylpiperazine analogues as high affinity dopamine transporter ligands.  


Selective ?2 ligands continue to be an active target for medications to attenuate the effects of psychostimulants. In the course of our studies to determine the optimal substituents in the ?2-selective phenyl piperazines analogues with reduced activity at other neurotransmitter systems, we discovered that 1-(3-chlorophenyl)-4-phenethylpiperazine actually had preferentially increased affinity for dopamine transporters (DAT), yielding a highly selective DAT ligand. PMID:24211020

Motel, William C; Healy, Jason R; Viard, Eddy; Pouw, Buddy; Martin, Kelly E; Matsumoto, Rae R; Coop, Andrew



Spectral study of suggested Apollo sites. [proposals for financial support and the electronic spectra of pyroxenes  

NASA Technical Reports Server (NTRS)

The spectrophotometry (0.3 to 1.1 microns) of visited and proposed Apollo landing sites is presented along with proposals for financial support of the spectral study. The electronic spectra of pyroxenes is investigated along with an interpretation of telescopic spectral reflectivity curves of the moon. Reprints of published articles related to these studies are included.

Mccord, T. B.



Information revelation and internet privacy concerns on social network sites: a case study of facebook  

Microsoft Academic Search

Despite concerns raised about the disclosure of personal information on social network sites, research has demonstrated that users continue to disclose personal information. The present study employs surveys and interviews to examine the factors that influence university students to disclose personal information on Facebook. Moreover, we study the strategies students have developed to protect themselves against privacy threats. The results

Alyson L. Young; Anabel Quan-Haase



Role of Polymeric Endosomolytic Agents in Gene Transfection: A Comparative Study of Poly(l-lysine) Grafted with Monomeric l-Histidine Analogue and Poly(l-histidine).  


Endosomal entrapment is one of the main barriers that must be overcome for efficient gene expression along with cell internalization, DNA release, and nuclear import. Introducing pH-sensitive ionizable groups into the polycationic polymers to increase gene transfer efficiency has proven to be a useful method; however, a comparative study of introducing equal numbers of ionizable groups in both polymer and monomer forms, has not been reported. In this study, we prepared two types of histidine-grafted poly(l-lysine) (PLL), a stacking form of poly(l-histidine) (PLL-g-PHis) and a mono- l-histidine (PLL-g-mHis) with the same number of imidazole groups. These two types of histidine-grafted PLL, PLL-g-PHis and PLL-g-mHis, showed profound differences in hemolytic activity, cellular uptake, internalization, and transfection efficiency. Cy3-labeled PLL-g-PHis showed strong fluorescence in the nucleus after internalization, and high hemolytic activity upon pH changes was also observed from PLL-g-PHis. The arrangement of imidazole groups from PHis also provided higher gene expression than mHis due to its ability to escape the endosome. mHis or PHis grafting reduced the cytotoxicity of PLL and changed the rate of cellular uptake by changing the quantity of free ?-amines available for gene condensation. The subcellular localization of PLL-g-PHis/pDNA measured by YOYO1-pDNA intensity was highest inside the nucleus, while the lysotracker, which stains the acidic compartments was lowest among these polymers. Thus, the polymeric histidine arrangement demonstrate the ability to escape the endosome and trigger rapid release of polyplexes into the cytosol, resulting in a greater amount of pDNA available for translocation to the nucleus and enhanced gene expression. PMID:25144273

Hwang, Hee Sook; Hu, Jun; Na, Kun; Bae, You Han



Using the Moon as a high-fidelity analogue environment to study biological and behavioral effects of long-duration space exploration  

NASA Astrophysics Data System (ADS)

Due to its proximity to Earth, the Moon is a promising candidate for the location of an extra-terrestrial human colony. In addition to being a high-fidelity platform for research on reduced gravity, radiation risk, and circadian disruption, the Moon qualifies as an isolated, confined, and extreme (ICE) environment suitable as an analog for studying the psychosocial effects of long-duration human space exploration missions and understanding these processes. In contrast, the various Antarctic research outposts such as Concordia and McMurdo serve as valuable platforms for studying biobehavioral adaptations to ICE environments, but are still Earth-bound, and thus lack the low-gravity and radiation risks of space. The International Space Station (ISS), itself now considered an analog environment for long-duration missions, better approximates the habitable infrastructure limitations of a lunar colony than most Antarctic settlements in an altered gravity setting. However, the ISS is still protected against cosmic radiation by the Earth magnetic field, which prevents high exposures due to solar particle events and reduces exposures to galactic cosmic radiation. On Moon the ICE environments are strengthened, radiations of all energies are present capable of inducing performance degradation, as well as reduced gravity and lunar dust. The interaction of reduced gravity, radiation exposure, and ICE conditions may affect biology and behavior - and ultimately mission success - in ways the scientific and operational communities have yet to appreciate, therefore a long-term or permanent human presence on the Moon would ultimately provide invaluable high-fidelity opportunities for integrated multidisciplinary research and for preparations of a manned mission to Mars.

Goswami, Nandu; Roma, Peter G.; De Boever, Patrick; Clément, Gilles; Hargens, Alan R.; Loeppky, Jack A.; Evans, Joyce M.; Peter Stein, T.; Blaber, Andrew P.; Van Loon, Jack J. W. A.; Mano, Tadaaki; Iwase, Satoshi; Reitz, Guenther; Hinghofer-Szalkay, Helmut G.



