These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Understanding Rubredoxin Redox Sites by Density Functional Theory Studies of Analogues  

PubMed Central

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

Luo, Yan; Niu, Shuqiang; Ichiye, Toshiko

2012-01-01

2

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

NASA Astrophysics Data System (ADS)

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

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

3

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

NASA Astrophysics Data System (ADS)

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

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

2011-12-01

4

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

NASA Astrophysics Data System (ADS)

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

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

2004-06-01

5

Space analogue studies in Antarctica  

NASA Astrophysics Data System (ADS)

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

Lugg, D.; Shepanek, M.

1999-09-01

6

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.

1999-01-01

7

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.

2012-01-01

8

Spectroscopic study of solar twins and analogues  

E-print Network

Context. Many large stellar surveys have been and are still being carried out, providing huge amounts of data, for which stellar physical parameters will be derived. Solar twins and analogues provide a means to test the calibration of these stellar catalogues because the Sun is the best-studied star and provides precise fundamental parameters. Solar twins should be centred on the solar values. Aims. This spectroscopic study of solar analogues selected from the Geneva-Copenhagen Survey (GCS) at a resolution of 48,000 provides effective temperatures and metallicities for these stars. We test whether our spectroscopic parameters, as well as the previous photometric calibrations, are properly centred on the Sun. In addition, we search for more solar twins in our sample. Methods. The methods used in this work are based on literature methods for solar twin searches and on methods we developed in previous work to distinguish the metallicity-temperature degeneracies in the differential comparison of spectra of solar ...

Datson, Juliet; Portinari, Laura

2014-01-01

9

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.

2011-01-01

10

Spectroscopic study of solar twins and analogues  

NASA Astrophysics Data System (ADS)

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

Datson, Juliet; Flynn, Chris; Portinari, Laura

2015-02-01

11

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.

2007-01-01

12

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

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

13

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

USGS Publications Warehouse

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

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

1992-01-01

14

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.

2004-01-01

15

FIGIFIGO as a tool to characterize and identify planetary analogue sites  

NASA Astrophysics Data System (ADS)

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

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

2014-07-01

16

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.

2010-12-01

17

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

SciTech Connect

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

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

2008-10-25

18

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

19

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

SciTech Connect

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

Denecke, Melissa A.; Brendebach, Boris; Rothe, Joerg; Simon, Rolf [Forschungszentrum Karlsruhe, P.O. Box 3640, D-76021 Karlsruhe (Germany); Janssens, Koen; Nolf, Wout de; Vekemans, Bart [Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp (Belgium); Falkenberg, Gerald [Hamburger Synchrotronstrahlungslabor (HASYLAB) at DESY, Notkestr. 85, D-22603 Hamburg (Germany); Somogyi, Andrea [Synchrotron Soleil, F-91192 Gif-sur-Yvette Cedex (France); Noseck, Ulrich [Gesellschaft fuer Anlagen- und Reaktorsicherheit (GRS) mbH, Theodor-Heuss-Strasse 4, D-38122 Braunschweig (Germany)

2007-02-02

20

Experimental Studies of Formation of Molecules on Dust Grain Analogues  

NASA Astrophysics Data System (ADS)

We illustrate our research program on molecule formation on dust grain analogues in ISM conditions. We present experimental results of the role of ice morphology on the formation of hydrogen molecules. These results are then applied to models of processes of molecule formation in dense clouds. A comparison of data of molecular hydrogen formation on different types of dust analogues is also presented. Finally, an addition to our apparatus to study the kinetics and roto-vibrational energy of the just formed molecules as they are ejected into the gas-phase is described and the first tests presented. We are grateful to NASA (through grants NAG5-11438 and NAG5-9093) and the Italian Ministry for University and Scientific Research (through grant 21043088 CNR) for financial support.

Vidali, Gianfranco; Roser, Joe; D'Agostino, Robert; Pirronello, Valerio; Manico', Giulio

21

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

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

22

The Gd(3+) complex of a fatty acid analogue of DOTP binds to multiple albumin sites with variable water relaxivities.  

PubMed

The 20 MHz water relaxivity (r(1)) of gadolinium(III) complexes formed with two fatty acid analogues of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) were shown to increase substantially in the presence of albumin. The r(1) values of Gd(C(8)-DOTP)(5-) and Gd(C(11)-DOTP)(5-) in water were similar to that of the parent GdDOTP(5-), a q = 0 complex known to relax water very efficiently via an outer-sphere mechanism. Neither fatty acid analogue formed apparent aggregates or micelles in water up to 20 mM, but both showed dramatic increases in r(1) upon addition of albumin. Further ultrafiltration studies of Gd(C(11)-DOTP)(5-) in the presence of non-defatted HSA showed that the complex binds at a minimum of five high-affinity fatty acid sites with stepwise binding constants ranging from 1.27 x 10(5) to 2.7 x 10(3) M(-1). The 20 MHz relaxivity of Gd(C(11)-DOTP)(5-) in the presence of excess HSA was 23 mM(-1) s(-1) at 25 degrees C. The NMRD curve showed a broad maximum 20-30 MHz which fitted well to standard theory for a q = 0 complex with rapid outer-sphere water exchange. The r(1b) of Gd(C(11)-DOTP)(5-) bound at the tightest site on HSA was approximately 40 mM(-1) s(-1) at 5 degrees C, an extraordinarily high value for an outer-sphere complex. However, the r(1b) of Gd(C(11)-DOTP)(5-) bound at the weaker sites on HSA was considerably lower, approaching the relaxivity of the free complex in water. This suggests that the complex bound in the highest affinity fatty acid site is less mobile than the same complex bound at the weaker affinity fatty acid sites. This combined ultrafiltration and relaxivity study demonstrates that the common assumption of a single r(1b) value for a Gd(3+) complex bound at several protein sites is not a valid approximation. PMID:11735466

Caravan, P; Greenfield, M T; Li, X; Sherry, A D

2001-12-17

23

Interaction of pentylsarin analogues with human acetylcholinesterase: a kinetic study.  

PubMed

Previous kinetic studies investigating the interactions between human acetylcholinesterase (AChE), structurally different organophosphorus compounds (OP) and oximes did not reveal a conclusive structure-activity relationship of the different reactions. The only exception was for a homologous series of methylphosphonofluoridates bearing C1-C4 O-n- or O-i-alkyl residues. Hence, it was tempting to investigate the kinetic interactions between different pentylsarin analogues, human AChE and two oximes, obidoxime and HI 6, in order to increase the understanding of structure-activity relationship between highly toxic OP and human AChE. The rate constants for the inhibition of human erythrocyte AChE by four pentylsarin compounds (k(i)), for the spontaneous dealkylation (aging, k(a)) and reactivation (k(s)) of inhibited AChE as well as for the oxime-induced reactivation of inhibited AChE by obidoxime and HI 6 reflected by the dissociation constant (K(D)) and the reactivity constant (k(r)) were determined. All pentylsarin analogues had a high inhibitory potency towards AChE. Inhibited AChE was subject to spontaneous reactivation which outweighed aging substantially. Pentylsarin-inhibited AChE could be reactivated by oximes, HI 6 being more potent than obidoxime. The determination of inhibition, reactivation and aging kinetics of pentylsarin analogues with human AChE extends the database on interactions between AChE and methylphosphonofluoridate homologues with C1-C4 n- and i-alkyl residues demonstrating a structure-activity relationship depending on the chain length with certain differences regarding inhibition and post-inhibitory reactions. Unfortunately, no structure-activity relationship could be observed for the oxime-induced reactivation of inhibited AChE. In view of previous results with numerous structurally different organophosphates, organophosphonates and phosphoramidates it has to be concluded that up to now kinetic studies did not provide decisive information for the development of more effective oxime-based reactivators. PMID:19429253

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

2009-06-01

24

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

SciTech Connect

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

McCarthy, J.F.

1994-10-01

25

Site-specific PEGylation of exenatide analogues markedly improved their glucoregulatory activity  

PubMed Central

BACKGROUND AND PURPOSE Exenatide is a 39-amino-acid peptide widely used to manage type 2 diabetes mellitus. However, it has a short plasma half-life and requires a twice daily injection regime. To overcome these drawbacks we used maleimide-polyethylene glycol to induce site-specific PEGylation. EXPERIMENTAL APPROACH The analogue PB-105 (ExC39) was produced by replacing cysteine at position 39 of exenatide to provide a free thiol group. PB-105 showed the same glucoregulatory activity as exenatide in mice. Site-specific PEGylation of PB-105 was performed to produce PB-110 (ExC39PEG5kDa), PB-106 (ExC39PEG20kDa), PB-107 (ExC39PEG30kDa) and PB-108 (ExC39PEG40kDa). Their effects on intracellular cAMP, acute glucoregulatory activity and pharmacokinetic profile were compared in mice and rats. KEY RESULTS PEGylation shifted the concentration–response curve of PB-105 to the right in a parallel, polyethylene glycol mass-dependent manner but with an inflexion point of at least 20 kDa. The activities of PB-107 and PB-108 but not PB-106 were reduced by 90% and 99%. PEGylation affected in vivo glucoregulatory activity in the same ‘Inflexion-Shift’ fashion at least at 20 kDa, but linearly increased plasma duration and systemic exposure without inflexion. PB-106 had a plasma t1/2 approximately 10-fold that of PB-105, and exhibited superior glucoregulatory activity compared with PB-105 in normal and diabetic mice. CONCLUSIONS AND IMPLICATIONS Site-specific PEGylation of exenatide with a permanent amide linkage affects its activity in a new type of ‘Inflexion-Shift’ fashion. PB-106 is a putative new analogue for treating diabetes; it possesses no loss of in vitro activity, prolonged plasma duration and superior, improved in vivo glucoregulatory activity compared with exenatide. PMID:21244372

Gong, Nian; Ma, Ai-Niu; Zhang, Li-Jie; Luo, Xiao-Su; Zhang, Yin-Hui; Xu, Michael; Wang, Yong-Xiang

2011-01-01

26

Fluorescence study of neurohypophyseal hormones and their analogues. Distance distributions in a series of arginine-vasopressin analogues.  

PubMed

Analogues of arginine-vasopressin (AVP) in which substitution of the proline residue in position 7 (by either sarcosine or N-methylalanine) combined with replacement of the cysteine residue in position 1 were the subject of a fluorescence and molecular mechanics study. We obtained two groups of analogues: selective antidiuretic agonists (cysteine or beta-mercaptopropionic acid in position 1) and pressor and uterotonic antagonists (deaminopenicillamine or beta-mercapto-beta, beta-cyclopentamethylenepropionic acid in position 1). Using frequency-domain measurements of fluorescence resonance energy transfer (FRET) we estimated the distance distribution between the phenolic ring of Tyr2 and the disulphide bridge Cys1-Cys6. We also analyzed acrylamide quenching of tyrosyl fluorescence to determine the exposure of the tyrosyl ring to the solvent. Results from fluorescence experiments were compared with those from Monte Carlo simulation (ECEPP/3 force-field). PMID:9232846

Wiczk, W; Lankiewicz, L; Kasprzykowski, F; O?dziej, S; Szmaci?ski, H; Lakowicz, J R; Grzonka, Z

1997-01-01

27

Active-site-mediated elimination of hydrogen fluoride from a fluorinated substrate analogue by isopenicillin N synthase.  

PubMed

Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of bicyclic isopenicillin N from delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). In this study we report a novel activity for the iron of the IPNS active site, which behaves as a Lewis acid to catalyse the elimination of HF from the fluorinated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-beta-fluorovaline (ACbetaFV). X-Ray crystallographic studies of IPNS crystals grown anaerobically with ACbetaFV reveal that the valinyl beta-fluorine is missing from the active site region, and suggest the presence of the unsaturated tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-isodehydrovaline in place of substrate ACbetaFV. (19)F NMR studies confirm the release of fluoride from ACbetaFV in the presence of the active IPNS enzyme. These results suggest a new mode of reactivity for the IPNS iron centre, a mechanism of action that has not previously been reported for any of the iron oxidase enzymes. PMID:15175003

Grummitt, Annaleise R; Rutledge, Peter J; Clifton, Ian J; Baldwin, Jack E

2004-09-01

28

Circular dichroism studies of some arginine-vasopressin analogues.  

PubMed

CD spectra of arginine-vasopressin (AVP) and of its analogues substituted in position 1 and/or 7 were measured in aqueous solution at different pH values. The shapes of the CD spectra of AVP analogues substituted in position 1 are strongly influenced by the type of group attached to the beta-carbon of residue 1. The substitution of the proline residues in position 7 by N-methylalanine also leads to a change in conformation of the peptide. The differences in the CD spectra are interpreted in terms of conformational changes, which are due to the interaction of the tyrosine side chain with neighbouring residues (for 1-substituted analogues of AVP), or to that between the hexapeptide ring and acyclic tripeptide chain (for 7-substituted analogues). PMID:3233295

Grzonka, Z; Gwizda?a, E; Kasprzykowski, F; Lankiewicz, L

1988-08-01

29

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

PubMed

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

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

2013-11-01

30

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

SciTech Connect

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

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

1988-10-01

31

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

32

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.

33

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

PubMed Central

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

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

2012-01-01

34

Antifreeze glycopeptide analogues: microwave-enhanced synthesis and functional studies.  

PubMed

Antifreeze glycoproteins enable life at temperatures below the freezing point of physiological solutions. They usually consist of the repetitive tripeptide unit (-Ala-Ala-Thr-) with the disaccharide alpha-D-galactosyl-(1-3)-beta-N-acetyl-D-galactosamine attached to each hydroxyl group of threonine. Monoglycosylated analogues have been synthesized from the corresponding monoglycosylated threonine building block by microwave-assisted solid phase peptide synthesis. This method allows the preparation of analogues containing sequence variations which are not accessible by other synthetic methods. As antifreeze glycoproteins consist of numerous isoforms they are difficult to obtain in pure form from natural sources. The synthetic peptides have been structurally analyzed by CD and NMR spectroscopy in proton exchange experiments revealing a structure as flexible as reported for the native peptides. Microphysical recrystallization tests show an ice structuring influence and ice growth inhibition depending on the concentration, chain length and sequence of the peptides. PMID:19165574

Heggemann, Carolin; Budke, Carsten; Schomburg, Benjamin; Majer, Zsuzsa; Wissbrock, Marco; Koop, Thomas; Sewald, Norbert

2010-01-01

35

Lithic microbial communities from a Mars analogue site in Utah desert  

NASA Astrophysics Data System (ADS)

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

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

2012-09-01

36

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

PubMed

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

2014-06-01

37

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

PubMed Central

A number of biochemical processes rely on isoprenoids, including the post-translational modification of signaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyl diphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics, photolabeling experiments, as well as x-ray crystallographic analysis with a protein prenyltransferase are described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this new analogue was explored by using it to photoaffinity label crude protein extracts obtained from Hevea brasiliensis latex. Those experiments suggest that a small protein, Rubber Elongation Factor, interacts directly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as a substrate. PMID:17477573

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

2008-01-01

38

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

NASA Astrophysics Data System (ADS)

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

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

2010-03-01

39

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

NASA Astrophysics Data System (ADS)

The behaviour of the magnetic field variations over the North China-Korea coastal region is studied with the aid of a scaled laboratory analogue model. The model source frequencies simulate naturally occurring geomagnetic variations of 3-60 min periods. In-phase and quadrature magnetic Bx, By and Bz field measurements for the modelled region are presented for E- and B-polarizations. Large anomalous in-phase and quadrature model magnetic fields are observed over the Korea-Japan strait for E-polarization and over the Bohai strait for B-polarization due to current channelling through the straits. Large responses of the peninsulas in the shallow coastal areas occur at short periods but decrease abruptly with increasing period. In general, the effects of peninsulas, straits, bays and irregularities in the coastlines play an important role in the magnetic field responses both on-shore and off-shore for this complex North China-Korea coastal region. Model and field site induction arrows are compared for three sites west of Bohai Bay.

Meng, Z.; Dosso, H. W.; Nienaber, W.

40

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

41

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

42

Study of IspH, A Key Enzyme in the Methylerythritol Phosphate Pathway Using Fluoro-substituted Substrate Analogues  

PubMed Central

IspH, a [4Fe-4S]-cluster-containing enzyme, catalyzes the reductive dehydroxylation of 4-hydroxy-3-methyl-butenyl diphosphate (HMBPP) to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) in the methylerythritol phosphate pathway. Studies of IspH using fluoro-substituted substrate analogues to dissect the contributions of several factors to IspH catalysis, including the coordination of the HMBPP C4-OH group to the iron-sulfur cluster, the H-bonding network in the active site, and the electronic properties of the substrates are reported. PMID:21981393

Xiao, Youli; Chang, Wei-chen; Liu, Hung-wen; Liu, Pinghua

2011-01-01

43

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

PubMed

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

2014-08-15

44

Cardiotonic site directed irreversible inhibition of Na+ + K+-ATPase by 3-azidoacetylstrophanthidin, a photochemical analogue of strophanthidin.  

PubMed

A photochemical analogue of strophanthidin, 3-azidoacetylstrophanthidin (AAS) was synthesized and tested as a cardiotonic steroid (CS) site directed photoaffinity label for Na+ + K+-ATPase (ATP phosphohydrolase, E.C. 3.6.1.3). AAS-inhibited rat brain ATPase with an I50 of about 1 x 10(-6) M readily displaced 3H-ouabain from its specific binding sites on this enzyme and produced a positive inotropic effect in guinea pig atrial strips. In the absence of UV light its interaction with the CS binding sites of Na+ + K+-ATPase appeared reversible. In the presence of UV light and acetylphosphate, AAS produced about 15% irreversible inhibition of Na+ + K+-ATPase, compared with about 5% irreversible inhibition in the absence of either UV light or acetyl phosphate. Since acetylphosphate supports specific glucoside binding at the CS binding sites of Na+ + K+-ATPase these data are consistent with the concept that AAS is a cardiotonic steroid site directed photoactivatable inhibitor of Na+ + K+-ATPase. PMID:130245

Tobin, T; Akera, T; Brody, T M; Taneja, H R

1976-01-01

45

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

PubMed

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

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

2013-05-10

46

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

NASA Astrophysics Data System (ADS)

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

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

2015-01-01

47

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

SciTech Connect

The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a high-level waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock Tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, x-ray diffraction, and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 40}Ar isotopic composition. Overall, the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 m of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

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

1995-03-01

48

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

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

2014-01-01

49

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

ERIC Educational Resources Information Center

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

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

2004-01-01

50

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

E-print Network

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

Paris-Sud XI, Université de

51

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

NASA Astrophysics Data System (ADS)

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

Gauthier-Lafaye, François

2002-10-01

52

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

SciTech Connect

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

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

1999-07-01

53

Synthesis, pro-apoptotic activity and 2D-QSAR studies of new analogues of fluphenazine.  

PubMed

A series of 10 novel analogues of fluphenazine (FPh) were synthesized. Influence of the synthesized analogues of FPh on frequency of apoptosis and necrosis in cultures of human lymphocytes genotoxically damaged in vitro with benzo[a]pyrene (B[a]P; 7,5 microM, 48 h) was compared with the effect of FPh. Activity of the tested compounds was expressed by ED50 (pro-apoptotic activity) and TD50 (pro-necrotic effect, cytotoxicity). It was noticed that compounds 3-9 and 12 exerted a pro-apoptotic effect markedly stronger than that of FPh. Additionally, compounds 3, 9 and 10 exhibited the weakest influence on frequency of necrotic lymphocyte in cultures. 2D-QSAR analysis was done in order to find quantitative relationship between structures of the tested analogues and their pro-apoptotic activity or pro-necrotic effect in B[a]P-damaged cell cultures. Several statistically significant QSAR models were generated. Information obtained from 2D-QSAR study will be used in further design of analogues of FPh more active in cancer chemoprevention. PMID:24779194

Zyta, Joanna; Jaszczyszyn, Agata; Swiatek, Piotr; Gasiorowski, Kazimierz; Malinka, Wies?aw

2014-01-01

54

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

NASA Astrophysics Data System (ADS)

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

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

2010-12-01

55

A Spectral, Chemical and Mineralogical Study of Mars Analogue Rocks  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

56

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.

57

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

PubMed Central

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

Sekharan, Sivakumar; Altun, Ahmet; Morokuma, Keiji

2010-01-01

58

Defining the selectivity of processes along the auxin response chain: a study using auxin analogues.  

PubMed

The mode of action of auxin is based on its non-uniform distribution within tissues and organs. Despite the wide use of several auxin analogues in research and agriculture, little is known about the specificity of different auxin-related transport and signalling processes towards these compounds. Using seedlings of Arabidopsis thaliana and suspension-cultured cells of Nicotiana tabacum (BY-2), the physiological activity of several auxin analogues was investigated, together with their capacity to induce auxin-dependent gene expression, to inhibit endocytosis and to be transported across the plasma membrane. This study shows that the specificity criteria for different auxin-related processes vary widely. Notably, the special behaviour of some synthetic auxin analogues suggests that they might be useful tools in investigations of the molecular mechanism of auxin action. Thus, due to their differential stimulatory effects on DR5 expression, indole-3-propionic (IPA) and 2,4,5-trichlorophenoxy acetic (2,4,5-T) acids can serve in studies of TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALLING F-BOX (TIR1/AFB)-mediated auxin signalling, and 5-fluoroindole-3-acetic acid (5-F-IAA) can help to discriminate between transcriptional and non-transcriptional pathways of auxin signalling. The results demonstrate that the major determinants for the auxin-like physiological potential of a particular compound are very complex and involve its chemical and metabolic stability, its ability to distribute in tissues in a polar manner and its activity towards auxin signalling machinery. PMID:23914741

Simon, Sibu; Kubeš, Martin; Baster, Pawel; Robert, Stéphanie; Dobrev, Petre Ivanov; Friml, Ji?í; Petrášek, Jan; Zažímalová, Eva

2013-12-01

59

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))

1988-02-01

60

Synthesis of reactive nucleic acid analogues and their application for the study of structure and functions of biopolymers  

NASA Astrophysics Data System (ADS)

Data on the synthesis of reactive derivatives of nucleic acid analogues and their application for the study of structure and functions of biopolymers are generalised. The main types of such analogues including photoactivated reagents containing azidoaryl, halogeno, and thiol groups, psoralen and its derivatives, platinum-based reagents, and nucleic acid analogues containing substituted pyrophosphate or acyl phosphate internucleotide groups are presented. The mechanisms of interaction of these compounds with proteins and nucleic acids are considered. The prospects for the in vivo application of reactive nucleic acids in various systems are discussed. The bibliography includes 76 references.

Kanevskii, Igor'E.; Kuznetsova, Svetlana A.

1998-07-01

61

Activation of adenylate cyclase and inhibition of glucose transport in rat adipocytes by forskolin analogues: structural determinants for distinct sites of action.  

