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Sample records for 119sb a potent auger

  1. 119Sb--a potent Auger emitter for targeted radionuclide therapy.

    PubMed

    Thisgaard, H; Jensen, M

    2008-09-01

    Auger electron emitting radionuclides in cancer therapy offer the opportunity to deliver a high radiation dose to the tumor cells with high radiotoxicity while minimizing toxicity to normal tissue. We have in this study identified the Auger emitter 119Sb as a potent nuclide for targeted radionuclide therapy based on theoretical dosimetry calculations at a subcellular scale. From these calculations we have determined the cellular S-values for this therapeutic isotope. Moreover, we have demonstrated the possibility of producing this isotope and also the SPECT-analogue 117Sb for patient-specific dosimetry, by measuring the proton irradiation yields for both isotopes using a low-energy cyclotron. The excellent SPECT imaging properties of the 117Sb radionuclide have been shown by scanning a Jaszczak SPECT Phantom. PMID:18841834

  2. {sup 119}Sb--A potent Auger emitter for targeted radionuclide therapy

    SciTech Connect

    Thisgaard, H.; Jensen, M.

    2008-09-15

    Auger electron emitting radionuclides in cancer therapy offer the opportunity to deliver a high radiation dose to the tumor cells with high radiotoxicity while minimizing toxicity to normal tissue. We have in this study identified the Auger emitter {sup 119}Sb as a potent nuclide for targeted radionuclide therapy based on theoretical dosimetry calculations at a subcellular scale. From these calculations we have determined the cellular S-values for this therapeutic isotope. Moreover, we have demonstrated the possibility of producing this isotope and also the SPECT-analogue {sup 117}Sb for patient-specific dosimetry, by measuring the proton irradiation yields for both isotopes using a low-energy cyclotron. The excellent SPECT imaging properties of the {sup 117}Sb radionuclide have been shown by scanning a Jaszczak SPECT Phantom.

  3. Hydrogen slush production with a large auger

    NASA Technical Reports Server (NTRS)

    Daney, D. E.; Arp, V. D.; Voth, R. O.

    1990-01-01

    The design and construction of a 178-mm-diameter auger-type hydrogen slush generator are described. A supercritical helium flow loop, which simulates the performance of a helium refrigerator, cools the generator. The coolant temperature varies down to 5 K and the flow varies about the 1.4 L/s (3 cfm) design point. The computer model of the auger-type generator shows that coolant temperature and auger speed have the greatest influence on slush production rate, although coolant flow rate and auger radial clearance are also important.

  4. Design of a rotary stepped auger for a lunar environment

    NASA Technical Reports Server (NTRS)

    Dardet, Eduardo; Hart, Derek; Herod, Chris; Homiller, Stephen; Meeks, Mickey; Platt, Kirsten

    1988-01-01

    A lunar outpost will have need for deep drilling operations for both explorative and practical purposes. As in any drilling operation, the cuttings must be cleared from the hole. The hard vacuum of the lunar environment renders conventional flushing methods of cutting removal unfeasible, and requires a new system of removal. A rotary stepped auger (RSA) is a simple mechanical method of removing dry cuttings from a deep hole, and is ideally suited to the lunar environment. The RSA consists of a helical auger with stepped ramps which allow cuttings to slide up the helix, but will prevent them from sliding back down. The auger is driven in a pulsed manner by applying a periodic function of acceleration to the auger shaft. These pulses will compel the cuttings to slide up the auger's helix while the stepped ramps prevent the cuttings from backsliding while the auger accelerates. A mathematical model of the RSA was developed and experimentally evaluated. The math model produced a good baseline design, but the experimental model required some tuning to account for the approximations made in the math model. This design is suited for lunar drilling because it is mechanically simple, integral to the drill string, requires no fluids, is suited to the dry soil, and has relatively low weight and power requirements.

  5. Auger-architectomics: introducing a new nanotechnology to infectious disease.

    PubMed

    Swart, Chantel W; Pohl, Carolina H; Kock, Johan L F

    2014-01-01

    In 2010, we developed a new imaging nanotechnology called Auger-architectomics, to study drug biosensors in nano-detail. We succeeded in applying Auger atom electron physics coupled to scanning electron microscopy (SEM) and Argon-etching to cell structure exploration, thereby exposing a new dimension in structure and element composition architecture. Auger-architectomics was used to expose the fate and effect of drugs on cells. This technology should now be expanded to diseased cells. This paper will outline the development, proof of concept, and application of this imaging nanotechnology. A virtual tour is available at: http://vimeo.com/user6296337 . PMID:24619614

  6. Differential auger spectrometry

    DOEpatents

    Strongin, Myron; Varma, Matesh Narayan; Anne, Joshi

    1976-06-22

    Differential Auger spectroscopy method for increasing the sensitivity of micro-Auger spectroanalysis of the surfaces of dilute alloys, by alternately periodically switching an electron beam back and forth between an impurity free reference sample and a test sample containing a trace impurity. The Auger electrons from the samples produce representative Auger spectrum signals which cancel to produce an Auger test sample signal corresponding to the amount of the impurity in the test samples.

  7. Upflow bioreactor having a septum and an auger and drive assembly

    DOEpatents

    Hansen, Carl S.; Hansen, Conly L.

    2007-11-06

    An upflow bioreactor includes a vessel having an inlet and an outlet configured for upflow operation. A septum is positioned within the vessel and defines a lower chamber and an upper chamber. The septum includes an aperture that provides fluid communication between the upper chamber and lower chamber. The bioreactor also includes an auger positioned in the aperture of the septum. The vessel includes an opening in the top for receiving the auger. The auger extends from a drive housing, which is position over the opening and provides a seal around the opening. The drive housing is adjustable relative to the vessel. The position of the auger in the aperture can be adjusted by adjusting the drive housing relative to the vessel. The auger adjustment mechanism allows the auger to be accurately positioned within the aperture. The drive housing can also include a fluid to provide an additional seal around the shaft of the auger.

  8. Fabrication manual for a reduced-noise auger miner cutting head. Information circular/1984

    SciTech Connect

    Pettitt, M.R.; Aljoe, W.W.

    1984-01-01

    After a long series of laboratory and in-mine tests, a cost-effective, mineworthy, reduced-noise auger miner cutting head was designed, fabricated, and field-tested by Wyle Laboratories under contract to the Bureau of Mines. Compared with standard auger cutting heads, the new heads reduced noise by 10 dBA at the jacksetter's position and by 6 dBA at the operator's position. This report contains detailed fabrication instructions, including engineering drawings, that show how a standard auger cutting head can be modified to produce a reduced-noise auger.

  9. Sequential double Auger decay in atoms: A quantum informatic analysis

    NASA Astrophysics Data System (ADS)

    Parida, S.; Chandra, N.

    2009-05-01

    We theoretically show that the process of inner-shell photoionization in an atom A, followed by the spontaneous sequential emission of two Auger electrons, produces various kinds of spin-entangled states of three flying electronic qubits. All properties of these states are completely pre-determined by the total spin quantum numbers of the electronic states of four atomic species (i.e., A, A, A, A) participating in this process in the Russell-Saunders coupling. These tripartite states are readily characterized experimentally by measuring only energies of the three emitted electrons, without requiring any entanglement witness or other such protocols.

  10. A new technique for Auger analysis of surface species subject to electron-induced desorption

    NASA Technical Reports Server (NTRS)

    Pepper, S. V.

    1973-01-01

    A method is presented to observe surface species subject to electron-induced desorption by Auger electron spectroscopy. The surface to be examined is moved under the electron beam at constant velocity, establishing a time independent condition and eliminating the time response of the electron spectrometer as a limiting factor. The dependence of the Auger signal on the surface velocity, incident electron current, beam diameter, and desorption cross section are analyzed. The method is illustrated by the Auger analysis of PTFE, in which the fluorine is removed by electron induced desorption.

  11. A faraway quasar in the direction of the highest energy Auger event

    SciTech Connect

    Albuquerque, Ivone F.M.; Chou, Aaron E-mail: achou@fnal.gov

    2010-08-01

    The highest energy cosmic ray event reported by the Auger Observatory has an energy of 148 EeV. It does not correlate with any nearby (z < 0.024) object capable of originating such a high energy event. Intrigued by the fact that the highest energy event ever recorded (by the Fly's Eye collaboration) points to a faraway quasar with very high radio luminosity and large Faraday rotation measurement, we have searched for a similar source for the Auger event. We find that the Auger highest energy event points to a quasar with similar characteristics to the one correlated to the Fly's Eye event. We also find the same kind of correlation for one of the highest energy AGASA events. We conclude that so far these types of quasars are the best source candidates for both Auger and Fly's Eye highest energy events. We discuss a few exotic candidates that could reach us from gigaparsec distances.

  12. Auger electron spectroscopy as a tool for measuring intramolecular charges of adsorbed molecules

    NASA Astrophysics Data System (ADS)

    Magkoev, T. T.

    A way for the determination of the values of intramolecular charges of adsorbed molecules of some binary dielectrics, based on Auger electron spectroscopy (AES), is proposed. These values can be obtained from the coverage dependences of the ratios of intensities of anion KL 23L 23 and KL 1L 1 Auger transitions, which are sensitive to the amount of charge at the 2p-orbitals. As an example, MgO adsorbed on Mo(110) is presented.

  13. Auger electron spectroscopy as a tool for measuring intramolecular charges of adsorbed molecules

    NASA Astrophysics Data System (ADS)

    Magkoev, T. T.

    1993-10-01

    A way for the determination of the values of intramolecular charges of adsorbed molecules of some binary dielectrics, based on Auger electron spectroscopy (AES), is proposed. These values can be obtained from the coverage dependences of the ratios of intensities of anion KL 23L 23 and KL 1L 1 Auger transitions, which are sensitive to the amount of charge at the 2p-orbitals. As an example, MgO adsorbed on Mo(110) is presented.

  14. Installation of observation wells on hazardous waste sites in Kansas using a hollow-stem auger

    USGS Publications Warehouse

    Perry, C.A.; Hart, R.J.

    1985-01-01

    Noncontaminating procedures were used during the hollow-stem auger installation of 12 observation wells on three hazardous waste sites in Kansas. Special precautions were taken to ensure that water samples were representative of the ground water in the aquifer and were not subjected to contamination from the land surface or cross contamination from within borehole. Precautions included thorough cleaning of the hollow-stem auger and casing, keeping drill cuttings from falling back into the borehole while drilling, and not adding water to the borehole. These procedures were designed to prevent contamination of the ground water during well installation. Because of the use of water during well installation could contaminate the aquifer or dilute contaminants already present in the aquifer, two methods of well installation that did not introduce outside water to the borehole were used. The first method involved using a slotted 3/4 -inch coupling that was attached to the bit plate of the hollow-stem auger, allowing formation water to enter the auger, thereby preventing sand-plug formation. This method proved to be adequate, except when drilling through clay layers, which tended to clog the slotted coupling. The second method involved screened well swab that allowed only formation water to enter the hollow-stem auger and prevented sand from plugging the hollow-stem auger when the bit plate was removed.

  15. Outreach activities within Auger

    NASA Astrophysics Data System (ADS)

    López Ramírez, Rebeca; Snow, Gregory

    2009-04-01

    The scale and scope of the physics studied at the Auger Observatory offer significant opportunities for original outreach work. Education, outreach, and public relations of the Auger collaboration are coordinated in a task of its own whose goals are to encourage and support a wide range of efforts that link schools and the public with the Auger scientists and the science of cosmic rays, particle physics, and associated technologies. This report focuses on the impact of the collaboration in Mendoza Province, Argentina, as: the Auger Visitor Center in Malargüe that has hosted over 29,000 visitors since 2001, the Auger Celebration and a collaboration-sponsored science fair held on the Observatory campus in November 2005, the opening of the James Cronin School in Malargüe in November 2006, public lectures, school visits, and courses for science teachers.

  16. QS-21: a potent vaccine adjuvant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

  17. Pointable Auger

    NASA Technical Reports Server (NTRS)

    Lewis, E. V.

    1985-01-01

    Machine drills, crushes, and feeds coal - and seeks out extra-hard inclusions. Auger mounted on gimbal, located at its center of gravity for ease of maneuvering. Opposing hydraulic cylinders cooperate to point auger under control of microprocessor. Its diamond teeth break up coal seam, it crushes coal fed to it by mining machine jaws, and its screw action pushes crushed coal into slurry-forming chamber.

  18. Auger decay of Ar 2p satellite states studied with a multielectron coincidence method

    NASA Astrophysics Data System (ADS)

    Nakano, M.; Hikosaka, Y.; Lablanquie, P.; Penent, F.; Huttula, S.-M.; Suzuki, I. H.; Soejima, K.; Kouchi, N.; Ito, K.

    2012-04-01

    The Auger decay channels of the Ar 2p satellite states have been investigated using a multielectron coincidence technique, using a magnetic bottle time-of-flight electron spectrometer. For the Ar+(2p-13p-1np) satellite states the 2p hole is filled first, while for the Ar+(2p-13s-14s) satellite states the 3s hole is filled first with leading to Ar2+(2p-13p-1) states, which subsequently undergo an Auger decay leading to the filling of the 2p hole.

  19. Angle-Resolved Auger Spectroscopy as a Sensitive Access to Vibronic Coupling

    NASA Astrophysics Data System (ADS)

    Knie, A.; Patanen, M.; Hans, A.; Petrov, I. D.; Bozek, J. D.; Ehresmann, A.; Demekhin, Ph. V.

    2016-05-01

    In the angle-averaged excitation and decay spectra of molecules, vibronic coupling may induce the usually weak dipole-forbidden transitions by the excitation intensity borrowing mechanism. The present complementary theoretical and experimental study of the resonant Auger decay of core-to-Rydberg excited CH4 and Ne demonstrates that vibronic coupling plays a decisive role in the formation of the angle-resolved spectra by additionally involving the decay rate borrowing mechanism. Thereby, we propose that the angle-resolved Auger spectroscopy can in general provide very insightful information on the strength of the vibronic coupling.

  20. Auger injuries in children.

    PubMed Central

    Letts, R. M.; Gammon, W.

    1978-01-01

    A 6-year review of auger injuries in Manitoba children revealed that 23 children sustained major injuries resulting in amputation of 17 limbs. Auger injuries are the main cause of traumatic amputation in children in Manitoba. Improved safety education for the entire farm family as well as better design of safety shields would decrease this carnage. Images FIG. 1 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 9 PMID:630513

  1. Characterization of Japanese cedar bio-oil produced using a bench-scale auger pyrolyzer.

    PubMed

    Kato, Yoshiaki; Enomoto, Ryohei; Akazawa, Minami; Kojima, Yasuo

    2016-01-01

    A bench-scale auger reactor was designed for use as a laboratory-scale fast pyrolyzer for producing bio-oil from Japanese cedar. An analytical pyrolysis method was performed simultaneously to determine the distribution of pyrolysis products. The pyrolysis temperature was found to have the greatest influence on the bio-oil characteristics; bio-oil yields increased as the pyrolysis temperature increased from 450 to 550 °C. The concentration of levoglucosan in the bio-oil, however, decreased significantly with increasing pyrolysis temperature, while it increased following analytical pyrolysis. The same results were obtained for 4-vinylguaiacol and E-isoeugenol, which were the major secondary products produced in the present study. Compared to the yields of these major products obtained via analytical pyrolysis, the yields from the auger reactor were very low, indicating that the auger reactor process had a longer vapor residence time than the analytical pyrolysis process, resulting in the acceleration of secondary reactions of the pyrolysates. The pH values and densities of the bio-oils produced in the auger reactor were similar to those reported by researchers using woody biomass, despite their lower viscosities. From these results, it was concluded that the pyrolysis temperature and residence time of the pyrolysates played a significant role in determining the characteristics of the cedar bio-oil. PMID:27047705

  2. A new technique for Auger analysis of surface species subject to electron-induced desorption.

    NASA Technical Reports Server (NTRS)

    Pepper, S. V.

    1973-01-01

    A method is presented to observe surface species subject to electron-induced desorption by Auger electron spectroscopy. The surface to be examined is moved under the electron beam at constant velocity, establishing a time-independent condition and eliminating the time response of the electron spectrometer as a limiting factor. The dependence of the Auger signal on the sample velocity, incident electron current, beam diameter, and desorption cross section is analyzed. It is shown that it is advantageous to analyze the moving sample with a high beam current, in contrast to the usual practice of using a low beam current to minimize desorption from a stationary sample. The method is illustrated by the analysis of a friction transfer film of PTFE, in which the fluorine is removed by electron-induced desorption. The method is relevant to surface studies in the field of lubrication and catalysis.

  3. Nuclear Targeting with an Auger Electron Emitter Potentiates the Action of a Widely Used Antineoplastic Drug.

    PubMed

    Imstepf, Sebastian; Pierroz, Vanessa; Raposinho, Paula; Bauwens, Matthias; Felber, Michael; Fox, Thomas; Shapiro, Adam B; Freudenberg, Robert; Fernandes, Célia; Gama, Sofia; Gasser, Gilles; Motthagy, Felix; Santos, Isabel R; Alberto, Roger

    2015-12-16

    We present the combination of the clinically well-proven chemotherapeutic agent, Doxorubicin, and (99m)Tc, an Auger and internal conversion electron emitter, into a dual-action agent for therapy. Chemical conjugation of Doxorubicin to (99m)Tc afforded a construct which autonomously ferries a radioactive payload into the cell nucleus. At this site, damage is exerted by dose deposition from Auger radiation. The (99m)Tc-conjugate exhibited a dose-dependent inhibition of survival in a selected panel of cancer cells and an in vivo study in healthy mice evidenced a biodistribution which is comparable to that of the parent drug. The homologous Rhenium conjugate was found to effectively bind to DNA, inhibited human Topoisomerase II, and exhibited cytotoxicity in vitro. The collective in vitro and in vivo data demonstrate that the presented metallo-conjugates closely mimic native Doxorubicin. PMID:26473388

  4. A Scanning Auger Microprobe analysis of corrosion products associated with sulfate reducing bacteria

    SciTech Connect

    Sadowski, R.A.; Chen, G.; Clayton, C.R.; Kearns, J.R.; Gillow, J.B.; Francis, A.J.

    1995-03-01

    A Scanning Auger Microprobe analysis was performed on the corrosion products of an austenitic AISI type 304 SS after a potentiostatic polarization of one volt for ten minutes in a modified Postgate`s C media containing sulfate reducing bacteria. The corrosion products were characterized and mapped in local regions where pitting was observed. A critical evaluation of the applicability of this technique for the examination of microbially influenced corrosion (MIC) is presented.

  5. Education of the Pierre Auger Observatory: The Cinema as a Tool in Science Education.

    NASA Astrophysics Data System (ADS)

    Garcia, B.; Raschia, C.

    2006-08-01

    The Auger collaboration's broad mission in education, outreach and public relations is coordinated in a separate task. Its goals are to encourage and support a wide range of outreach efforts that link schools and the public with the Auger scientists and the science of cosmic rays, particle physics, astrophysics in general, and associated technologies. This report focuses on recent activities and future initiatives and, especially, on a very recent professional production of two educative videos for children between 6 and 11 years: "Messengers of Space" (18 min), and for general audiences: "An Adventure of the Mind" (20 min). The use of new resources, as 2D- and 3D-animation, to teach and learn in sciences is also discussed.

  6. A study of native oxides of beta-SiC using Auger electron spectroscopy

    NASA Technical Reports Server (NTRS)

    Chaudhry, M. Iqbal

    1989-01-01

    Thermal and anodic oxide films of beta-SiC are analyzed using Auger electron spectroscopy. Auger depth-composition profiles are obtained in order to determine the chemical composition of the oxide films. The position and shape of silicon spectral peaks are used to estimate the chemical bonding of the oxide constituents. It is found that the wet thermal oxide is almost stoichiometric but contains about 14 pct C. Dry oxide, on the other hand, has less than 3 pct C but is highly nonstoichiometric. The C content in the anodic oxide is 12 pct. Anodic oxide films, like dry-oxide films, are nonstoichiometric. A model of the SiC oxidation process is presented.