U.S. Department of Energy remediation and restoration of radioactive sites: Project chariot case study  

SciTech Connect

The Project Chariot Site in the Cape Thompson Region of northwest Alaska was studied under the US Atomic Energy Commission`s Plowshare Program between 1958 and 1962 to determine environmental conditions and background radiation levels. Although no nuclear explosives were ever brought to the site, radioactive tracer studies were conducted by the US Geological Survey in 1962. The US Department of Energy took action to remediate the site in response to the concerns of local inhabitants. The remediation in July--August, 1993 involved sampling the environment for possible contamination, removing contaminated soils, and revegetating the disturbed tundra. Contaminated soil was excavated, packaged, and transported to the Nevada Test Site for disposal. Surface water, soil and sediment from surrounding areas and samples of small mammals, caribou, and vegetation were analyzed for radioisotopes. These results showed that the past risk to human health from site contamination was well within acceptable ranges. No unusual amounts of radioisotopes were detected in the biota. The site was successfully remediated, and no future risk to human health or the environment is expected. Disturbed areas were reseeded and fertilized, and Curlex Excelsior{trademark} blankets were used to keep soil in place. Results of reseeding and natural vegetation recovery were assessed one year after remediation.

Hopkins, A.; Mayasich, S.A. [International Technology Corp., Las Vegas, NV (United States); Wright, S.J. [Alaska Dept. of Natural Resources, Palmer, AK (United States); Hanson, W.C. [Hanson Environmental Research Services, Bellingham, WA (United States); Cabble, K.J. [Dept. of Energy, Las Vegas, NV (United States)



Somatostatin and analogues in the treatment of cancer. A review.  


Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized; however its clinical usefulness has been limited in the past by its extremely short plasma half-life. The development of long-acting somatostatin analogues has provided clinically useful agents for treatment of hormone-producing tumors. In addition to well-known inhibiting effects on hormone release and actions, recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms. The exact role of somatostatin analogues in cancer therapy has yet to be established; however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors. In this review, the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized. PMID:1671812

Evers, B M; Parekh, D; Townsend, C M; Thompson, J C



Remedial investigation/feasibility study for the David Witherspoon, Inc., 901 Site, Knoxville, Tennessee: Volume 1  

SciTech Connect

This remedial investigation (RI)/feasibility study (FS) supports the selection of remedial actions for the David Witherspoon, Inc. 901 Maryville Pike Site in Knoxville, Tennessee. Operations at the site, used as a recycling center, have resulted in past, present, and potential future releases of hazardous substances in to the environment. This Site is a Tennessee Superfund site. A phased approach was planned to (1) gather existing data from previous investigations managed by the Tenn. Dept. of Environment and Conservation; (2) perform a preliminary RI, including risk assessments, and an FS with existing data to identify areas where remedial action may be necessary; (3) gather additional field data to adequately define the nature and extent of risk-based contaminants that present identifiable threats to human and/or ecological receptors; and (4) develop remedial action alternatives to reduce risks to acceptable levels.




Ungeremine and Its hemisynthesized analogues as bactericides against Flavobacterium columnare.  


The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine. PMID:23331165

Schrader, Kevin K; Avolio, Fabiana; Andolfi, Anna; Cimmino, Alessio; Evidente, Antonio



Relation between food intake and visual analogue scale ratings of appetite and other sensations in healthy older and young subjects  

Microsoft Academic Search

Objective: Visual analogue scales are widely used in appetite research, yet the validity of these scales to evaluate appetite and mood has not been assessed in older subjects. The aim of this study was to determine the relations between food intake and visual analogue scale (VAS) ratings of appetite and nonappetite sensations in healthy older and young subjects.Design: Retrospective combined

B A Parker; K Sturm; C G MacIntosh; C Feinle; M Horowitz; I M Chapman



Relational Quadrilateralland. Analogues of Isospin and Hypercharge  

E-print Network

I consider the momenta and conserved quantities for CP^2 interpreted as the space of quadrilaterals. This builds on seminar I and II's kinematics via making use of MacFarlane's work considering the SU(3)-like (and thus particle physics-like) conserved quantities that occur for CP^2. I perform the additional step of further interpreting that as the configuration space of all relational quadrilaterals and thus an interesting toy model for whole-universe, relational and geometrodynamical-analogue physics. I also provide the Kuchar observables for the quadrilateral, which is a particular resolution of the Problem of Observables. I study HO-like and highly symmetric potentials. I also provide some exact solutions and qualitative behaviours for dynamics on CP^2. In each case, I reinterpret the results in terms of quadrilaterals. This paves the way for the quantum mechanical study of the relational quadrilateral and for investigations of a number of Problem of Time strategies and of a number of other foundational and qualitative investigations of Quantum Cosmology.

Edward Anderson



Work plan addendum for the remedial investigation and feasibility study of the Salmon Site  

SciTech Connect

This document is intended as an addendum to the Remedial Investigation and Feasibility Study (RI/FS) Work Plan for the Salmon Site (SS) (formerly the Tatum Dome Test Site) Lamar County, Mississippi. The original work plan - Remedial Investigation and Feasibility Study of the Tatum Dome Test Site, Lamar County, Mississippi (herein after called the Work Plan) was approved by the state of Mississippi in 1992 and was intended as the operative document for investigative activities at the Tatum Dome Test Site. Subsequent to the approval of the document a series of activities were undertaken under the auspices of the work plan. This document is organized in the same manner as the original work plan: (1) Introduction; (2) Site Background and History; (3) Initial Evaluation; (4) Data Quality Objectives; (5) RI/FS Tasks; (6) Project Schedule; (7) Project Management; and (8) Reference. This addendum will identify changes to the original work plan that are necessary because of additional information acquired at the SS. This document is not intended to replace the work plan, rather, it is intended to focus the remaining work in the context of additional site knowledge gained since the development of the original work plan. The U.S. Department of Energy (DOE) is conducting a focused and phased site characterization as a part, of the RI/FS. The RI/FS is the methodology under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) for evaluating hazardous waste sites on the National Priorities List (NPL). The SS is not listed on the NPL, but DOE has voluntarily elected to conduct the evaluation of the SS in accordance with CERCLA.