PubMed

Forskolin and four analogues of forskolin, 7-beta-[gamma-(N'-methylpiperazino)-butyryloxy]-7-desacet ylforskolin, 7-desacetylforskolin, 7-tosyl-7-desacetylforskolin, and 1,9-dideoxyforskolin, were tested for their ability to activate adenylate cyclase, inhibit glucose transport, and inhibit cytochalasin B binding in rat adipocyte membranes. Forskolin was the most potent analogue in activating adenylate cyclase with an EC50 of 2 microM, whereas 7-beta-[gamma-(N'-methylpiperazino)butyryloxy]-7-desacety lforskolin and 7-desacetylforskolin were less potent, with EC50 values of 3 microM and 20 microM, respectively. The 7-tosyl-7-desacetylforskolin and 1,9-dideoxyforskolin did not stimulate adenylate cyclase even at the highest concentrations tested (100 microM). In contrast, forskolin and all of the analogues were able to fully inhibit glucose transport in adipocyte plasma membranes. The order of potency for the inhibition was forskolin greater than 7-beta-[gamma-(N'-methylpiperazino)butyryloxy]-7-desacety lforskolin greater than 7-desacetylforskolin greater than 7-tosyl-7-desacetylforskolin greater than 1,9-dideoxyforskolin, and the EC50 values were 0.24 microM, 1.8 microM, 7.1 microM, 8.8 microM, and 12.8 microM, respectively. Cytochalasin B binding to rat adipocyte membranes was inhibited by forskolin and the four analogues with the same order of potency as observed for the inhibition of glucose transport. Thus, the site of action of forskolin which is responsible for the inhibition of glucose transport and cytochasin B binding exhibits structural requirements for forskolin and its analogues that are different from those of the site responsible for the activation of adenylate cyclase. PMID:3357486

Joost, H G; Habberfield, A D; Simpson, I A; Laurenza, A; Seamon, K B

1988-04-01

62

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

PubMed Central

Quantum chemical calculations of metal clusters in proteins for redox studies require both computational feasibility as well as accuracies of at least ?50 mV for redox energies but only ?0.05 Å for bond lengths. Thus, optimization of spin-unrestricted density functional theory (DFT) methods, especially the hybrid generalized gradient approximation functionals, for energies while maintaining good geometries is essential. Here, different DFT functionals with effective core potential (ECP) and full core basis sets for [Fe(SCH3)4]2-/1- and [Fe(SCH3)3]1-/0, which are analogs of the iron-sulfur protein rubredoxin, are investigated in comparison to experiment as well as other more computationally intensive electron correlation methods. In particular, redox energies are calibrated against gas-phase photoelectron spectroscopy data so no approximations for the environment are needed. B3LYP gives the best balance of accuracy in energy and geometry compared B97gga1 and BHandH and is better for energies than Møller-Plesset perturbation theory series (MP2, MP3, MP4SDQ) and comparable to coupled cluster [CCSD, CCSD(T)] methods. Of the full core basis sets tested, the 6-31G** basis sets give good geometries, and addition of diffuse functions to only the sulfur significantly improves the energies. Moreover, a basis set with an ECP on only the iron gives a less accurate but still reasonable geometries and energies. PMID:20161267

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

2009-01-01

63

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

PubMed Central

The enantiomer pair androsterone and ent-androsterone are positive allosteric modulators of ?-aminobutyric acid type A (GABAA) receptors. Each enantiomer was shown to bind at the same receptor site. Binding orientations of the enantiomers at this site were deduced using enantiomer pairs containing OBn substituents at either C-7 or C-11. 11?-OBn substituted steroids and 7?-OBn substituted ent-steroids potently displace [35S]TBPS, augment GABA currents and anesthetize tadpoles. In contrast, 7?-OBn substituted steroids and 11?-OBn substituted ent-steroids have diminished actions. The results suggest that the binding orientations of the active analogues are inverted relative to each other with the 7? and 11? substituents similarly located on the edges of the molecules not in contact with the receptor surface. Analogue potentiation of GABA current was abrogated by an ?1 subunit Q241L mutation indicating that the active analogues act at the same sites in ?1?2?2L receptors previously associated with positive neurosteroid modulation. PMID:22191644

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

2012-01-01

64

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

PubMed

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

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

2006-06-01

65

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.

2005-06-01

66

Synthetic studies on amipurimycin: total synthesis of a thymine nucleoside analogue.  

PubMed

Amipurimycin, a member of the complex peptidyl nucleoside family of antibiotics, is a Streptomyces-derived potent antifungal agent. The mechanism of action of amipurimycin, however, remains undetermined. Additionally, there are no reports on the total synthesis or structure-activity relationships (SAR) of this potentially useful bioactive compound. In a study aimed at the total synthesis and SAR studies of this natural product, the present research reports the development of a synthetic route to the central pyranosyl amino acid core of amipurimycin and its further elaboration, culminating in the synthesis of a unique thymine analogue. Utilizing a d-serine-derived dihydroaminopyrone as a strategic building block, the synthesis involves de novo construction of the fully functionalized C-3-branched carbohydrate amino acid core, followed by glycosidic attachment of thymine at C-1, and peptidic linking of the C-6 amine with the 1,2-aminocyclopentane carboxylic acid side chain. PMID:18465899

Stauffer, Christina S; Datta, Apurba

2008-06-01

67

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.

2010-01-01

68

Simulation of Traumatic Brain Injury Symptoms on the Personality Assessment Inventory: An Analogue Study.  

PubMed

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

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

2014-06-24

69

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

SciTech Connect

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

Dale Spall; Robert Villarreal

1998-08-01

70

Nonstationary analogue black holes  

E-print Network

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

Gregory Eskin

2014-11-26

71

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

1980-07-01

72

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

PubMed

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

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

2012-04-01

73

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

PubMed

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

2015-01-01

74

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.

2014-01-01

75

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

SciTech Connect

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

Alcouffe, G.; Cernogora, G.; Ouni, F.; Correia, J. J. [Universite de Versailles St-Quentin Service d'Aeronomie, BP 3 91371 Verrieres le Buisson (France); Cavarroc, M.; Boufendi, L. [GREMI Universite d'Orleans Route d'Issoudun BP Orleans Cedex (France); Szopa, C. [UPMC Univ. Paris 6, Service d'Aeronomie, BP 3 91371 Verrieres le Buisson (France)

2008-09-07

76

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

PubMed Central

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

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

2013-01-01

77

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

PubMed

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

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

2013-01-01

78

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

PubMed

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

2012-04-24

79

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

2009-01-01

80

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

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

2011-01-01

81

High-resolution mass spectrometry and hydrogen/deuterium exchange study of mitorubrin azaphilones and nitrogenized analogues.  

PubMed

Azaphilones represent numerous groups of wild fungal secondary metabolites that exhibit exceptional tendency to bind to nitrogen atoms in various molecules, especially those containing the amine group. Nitrogenized analogues of mitorubrin azaphilones, natural secondary metabolites of Hypoxylon fragiforme fungus, have been detected in the fungal methanol extract in very low concentrations. Positive electrospray ionization interfaced with high-resolution mass spectrometry was applied for confirmation of the elemental composition of protonated species. Collision-induced dissociation (CID) experiments have been performed, and fragmentation mechanisms have been proposed. Additional information regarding both secondary metabolite analogue families has been reached by application of gas-phase proton/deuterium (H/D) exchanges performed in the collision cell of a triple quadrupole mass spectrometer. An incomplete H/D exchange with one proton less than expected was observed for both protonated mitorubrin azaphilones and their nitrogenized analogues. By means of the density functional theory, an appropriate explanation of this behavior was provided, and it revealed some information concerning gas-phase H/D exchange mechanism and protonation sites. PMID:22899505

Svilar, Ljubica; Stankov-Jovanovic, Vesna; Lesage, Denis; Dossmann, Héloïse; Tabet, Jean-Claude

2012-08-01

82

Hyperspectral Study of Hydrous Magnesium Minerals (Serpentine) from Ultramafic Rocks Along the Rikhabhdev Lineament, Rajasthan, India: As an Analogue for Hydrous Magnesium Minerals on Mars  

NASA Astrophysics Data System (ADS)

The ultramafic rocks along the Rikhabhdev Lineament, Rajasthan, India is consider as a good analogue for the study study of serpentine. This study help in interpreting the environmental conditions on Mars in its past.

Jain, N.; Bhattacharya, S.; Chauhan, P.; Ajai

2012-03-01

83

TREATABILITY STUDIES FOR WOOD PRESERVING SITES  

EPA Science Inventory

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

84

Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study**  

PubMed Central

Background: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. Objective: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. Methods: Patients eligible for participation in the Recover Study are aged10 ?18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ?3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ?6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. Results: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18–67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6–156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]). Conclusions: The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART. PMID:24672118

Palacios, Rosario; Santos, Jesús; Camino, Xavier; Arazo, Piedad; Torres Perea, Rafael; Echevarrfa, Santiago; Ribera, Esteban; Sánchez de la Rosa, Rainel; Moreno Guillen, Santiago

2005-01-01

85

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

PubMed

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

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

2014-04-10

86

Lobatamide C: total synthesis, stereochemical assignment, preparation of simplified analogues, and V-ATPase inhibition studies.  

PubMed

The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C, as well as synthesis of simplified lobatamide analogues, is reported. Cu(I)-mediated enamide formation methodology has been developed to prepare the highly unsaturated enamide side chain of the natural product and analogues. A key fragment coupling employs base-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Three additional stereoisomers of lobatamide C have been prepared using related synthetic routes. The stereochemistry at C8, C11, and C15 of lobatamide C was assigned by comparison of stereoisomers and X-ray analysis of a crystalline derivative. Synthetic lobatamide C, stereoisomers, and simplified analogues have been evaluated for inhibition of bovine chromaffin granule membrane V-ATPase. The salicylate phenol, enamide NH, and ortho-substitution of the salicylate ester have been shown to be important for V-ATPase inhibitory activity. PMID:12823009

Shen, Ruichao; Lin, Cheng Ting; Bowman, Emma Jean; Bowman, Barry J; Porco, John A

2003-07-01

87

Developing Study Stations on Your School Site.  

ERIC Educational Resources Information Center

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

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

88

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

PubMed

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

2014-11-01

89

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

Microsoft Academic Search

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

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

1996-01-01

90

Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer—a pilot study  

Microsoft Academic Search

Objective: To evaluate the efficacy of bicalutamide vs cyproterone acetate in preventing PSA flare (as a surrogate for tumour flare) for patients requiring luteinizing hormone-releasing hormone (LHRH) analogue therapy for prostate cancer.Patients and Methods: In this pilot study, 40 men were randomized 1 : 1 to bicalutamide 50 mg o.d. or cyproterone acetate 100 mg t.i.d. 5 days prior to

M Sugiono; M H Winkler; A A Okeke; M Benney; D A Gillatt

2005-01-01

91

The Order Bicommutant A study of analogues of the von Neumann Bicommutant Theorem, reflexivity results and  

E-print Network

Theorem and related results are valid for Riesz spaces. Let H be a Hilbert space and D Lb(H) a -invariant by its reducing bands. This is the analogue of the fact that each von Neumann algebra in Lb(H subspaces and projections. Secondly, every -invariant subset of Lb(H) is reduced by each invariant sub

Galis, Frietson

92

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

PubMed

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

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

2015-01-30

93

ATBC Study - Links to Related Sites  

Cancer.gov

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

94

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

PubMed

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

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

2011-04-01

95

Comparative Study of the Anti-Human Cytomegalovirus Activities and Toxicities of a Tetrahydrofuran Phosphonate Analogue of Guanosine and Cidofovir  

PubMed Central

Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (?)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9?-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 ?g/ml for cidofovir and <0.05 to 0.09 ?g/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day. PMID:10049267

Bedard, Jean; May, Suzanne; Lis, Martin; Tryphonas, Leander; Drach, John; Huffman, John; Sidwell, Robert; Chan, Laval; Bowlin, Terry; Rando, Robert

1999-01-01

96

Mechanisms for the formation of a perched water zone in fractured tuff: A natural analogue study  

SciTech Connect

Perched water zones have been identified in the fractured, welded tuff in the semi-arid to arid environments of Yucca Mountain, Nevada and near Superior, Arizona. An understanding of the formation of such zones is necessary in order to predict where future perched water might form at Yucca Mountain, the proposed site of a high-level nuclear waste repository. The formation or growth of a perched zone near a repository is one of the factors to be considered in the risk assessment of the Yucca Mountain site. The Apache Leap Research Site near Superior, Arizona is a natural analog to the Yucca Mountain site in terms of geology, hydrology, and climate. Information used to study possible mechanisms for the formation of the perched zone included data regarding isotopic and geochemical properties of the waters in and above the perched water zone; measured hydrologic parameters of the perched zone; geophysical and measured parameters of the tuff; megascopic and microscopic observations of the tuff, including mineralogical, alteration, and structural features; and the lateral and vertical extent of perched water in the region. Aquifer test, geophysical, geochemical, and radioisotopic data show that fractures are the means by which water is recharging the perched zone. The reduced hydraulic conductivity of the formation in the perched zone appears to result from both a severe reduction in matrix porosity and permeability caused by welding, devitrification, and vapor phase crystallization; and by an increase in fracture filling which restricts the pathways for flow.

Woodhouse, E.G.; Bassett, R.L. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Hydrology and Water Resources

1997-12-31

97

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

PubMed Central

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

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

2013-01-01

98

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

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

99

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.

1997-01-01

100

Diagramming the Study Site for Others  

NSDL National Science Digital Library

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

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

2003-08-01

101

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

Microsoft Academic Search

We synthesized a pentamine (3-3-3-3) and two hex- amine (3-3-3-3-3 and 3-4-3-4-3) analogues of the natural polyamine, spermine (3-4-3) and studied their effectiveness in condensing pGL3 plasmid DNA, using light scattering and atomic force micro- scopic (AFM) techniques. The midpoint concentra- tion of the polyamines on pGL3 condensation (EC50) was 11.3, 10.6, 1.5, 0.49 and 0.52 mM, respectively, for 3-4-3,

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

2004-01-01

102

Protein engineering of antibody binding sites: recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli.  

PubMed Central

A biosynthetic antibody binding site, which incorporated the variable domains of anti-digoxin monoclonal antibody 26-10 in a single polypeptide chain (Mr = 26,354), was produced in Escherichia coli by protein engineering. This variable region fragment (Fv) analogue comprised the 26-10 heavy- and light-chain variable regions (VH and VL) connected by a 15-amino acid linker to form a single-chain Fv (sFv). The sFv was designed as a prolyl-VH-(linker)-VL sequence of 248 amino acids. A 744-base-pair DNA sequence corresponding to this sFv protein was derived by using an E. coli codon preference, and the sFv gene was assembled starting from synthetic oligonucleotides. The sFv polypeptide was expressed as a fusion protein in E. coli, using a leader derived from the trp LE sequence. The sFv protein was obtained by acid cleavage of the unique Asp-Pro peptide bond engineered at the junction of leader and sFv in the fusion protein [(leader)-Asp-Pro-VH-(linker)-VL]. After isolation and renaturation, folded sFv displayed specificity for digoxin and related cardiac glycosides similar to that of natural 26-10 Fab fragments. Binding between affinity-purified sFv and digoxin exhibited an association constant [Ka = (3.2 +/- 0.9) x 10(7) M-1] that was about a factor of 6 smaller than that found for 26-10 Fab fragments [Ka = (1.9 +/- 0.2) x 10(8) M-1] under the same buffer conditions, consisting of 0.01 M sodium acetate, pH 5.5/0.25 M urea. Images PMID:3045807

Huston, J S; Levinson, D; Mudgett-Hunter, M; Tai, M S; Novotný, J; Margolies, M N; Ridge, R J; Bruccoleri, R E; Haber, E; Crea, R

1988-01-01

103

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

PubMed Central

The branchial mechanism of urea retention in elasmobranchs was investigated using an in vitro isolated-perfused head preparation, as well as in vivo samples, in the spiny dogfish shark. Both in vivo and in control saline perfusions containing 350 mmol L?1 urea, calculated intracellular urea concentrations in gill epithelial cells were close to extracellular concentrations. Urea efflux to the external water fell only non-significantly, and calculated gill intracellular urea concentration did not change when perfusate urea concentration was reduced from 350 to 175 mmol?L?1 with osmotic compensation by 175 mmol L?1 mannitol. However, when the urea analogues thiourea or acetamide were present in the perfusate at concentrations equimolar (175 mmol L?1) to those of urea (175 mmol L?1), urea efflux rates were increased 4-fold and 6.5-fold respectively, and calculated gill intracellular urea concentrations were depressed by about 55%. Analogue efflux rates were similar to urea efflux rates. Previous studies have argued that either the basolateral or apical membranes provided the limiting permeability barrier, and/or that a back-transporter on the basolateral membranes of gill cells is responsible for urea retention. The present results provide new evidence that the apical membrane is the limiting factor in maintaining gill urea impermeability, and raise the prospect that a urea back-transporter, which can be competitively inhibited by thiourea and acetamide, operates at the apical membrane. PMID:23638369

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

2013-01-01

104

Liquid chromatography ion trap/time-of-flight mass spectrometric study on the fragmentation of an acetildenafil analogue.  

PubMed

Liquid chromatography ion-trap time-of-flight mass spectrometry was employed to elucidate the fragmentation pathways of an analogue of acetildenafil. Based on the accurate masses of the parent ion, product ions and neutral losses of acetildenafil analogue, its fragmentation pathways were proposed. The information is useful for the on-line structural identification of unknown analogues of acetildenafil found as adulterants in herbal products. PMID:17881792

Zou, Peng; Oh, Sharon Sze-Yin; Kiang, Kin-Har; Low, Min-Yong; Koh, Hwee-Ling

2007-01-01

105

Podophyllotoxin-resistant mutants of Chinese hamster ovary cells: cross-resistance studies with various microtubule inhibitors and podophyllotoxin analogues.  

PubMed

The cross-resistances of several mutants of Chinese hamster ovary cells which have been obtained after one and two selection steps in the presence of the microtubule inhibitor podophyllotoxin (PodRI and PodRII mutants, respectively) towards various other inhibitors of microtubule assembly (e.g., colchicine, Colcemid, vinblastine, griseofulvin, maytansine, steganacin, nocodazole, and taxol) have been examined. Based upon their specific patterns of cross-resistance/sensitivity to various microtubule inhibitors, both the PodRI and PodRII classes of mutants appear to be of more than one kind. Studies on the binding of [3H]podophyllotoxin to cytoplasmic extracts indicate that one of the PodRII mutants which has been shown previously to be affected in a Mr 66,000 to 68,000 microtubule-associated protein shows reduced binding of the drug in comparison to the parental PodS and PodRI cells. The different PodRI and PodRII mutants exhibited proportionally increased cross-resistances to various podophyllotoxin analogues (e.g., deoxypodophyllotoxin, epipodophyllotoxin, beta-peltatin, 4'-demethylpodophyllotoxin, alpha-peltatin, podophyllotoxin-beta-D-glucoside, beta-peltatin-beta-D-glucoside, picropodophyllotoxin, and podophyllic acid) which possess microtubule-inhibitory activity. However, with the exception of one PodRI class of mutant, none of the mutants exhibited any cross-resistance to 4'-demethylepipodophyllotoxin thenylidine-beta-D-glucoside and 4'-demethylepipodophyllotoxin ethylidine-beta-D-glucoside, the 2 podophyllotoxin analogues which lack microtubule-inhibitory activity. The cross-resistance studies with these mutants, which, based upon the biochemical studies and their highly specific patterns of cross-resistance, are presumably affected in microtubules, provide some very novel insights into the mechanisms of action of various microtubule inhibitors. The results presented in this paper also show that the cross-resistance studies with the set of podophyllotoxin-resistant mutants provide a sensitive and highly specific screening procedure for identifying compounds which possess podophyllotoxin-like activity and for investigating the structure-activity relationship among them. The results of structure-activity relationship studies for the various podophyllotoxin analogues examined are discussed. PMID:6848174

Gupta, R S

1983-02-01

106

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

PubMed

Binding affinities of fluconazole and its analogue 2-(2,4-dichlorophenyl)-1,3-di(1H-1,2,4-triazol-yl)-2-propanol (DTP) to human serum albumin (HSA) were investigated under approximately human physiological conditions. The obtained result indicated that HSA could generate fluorescent quenching by fluconazole and DTP because of the formation of non-fluorescent ground-state complexes. Binding parameters calculated from the Stern-Volmer and the Scatchard equations showed that fluconazole and DTP bind to HSA with binding affinities of the order 10(4)L/mol. The thermodynamic parameters revealed that the binding was characterized by negative enthalpy and positive entropy changes, suggesting that the binding reaction was exothermic. Hydrogen bonds and hydrophobic interaction were found to be the predominant intermolecular forces stabilizing the drug-protein. The effect of metal ions on the binding constants of fluconazole-HSA complex suggested that the presence of Mg(2+) and Zn(2+) ions could decrease the free drug level and extend the half-life in the systematic circulation. Docking experiments revealed that fluconazole and DTP binds in HSA mainly by hydrophobic interaction with the possibility of hydrogen bonds formation between the drugs and the residues Arg 222, Lys 199 and Lys 195 in HSA. PMID:25301772

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

2014-11-01

107

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.

1981-04-01

108

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

PubMed

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

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

2012-07-26

109

Meteorological study of Aklim site in Morocco  

NASA Astrophysics Data System (ADS)

Candidate sites of the future European Extremely Large Telescopes (E-ELT) need to be assessed and analytically compared in their observing characteristics. In the site selection process, meteorological, photometric and seeing qualities have to be studied and measured carefully. Aklim site in Morocco is one among four candidates in the ELT project. In this paper, we present meteorological studies of the Aklim site over eleven years. The meteorological parameters include wind speed and direction, relative humidity, air temperature, cloud cover and water vapour content. Most of these data are taken from the National Center for Environmental Prediction/National Center for Atmospheric Research NCEP/NCAR Reanalysis. The meteorological analysis covers the vertical profile as well as surface layer meteorology. Furthermore, in extensive literature, it has been demonstrated that the global circulation of atmospheric wind at 200 mb can be used as a criterion to establish the suitability for the development of adaptive optics techniques. By using the NOAA NCEP/NCAR reanalysis database, we analyse the monthly average wind velocity at 200 mb for eleven years period and compare with famous observatories.

Bounhir, Aziza; Benkhaldoun, Zouhair; Sarazin, Marc

2008-07-01

110

Solid-state gallium-69 and gallium-71 nuclear magnetic resonance spectroscopic studies of gallium analogue zeolites and related systems  

SciTech Connect

The authors have obtained solid-state 11.7-T /sup 69/Ga and /sup 71/Ga nuclear magnetic resonance (NMR) spectra of a series of gallosilicates (gallium analogues of zeolites Na-X, Na-Y, Na-sodalite, and Na-natrolite). From the apparent /sup 69/Ga and /sup 71/Ga chemical shifts, values of the nuclear quadrupole coupling constants (e/sup 2/qQ/h) and the true, isotropic chemical shifts (delta/sub i) have been deduced for the framework, tetrahedral, Ga(OSi)/sub 4/ sites. The e/sup 2/qQ/h values are in the range 1.9-2.7 MHz for /sup 69/Ga and 1.2-1.7 MHz for /sup 71/Ga. The isotropic chemical shifts are all in the range 171-186 ppm downfield from an external standard of 1 M Ga(NO/sub 3/)/sub 3/. Their results indicate that measurement of the apparent (second-order shifted) chemical shifts for pairs of isotopes of nonintegral spin quadrupolar nuclei in solids at one magnetic field strength is a useful new approach for determination of both isotropic chemical shifts and nuclear quadrupole coupling constant values.

Timken, H.K.; Oldfield, E.

1987-12-09

111

Representing the Study Site in a Diagram  

NSDL National Science Digital Library

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

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

2003-08-01

112

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

E-print Network

and dehair bison hides and compares the use-wear traces left on the tool edge by each activity. This suite of characteristics is then compared to those found on an assemblage of Clovis-age scrapers from the Gault site in central Texas....

Wiederhold, James Edward

2004-09-30

113

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

PubMed

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

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

2012-07-01

114

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

PubMed Central

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

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

2014-01-01

115

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

Microsoft Academic Search

Semi-synthetic analogues of ?-boswellic acid (BA) and 11-keto-?-boswellic acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with

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

2011-01-01

116

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

SciTech Connect

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

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

2009-02-16

117

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

PubMed

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

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

2012-05-01

118

Connecting the Parts of the Study Site  

NSDL National Science Digital Library

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

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

2003-08-01

119

Matrix metalloproteinase 2 (MMP2) inhibition: DFT and QM/MM studies of the deprotonation-initialized ring-opening reaction of the sulfoxide analogue of SB-3CT.  