  7. A universal algorithm for calculating the backscattering factor in Auger-electron spectroscopy

    NASA Astrophysics Data System (ADS)

    Jablonski, A.; Powell, C. J.

    2007-02-01

    We describe a universal Monte Carlo algorithm that can be used for the efficient calculation of backscattering factors (BFs) for quantitative Auger-electron spectroscopy (AES). This algorithm makes use of the continuous slowing-down approximation and the electron stopping power instead of simulation of individual inelastic-scattering events. This approach is attractive because it can be applied to any material with an empirical formula for the stopping power, available data for differential elastic-scattering cross sections, and an empirical formula for inner-shell ionization cross sections. We report BFs for the Si KL 23L 23, Cu L 3M 45M 45, Ag M 5N 45N 45, and Au M 5N 67N 67 Auger transitions in the corresponding elemental solids. These BFs were calculated for normal incidence of the primary beam, primary energies from near threshold for ionization of the relevant core levels to 20 keV, and Auger-electron emission angles of 10°, 60°, and 80°. We found satisfactory agreement between these BFs and values obtained from a more accurate algorithm in which individual inelastic-scattering events were simulated. Percentage deviations between BFs from the two algorithms were <2% for Au, <5% for Ag, <7% for Cu, and <10% for Si for primary energies likely to be used in practical AES. These deviations arise mainly from our use of stopping powers from the empirical formula rather than more reliable values calculated from experimental optical data.

  8. Sifuvirtide, a potent HIV fusion inhibitor peptide

    SciTech Connect

    Wang, Rui-Rui; Yang, Liu-Meng; Wang, Yun-Hua; Pang, Wei; Tam, Siu-Cheung; Tien, Po; Zheng, Yong-Tang

    2009-05-08

    Enfuvirtide (ENF) is currently the only FDA approved HIV fusion inhibitor in clinical use. Searching for more drugs in this category with higher efficacy and lower toxicity seems to be a logical next step. In line with this objective, a synthetic peptide with 36 amino acid residues, called Sifuvirtide (SFT), was designed based on the crystal structure of gp41. In this study, we show that SFT is a potent anti-HIV agent with relatively low cytotoxicity. SFT was found to inhibit replication of all tested HIV strains. The effective concentrations that inhibited 50% viral replication (EC{sub 50}), as determined in all tested strains, were either comparable or lower than benchmark values derived from well-known anti-HIV drugs like ENF or AZT, while the cytotoxic concentrations causing 50% cell death (CC{sub 50}) were relatively high, rendering it an ideal anti-HIV agent. A GST-pull down assay was performed to confirm that SFT is a fusion inhibitor. Furthermore, the activity of SFT on other targets in the HIV life cycle was also investigated, and all assays showed negative results. To further understand the mechanism of action of HIV peptide inhibitors, resistant variants of HIV-1{sub IIIB} were derived by serial virus passage in the presence of increasing doses of SFT or ENF. The results showed that there was cross-resistance between SFT and ENF. In conclusion, SFT is an ideal anti-HIV agent with high potency and low cytotoxicity, but may exhibit a certain extent of cross-resistance with ENF.

  9. Application of a new vertical profiling tool (ESASS) for sampling groundwater quality during hollow-stem auger drilling

    USGS Publications Warehouse

    Harte, Philip T.; Flanagan, Sarah M.

    2011-01-01

    A new tool called ESASS (Enhanced Screen Auger Sampling System) was developed by the U.S. Geological Survey. The use of ESASS, because of its unique U.S. patent design (U.S. patent no. 7,631,705 B1), allows for the collection of representative, depth-specific groundwater samples (vertical profiling) in a quick and efficient manner using a 0.305-m long screen auger during hollow-stem auger drilling. With ESASS, the water column in the flights above the screen auger is separated from the water in the screen auger by a specially designed removable plug and collar. The tool fits inside an auger of standard inner diameter (82.55 mm). The novel design of the system constituted by the plug, collar, and A-rod allows the plug to be retrieved using conventional drilling A-rods. After retrieval, standard-diameter (50.8 mm) observation wells can be installed within the hollow-stem augers. Testing of ESASS was conducted at one waste-disposal site with tetrachloroethylene (PCE) contamination and at two reference sites with no known waste-disposal history. All three sites have similar geology and are underlain by glacial, stratified-drift deposits. For the applications tested, ESASS proved to be a useful tool in vertical profiling of groundwater quality. At the waste site, PCE concentrations measured with ESASS profiling at several depths were comparable (relative percent difference <25%) to PCE concentrations sampled from wells. Vertical profiling with ESASS at the reference sites illustrated the vertical resolution achievable in the profile system; shallow groundwater quality varied by a factor of five in concentration of some constituents (nitrate and nitrite) over short (0.61 m) distances.

  10. Application of a new vertical profiling tool (ESASS) for sampling groundwater quality during hollow-stem auger drilling

    USGS Publications Warehouse

    Harte, P.T.; Flanagan, S.M.

    2011-01-01

    A new tool called ESASS (Enhanced Screen Auger Sampling System) was developed by the U.S. Geological Survey. The use of ESASS, because of its unique U.S. patent design (U.S. patent no. 7,631,705 B1), allows for the collection of representative, depth-specific groundwater samples (vertical profiling) in a quick and efficient manner using a 0.305-m long screen auger during hollow-stem auger drilling. With ESASS, the water column in the flights above the screen auger is separated from the water in the screen auger by a specially designed removable plug and collar. The tool fits inside an auger of standard inner diameter (82.55 mm). The novel design of the system constituted by the plug, collar, and A-rod allows the plug to be retrieved using conventional drilling A-rods. After retrieval, standard-diameter (50.8 mm) observation wells can be installed within the hollow-stem augers. Testing of ESASS was conducted at one waste-disposal site with tetrachloroethylene (PCE) contamination and at two reference sites with no known waste-disposal history. All three sites have similar geology and are underlain by glacial, stratified-drift deposits. For the applications tested, ESASS proved to be a useful tool in vertical profiling of groundwater quality. At the waste site, PCE concentrations measured with ESASS profiling at several depths were comparable (relative percent difference <25%) to PCE concentrations sampled from wells. Vertical profiling with ESASS at the reference sites illustrated the vertical resolution achievable in the profile system; shallow groundwater quality varied by a factor of five in concentration of some constituents (nitrate and nitrite) over short (0.61 m) distances. Ground Water Monitoring & Remediation ?? 2011, National Ground Water Association. No claim to original US government works.

  11. 30 CFR 56.7005 - Augers and drill stems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Augers and drill stems. 56.7005 Section 56.7005... Piercing Drilling § 56.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a moving stem or auger....

  12. 30 CFR 56.7005 - Augers and drill stems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Augers and drill stems. 56.7005 Section 56.7005... Piercing Drilling § 56.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a moving stem or auger....

  13. 30 CFR 56.7005 - Augers and drill stems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Augers and drill stems. 56.7005 Section 56.7005... Piercing Drilling § 56.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a moving stem or auger....

  14. 30 CFR 56.7005 - Augers and drill stems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Augers and drill stems. 56.7005 Section 56.7005... Piercing Drilling § 56.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a moving stem or auger....

  15. 30 CFR 56.7005 - Augers and drill stems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Augers and drill stems. 56.7005 Section 56.7005... Piercing Drilling § 56.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a moving stem or auger....

  16. Search for a Correlation between ANTARES Neutrinos and Pierre Auger Observatory UHECRs Arrival Directions

    NASA Astrophysics Data System (ADS)

    Adrián-Martínez, S.; Samarai, I. Al; Albert, A.; André, M.; Anghinolfi, M.; Anton, G.; Anvar, S.; Ardid, M.; Astraatmadja, T.; Aubert, J.-J.; Baret, B.; Basa, S.; Beemster, L. J.; Bertin, V.; Biagi, S.; Bigongiari, C.; Bogazzi, C.; Bou-Cabo, M.; Bouhou, B.; Bouwhuis, M. C.; Brunner, J.; Busto, J.; Camarena, F.; Capone, A.; Cârloganu, C.; Carminati, G.; Carr, J.; Cecchini, S.; Charif, Z.; Charvis, Ph.; Chiarusi, T.; Circella, M.; Coniglione, R.; Core, L.; Costantini, H.; Coyle, P.; Creusot, A.; Curtil, C.; De Bonis, G.; Decowski, M. P.; Dekeyser, I.; Deschamps, A.; Distefano, C.; Donzaud, C.; Dornic, D.; Dorosti, Q.; Drouhin, D.; Eberl, T.; Emanuele, U.; Enzenhöfer, A.; Ernenwein, J.-P.; Escoffier, S.; Fehn, K.; Fermani, P.; Ferri, M.; Ferry, S.; Flaminio, V.; Folger, F.; Fritsch, U.; Fuda, J.-L.; Galatà, S.; Gay, P.; Geyer, K.; Giacomelli, G.; Giordano, V.; Gómez-González, J. P.; Graf, K.; Guillard, G.; Halladjian, G.; Hallewell, G.; van Haren, H.; Hartman, J.; Heijboer, A. J.; Hello, Y.; Hernández-Rey, J. J.; Herold, B.; Hößl, J.; Hsu, C. C.; de Jong, M.; Kadler, M.; Kalekin, O.; Kappes, A.; Katz, U.; Kavatsyuk, O.; Kooijman, P.; Kopper, C.; Kouchner, A.; Kreykenbohm, I.; Kulikovskiy, V.; Lahmann, R.; Lambard, G.; Larosa, G.; Lattuada, D.; Lefèvre, D.; Lim, G.; Lo Presti, D.; Loehner, H.; Loucatos, S.; Louis, F.; Mangano, S.; Marcelin, M.; Margiotta, A.; Martínez-Mora, J. A.; Meli, A.; Montaruli, T.; Morganti, N.; Moscoso, L.; Motz, H.; Neff, M.; Nezri, E.; Palioselitis, D.; Păvălaş, G. E.; Payet, K.; Payre, P.; Petrovic, J.; Picot-Clemente, N.; Popa, V.; Pradier, T.; Presani, E.; Racca, C.; Reed, C.; Riccobene, G.; Richardt, C.; Richter, R.; Rivière, C.; Robert, A.; Roensch, K.; Rostovtsev, A.; Ruiz-Rivas, J.; Rujoiu, M.; Russo, G. V.; Salesa, F.; Samtleben, D. F. E.; Sánchez-Losa, A.; Sapienza, P.; Schöck, F.; Schuller, J.-P.; Schüssler, F.; Seitz, T.; Shanidze, R.; Simeone, F.; Spies, A.; Spurio, M.; Steijger, J. J. M.; Stolarczyk, Th.; Taiuti, M.; Tamburini, C.; Toscano, S.; Vallage, B.; Vallée, C.; Van Elewyck, V.; Vannoni, G.; Vecchi, M.; Vernin, P.; Visser, E.; Wagner, S.; Wijnker, G.; Wilms, J.; de Wolf, E.; Yepes, H.; Zaborov, D.; Zornoza, J. D.; Zúñiga, J.

    2013-09-01

    A multimessenger analysis optimized for a correlation of arrival directions of ultra-high energy cosmic rays (UHECRs) and neutrinos is presented and applied to 2190 neutrino candidate events detected in 2007-2008 by the ANTARES telescope and 69 UHECRs observed by the Pierre Auger Observatory between 2004 January 1 and 2009 December 31. No significant correlation is observed. Assuming an equal neutrino flux (E -2 energy spectrum) from all UHECR directions, a 90% CL upper limit on the neutrino flux of 5.0 × 10-8 GeV cm-2 s-1 per source is derived.

  17. Xenon N4,500 Auger spectrum - a useful calibration source

    SciTech Connect

    Carroll, T.X.; Bozek, J.D.; Kukk, E.; Myrseth, V.; Saethre, L.J.; Thomas, T.D.; Wiesner, Karoline

    2002-02-06

    In the xenon N4,5OO Auger spectrum there are 19 prominent lines ranging from 8 to 36 eV that provide a convenient set of standards for calibrating electron spectrometers. Combining optical data with recent measurements of this spectrum gives energies for these lines that are absolutely accurate to 11 meV. For most lines the relative accuracy is better than 1 meV; for a few it is about 3 meV. The spin-orbit splitting of the xenon 4d lines is measured to be 1979.0 +- 0.5meV.

  18. Chemisorption of Si on Al(111) surfaces: A local-chemical-bond analysis from Auger transition density of states

    NASA Astrophysics Data System (ADS)

    Muñoz, M. C.; Sacedón, J. L.; Soria, F.; Martinez, V.

    1986-07-01

    Auger and electron loss spectroscopies have been used to study the local chemical bond between Si and Al, in the first stages of growth of Si deposited at room temperature on Al(111) surfaces. Si follows a layer-by-layer mechanism up to 2 monolayers with the formation of an Al(111)-3 × 3-Si structure at about 0.44 monolayers. A detailed analysis of the L 2,3VV Auger spectra for this structure allows to interpret the Si and Al Auger transition density of states (TDOS) in terms of the actual p-like partial DOS centered on the Si and Al sites. The experimental results indicate a strong SiAl interaction with the formation of a p-type local covalent bond between the Si and Al surface atoms.

  19. Looking for Auger signatures in III-nitride light emitters: A full-band Monte Carlo perspective

    SciTech Connect

    Bertazzi, Francesco Goano, Michele; Zhou, Xiangyu; Calciati, Marco; Ghione, Giovanni; Matsubara, Masahiko; Bellotti, Enrico

    2015-02-09

    Recent experiments of electron emission spectroscopy (EES) on III-nitride light-emitting diodes (LEDs) have shown a correlation between droop onset and hot electron emission at the cesiated surface of the LED p-cap. The observed hot electrons have been interpreted as a direct signature of Auger recombination in the LED active region, as highly energetic Auger-excited electrons would be collected in long-lived satellite valleys of the conduction band so that they would not decay on their journey to the surface across the highly doped p-contact layer. We discuss this interpretation by using a full-band Monte Carlo model based on first-principles electronic structure and lattice dynamics calculations. The results of our analysis suggest that Auger-excited electrons cannot be unambiguously detected in the LED structures used in the EES experiments. Additional experimental and simulative work are necessary to unravel the complex physics of GaN cesiated surfaces.

  20. Calculations of Auger intensity versus beam position for a sample with layers perpendicular to its surface

    NASA Astrophysics Data System (ADS)

    Zommer, L.; Jablonski, A.

    2010-07-01

    Recent advances in nanotechnology are a driving force for the improvement of lateral resolution in advanced analytical techniques such as scanning electron microscopy or scanning Auger microscopy (SAM). Special samples with multilayers which are perpendicular to their surface are presently proposed for testing the lateral resolution, as discussed in recent works of Senoner et al (2004 Surf. Interface Anal. 36 1423). The relevant experiment needs a theoretical description based on recent progress in the theory. Monte Carlo simulations of electron trajectories make possible an accurate description of the considered system. We selected exemplary samples, with layers perpendicular to the surface. The layer materials are elemental solids with high, medium and low atomic numbers, i.e. Au|Cu|Au and Au|Si|Au. For these systems calculations of the Auger current versus beam position were performed. We found that, for a system with layers consisting of elements of considerably different atomic numbers, the relation can have an unexpected extreme. This observation can be important in analysis of SAM pictures.

  1. A new route to nanoscale tomographic chemical analysis: Focused ion beam-induced auger electron spectrosocpy

    NASA Astrophysics Data System (ADS)

    Parvaneh, Hamed

    This research project is aimed to study the application of ion-induced Auger electron spectroscopy (IAES) in combination with the characteristics of focused ion beam (FIB) microscopy for performing chemical spectroscopy and further evaluate its potential for 3-dimensional chemical tomography applications. The mechanism for generation of Auger electrons by bombarding ions is very different from its electron induced counterpart. In the conventional electron-induced Auger electron spectroscopy (EAES), an electron beam with energy typically in the range 1-10kV is used to excite inner-shell (core) electrons of the solid. An electron from a higher electron energy state then de-excites to fill the hole and the extra energy is then transferred to either another electron, i.e. the Auger electron, or generation of an X-ray (photon). In both cases the emitting particles have charac-teristic energies and could be used to identify the excited target atoms. In IAES, however, large excitation cross sections can occur by promotion of in-ner shell electrons through crossing of molecular orbitals. Originally such phenomenological excitation processes were first proposed [3] for bi-particle gas phase collision systems to explain the generation of inner shell vacancies in violent collisions. In addition to excitation of incident or target atoms, due to a much heavier mass of ions compared to electrons, there would also be a substantial momentum transfer from the incident to the target atoms. This may cause the excited target atom to recoil from the lattice site or alternatively sputter off the surface with the possibility of de-excitation while the atom is either in motion in the matrix or traveling in vacuum. As a result, one could expect differences between the spectra induced by incident electrons and ions and interpretation of the IAE spectra requires separate consideration of both excitation and decay processes. In the first stage of the project, a state-of-the-art mass

  2. The Auger Star Monitor

    NASA Astrophysics Data System (ADS)

    Diaz, Johana; Nitz, David; Fick, Brian

    2006-04-01

    The Auger Star Monitor (ASM) is designed to automatically measure the total vertical atmospheric extinction above the Auger Observatory. The system continually takes wide-field CCD images of the night sky through a Johnson U-Band filter. Photometry is performed on the star images. The change in recorded star brightness as a function of zenith angle is used to obtain values for the integrated density of atmospheric scattering components. The MTU group has installed two ASMs; one at the Southern Observatory atop the Los Leones Fluorescence Detector building and one at the future site of the Northern Observatory in Colorado. Both of these units have been routinely operating during the past year. Much of our effort has turned to developing better data-reduction algorithms and automated software. Significant work has done to perfect the algorithms for image processing, star identification and photometry. Partial results of extinction coefficients obtained by the ASM will be presented.

  3. Discovery of a Potent And Selective Aurora Kinase Inhibitor

    SciTech Connect

    Oslob, J.D.; Romanowski, M.J.; Allen, D.A.; Baskaran, S.; Bui, M.; Elling, R.A.; Flanagan, W.M.; Fung, A.D.; Hanan, E.J.; Harris, S.; Heumann, S.A.; Hoch, U.; Jacobs, J.W.; Lam, J.; Lawrence, C.E.; McDowell, R.S.; Nannini, M.A.; Shen, W.; Silverman, J.A.; Sopko, M.M.; Tangonan, B.T.

    2009-05-21

    This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.

  4. Vertically reciprocating auger

    NASA Technical Reports Server (NTRS)

    Etheridge, Mark; Morgan, Scott; Fain, Robert; Pearson, Jonathan; Weldi, Kevin; Woodrough, Stephen B., Jr.

    1988-01-01

    The mathematical model and test results developed for the Vertically Reciprocating Auger (VRA) are summarized. The VRA is a device capable of transporting cuttings that result from below surface drilling. It was developed chiefly for the lunar surface, where conventional fluid flushing while drilling would not be practical. The VRA uses only reciprocating motion and transports material through reflections with the surface above. Particles are reflected forward and land ahead of radially placed fences, which prevent the particles from rolling back down the auger. Three input wave forms are considered to drive the auger. A modified sawtooth wave form was chosen for testing, over a modified square wave or sine wave, due to its simplicity and effectiveness. The three-dimensional mathematical model predicted a sand throughput rate of 0.2667 pounds/stroke, while the actual test setup transported 0.075 pounds/stroke. Based on this result, a correction factor of 0.281 is suggested for a modified sawtooth input.

  5. Coal-Sizing Auger

    NASA Technical Reports Server (NTRS)

    Lewis, E. V.