Delta sleep-inducing peptide and its tetrapeptide analogue alleviate severity of metaphit seizures  

Microsoft Academic Search

The effects of delta sleep-inducing peptide (DSIP) and its tetrapeptide analogue, DSIP(1-4), on metaphit-induced audiogenic seizures were studied. Five groups of adult male Wistar rats were intraperitoneally treated with (1) saline, (2) metaphit, (3) DSIP, (4) metaphit+DSIP and (5) metaphit+DSIP(1-4). To examine blocking effects of DSIP and its analogue on fully developed metaphit seizures, the last two groups were injected

Olivera Stanojlovi?; Dragana Živanovi?; Slobodan Mirkovi?; Inessa Mikhaleva



Antifouling Activity of Bromotyrosine-Derived Sponge Metabolites and Synthetic Analogues  

Microsoft Academic Search

Eighteen brominated sponge-derived metabolites and synthetic analogues were analyzed for antilarval settlement of Balanus improvisus. Only compounds exhibiting oxime substituents including bastadin-3 (4), ?4 (1), ?9 (2), and ?16 (3), hemibastadin-1 (6), aplysamine-2 (5), and psammaplin A (10) turned out to inhibit larval settling at 1 to 10 ?M. Analogues of hemibastadin-1 (6) were synthesized and tested for structure activity studies.

Sofia Ortlepp; Martin Sjögren; Mia Dahlström; Horst Weber; Rainer Ebel; RuAngelie Edrada; Carsten Thoms; Peter Schupp; Lars Bohlin; Peter Proksch



Pseudo-schwarzschild spherical accretion as a classical black hole analogue  

Microsoft Academic Search

We demonstrate that a spherical accretion onto astrophysical black holes, under the influence of Newtonian or various post-Newtonian\\u000a pseudo-Schwarzschild gravitational potentials, may constitute a concrete example of classical analogue gravity naturally found\\u000a in the Universe. We analytically calculate the corresponding analogue Hawking temperature as a function of the minimum number\\u000a of physical parameters governing the accretion flow. We study both

Surajit Dasgupta; Neven Bilic; Tapas K. Das



Antioxidant capacity of curcumin-directed analogues: Structure–activity relationship and influence of microenvironment  

Microsoft Academic Search

Curcumin is the active ingredient of turmeric powder with a variety of biological activities including antioxidative activity. In order to find more active antioxidants with curcumin as the lead compound we synthesised a series of enone analogues of curcumin. The present work studied and compared the capacity of curcumin-directed analogues to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and protect human red blood cells

Ya-Jing Shang; Xiao-Ling Jin; Xian-Ling Shang; Jiang-Jiang Tang; Guo-Yun Liu; Fang Dai; Yi-Ping Qian; Gui-Juan Fan; Qiang Liu; Bo Zhou



Giving Back: Collaborations with Others in Ecological Studies on the Nevada National Security Site - 13058  

SciTech Connect

Formerly named the Nevada Test Site, the Nevada National Security Site (NNSS) was the historical site for nuclear weapons testing from the 1950's to the early 1990's. The site was renamed in 2010 to reflect the diversity of nuclear, energy, and homeland security activities now conducted at the site. Biological and ecological programs and research have been conducted on the site for decades to address the impacts of radiation and to take advantage of the relatively undisturbed and isolated lands for gathering basic information on the occurrence and distribution of native plants and animals. Currently, the Office of the Assistant Manager for Environmental Management of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) oversees the radiological biota monitoring and ecological compliance programs on the NNSS. The top priority of these programs are compliance with federal and state regulations. They focus on performing radiological dose assessments for the public who reside near the NNSS and for populations of plants and animals on the NNSS and in protecting important species and habitat from direct impacts of mission activities. The NNSS serves as an invaluable outdoor laboratory. The geographic and ecological diversity of the site offers researchers many opportunities to study human influences on ecosystems. NNSA/NSO has pursued collaborations with outside agencies and organizations to be able to conduct programs and studies that enhance radiological biota monitoring and ecosystem preservation when budgets are restrictive, as well as to provide valuable scientific information to the human health and natural resource communities at large. NNSA/NSO is using one current collaborative study to better assess the potential dose to the off-site public from the ingestion of game animals, the most realistic pathway for off-site public exposure at this time from radionuclide contamination on the NNSS. A second collaborative study is furthering desert tortoise conservation measures onsite. It is the goal of NNSA/NSO to continue to develop such collaborations in the sharing of resources, such as personnel, equipment, expertise, and NNSS land access, with outside entities to meet mutually beneficial goals cost effectively. (authors)

Wade, Scott A.; Knapp, Kathryn S. [U.S. Department of Energy National Nuclear Security Agency, Nevada Site Office, P.O. Box 98518, Las Vegas, NV 89193-8518 (United States)] [U.S. Department of Energy National Nuclear Security Agency, Nevada Site Office, P.O. Box 98518, Las Vegas, NV 89193-8518 (United States); Wills, Cathy A. [National Nuclear Security Technologies, LLC, P.O. Box 98521, M/S 260, Las Vegas, NV 89193-8521 (United States)] [National Nuclear Security Technologies, LLC, P.O. Box 98521, M/S 260, Las Vegas, NV 89193-8521 (United States)



Giving Back: Collaborations with Others in Ecological Studies on the Nevada National Security Site  