PubMed

(4-Phenoxyphenylsulfonyl)methylthiirane (SB-3CT) is the selective inhibitor of matrix metalloproteinase 2 (MMP2). The inhibition mechanism of MMP2 by SB-3CT involves C-H deprotonation with concomitant opening of the three-membered heterocycle. In this study, the energetics of the deprotonation-induced ring-opening of (4-phenoxyphenylsulfinyl)methylthiirane, the sulfoxide analogue of SB-3CT, are examined computationally using DFT and QM/MM calculations. A model system, 2-(methylsulfinylmethyl)thiirane, is used to study the stereoelectronic and conformational effects of reaction barriers in methanol. For the model system in methanol solution (using the polarizable continuum model), the reaction barriers range from 17 to 23 kcal/mol with significant stereoelectronic effects. However, the lowest barriers of the (R,R) and (S,R) diastereomers are similar. Two diastereomers of the sulfoxide analogue of SB-3CT are studied in the active site of MMP2 by QM/MM methods with an accurate partial charge fitting procedure. The ring-opening reactions of these two diastereomers have similar reaction energetics. Both are exothermic from the reactant to the ring-opening product (thiolate). The protonation of the thiolate by a water molecule is endothermic in both cases. However, the deprotonation/ring-opening barriers in the MMP2 active site using QM/MM methods for the (R,R) and (S,R) inhibitions are quite different (23.3 and 28.5 kcal/mol, respectively). The TSs identified in QM/MM calculations were confirmed by vibrational frequency analysis and following the reaction path. The (R,R) diastereomer has a hydrogen bond between the sulfoxide oxygen and the backbone NH of Leu191, while the (S,R) has a hydrogen bond between the sulfoxide oxygen and a water molecule. The dissimilar strengths of these hydrogen bonds as well as minor differences in the TS structures contribute to the difference between the barriers. Compared to SB-3CT, both diastereomers of the sulfoxide analogue have higher reaction barriers and have less exothermic reaction energies. This agrees well with the experiments, where SB-3CT is a more effective inhibitor of MMP2 than its sulfoxide analogue. PMID:20039633

Tao, Peng; Fisher, Jed F; Shi, Qicun; Mobashery, Shahriar; Schlegel, H Bernhard

2010-01-21

120

Insulin analogues: fears, facts and fantasies  

Microsoft Academic Search

IGF-1 and insulin, acting through both IGF-1 and insulin receptors, have been studied widely to evaluate their oncogenic and teratogenic properties. These two properties need to be studied for each new insulin analogue, in addition to measurements of their metabolic and pharmacodynamic features. This editorial critiques a study in this issue of the journal of several insulin analogues in their

Renzo Cordera; Barbara Salani; Lucia Briatore

2009-01-01

121

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

PubMed

Beetle luciferases produce different bioluminescence colors from green to red using the same d-luciferin substrate. Despite many studies of the mechanisms and structural determinants of bioluminescence colors with firefly luciferases, the identity of the emitters and the specific active site interactions responsible for bioluminescence color modulation remain elusive. To address these questions, we analyzed the bioluminescence spectra with 6'-amino-D-luciferin (aminoluciferin) and its 5,5-dimethyl analogue using a set of recombinant beetle luciferases that naturally elicit different colors and different pH sensitivities (pH-sensitive, Amydetes vivianii ?max=538 nm, Macrolampis sp2 ?max=564 nm; pH-insensitive, Phrixotrix hirtus ?max=623 nm, Phrixotrix vivianii ?max=546 nm, and Pyrearinus termitilluminans ?max=534 nm), a luciferase-like enzyme (Tenebrionidae, Zophobas morio ?max=613 nm), and mutants of C311 (S314). The green-yellow-emitting luciferases display red-shifted bioluminescence spectra with aminoluciferin in relation to those with D-luciferin, whereas the red-emitting luciferases displayed blue-shifted spectra. Bioluminescence spectra with 5,5-dimethylaminoluciferin, in which enolization is blocked, were almost identical to those of aminoluciferin. Fluorescence probing using 2-(4-toluidino)naphthalene-6-sulfonate and inference with aminoluciferin confirm that the luciferin binding site of the red-shifted luciferases is more polar than in the case of the green-yellow-emitting luciferases. Altogether, the results show that the keto form of excited oxyluciferin is the emitter in beetle bioluminescence and that bioluminescence colors are essentially modulated by interactions of the 6'-hydroxy group of oxyluciferin and basic moieties under the influence of the microenvironment polarity of the active site: a strong interaction between a base moiety and oxyluciferin phenol in a hydrophobic microenvironment promotes green-yellow emission, whereas a more polar environment weakens such interaction promoting red shifts. In pH-sensitive luciferases, a pH-mediated switch from a closed hydrophobic conformation to a more open polar conformation promotes the typical red shift. PMID:25025160

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

2014-08-19

122

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

PubMed

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

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

2010-10-01

123

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

PubMed Central

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

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

2010-01-01

124

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

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

125

Argillization processes at the El Berrocal analogue granitic system (Spain): mineralogy, isotopic study and implications for the performance assessment of radwaste geological disposal  

Microsoft Academic Search

The El Berrocal granite\\/U-bearing quartz vein (UQV) system has been studied as a natural analogue of a high-level radioactive waste repository. The main objective was to understand the geochemical behaviour of natural nuclides under different physicochemical conditions. Within this framework, the argillization processes related to fracturing and formation of the uranium–quartz vein were studied from a mineralogical and isotopic standpoint

L Pérez del Villar; E Reyes; A Delgado; R Núñez; M Pelayo; J. S Cózar

2003-01-01

126

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

PubMed Central

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

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

2014-01-01

127

Arabinose 5-phosphate isomerase as a target for antibacterial design: studies with substrate analogues and inhibitors.  

PubMed

Structural requirements of D-arabinose 5-phosphate isomerase (KdsD, E.C. 5.3.1.13) from Pseudomonas aeruginosa were analysed in detail using advanced NMR techniques. We performed epitope mapping studies of the binding between the enzyme and the most potent KdsD inhibitors found to date, together with studies of a set of newly synthesised arabinose 5-phosphate (A5P) mimetics. We report here the first experimental evidence that KdsD may bind the furanose form of A5P, suggesting that catalysis of ring opening may be an important part of KdsD catalysis. PMID:24680056

Gabrielli, Luca; Merlo, Silvia; Airoldi, Cristina; Sperandeo, Paola; Gianera, Serena; Polissi, Alessandra; Nicotra, Francesco; Holler, Tod P; Woodard, Ronald W; Cipolla, Laura

2014-04-15

128

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

ERIC Educational Resources Information Center

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

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

2010-01-01

129

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

2011-01-01

130

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

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

131

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.

1992-01-01

132

Spectroscopic investigations and hydrogen bond interactions of 8-aza analogues of xanthine, theophylline and caffeine: a theoretical study.  

PubMed

The structure, spectral properties and the hydrogen bond interactions of 8-aza analogues of xanthine, theophylline and caffeine have been studied by using quantum chemical methods. The time-dependent density functional theory (TD-DFT) and the singly excited configuration interaction (CIS) methods are employed to optimize the excited state geometries of isolated 8-azaxanthine, 8-azatheophylline tautomers and 8-azacaffeine in both the gas and solvent phases. The solvent phase calculations are performed using the polarizable continuum model (PCM). The absorption and emission spectra are calculated using the time-dependent density functional theory (TD-DFT) method. The results from the TD-DFT calculations reveal that the excitation spectra are red shifted relative to absorption in aqueous medium. These changes in the transition energies are qualitatively comparable to the experimental data. The examination of molecular orbital reveals that the molecules with a small H?L energy gap possess maximum absorption and emission wavelength. The relative stability and hydrogen bonded interactions of mono and heptahydrated 8-azaxanthine, 8-azatheophylline tautomers and 8-azacaffeine have been studied using the density functional theory (DFT) and Møller Plesset perturbation theory (MP2) implementing the 6-311++G(d,p) basis set. The formation of strong N-H...O bond has resulted in the highest interaction energy among the monohydrates. Hydration does not show any significant impact on the stability of heptahydrated complexes. The atoms in molecule (AIM) and natural bonding orbital (NBO) analyses have been performed to elucidate the nature of the hydrogen bond interactions in these complexes. PMID:23315214

Karthika, Mylsamy; Kanakaraju, Ramasamy; Senthilkumar, Lakshmipathi

2013-04-01

133

Dynamics and conformational studies of TOAC spin labeled analogues of Ctx(Ile(21))-Ha peptide from Hypsiboas albopunctatus.  

PubMed

Antimicrobial peptides (AMPs) isolated from several organisms have been receiving much attention due to some specific features that allow them to interact with, bind to, and disrupt cell membranes. The aim of this paper was to study the interactions between a membrane mimetic and the cationic AMP Ctx(Ile(21))-Ha as well as analogues containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) incorporated at residue positions n?=?0, 2, and 13. Circular dichroism studies showed that the peptides, except for [TOAC(13)]Ctx(Ile(21))-Ha, are unstructured in aqueous solution but acquire different amounts of ?-helical secondary structure in the presence of trifluorethanol and lysophosphocholine micelles. Fluorescence experiments indicated that all peptides were able to interact with LPC micelles. In addition, Ctx(Ile(21))-Ha and [TOAC(13)]Ctx(Ile(21))-Ha peptides presented similar water accessibility for the Trp residue located near the N-terminal sequence. Electron spin resonance experiments showed two spectral components for [TOAC(0)]Ctx(Ile(21))-Ha, which are most likely due to two membrane-bound peptide conformations. In contrast, TOAC(2) and TOAC(13) derivatives presented a single spectral component corresponding to a strong immobilization of the probe. Thus, our findings allowed the description of the peptide topology in the membrane mimetic, where the N-terminal region is in dynamic equilibrium between an ordered, membrane-bound conformation and a disordered, mobile conformation; position 2 is most likely situated in the lipid polar head group region, and residue 13 is fully inserted into the hydrophobic core of the membrane. PMID:23585852

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

2013-01-01

134

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

PubMed Central

Antimicrobial peptides (AMPs) isolated from several organisms have been receiving much attention due to some specific features that allow them to interact with, bind to, and disrupt cell membranes. The aim of this paper was to study the interactions between a membrane mimetic and the cationic AMP Ctx(Ile21)-Ha as well as analogues containing the paramagnetic amino acid 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) incorporated at residue positions n?=?0, 2, and 13. Circular dichroism studies showed that the peptides, except for [TOAC13]Ctx(Ile21)-Ha, are unstructured in aqueous solution but acquire different amounts of ?-helical secondary structure in the presence of trifluorethanol and lysophosphocholine micelles. Fluorescence experiments indicated that all peptides were able to interact with LPC micelles. In addition, Ctx(Ile21)-Ha and [TOAC13]Ctx(Ile21)-Ha peptides presented similar water accessibility for the Trp residue located near the N-terminal sequence. Electron spin resonance experiments showed two spectral components for [TOAC0]Ctx(Ile21)-Ha, which are most likely due to two membrane-bound peptide conformations. In contrast, TOAC2 and TOAC13 derivatives presented a single spectral component corresponding to a strong immobilization of the probe. Thus, our findings allowed the description of the peptide topology in the membrane mimetic, where the N-terminal region is in dynamic equilibrium between an ordered, membrane-bound conformation and a disordered, mobile conformation; position 2 is most likely situated in the lipid polar head group region, and residue 13 is fully inserted into the hydrophobic core of the membrane. PMID:23585852

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

2013-01-01

135

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

NASA Astrophysics Data System (ADS)

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

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

2014-05-01

136

CO2 Capture with Enzyme Synthetic Analogue  

SciTech Connect

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

Harry Cordatos

2010-11-08

137

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

PubMed

The data are reported for an in vitro metabolism study of two novel synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and its fluorinated analog N-(1-adamantyl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (5F-APICA, STS-135), which are active ingredients of smoking mixtures sold in Russia since 2012. The cannabinoids were isolated from herbal mixtures using preparative liquid chromatography and then incubated with human liver microsomes (HLMs). The formed metabolites were characterized by liquid chromatography - triple quadrupole mass spectrometry and high-resolution mass spectrometry with electrospray ionization in positive ion mode. It was found that HLMs produce mono-, di-, and trihydroxylated metabolites, as well as N-desalkyl metabolites, which can be further hydroxylated; the amide bond resisted the metabolic cleavage. For 5F-APICA, a series of oxidative defluorination products formed as well. For in vivo confirmation of the formed in vitro metabolites, spot urine samples from drug users were analyzed with the created method. It was shown that for the detection of APICA abuse, the preferred metabolites are the di- and tri-hydroxylated species, while in case of 5F-APICA, a monohydroxy metabolite is a better target. The N-despentyl (desfluoropentyl) hydroxyadamantyl metabolite also provides good retrospectivity to confirm the administration of any of these cannabinoids. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25428705

Sobolevsky, Tim; Prasolov, Ilya; Rodchenkov, Grigory

2014-11-26

138

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

ERIC Educational Resources Information Center

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

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

2014-01-01

139

Pena Blanca Natural Analogue Project: Summary of activities  

SciTech Connect

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

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

2011-02-01

140

Pena blanca natural analogue project: summary of activities  

SciTech Connect

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

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

2010-12-08

141

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.

1990-01-01

142

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.

2012-04-01

143

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

PubMed Central

Sphingolipids inhibit the activation of the neutrophil (PMN) NADPH oxidase by protein kinase C pathway. By electron spin resonance spectroscopy (ESR) and chemiluminescence (CL), we studied the effects of sphingosine (SPN) and ceramide analogues on phorbol 12-myristate 13-acetate (PMA, 5 × 10-7M) stimulated PMN (6 × 106 cells). By ESR with spin trapping (100 mM DMPO: 5,5-dimethyl-1-pyrroline-Noxide), we showed that SPN (5 to 8 × 10-6M), C2-ceramide (N-acetyl SPN) and C6-ceramide (N-hexanoyl SPN) at the final concentration of 2 × 10-5 and 2 × 10-4M inhibit the production of free radicals by stimulated PMN. The ESR spectrum of stimulated PMN was that of DMPO-superoxide anion spin adduct. Inhibition by 5 × 10-6M SPN was equivalent to that of 30 U/ml SOD. SPN (5 to 8 × 10-6M) has no effect on in vitro systems generating superoxide anion (xanthine 50 mM/xanthine oxidase 110 mU/ml) or hydroxyl radical (Fenton reaction: 88 mM H2O2, 0.01 mM Fe2+ and 0.01 mM EDTA). SPN and N-acetyl SPN also inhibited the CL of PMA stimulated PMN in a dose dependent manner (from 2 × 10-6 to 10-5M), but N-hexanoyl SPN was less active (from 2 × 10-5 to 2 × 10-4M). These effects were compared with those of known PMN inhibitors, superoxide dismutase, catalase and azide. SPN was a better inhibitor compared with these agents. The complete inhibition by SPN of ESR signal and CL of stimulated PMN confirms that this compound or one of its metabolites act at the level of NADPH-oxidase, the key enzyme responsible for production of oxygen-derived free radicals. PMID:18472867

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

1997-01-01

144

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

PubMed

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

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

2012-06-01

145

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.

2012-01-01

146

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

Microsoft Academic Search

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

K. C. Cloyd; P. W. Concannon

1993-01-01

147

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

1980-07-01

148

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

2011-01-01

149

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

Microsoft Academic Search

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

A Flint; A Raben; JE Blundell; A Astrup

2000-01-01

150

A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly  

Microsoft Academic Search

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg\\/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria

L. K. Dawson; D. I. Jodrell; A. Bowman; R. Rye; B. Byrne; A. Bernareggi; G. Camboni; J. F. Smyth

2000-01-01

151

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.

152

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.

2011-01-01

153

Solid-state gallium-69 and gallium-71 nuclear magnetic resonance spectroscopic studies of gallium analogue zeolites and related systems  

Microsoft Academic Search

The authors have obtained solid-state 11.7-T ⁶⁹Ga and ⁷¹Ga nuclear magnetic resonance (NMR) spectra of a series of gallosilicates (gallium analogues of zeolites Na-X, Na-Y, Na-sodalite, and Na-natrolite). From the apparent ⁶⁹Ga and ⁷¹Ga chemical shifts, values of the nuclear quadrupole coupling constants (e²qQ\\/h) and the true, isotropic chemical shifts (delta\\/sub i) have been deduced for the framework, tetrahedral, Ga(OSi)â

Hye Kyung C. Timken; Eric Oldfield

1987-01-01

154

Plant volatile analogues strengthen attractiveness to insect.  

PubMed

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

2014-01-01

155

A phase I study of the vitamin D 3 analogue ILX23-7553 administered orally to patients with advanced solid tumors  

Microsoft Academic Search

Summary  \\u000a Purpose ILX23-7553 (1,25-dihydroxy-16-ene-23-yne vitamin D3) is a vitamin D analogue that was developed to avoid the hypercalcemia\\u000a that may limit the use of vitamin D as an anti-cancer agent. We performed a phase I study of ILX23-7553 to determine its side-effect\\u000a profile, pharmacokinetics, and to document any observed antitumor activity. Patients and Methods Adult patients with refractory solid tumors

Rajul K. Jain; Donald L. Trump; Merrill J. Egorin; Manuel Fernandez; Candace S. Johnson; Ramesh K. Ramanathan

156

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

2007-01-01

157

A structure-based 3D-QSAR study of anthrapyrazole analogues of the anticancer agents losoxantrone and piroxantrone.  

PubMed

A series of 13 anthrapyrazole compounds that are analogues of piroxantrone and losoxantrone were synthesized, and their cell growth inhibitory effects, DNA binding, topoisomerase IIalpha mediated (EC 5.99.1.3) cleavage of DNA, and inhibition of DNA topoisomerase IIalpha decatenation catalytic activities were determined. Cell growth inhibitory activity was well-correlated with DNA binding, suggesting that these compounds may act by targeting DNA. However, cell growth inhibition was not well-correlated with the inhibition of topoisomerase IIalpha catalytic activity, suggesting that these anthrapyrazoles did not act solely by inhibiting the catalytic activity of topoisomerase II. Most of the analogues were able to induce DNA cleavage, and thus, it was concluded that they acted, at least in part, as topoisomerase II poisons. Structure-based three-dimensional quantitative structure-activity analyses (3D-QSAR) were carried out on the aligned structures of the anthrapyrazoles docked into DNA using comparative molecular field analysis (CoMFA) and comparative molecular similarity index (CoMSIA) analyses in order to determine the structural features responsible for their activity. Both CoMFA and CoMSIA yielded statistically significant models upon partial least-squares analyses. The 3D-QSAR analyses showed that hydrogen-bond donor interactions and electrostatic interactions with the protonated amino side chains of the anthrapyrazoles led to high cell growth inhibitory activity. PMID:16859314

Liang, Hong; Wu, Xing; Guziec, Lynn J; Guziec, Frank S; Larson, Kimberly K; Lang, Jennifer; Yalowich, Jack C; Hasinoff, Brian B

2006-01-01

158

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

PubMed Central

The effects of three ATP analogues, alpha,beta-methylene-ATP [ATP(alpha,beta-CH1)], adenosine 5'-0-(3-thiotrophosphate) [ATP(gamma-S)], and beta,gamma-amino-ATP [ATP(beta,gamma-NH)] at various concentrations and temperatures on the X-ray fiber diagrams of glycerinated flight muscles from a water bug (Lethocerus maximus) have been investigated. It is shown that the "relaxed" state can be obtained with all three analogues at high concentrations, the result being particularly clear with ATP(gamma-S). It is inferred that the binding of an ATP-like molecule suffices to produce the relaxed state. At low concentrations ATP(beta,gamma-NH) produces state intermediate between rigor and relaxed which is not simply a mixture of the two. The possible nature of the intermediate is discussed. Images FIGURE 2a FIGURE 2b FIGURE 4a FIGURE 4b FIGURE 5 FIGURE 6a FIGURE 6b FIGURE 6c FIGURE 6d FIGURE 6e PMID:1139036

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

1975-01-01

159

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

SciTech Connect

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

Not Available

1987-06-01

160

Use of NMR and fluorescence spectroscopy as well as theoretical conformational analysis in conformation-activity studies of cyclic enkephalin analogues.  

PubMed

In this review the conformational studies of natural enkephalins (H-Tyr-Gly-Gly-Phe-Met-OH; the [Met(5)]enkephalin and H-Tyr-Gly-Gly-Phe-Leu-OH; the [Leu(5)]enkephalin), their acyclic and cyclic analogues, including those carried out in our laboratory, performed by experimental and theoretical methods and their combination, are described. Emphasis is given on the role of conformational constraints introduced by cyclization on activity at the micro and delta opioid receptors. Comparison of the conformations of cyclic enkephalin analogues with high delta-receptor activity with those of potent rigid non-peptide delta-receptor agonists indicates that the proximity of the aromatic side chains in positions 1 and 4 as well as the N-terminal amino group is desirable for the activity at the delta opioid receptors; early conformational studies also suggested that spatial separation of the aromatic side chains and rigidity of the cyclic backbone is desirable for micro-receptor activity. The results of our recent conformational studies performed with the use of fluorescence and NMR spectroscopy as well as theoretical calculations indicate, however, that these structural features are not necessary for activity at the micro opioid receptors. Methods applied to the determination of the conformation of flexible peptides, such as Nuclear Magnetic Resonance (NMR), fluorescence spectroscopy, and theoretical conformational analysis are also discussed briefly. PMID:14754380

Malicka, Joanna; Czaplewski, Cezary; Groth, Malgorzata; Wiczk, Wieslaw; Oldziej, Stanislaw; Lankiewicz, Leszek; Ciarkowski, Jerzy; Liwo, Adam

2004-01-01

161

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

PubMed

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

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

2014-07-01

162

An estrogen analogue and promising anticancer agent refrains from inducing morphological damage and reactive oxygen species generation in erythrocytes, fibrin and platelets: a pilot study  

PubMed Central

Background 2-Methoxyestradiol is known to have antitumour and antiproliferative action in vitro and in vivo. However, when 2-methoxyestradiol is orally administered, it is rapidly oxidized by the enzyme 17β-hydroxysteriod dehydrogenase in the gastrointestinal tract. Therefore, 2-methoxyestradiol never reaches high enough concentrations in the tissue to be able to exert these antitumour properties. This resulted in the in silico-design of 2-methoxyestradiol analogues in collaboration with the Bioinformatics and Computational Biology Unit (UP) and subsequent synthesis by iThemba Pharmaceuticals (Pty) Ltd (Modderfontein, Midrand, South Africa). One such a novelty-designed analogue is 2-ethyl-3-O-sulphamoyl-estra-1, 3, 5(10)16-tetraene (ESE-16). Methods This pilot study aimed to determine the morphological effect and possible generation of reactive oxygen species by ESE-16 on erythrocytes and platelet samples (with and without added thrombin) by means of scanning electron microscopy, transmission electron microscopy and flow cytometry. Results Erythrocytes and platelets were exposed to ESE-16 at a concentration of 180nM for 24 hours. Scanning- and transmission electron microscopy indicated that ESE-16 did not cause changes to erythrocytes, platelets or fibrin networks. Flow cytometry measurements of hydrogen peroxide and superoxide indicated that ESE-16 does not cause an increase in the generation of reactive oxygen species in these blood samples. Conclusion Further in vivo research is warranted to determine whether this novel in silico-designed analogue may impact on development of future chemotherapeutic agents and whether it could be considered as an antitumour agent. PMID:24932135

2014-01-01

163

Multidisciplinary study on Wyoming test sites  

NASA Technical Reports Server (NTRS)

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

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

1975-01-01

164

Pharmacological actions of some cyclic analogues of choline.  