    1985-01-01

    Aft end of auger, like forward, face-piercing end, equipped with hard cutting bits such as diamonds. As auger breaks face, pulls broken coal lumps into jaws and forces them into hardened throat section. There, cutting bits chew up lumps: Clearance between throat and auger shaft sets maximum size for coal particles that pass through. Auger motion pushes coal particles into mixing chamber, where paddles combine them with water.

  6. Operations of and Future Plans for the Pierre Auger Observatory

    SciTech Connect

    Abraham, : J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Ahn, E.J.; Allard, D.; Allekotte, I.; Allen, J.; Alvarez-Muniz, J.; Ambrosio, M.; Anchordoqui, L.

    2009-06-01

    These are presentations to be presented at the 31st International Cosmic Ray Conference, in Lodz, Poland during July 2009. It consists of the following presentations: (1) Performance and operation of the Surface Detectors of the Pierre Auger Observatory; (2) Extension of the Pierre Auger Observatory using high-elevation fluorescence telescopes (HEAT); (3) AMIGA - Auger Muons and Infill for the Ground Array of the Pierre Auger Observatory; (4) Radio detection of Cosmic Rays at the southern Auger Observatory; (5) Hardware Developments for the AMIGA enhancement at the Pierre Auger Observatory; (6) A simulation of the fluorescence detectors of the Pierre Auger Observatory using GEANT 4; (7) Education and Public Outreach at the Pierre Auger Observatory; (8) BATATA: A device to characterize the punch-through observed in underground muon detectors and to operate as a prototype for AMIGA; and (9) Progress with the Northern Part of the Pierre Auger Observatory.

  7. A Complete Set of Radiative and Auger Rates for K-vacancy States in Fe XVIII-Fe-XXV

    NASA Technical Reports Server (NTRS)

    Palmeri, P.; Mendoza, C.; Kallman, T. R.; Bautista, M. A.

    2003-01-01

    A complete set of level energies, wavelengths, A-values, and total and partial Auger rates have been computed for transitions involving the K-vacancy states within the n = 2 complex of Fe XVIII-Fe XXV. Three different standard numerical packages are used for this purpose, namel y AUTOSTRUCTURE, the Breit-Pauli R-matrix suite (BPRM) and HFR, which allow reliable estimates of the physical effects involved and of the accuracy of the resulting data sets. The Breit interaction is taken i nto account because its contributions to the small A-values and partial Auger rates cannot be neglected with increasing electron occupancy. Semiempirical adjustments can also lead to large differences in both the radiative and Auger decay data of strongly mixed levels. Several experimental level energies and wavelengths are questioned, and significant discrepancies are found with previously computed decay rates th at are attributed to numerical problems. The statistical accuracy of the present level energies and wavelengths is ranked at +/-3 eV and +/ -2 mA, respectively, and that for A-values and partial Auger rates greater than lO(exp 13)/s at better than 20%.

  8. Vertical-Screw-Auger Conveyer Feeder

    NASA Technical Reports Server (NTRS)

    Walton, Otis (Inventor); Vollmer, Hubert J. (Inventor)

    2016-01-01

    A conical feeder is attached to a vertically conveying screw auger. The feeder is equipped with scoops and rotated from the surface to force-feed regolith the auger. Additional scoops are possible by adding a cylindrical section above the conical funnel section. Such then allows the unit to collect material from swaths larger in diameter than the enclosing casing pipe of the screw auger. A third element includes a flexible screw auger. All three can be used in combination in microgravity and zero atmosphere environments to drill and recover a wide area of subsurface regolith and entrained volatiles through a single access point on the surface.

  9. A Complete Set of Radiative and Auger Rates for K-vacancy States in Fe XVIII-Fe XXV

    NASA Technical Reports Server (NTRS)

    Palmeri, P.; Mendoza, C.; Kallman, T. R.; Bautista, M. A.

    2002-01-01

    A complete set of level energies, wavelengths, A-values, and total and partial Auger rates have been computed for transitions involving the K-vacancy states within the n = 2 complex of Fe XVIII-Fe XXV. Three different standard numerical packages are used for this purpose, namely AUTOSTRUCTURE, the Breit-Pauli R-matrix suite (BPRM) and HFR, which allow reliable estimates of the physical effects involved and of the accuracy of the resulting data sets. It is found that the Breit interaction must be always taken into account as the contributions to the small A-values and partial Auger rates does not decrease with electron occupancy. Semi-empirical adjustments can also lead to large differences in both the radiative and Auger decay data of strongly mixed levels. Several experimental energy levels and wavelengths are questioned, and significant discrepancies are found with previously computed decay rates that are attributed to numerical problems. The statistical accuracy of the present level energies and wavelengths is ranked at plus or minus 3 eV and plus or minus 2 mAngstroms, respectively, whereas that for A-values and partial Auger rates greater than 10(exp 13) per second is estimated at better than 20%.

  10. New method for atmospheric calibration at the Pierre Auger Observatory using FRAM, a robotic astronomical telescope

    NASA Astrophysics Data System (ADS)

    Trávníček, Petr; Benzvi, Segev; Boháčová, Martina; Connolly, Brian; Grygar, Jiří; Hrabovský, Miroslav; Kárová, Tatiana; Mandát, Dušan; Nečesal, Petr; Nosek, Dalibor; Nožka, Libor; Palatka, Miroslav; sPech, Miroslav; Prouza, Michael; Řídký, Jan; Schovánek, Petr; Šmída, Radomír; Vitale, Primo; Westerhoff, Stefan

    FRAM - F/(Ph)otometric Robotic Atmospheric Monitor is the latest addition to the atmospheric monitoring instruments of the Pierre Auger Observatory. An optical telescope equipped with CCD camera and photometer, it automatically observes a set of selected standard stars and a calibrated terrestrial source. Primarily, the wavelength dependence of the attenuation is derived and the comparison between its vertical values (for stars) and horizontal values (for the terrestrial source) is made. Further, the integral vertical aerosol optical depth can be obtained. A secondary program of the instrument, the detection of optical counterparts of gamma-ray bursts, has already proven successful. The hardware setup, software system, data taking procedures, and first analysis results are described in this paper.

  11. Comparison of Numerical Analyses with a Static Load Test of a Continuous Flight Auger Pile

    NASA Astrophysics Data System (ADS)

    Hoľko, Michal; Stacho, Jakub

    2014-12-01

    The article deals with numerical analyses of a Continuous Flight Auger (CFA) pile. The analyses include a comparison of calculated and measured load-settlement curves as well as a comparison of the load distribution over a pile's length. The numerical analyses were executed using two types of software, i.e., Ansys and Plaxis, which are based on FEM calculations. Both types of software are different from each other in the way they create numerical models, model the interface between the pile and soil, and use constitutive material models. The analyses have been prepared in the form of a parametric study, where the method of modelling the interface and the material models of the soil are compared and analysed. Our analyses show that both types of software permit the modelling of pile foundations. The Plaxis software uses advanced material models as well as the modelling of the impact of groundwater or overconsolidation. The load-settlement curve calculated using Plaxis is equal to the results of a static load test with a more than 95 % degree of accuracy. In comparison, the load-settlement curve calculated using Ansys allows for the obtaining of only an approximate estimate, but the software allows for the common modelling of large structure systems together with a foundation system.

  12. Auger analysis of a fiber/matrix interface in a ceramic matrix composite

    NASA Technical Reports Server (NTRS)

    Honecy, Frank S.; Pepper, Stephen V.

    1988-01-01

    Auger electron spectroscopy (AES) depth profiling was used to characterize the fiber/matrix interface of an SiC fiber, reaction bonded Si3N4 matrix composite. Depth profiles of the as received double coated fiber revealed concentration oscillations which disappeared after annealing the fiber in the environment used to fabricate the composite. After the composite was fractured, the Auger depth profiles showed that failure occurred in neither the Beta-SiC fiber body nor in the Si3N4 matrix but, concurrently, at the fiber coating/matrix interface and within the fiber coating itself.

  13. A new potent immunosuppressive isoflavanonol from Campylotropis hirtella.

    PubMed

    Xuan, Bixia; Du, Xing; Li, Xiaoping; Shen, Zhengwu

    2016-06-01

    Four new flavonoids were isolated from Campylotropis hirtella and these are a chromone and a 2H-chromene, an isoflavone and an isoflavanonol. The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Compound 4 showed very strong T lymphocyte suppression activity (IC50: 0.13 μM) and potent B lymphocyte suppression activity (IC50: 0.26 μM). Due to its potent immunosuppressive activity and lower cytotoxicity, further structure-activity studies will be pursued on this compound. PMID:26221996

  14. Presidents' Pay Remains a Potent Political Target

    ERIC Educational Resources Information Center

    Stripling, Jack; Fuller, Andrea

    2012-01-01

    In a long-simmering national fight over compensation for public-college presidents, the State of California emerged this year as the primary battleground. More than any other institution in recent memory, California State University has publicly and sometimes bitterly wrestled with a vexing question for higher education: How much does a public…

  15. Dihydro-resveratrol-A potent dietary polyphenol

    SciTech Connect

    Gakh, Andrei A; Anisimova, Natalia Yu; Kiselevsky, Mikhail V; Sadovnikov, Sergey V; Stankov, Ivan N; Yudin, Mikhail V; Rufanov, Konstantin A; Krasavin, Mikhail Yu; Sosnov, Andrey V

    2010-01-01

    Dihydro-resveratrol (dihydro-R), a prominent polyphenol component of red wine, has a profound proliferative effect on hormone-sensitive tumor cell lines such as breast cancer cell line MCF7. We found a significant increase in MCF7 tumor cells growth rates in the presence of picomolar concentrations of this compound. The proliferative effect of dihydro-R was not observed in cell lines that do not express hormone receptors (MDA-MB-231, BT-474, and -562).

  16. A potent probiotic strain from cheddar cheese.

    PubMed

    Shobharani, P; Agrawal, Renu

    2011-07-01

    A lactic acid bacteria Leuconostoc paramesenteroides was isolated and characterized from cheddar cheese and was adapted to grow at low pH (2.0) and high bile salt concentration (2%) by sequential sub-culturing so that it can survive the extreme environmental condition of gut. Cell hydrophobicity assay shows the maximum adherence of the culture to toluene (46.11%). Adhesion ability was confirmed by in vitro assay using rat intestinal epithelial layer. The culture has an antimicrobial activity against food borne pathogens and is vancomycin sensitive. The culture shows a β-galactosidase activity of 3.42 μM/mg protein, which indicates the ability of the culture to hydrolyze lactose for easy absorption. All these properties determine the ability of the culture to be used as a probiotic. PMID:22753999

  17. Ganoderma lucidum: a potent pharmacological macrofungus.

    PubMed

    Sanodiya, Bhagwan S; Thakur, Gulab Singh; Baghel, Rakesh K; Prasad, G B K S; Bisen, P S

    2009-12-01

    Ganoderma lucidum (Ling Zhi) is a basidiomycete white rot macrofungus which has been used extensively as "the mushroom of immortality" in China, Japan, Korea and other Asian countries for 2000 years. A great deal of work has been carried out on therapeutic potential of Ganoderma lucidum. The basidiocarp, mycelia and spores of Ganoderma lucidum contain approximately 400 different bioactive compounds, which mainly include triterpenoids, polysaccharides, nucleotides, sterols, steroids, fatty acids, proteins/peptides and trace elements which has been reported to have a number of pharmacological effects including immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemo-preventive, antitumor, chemo and radio protective, sleep promoting, antibacterial, antiviral (including anti-HIV), hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, anti-androgenic, anti-angiogenic, anti-herpetic, antioxidative and radical-scavenging, anti-aging, hypoglycemic, estrogenic activity and anti-ulcer properties. Ganoderma lucidum has now become recognized as an alternative adjuvant in the treatment of leukemia, carcinoma, hepatitis and diabetes. The macrofungus is very rare in nature rather not sufficient for commercial exploitation for vital therapeutic emergencies, therefore, the cultivation on solid substrates, stationary liquid medium or by submerged cultivation has become an essential aspect to meet the driving force towards the increasing demands in the international market. Present review focuses on the pharmacological aspects, cultivation methods and bioactive metabolites playing a significant role in various therapeutic applications. PMID:19939212

  18. Hesperetin: a potent antioxidant against peroxynitrite.

    PubMed

    Kim, Ji Young; Jung, Kyung Jin; Choi, Jae Sue; Chung, Hae Young

    2004-07-01

    Peroxynitrite (ONOO-) is a reactive oxidant formed from superoxide (*O2(-)) and nitric oxide (*NO), that can oxidize several cellular components, including essential protein, non-protein thiols, DNA, low-density lipoproteins (LDL), and membrane phospholipids. ONOO- has contributed to the pathogenesis of diseases such as stroke, heart disease, Alzheimer's disease, and atherosclerosis. Because of the lack of endogenous enzymes to thwart ONOO- activation, developing a specific ONOO- scavenger is remarkably important. In this study, the ability of hesperetin (3',5,7-trihydroxy-4-methoxyflavanone) to scavenge ONOO- and to protect cells against ONOO- and ROS was investigated. The data gained show that hesperetin can efficiently scavenge authentic ONOO- . In spectrophotometric analysis, the data revealed that hesperetin led to declined ONOO- -mediated nitration of tyrosine through electron donation. Hesperetin exhibited significant inhibition on the nitration of bovine serum albumin (BSA) by ONOO- in a dose-dependent manner. Hesperetin also manifested cytoprotection from cell damage induced by ONOO- and ROS. The present study suggests that hesperetin is a powerful ONOO- scavenger and promotes cellular defense activity in the protection against ONOO- involved diseases. PMID:15453641

  19. Diethylamide of thujic acid: a potent repellent of Aedes aegypti.

    PubMed

    Hach, V; McDonald, E C

    1971-10-01

    A series of novel, representatively substituted amides of thujic acid were prepared and screened for insect repellent and attractant potential. In repel-lency tests the N,N-diethylamide was the most potent compound, surpassing the activity of the standard repellents dimethyl phthalate and fencholic acid. In contrast, the N-monoethylamide displayed attractant activity. PMID:5119622

  20. Discovery of DF-461, a Potent Squalene Synthase Inhibitor

    PubMed Central

    2013-01-01

    We report the development of a new trifluoromethyltriazolobenzoxazepine series of squalene synthase inhibitors. Structure–activity studies and pharmacokinetics optimization on this series led to the identification of compound 23 (DF-461), which exhibited potent squalene synthase inhibitory activity, high hepatic selectivity, excellent rat hepatic cholesterol synthesis inhibitory activity, and plasma lipid lowering efficacy in nonrodent repeated dose studies. PMID:24900587

  1. Oleandrin: A cardiac glycosides with potent cytotoxicity

    PubMed Central

    Kumar, Arvind; De, Tanmoy; Mishra, Amrita; Mishra, Arun K.

    2013-01-01

    Cardiac glycosides are used in the treatment of congestive heart failure and arrhythmia. Current trend shows use of some cardiac glycosides in the treatment of proliferative diseases, which includes cancer. Nerium oleander L. is an important Chinese folk medicine having well proven cardio protective and cytotoxic effect. Oleandrin (a toxic cardiac glycoside of N. oleander L.) inhibits the activity of nuclear factor kappa-light-chain-enhancer of activated B chain (NF-κB) in various cultured cell lines (U937, CaOV3, human epithelial cells and T cells) as well as it induces programmed cell death in PC3 cell line culture. The mechanism of action includes improved cellular export of fibroblast growth factor-2, induction of apoptosis through Fas gene expression in tumor cells, formation of superoxide radicals that cause tumor cell injury through mitochondrial disruption, inhibition of interleukin-8 that mediates tumorigenesis and induction of tumor cell autophagy. The present review focuses the applicability of oleandrin in cancer treatment and concerned future perspective in the area. PMID:24347921

  2. Towards a Joint Analysis of Data from the IceCube Neutrino Telescope, the Pierre Auger Observatory and Telescope Array

    NASA Astrophysics Data System (ADS)

    Christov; Golup, G.; Montaruli, T.; Rameez, M.; Aublin, J.; Caccianiga, L.; Ghia, P. L.; Roulet, E.; Unger, M.; Sagawa, H.; Tinyakov, P.

    A joint point-source analysis to search for correlations between the arrival directions of neutrinos and ultra-high energy cosmic rays (UHECRs) is being planned by the IceCube, Pierre Auger and Telescope Array Collaborations. A cross-correlation analysis will be performed using ten years of Auger data, six years of Telescope Array data and a signal-rich set of neutrino candidate events detected at IceCube. Also, a likelihood analysis will be applied to the same sample of neutrinos, stacking their arrival directions, and to UHECRs. Finally, another likelihood analysis will be performed on stacked UHECRs and the IceCube 4-year sample of clean, through-going muons that could be associated with charged-current muon neutrino interactions. An outline of the analyses, their sensitivities and discovery potentials is presented here.

  3. Enhancement of double auger decay probability in xenon clusters irradiated with a soft-x-ray laser pulse.

    PubMed

    Namba, S; Hasegawa, N; Nishikino, M; Kawachi, T; Kishimoto, M; Sukegawa, K; Tanaka, M; Ochi, Y; Takiyama, K; Nagashima, K

    2007-07-27

    The interaction of large Xe clusters with a soft x-ray laser pulse having a wavelength of 13.9 nm and an intensity of up to 2x10(10) W/cm2 was investigated using a time-of-flight ion mass spectrometer. The corresponding laser photon energy was sufficiently high to photoionize Xe 4d innershell electrons. It was found that Xe3+ ions (which result from double Auger decay of 4d vacancies) became the dominant final ionic product with increasing cluster size and x-ray intensity. This is in contrast to the results of synchrotron radiation experiments involving free Xe atoms, in which Xe2+ is the dominant resultant ion species. Possible mechanisms responsible for the enhancement of the double Auger transition probability in x-ray laser and cluster interaction are discussed. PMID:17678361

  4. Positron annihilation induced Auger electron spectroscopy

    NASA Technical Reports Server (NTRS)

    Weiss, Alex; Koymen, A. R.; Mehl, David; Jensen, K. O.; Lei, Chun; Lee, K. H.

    1990-01-01

    Recently, Weiss et al. have demonstrated that it is possible to excite Auger transitions by annihilating core electrons using a low energy (less than 30eV) beam of positrons. This mechanism makes possible a new electron spectroscopy, Positron annihilation induced Auger Electron Spectroscopy (PAES). The probability of exciting an Auger transition is proportional to the overlap of the positron wavefunction with atomic core levels. Since the Auger electron energy provides a signature of the atomic species making the transition, PAES makes it possible to determine the overlap of the positron wavefunction with a particular element. PAES may therefore provide a means of detecting positron-atom complexes. Measurements of PAES intensities from clean and adsorbate covered Cu surfaces are presented which indicate that approx. 5 percent of positrons injected into CU at 25eV produce core annihilations that result in Auger transitions.

  5. Impact of a new Cerenkov light parameterisation on the reconstruction of shower profiles from Auger hybrid data

    SciTech Connect

    Nerling, Frank; Bluemer, J.; Engel, R.; Unger, M.; /Karlsruhe, Forschungszentrum

    2005-07-01

    The light signal measured by fluorescence telescopes receives--strongly depending on the shower geometry with respect to the detector--a non-negligible contribution from additionally produced Cherenkov light. This Cherenkov contribution has to be accounted for to determine primary parameters properly. In comparison to the previous ansatz used by other experiments, the impact of a new analytical description of Cherenkov light production in EAS on the Auger event reconstruction is investigated.

  6. 30 CFR 77.1501 - Auger mining; inspections.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Auger mining; inspections. 77.1501 Section 77.1501 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND... Auger Mining § 77.1501 Auger mining; inspections. (a) The face of all highwalls, to a distance of...