SciTech Connect

Formerly named the Nevada Test Site, the Nevada National Security Site (NNSS) was the historical site for nuclear weapons testing from the 1950s to the early 1990s. The site was renamed in 2010 to reflect the diversity of nuclear, energy, and homeland security activities now conducted at the site. Biological and ecological programs and research have been conducted on the site for decades to address the impacts of radiation and to take advantage of the relatively undisturbed and isolated lands for gathering basic information on the occurrence and distribution of native plants and animals. Currently, the Office of the Assistant Manager for Environmental Management of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) oversees the radiological biota monitoring and ecological compliance programs on the NNSS. The top priority of these programs are compliance with federal and state regulations. They focus on performing radiological dose assessments for the public who reside near the NNSS and for populations of plants and animals on the NNSS and in protecting important species and habitat from direct impacts of mission activities. The NNSS serves as an invaluable outdoor laboratory. The geographic and ecological diversity of the site offers researchers many opportunities to study human influences on ecosystems. NNSA/NSO has pursued collaborations with outside agencies and organizations to be able to conduct programs and studies that enhance radiological biota monitoring and ecosystem preservation when budgets are restrictive, as well as to provide valuable scientific information to the human health and natural resource communities at large. NNSA/NSO is using one current collaborative study to better assess the potential dose to the off-site public from the ingestion of game animals, the most realistic pathway for off-site public exposure at this time from radionuclide contamination on the NNSS. A second collaborative study is furthering desert tortoise conservation measures onsite. It is the goal of NNSA/NSO to continue to develop such collaborations in the sharing of resources, such as personnel, equipment, expertise, and NNSS land access, with outside entities to meet mutually beneficial goals cost effectively.

Scott A. Wade (NFO); Kathryn S. Knapp (NFO); Cathy A. Wills (NSTec)



Anaerobic oxidation of toluene (analogues) to benzoate (analogues) by whole cells and by cell extracts of a denitrifying Thauera sp  

Microsoft Academic Search

Toluene and related aromatic compounds can be mineralized to CO2 under anoxic conditions. Oxidation requires new dehydrogenase-type enzymes and water as oxygen source, as opposed to the aerobic enzymatic attack by oxygenases, which depends on molecular oxygen. We studied the anaerobic process in the denitrifying bacterium Thauera sp. strain K172. Toluene and a number of its fluoro-, chloro- and methyl-analogues

Thomas Biegert; Georg Fuchs



A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis  

NASA Astrophysics Data System (ADS)

EXPERIMENTAL allergic encephalomyelitis (EAE) is an acute inflammatory autoimmune disease of the central nervous system that can be elicited in rodents and is the major animal model for the study of multiple sclerosis (MS)1,2. The pathogenesis of both EAE and MS directly involves the CD4+ helper T-cell subset3-5. Anti-CD4 monoclonal antibodies inhibit the development of EAE in rodents6-9, and are currently being used in human clinical trials for MS. We report here that similar therapeutic effects can be achieved in mice using a small (rationally designed) synthetic analogue of the CD4 protein surface. It greatly inhibits both clinical incidence and severity of EAE with a single injection, but does so without depletion of the CD4+ subset and without the inherent immunogenicity of an antibody. Furthermore, this analogue is capable of exerting its effects on disease even after the onset of symptoms.

Jameson, Bradford A.; McDonnell, James M.; Marini, Joseph C.; Korngold, Robert



Sustaining Programs in Physics Teacher Education: A Study of PhysTEC Supported Sites  

NSDL National Science Digital Library

For over a decade, physics teacher education programs have been transformed at a number of institutions around the country through support from the Physics Teacher Education Coalition (PhysTEC), led by the American Physical Society in partnership with the American Association of Physics Teachers. In 2012-2013, PhysTEC supported an independent study on the sustainability of its sites after project funding ends. The study sought to measure the extent to which programs have been sustained and to identify what features should be prioritized for building sustainable physics teacher education programs. Most PhysTEC legacy sites studied have sustained their production of physics teachers. Some sites studied have thriving physics teacher education programs, that is, programs that have continued to substantially increase their production of teachers since the PhysTEC award. All of the studied sites that sustained their production of physics teachers have a champion of physics teacher education and corresponding institutional motivation and commitment. At some sites, PhysTEC support has precipitated an institutional focus on physics teacher education, leveraging other resources (including both awards and personnel) benefiting physics teacher education. The study also documented the sustainability of components of physics teacher education programs, such as recruitment, early teaching experiences, and a teacher in residence. The number of sustained components does not appear to correspond to teacher production; that is, sites that have sustained more (or fewer) components do not produce larger (or smaller) numbers of teachers. This result further supports the finding that the presence of the champion and corresponding institutional motivation and commitment are the key features of successful physics teacher education programs. 2014 PhysTEC Conference

Plisch, Monica; Goertzen, Renee M.; Scherr, Rachel E.



Enzymatic and Cryoreduction EPR Studies of the Hydroxylation of Methylated N(?)-Hydroxy-l-arginine Analogues by Nitric Oxide Synthase from Geobacillus stearothermophilus.  


Nitric oxide synthase (NOS) catalyzes the conversion of l-arginine to l-citrulline and NO in a two-step process involving the intermediate N(?)-hydroxy-l-arginine (NHA). It was shown that Cpd I is the oxygenating species for l-arginine; the hydroperoxo ferric intermediate is the reactive intermediate with NHA. Methylation of the N(?)-OH and N(?)-H of NHA significantly inhibits the conversion of NHA into NO and l-citrulline by mammalian NOS. Kinetic studies now show that N(?)-methylation of NHA has a qualitatively similar effect on H2O2-dependent catalysis by bacterial gsNOS. To elucidate the effect of methylating N(?)-hydroxy l-arginine on the properties and reactivity of the one-electron-reduced oxy-heme center of NOS, we have applied cryoreduction/annealing/EPR/ENDOR techniques. Measurements of solvent kinetic isotope effects during 160 K cryoannealing cryoreduced oxy-gsNOS/NHA confirm the hydroperoxo ferric intermediate as the catalytically active species of step two. Product analysis for cryoreduced samples with methylated NHA's, NHMA, NMOA, and NMMA, annealed to 273 K, show a correlation of yields of l-citrulline with the intensity of the g 2.26 EPR signal of the peroxo ferric species trapped at 77 K, which converts to the reactive hydroperoxo ferric state. There is also a correlation between the yield of l-citrulline in these experiments and kobs for the H2O2-dependent conversion of the substrates by gsNOS. Correspondingly, no detectable amount of cyanoornithine, formed when Cpd I is the reactive species, was found in the samples. Methylation of the NHA guanidinium N(?)-OH and N(?)-H inhibits the second NO-producing reaction by favoring protonation of the ferric-peroxo to form unreactive conformers of the ferric-hydroperoxo state. It is suggested that this is caused by modification of the distal-pocket hydrogen-bonding network of oxy gsNOS and introduction of an ordered water molecule that facilitates delivery of the proton(s) to the one-electron-reduced oxy-heme moiety. These results illustrate how variations in the properties of the substrate can modulate the reactivity of a monooxygenase. PMID:25251261