PubMed Central

Two cyclic choline analogues (3-hydroxy-N,N- dimethylpiperidinium and 2-hydroxymethyl-N,N- dimethylpiperidinium ) and two cyclic homocholine analogues (4-hydroxy-N,N- dimethylpiperidinium and 3-hydroxymethyl-N,N- dimethylpiperidinium ) have been studied with regard to their actions at the cholinergic synapse. All the analogues had some direct depolarizing activity on the frog rectus abdominis muscle but they were less potent in this respect than acetylcholine. Compared to physostigmine, the analogues were weak inhibitors of cholinesterase enzymes. All the analogues were found to have a presynaptic blocking action on the rat phrenic nerve-hemidiaphragm preparation, which was reversed by choline. In addition, they all inhibited the high affinity transport of choline into synaptosomes but only the cyclic choline analogues were found to be acetylated by soluble choline acetyltransferase in vitro. We conclude that the hydroxypiperidinium analogues caused the presynaptic block seen at the neuromuscular junction by inhibiting acetylcholine synthesis. PMID:6326923

Hemsworth, B. A.; Shreeve, S. M.; Veitch, G. B.

1984-01-01

165

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

PubMed

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

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

2014-01-01

166

Ab initio study of the geometry, stability, and aromaticity of the cyclic S2N3(+) cation isomers and their isoelectronic analogues.  

PubMed

A theoretical study of the geometries, energies, dissociation pathways, and aromaticity of the isomeric sulfur-nitrogen S(2)N(3)(+) rings reveals that the experimentally known 1,2-isomer is only stable kinetically. A rather high barrier inhibits its dissociation into the slightly lower energy N(2) and NSS(+) fragments via a stepwise mechanism. A second possible dissociation mode, into NNS and NS(+) via a concerted [3 + 2] mechanism, is endothermic. Instead, the reverse cycloaddition reaction has a low barrier and offers an exothermic route for the formation of cyclic 1,2-S(2)N(3)(+). Despite being thermodynamically more stable, the 1,3-isomer has only fleeting existence: its facile exothermic [3 + 2] cycloreversion into N(2) and SNS(+) fragments precludes observation. Nucleus independent chemical shifts (NICS) analysis reveals considerable six pi electron aromaticity for both cyclic S(2)N(3)(+) isomers, as well as their five membered ring valence isoelectronic analogues, N(5)(-), SN(4), and S(3)N(2)(2+). The decomposition routes and the energetics of these analogues also provide comparisons along the series. PMID:19496559

Zhang, Guo-Hua; Zhao, Yong-Fang; Wu, Judy I; Schleyer, Paul V R

2009-07-20

167

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

PubMed Central

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

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

2014-01-01

168

Facies and geothermal reservoir characteristics of sedimentary rocks: an outcrop analogue study of the Meso- and Cenozoic series of Budapest (Hungary)  

NASA Astrophysics Data System (ADS)

Sedimentary basins located in regions exhibiting geothermal anomalies are very promising for hydrothermal exploration. Facies model integration into seismic 3D interpretation allow description of reservoir parameters such as permeability, thermal conductivity and reservoir heat flow, as these properties are directly correlative to facies heterogeneity integrated from outcrop studies. Outcrop analogue studies support the characterization of deep geothermal reservoirs and their geothermal operations. 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.

Götz, Annette E.; Sass, Ingo; Török, Ákos

2010-05-01

169

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

PubMed

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

2012-10-01

170

High Plains Regional Ground-water Study web site  

USGS Publications Warehouse

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

Qi, Sharon L.

2000-01-01

171

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

SciTech Connect

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

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

1991-09-01

172

Transverse analogue tomography in radiotherapy.  

PubMed

This paper describes the design and development of a single unit to combine the advantages of precision high-energy simulation and X-ray body scanning. Good detail transverse-axial-tomograms are produced on the basis of analogue technology where the X-ray density values of the slice of the object are produced in analogue instead of digital form. In broad terms, the development of this unit now for the first time enables the radiotherapist (after localising the tumour site by conventional diagnostic X-ray screening on the simulator) to proceed immediately (without moving the patient) to transverse-axial-tomography, slicing the target volume to give three dimensional evidence of the spread and position of the growth relative to adjacent normal structures. This information is fed into a computer-controlled treatment-planning system quickly to facilitate the preparation of precise treatment presciriptions. The running costs and the staff needed to operate and maintain this dual-function machine do not appear greater than the normally accepted requirements for a conventional radiotherapy simulator. PMID:6769137

Crooks, S H; Hanna, F A

1980-03-01

173

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.

1994-12-01

174

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

Microsoft Academic Search

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

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

2008-01-01

175

Continuous\\/discrete geochemical monitoring of CO 2 natural analogues and of Diffuse Degassing Structures (DDS): Hints for CO 2 storage sites geochemical monitoring protocol  

Microsoft Academic Search

Italy is one of the most promising prone areas to study the CO2 behavior underground, the caprock integrity to the CO2 leakage, mostly in presence of pervious\\/geochemically active faults, due to a wide availability of CO2 rich reservoirs at a depth between 1 and 10 km, as highlighted by recent literature. These deep CO2 reservoirs generate at least 200 leakage areas

F. Quattrocchi; B. Cantucci; D. Cinti; G. Galli; L. Pizzino; A. Sciarra; N. Voltattorni

2009-01-01

176

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.

2009-01-01

177

Emerald Lake Watershed study: Introduction and site description  

Microsoft Academic Search

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

Kathy A. Tonnessen

1991-01-01

178

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

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

179

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

SciTech Connect

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

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

1994-07-01

180

TWRS privatization phase I site development engineering study  

SciTech Connect

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

Shord, A.L.

1996-09-30

181

Study Abroad in Venezuela ON-SITE GUIDE 201415  

E-print Network

Study Abroad in Venezuela ON-SITE GUIDE 2014­15 S T U D Y A B R O A D THE AMERICAS #12;2 Important and can contact the on-site director if needed. In Venezuela VENUSA College 49-49 Avenida Urdaneta Edificio Guilam Mérida, Venezuela Phone: 58.274.263.7631 Fax: 58.274.263.3525 www

Weiblen, George D

182

Study Abroad in Venezuela ON-SITE GUIDE 201415  

E-print Network

Study Abroad in Venezuela ON-SITE GUIDE 2014­15 S T U D Y A B R O A D THE AMERICAS #12;2 Important and can contact the on-site director if needed. In Venezuela VENUSA College 49-49 Avenida Urdaneta Edificio Guilam Mérida, Venezuela Phone: 58.274.263.7631 Fax: 58.274.263.3525 www.VENUSAcollege.org Francy

Minnesota, University of

183

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

SciTech Connect

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

Not Available

1987-06-01

184

Application of a fluorescent cobalamin analogue for analysis of the binding kinetics. A study employing recombinant human transcobalamin and intrinsic factor.  

PubMed

Fluorescent probe rhodamine was appended to 5' OH-ribose of cobalamin (Cbl). The prepared conjugate, CBC, bound to the transporting proteins, intrinsic factor (IF) and transcobalamin (TC), responsible for the uptake of Cbl in an organism. Pronounced increase in fluorescence upon CBC attachment facilitated detailed kinetic analysis of Cbl binding. We found that TC had the same affinity for CBC and Cbl (K(d) = 5 x 10(-15) m), whereas interaction of CBC with the highly specific protein IF was more complex. For instance, CBC behaved normally in the partial reactions CBC + IF(30) and CBC + IF(20) when binding to the isolated IF fragments (domains). The ligand could also assemble them into a stable complex IF(30)-CBC-IF(20) with higher fluorescent signal. However, dissociation of IF(30)-CBC-IF(20) and IF-CBC was accelerated by factors of 3 and 20, respectively, when compared to the corresponding Cbl complexes. We suggest that the correct domain-domain interactions are the most important factor during recognition and fixation of the ligands by IF. Dissociation of IF-CBC was biphasic, and existence of multiple protein-analogue complexes with normal and partially corrupted structure may explain this behaviour. The most stable component had K(d) = 1.5 x 10(-13) m, which guarantees the binding of CBC to IF under physiological conditions. The specific intestinal receptor cubilin bound both IF-CBC and IF-Cbl with equal affinity. In conclusion, the fluorescent analogue CBC can be used as a reporting agent in the kinetic studies, moreover, it seems to be applicable for imaging purposes in vivo. PMID:16984395

Fedosov, Sergey N; Grissom, Charles B; Fedosova, Natalya U; Moestrup, Søren K; Nexø, Ebba; Petersen, Torben E

2006-10-01

185

Matrix Metalloproteinase 2 (MMP2) Inhibition: DFT and QM/MM Studies of the Deprotonation-Initialized Ring-Opening Reaction of the Sulfoxide Analogue of SB-3CT  

E-print Network

Matrix Metalloproteinase 2 (MMP2) Inhibition: DFT and QM/MM Studies of the Deprotonation-Phenoxyphenylsulfonyl)methylthiirane (SB-3CT) is the selective inhibitor of matrix metalloproteinase 2 (MMP2 analogue. Introduction Matrix metalloproteinases (MMPs) regulate functions of the extracellular matrix (ECM

Schlegel, H. Bernhard

186

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.

2004-01-01

187

Overview of Ground-Water Recharge Study Sites  

USGS Publications Warehouse

Multiyear studies were done to examine meteorologic and hydrogeologic controls on ephemeral streamflow and focused ground-water recharge at eight sites across the arid and semiarid southwestern United States. Campaigns of intensive data collection were conducted in the Great Basin, Mojave Desert, Sonoran Desert, Rio Grande Rift, and Colorado Plateau physiographic areas. During the study period (1997 to 2002), the southwestern region went from wetter than normal conditions associated with a strong El Ni?o climatic pattern (1997?1998) to drier than normal conditions associated with a La Ni?a climatic pattern marked by unprecedented warmth in the western tropical Pacific and Indian Oceans (1998?2002). The strong El Ni?o conditions roughly doubled precipitation at the Great Basin, Mojave Desert, and Colorado Plateau study sites. Precipitation at all sites trended generally lower, producing moderate- to severe-drought conditions by the end of the study. Streamflow in regional rivers indicated diminishing ground-water recharge conditions, with annual-flow volumes declining to 10?46 percent of their respective long-term averages by 2002. Local streamflows showed higher variability, reflecting smaller scales of integration (in time and space) of the study-site watersheds. By the end of the study, extended periods (9?15 months) of zero or negligible flow were observed at half the sites. Summer monsoonal rains generated the majority of streamflow and associated recharge in the Sonoran Desert sites and the more southerly Rio Grande Rift site, whereas winter storms and spring snowmelt dominated the northern and westernmost sites. Proximity to moisture sources (primarily the Pacific Ocean and Gulf of California) and meteorologic fluctuations, in concert with orography, largely control the generation of focused ground-water recharge from ephemeral streamflow, although other factors (geology, soil, and vegetation) also are important. Watershed area correlated weakly with focused infiltration volumes, the latter providing an upper bound on associated ground-water recharge. Estimates of annual focused infiltration for the research sites ranged from about 105 to 107 cubic meters from contributing areas that ranged from 26 to 2,260 square kilometers.

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

2007-01-01

188

Phosphate binding and ATP-binding sites coexist in Na+/K(+)-transporting ATPase, as demonstrated by the inactivating MgPO4 complex analogue Co(NH3)4PO4.  

PubMed

Tetrammine cobalt(III) phosphate [Co(NH3)4PO4] inactivates Na+/K(+)-ATPase in the E2 conformational state, dependent on time and concentration, according to Eqn (1): Co(NH3)4PO4 + E2 Kd in equilibrium E2.Co(NH3)4PO4k2----E'2.Co(NH3)4PO4. The inactivation rate constant k2 for the formation of a stable E'2.Co(NH3)4PO4 at 37 degrees C was 0.057 min-1; the dissociation constant, Kd = 300 microM. The activation energy for the inactivation process was 149 kJ/mol. ATP and the uncleavable adenosine 5'-[beta, gamma-methylene]triphosphate competed with Co(NH3)4PO4 for its binding site with Ks = 0.41 mM and 5 mM, respectively. MgPO4 competed with Co(NH3)4PO4 linearly, with Ks = 50 microM, as did phosphate (Ks = 16 mM) and Mg2+ (Ks = 160 microM). It is concluded that the MgPO4 analogue binds to the MgPO4-binding subsite of the low-affinity ATP-binding site (of the E2 conformation). Also, Na+ (Ks = 860 microM) protected the enzyme against inactivation in a competitive manner. From the intersecting (slope and intercept linear) noncompetitive effect of Na+ against the inactivation by Co(NH3)4PO4, apparent affinities of K+ for the free enzyme of 41 microM, and for the E.Co(NH3)4PO4 complex of 720 microM, were calculated. Binding of Co(NH3)4PO4 to the enzyme inactivated Na+/K(+)-ATPase and K(+)-activated phosphatase, and, moreover, prevented the occlusion of 86Rb+; however, the activity of the Na(+)-ATPase, the phosphorylation capacity of the high-affinity ATP-binding site and the ATP/ADP-exchange reaction remained unchanged. With Co(NH3)432PO4 a binding capacity of 135 pmol unit enzyme was found. Phosphorylation and complete inactivation of the enzyme with Co(NH3)432PO4 or the 32P-labelled tetramminecobalt ATP ([gamma-32P]Co(NH3)4ATP) at the low-affinity ATP-binding site, allowed (independent of the purity of the Na+/K(+)-ATPase preparation) a further incorporation of radioactivity from 32P-labelled tetraaquachromium(III) ATP ([gamma-32P]CrATP) to the high-affinity ATP-binding site with unchanged phosphorylation capacity. However, inactivation and phosphorylation of Na+/K(+)-ATPase by [gamma-32P]CrATP prevented the binding of Co(NH3)4 32PO4 or [gamma-32P]Co(NH3)4ATP to the enzyme. [gamma-32P]CO(NH3)4ATP and Co(NH3)432PO4 are mutually exclusive. The data are consistent with the assumption of a cooperation of catalytic subunits within an (alpha,beta)2-diprotomer, which change their interactions during the Na+/K(+)-pumping process. Our findings seem not to support a symmetrical Repke and Stein model of enzyme action. PMID:1847680

Buxbaum, E; Schoner, W

1991-01-30

189

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

PubMed

The quality of stored roof runoff in terms of pesticide pollution was assessed over a one-year period. Two tanks, located at a rural and suburban site, respectively, were sampled monthly. The two studied collection surface were respectively a tile slope roof and a bituminous flat roof. Four hundred and five compounds and metabolites were screened using liquid and gas chromatography coupled with various detection systems. Principal Component Analysis was applied to the data sets to elucidate patterns. At the rural site, two groups of compounds associated with two different types of agriculture, vineyard and crops, were distinguished. The most frequently detected compound was glyphosate (83%) which is the most commonly used herbicide in French vineyards. At the suburban site, quantified compounds were linked to agriculture rather than urban practices. In addition, all samples were contaminated with mecoprop which is a roof-protecting agent. Its presence was attributed to the nature of roofing material used for rainwater collection. For both sites, the highest number and concentrations of compounds and metabolites were recorded at the end of spring and through summer. These results are consistent with treatment periods and higher temperatures. PMID:23500648

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

2013-05-15

190

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

Microsoft Academic Search

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

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

1996-01-01

191

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

SciTech Connect

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

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

2002-04-01

192

Molecular dynamics study of the ribosomal A-site  

PubMed Central

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

Romanowska, Julia; Setny, Piotr; Trylska, Joanna

2009-01-01

193

Natural analogues of nuclear waste glass corrosion  

Microsoft Academic Search

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

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

1999-01-01

194

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

Microsoft Academic Search

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

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

2006-01-01

195

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

Microsoft Academic Search

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

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

2005-01-01

196

Surgical site infections in Italian Hospitals: a prospective multicenter study  

Microsoft Academic Search

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

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

2008-01-01

197

Surgical Site Infections in Breast Surgery: Case-control Study  

Microsoft Academic Search

The purpose of this study was to estimate the frequency of surgical site infections (SSIs) and identify associated risk factors for each type of breast surgery at a cancer hospital. We used a nested case-control design. Between February 1, 2000 and July 31, 2000, all breast surgeries performed were recorded on a daily basis. After hospital discharge, we evaluated patients

Diana Vilar-Compte; Benedicte Jacquemin; Carlos Robles-Vidal; Patricia Volkow

2004-01-01

198

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

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

199

Site matching of wind turbine generators: A case study  

SciTech Connect

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

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

1999-12-01

200

Mars sample return: Site selection and sample acquisition study  

NASA Technical Reports Server (NTRS)

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

Nickle, N. (editor)

1980-01-01

201

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

SciTech Connect

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

Assary, R. S.; Curtiss, L. A. (Center for Nanoscale Materials); ( MSD); (Northwestern Univ.)

2011-08-01

202

Hanford Site Annual Treatability Studies Report, Calendar Year 2002  

SciTech Connect

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

Grohs, Eugene L.

2003-02-28

203

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

PubMed

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

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

2013-04-01

204

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

PubMed

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

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

2013-04-01

205

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

PubMed

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

2014-08-01

206

Genetics of site specific colon cancer: a family study.  

PubMed

In a kindred of 46 individuals of an Indian Sikh family with no history of consanguinity, 8 suffered from site specific colon (caecum) cancer (not associated with polyposis). The clinical features in the affected kindred were indicative of a "cancer family syndrome". The study of the family depicted an autosomal dominant transmission pattern of site specific colon cancer, with probably 100% penetrance in the affected individuals. A low percentage of mitotic index (MI) was observed in the two probands who were available for the study. No structural or numerical chromosomal aberrations were observed in either case. It is probable that the gene responsible in this family could have begun by mutation at the germ cell level in the 1st generation and remained in a heterozygous condition in the affected individuals. PMID:6088133

Bamezai, R; Singh, G; Khanna, N N; Singh, S

1984-08-01

207

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.

1994-12-01

208

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

1997-01-01

209

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

PubMed

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

Choudhry, Rafiq M

2014-09-01

210

Comparing the Study Site to One in Another Region  

NSDL National Science Digital Library

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

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

2003-08-01

211

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

Microsoft Academic Search

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

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

2005-01-01

212

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

NASA Astrophysics Data System (ADS)

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

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

2012-04-01

213

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.

2005-12-01

214

Design of granulatimide and isogranulatimide analogues as potential Chk1 inhibitors: Study of amino-platforms for their synthesis.  

PubMed

The two marine alkaloids granulatimide and isogranulatimide have been shown to inhibit the checkpoint kinase 1 (Chk1), a promising target for cancer treatment. A molecular docking study allowing the design of new potential Chk1 inhibitors based on the natural products skeleton and the synthetic work to an amino-target platform to prepare them are described. PMID:25047935

Lavrard, Hubert; Rodriguez, Frédéric; Delfourne, Evelyne

2014-09-01

215

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

PubMed

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

2012-11-01

216

Towards adaptive Web sites: Conceptual framework and case study  

Microsoft Academic Search

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

Mike Perkowitz; Oren Etzioni

2000-01-01

217

Summary of 1990 eolian characterization studies, Hanford Site, Washington  

SciTech Connect

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

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

1993-12-01

218

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

SciTech Connect

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

NONE

1996-05-03

219

Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues  

PubMed Central

Progesterone antagonist RU486 (mifepristone) has been implicated for many anti-neoplastic and obstetrical applications. But the compound has demonstrated undesired agonist-like effect depending on cell, tissue and species studied. Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK). Like progesterone, RU486 inhibited cells growth by arresting the cells in G0/G1 phase of the cell cycle. In contrast to progesterone that induced cell spreading, RU486 induced a multipolar, stellate morphology. RU486-treated cells showed no increase of stress fibers, nor was there any increase of focal adhesions as progesterone-treated cells did. Furthermore, despite of the fact that both compounds inhibited cell growth, RU486 significantly stimulated the activation of p44/p42 MAP kinases whereas progesterone markedly inhibited the activation. Nonetheless, the effects of RU486 were PR-mediated and RU486 was able to antagonize the effect of progesterone on cell growth and focal adhesion. In conclusion, RU486 can act not only as a progesterone antagonist, a progesterone agonist but also induced morphological and molecular changes that were distinct from progesterone-mediated effects in PR-transfected MDA-MB-231 cells. The non-progesterone-like effect of RU486 may be mediated through a pathway that is different from the progesterone-mediated pathway, or it is the result of a blockade of certain critical step(s) in the progesterone-mediated pathway. In any case, undesired side effects of antiprogestin may create clinical complications. PR-transfected MDA-MB-231 breast cancer cells provide a model for studying the functions of progesterone analogues.© 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11747343

Lin, V C-L; Aw, S E; Ng, E H; Ng, E H-L; Tan, M G-K

2001-01-01

220

One-electron redox reactions of pyrazolin-5-ones. A pulse radiolysis study of antipyrine and analogues  

SciTech Connect

One-electron oxidation of several derivatives of pyrazolin-5-one, including the drug antipyrine, were studied by pulse radiolysis of aqueous solutions. All the compounds were found to be oxidized by Br2 rapidly but considerably more slowly by weaker oxidants, such as peroxyl radicals. From redox equilibria using p-methoxyphenol and N,N,N',N'-tetramethyl-p-phenylenediamine as reference compounds, the one-electron oxidation potentials of the methyl-substituted 2-pyrazolin-5-ones were found to be in the range of 0.32-0.39 V versus normal hydrogen electrode. The relevance of these findings to the properties of the drug nafazatrom is discussed. Antipyrine was found to have a much higher oxidation potential, estimated as 1.2-1.5 V, which is rationalized on the basis of the phenyl substitution and lack of resonance stabilization of the radical cation.

Jovanovic, S.V.; Neta, P.; Simic, M.G.

1985-10-01

221

Targeted Melanoma Imaging and Therapy with Radiolabeled Alpha-Melanocyte Stimulating Hormone Peptide Analogues  

PubMed Central

Radiolabeled alpha-melanocyte stimulating hormone (?-MSH) analogues have been used to define the expression, affinity and function of the melanocortin-1 receptor (MC1-R). The MC1-R is one of a family of five G-protein linker receptors, which is primarily involved in regulation of skin pigmentation. Over-expression of the MC1-R on melanoma tumor cells has made it an attractive target for the development of ?-MSH peptide based imaging and therapeutic agents. Initially, the native ?-MSH peptide was radiolabeled directly, but it suffered from low specific activity and poor stability. The addition of non-natural amino acids yielded ?-MSH analogues with greater MC-1R affinity and stability. Furthermore, peptide cyclization via disulfide and lactam bond formation as well as site-specific metal coordination resulted in additional gains in receptor affinity and peptide stability in vitro and in vivo. Radiochemical stability of the ?-MSH analogues was improved through the conjugation of metal chelators to the peptide’s N-terminus or lysine residues for radionuclide coordination. In vitro cell binding studies demonstrated that the radiolabeled ?-MSH analogues had low to subnanomolar affinities for the MC1-R. Biodistribution and imaging studies in the B16 mouse melanoma modeled showed rapid tumor uptake of the radiolabeled peptides, with the cyclic peptides demonstrating prolonged tumor retention. Cyclic ?-MSH analogues labeled with beta and alpha emitting radionuclides demonstrated melanoma therapeutic efficacy in the B16 melanoma mouse model. Strong pre-clinical imaging and therapy data highlight the clinical potential use of radiolabeled ?-MSH peptides for melanoma imaging and treatment of disseminated disease. PMID:20467398

Quinn, Thomas; Zhang, Xiuli; Miao, Yubin

2010-01-01

222

3D structure of a heparin mimetic analogue of a FGF-1 activator. A NMR and molecular modelling study.  

PubMed

The motional behaviour of heparin oligosaccharides in solution is best described as a top rotor having two perpendicular rotation axes. This prevents an accurate extraction of interprotonic distances by NOESY/ROESY based methods. In this paper, we describe the solution structure of the hexasaccharide 1 calculated from high exactitude distance data obtained from off-resonance ROESY combined with a long MD simulation of 500 ns. In previous studies, we have found that two synthetic hexasaccharides having the sulphate groups directed towards one side of its central plane have an opposite biological activity, while 1 is unable to activate the FGF-1 signalling pathway, the other (2) is even more active than the regular region derived hexasaccharide (3) that mimics the natural active compound, heparin. From the structural analysis it was concluded that 1 has similar three-dimensional characteristics to 2 or 3 and therefore the differences in the activity should be due to the arrangement of the sulphate groups within the hexasaccharidic sequence. PMID:24178304

Muñoz-García, Juan C; Solera, Cristina; Carrero, Paula; de Paz, José L; Angulo, Jesús; Nieto, Pedro M

2013-12-21

223

Minero-petrographic studies of a possible Martian analogue environment: Specchio DI Venere Lake, Pantelleria Island (Italy).  