  7. 30 CFR 77.1501 - Auger mining; inspections.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Auger mining; inspections. 77.1501 Section 77.1501 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND... Auger Mining § 77.1501 Auger mining; inspections. (a) The face of all highwalls, to a distance of...

  8. 30 CFR 77.1501 - Auger mining; inspections.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Auger mining; inspections. 77.1501 Section 77.1501 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND... Auger Mining § 77.1501 Auger mining; inspections. (a) The face of all highwalls, to a distance of...

  9. 30 CFR 77.1501 - Auger mining; inspections.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Auger mining; inspections. 77.1501 Section 77.1501 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND... Auger Mining § 77.1501 Auger mining; inspections. (a) The face of all highwalls, to a distance of...

  10. 30 CFR 77.1501 - Auger mining; inspections.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Auger mining; inspections. 77.1501 Section 77.1501 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND... Auger Mining § 77.1501 Auger mining; inspections. (a) The face of all highwalls, to a distance of...

  11. Trigocherrierin A, a potent inhibitor of chikungunya virus replication.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Neyts, Johan; Dumontet, Vincent; Litaudon, Marc

    2014-01-01

    Trigocherrierin A (1) and trigocherriolide E (2), two new daphnane diterpenoid orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A-C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV) replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC₅₀ = 0.6 ± 0.1 µM, SI = 71.7). PMID:24662077

  12. Demonstration of the waste tire pyrolysis process on pilot scale in a continuous auger reactor.

    PubMed

    Martínez, Juan Daniel; Murillo, Ramón; García, Tomás; Veses, Alberto

    2013-10-15

    This work shows the technical feasibility for valorizing waste tires by pyrolysis using a pilot scale facility with a nominal capacity of 150 kWth. A continuous auger reactor was operated to perform thirteen independent experiments that conducted to the processing of more than 500 kg of shredded waste tires in 100 h of operation. The reaction temperature was 550°C and the pressure was 1 bar in all the runs. Under these conditions, yields to solid, liquid and gas were 40.5 ± 0.3, 42.6 ± 0.1 and 16.9 ± 0.3 wt.% respectively. Ultimate and proximate analyses as well as heating value analysis were conducted for both the solid and liquid fraction. pH, water content, total acid number (TAN), viscosity and density were also assessed for the liquid and compared to the specifications of marine fuels (standard ISO 8217). Gas chromatography was used to calculate the composition of the gaseous fraction. It was observed that all these properties remained practically invariable along the experiments without any significant technical problem. In addition, the reaction enthalpy necessary to perform the waste tire pyrolysis process (907.1 ± 40.0 kJ/kg) was determined from the combustion and formation enthalpies of waste tire and conversion products. Finally, a mass balance closure was performed showing an excellent reliability of the data obtained from the experimental campaign. PMID:23995560

  13. Evaluation of the effective solid angle of a hemispherical deflector analyser with injection lens for metastable Auger projectile states

    NASA Astrophysics Data System (ADS)

    Benis, E. P.; Doukas, S.; Zouros, T. J. M.; Indelicato, P.; Parente, F.; Martins, C.; Santos, J. P.; Marques, J. P.

    2015-12-01

    The accurate determination of the electron yield of a metastable projectile Auger state necessitates the careful evaluation of the corresponding effective solid angle, i.e. the geometrical solid angle convoluted with the decay time of the metastable state. Recently, we presented (Doukas et. al., 2015) SIMION Monte Carlo type simulations of the effective solid angle for long lived projectile Auger states (lifetime τ ∼10-9-10-5s) recorded by a hemispherical spectrograph with injection lens and position sensitive detector in the direction of the projectile ion. These results are important for the accurate evaluation of the 1 s 2 s 2 p4P/2 P ratio of K-Auger cross sections whose observed non-statistical production by electron capture into He-like ions, recently a field of interesting interpretations, awaits final resolution. Here we expand and systematize our investigation using the same techniques to expose universal behaviors of the effective solid angle covering life times of 1 s 2 s 2 p4P states for all first row ions. Our results are also compared to purely geometrical calculations of the solid angle that omit the lensing effects and serve as a benchmark for a deeper insight into the effect.

  14. A Bayesian analysis of the 69 highest energy cosmic rays detected by the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Khanin, Alexander; Mortlock, Daniel J.

    2016-08-01

    The origins of ultra-high energy cosmic rays (UHECRs) remain an open question. Several attempts have been made to cross-correlate the arrival directions of the UHECRs with catalogs of potential sources, but no definite conclusion has been reached. We report a Bayesian analysis of the 69 events from the Pierre Auger Observatory (PAO), that aims to determine the fraction of the UHECRs that originate from known AGNs in the Veron-Cety & Veron (VCV) catalog, as well as AGNs detected with the Swift Burst Alert Telescope (Swift-BAT), galaxies from the 2MASS Redshift Survey (2MRS), and an additional volume-limited sample of 17 nearby AGNs. The study makes use of a multi-level Bayesian model of UHECR injection, propagation and detection. We find that for reasonable ranges of prior parameters, the Bayes factors disfavour a purely isotropic model. For fiducial values of the model parameters, we report 68% credible intervals for the fraction of source originating UHECRs of 0.09+0.05-0.04, 0.25+0.09-0.08, 0.24+0.12-0.10, and 0.08+0.04-0.03 for the VCV, Swift-BAT and 2MRS catalogs, and the sample of 17 AGNs, respectively.

  15. A Bayesian analysis of the 69 highest energy cosmic rays detected by the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Khanin, Alexander; Mortlock, Daniel J.

    2016-08-01

    The origins of ultrahigh energy cosmic rays (UHECRs) remain an open question. Several attempts have been made to cross-correlate the arrival directions of the UHECRs with catalogues of potential sources, but no definite conclusion has been reached. We report a Bayesian analysis of the 69 events, from the Pierre Auger Observatory (PAO), that aims to determine the fraction of the UHECRs that originate from known AGNs in the Veron-Cety & Verson (VCV) catalogue, as well as AGNs detected with the Swift Burst Alert Telescope (Swift-BAT), galaxies from the 2MASS Redshift Survey (2MRS), and an additional volume-limited sample of 17 nearby AGNs. The study makes use of a multilevel Bayesian model of UHECR injection, propagation and detection. We find that for reasonable ranges of prior parameters the Bayes factors disfavour a purely isotropic model. For fiducial values of the model parameters, we report 68 per cent credible intervals for the fraction of source originating UHECRs of 0.09^{+0.05}_{-0.04}, 0.25^{+0.09}_{-0.08}, 0.24^{+0.12}_{-0.10}, and 0.08^{+0.04}_{-0.03} for the VCV, Swift-BAT and 2MRS catalogues, and the sample of 17 AGNs, respectively.

  16. The Fluorescence Detector of the Pierre Auger Observatory - a Calorimeter for UHECR

    SciTech Connect

    Keilhauer, B.

    2006-10-27

    The Pierre Auger Observatory is a hybrid detector for ultrahigh energy cosmic rays (UHECR) with energies above 1018.5 eV. Currently the first part of the Observatory nears completion in the southern hemisphere in Argentina. One detection technique uses over 1600 water Cherenkov tanks at ground where samples of secondary particles of extensive air showers (EAS) are detected. The second technique is a calorimetric measurement of the energy deposited by EAS in the atmosphere. Charged secondary particles of EAS lose part of their energy in the atmosphere via ionization. The deposited energy is converted into excitation of molecules of the air and afterwards partly emitted as fluorescence light mainly from nitrogen in the wavelength region between 300 and 400 nm. This light is observed with 24 fluorescence telescopes in 4 stations placed at the boundary of the surface array. This setup provides a combined measurement of the longitudinal shower development and the lateral particle distribution at ground of the same event. Details on the fluorescence technique and the necessary atmospheric monitoring will be presented, as well as first physics results on UHECR.

  17. 30 CFR 57.7005 - Augers and drill stems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Augers and drill stems. 57.7005 Section 57.7005... Jet Piercing Drilling-Surface Only § 57.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a...

  18. 30 CFR 819.15 - Auger mining: Hydrologic balance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Auger mining: Hydrologic balance. 819.15 Section 819.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE... MINING § 819.15 Auger mining: Hydrologic balance. (a) Auger mining shall be planned and conducted...

  19. 30 CFR 819.19 - Auger mining: Backfilling and grading.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Auger mining: Backfilling and grading. 819.19 Section 819.19 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE... MINING § 819.19 Auger mining: Backfilling and grading. (a) General. Auger mining shall be conducted...

  20. 30 CFR 819.15 - Auger mining: Hydrologic balance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Auger mining: Hydrologic balance. 819.15... MINING § 819.15 Auger mining: Hydrologic balance. (a) Auger mining shall be planned and conducted to minimize disturbances of the prevailing hydrologic balance in accordance with the requirements of §§...

  1. 30 CFR 819.15 - Auger mining: Hydrologic balance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Auger mining: Hydrologic balance. 819.15... MINING § 819.15 Auger mining: Hydrologic balance. (a) Auger mining shall be planned and conducted to minimize disturbances of the prevailing hydrologic balance in accordance with the requirements of §§...

  2. 30 CFR 819.15 - Auger mining: Hydrologic balance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Auger mining: Hydrologic balance. 819.15... MINING § 819.15 Auger mining: Hydrologic balance. (a) Auger mining shall be planned and conducted to minimize disturbances of the prevailing hydrologic balance in accordance with the requirements of §§...

  3. 30 CFR 819.15 - Auger mining: Hydrologic balance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Auger mining: Hydrologic balance. 819.15... MINING § 819.15 Auger mining: Hydrologic balance. (a) Auger mining shall be planned and conducted to minimize disturbances of the prevailing hydrologic balance in accordance with the requirements of §§...

  4. 30 CFR 57.7005 - Augers and drill stems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Augers and drill stems. 57.7005 Section 57.7005... Jet Piercing Drilling-Surface Only § 57.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a...

  5. 30 CFR 57.7005 - Augers and drill stems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Augers and drill stems. 57.7005 Section 57.7005... Jet Piercing Drilling-Surface Only § 57.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a...

  6. 30 CFR 57.7005 - Augers and drill stems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Augers and drill stems. 57.7005 Section 57.7005... Jet Piercing Drilling-Surface Only § 57.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a...

  7. 30 CFR 57.7005 - Augers and drill stems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Augers and drill stems. 57.7005 Section 57.7005... Jet Piercing Drilling-Surface Only § 57.7005 Augers and drill stems. Drill crews and others shall stay clear of augers or drill stems that are in motion. Persons shall not pass under or step over a...

  8. Measurement of the Spectral Distribution of Low Energy Electrons emitted as a result of MVV Auger Transition in Cu(100)

    NASA Astrophysics Data System (ADS)

    Satyal, Suman; Joglekar, P. V.; Shastry, K.; Weiss, A. H.; Hulbert, S. L.

    2011-10-01

    Auger Photoelectron Coincidence Spectroscopy (APECS) was used to investigate the physics of the Low Energy tail (LET) region of the Auger spectrum of a Cu (100) sample. A beam of 200eV photons was incident on the sample and two Cylindrical Mirror Analyzers (CMA's) were used to select the energy of electrons emitted from the sample. An APECS spectra was obtained with one of the CMA's fixed at the energy 136.25eV, which corresponds to the core photoemission peak. The APECS spectra contains the contributions from electrons excited by the MVV Auger transition plus a background due to true coincidences between photo-emitted valence band electrons that undergo inelastic scattering and transfer part of their energy with other valence electrons. Coincidence measurements were made with the fixed analyzer set at various energies between the core and the valence band. These measurements were used to obtain an estimate of the background due to the inelastically scattered valence band electrons.

  9. Properties of bio-oil generated by a pyrolysis of forest cedar residuals with the movable Auger-type reactor

    NASA Astrophysics Data System (ADS)

    Nishimura, Shun; Miyazato, Akio; Ebitani, Kohki

    2016-02-01

    Our research project has developed the new movable reactor for bio-oil production in 2013 on the basis of Auger-type system. This package would be a great impact due to the concept of local production for local consumption in the hilly and mountainous area in not only Japan but also in the world. Herein, we would like to report the properties of the bio-oil generated by the developing Auger-type movable reactor. The synthesized bio-oil possessed C: 46.2 wt%, H: 6.5 wt%, N: wt%, S: <0.1 wt%, O: 46.8 wt% and H2O: 18.4 wt%, and served a good calorific value of 18.1 MJ/kg. The spectroscopic and mass analyses such as FT-IR, GC-MS, 13C-NMR and FT-ICR MS supported that the bio-oil was composed by the fine mixtures of methoxy phenols and variety of alcohol or carboxylic acid functional groups. Thus, it is suggested that the bio-oil generated by the new movable Auger-type reactor has a significant potential as well as the existing bio-oil reported previously.

  10. Auger spectrum of a water molecule after single and double core ionization

    SciTech Connect

    Inhester, L.; Burmeister, C. F.; Groenhof, G.; Grubmueller, H.

    2012-04-14

    The high intensity of free electron lasers opens up the possibility to perform single-shot molecule scattering experiments. However, even for small molecules, radiation damage induced by absorption of high intense x-ray radiation is not yet fully understood. One of the striking effects which occurs under intense x-ray illumination is the creation of double core ionized molecules in considerable quantity. To provide insight into this process, we have studied the dynamics of water molecules in single and double core ionized states by means of electronic transition rate calculations and ab initio molecular dynamics (MD) simulations. From the MD trajectories, photoionization and Auger transition rates were computed based on electronic continuum wavefunctions obtained by explicit integration of the coupled radial Schroedinger equations. These rates served to solve the master equations for the populations of the relevant electronic states. To account for the nuclear dynamics during the core hole lifetime, the calculated electron emission spectra for different molecular geometries were incoherently accumulated according to the obtained time-dependent populations, thus neglecting possible interference effects between different decay pathways. We find that, in contrast to the single core ionized water molecule, the nuclear dynamics for the double core ionized water molecule during the core hole lifetime leaves a clear fingerprint in the resulting electron emission spectra. The lifetime of the double core ionized water was found to be significantly shorter than half of the single core hole lifetime.

  11. Angular distributions of molecular Auger electrons: The case of C 1s Auger emission in CO

    SciTech Connect

    Semenov, S. K.; Kuznetsov, V. V.; Cherepkov, N. A.; Bolognesi, P.; Feyer, V.; Lahmam-Bennani, A.; Casagrande, M. E. Staicu; Avaldi, L.

    2007-03-15

    The results of a study of the Auger-electron-photoelectron angular correlations in the case of the C 1s ionization of the CO molecule are presented and compared with theoretical calculations in the Hartree-Fock approximation based on the two-step model. The measurements have been performed at two photon energies, 305 and 318 eV, respectively, and at three angles of photoelectron emission relative to the light polarization vector: namely, 0 degree sign , 30 degree sign , and 60 degree sign . A general agreement is found between theory and experiment for the coincidence angular distributions and the relative magnitudes of the Auger-electron-photoelectron angular correlations. However, both experiment and theory show that the Auger-electron-photoelectron angular correlations are not sufficiently sensitive to the details of the Auger-electron wave function to allow a 'complete' Auger experiment in molecules. On the other hand, our calculations demonstrate that the Auger-electron angular distribution measured in the molecular frame is very sensitive to the individual contributions of different partial waves of the Auger electron. Therefore we conclude that the complete experiment for the Auger decay in molecules can be realized only measuring the Auger-electron angular distributions in the molecular frame.

  12. Maraba Virus as a Potent Oncolytic Vaccine Vector

    PubMed Central

    Pol, Jonathan G; Zhang, Liang; Bridle, Byram W; Stephenson, Kyle B; Rességuier, Julien; Hanson, Stephen; Chen, Lan; Kazdhan, Natasha; Bramson, Jonathan L; Stojdl, David F; Wan, Yonghong; Lichty, Brian D

    2014-01-01

    The rhabdovirus Maraba has recently been characterized as a potent oncolytic virus. In the present study, we engineered an attenuated Maraba strain, defined as MG1, to express a melanoma-associated tumor antigen. Its ability to mount an antitumor immunity was evaluated in tumor-free and melanoma tumor-bearing mice. Alone, the MG1 vaccine appeared insufficient to prime detectable adaptive immunity against the tumor antigen. However, when used as a boosting vector in a heterologous prime-boost regimen, MG1 vaccine rapidly generated strong antigen-specific T-cell immune responses. Once applied for treating syngeneic murine melanoma tumors, our oncolytic prime-boost vaccination protocol involving Maraba MG1 dramatically extended median survival and allowed complete remission in more than 20% of the animals treated. This work describes Maraba virus MG1 as a potent vaccine vector for cancer immunotherapy displaying both oncolytic activity and a remarkable ability to boost adaptive antitumor immunity. PMID:24322333

  13. InGaN/GaN multiple-quantum-well light-emitting diodes with a grading InN composition suppressing the Auger recombination

    SciTech Connect

    Zhang, Zi-Hui; Liu, Wei; Ju, Zhengang; Tan, Swee Tiam; Ji, Yun; Kyaw, Zabu; Zhang, Xueliang; Wang, Liancheng; Sun, Xiao Wei E-mail: VOLKAN@stanfordalumni.org; Demir, Hilmi Volkan E-mail: VOLKAN@stanfordalumni.org

    2014-07-21

    In conventional InGaN/GaN light-emitting diodes (LEDs), thin InGaN quantum wells are usually adopted to mitigate the quantum confined Stark effect (QCSE), caused due to strong polarization induced electric field, through spatially confining electrons and holes in small recombination volumes. However, this inevitably increases the carrier density in quantum wells, which in turn aggravates the Auger recombination, since the Auger recombination scales with the third power of the carrier density. As a result, the efficiency droop of the Auger recombination severely limits the LED performance. Here, we proposed and showed wide InGaN quantum wells with the InN composition linearly grading along the growth orientation in LED structures suppressing the Auger recombination and the QCSE simultaneously. Theoretically, the physical mechanisms behind the Auger recombination suppression are also revealed. The proposed LED structure has experimentally demonstrated significant improvement in optical output power and efficiency droop, proving to be an effective solution to this important problem of Auger recombination.

  14. Discovery of a highly potent glucocorticoid for asthma treatment

    PubMed Central

    He, Yuanzheng; Shi, Jingjing; Yi, Wei; Ren, Xin; Gao, Xiang; Li, Jianshuang; Wu, Nanyan; Weaver, Kevin; Xie, Qian; Khoo, Sok Kean; Yang, Tao; Huang, Xiaozhu; Melcher, Karsten; Xu, H Eric

    2015-01-01

    Glucocorticoids are the most effective treatment for asthma. However, their clinical applications are limited by low efficacy in severe asthma and by undesired side effects associated with high dose or prolonged use. The most successful approach to overcome these limitations has been the development of highly potent glucocorticoids that can be delivered to the lungs by inhalation to achieve local efficacy with minimal systemic effects. On the basis of our previous structural studies, we designed and developed a highly potent glucocorticoid, VSGC12, which showed an improved anti-inflammation activity in both cell-based reporter assays and cytokine inhibition experiments, as well as in a gene expression profiling of mouse macrophage RAW264.7 cells. In a mouse asthma model, VSGC12 delivered a higher efficacy than fluticasone furoate, a leading clinical compound, in many categories including histology and the number of differentiated immune cells. VSGC12 also showed a higher potency than fluticasone furoate in repressing most asthma symptoms. Finally, VSGC12 showed a better side effect profile than fluticasone furoate at their respective effective doses, including better insulin response and less bone loss in an animal model. The excellent therapeutic and side effect properties of VSGC12 provide a promising perspective for developing this potent glucocorticoid as a new effective drug for asthma. PMID:27066265

  15. A potent antibacterial indole alkaloid from Psychotria pilifera.

    PubMed

    Liu, Lu; Song, Chang-Wei; Khan, Afsar; Li, Xiao-Ning; Yang, Xing-Wei; Cheng, Gui-Guang; Liu, Ya-Ping; Luo, Xiao-Dong

    2016-08-01

    A new strychnine alkaloid, 16,17,19,20-tetrahydro-2,16-dehydro-18-deoxyisostrychnine (1), and fourteen known alkaloids were isolated from the leaves of Psychotria pilifera. Their structures were identified on the basis of extensive spectroscopic analysis, as well as by comparison with the reported spectroscopic data. The new alkaloid (1) exhibited potent antibacterial activity against Escherichia coli, equivalent to cefotaxime with MIC value of 0.781 μg/ml. PMID:26963582

  16. Proof of principal for staircase auger chip removal theory

    NASA Technical Reports Server (NTRS)

    Barron, Jeffrey B.; Brewer, Steve; Kerns, Kenneth; Moody, Kyle; Rossi, Richard A.