Davydov, Roman; Labby, Kristin Jansen; Chobot, Sarah E; Lukoyanov, Dmitriy A; Crane, Brian R; Silverman, Richard B; Hoffman, Brian M



Ester groups as carriers of antivirally active tricyclic analogue of acyclovir in prodrugs designing: synthesis, lipophilicity--comparative statistical study of the chromatographic and theoretical methods, validation of the HPLC method.  


Knowledge of the lipophilicity of candidate compounds for prodrugs may predict their predetermined course/effect in the body. Acyclovir (ACV) belongs to a class of drugs with low bioavailability. Its tricyclic analogues, the derivatives of 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-9-oxo-5H-imidazo[1,2-a]purine (TACV) exhibit similar antiviral activities and are more lipophilic as compared with acyclovir itself. In the search for new antiviral prodrugs 6-(4- methoxyphenyl) tricyclic compound (6-(4-MeOPh)-TACV) was modified by esterification of a hydroxyl group in the aliphatic chain. Selected esters (acetyl, isobutyryl, pivaloyl, ethoxycarbonyl and nicotinoyl) were synthesized and their lipophilicity was determined by the HPLC-RP method. The study compared the log kw calculated from the linear and quadratic equations and proved the correctness of the application of the linear relationship log k as a function of the concentration of ACN in the mobile phase (30-60%). Statistical analyses of the comparative values of log kw and clogP were carried out using computational methods. It was proved that the AC logP algorithm can be useful for the analysis of these compounds, which can have a statistically justified application in the assessment of the quantitative structure- activity relationship (QSAR). The lipophilicity determined by the HPLC method appears as follows: 6-(4-MeOPh)-TACV < Ac- < Nic- < Etc- < iBut- < Piv- (log kw = 0.65-2.26). Finally, the HPLC-RP method was developed and validated for simultaneous determination of synthesized esters. PMID:24855987

Lesniewska, Monika A; Ostrowski, Tomasz; Zeidler, Joanna; Muszalska, Izabela



Rational design of ?-helix-stabilized exendin-4 analogues.  


Exendin-4 (Ex4) is a potent glucagon-like peptide-1 receptor agonist, a drug regulating the plasma glucose level of patients suffering from type 2 diabetes. The molecule's poor solubility and its readiness to form aggregates increase the likelihood of unwanted side effects. Therefore, we designed Ex4 analogues with improved structural characteristics and better water solubility. Rational design was started from the parent 20-amino acid, well-folded Trp cage (TC) miniprotein and involved the step-by-step N-terminal elongation of the TC head, resulting in the 39-amino acid Ex4 analogue, E19. Helical propensity coupled to tertiary structure compactness was monitored and quantitatively analyzed by electronic circular dichroism and nuclear magnetic resonance (NMR) spectroscopy for the 14 peptides of different lengths. Both (15)N relaxation- and diffusion-ordered NMR measurements were established to investigate the inherent mobility and self-association propensity of Ex4 and E19. Our designed E19 molecule has the same tertiary structure as Ex4 but is more helical than Ex4 under all studied conditions; it is less prone to oligomerization and has preserved biological activity. These conditions make E19 a perfect lead compound for further drug discovery. We believe that this structural study improves our understanding of the relationship between local molecular features and global physicochemical properties such as water solubility and could help in the development of more potent Ex4 analogues with improved pharmacokinetic properties. PMID:24828921

Rovó, Petra; Farkas, Viktor; Stráner, Pál; Szabó, Mária; Jermendy, Agnes; Hegyi, Orsolya; Tóth, Gábor K; Perczel, András



Contact zones and hydrothermal systems as analogues to repository conditions  

SciTech Connect

Radioactive waste isolation efforts in the US are currently focused on examining basalt, tuff, salt, and crystalline rock as candidate rock types to encompass waste repositories. As analogues to near-field conditions, the distributions of radio- and trace-elements have been examined across contacts between these rocks and dikes and stocks that have intruded them. The intensive study of the Stripa quartz monzonite has also offered the opportunity to observe the distribution of uranium and its daughters in groundwater and its relationship to U associated with fracture-filling and alteration minerals. Investigations of intrusive contact zones to date have included (1) a tertiary stock into Precambrian gneiss, (2) a stock into ash flow tuff, (3) a rhyodacite dike into Columbia River basalt, and (4) a kimberlite dike into salt. With respect to temperature and pressure, these contact zones may be considered "worst-case scenario" analogues. Results indicate that there has been no appreciable migration of radioelements from the more radioactive intrusives into the less radioactive country rocks, either in response to the intrusions or in the fracture-controlled hydrological systems that developed following emplacement. In many cases, the radioelements are locked up in accessory minerals, suggesting that artificial analogues to these would make ideal waste forms. Emphasis should now shift to examination of active hydrothermal systems, studying the distribution of key elements in water, fractures, and alteration minerals under pressure and temperature conditions most similar to those expected in the near-field environment of a repository. 14 refs.