NASA Astrophysics Data System (ADS)

It's generally accepted that the development of life needs, at least, the presence of liquid water, sources of energy and biogenic elements. It seems that, on Mars, the above mentioned conditions were often present in the past, due to several reasons such as volcanic activity, greenhouse periods and impact cratering. In this scenario, it's probable that biological remnants (if there any) could have been localised in sedimentary rocks deposited in lacustrine (wet periods) or in sabkha (dry periods) conditions. In particular, hydrothermal environments widespread present on Mars surface, could have been suitable habitats for bacterial proliferation as it happens on Earth at present. For this reason we choose the environments of volcanic islands close to Sicily (Italy) that are rich in young hydrothermal activity. In Pantelleria Island there is a crater lake, Specchio di Venere, were diffuse and small hot springs bubble under the water. The development of life forms is strictly related to the presence of these gaseous veneers that provide the ideal microhabitat. We analysed the mineralogy of sediments coming from Specchio di Venere Lake and the results were in a good agreement with the mineral assemblages predicted for similar environments on Mars on the basis of previous studies.

Baliva, A.; Marinangeli, L.; Piluso, E.; Ori, G. G.; Ruscito, V.

1999-09-01

224

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

PubMed

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

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

2011-01-01

225

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

PubMed

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

2013-01-01

226

Inactivation of two hyperactive LH-RH analogues by rat hypothalamic peptidases.  

PubMed

Hyperactive analogues of luteinizing hormone-releasing hormone (LH-RH) are beleived to derive their properties from either increased binding affinity to anterior pituitary receptor sites or through decreased susceptibility to enzymic degradation. To investigate the latter suggestion and to examine the possible sites of hypothalamic peptidases inactivating LH-RH, D-Ser(TBU)6-EA10-LH-RH and D-Leu6-EA10-LH-RH, which are known to have considerably greater activity than LH-RH, were incubated with a hypothalamic supernatant fraction containing active peptidases degrading LH-RH, and their gonadotrophin-releasing ability after incubation with the enzymes was tested in normal, adult male rats; LH-RH was also tested in the same way. From a comparison of the relative losses of biological activity, both the LH-RH analogues treated proved to be more resistant to the hypothalamic peptidases than LH-RH itself; the D-Leu6-EA10-LH-RH retained its gonadotrophin-releasing activity longer than the D-Ser(TUB)6-EA10-LH-RH. These findings indicate that increased activity of the analogues may, in part be due to increased resistance to enzymic inactivation and suggest initial sites of cleavage at the Gly-leu and Pro-Gly NH2 bonds in the LH-RH decapeptide by the hypothalamic enzymes. Studies on the action of peptidases on LH-RH and its analogues may yield useful information in the design of peptidase with increased biological activity. PMID:378806

Griffiths, E C; Hopkinson, C R

1979-01-01

227

Comparison of the Antiviral Effects of Different Nucleos(t)ide Analogues in Chinese Patients with Chronic Hepatitis B: A Head-to-Head Study  

PubMed Central

Background/Aims: To assess the antiviral efficacy of lamivudine (LAM), entecavir (ETV), telbivudine (LDT), and lamivudine and adefovir dipivoxil (CLA) combination in previously untreated hepatitis B patients at different time points during a 52-week treatment period. Patients and Methods: A total of 164 patients were included in this prospective, open-label, head-to-head study. Serum levels of alanine transaminase (ALT), hepatitis B virus (HBV) DNA, and hepatitis B e antigen (HBeAg) were measured at baseline, and at 12, 24, and 52 weeks of treatment. Results: Median reductions in serum HBV DNA levels at 52 weeks (log10 copies/mL) were as follows: LAM, 3.98; ETV, 3.89; LDT, 4.11; and CLA, 3.36. The corresponding HBV DNA undetectability rates were 83%, 96%, 91%, and 89%, respectively. These two measures showed no significant intergroup differences. Clinical efficacy appeared related to HBV DNA level reduction after 24 weeks of therapy. Patients were divided into three groups based on HBV DNA levels at week 24: Undetectable (<103 copies/mL), detectable but <104 copies/mL, and >104 copies/mL. Patients with levels below quantitation limit (QL) were analyzed at 52 weeks for HBV DNA undetectability rate (94%), ALT normalization rate (83%), and viral breakthrough rate (0%). The corresponding values in the QL-104 copies/mL group were 50%, 75%, and 13%, whereas those in the above 104 copies/mL group were 53%, 65%, and 18%. There were significant differences at week 52 for HBV DNA levels and viral breakthrough rate between the three groups. Conclusions: Different nucleos(t)ide (NUC) analogues tested exhibited no significant differences in effectiveness for Chinese NUC-naive HBV patients during 1-year treatment period. PMID:25434315

Yu, Shu; Zhou, Qin; Zhao, Xiao Miao; Yuan, Min; Wang, Chang Tai; Cheng, Xiao Guang; Zhang, Zhen Hua; Li, Xu

2014-01-01

228

Web Site Accessibility: A Study of Six Genres.  

ERIC Educational Resources Information Center

Examines the accessibility of six categories of Web sites using the evaluation software Bobby. Discusses universal access for users with disabilities; application of the Americans with Disabilities Act and Rehabilitation Act Amendments of 1998; government sites versus commercial sites; and Web site design. (Author/LRW)

Jackson-Sanborn, Emily; Odess-Harnish, Kerri; Warren, Nikki

2002-01-01

229

Identification of competitive antagonists of the rod photoreceptor cGMP-gated cation channel: beta-phenyl-1,N2-etheno-substituted cGMP analogues as probes of the cGMP-binding site.  

PubMed

cGMP is the natural activator of the cyclic nucleotide-gated channel originally isolated from rod photoreceptors but now known to be expressed in a wide variety of neural and non-neural cells. To identify antagonists of cGMP action and to better understand the interaction between cGMP and the channel protein, experimental studies were undertaken using four synthetic cGMP analogues, PET-cGMP, 8-Br-PET-cGMP, Rp-8-Br-PET-cGMPS, and Sp-8-Br-PET-cGMPS. With excised patches from either Xenopus oocytes expressing a cloned rat rod channel alpha-subunit or from native Xenopus rod photoreceptors, Rp-8-Br-PET-cGMPS competitively suppressed the cGMP-induced current with an IC50 of 25 microM and Sp-8-Br-PET-cGMPS inhibited this current with an IC50 of 105 microM. On the expressed rat rod channel, 8-Br-PET-cGMP behaved as a very weak partial agonist at high concentrations and an antagonist (IC50 = 64 microM) at lower concentrations when coapplied with cGMP. PET-cGMP did not activate channel currents alone but showed a synergism when coapplied with subsaturating concentrations of cGMP. Because Sp-8-Br-PET-cGMPS is a potent activator of type I cGMP-dependent protein kinase, but a competitive antagonist of channel activation, it will be a useful reagent for discriminating between those effects of cGMP that are mediated by a protein kinase and those mediated by channel activation. Because the PET derivatives all contain a phenyl-substituted 5-membered ring system fused to the amino group in position 2 and the nitrogen in position 1 of the guanine ring, the results support the idea that N1 and N2 are important for channel activation. They also suggest a minor role for the cyclic phosphate group in binding or activation. PMID:8988020

Wei, J Y; Cohen, E D; Yan, Y Y; Genieser, H G; Barnstable, C J

1996-12-24

230

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.

2009-01-01

231

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.

2013-01-01

232

Antitumor Potential of Conjugable Valinomycins Bearing Hydroxyl Sites: In Vitro Studies  

PubMed Central

Following our pioneering studies on the direct and efficient introduction of derivatizable hydroxyl handles into the valinomycin (VLM, 1) structure, a K+-ionophore with potent antitumor activity, the ensuing conjugable analogues (HyVLMs 2, 3, and 4) have herein been compared to the parent macrocycle for their potential antiproliferative effects on a panel of cancer cell lines, namely, human MCF-7, A2780, and HepG2, as well as rat C6 cells. On the basis of IC50 values, we find that hydroxyl analogues 3 and 4 are only moderately less active than 1, while analogue 2 experiences a heavily diminished activity. Cytofluorimetric analyses of MCF-7 cells treated with HyVLMs suggest that the latter depolarize mitochondria, thus retaining the typical VLM behavior. It is likely that C6 cells, for which the exceptionally potent cytotoxicity of VLM has never reported previously, follow the same fate, as evidenced by alteration of mitochondrial morphology upon incubation with each ionophore. PMID:24900628

2013-01-01

233

Analogue to digital transformation  

NASA Astrophysics Data System (ADS)

ESDU 92044 examines the replacement of an analog controller element by an equivalent digital controller element while retaining for the new hybrid system performance characteristics that are acceptably similar to those of the original continuous system. The main features are described of a system containing both analog and digital elements within the same loop, and the analog-to-digital and digital-to-analog components that are then necessarily a part of the system. The frequency response characteristics of transformation are discussed, introducing the problem of aliasing whereby a digital output can be matched by continuous sine waves of different frequencies that are then indistinguishable to the digital sampler. The need to avoid aliasing is considered and the concept of a folding frequency introduced below which aliasing is impossible. Two transformation methods for designing digital filters equivalent to analog filters are discussed: the impulse invariance and bilinear transformations. They are compared by examining digital equivalents of such analogue filters as simple and compound first-order lag and lead filters, second-order lag filters and first-order notch filters. The methods are compared for two sampling rates using Bode plots illustrating the gain and phase variation with frequency. An example based on an electromechanical instrument servo illustrates the transformation of an analog lag-lead controller using the bilinear transformation.

1992-12-01

234

BIOREMEDIATION TREATABILITY STUDIES OF CONTAMINATED SOILS AT WOOD PRESERVING SITES  

EPA Science Inventory

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

235

Synthesis and solution conformation studies of the modified nucleoside N4, 2?-O-dimethylcytidine (m4Cm) and its analogues  

PubMed Central

The dimethylated ribosomal nucleoside m4Cm and its monomethylated analogues Cm and m4C were synthesized. The conformations (syn versus anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O versus N methylation) was found to have an effect on the sugar pucker of cytidine. PMID:18805697

Mahto, Santosh K.; Chow, Christine S.

2008-01-01

236

Tetragonal Lysozyme Interactions Studied by Site Directed Mutagenesis  

NASA Technical Reports Server (NTRS)

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

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

1999-01-01

237

Tetragonal Lysozyme Interactions Studied by Site Directed Mutagenesis  

NASA Technical Reports Server (NTRS)

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

Crawford, Lisa; Karr, Laurel; Pusey, Marc

1998-01-01

238

A Study of Automated Web Site Evaluation Tools  

Microsoft Academic Search

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

Melody Y. Ivory

2002-01-01

239

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

2004-04-22

240

Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors  

PubMed Central

Background Lipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on Toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was conducted to determine the maximum tolerated dose, the recommended phase II dose and biological response associated with OM-174 administered as intravenous infusion. Methods Patients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 ?g/m2. Blood samples for pharmacokinetic analysis and cytokine dosages were collected. NK cells activity and Toll-like receptors 4 polymorphism analysis were also performed. Results Seventeen patients were included. The highest dose administered was 1000 ?g/m2 repeated in 15 injections. The most common toxicities were a chills, fever, nausea/vomiting, diarrhea, fatigue and headache. No patient experienced haematological side effects. As no dose limiting toxicity was observed, despite a grade 3 respiratory complication, the maximal tolerated dose and recommended dose were not established. Three patients exhibited disease stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174 was characterized by a low distribution volume and clearance. Analysis of TLR 4 polymorphysm showed that most (16/17) patients carried the wild type alleles. A progressive increase in NK cell number and activity was observed only in patients receiving 1000 ?g/m2 of OM-174. A peak of IL-8 and IL-10 concentrations were observed after each OM-174 injection. Peaks of TNF-alpha and IL-6 concentrations were detected after the first infusion and decreased progressively suggesting tolerance. Conclusion OM-174 therapy was well tolerated at biologically active concentrations. Whereas the recommended dose was not determined, further studies are planned in combination with chemotherapy as animal models suggest a strong synergistic antitumor effect. Trial registration NCT01800812 (ClinicalTrials.gov Identifier). PMID:23547558

2013-01-01

241

Cell-Cycle Analyses Using Thymidine Analogues in Fission Yeast  

PubMed Central

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

Anda, Silje; Boye, Erik; Grallert, Beata

2014-01-01

242

Somatostatin Analogues for Receptor Targeted Photodynamic Therapy  

PubMed Central

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

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

2014-01-01

243

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

2000-01-01

244

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

PubMed

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

2000-01-01

245

Inhibition of ATP Synthase by Chlorinated Adenosine Analogue  

PubMed Central

8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing ? and ? subunits. Crystal structures of both ? and ? subunits that bind to the substrate, ADP, are known in tight binding (?dp?dp) and loose binding (?tp?tp) states. Molecular docking demonstrated that 8-Cl-ADP/8-Cl-ATP occupied similar binding modes as ADP/ATP in the tight and loose binding sites of ATP synthase, respectively, suggesting that the chlorinated nucleotide metabolites may be functional substrates and inhibitors of the enzyme. The computational predictions were consistent with our whole cell biochemical results. Oligomycin, an established pharmacological inhibitor of ATP synthase, decreased both ATP and 8-Cl-ATP formation from exogenous substrates, however, did not affect pyrimidine nucleoside analogue triphosphate accumulation. Synthesis of ATP from ADP was inhibited in cells loaded with 8-Cl-ATP. These biochemical studies are in consent with the computational modeling; in the ?tp?tp state 8-Cl-ATP occupies similar binding as ANP, a non-hydrolyzable ATP mimic that is a known inhibitor. Similarly, in the substrate binding site (?dp?dp) 8-Cl-ATP occupies a similar position as ATP mimic ADP-BeF3 ?. Collectively, our current work suggests that 8-Cl-ADP may serve as a substrate and the 8-Cl-ATP may be an inhibitor of ATP synthase. PMID:19477165

Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

2009-01-01

246

Emerald Lake Watershed study: Introduction and site description  

SciTech Connect

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

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

1991-07-01

247

The Emerald Lake Watershed Study: Introduction and site description  

NASA Astrophysics Data System (ADS)

The Emerald Lake Watershed study was organized to investigate the effects of acidic deposition on high-elevation watersheds and surface waters of the Sierra Nevada, California. Some of the results of this comprehensive study of aquatic and terrestrial ecosystems at a small, headwater basin are presented in four papers in this series. The watershed study site is in Sequoia National Park, on the western slope of the Sierra Nevada. This glacial cirque is located in the upper Marble Fork of the Kaweah River. This 120-ha watershed ranges from Alta Peak (3416 m) down to Emerald Lake (2400 m). Most of the watershed surface area is exposed granite and granodiorite rocks, with limited coverage (about 20%) by thin, acidic soils. The hydrology of the basin is dominated by snowmelt runoff during March-June. Emerald Lake, a glacial tarn, is 2.72 ha in area, with a maximum depth of 10.5 m. Surface waters are poorly buffered and dominated by calcium and bicarbonate. Most of the yearly precipitation falls as dilute snow (pH 5.2-5.4), with acidic rain storms sampled during May-October.

Tonnessen, Kathy A.

1991-07-01

248

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

1964-01-01

249

Dynamic analogue initialization for ensemble forecasting  

NASA Astrophysics Data System (ADS)

This paper introduces a new approach for the initialization of ensemble numerical forecasting: Dynamic Analogue Initialization (DAI). DAI assumes that the best model state trajectories for the past provide the initial conditions for the best forecasts in the future. As such, DAI performs the ensemble forecast using the best analogues from a full size ensemble. As a pilot study, the Lorenz63 and Lorenz96 models were used to test DAI's effectiveness independently. Results showed that DAI can improve the forecast significantly. Especially in lower-dimensional systems, DAI can reduce the forecast RMSE by ˜50% compared to the Monte Carlo forecast (MC). This improvement is because DAI is able to recognize the direction of the analysis error through the embedding process and therefore selects those good trajectories with reduced initial error. Meanwhile, a potential improvement of DAI is also proposed, and that is to find the optimal range of embedding time based on the error's growing speed.

Li, Shan; Rong, Xingyao; Liu, Yun; Liu, Zhengyu; Fraedrich, Klaus

2013-09-01

250

Design and synthesis of celecoxib and rofecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: replacement of sulfonamide and methylsulfonyl pharmacophores by an azido bioisostere.  

PubMed

Celecoxib (13) and rofecoxib (17) analogues, in which the respective SO2NH2 and SO2Me hydrogen-bonding pharmacophores were replaced by a dipolar azido bioisosteric substituent, were investigated. Molecular modeling (docking) studies showed that the azido substituent of these two analogues (13, 17) was inserted deep into the secondary pocket of the human COX-2 binding site where it undergoes electrostatic interaction with Arg(513). The azido analogue of rofecoxib (17), the most potent and selective inhibitor of COX-2 (COX-1 IC(50) = 159.7 microM; COX-2 IC(50) = 0.196 microM; COX-2 selectivity index = 812), exhibited good oral antiinflammatory and analgesic activities. PMID:11520213

Habeeb, A G; Praveen Rao, P N; Knaus, E E

2001-08-30

251

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

PubMed

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

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

2015-02-01

252

New materials for analogue experiments: Preliminary tests of magnetorheological fluids  

NASA Astrophysics Data System (ADS)

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

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

2014-09-01

253

Observational Study of Contracts Processing at 29 CTSA Sites  

PubMed Central

We measured contracts Final Negotiation (FN) and Full Execution (FE) times using shared definitions in a prospective observational study of management of contracts for clinical trials at 29 CTSA institutions. Median FN and FE times were reached in 39 and 91 days, respectively; mean times for FN and FE were 55 and 103 days, respectively. Individual site medians ranged from 3 to 116 days for FN and 34 to 197 days for FE. The use of Master Agreements (MAs) and Previously Negotiated Terms (PNTs) was associated with significant reduction of FN times by a mean of 33 days (p<0) and 22 days (p<0.001), respectively. PNTs, but not MAs, were associated with significantly reduced FE time (22 days, p<.007). Gap analysis revealed a gap of 22 days between contracts negotiation and Institutional Review Board (IRB) review and intervals of 33 days (contracts) and 48 days (IRB review) during which the process steps were being conducted alone, suggesting a potential benefit with parallel processing. These baseline data support a plan to investigate root causes of prolonged study startup time by examining causes of variation and outliers. PMID:23919362

Kiriakis, James; Gaich, Nicholas; Johnston, S Claiborne; Kitterman, Darlene; Rosenblum, Daniel; Salberg, Libby; Rifkind, Adam

2013-01-01

254

Antimicrobial activity of resveratrol analogues.  

PubMed

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

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

2014-01-01

255

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

PubMed Central

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

2015-01-01

256

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.

2005-12-01

257

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.

2006-12-01

258

Report of the Fermilab Committee for Site Studies  

SciTech Connect

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

Steve Holmes, Vic Kuchler et. al.

2001-09-10

259

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.

2001-01-01

260

LH-RH analogues in the treatment of young women with early breast cancer: Long-term follow-up of a phase II study.  

PubMed

To prevent premature ovarian failure (POF), high-risk, premenopausal women with early breast cancer were given a luteinizing-hormone releasing hormone (LH-RH) analogue during adjuvant chemotherapy. After an adriamycin-based regimen, patients received radiation therapy concomitant with cyclophosphamide, methotrexate and 5-fluorouracil. An aromatase inhibitor was given to patients positive for the estrogen receptor (ER+). The median age was 43 years (range, 26-45). Among 200 consecutive patients, 46% had no axillary node, and 54% had a mean of 5.4 positive nodes (range, 1-25); 56% were ER+, 44% were estrogen receptor negative (ER-), 13% were triple negative, and 20 had tumors positive for the oncogene, c-erb-B2 (identified with fluorescent in situ hybridization). After a median follow-up of 105 months (range, 65-180), no patient under 40 years old exhibited POF, while 44% of patients over 40 years old exhibited POF. Eight pregnancies were recorded: 7 at term and 1 voluntary interruption. The 10-year disease-free survival and overall survival rates were 85 and 91%, respectively. These data showed that, in premenopausal patients with early breast cancer, the addition of an LH-RH analogue to adjuvant chemotherapy was well tolerated, prevented POF, and was associated with excellent disease-free survival and overall survival rates. PMID:25572674

Recchia, Francesco; Necozione, Stefano; Bratta, Massimo; Rosselli, Michele; Guerriero, Gabriele; Rea, Silvio

2015-03-01

261

Further studies on proctolin analogues modified in position 2 of the peptide chain and their influence on heart-beat frequency of insects.  

PubMed

Seven proctolin analogues (I-VII) modified in position 2 of the peptide chain by Phe (p-guanidino) (I), Phe (p-OEt) (II), Tyr (3'-NH2) (III), Tyr (3'-NO2) (IV), Afb (p-OH) (V) (Afb = 3-amino-4-phenyl-L-butyric acid), Afb (p-NH2) (VI), Afb (p-NO2) (VII), and the tetrapeptide Tyr (3'-NH2)-Leu-Pro-Thr (VIII) were synthesized by the classic liquid-phase method. The biological effects of the peptides were investigated in cardioexcitatory tests on two insect species, the cockroach Periplaneta americana L., and the yellow mealworm, Tenebrio molitor L. Within physiological concentrations (10(-9)-10(-7) M) peptides II, III, and IV stimulated the heart action of P. americana like proctolin itself. Under identical conditions, in the case of T. molitor, only peptide III showed cardiostimulatory properties, whereas other compounds (including II and IV) were inactive at concentrations up to 10(-7) M. Results reported here reflect, with reference to the analogues I-VII, selective recognition of receptors on myocardium of both insect species. The tetrapeptide VIII revealed a weak deacceleratory effect on P. americana and T. molitor heart action. PMID:2276873

Bartosz-Bechowski, H; Rosi?ski, G; Konopi?ska, D; Sujak, P; Sobótka, W

1990-11-01

262

Habitability & Astrobiology Research in Mars Terrestrial Analogues  

NASA Astrophysics Data System (ADS)

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

Foing, Bernard

2014-05-01

263

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

2012-04-01

264

Condensed matter analogues of cosmology  

NASA Astrophysics Data System (ADS)

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

Kibble, Tom; Srivastava, Ajit

2013-10-01

265

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

PubMed

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

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

2015-02-01

266

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

267

Surgical site infections in Italian Hospitals: a prospective multicenter study  

PubMed Central

Background Surgical site infections (SSI) remain a major clinical problem in terms of morbidity, mortality, and hospital costs. Nearly 60% of SSI diagnosis occur in the postdischarge period. However, literature provides little information on risk factors associated to in-hospital and postdischarge SSI occurrence. A national prospective multicenter study was conducted with the aim of assessing the incidence of both in-hospital and postdisharge SSI, and the associated risk factors. Methods In 2002, a one-month, prospective national multicenter surveillance study was conducted in General and Gynecological units of 48 Italian hospitals. Case ascertainment of SSI was carried out using standardized surveillance methodology. To assess potential risk factors for SSI we used a conditional logistic regression model. We also reported the odds ratios of in-hospital and postdischarge SSI. Results SSI occurred in 241 (5.2%) of 4,665 patients, of which 148 (61.4%) during in-hospital, and 93 (38.6%) during postdischarge period. Of 93 postdischarge SSI, sixty-two (66.7%) and 31 (33.3%) were detected through telephone interview and questionnaire survey, respectively. Higher SSI incidence rates were observed in colon surgery (18.9%), gastric surgery (13.6%), and appendectomy (8.6%). If considering risk factors for SSI, at multivariate analysis we found that emergency interventions, NNIS risk score, pre-operative hospital stay, and use of drains were significantly associated with SSI occurrence. Moreover, risk factors for total SSI were also associated to in-hospital SSI. Additionally, only NNIS, pre-operative hospital stay, use of drains, and antibiotic prophylaxis were associated with postdischarge SSI. Conclusion Our study provided information on risk factors for SSI in a large population in general surgery setting in Italy. Standardized postdischarge surveillance detected 38.6% of all SSI. We also compared risk factors for in-hospital and postdischarge SSI, thus providing additional information to that of the current available literature. Finally, a large amount of postdischarge SSI were detected through telephone interview. The evaluation of the cost-effectiveness of the telephone interview as a postdischarge surveillance method could be an issue for further research. PMID:18328101

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

2008-01-01

268

A study of active sites for isosynthesis over zirconium dioxide  

SciTech Connect

Sulfur trioxide, CO and CO/H{sub 2} were used in adsorption, titration and steady state experiments over undoped zirconias, yttria stabilized zirconias, and calcia stabilized zirconias to determine that surface oxygen anion vacancies are the active site for isosynthesis over zirconia. The sulfur trioxide was adsorbed as a (ZrO){sub 3}S=O sulfate and the carbon monoxide was adsorbed as a formate. CO/H{sub 2} preformed methoxide on the catalyst surface which was then titrated off with water to form methanol. CO/H{sub 2} were also reacted over zirconia catalysts under steady state conditions to form methanol and methane. A correlation between the amount of SO{sub 3} adsorbed and the vacancy mobility in yttria doped zirconia formed the basis for proposing that SO{sub 3} titrates the anion vacancy sites on the surface of zirconia. Correlations were also found between the amount of methoxide titrated, the amount of CO adsorbed, the steady state catalytic reaction rate, and the amount of SO{sub 3} adsorbed over zirconia in general. Another correlation was found between the amount of methoxide titrated over calcia stabilized zirconia and the vacancy mobility in that same catalyst. These correlations support the hypothesis that the active site for CO hydrogenation and isosynthesis over zirconia is an oxygen anion vacancy. Results over undoped zirconias were used to explore the effects of calcination treatment, cooling time and pretreatment on the concentrations of active sites per unit area. Increased severity of calcination led to an increase in active site concentration but a decrease in surface area. Slow cooling (hours) versus quenching the catalyst in air led to a decrease on both active site concentration and surface area. Oxygen/hydrogen pretreatment at 600{degree}C was found to increase the concentration of active sites relative to oxygen pretreatment at 600C alone.