    1987-01-01

    A proof of principal design of the staircase auger theory is provided for lunar drilling. The drill is designed to drill holes 30 meters deep and 0.1 meters in diameter. The action of the auger is 0.01 meter strokes at a varying number of strokes per second. A detailed analysis of the interaction of the auger and particle was done to optimize the parameters of the auger. This optimum design will allow for proper heat removal and reasonable drilling time. The drill bit is designed to scoop the particles into the auger while efficiently cutting through the moon's surface.

  17. Pierre Auger Results

    SciTech Connect

    Chou, Aaron

    2008-01-14

    Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrate that there is a correlation between the arrival directions of cosmic rays with energy above 6 [1] 1019 eV and the positions of active galactic nuclei (AGN) lying within 75 Mpc. We reject the hypothesis of an isotropic distribution of these cosmic rays at over 99% confidence level from a prescribed a priori test. The correlation we observe is compatible with the hypothesis that the highest energy particles originate from relatively nearby extragalactic sources whose fluxes have therefore not been significantly reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

  18. Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

    PubMed Central

    Zuo, Jun; Quinn, Kevin K.; Kye, Steve; Cooper, Paige; Damoiseaux, Robert

    2012-01-01

    No antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and protein. In view of its favorable pharmacokinetics and safety profile, fluoxetine warrants additional study as a potential antiviral agent for enterovirus infections. PMID:22751539

  19. Inner-shell ionization of rotating linear molecules in the presence of spin-dependent interactions: Entanglement between a photoelectron and an auger electron

    NASA Astrophysics Data System (ADS)

    Ghosh, R.; Chandra, N.; Parida, S.

    2009-03-01

    This paper reports results of a theoretical study of angle- and spin-resolved photo-Auger electron coincident spectroscopy in the form of entanglement between these two particles emitted from a linear molecule. First, we develop an expression for a density matrix needed for studying spin-entanglement between a photoelectron and an Auger electron. In order to properly represent the molecular symmetries, nuclear rotation, and the spin-dependent interactions (SDIs), we have used symmetry adapted wavefunctions in Hund’s coupling scheme (a) for all the species participating in this two-step process. This expression shows that spin-entanglement in a photo-Auger electron pair in the presence of SDIs very strongly depends upon, among other things, polarization of the ionizing radia- tion, directions of motion and of spin polarization of two ejected electrons, and the dynamics of photoionization and of Auger decay. We have applied this expression, as an example, to a generic linear molecule in its J0, M0 = 0 state. This model calculation clearly brings out the salient features of the spin-entanglement of a photo-Auger electron pair in the presence of the SDIs.

  20. Carrageenan Is a Potent Inhibitor of Papillomavirus Infection

    PubMed Central

    Buck, Christopher B; Thompson, Cynthia D; Roberts, Jeffrey N; Müller, Martin; Lowy, Douglas R; Schiller, John T

    2006-01-01

    Certain sexually transmitted human papillomavirus (HPV) types are causally associated with the development of cervical cancer. Our recent development of high-titer HPV pseudoviruses has made it possible to perform high-throughput in vitro screens to identify HPV infection inhibitors. Comparison of a variety of compounds revealed that carrageenan, a type of sulfated polysaccharide extracted from red algae, is an extremely potent infection inhibitor for a broad range of sexually transmitted HPVs. Although carrageenan can inhibit herpes simplex viruses and some strains of HIV in vitro, genital HPVs are about a thousand-fold more susceptible, with 50% inhibitory doses in the low ng/ml range. Carrageenan acts primarily by preventing the binding of HPV virions to cells. This finding is consistent with the fact that carrageenan resembles heparan sulfate, an HPV cell-attachment factor. However, carrageenan is three orders of magnitude more potent than heparin, a form of cell-free heparan sulfate that has been regarded as a highly effective model HPV inhibitor. Carrageenan can also block HPV infection through a second, postattachment heparan sulfate–independent effect. Carrageenan is in widespread commercial use as a thickener in a variety of cosmetic and food products, ranging from sexual lubricants to infant feeding formulas. Some of these products block HPV infectivity in vitro, even when diluted a million-fold. Clinical trials are needed to determine whether carrageenan-based products are effective as topical microbicides against genital HPVs. PMID:16839203

  1. Determination of the solid angle and response function of a hemispherical spectrograph with injection lens for Auger electrons emitted from long lived projectile states

    SciTech Connect

    Doukas, S.; Madesis, I.; Dimitriou, A.; Zouros, T. J. M.; Laoutaris, A.; Benis, E. P.

    2015-04-15

    We present SIMION 8.1 Monte Carlo type simulations of the response function and detection solid angle for long lived Auger states (lifetime τ ∼ 10{sup −9} − 10{sup −5} s) recorded by a hemispherical spectrograph with injection lens and position sensitive detector used for high resolution Auger spectroscopy of ion beams. Also included in these simulations for the first time are kinematic effects particular to Auger emission from fast moving projectile ions such as line broadening and solid angle limitations allowing for a more accurate and realistic line shape modeling. Our results are found to be in excellent agreement with measured electron line shapes of both long lived 1s2s2p{sup 4}P and prompt Auger projectile states formed by electron capture in collisions of 25.3 MeV F{sup 7+} with H{sub 2} and 12.0 MeV C{sup 4+} with Ne recorded at 0{sup ∘} to the beam direction. These results are important for the accurate evaluation of the 1s2s2p {sup 4}P/{sup 2}P ratio of K-Auger cross sections whose observed non-statistical production by electron capture into He-like ions, recently a field of interesting interpretations, awaits further resolution.

  2. Potent inhibition of tau fibrillization with a multivalent ligand

    SciTech Connect

    Honson, Nicolette S.; Jensen, Jordan R.; Darby, Michael V.; Kuret, Jeff

    2007-11-09

    Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at {approx}80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors.

  3. Evidence for Chirped Auger-Electron Emission

    NASA Astrophysics Data System (ADS)

    Schütte, B.; Bauch, S.; Frühling, U.; Wieland, M.; Gensch, M.; Plönjes, E.; Gaumnitz, T.; Azima, A.; Bonitz, M.; Drescher, M.

    2012-06-01

    Auger decay carries valuable information about the electronic structure and dynamics of atoms, molecules, and solids. Here we furnish evidence that under certain conditions Auger electrons are subject to an energetic chirp. The effect is disclosed in time-resolved streaking experiments on the Xe NOO and Kr MNN Auger decay using extreme-ultraviolet pulses from the free-electron laser in Hamburg as well as from a high-order harmonic laser source. The origin of this effect is found to be an exchange of energy between the Auger electron and an earlier emitted correlated photoelectron. The observed time-dependent spectral modulations are understood within an analytical model and confirmed by extensive computer simulations.

  4. Positron annihilation induced Auger electron emission

    SciTech Connect

    Weiss, A.; Jibaly, M.; Lei, Chun; Mehl, D.; Mayer, R.; Lynn, K.G.

    1988-01-01

    We report on measurements of Auger electron emission from Cu and Fe due to core hole excitations produced by the removal of core electrons by matter-antimatter annihilation. Estimates are developed of the probability of positrons annihilating with a 3p electron in these materials. Several important advantages of Positron annihilation induced Auger Electron Spectroscopy (PAES) for surface analysis are suggested. 10 refs., 2 figs.

  5. Nonradiative Auger recombination in semiconductor nanocrystals.

    PubMed

    Vaxenburg, Roman; Rodina, Anna; Shabaev, Andrew; Lifshitz, Efrat; Efros, Alexander L

    2015-03-11

    We calculate the rate of nonradiative Auger recombination in negatively charged CdSe nanocrystals (NCs). The rate is nonmonotonic, strongly oscillating with NC size, and sensitive to the NC surface. The oscillations result in nonexponential decay of carriers in NC ensembles. Using a standard single-exponential approximation of the decay dynamics, we determine the apparent size dependence of the Auger rate in an ensemble and derive CdSe surface parameters consistent with the experimental dependence on size. PMID:25693512

  6. High-resolution absorption spectroscopy of photoionized silicon plasma, a step toward measuring the efficiency of Resonant Auger Destruction

    NASA Astrophysics Data System (ADS)

    Loisel, Guillaume; Bailey, James; Hansen, Stephanie; Nagayama, Taisuke; Rochau, Gregory; Liedhal, Duane; Mancini, Roberto

    2013-10-01

    A remarkable opportunity to observe matter in a regime where the effects of General Relativity are significant has arisen through measurements of strongly red-shifted iron x-ray lines emitted from black hole accretion disks. A major uncertainty in the spectral formation models is the efficiency of Resonant Auger Destruction (RAD), in which fluorescent K α photons are resonantly absorbed by neighbor ions. The absorbing ion preferentially decays by Auger ionization, thus reducing the emerging K α intensity. If K α lines from L-shell ions are not observed in iron spectral emission, why are such lines observed from silicon plasma surrounding other accretion powered objects? To help answer this question, we are investigating photoionized silicon plasmas produced using intense x-rays from the Z facility. The incident spectral irradiance is determined with time-resolved absolute power measurements, multiple monochromatic gated images, and a 3-D view factor model. The charge state distribution, electron temperature, and electron density are determined using space-resolved backlit absorption spectroscopy. The measurements constrain photoionized plasma models and set the stage for future emission spectroscopy directly investigating the RAD process. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under contract DE-AC04-94AL85000.

  7. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  8. Correlation between energy deposition and molecular damage from Auger electrons: A case study of ultra-low energy (5–18 eV) electron interactions with DNA

    PubMed Central

    Rezaee, Mohammad; Hunting, Darel J.; Sanche, Léon

    2015-01-01

    Purpose The present study introduces a new method to establish a direct correlation between biologically related physical parameters (i.e., stopping and damaging cross sections, respectively) for an Auger-electron emitting radionuclide decaying within a target molecule (e.g., DNA), so as to evaluate the efficacy of the radionuclide at the molecular level. These parameters can be applied to the dosimetry of Auger electrons and the quantification of their biological effects, which are the main criteria to assess the therapeutic efficacy of Auger-electron emitting radionuclides. Methods Absorbed dose and stopping cross section for the Auger electrons of 5–18 eV emitted by 125I within DNA were determined by developing a nanodosimetric model. The molecular damages induced by these Auger electrons were investigated by measuring damaging cross section, including that for the formation of DNA single- and double-strand breaks. Nanoscale films of pure plasmid DNA were prepared via the freeze-drying technique and subsequently irradiated with low-energy electrons at various fluences. The damaging cross sections were determined by employing a molecular survival model to the measured exposure–response curves for induction of DNA strand breaks. Results For a single decay of 125I within DNA, the Auger electrons of 5–18 eV deposit the energies of 12.1 and 9.1 eV within a 4.2-nm3 volume of a hydrated or dry DNA, which results in the absorbed doses of 270 and 210 kGy, respectively. DNA bases have a major contribution to the deposited energies. Ten-electronvolt and high linear energy transfer 100-eV electrons have a similar cross section for the formation of DNA double-strand break, while 100-eV electrons are twice as efficient as 10 eV in the induction of single-strand break. Conclusions Ultra-low-energy electrons (<18 eV) substantially contribute to the absorbed dose and to the molecular damage from Auger-electron emitting radionuclides; hence, they should be considered in the

  9. Correlation between energy deposition and molecular damage from Auger electrons: A case study of ultra-low energy (5–18 eV) electron interactions with DNA

    SciTech Connect

    Rezaee, Mohammad Hunting, Darel J.; Sanche, Léon

    2014-07-15

    Purpose: The present study introduces a new method to establish a direct correlation between biologically related physical parameters (i.e., stopping and damaging cross sections, respectively) for an Auger-electron emitting radionuclide decaying within a target molecule (e.g., DNA), so as to evaluate the efficacy of the radionuclide at the molecular level. These parameters can be applied to the dosimetry of Auger electrons and the quantification of their biological effects, which are the main criteria to assess the therapeutic efficacy of Auger-electron emitting radionuclides. Methods: Absorbed dose and stopping cross section for the Auger electrons of 5–18 eV emitted by{sup 125}I within DNA were determined by developing a nanodosimetric model. The molecular damages induced by these Auger electrons were investigated by measuring damaging cross section, including that for the formation of DNA single- and double-strand breaks. Nanoscale films of pure plasmid DNA were prepared via the freeze-drying technique and subsequently irradiated with low-energy electrons at various fluences. The damaging cross sections were determined by employing a molecular survival model to the measured exposure–response curves for induction of DNA strand breaks. Results: For a single decay of{sup 125}I within DNA, the Auger electrons of 5–18 eV deposit the energies of 12.1 and 9.1 eV within a 4.2-nm{sup 3} volume of a hydrated or dry DNA, which results in the absorbed doses of 270 and 210 kGy, respectively. DNA bases have a major contribution to the deposited energies. Ten-electronvolt and high linear energy transfer 100-eV electrons have a similar cross section for the formation of DNA double-strand break, while 100-eV electrons are twice as efficient as 10 eV in the induction of single-strand break. Conclusions: Ultra-low-energy electrons (<18 eV) substantially contribute to the absorbed dose and to the molecular damage from Auger-electron emitting radionuclides; hence, they should

  10. A Potent and Site-Selective Agonist of TRPA1.

    PubMed

    Takaya, Junichiro; Mio, Kazuhiro; Shiraishi, Takuya; Kurokawa, Tatsuki; Otsuka, Shinya; Mori, Yasuo; Uesugi, Motonari

    2015-12-23

    TRPA1 is a member of the transient receptor potential (TRP) cation channel family that is expressed primarily on sensory neurons. This chemosensor is activated through covalent modification of multiple cysteine residues with a wide range of reactive compounds including allyl isothiocyanate (AITC), a spicy component of wasabi. The present study reports on potent and selective agonists of TRPA1, discovered through screening 1657 electrophilic molecules. In an effort to validate the mode of action of hit molecules, we noted a new TRPA1-selective agonist, JT010 (molecule 1), which opens the TRPA1 channel by covalently and site-selectively binding to Cys621 (EC50 = 0.65 nM). The results suggest that a single modification of Cys621 is sufficient to open the TRPA1 channel. The TRPA1-selective probe described herein might be useful for further mechanistic studies of TRPA1 activation. PMID:26630251

  11. Deoxygedunin, a natural product with potent neurotrophic activity in mice.

    PubMed

    Jang, Sung-Wuk; Liu, Xia; Chan, Chi Bun; France, Stefan A; Sayeed, Iqbal; Tang, Wenxue; Lin, Xi; Xiao, Ge; Andero, Raul; Chang, Qiang; Ressler, Kerry J; Ye, Keqiang

    2010-01-01

    Gedunin, a family of natural products from the Indian neem tree, possess a variety of biological activities. Here we report the discovery of deoxygedunin, which activates the mouse TrkB receptor and its downstream signaling cascades. Deoxygedunin is orally available and activates TrkB in mouse brain in a BDNF-independent way. Strikingly, it prevents the degeneration of vestibular ganglion in BDNF -/- pups. Moreover, deoxygedunin robustly protects rat neurons from cell death in a TrkB-dependent manner. Further, administration of deoxygedunin into mice displays potent neuroprotective, anti-depressant and learning enhancement effects, all of which are mediated by the TrkB receptor. Hence, deoxygedunin imitates BDNF's biological activities through activating TrkB, providing a powerful therapeutic tool for treatment of various neurological diseases. PMID:20644624

  12. Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

    NASA Astrophysics Data System (ADS)

    Torres-García, E.; Carrillo-Cazares, T. A.

    2011-01-01

    The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency-mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

  13. Nanosulfur: A Potent Fungicide Against Food Pathogen, Aspergillus niger

    NASA Astrophysics Data System (ADS)

    Choudhury, Samrat Roy; Nair, Kishore K.; Kumar, Rajesh; Gogoi, Robin; Srivastava, Chitra; Gopal, Madhuban; Subhramanyam, B. S.; devakumar, C.; Goswami, Arunava

    2010-10-01

    Elemental sulfur (S0), man's oldest eco-friendly fungicide for curing fungal infections in plants and animals, is registered in India as a non-systemic and contact fungicide. However due to its high volume requirement, Indian agrochemical industry and farmers could not effectively use this product till date. We hypothesize that intelligent nanoscience applications might increase the visibility of nanosulfur in Indian agriculture as a potent and eco-safe fungicide. Sulfur nanoparticles (NPs) were synthesized bottom-up via a liquid synthesis method with average particle size in the range of 50-80 nm and the shapes of the NPs were spherical. A comparative study of elemental and nano-sulfur produced has been tested against facultative fungal food pathogen, Aspergillus niger. Results showed that nanosulfur is more efficacious than its elemental form.

  14. Nanosulfur: A Potent Fungicide Against Food Pathogen, Aspergillus niger

    SciTech Connect

    Choudhury, Samrat Roy; Goswami, Arunava; Nair, Kishore K.; Kumar, Rajesh; Gopal, Madhuban; Devakumar, C.; Gogoi, Robin; Srivastava, Chitra; Subhramanyam, B. S.

    2010-10-04

    Elemental sulfur (S{sup 0}), man's oldest eco-friendly fungicide for curing fungal infections in plants and animals, is registered in India as a non-systemic and contact fungicide. However due to its high volume requirement, Indian agrochemical industry and farmers could not effectively use this product till date. We hypothesize that intelligent nanoscience applications might increase the visibility of nanosulfur in Indian agriculture as a potent and eco-safe fungicide. Sulfur nanoparticles (NPs) were synthesized bottom-up via a liquid synthesis method with average particle size in the range of 50-80 nm and the shapes of the NPs were spherical. A comparative study of elemental and nano-sulfur produced has been tested against facultative fungal food pathogen, Aspergillus niger. Results showed that nanosulfur is more efficacious than its elemental form.