Wollenberg, H.A.; Flexser, S.



Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D  

NASA Astrophysics Data System (ADS)

The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from -42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain), considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra) climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from -69% to -14% compared to the present-day climate.

Leterme, B.; Mallants, D.; Jacques, D.



Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro  

NASA Astrophysics Data System (ADS)

Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues using a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current clinical candidate for latent virus induction. This study provides the first demonstration that designed, synthetically accessible bryostatin analogues could serve as superior candidates for the eradication of HIV/AIDS through induction of latent viral reservoirs in conjunction with current antiretroviral therapy.

Dechristopher, Brian A.; Loy, Brian A.; Marsden, Matthew D.; Schrier, Adam J.; Zack, Jerome A.; Wender, Paul A.



[A comparative study of early degradation of PLLA and PLGA rods at various sites in rabbit].  


This study was designed to assess the effect of implantation site and environment on early in vivo degradation behaviors of poly(L-lactide) (PLLA) and poly(L-lactide-co-glycolide) (PLGA) copolymer. The rods were implanted at two sites in each of 24 New Zealand White rabbits. The first site was within the suprapatellar bursa of the joint cavities (JC) and the second site was in the opposite condyles of femurs (CF). Three rabbits of each group underwent explantation of rods after 4, 8, 12, and 16 weeks. At each interval, measures were taken to evaluate the molecular weight, shear strength, weight loss and thermal properties of PLLA and PLGA. It was found that PLGA degraded slightly faster than PLLA. After 16 weeks, PLLA's initial inherent viscosity of 4.6 decreased to about 3.4 in both implantation sites while that of PLGA decreased from 4.6 to about 2.2. Both PLGA and PLLA showed enough shear strength retention in 16 weeks (> or = 53MPa) within 16 weeks. Autocatalysis mechanism was confirmed by the fact of accelerated weight loss of PLGA after 8 weeks and of PLLA after 12 weeks. The results revealed that PLGA could be a promising candidate material as a replacement of PLLA in internal fixation of bone fractures, and no significant difference of early in vivo degradation behaviors between PLLA and PLGA was observed in regard to different implantation sites in 16 weeks. PMID:21374982

Pang, Di; Ye, Jingbing; Chen, Dongliang; Li, Jian; Xiong, Chengdong; Li, Qing



Overview of analogue science activities at the McGill Arctic Research Station, Axel Heiberg Island, Canadian High Arctic  

NASA Astrophysics Data System (ADS)

The Canadian High Arctic contains several of the highest fidelity Mars analogue sites in the world. Situated at nearly 80° north, Expedition Fjord on Axel Heiberg Island is located within a polar desert climate, with the surrounding landscape and conditions providing an invaluable opportunity to examine terrestrial processes in a cold, dry environment. Through the Canadian Space Agency's Analogue Research Network program, scientific activities based out of the McGill Arctic Research Station (M.A.R.S.) are extremely broad in scope, representing physical, biological, and technological investigations. Some of the most unique hydrogeologic features under investigation near M.A.R.S. are a series of cold saline springs that maintain liquid-state flow year round regardless of air temperature. Previous studies have examined their geomorphic relation to discharge-related formations, water chemistry, temperature monitoring, discharge rates, and combined flow/thermal modeling. Recent investigations have identified microbial communities and characterized biological activity within the springs and within permafrost sections, having direct relevance to astrobiological analogue research goals. Another main thrust of research activities based at M.A.R.S. pertains to the detection, mapping, and quantification of subsurface ice deposits. A long-term study is presently underway examining polygonal terrain, comparing surficial patterns found in the region with those identified on Mars, and using surface morphology to estimate ice wedge volumes through a combination of aerial photography interpretation and ground-based geophysical techniques. Other technological developments include the use of in situ microscopy for the detection of biomarkers and improved permafrost drilling techniques. This paper presents an overview of previous studies undertaken at M.A.R.S. over the past decades and will describe in detail both present and upcoming work.

Pollard, Wayne; Haltigin, Tim; Whyte, Lyle; Niederberger, Thomas; Andersen, Dale; Omelon, Christopher; Nadeau, Jay; Ecclestone, Miles; Lebeuf, Martin



Site-directed fragment-based generation of virtual sialic acid databases against influenza A hemagglutinin.  


In this study fragment-based drug design is combined with molecular docking simulation technique, to design databases of virtual sialic acid (SA) analogues with new substitutions at C2, C5 and C6 positions of SA scaffold. Using spaces occupied by C2, C5 and C6 natural moieties of SA when bound to hemagglutinin (HA) crystallographic structure, new fragments that are commercially available were docked independently in all the pockets. The oriented fragments were then connected to the SA scaffold with or without incorporation of linker molecules. The completed analogues were docked to the whole SA binding site to estimate their binding conformations and affinities, generating three databases of HA-bound SA analogues. Selected new analogues showed higher estimated affinities than the natural SA when tested against H3N2, H5N1 and H1N1 subtypes of influenza A. An improvement in the binding energies indicates that fragment-based drug design when combined with molecular docking simulation is capable to produce virtual analogues that can become lead compound candidates for anti-flu drug discovery program. PMID:19856192

Al-qattan, Mohammed Noor; Mordi, Mohd Nizam



Specific binding of (/sup 3/H)LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles  

SciTech Connect

LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for (/sup 3/H)LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound (/sup 3/H)LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that (/sup 3/H)LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs.

Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.