Silver, R.G.

1989-01-01

269

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

SciTech Connect

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

Not Available

1987-06-01

270

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.

1981-01-01

271

Experimental and theoretical vibrational study of isatin, its 5-(NO 2, F, Cl, Br, I, CH 3) analogues and the isatinato anion  

NASA Astrophysics Data System (ADS)

Effects of 5- R substitution ( R=NO 2, F, Cl, Br, I, CH 3) and N-deprotonation on the 4000-400 cm -1 region of the low temperature FT IR spectrum and the molecular structure of solid isatin are investigated. Harmonic IR spectra and molecular geometries of the 5- R isatins (except for Br and I analogues) are calculated at the HF/6-31G( d, p) level and compared with the experimental solid-state data. In general, substitution has small effect on the molecular structure and the IR spectrum of isatin. The ?(CO) triplet in the IR spectra of isatin and its 5-substituted analogues is resulted by vibrational splitting of the out-of-phase CO stretching, ?op[(CO) 2]. While the frequency of the ?op[(CO) 2] mode is relatively less affected by 5-substitution and mainly depends on the substituent mass, the frequency of the in-phase stretching, ?ip[(CO) 2], is strongly sensitive to both mass and electronic properties of the substituent. Substitution at C5 has relatively greater influence on the electron density and the force constant of the amide than on the ketone carbonyl group. Strong electron-donors shorten and stabilize the unusually long ?-dicarbonyl CC bond, while electron-accepting groups tend to stretch this bond further. N-Deprotonation brings to elongation of the five membered-ring along the N?C CO(ketone) vector and expansion of the bonds within the ?-dicarbonyl part. Theoretical ?(CO) frequency of isatin is lowered for about 180 cm -1 upon conversion into isatinato ion. Harmonic vibrational analysis reveals that only the highest-frequency ?(CO) mode of the isolated isatinato anion can be considered good group vibration for empirical assignments in spectra of solid isatinates. Owing to the solid-state influences on the ?[(CO) 2] modes, no reliable spectra-structure correlations could be established from the present experimental spectroscopic data.

Naumov, Pan?e; Anastasova, Frosa

2001-03-01

272

A Preliminary Case Study for Rectenna Sites in Indonesia  

NASA Astrophysics Data System (ADS)

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

Purwanto, Y.; Collins, P.

2004-12-01

273

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

ERIC Educational Resources Information Center

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

Williams, Sarah C.

2010-01-01

274

RESEARCH STUDIES AT THE GILT EDGE MINE SUPERFUND SITE  

EPA Science Inventory

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

275

CASE STUDY: SITE CONCEPTUAL MODEL FOR ENHANCED MNA OF ARSENIC  

EPA Science Inventory

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

276

Current Research at the Endeavour Ridge 2000 Integrated Studies Site  

NASA Astrophysics Data System (ADS)

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

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

2004-12-01

277

THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL  

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

G. Saulnier and W. Statham

2006-04-16

278

64Cu-labeled somatostatin analogues conjugated with cross-bridged phosphonate-based chelators via strain-promoted click chemistry for PET imaging: in silico through in vivo studies.  

PubMed

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

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

2014-07-24

279

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

2009-01-01

280

Residents' reappraisal of the Halton Regional Landfill site: A longitudinal study of psychosocial impacts  

Microsoft Academic Search

This thesis examines psychosocial effects in a population living near the Halton Regional Landfill site in Milton, Ontario. The data described and analyzed in this research were collected between 1990 and 1995 and capture key events in the landfill site's history--site approval, construction and operation. This longitudinal study, which examines indicators of stress, reappraisal and coping at three different points

Christine Lynne Hampson

1997-01-01

281

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.

1976-01-01

282

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.

1993-05-01

283

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.

1993-01-01

284

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

2009-01-01

285

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.

2010-01-01

286

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.

2013-01-01

287

Probing Human Red Cone Opsin Activity with Retinal Analogues?  

PubMed Central

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 agonist nor 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.

2011-01-01

288

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.

1996-05-09

289

Residual herbicide study on selected Hanford Site roadsides  

SciTech Connect

Westinghouse Hanford Company routinely treats roadsides with herbicides to control undesirable plant growth. An experiment was conducted to test perennial grass germination in soils adjacent to roadways of the Hanford Site. The primary variable was the distance from the roadside. A simple germination test was executed in a controlled-environment chamber to determine the residual effects of these applications. As expected, the greatest herbicide activity was found directly adjacent to the roadway, approximately 0 to 20 ft (0 to 6.3 m) from the roadway.

Smith, J.L.; Kemp, C.J.; Sackschewsky, M.R.

1993-08-01

290

Web Site Usability: A Case Study of Student Perceptions of Educational Web Sites  

ERIC Educational Resources Information Center

The purpose of this research study was to understand the construct of usability from the perspective of 74 students enrolled in six online courses offered by one online and distance learning program at a large, public university in the Midwest. Six courses, designed and developed by two different groups, professional and nonprofessional…

Ballard, Joyce Kimberly

2010-01-01

291

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

2014-05-01

292

Synthesis of novel gamma-aminobutyric acid (GABA) uptake inhibitors. 5.(1) Preparation and structure-activity studies of tricyclic analogues of known GABA uptake inhibitors.  

PubMed

On the basis of the SAR of a series of known gamma-aminobutyric acid (GABA) uptake inhibitors, including 4 (SKF 89976), new tricyclic analogues have been prepared. These novel compounds are derivatives of nipecotic acid, guvacine, and homo-beta-proline, substituted at the nitrogen of these amino acids by various lipophilic moieties such as (10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)alkoxyalkyl or (10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)alkoxyalkyl. The in vitro values for inhibition of [(3)H]-GABA uptake in rat synaptosomes was determined for each compound in this new series, and it was found that several of the novel compounds showed a high potency comparable with that of the reference compounds 4, 5 (tiagabine), and 6 (CI-966). Several of the novel compounds were also evaluated for their ability in vivo to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). One compound, (R)-1-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid (23), was selected for further biological investigations and showed a protective index comparable to or slightly better than that of the recently launched anticonvulsant product 5 ((R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid). PMID:11405652

Andersen, K E; Sørensen, J L; Lau, J; Lundt, B F; Petersen, H; Huusfeldt, P O; Suzdak, P D; Swedberg, M D

2001-06-21

293

Femtosecond transient absorption spectroscopic study of a carbonyl-containing carotenoid analogue, 2-(all-trans-retinylidene)-indan-1,3-dione.  

PubMed

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

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

2011-03-24

294

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

PubMed Central

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

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

2011-01-01

295

Analogue models for FRW cosmologies  

E-print Network

It is by now well known that various condensed matter systems may be used to mimic many of the kinematic aspects of general relativity, and in particular of curved-spacetime quantum field theory. In this essay we will take a look at what would be needed to mimic a cosmological spacetime -- to be precise a spatially flat FRW cosmology -- in one of these analogue models. In order to do this one needs to build and control suitable time dependent systems. We discuss here two quite different ways to achieve this goal. One might rely on an explosion, physically mimicking the big bang by an outflow of whatever medium is being used to carry the excitations of the analogue model, but this idea appears to encounter dynamical problems in practice. More subtly, one can avoid the need for any actual physical motion (and avoid the dynamical problems) by instead adjusting the propagation speed of the excitations of the analogue model. We shall focus on this more promising route and discuss its practicality.

Carlos Barcelo; Stefano Liberati; Matt Visser

2003-05-16

296

Substrate analogues for isoprenoid enzymes  

SciTech Connect

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

Stremler, K.E.

1987-01-01

297

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)

None

1980-12-01

298

Prospective Observational Study of Single-Site Multiport Per-umbilical Laparoscopic Endosurgery versus Conventional Multiport Laparoscopic Cholecystectomy: Critical Appraisal of a Unique Umbilical Approach  

PubMed Central

Purpose. This prospective observational study compares an innovative approach of Single-Site Multi-Port Per-umbilical Laparoscopic Endo-surgery (SSMPPLE) cholecystectomy with the gold standard—Conventional Multi-port Laparoscopic Cholecystectomy (CMLC)—to assess the feasibility and efficacy of the former. Methods. In all, 646 patients were studied. SSMPPLE cholecystectomy utilized three ports inserted through three independent mini-incisions at the umbilicus. Only the day-to-day rigid laparoscopic instruments were used in all cases. The SSMPPLE cholecystectomy group had 320 patients and the CMLC group had 326 patients. The outcomes were statistically compared. Results. SSMPPLE cholecystectomy had average operative time of 43.8?min and blood loss of 9.4?mL. Their duration of hospitalization was 1.3 days (range, 1–5). Six patients (1.9%) of this group were converted to CMLC. Eleven patients had controlled gallbladder perforations at dissection. The Visual Analogue Scores for pain on postoperative days 0 and 7, the operative time, and the scar grades were significantly better for SSMPPLE than CMLC. However, umbilical sepsis and seroma outcomes were similar. We had no bile-duct injuries or port-site hernias in this study. Conclusion. SSMPPLE cholecystectomy approach complies with the principles of laparoscopic triangulation; it seems feasible and safe method of minimally invasive cholecystectomy. Overall, it has a potential to emerge as an economically viable alternative to single-port surgery. PMID:24876955

Jategaonkar, Priyadarshan Anand; Yadav, Sudeep Pradeep

2014-01-01

299

Crystal structure of Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase complexed with an analogue of 1,3-bisphospho-d-glyceric acid.  

PubMed

We report here the first crystal structure of a stable isosteric analogue of 1,3-bisphospho-d-glyceric acid (1,3-BPGA) bound to the catalytic domain of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) in which the two phosphoryl moieties interact with Arg249. This complex possibly illustrates a step of the catalytic process by which Arg249 may induce compression of the product formed, allowing its expulsion from the active site. Structural modifications were introduced into this isosteric analogue and the respective inhibitory effects of the resulting diphosphorylated compounds on T. cruzi and Trypanosoma brucei gGAPDHs were investigated by enzymatic inhibition studies, fluorescence spectroscopy, site-directed mutagenesis, and molecular modelling. Despite the high homology between the two trypanomastid gGAPDHs (> 95%), we have identified specific interactions that could be used to design selective irreversible inhibitors against T. cruzi gGAPDH. PMID:14622286

Ladame, Sylvain; Castilho, Marcelo S; Silva, Carlos H T P; Denier, Colette; Hannaert, Véronique; Périé, Jacques; Oliva, Glaucius; Willson, Michèle

2003-11-01

300

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.

1975-01-01

301

Two-metal ion mechanism of bovine lens leucine aminopeptidase: active site solvent structure and binding mode of L-leucinal, a gem-diolate transition state analogue, by X-ray crystallography.  

PubMed

The three-dimensional structures of bovine lens leucine aminopeptidase (blLAP) complexed with L-leucinal and of the unliganded enzyme have been determined at crystallographic resolutions of 1.9 and 1.6 A, respectively. Leucinal binds as a hydrated gem-diol to the active site of b1LAP), resembling the presumed gem-diolated intermediate in the catalytic pathway. One hydroxyl group bridges the two active site metal ions, and the other OH group is coordinated to Zn1. The high-resolution structure of the unliganded enzyme reveals one metal-bound water ligand, which is bridging both zinc ions. Together, these structures support a mechanism in which the bridging water ligand is the attacking hydroxide ion nucleophile. The gem-diolate intermediate is probably stabilized by four coordinating bonds to the dizinc center and by interaction with Lys-262 and Arg-336. In the mechanism, Lys-262 polarizes the peptide carbonyl group, which is also coordinated to Zn1. The Arg-336 side chain interacts with the substrate and the gem-diolate intermediate via water molecules. Near Arg-336 in the b1LAP-leucinal structure, an unusually short hydrogen bond is found between two active site water molecules. PMID:7578088

Sträter, N; Lipscomb, W N

1995-11-14

302

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

PubMed Central

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

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

1998-01-01

303

The Library Web: Case Studies in Web Site Creation and Implementation.  

ERIC Educational Resources Information Center

This book presents 19 case studies in library web site creation and implementation. The book begins with an introduction--"Introduction: Step into My Parlor" (Julie M. Still)--and is divided into three sections. The first section, Academic Library Web Sites, contains six case studies: "U-SEARCH: The University of Saskatchewan Library Web" (David…

Still, Julie M., Ed.

304

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.

1996-03-01

305

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

NASA Astrophysics Data System (ADS)

In an attempt to reduce CO2 emissions, CO2 capture and storage in depleted oil and gas reservoirs is seen as one of the most important mitigation strategies. However, in order to achieve safe storage on geological timescales, it is key to maintain integrity of the caprock and any faults penetrating the seal. One of the largest uncertainties lies in the prediction of the effects of fluid-rock interaction on the mechanical integrity and sealing capacity of the reservoir-seal system in the very long term, i.e. on timescales of the order of 103 or 104 years. As chemical interactions in the rock/CO2/brine system are slow, their long-term effects on rock composition, microstructure, mechanical properties and transport properties cannot be properly reproduced in laboratory experiments. One way of addressing this issue is to conduct experiments on reservoir, caprock and fault rock samples taken from natural CO2 reservoir-seal systems, which can serve as natural analogues for CO2 storage fields. The transport and mechanical properties of these rock samples, which have reacted with CO2 over geological timescales, can then be compared with data obtained for laterally equivalent materials that are unaffected by CO2. The observed changes in rock properties can subsequently be used as input for numerical models aimed at assessing the long-term effects of CO2 on reservoir compaction, caprock damage, fault reactivation and fault permeability. We assessed the mechanical behaviour and transport properties of fault rocks. To this end, we performed triaxial direct shear experiments at room temperature under nominally dry conditions, at normal stresses up to 90 MPa and shear velocities of 0.22 -10.9 ?m/s. Simulated fault rocks were prepared by crushing material obtained from surface outcrops of the Entrada Sandstone, one of the CO2-bearing formations from an analogue field under the Colorado Plateau, Utah, USA. Three types of starting material were obtained: 1) red-coloured samples consisting mainly of quartz and feldspar, some minor clay minerals and hematite/goethite grain coatings, 2) yellow-coloured, (so-called) bleached samples additionally containing various amounts of kaolinite, calcite and dolomite, and 3) heavily cemented samples from the surface outcrop of the fault core of the Little Grand Wash Fault, containing a high percentage of carbonates (> 40 wt%). Previous work demonstrates that the bleached samples and the material from the fault were altered as a result of interaction with CO2-rich fluids. Over the experimental range investigated, we measured friction coefficients of 0.55-0.85 for unbleached material and 0.55-0.80 for bleached material, while the fault core material showed higher friction coefficients (0.60-0.95), all showing a minor decrease with decreasing shear velocity and normal stress. Almost all samples showed velocity-strengthening slip behaviour. Overall, the frictional behaviour of Entrada Sandstone does not seem to be strongly influenced by CO2/brine/rock interactions.

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

2012-04-01

306

Design of novel CSA analogues as potential safeners and fungicides.  

PubMed

Study of safeners has been seldom reported in literature. In this work, a series of novel acylsulfamoylbenzamide analogues was designed and synthesized with newly developed safener cyprosulfamide (CSA) as the leading compound. The activity assay against the herbicide thiencarbazone-methyl (TCM) on maize revealed that fifteen compounds showed better protective effect than CSA on the fresh weight of aerial parts, twelve compounds exhibited better activity on the dry weight of aerial parts. Remarkably, two compounds (6Ih, 7II) had protective effect on the four aspects of TCM treated maize. Further antifungal assay showed their excellent activity against Physollospora piricola. The structure-activity relationships of CSA analogues as safeners and fungicides were discussed and it might be valuable for further molecular modification of new CSA analogues. PMID:25582601

Zheng, Yang; Liu, Bin; Gou, Zhaopin; Li, Yao; Zhang, Xiao; Wang, Yanqing; Yu, Shujing; Li, Yonghong; Sun, Dequn

2015-02-15

307

Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors.  

PubMed

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

2014-11-01

308

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

PubMed

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

2014-10-01

309

3D-QSAR and 3D-QSSR studies of thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as CDK4 inhibitors by CoMFA analysis  

PubMed Central

Aim: To investigate the structural basis underlying potency and selectivity of a series of novel analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones as cyclin-dependent kinase 4 (CDK4) inhibitors and to use this information for drug design strategies. Methods: Three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models using comparative molecular field analysis (CoMFA) were conducted on a training set of 48 compounds. Partial least squares (PLS) analysis was employed. External validation was performed with a test set of 9 compounds. Results: The obtained 3D-QSAR model (q2=0.724, r2=0.965, r2pred=0.945) and 3D-QSSR model (q2=0.742, r2=0.923, r2pred=0.863) were robust and predictive. Contour maps with good compatibility to active binding sites provided insight into the potentially important structural features required to enhance activity and selectivity. The contour maps indicated that bulky groups at R1 position could potentially enhance CDK4 inhibitory activity, whereas bulky groups at R3 position have the opposite effect. Appropriate incorporation of bulky electropositive groups at R4 position is favorable and could improve both potency and selectivity to CDK4. Conclusion: These two models provide useful information to guide drug design strategies aimed at obtaining potent and selective CDK4 inhibitors. PMID:24122012

Cai, Bao-qin; Jin, Hai-xiao; Yan, Xiao-jun; Zhu, Peng; Hu, Gui-xiang

2014-01-01

310

12-Amino-andrographolide analogues: synthesis and cytotoxic activity.  

PubMed

Andrographolide, a diterpenoid lactone of the plant Andrographis paniculata, has been shown to be cytotoxic against various cancer cells in vitro. In the present study, a series of ?-amino-?-butyrolactone analogues has been synthesized from naturally occurring andrographolide via one pot tandem aza-conjugate addition-elimination reaction. By using economic procedure without any base or catalyst at room temperature, the products obtained were in fair to excellent yields with high stereoselectivity. The cytotoxicity of all new amino analogues were evaluated against six cancer cell lines and revealed their potential for being developed as promising anti-cancer agents. PMID:23709127

Kasemsuk, Sakkasem; Sirion, Uthaiwan; Suksen, Kanoknetr; Piyachaturawat, Pawinee; Suksamrarn, Apichart; Saeeng, Rungnapha

2013-12-01

311

Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors  

PubMed Central

A series of novel bis-tetrahydropyran 1,4-triazole analogues based on the acetogenin framework display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness. A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure activity relationship studies. PMID:25145275

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

2015-01-01

312

Charged analogue of Finch-Skea stars  

E-print Network

We present solutions to the Einstein-Maxwell system of equations in spherically symmetric gravitational fields for static interior spacetimes with a specified form of the electric field intensity. The condition of pressure isotropy yields three category of solutions. The first category is expressible in terms of elementary functions and does not have an uncharged limit. The second category is given in terms of Bessel functions of half-integer order. These charged solutions satisfy a barotropic equation of state and contain Finch-Skea uncharged stars. The third category is obtained in terms of modified Bessel functions of half-integer order and does not have an uncharged limit. The physical features of the charged analogue of the Finch-Skea stars are studied in detail. In particular the condition of causality is satisfied and the speed of sound does not exceed the speed of light. The physical analysis indicates that this analogue is a realistic model for static charged relativistic perfect fluid spheres.

S. Hansraj; S. D. Maharaj

2006-05-11

313

Andrographolide and analogues in cancer prevention.  

PubMed

Andrographis paniculata is a medicinal plant traditionally used for treatment of cough and cold, fever, laryngitis, and several infectious diseases. Extracts of A. paniculata have shown versatile potency against various diseases including cancer. The active biomolecules of A. paniculata mainly are lactone and diterpene. Andrographolide and analogues have been widely used for prevention of different diseases. Andrographolides have shown potent antiinflammatory and anticancer activities. It showed potentials as chemopreventive agents by suppressing growth of cancer cells by inhibiting NF-kappaB, PI3K/AKT and other kinase pathways and by inducing apoptosis. Andrographolide induced both intrinsic and extrinsic apoptosis pathway in different cancer cells via expression of different anti-apoptotic protein like Bax, p53, and activated caspases. Andrographolide was successfully used as an antineoplastic drug in cancer chemotherapy. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide and analogues need to be subjected to further clinical and biomedical studies in cancer chemoprevention. Andrographolide could be potent anticancer agent when used in combination with other chemotherapeutic agents. PMID:25553378

Mishra, Siddhartha Kumar; Tripathi, Swati; Shukla, Archana; Oh, Seung Hyun; Kim, Hwan Mook

2015-01-01

314

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.

1979-01-01

315

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.

2011-12-01

316

Chemical modification and inactivation of phospholipases A2 by a manoalide analogue.  