  15. Allylmagnolol, a novel magnolol derivative as potent antioxidant.

    PubMed

    Li, Chi-Yuan; Wang, Yvonne; Hu, Ming-Kuan

    2003-08-15

    We reported the discovery of potent antioxidants based on magnolol, a naturally occurring biphenolic obtained from the bark of Magnolia officinalis. The allylmagnolols 3a,b were synthesized via O-alkylation of the biphenols followed by Claisen rearrangement. In-vitro using enhanced chemiluminescence (CL) and flow cytometric assays in whole cells revealed that both 3a and 3b displayed promising free radical scavenging effects in PMA- and LPS-stimulated models as compared with magnolol. Further DNA labeling analysis for cytotoxicity indicated that these analogues show no cytotoxic effects for the scavenging of the oxygen-derived free radicals under PMA-stimulated concentrations. The results from 3,3'-bisallylmagnolol (3b) suggested that the naturally occurring constituent was suitable to be a lead compound for the development of potential antioxidants for certain diseases. PMID:12901912

  16. Maleopimaric acid--a potent sensitizer in modified rosin.

    PubMed

    Karlberg, A T; Gäfvert, E; Hagelthorn, G; Nilsson, J L

    1990-04-01

    The allergenicity of the maleic-modified rosins and their esters has been studied. The unesterified resins are mainly used in paper size and the esters in printing inks, varnishes and adhesives. The levopimaric-maleic anhydride Diels-Alder adduct (maleopimaric acid) is the main component obtained in the maleic-modified rosins. This compound was synthesized and its structure was determined. Its sensitizing potential was investigated in guinea pigs according to different methods. It was shown that maleopimaric acid is a very potent sensitizer, comparable with the strongest allergen isolated from unmodified gum rosin. The allergen may also be present after esterification unless the process is carried out to completion. The animals sensitized to maleopimaric acid did not react to unmodified rosin, which shows that maleopimaric acid is structurally different from the allergens in rosin. PMID:2347173

  17. The Auger Engineering Radio Array

    NASA Astrophysics Data System (ADS)

    Fuchs, Benjamin

    2012-11-01

    High and ultra-high energy cosmic rays hitting the Earth's atmosphere cause extensive air showers (EAS). In recent years, these cosmic rays have been extensively studied at the Pierre Auger Observatory in Argentina. The EAS mainly consist of charged particles, especially electrons and positrons, which cause electro-magnetic emission in the MHz range by interaction with the Earth's magnetic field. To measure this radio emission, AERA, the Auger Engineering Radio Array, was deployed in October 2010 and commenced regular data acquisition in April 2011. AERA was designed as an engineering array for technology and methodology development towards future large-scale radio arrays. It will allow studies on the radio emission mechanism and the physics capabilities of the detection technique. AERA's unique site within the surface detector array (SD) of the Pierre Auger Observatory provides the possibility of coincident hybrid and super-hybrid EAS detection especially in overlap with the fluorescence telescopes Coihueco and HEAT. Besides a description of the setup, we present an overview of analyses of commissioning data taken between November 2010 and April 2011. Also, we show the first hybrid and self-triggered events detected with AERA in April 2011.

  18. RS 30026: a potent and effective calcium channel agonist.

    PubMed Central

    Patmore, L.; Duncan, G. P.; Clarke, B.; Anderson, A. J.; Greenhouse, R.; Pfister, J. R.

    1990-01-01

    1. A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2 nM. 3. Compounds were also evaluated for their effects on guinea-pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10(-9) and 10(-6) M (pEC200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10(-6) M (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10(-10) and 10(-7) M. 4. Calcium channel currents in single embryonic chick myocytes were recorded by whole-cell voltage clamp techniques. RS 30026 (100 nM-500 nM) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 nM) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 nM) were much less marked.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1694461

  19. Tool for Guiding An Auger

    NASA Technical Reports Server (NTRS)

    Wesselski, C. J.

    1983-01-01

    Auger and Ram have same pitch, which minimizes damage to workpiece and load carried by auger. Auger firmly fastened onto ram shaft by screw and kept from rotating on shaft by slot machined into end of stem and male driving lug that engages slot. Used to install threaded studs in plastic or rubber where impractical to mold them in.

  20. Multielectron Spectroscopy: The Xenon 4d Hole Double Auger Decay

    SciTech Connect

    Penent, F.; Palaudoux, J.; Lablanquie, P.; Andric, L.; Feifel, R.; Eland, J.H.D.

    2005-08-19

    A magnetic bottle spectrometer of the type recently developed by Eland et al. [Phys. Rev. Lett. 90, 053003 (2003).] has been implemented for use with synchrotron radiation, allowing multidimensional electron spectroscopy. Its application to the Xe 4d double Auger decay reveals all the energy pathways involved. The dominant path is a cascade process with a rapid (6 fs) ejection of a first Auger electron followed by the slower (>23 fs) emission of a second Auger electron. Weaker processes implying 3 electron processes are also revealed, namely, direct double Auger and associated Rydberg series.

  1. Auger electron spectroscopy study of oxidation of a PdCr alloy used for high-temperature sensors

    NASA Technical Reports Server (NTRS)

    Boyd, Darwin L.; Zeller, Mary V.; Vargas-Aburto, Carlos

    1993-01-01

    A Pd-13 wt. percent Cr solid solution is a promising high-temperature strain gage alloy. In bulk form it has a number of properties that are desirable in a resistance strain gage material, such as a linear electrical resistance versus temperature curve to 1000 C and stable electrical resistance in air at 1000 C. However, unprotected fine wire gages fabricated from this alloy perform well only to 600 C. At higher temperatures severe oxidation degrades their electrical performance. In this work Auger electron spectroscopy was used to study the oxidation chemistry of the alloy wires and ribbons. Results indicate that the oxidation is caused by a complex mechanism that is not yet fully understood. As expected, during oxidation, a layer of chromium oxide is formed. This layer, however, forms beneath a layer of metallic palladium. The results of this study have increased the understanding of the oxidation mechanism of Pd-13 wt. percent Cr.

  2. Auger electron spectroscopy, secondary ion mass spectroscopy and optical characterization of a-C-H and BN films

    NASA Technical Reports Server (NTRS)

    Pouch, J. J.; Alterovitz, S. A.; Warner, J. D.

    1986-01-01

    The amorphous dielectrics a-C:H and BN were deposited on III-V semiconductors. Optical band gaps as high as 3 eV were measured for a-C:H generated by C4H10 plasmas; a comparison was made with bad gaps obtained from films prepared by CH4 glow discharges. The ion beam deposited BN films exhibited amorphous behavior with band gaps on the order of 5 eV. Film compositions were studied by Auger electron spectroscopy (AES), x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). The optical properties were characterized by ellipsometry, UV/VIS absorption, and IR reflection and transmission. Etching rates of a-C:H subjected to O2 dicharges were determined.

  3. Electronic Doppler effect in resonant Auger decay of CO molecules upon excitation near a shake-up {pi} resonance

    SciTech Connect

    Sorensen, S. L.; Kitajima, M.; Tanaka, T.; Hoshino, M.; Tanaka, H.; Tamenori, Y.; Sankari, R.; Piancastelli, M. N.; Ueda, K.; Velkov, Y.; Minkov, I.; Carravetta, V. |; Gel'mukhanov, F. |

    2007-12-15

    We present an experimental observation of the electronic Doppler effect in resonant Auger spectra upon core excitation slightly above the carbon K edge of the CO molecule. Thus the electronic Doppler effect has been identified in above-threshold excitation, and in a transition of {pi} symmetry. Ab initio calculations of the potential energy curves of the relevant states of CO and the wave packet technique have been employed to provide a theoretical background to the experimental studies. The weak feature around 299.4 eV in the photoabsorption spectrum, whose decay has been investigated by the present experiment, is assigned to double (core-valence) excitations to C 1s shake-up states |1s{sub C}{sup -1}1{pi}{sup -1}{pi}*{sup 2}> with a strong dissociative character, and the Doppler splitting of the atomic peak has been reproduced by the simulation.

  4. Thermal effects in equilibrium surface segregation in a copper/10-atomic-percent-aluminum alloy using Auger electron spectroscopy

    NASA Technical Reports Server (NTRS)

    Ferrante, J.

    1972-01-01

    Equilibrium surface segregation of aluminum in a copper-10-atomic-percent-aluminum single crystal alloy oriented in the /111/ direction was demonstrated by using Auger electron spectroscopy. This crystal was in the solid solution range of composition. Equilibrium surface segregation was verified by observing that the aluminum surface concentration varied reversibly with temperature in the range 550 to 850 K. These results were curve fitted to an expression for equilibrium grain boundary segregation and gave a retrieval energy of 5780 J/mole (1380 cal/mole) and a maximum frozen-in surface coverage three times the bulk layer concentration. Analyses concerning the relative merits of sputtering calibration and the effects of evaporation are also included.

  5. Multiple direct and sequential Auger effect in the rare gases

    SciTech Connect

    Penent, F.; Lablanquie, P.; Palaudoux, J.; Andric, L.; Aoto, T.; Ito, K.; Hikosaka, Y.; Feifel, R.; Eland, J. H. D.

    2006-01-09

    The use of a magnetic bottle spectrometer with synchrotron radiation allows multi dimensional electron spectroscopy to be performed by detecting in coincidence all electrons (2, 3, 4) ejected in multiple ionization events. Multiple Auger effect following inner-shell ionization can be investigated in this way. Application of the technique to rare gases (Xe 4d and Kr 3d) double Auger decay reveals all the energy pathways involved. The dominant decay path proceeds by Auger cascade through autoionizing states of the doubly charged ion. Processes where 3 electrons are involved are also observed as direct double Auger and as involving precursor Rydberg series.

  6. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    PubMed

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID:26272937

  7. Marizomib, a potent second generation proteasome inhibitor from natural origin.

    PubMed

    Ma, Long; Diao, Aipo

    2015-01-01

    The malignance of cancers reinforces the need to find potent antineoplastic agents. In the past decades, proteasome has been witnessed as a potential target to fulfil this purpose, as evidenced by the fact that the first-in-class proteasome inhibitor Bortezomib was marketed in 2003. Marizomib (Salinosporamide A, NPI-0052), as a marine natural product, promises to be of high efficacy against multiple myeloma (MM), relapsed/refractory MM and other types of solid tumours. Compared with Bortezomib, it arguably has fewer severe side effects. Marizomib has been termed as orphan drug against multiple myeloma by US Food and Drug Administration (FDA) in 2013 and by European Medicines Agency (EMA) in 2014. As one of the second generation proteasome inhibitors (PIs), Marizomib is expected to bring about a sustained and complete therapeutic to extend cancer patients' life span. In this article, we intended to briefly review the historical developments, mechanisms, pharmacology, biosynthesis and side effects of this agent, aiming to provide concise coverage for a broad readership. In the end, we proposed our perspective for its futuristic applications. PMID:25403165

  8. Potent Adjuvanticity of a Pure TLR7-Agonistic Imidazoquinoline Dendrimer

    PubMed Central

    Shukla, Nikunj M.; Salunke, Deepak B.; Balakrishna, Rajalakshmi; Mutz, Cole A.; Malladi, Subbalakshmi S.; David, Sunil A.

    2012-01-01

    Engagement of toll-like receptors (TLRs) serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. We synthesized a dendrimeric molecule bearing six units of a potent TLR7/TLR8 dual-agonistic imidazoquinoline to explore if multimerization of TLR7/8 would result in altered activity profiles. A complete loss of TLR8-stimulatory activity with selective retention of the TLR7-agonistic activity was observed in the dendrimer. This was reflected by a complete absence of TLR8-driven proinflammatory cytokine and interferon (IFN)-γ induction in human PBMCs, with preservation of TLR7-driven IFN-α induction. The dendrimer was found to be superior to the imidazoquinoline monomer in inducing high titers of high-affinity antibodies to bovine α-lactalbumin. Additionally, epitope mapping experiments showed that the dendrimer induced immunoreactivity to more contiguous peptide epitopes along the amino acid sequence of the model antigen. PMID:22952720

  9. SCH 48973: a potent, broad-spectrum, antienterovirus compound.

    PubMed Central

    Buontempo, P J; Cox, S; Wright-Minogue, J; DeMartino, J L; Skelton, A M; Ferrari, E; Albin, R; Rozhon, E J; Girijavallabhan, V; Modlin, J F; O'Connell, J F

    1997-01-01

    SCH 48973 is a novel molecule with potent, selective, antienterovirus activity. In assays of the cytopathic effect against five picornaviruses, SCH 48973 had antiviral activity (50% inhibitory concentrations [IC50s]) of 0.02 to 0.11 microg/ml, with no detectable cytotoxicity at 50 microg/ml. SCH 48973 inhibited 80% of 154 recent human enterovirus isolates at an IC50 of 0.9 microg/ml. The antiviral activity of SCH 48973 is derived from its specific interaction with viral capsid, as confirmed by competition binding studies. The affinity constant (Ki) for SCH 48973 binding to poliovirus was 8.85 x 10(-8) M. In kinetic studies, a maximum of approximately 44 molecules of SCH 48973 were bound to poliovirus capsid. SCH 48973 demonstrated efficacy in a murine poliovirus model of enterovirus disease. SCH 48973 increased the survival of infected mice when it was administered orally at dosages of 3 to 20 mg/kg of body weight/day. Oral administration of SCH 48973 also reduced viral titers in the brains of infected mice. On the basis of its in vitro and in vivo profiles, SCH 48973 represents a potential candidate for therapeutic intervention against enterovirus infections. PMID:9174174

  10. Electronic state-lifetime interference in resonant Auger spectra: a tool to disentangle overlapping core-excited states.

    PubMed

    Goldsztejn, Gildas; Marchenko, Tatiana; Céolin, Denis; Journel, Loïc; Guillemin, Renaud; Rueff, Jean-Pascal; Kushawaha, Rajesh K; Püttner, Ralph; Piancastelli, Maria Novella; Simon, Marc

    2016-06-01

    We have measured resonant-Auger decay following Cl 1s(-1) excitations in HCl and CH3Cl molecules, and extracted the pseudo-cross sections of different Cl 2p(-2) final states. These cross sections show clear evidence of shake processes as well as contributions of electronic state-lifetime interference (ELI). To describe the spectra we developed a fit approach that takes into account ELI contributions and ultrafast nuclear dynamics in dissociative core-excited states. Using this approach we utilized the ELI contributions to obtain the intensity ratios of the overlapping states Cl 1s(-1)4pπ/1s(-1)4pσ in HCl and Cl 1s(-1)4pe/1s(-1)4pa1 in CH3Cl. The experimental value for HCl is compared with theoretical results showing satisfactory agreement. PMID:27199185

  11. Hemin as a generic and potent protein misfolding inhibitor

    SciTech Connect

    Liu, Yanqin; Carver, John A.; Ho, Lam H.; Elias, Abigail K.; Musgrave, Ian F.; Pukala, Tara L.

    2014-11-14

    Highlights: • Hemin prevents Aβ42, α-synuclein and RCM-κ-casein forming amyloid fibrils. • Hemin inhibits the β-sheet structure formation of Aβ42. • Hemin reduces the cell toxicity caused by fibrillar Aβ42. • Hemin dissociates partially formed Aβ42 fibrils. • Hemin prevents amorphous aggregation by ADH, catalase and γs-crystallin. - Abstract: Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer’s disease, Parkinson’s disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics for the treatment of these diseases. In the present study, thioflavin T fluorescence and transmission electron microscopy experiments demonstrated that hemin prevents amyloid fibril formation of kappa-casein, amyloid beta peptide and α-synuclein by blocking β-sheet structure assembly which is essential in fibril aggregation. Further, inhibition of fibril formation by hemin significantly reduces the cytotoxicity caused by fibrillar amyloid beta peptide in vitro. Interestingly, hemin degrades partially formed amyloid fibrils and prevents further aggregation to mature fibrils. Light scattering assay results revealed that hemin also prevents protein amorphous aggregation of alcohol dehydrogenase, catalase and γs-crystallin. In summary, hemin is a potent agent which generically stabilises proteins against aggregation, and has potential as a key molecule for the development of therapeutics for protein misfolding diseases.

  12. Carvacrol as a potent natural acaricide against Dermanyssus gallinae.

    PubMed

    Tabari, Mohaddeseh Abouhosseini; Youssefi, Mohammad Reza; Barimani, Alireza; Araghi, Atefeh

    2015-10-01

    Resistance to conventional synthetic pesticides has been widely reported in Dermanyssus gallinae in poultry production systems. Introducing novel acaricides to poultry industry today is more urgent than ever. Research in this field recently focused on plants and plant-derived compounds as acaricides. In the present study, acaricidal activity of three plant bioactive components, carvacrol, thymol, and farnesol, was assessed against D. gallinae and compared with synthetic pesticide permethrin. Mode of acaricidal action was determined by contact toxicity and fumigant toxicity bioassays. Except farnesol which did not cause any mortality, carvacrol and thymol were found to be toxic to D. gallinae with LD50 values of 1 and 3.15 μg/cm(3), respectively. Permethrin gave the LD50 value of 31.95 μg/cm(3) which was less efficient than carvacrol and thymol. In fumigant toxicity bioassay, mortality rate in carvacrol- and thymol-treated groups in closed method was significantly higher than the open one. On the other hand, permethrin exhibited poor fumigant toxicity as there was no statistically significant difference between mortality rate in open and closed methods. These findings revealed that mechanism of acaricidal activity of carvacrol and thymol but not permethrin was mainly due to fumigant action. Results of the present study suggested that carvacrol and thymol, especially carvacrol, can be developed as a novel potent bioacaricide against D. gallinae. PMID:26143865

  13. Acetone Extract from Rhodomyrtus tomentosa: A Potent Natural Antioxidant

    PubMed Central

    Lavanya, Goodla; Voravuthikunchai, Supayang Piyawan; Towatana, Nongporn Hutadilok

    2012-01-01

    Rhodomyrtus tomentosa (Myrtaceae) has been employed in traditional Thai medicine to treat colic diarrhoea, dysentery, abscesses, haemorrhage, and gynaecopathy. In addition, it has been used to formulate skin-whitening, anti-aging and skin beautifying agents. Ethnomedical activities of this plant may be due its antioxidant property. Hence, the aim of this study was to evaluate both in vitro and in vivo antioxidant activities of R. tomentosa leaf extract. In vitro antioxidant activity of the extract was assessed by lipid peroxidation inhibition capacity, ferric reducing antioxidant power, and metal chelating activity. R. tomentosa extract demonstrated its free radical scavenging effects in concentration dependent manner. In vivo antioxidant activity of the extract was conducted in Swiss Albino mice. Levels of thio-barbituric acid reactive substances (TBARS), glutathione (GSH), and the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in blood, liver, and kidney were analyzed using microtitre plate photometer. Administration of CCl4 caused significant increase in TBARS and decrease in GSH, SOD, CAT and GPx levels. In contrast, R. tomentosa extract (0.8 g/kg) effectively prevented these alterations and maintained the antioxidant status. The results suggest that R. tomentosa extract can serve as a potent antioxidant. PMID:23125869

  14. El proyecto AUGER

    NASA Astrophysics Data System (ADS)

    Etchegoyen, A.

    Hace ya más de 30 años en Volcano Ranch, EE.UU., un extenso chubasco cósmico (ECC) fue detectado con energía en exceso de 1020 eV. Desde entonces, observatorios ubicados en Haverah Park del Reino Unido, Yakutsk de Rusia, AGASA de Japón y Dugway de EE.UU. también han observado ECC con energías mayores que 1020 eV. Poco se sabe de dichos rayos, y en particular cuál es la naturaleza del primario, de dónde provienen, y cómo son acelerados, pero su naturaleza ultrarelativista excluye la mayoría de las respuestas dejando sólo algunas plausibles de ser investigadas experimentalmente. Grupos de científicos de 20 países están trabajando con el fin de construir dos arreglos de detectores gigantes, uno en cada hemisferio a lo largo de 3000 km2 c/u. Dichas dimensiones son necesarias debido al flujo estimado de 1 rayo cósmico/centuria/km2/sr. La sede del Observatorio del Sur es la Argentina. El proyecto fue nombrado Pierre Auger en conmemoración del célebre físico francés que detectó por primera vez chubascos cósmicos en 1938. El proyecto focaliza su interés en rayos cósmicos con energías mayores que 1020 eV.