Imperial College London EEE 1L1 Autumn 2009 E2.2 Analogue Electronics E2.2 Analogue Electronics  

E-print Network

Imperial College London ­ EEE 1L1 Autumn 2009 E2.2 Analogue Electronics E2.2 Analogue Electronics Autumn 2009 E2.2 Analogue Electronics What analogue electronics is · Engineering, i.e. the analysis ­ EEE 3L1 Autumn 2009 E2.2 Analogue Electronics analogue electronics is not only · CMOS integrated

Papavassiliou, Christos


A Multi-Site Study of the Clinical Diagnosis of Different Autism Spectrum Disorders  

PubMed Central

Context Clinical best estimate diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, Asperger’s disorder) have been used as the diagnostic gold standard, even when information from standardized instruments is available. Objective To determine if the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. Design Multi-site observational study collecting clinical phenotype data (diagnostic, developmental and demographic) for genetic research. Classification trees were employed to identify characteristics that predicted diagnosis across and within sites. Setting Participants were recruited through 12 university-based autism service providers into a genetic study of autism. Participants 2102 probands (1814 males) between 4 and 18 years of age (M age=8.93, SD=3.5 years) who met autism spectrum criteria on the Autism Diagnostic Interview–Revised and Autism Diagnostic Observation Schedule and had a clinical diagnosis of an autism spectrum disorder. Main Outcome Measures Best estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. Results Though distributions of scores on standardized measures were similar across sites, significant site differences emerged in best estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level and core diagnostic features, varied across sites in weighting of information and cut-offs. Conclusions Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing sub-groupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors, together with characteristics such as language level and cognitive function. PMID:22065253

Lord, Catherine; Petkova, Eva; Hus, Vanessa; Gan, Weijin; Lu, Feihan; Martin, Donna M.; Ousley, Opal; Guy, Lisa; Bernier, Raphael; Gerdts, Jennifer; Algermissen, Molly; Whitaker, Agnes; Sutcliffe, James S.; Warren, Zachary; Klin, Ami; Saulnier, Celine; Hanson, Ellen; Hundley, Rachel; Piggot, Judith; Fombonne, Eric; Steiman, Mandy; Miles, Judith; Kanne, Stephen M.; Goin-Kochel, Robin P.; Peters, Sarika U.; Cook, Edwin H.; Guter, Stephen; Tjernagel, Jennifer; Green-Snyder, Lee Anne; Bishop, Somer; Esler, Amy; Gotham, Katherine; Luyster, Rhiannon; Miller, Fiona; Olson, Jennifer; Richler, Jennifer; Risi, Susan



Antizyme induction mediates feedback limitation of the incorporation of specific polyamine analogues in tissue culture  

PubMed Central

Spermidine, spermine and putrescine are essential for mammalian cell growth, and there has been a pervasive effort to synthesize analogues of these polyamines that will disrupt their function and serve as tools to inhibit cell proliferation. Recently, we demonstrated that a number of such polyamine analogues are also capable of inducing the regulatory protein AZ (antizyme). In the present study the incorporation of a few sample analogues [mimics of bis(ethyl)spermine] was shown to be significantly limited by a decrease in the Vmax for the polyamine transport system in response to analogue-induced AZ. This creates an unusual circumstance in which compounds that are being designed for therapeutic use actually inhibit their own incorporation into targeted cells. To explore the impact of this feedback system, cultures of rat hepatoma HTC cells were pre-treated to exhibit either low or high polyamine uptake activity and then exposed to polyamine analogues. As predicted, regardless of initial uptake activity, all cultures eventually achieved the same steady-state levels of the cellular analogue and AZ. Importantly, analogue-induced AZ levels remained elevated with respect to controls even after the native polyamines were reduced by more than 70%. To model the insufficient AZ expression found in certain tumours, GS-CHO (GS Chinese-hamster ovary) cells were transfected to express high levels of exogenic AZI (AZ inhibitor). As anticipated, this clone incorporated significantly higher levels of the polyamine analogues examined. This study reveals a potential limitation in the use of polyamine-based compounds as therapeutics, and strategies are presented to either circumvent or exploit this elegant transport feedback system. PMID:15315476



Design, synthesis, and pharmacological characterization of novel endomorphin-1 analogues as extremely potent ?-opioid agonists.  


Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural ?-methylene-?-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-?Pro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the ?-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-?Pro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki(?) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, Emax = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier. PMID:23477419

Liu, Xin; Wang, Yuan; Xing, Yanhong; Yu, Jing; Ji, Hong; Kai, Ming; Wang, Zilong; Wang, Dan; Zhang, Yixin; Zhao, Depeng; Wang, Rui



Studies on identifying the binding sites of folate and its derivatives in Lactobacillus casei thymidylate synthase  

SciTech Connect

It was shown that folate and its derivatives have a profound effect on stabilizing thymidylate synthase in vitro and in vivo, as a consequence of ternary formation between the folate, dUMP, or FdUMP, and the synthase. The degree to which complex formation is affected can be revealed qualitatively by circular dichroism and quantitatively by equilibrium dialysis using the Lactobacillus casei synthase. In contrast to the pteroylmonoglutamates, the pteroylpolyglutamates bind to thymidylate synthase in the absence of dUMP, but even their binding affinity is increased greatly by this nucleotide or its analogues. Similarly, treatment of the synthase with carboxypeptidase A prevents the binding of the pteroylmonoglutamates and reduces the binding of the polyglutamates without affecting dUMP binding. The latter does not protect against carboxypeptidase inactivation but does potentiate the protective effect of the pteroylpolyglutamates. To determine the region of the synthase involved in the binding of the glutamate residues, Pte(/sup 14/C)GluGlu6 was activated by a water soluble carbodiimide in the presence and absence of dUMP. This folate derivative behaved as a competitive inhibitor of 5,10-CH/sub 2/H/sub 4/PteGlu, in contrast to methotrexate which was non-competitive. Separation of the five cyanogen bromide peptides from the L. casei synthase revealed 80% of the radioactivity to be associated with CNBr-2 and about 15% with CNBr-4. Chymotrypsin treatment of CNBr-2 yielded two /sup 14/C-labeled peaks on high performance liquid chromatography, with the slower migrating one being separated further into two peaks by Bio-gel P2 chromatography. All three peptides came from the same region of CNBr-2, encompassing residues 47-61 of the enzyme. From these studies it would appear that the residues most probably involved in the fixation of PteGlu7 are lysines 50 and 58. In contrast, methotrexate appeared to bind to another region of CNBr-2.