PubMed Central

Chemical modification and inactivation of bovine pancreatic, porcine pancreatic, Naja naja atra and Pseudechis australis phospholipases A2 (PLA2s), belonging to Group I, and of Trimeresurus flavoviridis, Vipera russelli russelli and Agkistrodon halys blomhoffii PLA2s, belonging to Group II, were investigated by the use of a manoalide (MLD)-analogue, 1-(2,5-dihydro-hydroxy-5-oxo-3-furanyl)-8,12-dimethyl-4-formyl-3,7, 11-tridecatrienol. At appropriate time intervals, residual PLA2 activities towards monodispersed, anionic mixed micellar and non-ionic mixed micellar substrates were measured. We tested the protective effect of micellar n-dodecylphosphocholine (n-C12PC) on enzyme inactivation. Inactivation of pancreatic PLA2s (Group I) was only observed towards anionic mixed micellar substrates. This inactivation was completely prevented by the presence of micellar n-C12PC. From a fragmentation study of modified bovine pancreatic PLA2 using lysyl endopeptidase, we speculated that Lys-56 of this enzyme was modified by MLD-analogue and that this modification was responsible for enzyme inactivation. Inactivation of non-pancreatic PLA2s was observed towards all types of substrate, except that no significant inactivation of N. naja atra PLA2 (Group I) towards monodispersed substrate was noted. Micellar n-C12PC protected N. naja atra PLA2 (Group I) completely from inactivation by MLD-analogue, but had lesser protective effects on P. australis PLA2 (Group I), T. flavoviridis and V. russelli russelli PLA2s (Group II). However, no significant protection of A. halys blomhoffii PLA2s (Group II) activity was observed. These results indicate that the inactivation of pancreatic and N. naja atra PLA2s originates from the modification of Lys residues at the interfacial recognition site, and that inactivation of P. australis, T. flavoviridis and V. russelli PLA2s arises from the modification of Lys residues at the catalytic site, interfacial recognition site and regions outside both sites. The inactivation of A. halys blomhoffii PLA2 was assumed to be due to the modification of Lys residues outside the two sites described above. Images Figure 7 PMID:7755577

Fujii, S; Tahara, Y; Toyomoto, M; Hada, S; Nishimura, H; Inoue, S; Ikeda, K; Inagaki, Y; Katsumura, S; Samejima, Y

1995-01-01

317

Nitrogen Analogues of Thiele's Hydrocarbon.  

PubMed

A series of bis[N,N-di-(4-methoxylphenyl)amino]arene dications 1(2+) -3(2+) have been synthesized and characterized. Their electronic structures were investigated by various experiments assisted by theoretical calculations. It was found that they are singlets in the ground state and that their diradical character is dependent on the bridging moiety. 3(2+) has a smaller singlet-triplet energy gap and its excited triplet state is thermally readily accessible. The work provides a nitrogen analogue of Thiele's hydrocarbon with considerable diradical character. PMID:25504531

Su, Yuanting; Wang, Xingyong; Li, Yuantao; Song, You; Sui, Yunxia; Wang, Xinping

2015-01-26

318

Exploring NMR methods as a tool to select suitable fluorescent nucleotide analogues.  

PubMed

Fluorescent analogues provide important tools for biochemical/biophysical research. However, the analogues contain chemical modifications much larger than those known to affect ligand-binding, such as the inversion of a carbon centre or substitution of an atom. We lack experimental tools and protocols to select the most appropriate fluorescent analogue. Herein, we use several NMR spectroscopy methods, including Saturation Transfer Difference (STD), STD competition and transferred nuclear Overhauser effect spectroscopy (Tr-NOESY), as tools to select appropriate fluorescent probes. Annexin A6 (AnxA6) is a ubiquitous protein that forms in vitro GTP-induced ion channels. We used this protein as a model and screened guanosine triphosphate (GTP) and four fluorescent analogues against AnxA6. STD reported that the GTP moiety of all ligands made similar contacts with the protein, despite additional interactions between the fluorescent tags and AnxA6. Competition STD experiments verified that the analogues and GTP bind to the same site. Tr-NOESY indicated that the bound conformation of the base relative to ribose is altered for some analogues compared to GTP. MANT-GTP or the BODIPY thioester of guanosine 5'-O-(3-thiotriphosphate) are the most suitable fluorescent analogues for AnxA6, according to NMR. These results reveal NMR as a useful technique to select and design proper fluorescent tags for biochemical/biophysical assays. PMID:23842795

Groves, Patrick; Strzelecka-Kiliszek, Agnieszka; Sekrecka-Belniak, Anna; Canales, Angeles; Jiménez-Barbero, Jesús; Bandorowicz-Pikula, Joanna; Pikula, S?awomir; Cañada, F Javier

2013-08-28

319

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.

320

The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor  

PubMed Central

In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as ‘designer drugs’ and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)-2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects. PMID:23527166

Roth, Bryan L.; Gibbons, Simon; Arunotayanun, Warunya; Huang, Xi-Ping; Setola, Vincent; Treble, Ric; Iversen, Les

2013-01-01

321

The Analogue-I and the Analogue-Me: The Avatars of the Self  

Microsoft Academic Search

The analogue-I and analogue-me refer to mental self-relevant images that take a first-person vs. third-person perspective, respectively. Mental self-analogues are essential for goal setting, planning, and rehearsal of behavioral strategies, but they often fuel emotional and interpersonal problems when people react to their analogue selves as if they were real. This article examines the beneficial and detrimental consequences of the

Mark R. Leary; Marie-Joelle Estrada; Ashley Batts Allen

2009-01-01

322

ACCEPTED MANUSCRIPT Gelatine as a crustal analogue: Determining  

E-print Network

58 59 60 61 62 63 64 65 Gelatine as a crustal analogue: Determining elastic properties for modelling.1016/j.tecto.2012.09.032 #12;ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT Abstract Gelatine has often been's brittle and elastic crust. Despite this, there are few studies of the elastic properties of gelatine

Paris-Sud XI, Université de

323

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

2011-01-01

324

Mode of lithospheric extension: Conceptual models from analogue modeling  

Microsoft Academic Search

Comparison of analogue experiments at crustal and lithospheric scale provides essential information concerning the mode of deformation during lithospheric extension. This study shows that during extension, lithospheric deformation is controlled by the development of shear zones in the ductile parts (i.e., the lower crust and the ductile mantle lithosphere). At lithospheric scale, the global deformation is initiated by the rupture

Laurent Michon; Olivier Merle

2003-01-01

325

Mode of lithospheric extension: Conceptual models from analogue modeling  

Microsoft Academic Search

Comparison of analogue experiments at crustal and lithospheric scale provides essential information concerning the mode of deformation during lithospheric extension. This study shows that during extension, lithospheric deformation is controlled by the development of shear zones in the ductile parts. At lithospheric scale, the global deformation is initiated by the rupture of the brittle mantle lithosphere. This failure generates the

Laurent Michon; Olivier Merle

2003-01-01

326

Quantum analogues of Schubert varieties in the grassmannian.  

E-print Network

Quantum analogues of Schubert varieties in the grassmannian. T.H. Lenagan and L. Rigal Abstract We study quantum Schubert varieties from the point of view of regularity conditions. More precisely, we which of them are AS-Gorenstein. One key fact that enables us to prove these results is that quantum

Lenagan, Tom

327

Mechanistic and active-site studies on D(--)-mandelate dehydrogenase from Rhodotorula graminis.  

PubMed Central

D(--)-Mandelate dehydrogenase, the first enzyme of the mandelate pathway in the yeast Rhodotorula graminis, catalyses the NAD(+)-dependent oxidation of D(--)-mandelate to phenylglyoxylate. D(--)-2-(Bromoethanoyloxy)-2-phenylethanoic acid ['D(--)-bromoacetylmandelic acid'], an analogue of the natural substrate, was synthesized as a probe for reactive and accessible nucleophilic groups within the active site of the enzyme. D(--)-Mandelate dehydrogenase was inactivated by D(--)-bromoacetylmandelate in a psuedo-first-order process. D(--)-Mandelate protected against inactivation, suggesting that the residue that reacts with the inhibitor is located at or near the active site. Complete inactivation of the enzyme resulted in the incorporation of approx. 1 mol of label/mol of enzyme subunit. D(--)-Mandelate dehydrogenase that had been inactivated with 14C-labelled D(--)-bromoacetylmandelate was digested with trypsin; there was substantial incorporation of 14C into two tryptic-digest peptides, and this was lowered in the presence of substrate. One of the tryptic peptides had the sequence Val-Xaa-Leu-Glu-Ile-Gly-Lys, with the residue at the second position being the site of radiolabel incorporation. The complete sequence of the second peptide was not determined, but it was probably an N-terminally extended version of the first peptide. High-voltage electrophoresis of the products of hydrolysis of modified protein showed that the major peak of radioactivity co-migrated with N tau-carboxymethylhistidine, indicating that a histidine residue at the active site of the enzyme is the most likely nucleophile with which D(--)-bromoacetylmandelate reacts. D(--)-Mandelate dehydrogenase was incubated with phenylglyoxylate and either (4S)-[4-3H]NADH or (4R)-[4-3H]NADH and then the resulting D(--)-mandelate and NAD+ were isolated. The enzyme transferred the pro-R-hydrogen atom from NADH during the reduction of phenylglyoxylate. The results are discussed with particular reference to the possibility that this enzyme evolved by the recruitment of a 2-hydroxy acid dehydrogenase from another metabolic pathway. PMID:1731758

Baker, D P; Kleanthous, C; Keen, J N; Weinhold, E; Fewson, C A

1992-01-01

328

Why We Are Not Google: Lessons from a Library Web Site Usability Study  

ERIC Educational Resources Information Center

In the Fall of 2009, the Moraine Valley Community College Library, using guidelines developed by Jakob Nielsen, conducted a usability study to determine how students were using the library Web site and to inform the redesign of the Web site. The authors found that Moraine Valley's current gateway design was a more effective access point to library…

Swanson, Troy A.; Green, Jeremy

2011-01-01

329

Phytoremediation of an Arsenic-Contaminated Site Using Pteris vittata L.: A Two-Year Study  

Microsoft Academic Search

A field study was conducted to determine the efficiency of Chinese brake fern (Pteris vittata L.), an arsenic hyperaccumulator, on removal of arsenic from soil at an arsenic- contaminated site. Chinese brake ferns were planted on a site previously used to treat wood with chromated copper arsenate (CCA). Arsenic concentrations in surface and profile soil samples were determined for 2000,

G. M. Kertulis-Tartar; L. Q. Ma; C. Tu; T. Chirenje

2006-01-01

330

The Costs of Pursuing Accreditation for Methadone Treatment Sites: Results from a National Study  

ERIC Educational Resources Information Center

The use of accreditation has been widespread among medical care providers, but accreditation is relatively new to the drug abuse treatment field. This study presents estimates of the costs of pursuing accreditation for methadone treatment sites. Data are from 102 methadone treatment sites that underwent accreditation as part of the Center for…

Zarkin, Gary A.; Dunlap, Laura J.; Homsi, Ghada

2006-01-01

331

OHIO RIVER VALLEY STUDY. SITES, METHODS, DATA SUMMARY FOR 1980. VOLUME 2. APPENDICES  

EPA Science Inventory

The Ohio River Valley Study was initiated to gather air quality data at sites representative of regional conditions in an area where current coal usage and projected increases are exceptionally large. This report describes procedures for site location and for station preparation,...

332

SOLVENT EXTRACTION AND SOIL WASHING TREATMENT OF CONTAMINATED SOILS FROM WOOD PRESERVING SITES: BENCH SCALE STUDIES  

EPA Science Inventory

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

333

Site specific mutagenesis study of the protein folding process of luciferase  

E-print Network

SITE SPECIFIC MUTAGENESIS STUDY OF THE PROTEIN FOLDING PROCESS OF LUCIFERASE A Thesis KE WEI Submitted to the Office of Graduate Studies of Texas A8 M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE... MAY 1990 Major Subject: Genetics SITE SPECIFIC MUTAGENESIS STUDY OF THE PROTEIN FOLDING PROCESS OF LUCIFERASE A Thesis by KE WEI Approved as to style and content by: T. O. aldwin ( Chair of Committee ) C. N. Pace ( Member ) M. D. Manson...

Wei, Ke

2012-06-07

334

Current Research at the Endeavour Ridge 2000 Integrated Studies Site  

Microsoft Academic Search

Integrated geophysical, geological, chemical, and biological studies are being conducted on the Endeavour segment with primary support from NSF, the W.M. Keck Foundation, and NSERC (Canada). The research includes a seismic network, physical and chemical sensors, high-precision mapping and time-series sampling. Several research expeditions have taken place at the Endeavour ISS in the past year. In June 2003, an NSF-sponsored

D. A. Butterfield; D. S. Kelley

2004-01-01

335

Synthesis and evaluation of heterocyclic analogues of bromoxynil.  

PubMed

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

2014-01-15

336

Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases*  

PubMed Central

The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nm. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5?-phosphate bound to OPRTs with Kd values near 40 nm. Analogues designed with a C5-pyrimidine carbon–carbon bond to ribocation mimics gave Kd values in the range of 80–500 nm. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5?-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

Zhang, Yong; Evans, Gary B.; Clinch, Keith; Crump, Douglas R.; Harris, Lawrence D.; Fröhlich, Richard F. G.; Tyler, Peter C.; Hazleton, Keith Z.; Cassera, María B.; Schramm, Vern L.

2013-01-01

337

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.

1999-01-06

338

Case study: using sequence homology to identify putative phosphorylation sites in an evolutionarily distant species (honeybee).  

PubMed

The majority of scientific resources are devoted to studying a relatively small number of model species, meaning that the ability to translate knowledge across species is of considerable importance. Obtaining species-specific knowledge enables targeted investigations of the biology and pathobiology of a particular species, and facilitates comparative analyses. Phosphorylation is the most widespread posttranslational modification in eukaryotes, and although many phosphorylation sites have been experimentally identified for some species, little or no data are available for others. Using the honeybee as a test organism, this case study illustrates the process of using protein sequence homology to identify putative phosphorylation sites in a species of interest using experimentally determined sites from other species. A number of issues associated with this process are examined and discussed. Several databases of experimentally determined phosphorylation sites exist; however, it can be difficult for the nonspecialist to ascertain how their contents compare. Thus, this case study assesses the content and comparability of several phosphorylation site databases. Additional issues examined include the efficacy of homology-based phosphorylation site prediction, the impact of the level of evolutionary relatedness between species in making these predictions, the ability to translate knowledge of phosphorylation sites across large evolutionary distances and the criteria that should be used in selecting probable phosphorylation sites in the species of interest. Although focusing on phosphorylation, the issues discussed here also apply to the homology-based cross-species prediction of other posttranslational modifications, as well as to sequence motifs in general. PMID:25380664

Trost, Brett; Napper, Scott; Kusalik, Anthony

2014-11-01

339

Site characterization and impact study prototype for secondary schools  

SciTech Connect

Secondary Education tends to be departmentalized to a degree that science disciplines are taught as separate entities with concepts and programs that are fragmented from the aggregate base of scientific knowledge. There is a need to synthesize these disciplines into one curricula that will provide a holistic approach rather than a narrow focus. Isolated disciplines foster isolated and disjointed strategies in environmental problem solving. Real world solutions to environmental challenges require an interdisciplinary team of specialists if goals are to be realized. This prototype incorporates various aspects of an impact study, including air and water quality, wildlife resources, agriculture and forest land, geologic data, socioeconomic impacts, historic and cultural preservation, politics and aesthetics into one curriculum to demonstrate the interconnectedness of these subjects.

Davin, R.G. [Durango High School, Las Vegas, NV (United States)

1995-12-01

340

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.

2008-12-01

341

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

2010-09-01

342

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

1993-01-01

343

Crystallographic studies of the catalytic and a second site in fumarase C from Escherichia coli.  

PubMed

Fumarase C catalyzes the stereospecific interconversion of fumarate to L-malate as part of the metabolic citric acid or Kreb's cycle. The recent three-dimensional structure of fumarase C from Escherichia coli has identified a binding site for anions which is generated by side chains from three of the four subunits within the tetramer (Weaver et al., 1995). These same side chains are found in the three most highly conserved regions within the class II fumarase superfamily. The site was initially characterized by crystallographic studies through the binding of a heavy atom derivative, tungstate. A number of additional crystallographic structures using fumarase crystals with bound inhibitors and poor substrates have now been studied. The new structures have both confirmed the originally proposed active site, site A, and led to the discovery of a novel second binding site that is structurally nearby, site B. Site A utilizes a combination of residues, including H188, T187, K324, N326, T100, N141, S139, and S140, to form direct hydrogen bonds to each of the inhibitors. The A-site has been demonstrated by studying crystalline fumarase with the bound competitive inhibitors-citrate and 1,2,4,5-benzenetetracarboxylic acid. The crystal structure of fumarase C with beta-(trimethylsilyl)maleate, a cis substrate for fumarase, has led to the discovery of the second site or B-site. Sites A and B have different properties in terms of their three-dimensional structures. Site B, for example, is formed by atoms from only one of the subunits within the tetramer and mainly by atoms from a pi-helix between residues H129 through N135. The crystal structures show that the two locations are separated by approximately 12 A. A highly coordinated buried water molecule is also found at the active or A-site. The high-resolution crystal structures describe both sites, and atoms near the A-site are used to propose a likely enzyme/substrate complex. PMID:8909293

Weaver, T; Banaszak, L

1996-11-01

344

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.

1986-04-08

345

STUDIES OF INTERFACIAL REACTIONS BETWEEN ARSENIC AND MINERALS AND ITS SIGNIFICANCE TO SITE CHARACTERIZATION : JOURNAL ARTICLE  

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). ...

346

Brookland Site Development Study, Brookland, bounded by B&O Railroad Tracks, ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Brookland Site Development Study, Brookland, bounded by B&O Railroad Tracks, Rhode Island & Brentwood Avenues on the south, 18th Street & South Dakota Avenue on the east, and Michigan Avenue on the North, Washington, District of Columbia, DC

347

Studying water budget of paved urban sites using weighable lysimeters  

NASA Astrophysics Data System (ADS)

Our lysimeter study addresses high-resolution analysis of the water balance of permeable pavements used for sidewalks and streets. Berlin's typical pavers, "Bernburg cobble stone" and "concrete paver" are analysed for actual evaporation, runoff and groundwater recharge. To achieve the reasonable boundary condition realistic seam material were bed in surface construction. The lysimeter bodies, filled with construction sand, stand in 1.5 m deep stainless cave on a scale with a 100g/sec resolution. The seepage water is captured by four suction plates with a suction of 63 hPa. To measure the run-off separately, special gutters are set up directly along the surface edge. This gutter leads the run-off water immediately to a separate discharge pipe and the run-off will be measured with a resolution of 0.0005 mm/sec; no water gets lost within this procedure. A dynamic runoff coefficient could be gained for a span of typical rainfall intensities. We will present runoff coefficients (RC) from both pavements as functions of the rainfall intensity, based on about 40 individual precipitation events. We could show that the rainfall intensity is the best predictor for the runoff behaviour. Concrete pavers can cause runoff with higher RC at lower intensity. However, for intensities > 0.1 mm/min their RCs tend to increase slower than those of mosaic cobble stone pavements. RCs might not be dependent on pavements during strong precipitation events. The measured RC are typical for the rainfall characteristic of Berlin, Germany and should not be used for other climate regions. First, the controlling variable must be identified and incorporated into process based models. Such models are essential for the prediction of urban evaporation so as to develop new urban water and climate management strategies.

Rim, Yong-Nam; Nehls, Thomas; Litz, Norbert; Trinks, Steffen; Wessolek, Gerd

2010-05-01

348

Solid-state Zn-67 NMR Spectroscopic Studies and ab initio Molecular Orbital Calculations on a Synthetic Analogue of Carbonic Anhydrase.  

SciTech Connect

The tris(pyrazolyl)hydroborato zinc complexes [TpBut,Me]ZnX (where X = Br, Cl, and OH) have been examined by low temperature solid-state 67Zn NMR spectroscopy. The value of the quadrupole coupling constant, Cq, for the zinc increased monotonically with the electronegativity of the bound substituent X, e.g. Br < Cl << OH. Calculations on the methylimidazole complex [(MeImH)3Zn(OH)]+ as a model for the active site of carbonic anhydrase indicate that the computed electric field gradient tensor is in good agreement with the experimental and calculated values for [TpBut,Me]ZnOH.

Lipton, Andrew S.; Bergquist, Catherine; Parkin, Gerard; Ellis, Paul D.

2003-04-02

349

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.)

1988-12-01

350

Structural Basis of Ligand Binding to UDP-Galactopyranose Mutase from Mycobacterium tuberculosis Using Substrate and Tetrafluorinated Substrate Analogues.  

PubMed

UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized flavin and reduced flavin). In addition, we have determined the complex structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated analogues of both UDP-Galp (UDP-F4-Galp) and UDP-Galf (UDP-F4-Galf)), which represent the first complex structures of UGM with an analogue in the furanose form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues bound to a protein. These structures provide detailed insight into ligand recognition by MtUGM and show an overall binding mode similar to those reported for other prokaryotic UGMs. The binding of the ligand induces conformational changes in the enzyme, allowing ligand binding and active-site closure. In addition, the complex structure of MtUGM with UDP-F4-Galf reveals the first detailed insight into how the furanose moiety binds to UGM. In particular, this study confirmed that the furanoside adopts a high-energy conformation ((4)E) within the catalytic pocket. Moreover, these investigations provide structural insights into the enhanced binding of the dideoxy-tetrafluorinated sugars compared to unmodified analogues. These results will help in the design of carbohydrate mimetics and drug development, and show the enormous possibilities for the use of polyfluorination in the design of carbohydrate mimetics. PMID:25562380

van Straaten, Karin E; Kuttiyatveetil, Jijin R A; Sevrain, Charlotte M; Villaume, Sydney A; Jiménez-Barbero, Jesús; Linclau, Bruno; Vincent, Stéphane P; Sanders, David A R

2015-01-28

351

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

PubMed

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

2014-05-01

352

3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine  

SciTech Connect

The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))

1991-03-01

353

Sulphamoylated 2-Methoxyestradiol Analogues Induce Apoptosis in Adenocarcinoma Cell Lines  

PubMed Central

2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1–25 ?M) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 ?M of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues. PMID:24039728

Visagie, Michelle; Theron, Anne; Mqoco, Thandi; Vieira, Warren; Prudent, Renaud; Martinez, Anne; Lafanechère, Laurence; Joubert, Annie

2013-01-01

354

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

PubMed

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

2013-11-01

355

Synthetic Neurotensin Analogues Are Nontoxic Analgesics for the Rabbit Cornea  

PubMed Central

Purpose. To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Methods. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. Results. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Conclusions. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. PMID:24825106

Kim, Charles; Barbut, Denise; Heinemann, Murk H.; Pasternak, Gavril; Rosenblatt, Mark I.

2014-01-01

356

Somatostatin analogue treatment of neuroendocrine tumours.  

PubMed Central

The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. Somatostatin analogues are not useful in the treatment of patients with prolactinomas, or adrenocorticotropin (ACTH)-secreting adenomas. However, the somatostatin analogue octreotide suppressed pathological ACTH release in some patients with Nelson's syndrome and ACTH and cortisol secretion in several patients with Cushing's syndrome caused by ectopic ACTH secretion. Somatostatin analogues are effective in the sympatomatic treatment of most (metastatic) pancreatic islet cell tumours and most (metastatic) carcinoids. In some of these patients, they also induce tumour stabilisation or reduction. In some patients with (metastatic) medullary thyroid carcinomas, continuous treatment with very high doses of octreotide can be of temporary relief. The clinical effectiveness of somatostatin analogues in patients with small cell lung cancer is currently under investigation. Long-term therapy with somatostatin analogues of catecholamine-secreting (malignant) paragangliomas and phaeochromocytomas has not shown clinical benefits. PMID:8935599

de Herder, W. W.; van der Lely, A. J.; Lamberts, S. W.

1996-01-01

357

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.

1993-02-01

358

Biological evaluation of a novel sorafenib analogue, t-CUPM.  