  15. Aminoindoles, a novel scaffold with potent activity against Plasmodium falciparum.

    PubMed

    Barker, Robert H; Urgaonkar, Sameer; Mazitschek, Ralph; Celatka, Cassandra; Skerlj, Renato; Cortese, Joseph F; Tyndall, Erin; Liu, Hanlan; Cromwell, Mandy; Sidhu, Amar Bir; Guerrero-Bravo, Jose E; Crespo-Llado, Keila N; Serrano, Adelfa E; Lin, Jing-Wen; Janse, Chris J; Khan, Shahid M; Duraisingh, Manoj; Coleman, Bradley I; Angulo-Barturen, Inigo; Jiménez-Díaz, María Belén; Magán, Noemí; Gomez, Vanesa; Ferrer, Santiago; Martínez, María Santos; Wittlin, Sergio; Papastogiannidis, Petros; O'Shea, Thomas; Klinger, Jeffrey D; Bree, Mark; Lee, Edward; Levine, Mikaela; Wiegand, Roger C; Munoz, Benito; Wirth, Dyann F; Clardy, Jon; Bathurst, Ian; Sybertz, Edmund

    2011-06-01

    This study characterizes aminoindole molecules that are analogs of Genz-644442. Genz-644442 was identified as a hit in a screen of ~70,000 compounds in the Broad Institute's small-molecule library and the ICCB-L compound collection at Harvard Medical School. Genz-644442 is a potent inhibitor of Plasmodium falciparum in vitro (50% inhibitory concentrations [IC₅₀s], 200 to 285 nM) and inhibits P. berghei in vivo with an efficacy of > 99% in an adapted version of Peters' 4-day suppressive test (W. Peters, Ann. Trop. Med. Parasitol. 69:155-171, 1975). Genz-644442 became the focus of medicinal chemistry optimization; 321 analogs were synthesized and were tested for in vitro potency against P. falciparum and for in vitro absorption, distribution, metabolism, and excretion (ADME) properties. This yielded compounds with IC₅₀s of approximately 30 nM. The lead compound, Genz-668764, has been characterized in more detail. It is a single enantiomer with IC₅₀s of 28 to 65 nM against P. falciparum in vitro. In the 4-day P. berghei model, when it was dosed at 100 mg/kg of body weight/day, no parasites were detected on day 4 postinfection. However, parasites recrudesced by day 9. Dosing at 200 mg/kg/day twice a day resulted in cures of 3/5 animals. The compound had comparable activity against P. falciparum blood stages in a human-engrafted NOD-scid mouse model. Genz-668764 had a terminal half-life of 2.8 h and plasma trough levels of 41 ng/ml when it was dosed twice a day orally at 55 mg/kg/day. Seven-day rat safety studies showed a no-observable-adverse-effect level (NOAEL) at 200 mg/kg/day; the compound was not mutagenic in Ames tests, did not inhibit the hERG channel, and did not have potent activity against a broad panel of receptors and enzymes. Employing allometric scaling and using in vitro ADME data, the predicted human minimum efficacious dose of Genz-668764 in a 3-day once-daily dosing regimen was 421 mg/day/70 kg, which would maintain plasma trough levels

  16. Auger resonant Raman spectroscopy

    SciTech Connect

    Azuma, Y.; LeBrun, T.; MacDonald, M.; Southworth, S.H.

    1995-08-01

    As noted above, traditional spectroscopy of the electronic structure of the inner shells of atoms, molecules, and solids is limited by the lifetime broadening of the core-excited states. This limitation can also be avoided with the non-radiative analog of X-ray Raman scattering - resonant Auger Raman spectroscopy. We have used this technique to study the K-shell excitation spectrum of argon as the photon energy is continuously scanned across threshold.

  17. Potent Inhibitors of a Shikimate Pathway Enzyme from Mycobacterium tuberculosis

    PubMed Central

    Reichau, Sebastian; Jiao, Wanting; Walker, Scott R.; Hutton, Richard D.; Baker, Edward N.; Parker, Emily J.

    2011-01-01

    Tuberculosis remains a serious global health threat, with the emergence of multidrug-resistant strains highlighting the urgent need for novel antituberculosis drugs. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step of the shikimate pathway for the biosynthesis of aromatic compounds. This pathway has been shown to be essential in Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. DAH7PS catalyzes a condensation reaction between P-enolpyruvate and erythrose 4-phosphate to give 3-deoxy-d-arabino-heptulosonate 7-phosphate. The enzyme reaction mechanism is proposed to include a tetrahedral intermediate, which is formed by attack of an active site water on the central carbon of P-enolpyruvate during the course of the reaction. Molecular modeling of this intermediate into the active site reported in this study shows a configurational preference consistent with water attack from the re face of P-enolpyruvate. Based on this model, we designed and synthesized an inhibitor of DAH7PS that mimics this reaction intermediate. Both enantiomers of this intermediate mimic were potent inhibitors of M. tuberculosis DAH7PS, with inhibitory constants in the nanomolar range. The crystal structure of the DAH7PS-inhibitor complex was solved to 2.35 Å. Both the position of the inhibitor and the conformational changes of active site residues observed in this structure correspond closely to the predictions from the intermediate modeling. This structure also identifies a water molecule that is located in the appropriate position to attack the re face of P-enolpyruvate during the course of the reaction, allowing the catalytic mechanism for this enzyme to be clearly defined. PMID:21454647

  18. Oxidized mucus proteinase inhibitor: a fairly potent neutrophil elastase inhibitor.

    PubMed Central

    Boudier, C; Bieth, J G

    1994-01-01

    N-chlorosuccinimide oxidizes one of the methionine residues of mucus proteinase inhibitor with a second-order rate constant of 1.5 M-1.s-1. Cyanogen bromide cleavage and NH2-terminal sequencing show that the modified residue is methionine-73, the P'1 component of the inhibitor's active centre. Oxidation of the inhibitor decreases its neutrophil elastase inhibitory capacity but does not fully abolish it. The kinetic parameters describing the elastase-oxidized inhibitor interaction are: association rate constant kass. = 2.6 x 10(5) M-1.s-1, dissociation rate constant kdiss. = 2.9 x 10(-3) s-1 and equilibrium dissociation constant Ki = 1.1 x 10(-8) M. Comparison with the native inhibitor indicates that oxidation decreases kass. by a factor of 18.8 and increases kdiss. by a factor of 6.4, and therefore leads to a 120-fold increase in Ki. Yet, the oxidized inhibitor may still act as a potent elastase inhibitor in the upper respiratory tract where its concentration is 500-fold higher than Ki, i.e. where the elastase inhibition is pseudo-irreversible. Experiments in vitro with fibrous human lung elastin, the most important natural substrate of elastase, support this view: 1.35 microM elastase is fully inhibited by 5-6 microM oxidized inhibitor whether the enzyme-inhibitor complex is formed in the presence or absence of elastin and whether elastase is pre-adsorbed on elastin or not. PMID:7945266

  19. Toluidine blue O is a potent inhibitor of human cholinesterases.

    PubMed

    Biberoglu, Kevser; Tek, Melike Yuksel; Ghasemi, Seyhan Turk; Tacal, Ozden

    2016-08-15

    In this study, the inhibitory effects of three phenothiazines [toluidine blue O (TBO), thionine (TH) and methylene violet (MV)] were tested on human plasma butyrylcholinesterase (BChE) and their inhibitory mechanisms were studied in detail. MV acted as a linear mixed type inhibitor of human BChE with Ki = 0.66 ± 0.06 μM and α = 13.6 ± 3.5. TBO and TH caused nonlinear inhibition of human BChE, compatible to double occupancy. Ki values estimated by nonlinear regression analysis for TBO and TH were 0.008 ± 0.003 μM and 2.1 ± 0.42 μM, respectively. The inhibitory potential of TBO was also tested on human erythrocyte AChE. TBO acted as a linear mixed type inhibitor of human AChE with Ki = 0.041 ± 0.005 μM and α = 1.6 ± 0.007. Using four site-directed BChE mutants, the role of peripheral anionic site residues of human BChE was also investigated in the binding of TBO to BChE. The peripheral anionic site mutants of BChE caused 16-69-fold increase in Ki value of TBO, compared to recombinant wild-type, suggesting that peripheral anionic site residues are involved in the binding of TBO to human BChE. In conclusion, TBO which is a potent inhibitor of human cholinesterases, may be a potential drug candidate for the treatment of Alzheimer's disease. PMID:27296777

  20. 5% CO2 is a potent, fast acting inhalation anticonvulsant

    PubMed Central

    Tolner, Else A.; Hochman, Daryl W.; Hassinen, Pekka; Otáhal, Jakub; Gaily, Eija; Haglund, Michael M.; Kubová, Hana; Schuchmann, Sebastian; Vanhatalo, Sampsa; Kaila, Kai

    2010-01-01

    Purpose CO2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO2 can be used to suppress seizures in epilepsy patients. The effect of CO2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and a non-human primate and based on these data, preliminary tests were carried out in humans. Methods In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. 5% CO2 was applied for 5 minutes, 3 minutes before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG and received 5% CO2 in medical carbogen shortly after electrographic seizure onset. Results In rats, 5% CO2 strongly suppressed cortical afterdischarges, by ca. 75%, while responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO2 from 37 to 44-45 mmHg (corresponding to inhalation of 5% CO2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by ca. 25%. In a pilot trial carried out in 7 patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO2 was started after seizure generalization. Conclusions 5% CO2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO2 can be used for acute treatment to suppress seizures in epilepsy patients. PMID:20887367

  1. Auger processes in the 21st century

    PubMed Central

    Howell, Roger W.

    2012-01-01

    Purpose The extreme radiotoxicity of Auger electrons and their exquisite capacity to irradiate specific molecular sites has prompted scientists to extensively investigate their radiobiological effects. Their efforts have been punctuated by quadrennial international symposia that have focused on biophysical aspects of Auger processes. The latest meeting, the 6th International Symposium on Physical, Molecular, Cellular, and Medical Aspects of Auger Processes, was held 5–6 July 2007 at Harvard Medical School in Boston, Massachusetts, USA. This article provides a review of the research in this field that was published during the years 2004–2007, the period that has elapsed since the previous meeting. Conclusion The field has advanced considerably. A glimpse of the potential of this unique form of ionizing radiation to contribute to future progress in a variety of fields of study is proffered. PMID:19061120

  2. A review on cylindrospermopsin: The global occurrence, detection, toxicity and degradation of a potent cyanotoxin

    EPA Science Inventory

    Abstract: Cylindrospermopsin is now recognized as a potent cyanobacterial toxin found in water bodies worldwide. The ever-increasing and global occurrence of massive and prolonged blooms of cylindrospermopsin-producing cyanobacteria in freshwater poses a potential threat to both ...

  3. Education and public outreach of the Pierre Auger Observatory

    SciTech Connect

    Garcia, B.; Snow, G.

    2005-08-01

    The Auger collaboration's broad mission in education, outreach and public relations is coordinated in a separate task. Its goals are to encourage and support a wide range of outreach efforts that link schools and the public with the Auger scientists and the science of cosmic rays, particle physics, and associated technologies. This report focuses on recent activities and future initiatives.

  4. Angular dependence of the auger lineshape of graphite

    SciTech Connect

    Rogers, J.W. Jr.; Houston, J.E.; Rye, R.R.

    1986-01-01

    The Auger lineshape of graphite is of interest as a model for studying initial-state, core-hole screening and final-state, hole-hole correlation effects in aromatic systems. We have obtained the Auger spectra from POCO (amorphous) and HOPG (highly-oriented pyrolytic) graphite.

  5. A potent bidirectional promoter from the monocot cereal Eleusine coracana.

    PubMed

    Sen, Saswati; Dutta, Samir Kr

    2016-09-01

    Ragi bifunctional α-amylase-trypsin inhibitor (RBI) of Eleusine coracana (L.) Gaertn. (finger millet) simultaneously inhibits α-amylase and trypsin. In continuation of previous work on the cloning, expression and characterization of RBI, a bidirectional promoter from finger millet was explored on the basis of experimental observations. Two trypsin inhibitors were identified while purifying RBI from a trypsin-Sepharose column eluent. Using an FPLC gel filtration column, these three inhibitors were purified to homogeneity and subjected to MALDI-TOF-TOF-MS/MS analysis and N-terminal sequencing. Both ragi trypsin inhibitors (RTIs) showed the same N-terminal sequence and considerable sequence similarity to RBI, indicating the presence of a multigene protease inhibitor family in finger millet. To gain insight into the evolution of these genes, the upstream region of RBI was explored by Genome Walking. Interestingly, on sequencing, a genome walking product of ∼1 Kb showed presence of an N-terminal RBI specific primer sequence twice but in opposite directions and leaving an intervening region of ∼0.9 Kb. The intervening region was presumed to represent an E. coracana bidirectional promoter (EcBDP), intuitively having a divergent RBI-RTI gene pair at two sides. For assaying the bidirectionality of promoter activity, a dual reporter GUS-GFP vector construct was made for plant expression containing the reporter genes at two ends of EcBDP, which was used to transform Agrobacterium tumefaciens LBA 4404. Transient plant transformation by recombinant Agrobacterium cells was carried out in onion scale epidermal cells and finger millet seedling leaves. Simultaneous expression of GUS and GFP under EcBDP established it as a potent natural bidirectional promoter from monocot origin, thereby potentially having vast application in cereal gene manipulations. In addition, inducibility of the EcBDP by either abscisic acid or cold treatment, as determined by transient

  6. Auger anchors produce major cost savings

    SciTech Connect

    Webb, B.C.

    1981-10-01

    To meet specific-gravity standards, a 42-in.-diam, 0.598-in.-wall-thickness pipeline being installed in a glacial area full of potholes, peat swamps, and low-lying sections required 425 lb/ft of anchor hold-down. In spots where the underlying soil had an acceptable shear strength, the crew installed auger anchors (costing only $8/ft of pipeline) instead of the concrete set-on weights (at $80/ft) required in areas where the auger anchors would not hold; the savings amounted to about $380,000/mile of line laid.

  7. Latest results from the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Lhenry-Yvon, Isabelle

    2016-07-01

    The Pierre Auger Observatory has been designed to investigate the origin and nature of Ultra High Energy Cosmic Rays (UHECR) with energies from 1017 to 1020 eV. In this paper we will review some of the most recent results obtained from data of the Pierre Auger Observatory, namely the spectrum of cosmic rays, the anisotropies in arrival directions and the studies related to mass composition and to the number of muons measured at the ground. We will also discuss the implication of these results for assembling a consistent description of the composition, origin and propagation of cosmic rays.

  8. Echistatin is a potent inhibitor of bone resorption in culture.

    PubMed

    Sato, M; Sardana, M K; Grasser, W A; Garsky, V M; Murray, J M; Gould, R J

    1990-10-01

    The venom protein, s-echistatin, originally derived from the saw-scaled viper Echis carinatus, was found to be a potent inhibitor of bone resorption by isolated osteoclasts. This Arg24-Gly25-Asp26-(RGD)-containing protein inhibited the excavation of bone slices by rat osteoclasts (IC50 = 0.1 nM). It also inhibited the release of [3H]proline from labeled bone particles by chicken osteoclasts (IC50 = 100 nM). By comparison, the tetrapeptide Arg-Gly-Asp-Ser (RGDS) inhibited resorption by rat or chicken osteoclasts with an IC50 of 0.1 mM while ala24-echistatin was inactive. Video microscopy showed that rat osteoclast attachment to substrate was more sensitive to s-echistatin than was the attachment of mononuclear cells or chicken osteoclasts. The difference in sensitivity of rat and chicken osteoclasts to s-echistatin may be due to differences between receptors on rat and chicken osteoclasts for s-echistatin. Antibody localization of echistatin on these cells showed much greater echistatin binding to rat osteoclasts than to chicken osteoclasts. Laser scanning confocal microscopy after immunohistochemical staining showed that s-echistatin binds to osteoclasts, that s-echistatin receptors are most abundant at the osteoclast/glass interface, and that s-echistatin colocalizes with vinculin. Confocal interference reflection microscopy of osteoclasts incubated with s-echistatin, demonstrated colocalization of s-echistatin with the outer edges of clusters of grey contacts at the tips of some lamellipodia. Identification of the echistatin receptor as an integrin was confirmed by colocalization of echistatin fluorescence with staining for an alpha-like subunit. Attachment of bone particles labeled with [3H]proline to chicken osteoclasts confirmed that the mechanism of action of echistatin was to inhibit osteoclast binding to bone presumably by disrupting adhesion structures. These data demonstrate that osteoclasts bind to bone via an RGD-sequence as an obligatory step in bone

  9. Development of a miniature double-pass cylindrical mirror electron energy analyzer (DPCMA), and its application to Auger photoelectron coincidence spectroscopy (APECS)

    NASA Astrophysics Data System (ADS)

    Kobayashi, Eiichi; Seo, Junya; Nambu, Akira; Mase, Kazuhiko

    2007-09-01

    We have developed a miniature double-pass cylindrical mirror electron energy analyzer (DPCMA) with an outer diameter of 26 mm. The DPCMA consists of a shield for the electric field, inner and outer cylinders, two pinholes with a diameter of 2.0 mm, and an electron multiplier. By assembling the DPCMA in a coaxially symmetric mirror electron energy analyzer (ASMA) coaxially and confocally we developed an analyzer for Auger photoelectron coincidence spectroscopy (APECS). The performance was estimated by measuring the Si-LVV-Auger Si-1s-photoelectron coincidence spectra of clean Si(1 1 1). The electron-energy resolution of the DPCMA was estimated to be E/Δ E = 20. This value is better than that of the miniature single-pass CMA ( E/Δ E = 12) that was used in the previous APECS analyzer.

  10. A detailed Auger electron spectroscopy study of the first stages of the growth of C60 thin films

    NASA Astrophysics Data System (ADS)

    Vidal, R. A.; Ferrón, J.

    2015-11-01

    In this work we take advantage of the large sensitivity and in-depth resolution of Auger electron spectroscopy (AES) to study in a detailed way the growth of C60 over different substrates, namely Cu(1 1 1), Si(1 0 0) and graphene. The ability of AES, as compared to more local probes like STM or AFM, to follow the process in a dynamic way, allows us to study the growth of C60 below and over one ML, including the change of C60 over either Si or Cu to the growth of C60 over a C60 film. We found that the growth always proceeds layer by layer. This result shows that differences in diffusion barriers are not as important as one may think following the idea of diffusion by a jumping mechanism. We propose that the sticking coefficient, governed by the adsorption energy, is responsible for the differences observed between Cu and Si. Our results also point to a different charge transfer among fullerene molecules and these surfaces. The same result is suggested in the case of C60 over graphene, but in this case our conclusion comes from the variable temperature experiments.

  11. A Bayesian self-clustering analysis of the highest energy cosmic rays detected by the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Khanin, Alexander; Mortlock, Daniel J.

    2014-10-01

    Cosmic rays are protons and atomic nuclei that flow into our Solar system and reach the Earth with energies of up to ˜1021 eV. The sources of ultrahigh energy cosmic rays (UHECRs) with E ≳ 1019 eV remain unknown, although there are theoretical reasons to think that at least some come from active galactic nuclei (AGNs). One way to assess the different hypotheses is by analysing the arrival directions of UHECRs, in particular their self-clustering. We have developed a fully Bayesian approach to analysing the self-clustering of points on the sphere, which we apply to the UHECR arrival directions. The analysis is based on a multistep approach that enables the application of Bayesian model comparison to cases with weak prior information. We have applied this approach to the 69 highest energy events recorded by the Pierre Auger Observatory, which is the largest current UHECR data set. We do not detect self-clustering, but simulations show that this is consistent with the AGN-sourced model for a data set of this size. Data sets of several hundred UHECRs would be sufficient to detect clustering in the AGN model. Samples of this magnitude are expected to be produced by future experiments, such as the Japanese Experiment Module Extreme Universe Space Observatory.