Maley, F.; Maley, G.F.



'Carba'-Analogues of Fentanyl are Opioid Receptor Agonists‡  

PubMed Central

There is evidence to indicate that the Asp residue in the third transmembrane helix (TMH) of opioid receptors forms a salt bridge with the positively charged nitrogen of endogenous and exogenous opioid ligands. To further examine the role of this electrostatic interaction in receptor binding and activation, we synthesized ‘carba’-analogues of a published fentanyl analogue containing a 3-(guanidinomethyl)-benzyl group in place of the phenyl moiety attached to the ethylamido group (C. Dardonville et al., Bioorg. Med. Chem. 2006, 14, 6570–6580 (1)), in which the piperidine ring nitrogen was replaced with a carbon. As expected, the resulting cis and trans isomers (8a and 8b) showed reduced ? and ? opioid receptor binding affinities as compared to 1, but surprisingly, retained opioid full agonist activity with about half the potency of leucine-enkephalin in the guinea pig ileum assay. In conjunction with performed receptor docking studies, these results indicate that the electrostatic interaction of the protonated nitrogen in the piperidine ring of fentanyl analogues with the Asp residue in the third TMH is not a conditio sine qua non for opioid receptor activation. PMID:20218625

Weltrowska, Grazyna; Chung, Nga N.; Lemieux, Carole; Guo, Jianxin; Lu, Yixin; Wilkes, Brian C.; Schiller, Peter W.



Norcantharidin analogues with nematocidal activity in Haemonchus contortus.  


With the major problems with resistance in parasitic nematodes of livestock to anthelmintic drugs, there is an urgent need to develop new nematocides. In the present study, we employed a targeted approach for the design of a series of norcantharidin analogues (n=54) for activity testing against the barber's pole worm (Haemonchus contortus) of small ruminants in a larval development assay (LDA) and also for toxicity testing on nine distinct human cell lines. Although none of the 54 analogues synthesized were toxic to any of these cell lines, three of them (N-octyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B2), N-decyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B3) and 4-[(4-methyl)-3-ethyl-2-methyl-5-phenylfuran-10-oxa-4-azatricyclo[5.2.1]decane-3,5-dione (B21) reproducibly displayed 99-100% lethality to H. contortus in LDA, with LD(50s) of 25-40 ?M. The high 'hit rate' (5.6%) indicates that the approach taken here has advantages over conventional drug screening methods. A major advantage of norcantharidin analogues over some other currently available anthelmintics is that they can be produced in one to two steps in large amounts at low cost and high purity, and do not require any additional steps for the isolation of the active isomer. This positions them well for commercial development. PMID:21536433

Campbell, Bronwyn E; Tarleton, Mark; Gordon, Christopher P; Sakoff, Jennette A; Gilbert, Jayne; McCluskey, Adam; Gasser, Robin B



Noble gas encapsulation: clathrate hydrates and their HF doped analogues.  


The significance of clathrate hydrates lies in their ability to encapsulate a vast range of inert gases. Although the natural abundance of a few noble gases (Kr and Xe) is poor their hydrates are generally abundant. It has already been reported that HF doping enhances the stability of hydrogen hydrates and methane hydrates, which prompted us to perform a model study on helium, neon and argon hydrates with their HF doped analogues. For this purpose 5(12), 5(12)6(8) and their HF doped analogues are taken as the model clathrate hydrates, which are among the building blocks of sI, sII and sH types of clathrate hydrate crystals. We use the dispersion corrected and gradient corrected hybrid density functional theory for the calculation of thermodynamic parameters as well as conceptual density functional theory based reactivity descriptors. The method of the ab initio molecular dynamics (AIMD) simulation is used through atom centered density matrix propagation (ADMP) techniques to envisage the structural behaviour of different noble gas hydrates on a 500 fs timescale. Electron density analysis is carried out to understand the nature of Ng-OH2, Ng-FH and Ng-Ng interactions. The current results noticeably demonstrate that the noble gas (He, Ne, and Ar) encapsulation ability of 5(12), 5(12)6(8) and their HF doped analogues is thermodynamically favourable. PMID:25047071

Mondal, Sukanta; Chattaraj, Pratim Kumar



Kinetic mechanisms of the nucleotide cofactor binding to the strong and weak nucleotide-binding site of the Escherichia coli PriA helicase. 2.  


Kinetics of the nucleotide binding to the strong (S) and weak (W) nucleotide-binding site of the Escherichia coli PriA helicase have been studied using the fluorescence stopped-flow technique. Experiments were performed with TNP-ADP and TNP-ATP analogues. Binding of the ADP analogue to the strong binding site is a four-step sequential reaction: (PriA)S + D (k1)<-->(k(-1)) + (S)1 (k2)<-->(k(-2)) (S)2 (k3)<-->(k(-3)) (S)3 (k4)<-->(k(-4)) (S)4. Association of TNP-ATP proceeds through an analogous three-step mechanism. The first two steps and intermediates are similar for both cofactors. However, the (S)3 intermediate is dramatically different for ADP and ATP analogues. Its emission is close to the emission of the free TNP-ADP, while it is by a factor of approximate