PubMed

Sorafenib (Nexavar(®)) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGFR-2, and an enzyme shown to be a potent off-target of sorafenib, soluble epoxide hydrolase. In the current work, we present the biological data on our lead sorafenib analogue, t-CUPM, demonstrating that this analogue retains cytotoxicity similar to sorafenib in various human cancer cell lines and strongly inhibits growth in the NCI-60 cell line panel. Co-treatment with the pan-caspase inhibitor, Z-VAD-FMK, failed to rescue the cell viability responses of both sorafenib and t-CUPM, and immunofluorescence microscopy shows similar mitochondrial depolarization and apoptosis-inducing factor release for both compounds. These data suggest that both compounds induce a similar mechanism of caspase-independent apoptosis in hepatoma cells. In addition, t-CUPM displays anti-proliferative effects comparable to sorafenib as seen by a halt in G0/G1 in cell cycle progression. The structural difference between sorafenib and t-CUPM significantly reduces inhibitory spectrum of kinases by this analogue, and pharmacokinetic characterization demonstrates a 20-fold better oral bioavailability of t-CUPM than sorafenib in mice. Thus, t-CUPM may have the potential to reduce the adverse events observed from the multikinase inhibitory properties and the large dosing regimens of sorafenib. PMID:25413440

Wecksler, Aaron T; Hwang, Sung Hee; Liu, Jun-Yan; Wettersten, Hiromi I; Morisseau, Christophe; Wu, Jian; Weiss, Robert H; Hammock, Bruce D

2015-01-01

359

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.; Harpsøe, Kasper; Skonberg, Christian; Liljefors, Tommy; Strømgaard, Kristian

2009-01-01

360

Surgical site infections at the National Cancer Institute in Mexico: A case-control study  

Microsoft Academic Search

Objectives: To quantify the surgical infection rate and to identify risk factors associated with surgical site infection.Methods: We conducted a case-control study of all surgical patients between January 1, 1993, and June 30, 1994. The frequency of surgical site infection per 100 surgeries was calculated. The odds ratio (OR) was estimated by using logistic regression analysis.setting: A 130-bed tertiary-care teaching

Diana Vilar-Compte; Alejandro Mohar; Silvia Sandoval; Margarita de la Rosa; Gordillo Patricia; Patricia Volkow

2000-01-01

361

Communicating with local publics: a case study of Coca-Cola's Chinese web site  

Microsoft Academic Search

Purpose – This is a case study of Coca-Cola's Chinese web site. It aims to examine how Coca-Cola, the number one brand in the world, is using its web site to communicate with the publics in the world's largest market. Design\\/methodology\\/approach – Uses a qualitative text analysis. Findings – Coca-Cola is practicing a “glocal” strategy, which integrates the ethnocentric and

Yan Tian

2006-01-01

362

Geochemical and mineralogical study of a site severely polluted with heavy metals (Maatheide, Lommel, Belgium)  

Microsoft Academic Search

The former zinc smelter site ‘de Maatheide’ in Lommel (Belgium) was severely polluted with heavy metals and the pollution spread into the surroundings by rain water leaching and wind transportation. This study focuses on the processes of immobilization and natural attenuation that took place on the site. Three important factors were found. Firstly, the high pH values (pH 7–8) in

L. Horckmans; R. Swennen; J. Deckers

2006-01-01

363

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

2008-01-01

364

MAIIA EPO SeLect - a rapid screening kit for the detection of recombinant EPO analogues in doping control: Inter-laboratory prevalidation and normative study of athlete urine and plasma samples.  

PubMed

Recombinant analogues of erythropoietin (EPO), epoetins, have been misused by athletes due to their performance enhancing effect since the first pharmaceutical epoetin was launched in 1987. The current methods for screening urine and plasma samples for the presence of epoetins, IEF and SAR-PAGE, have high sensitivity but are time-consuming to carry out. In an effort to ease and speed up the screening procedure for EPO, MAIIA Diagnostics has developed a combined affinity chromatography and lateral flow immunoassay, MAIIA EPO SeLect, which determines the percentage of migrated isoforms (PMI) of EPO in a sample. The reproducibility of the kit was tested by analyzing a set of negative and positive urine and plasma samples in three different laboratories. All data were analyzed with both curve fit parameters from the individual assay runs, and with lot-specific predefined curve calibration. To get a measure of endogenous variation, a normative study with athlete urine and plasma samples was conducted. The average intra-laboratory variation was 6.7% while the inter-laboratory variation for all samples was calculated to 8.8%. The athlete samples yielded an average PMI and standard deviation of 71.4?±?7.7 for urine and 83.1?±?10.2 for plasma, respectively. There were no signs of deviating results from tested effort urines. The results also support the use of predefined curve parameters. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25421537

Dehnes, Yvette; Myrvold, Linda; Ström, Helene; Ericsson, Magnus; Hemmersbach, Peter

2014-11-01

365

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.

2011-01-01

366

Phosphonomethyl analogues of phosphate ester glycolytic intermediates  

PubMed Central

Analogues of dihydroxyacetone phosphate and of 3-phosphoglycerate were made in which the phosphate group, –O–PO3H2, is replaced by the phosphonomethyl group, –CH2–PO3H2. The analogue of dihydroxyacetone phosphate is a substrate for aldolase and glycerol 1-phosphate dehydrogenase (Stribling, 1974), but not for triose phosphate isomerase. The analogue of 3-phosphoglycerate oxidizes NADH under the combined action of 3-phosphoglycerate kinase and glyceraldehyde 3-phosphate dehydrogenase if ATP is added. Thus four out of the five glycolytic enzymes tested handle the phosphonomethyl compounds like the natural phosphates. PMID:4377103

Dixon, Henry B. F.; Sparkes, Michael J.

1974-01-01

367

Synthesis and Antibacterial Activities of Yanglingmycin Analogues.  

PubMed

The synthesis of Yanglingmycin and its enantiomer, along with eighteen Yanglingmycin analogues is reported. The structures were confirmed mainly by analyses of NMR spectral data. Antibacterial activity assays showed that Yanglingmycin and some of its analogues exhibited significant antibacterial activities against two important agricultural pathogenic bacteria, Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae, with MIC values ranging from 3.91 to 15.62 ?g/mL. The antibacterial activities exhibited by Yanglingmycin and its analogues are promising, suggesting potential in the development of compounds for novel bactericides. PMID:25355464

Li, Long-Bo; Dan, Wen-Jia; Tan, Fang-Fang; Cui, Li-Hui; Yuan, Zhi-Peng; Wu, Wen-Jun; Zhang, Ji-Wen

2014-10-30

368

Synthesis of Phosphatidylcholine Analogues Derived from Glyceric Acid: a New Class of Biologically Active Phospholipid Compounds.  

PubMed

Synthesis of a new class of phosphatidylcholine analogues derived from glyceric acid is reported for spectroscopic studies of phospholipases and conformation of phospholipid side-chains in biological membranes, using fluorescence resonance energy transfer (FRET) techniques. PMID:19844592

Rosseto, Renato; Tcacenco, Celize M; Ranganathan, Radha; Hajdu, Joseph

2008-05-19

369

Relationships between peroxyacetyl nitrate, O3, and NO(y) at the rural Southern Oxidants Study site in central Piedmont, North Carolina, site SONIA  

Microsoft Academic Search

Ambient peroxyacetyl nitrate (PAN) concentrations were measured during June and early July 1992 at site SONIA (Southeast Oxidants and Nitrogen Intensive Analysis), a rural site in the central Piedmont region of North Carolina, as part of the Southern Oxidants Study. PAN measurements were made as part of an effort to provide a comprehensive chemical climatology and to investigate the total

Benjamin E. Hartsell; Viney P. Aneja; William A. Lonneman

1994-01-01

370

IN-SITU DUOX¿ CHEMICAL OXIDATION TECHNOLOGY TO TREAT CHLORINATED ORGANICS AT THE ROOSEVELT MILLS SITE, VERNON, CT: SITE CHARACTERIZATION AND TREATABILITY STUDY  

EPA Science Inventory

A study was performed investigating the feasibility of applying the DUOX¿ chemical oxidation technology to chlorinated solvent contaminated media at the Roosevelt Mills site in Vernon, Connecticut. The Roosevelt Mills site is a former woolen mill that included dry cleaning operat...

371

Divergent total synthesis of triptolide, triptonide, tripdiolide, 16-hydroxytriptolide, and their analogues.  

PubMed

A divergent route was developed for the formal total synthesis of triptolide, triptonide, and tripdiolide, as well as a total synthesis of 16-hydroxytriptolide and their analogues in an enantioselective form. Common advanced intermediate 5 was concisely assembled by employing an indium(III)-catalyzed cationic polycyclization reaction and a palladium-catalyzed carbonylation-lactone formation reaction as key steps. This advanced intermediate was readily converted to the above natural products by using palladium-catalyzed cross-coupling or the Claisen rearrangement reaction as key steps. Additionally, preliminary structure-cytotoxic activity relationship studies of C13 suggested that it might be a new modification site that could still retain the cytotoxicity. PMID:25296383

Xu, Hongtao; Tang, Huanyu; Feng, Huijin; Li, Yuanchao

2014-11-01

372

Conversion of trans-diboran(4)yl platinum complexes into their cis-bisboryl analogues.  

PubMed

The diboran(4)yl trans-[(iPr3 P)2 Pt(Br){B(NMe2 )B(NMe2 )Br}] (1) is readily converted into its cis-bisboryl analogues 2 and 3 by reaction with the chelating bisphosphines 1,2-bis(dicyclohexylphosphino)ethane (dcpe) and 1,1-bis(dicyclohexylphosphino)methane (dcpm), respectively. A plausible mechanism of this transformation consists of a sequence of reductive diborane(4) elimination and subsequent reoxidative addition of its B?B bond to the low-valent platinum centers. Thus, the forced cis configuration of the phosphine ligands induces a change in the preferred reaction site of the diborane(4) with respect to oxidative addition. The reactions proceed with high selectivities, and the cis-bisboryl complexes 2 and 3 were isolated in moderate yields (55 and 46?%). Moreover, their identity was clearly verified by NMR spectroscopy and X-ray diffraction studies. PMID:24027132

Braunschweig, Holger; Damme, Alexander; Kupfer, Thomas

2013-10-18

373

The interaction of borate ions with cytochrome c surface sites: a molecular dynamics study.  

PubMed Central

Ionic interactions of cytochrome c play an important role in the electron transfer process. Molecular dynamics simulations of the binding of borate ion, which serves as a model ion, at three different cytochrome c surface sites are performed. This work is motivated by previous NMR studies of cytochrome c in borate solution, which indicate the existence of two types of binding sites, a slow exchange site and a fast exchange site. These two types of binding behavior were observed in the dynamic simulations, offering a molecular interpretation of "loose" and "tight" binding. At the "loose" binding sites (near Lys25/Lys27 and Lys55/Lys73) the ion forms two to three hydrogen bonds to the nearest lysine residue. This binding is transient on the time scale of the simulation, demonstrating the feasibility of fast exchange. At the "tight" binding site (near Lys13/Lys86), on the other hand, the ion becomes integrated into the protein hydrogen bond network and remains there for the duration of the simulation (exemplifying slow exchange). Binding simulations of the ion at the "tight" site of H26Q mutant cytochrome c also showed integration of the ion into the protein's hydrogen bond network. However, this integration differs in details from the binding of the ion to the native protein, in agreement with previous NMR observations. PMID:9788941

Taler, G; Navon, G; Becker, O M

1998-01-01

374

Study plan for urban stream indicator sites of the National Water-Quality Assessment Program  

USGS Publications Warehouse

Urban Indicator Sites are one component of the U.S. Geological Survey?s National Water- Quality Assessment (NAWQA) Program. The objectives of monitoring at the Urban Indicator Sites are to: (1) characterize stream quality from drainage basins with predominantly residential and commercial land use, and (2) determine which selected natural and human factors most strongly affect stream quality. Urban Indicator Sites will be distributed across the United States in settings with statistically different climate and in metropolitan areas that have a population of 250,000 or more. Multiple sites in the same climatic setting will have a range in population density. Ideally, Urban Indicator Sites will monitor drainage basins that have only residential and commercial land use, are 50 square kilometers or larger, are in the same physiographic setting as other Indicator Sites, have sustained flow, and overlap other NAWQA study components. Ideal drainage basins will not have industrial or agricultural land use and will not have point-source-contamination discharges. Stream quality will be characterized by collecting and analyzing samples of streamflow, bed sediment, and tissue of aquatic organisms for selected constituents. Factors affecting stream quality will be determined by statistical analysis of ancillary data associated with Urban Indicator Sites and stream-quality samples.

Lopes, T.J.; Price, C.V.

1997-01-01

375

Landfill site selection using spatial information technologies and AHP: a case study in Beijing, China.  

PubMed

Site selection is an important and necessary issue for waste management in fast-growing regions. Because of the complexity of waste management systems, the selection of the appropriate solid waste landfill site requires consideration of multiple alternative solutions and evaluation criteria. Based on actual conditions of the study area, we considered economic factors, calculated criteria weights using the analytical hierarchy process (AHP), and built a hierarchy model for solving the solid waste landfill site-selection problem in Beijing, China. A geographic information system (GIS) was used to manipulate and present spatial data. All maps are graded from 1 (lowest suitability) to 5 (highest suitability) using spatial information technologies. The candidate sites were determined by aggregation based on the criteria weights. The candidate sites are divided by 'best', 'good' and 'unsuitable' landfill areas. Best landfill areas represent optimal sites; good landfill areas can be used as back-up candidate sites. Our work offers a sitting methodology and provides essential support for decision-makers in the assessment of waste management problems in Beijing and other rapidly developing cities in developing countries. PMID:19375842

Wang, Guiqin; Qin, Li; Li, Guoxue; Chen, Lijun

2009-06-01

376

PM2.5 Indoor Air Quality at Two Sites in London Ontario - A Case Study  

NASA Astrophysics Data System (ADS)

Studies have shown an association between ambient fine particulate matter (PM2.5) and health impacts, particularly for the elderly and children. As part of a larger study, PM2.5 concentrations were measured using the DustTrak (Model 8520, TSI, St. Paul, MN, USA) at two schools within the city of London, Ontario (Canada). Site A was in a suburban environment while site B was in an urban setting. Monitoring took place for 3 weeks during winter (Feb. 16 - Mar. 8) and 3 weeks during spring (May 05 - 25) of 2010. The winter campaign monitored indoor PM2.5 only, while the spring campaign added outdoor monitors (PM2.5 and CO2) after the first week. Ten min. concentrations were used for analysis. Indoor measurements were split into weekday and weekend. For the same time interval, the outdoor concentrations showed mean values of 18 and 21 ?g/m3 for sites A & B, respectively, both under the Canada Wide Standard of 30 ?g/m3. Measurements at the two sites showed good associations (R^2 = 0.44), during the spring campaign. This indicates that the outdoor PM2.5 had similar sources. For indoor concentrations, Site B showed a significantly different mean concentration 5 times higher compared to site A during the winter ( 8.1 vs. 1.5 ?g/m3 ) and 3 times higher (11.9 vs. 3.7 ?g/m3) during the spring campaign. Since the outdoor concentrations were similar the large difference in indoor concentrations could be attributed to the following factors: site B being an older building, and the different physical characteristics between the two sites. The spring measurements showed an increase of 50% from weekday to weekend for site A and 22% for site B. The higher level of PM2.5 during weekends is possibly due to the infiltration of outdoor air while the ventilation/filtration system is shut off. During the winter campaign, Site A showed a 14% higher concentration during weekdays compared to weekends while site B weekend concentrations were 17% higher compared to weekday, which will be further investigated. The CO2 levels will be analyzed for the effect of outdoor air infiltration. The weekday data will be further split into activity and non-activity hours to explore the PM2.5 concentration increases associated with activity.

Mates, A. V.; Xu, X.; Gilliland, J.; Maltby, M. J.

2010-12-01

377

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

2001-01-01

378

Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases  

Microsoft Academic Search

BACKGROUND: Several risk factors for ectopic pregnancy (EP) have been identified, but the site of implantation of EP has been little studied. METHODS: A total of 1800 surgically treated EP was registered between January 1992 and December 2001 in the Auvergne EP register and the women concerned were followed up. In this large population-based sample, we studied the distribution of

J. Bouyer; J. Coste; H. Fernandez; J. L. Pouly; N. Job-Spira

2002-01-01

379

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.

1973-01-01

380

OSI-930 ANALOGUES AS NOVEL REVERSAL AGENTS FOR ABCG2-MEDIATED MULTIDRUG RESISTANCE  

PubMed Central

OSI-930, a dual c-Kit and KDR tyrosine kinase inhibitor, is reported to have undergone a Phase I dose escalation study in patients with advanced solid tumors. A series of fifteen pyridyl and phenyl analogues of OSI-930 were designed and synthesized. Extensive screening of these compounds led to the discovery that nitropyridyl and ortho-nitrophenyl analogues, VKJP1 and VKJP3, were effective in reversing ABC subfamily G member 2 (ABCG2) transporter-mediated multidrug resistance (MDR). VKJP1 and VKJP3 significantly sensitized ABCG2-expressing cells to established substrates of ABCG2 including mitoxantrone, SN-38, and doxorubicin in a concentration-dependent manner, but not to the non-ABCG2 substrate cisplatin. However, they were unable to reverse ABCB1- or ABCC1-mediated MDR indicating their selectivity for ABCG2. Western blotting analysis was performed to evaluate ABCG2 expression and it was found that neither VKJP1 nor VKJP3 significantly altered ABCG2 protein expression for up to 72 h. [3H]-mitoxantrone accumulation study demonstrated that VKJP1 and VKJP3 increased the intracellular accumulation of [3H]-mitoxantrone, a substrate of ABCG2. VKJP1 and VKJP3 also remarkably inhibited the transport of [3H]-methotrexate by ABCG2 membrane vesicles. Importantly, both VKJP1 and VKJP3 were efficacious in stimulating the activity of ATPase of ABCG2 and inhibited the photoaffinity labeling of this transporter by its substrate [125I]-iodoarylazidoprazosin. The results suggested that VKJP1 and VKJP3, specifically inhibit the function of ABCG2 through direct interaction with its substrate binding site(s). Thus VKJP1 and VKJP3 represent a new class of drugs for reducing MDR in ABCG2 over-expressing tumors. PMID:22750060

Kuang, Ye-Hong; Patel, Jay P.; Sodani, Kamlesh; Wu, Chun-Pu; Liao, Li-Qiu; Patel, Atish; Tiwari, Amit K.; Dai, Chun-Ling; Chen, Xiang; Fu, Li-Wu; Ambudkar, Suresh V.; Korlipara, Vijaya L.; Chen, Zhe-Sheng

2012-01-01

381

Comparative transport efficiencies of urea analogues through urea transporter UT-B.  

PubMed

Expression of urea transporter UT-B confers high urea permeability to mammalian erythrocytes. Erythrocyte membranes also permeate various urea analogues, suggesting common transport pathways for urea and structurally similar solutes. In this study, we examined UT-B-facilitated passage of urea analogues and other neutral small solutes by comparing transport properties of wildtype to UT-B-deficient mouse erythrocytes. Stopped-flow light-scattering measurements indicated high UT-B permeability to urea and chemical analogues formamide, acetamide, methylurea, methylformamide, ammonium carbamate, and acrylamide, each with P(s)>5.0 x 10(-6) cm/s at 10 degrees C. UT-B genetic knockout and phloretin treatment of wildtype erythrocytes similarly reduced urea analogue permeabilities. Strong temperature dependencies of formamide, acetamide, acrylamide and butyramide transport across UT-B-null membranes (E(a)>10 kcal/mol) suggested efficient diffusion of these amides across lipid bilayers. Urea analogues dimethylurea, acryalmide, methylurea, thiourea and methylformamide inhibited UT-B-mediated urea transport by >60% in the absence of transmembrane analogue gradients, supporting a pore-blocking mechanism of UT-B inhibition. Differential transport efficiencies of urea and its analogues through UT-B provide insight into chemical interactions between neutral solutes and the UT-B pore. PMID:17506977

Zhao, Dan; Sonawane, N D; Levin, Marc H; Yang, Baoxue

2007-07-01

382

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)

1994-12-31

383

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.

NONE

1996-10-01

384

Site-directed mutagenesis studies of the aromatic residues at the active site of a lipase from Malassezia globosa.  

PubMed

The lipase from Malassezia globosa (SMG1) has specific activity on mono- and diacylglycerol but not on triacylglycerol. The structural analysis of SMG1 structure shows that two bulky aromatic residues, W116 and W229, lie at the entrance of the active site. To study the functions of these two residues in the substrate recognition and the catalytic reaction, they were mutated to a series of amino acids. Subsequently, biochemical properties of these mutants were investigated. Although the activities decrease, W229L and W116A show a significant shift in substrate preference. W229L has an increased preference for short-chain substrates whereas W116A has preference for long-chain substrates. Besides, the half-lives of W116A and W116H at 45 °C are 346.6 min and 115.5 min respectively, which improve significantly compared to that of native enzyme. Moreover, the optimum substrate of W116A, W116F and W229F mutants shifted from p-nitrophenyl caprylate to p-nitrophenyl myristate. These findings not only shed light onto the lipase structure/function relationship but also lay the framework for the potential industrial applications. PMID:24556587

Gao, Chongliang; Lan, Dongming; Liu, Lu; Zhang, Houjin; Yang, Bo; Wang, Yonghua

2014-07-01

385

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.

NONE

1995-11-01

386

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)

2013-07-01

387

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)

2013-02-24

388

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

SciTech Connect

Phase II of a 5-phase overall compressed air energy storage (CAES) development program was performed to characterize and explore potential CAES sites and to prepare a research and development plan. This volume for Phase II activities contains an evaluation of the suitability of seven selected sites to undergo field drilling and air injection testing; a bibliography; results of a literature search on the effects of air injection of aquifer-caprock well systems; reservoir data for the sites; cost estimates; and predicted potential risks from a CAES plant. (LCL)

None

1980-12-01

389

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.

2014-07-17

390

Studies on the binding of lambda Int protein to attachment site DNA: identification of a tight-binding site in the P' region.  

PubMed Central

We have used three approaches to studying the interaction of lambda Int protein with bacteriophage attachment site DNA, POP': location of binding sites by retention of DNA fragments in a filter binding assay, reconstruction of a binding site by DNA synthesis and protection of a binding site from an exonuclease. Retention of restriction fragments on nitrocellulose filters in the presence of Int protein was used to locate binding sites. A high affinity binding site lies in P' between base pairs -6 and +173 from the center of the common core sequence, and low affinity sites are found in the 200 base pair region left of position -6. Reconstruction of the high affinity binding site region from the right using primed DNA synthesis and testing for filter binding in the presence of Int protein shows that sequences sufficient for tight binding of Int protein lie to the right of position +66. When attachment site DNA is protected by bound Int protein against digestion by exonuclease III, four Int dependent protection bands are seen in positions +58, +68, +79 and +88. This can be interpreted either as showing that four Int protein monomers bind to the high affinity region in series, or as evidence for wrapping of the DNA around Int protein, leading to structural changes resembling those occurring to DNA in nucleosomes. Images PMID:160545

Davies, R W; Schreier, P H; Kotewicz, M L; Echols, H

1979-01-01

391

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

392

Interaction of natural polyamines and dimethylsilyl analogues with a phospholipid monolayer: a study by Brewster angle microscopy and PM-IRRAS  

Microsoft Academic Search

This work presents an analysis of the physicochemical interactions of natural and dimethylsilyl polyamines with an anionic deuterated phospholipid monolayer, d62DPPG (dipalmitoyl phosphatidyl glycerol), at the air–water interface. It was motivated by previous studies, which suggested an antitumour strategy based on the accumulation of derivatives such as bis(7-amino-4-azaheptyl) dimethylsilyl (azhepSi), in order to diminish the concentration of natural polyamines (spermine

Olga Berdycheva; Bernard Desbat; Michel Vaultier; Michèle Saint-Pierre-Chazalet

2003-01-01

393

Acoustic clouds: standing sound waves around a black hole analogue  

E-print Network

Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

Carolina L. Benone; Luis C. B. Crispino; Carlos Herdeiro; Eugen Radu

2015-01-28

394

Acoustic clouds: standing sound waves around a black hole analogue  

E-print Network

Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

Benone, Carolina L; Herdeiro, Carlos; Radu, Eugen

2014-01-01