  12. Dosimetry at the sub-cellular scale of Auger-electron emitter 99mTc in a mouse single thyroid follicle.

    PubMed

    Taborda, A; Benabdallah, N; Desbrée, A

    2016-02-01

    The Auger-electrons emitted by (99m)Tc have been recently associated with the induction of thyroid stunning in in vivo experiments in mice, making the dosimetry at the sub-cellular level of (99m)Tc a pertinent and pressing subject. The S-values for (99m)Tc were calculated using MCNP6, which was first validated for studies at the sub-cellular scale and for low energies electrons. The calculation was then performed for (99m)Tc within different cellular compartments in a single mouse thyroid follicle model, considering the radiative and non-radiative transitions of the (99m)Tc radiation spectrum. It was shown that the contribution of the (99m)Tc Auger and low energy electrons to the absorbed dose to the follicular cells' nucleus is important, being at least of the same order of magnitude compared to the emitted photons' contribution and cannot be neglected. The results suggest that Auger-electrons emitted by (99m)Tc play a significant role in the occurrence of the thyroid stunning effect in mice. PMID:26704702

  13. Fake Xanax Cut with Potent Pain Med Can Be a Killer

    MedlinePlus

    ... is 100 times more potent than morphine. The rock star Prince died of a fentanyl overdose at ... Francisco General Hospital after consuming the pills. A third person with them, a woman in her 30s, ...

  14. Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.

    PubMed

    Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

    2006-07-01

    A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

  15. Auger, zero-energy photoelectron, coincidence spectroscopy (AZEPECO): Chemical-site-selective Auger electron spectroscopy

    SciTech Connect

    Lee, K.; Ji, D.; Hanson, D.M.; Hulbert, S.L.; Kuiper, P.

    1993-12-31

    The Auger electron spectrum associated with decay of a core-hole on the terminal nitrogen and that associated with the central nitrogen of nitrous oxide, N{sub 2}O, are obtained individually through the use of a coincidence technique. Specifically, each of the two Auger electron spectra is obtained by detection of Auger electrons in coincidence with near zero energy (threshold) photoelectrons at the respective ionization thresholds. These zero energy electrons serve to identify the core-ionization continuum associated with the different Auger electrons. The salient features of the experimental spectra are in good agreement with theoretical calculations. The low counting rate generally associated with coincidence experiments, especially in the gas phase, is not encountered because the low energy electrons are collected over a 4{pi} solid angle. Also, velocity discrimination is accomplished by a spatial filter rather than by time-of-flight to utilize the maximum duty cycle of the synchrotron source. These data are believed to be the first examples of chemical-site-selective molecular Auger spectra.

  16. Auger Spectroscopy of Hydrogenated Diamond Surfaces

    NASA Technical Reports Server (NTRS)

    Krainsky, I. L.; Asnin, V. M.; Petukhov, A. G.; Foygel, M.

    1997-01-01

    An energy shift and a change of the line shape of the carbon core-valence-valence Auger spectra are observed for diamond surfaces after their exposure to an electron beam, or annealing at temperatures higher then 950 C. The effect is studied for both natural diamond crystals and chemical-vapor-deposited diamond films. A theoretical model is proposed for Auger spectra of hydrogenated diamond surfaces. The observed changes of the carbon Auger line shape are shown to be related to the redistribution of the valence-band local density of states caused by the hydrogen desorption from the surface. One-electron calculation of Auger spectra of diamond surfaces with various hydrogen coverages are presented. They are based on self-consistent wave functions and matrix elements calculated in the framework of the local-density approximation and the self-consistent linear muffin-tin orbital method with static core-hole effects taken into account. The major features of experimental spectra are explained.

  17. Soil chip convey of lunar subsurface auger drill

    NASA Astrophysics Data System (ADS)

    Zhao, Deming; Tang, Dewei; Hou, Xuyan; Jiang, Shengyuan; Deng, Zongquan

    2016-05-01

    Celestial body subsurface drilling and sampling is a key aspect of near-earth exploration projects. In these sample return missions, the auger drill system is universally used due to the environment and detector load limits. The common failure that the auger faces is chip chocking, which can raise the torque and cause the drill to stick. This paper builds auger drill models describing chip flow in the auger groove to balance geometric parameters, functional capability, and reliability. The features of chip flow are summarized and verified by a series of discrete element method simulations. In contrast to previous auger design, a convey capability factor is defined to indicate the auger's chip removal capacity, and the role of pitch angle and other parameters is assessed through motion analysis of the lunar soil flow process. The theory is verified by testing the drill penetrating speed limit, which combines drill geometry and motion parameters. This work provides a new method for design and optimization of low speed auger drill systems and research on particle flow with small scale mechanical constraints.

  18. Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating agent.

    PubMed

    Purushottamachar, Puranik; Khandelwal, Aakanksha; Vasaitis, Tadas S; Bruno, Robert D; Gediya, Lalji K; Njar, Vincent C O

    2008-04-01

    The search for novel androgen receptor (AR) down-regulating agents by catalyst HipHop pharmacophore modeling led to the discovery of some lead molecules. Unexpectedly, the effect of these leads on human prostate cancer LNCaP cell viability did not correlate with the ability of the compounds to cause down-regulation of AR protein expression. Through rational synthetic optimization of the lead compound (BTB01434), we have discovered a series of novel substituted diaryl molecules as potent anti-prostate cancer agents. Some compounds (1-6) were shown to be extremely potent inhibitors of LNCaP cell viability with GI(50) values in the nanomolar range (1.45-83 nM). The most potent compound (4-methylphenyl)[(4-methylphenyl)sulfonyl]amine (5) with a GI(50) value of 1.45 nM is 27,000 times more potent than our lead compound BTB01434 (GI(50)=39.8 microM). In addition, some of the compounds exhibited modest anti-androgenic activities and one was also a potent inhibitor (GI(50)=850 nM) of PC-3 (AR-null) cell growth. A clear structure-activity relationship (SAR) has been established for activity against LNCaP cells, where potent molecules possess two substituted/unsubstituted aromatic rings connected through a sulfonamide linker. These novel compounds are strong candidates for development for the treatment of hormone-sensitive and importantly hormone-refractory prostate cancers in humans. PMID:18316193

  19. The Pierre Auger Observatory progress and first results

    SciTech Connect

    Mantsch, Paul M.

    2005-08-01

    The Pierre Auger Observatory was designed for a high statistics, full sky study of cosmic rays at the highest energies. Energy, direction and composition measurements are intended to illuminate the mysteries of the most energetic particles in nature. The Auger Observatory utilizes a surface array together with air fluorescence telescopes which together provide a powerful instrument for air shower reconstruction. The southern part of the Auger Observatory, now under construction in the Province of Mendoza, Argentina, is well over half finished. Active detectors have been recording events for one and a half years. Preliminary results based on this first data set are presented.

  20. Studies of Cosmic Ray Composition and Air Shower Structure with the Pierre Auger Observatory

    SciTech Connect

    Abraham, : J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Ahn, E.J.; Allard, D.; Allekotte, I.; Allen, J.; Alvarez-Muniz, J.; Ambrosio, M.; Anchordoqui, L.

    2009-06-01

    These are presentations to be presented at the 31st International Cosmic Ray Conference, in Lodz, Poland during July 2009. It consists of the following presentations: (1) Measurement of the average depth of shower maximum and its fluctuations with the Pierre Auger Observatory; (2) Study of the nuclear mass composition of UHECR with the surface detectors of the Pierre Auger Observatory; (3) Comparison of data from the Pierre Auger Observatory with predictions from air shower simulations: testing models of hadronic interactions; (4) A Monte Carlo exploration of methods to determine the UHECR composition with the Pierre Auger Observatory; (5) The delay of the start-time measured with the Pierre Auger Observatory for inclined showers and a comparison of its variance with models; (6) UHE neutrino signatures in the surface detector of the Pierre Auger Observatory; and (7) The electromagnetic component of inclined air showers at the Pierre Auger Observatory.

  1. A search for anisotropy in the arrival directions of ultra high energy cosmic rays recorded at the Pierre Auger Observatory

    SciTech Connect

    Abreu, P.

    2012-01-01

    Observations of cosmic ray arrival directions made with the Pierre Auger Observatory have previously provided evidence of anisotropy at the 99% CL using the correlation of ultra high energy cosmic rays (UHECRs) with objects drawn from the Veron-Cetty Veron catalog. In this paper we report on the use of three catalog independent methods to search for anisotropy. The 2pt-L, 2pt+ and 3pt methods, each giving a different measure of self-clustering in arrival directions, were tested on mock cosmic ray data sets to study the impacts of sample size and magnetic smearing on their results, accounting for both angular and energy resolutions. If the sources of UHECRs follow the same large scale structure as ordinary galaxies in the local Universe and if UHECRs are deflected no more than a few degrees, a study of mock maps suggests that these three methods can efficiently respond to the resulting anisotropy with a P-value = 1.0% or smaller with data sets as few as 100 events. Using data taken from January 1, 2004 to July 31, 2010 we examined the 20, 30, ..., 110 highest energy events with a corresponding minimum energy threshold of about 51 EeV. The minimum P-values found were 13.5% using the 2pt-L method, 1.0% using the 2pt+ method and 1.1% using the 3pt method for the highest 100 energy events. In view of the multiple (correlated) scans performed on the data set, these catalog-independent methods do not yield strong evidence of anisotropy in the highest energy cosmic rays.

  2. Final-state screening dynamics in resonant Auger decay at the 2p edge of vanadium

    NASA Astrophysics Data System (ADS)

    Ilakovac, V.; Kralj, M.; Pervan, P.; Richter, M. C.; Goldoni, A.; Larciprete, R.; Petaccia, L.; Hricovini, K.

    2005-02-01

    We investigated the resonant Auger process near the V 2p3/2 edge in vanadium metal. Attention is centered on the onset of Auger decays and their behavior below the 2p3/2 resonance. The 2p3/23d3d decay has a crossover from the Raman-Auger to the normal Auger regime at the 2p ionization threshold. Meanwhile, Auger decays with core holes in the final state have normal Auger behavior even below the ionization threshold, the 2p3/23p3p process being visible at 2.2 eV lower photon energy. The different resonant behavior of these Auger decays can be understood within the one-step model as final-state screening effects affecting the photoexcitation.

  3. Pharmacologic Characterization in the Rat of a Potent Analgesic Lacking Respiratory Depression, IBNtxA

    PubMed Central

    Grinnell, Steven G.; Majumdar, Susruta; Narayan, Ankita; Le Rouzic, Valerie; Ansonoff, Michael; Pintar, John E.

    2014-01-01

    IBNtxA (3′-iodobenzoyl-6β-naltrexamide) is a potent analgesic in mice lacking many traditional opioid side effects. In mice, it displays no respiratory depression, does not produce physical dependence with chronic administration, and shows no cross-tolerance to morphine. It has limited effects on gastrointestinal transit and shows no reward behavior. Biochemical studies indicate its actions are mediated through a set of μ-opioid receptor clone MOR-1 splice variants associated with exon 11 that lack exon 1 and contain only six transmembrane domains. Like the mouse and human, rats express exon 11–associated splice variants that also contain only six transmembrane domains, raising the question of whether IBNtxA would have a similar pharmacologic profile in rats. When given systemically, IBNtxA is a potent analgesic in rats, with an ED50 value of 0.89 mg/kg s.c., approximately 4-fold more potent than morphine. It shows no analgesic cross-tolerance in morphine-pelleted rats. IBNtxA displays no respiratory depression as measured by blood oxygen saturation. In contrast, oximetry shows that an equianalgesic dose of morphine lowers blood oxygen saturation values by 30%. IBNtxA binding is present in a number of brain regions, with the thalamus standing out with very high levels and the cerebellum with low levels. As in mice, IBNtxA is a potent analgesic in rats with a favorable pharmacologic profile and reduced side effects. PMID:24970924

  4. Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA.

    PubMed

    Grinnell, Steven G; Majumdar, Susruta; Narayan, Ankita; Le Rouzic, Valerie; Ansonoff, Michael; Pintar, John E; Pasternak, Gavril W

    2014-09-01

    IBNtxA (3'-iodobenzoyl-6β-naltrexamide) is a potent analgesic in mice lacking many traditional opioid side effects. In mice, it displays no respiratory depression, does not produce physical dependence with chronic administration, and shows no cross-tolerance to morphine. It has limited effects on gastrointestinal transit and shows no reward behavior. Biochemical studies indicate its actions are mediated through a set of μ-opioid receptor clone MOR-1 splice variants associated with exon 11 that lack exon 1 and contain only six transmembrane domains. Like the mouse and human, rats express exon 11-associated splice variants that also contain only six transmembrane domains, raising the question of whether IBNtxA would have a similar pharmacologic profile in rats. When given systemically, IBNtxA is a potent analgesic in rats, with an ED50 value of 0.89 mg/kg s.c., approximately 4-fold more potent than morphine. It shows no analgesic cross-tolerance in morphine-pelleted rats. IBNtxA displays no respiratory depression as measured by blood oxygen saturation. In contrast, oximetry shows that an equianalgesic dose of morphine lowers blood oxygen saturation values by 30%. IBNtxA binding is present in a number of brain regions, with the thalamus standing out with very high levels and the cerebellum with low levels. As in mice, IBNtxA is a potent analgesic in rats with a favorable pharmacologic profile and reduced side effects. PMID:24970924

  5. Atomic Auger Doppler effects upon emission of fast photoelectrons.

    PubMed

    Simon, Marc; Püttner, Ralph; Marchenko, Tatiana; Guillemin, Renaud; Kushawaha, Rajesh K; Journel, Loïc; Goldsztejn, Gildas; Piancastelli, Maria Novella; Ablett, James M; Rueff, Jean-Pascal; Céolin, Denis

    2014-01-01

    Studies of photoemission processes induced by hard X-rays including production of energetic electrons have become feasible due to recent substantial improvement of instrumentation. Novel dynamical phenomena have become possible to investigate in this new regime. Here we show a significant change in Auger emission following 1s photoionization of neon, which we attribute to the recoil of the Ne ion induced by the emission of a fast photoelectron. Because of the preferential motion of the ionized Ne atoms along two opposite directions, an Auger Doppler shift is revealed, which manifests itself as a gradual broadening and doubling of the Auger spectral features. This Auger Doppler effect should be a general phenomenon in high-energy photoemission of both isolated atoms and molecules, which will have to be taken into account in studies of other recoil effects such as vibrational or rotational recoil in molecules, and may also have consequences in measurements in solids. PMID:24906107

  6. A perfect wetting of Mg monolayer on Ag(111) under atomic scale investigation: First principles calculations, scanning tunneling microscopy, and Auger spectroscopy

    NASA Astrophysics Data System (ADS)

    Migaou, Amani; Sarpi, Brice; Guiltat, Mathilde; Payen, Kevin; Daineche, Rachid; Landa, Georges; Vizzini, Sébastien; Hémeryck, Anne

    2016-05-01

    First principles calculations, scanning tunneling microscopy, and Auger spectroscopy experiments of the adsorption of Mg on Ag(111) substrate are conducted. This detailed study reveals that an atomic scale controlled deposition of a metallic Mg monolayer perfectly wets the silver substrate without any alloy formation at the interface at room temperature. A liquid-like behavior of the Mg species on the Ag substrate is highlighted as no dot formation is observed when coverage increases. Finally a layer-by-layer growth mode of Mg on Ag(111) can be predicted, thanks to density functional theory calculations as observed experimentally.

  7. A perfect wetting of Mg monolayer on Ag(111) under atomic scale investigation: First principles calculations, scanning tunneling microscopy, and Auger spectroscopy.

    PubMed

    Migaou, Amani; Sarpi, Brice; Guiltat, Mathilde; Payen, Kevin; Daineche, Rachid; Landa, Georges; Vizzini, Sébastien; Hémeryck, Anne

    2016-05-21

    First principles calculations, scanning tunneling microscopy, and Auger spectroscopy experiments of the adsorption of Mg on Ag(111) substrate are conducted. This detailed study reveals that an atomic scale controlled deposition of a metallic Mg monolayer perfectly wets the silver substrate without any alloy formation at the interface at room temperature. A liquid-like behavior of the Mg species on the Ag substrate is highlighted as no dot formation is observed when coverage increases. Finally a layer-by-layer growth mode of Mg on Ag(111) can be predicted, thanks to density functional theory calculations as observed experimentally. PMID:27208966

  8. Auger decay of 3p-ionized krypton

    SciTech Connect

    Jonauskas, V.; Kucas, S.; Karazija, R.

    2011-11-15

    A theoretical study of Auger cascades during the decay of 3p{sub 1/2} and 3p{sub 3/2} vacancies in krypton has been performed by level-by-level calculations using a wide configuration interaction basis. Auger spectra for all steps of the cascades are presented and are compared with the existing experimental data. Good agreement of our results with the branching ratios of ions measured by a coincidence technique is obtained.

  9. The Surface Detector System of the Pierre Auger Observatory

    SciTech Connect

    Allekotte, I.; Barbosa, A.F.; Bauleo, P.; Bonifazi, C.; Civit, B.; Escobar, C.O.; Garcia, B.; Guedes, G.; Gomez Berisso, M.; Harton, J.L.; Healy, M.; /Cuyo U. /Buenos Aires, CONICET /Natl. Tech. U., San Rafael /Campinas State U. /UEFS, Feira de Santana /Bahia U. /BUAP, Puebla /Santiago de Compostela U. /Fermilab /UCLA /Colorado State U.

    2007-11-01

    The Pierre Auger Observatory is designed to study cosmic rays with energies greater than 10{sup 19} eV. Two sites are envisaged for the observatory, one in each hemisphere, for complete sky coverage. The southern site of the Auger Observatory, now approaching completion in Mendoza, Argentina, features an array of 1600 water-Cherenkov surface detector stations covering 3000 km{sup 2}, together with 24 fluorescence telescopes to record the air shower cascades produced by these particles. The two complementary detector techniques together with the large collecting area form a powerful instrument for these studies. Although construction is not yet complete, the Auger Observatory has been taking data stably since January 2004 and the first physics results are being published. In this paper we describe the design features and technical characteristics of the surface detector stations of the Pierre Auger Observatory.

  10. Interference and PCI in argon Auger (e, 2e) spectra

    NASA Astrophysics Data System (ADS)

    Waterhouse, D. K.; Williams, J. F.

    1997-06-01

    Angle-dependent interference is observed in electron-impact ionization (e, 2e) coincidence experiments on the argon 0953-4075/30/12/013/img1 and 0953-4075/30/12/013/img2 Auger transitions. Recapture of the slow ejected electron from the Auger process leads to interference with the satellite-state ionization processes. The post-collision interaction (PCI) and interference effects are quantified for a large range of excess energies.

  11. Adhesion of metals to a clean iron surface studied with LEED and Auger emission spectroscopy.

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1972-01-01

    Discussion of the results of adhesion experiments conducted with various metals contacting a clean iron surface. The metals included gold, silver, nickel, platinum, lead, tantalum, aluminum, and cobalt. Some of the metals were examined with oxygen present on their surface as well as in the clean state. The results indicate that, with the various metals contacting iron, the cohesively weaker will adhere and transfer to the cohesively stronger. The chemical activity of the metal also influenced the adhesive forces measured. With oxygen present on the metal surface, the adhesive forces measured could be correlated with the binding energy of the metal to oxygen.

  12. Swine Interferon-Inducible Transmembrane Proteins Potently Inhibit Influenza A Virus Replication

    PubMed Central

    Lanz, Caroline; Yángüez, Emilio; Andenmatten, Dario

    2014-01-01

    Human interferon-inducible transmembrane proteins (IFITMs) were identified as restriction factors of influenza A virus (IAV). Given the important role of pigs in the zoonotic cycle of IAV, we cloned swine IFITMs (swIFITMs) and found two IFITM1-like proteins, one homologue of IFITM2, and a homologue of IFITM3. We show that swIFITM2 and swIFITM3 localize to endosomes and display potent antiviral activities. Knockdown of swIFITMs strongly reduced virus inhibition by interferon, establishing the swIFITMs as potent restriction factors in porcine cells. PMID:25320322

  13. Valence Auger decay following 3 s photoionization in potassium

    NASA Astrophysics Data System (ADS)

    Palaudoux, J.; Sheinerman, S.; Soronen, J.; Huttula, S.-M.; Huttula, M.; Jänkälä, K.; Andric, L.; Ito, K.; Lablanquie, P.; Penent, F.; Bizau, J.-M.; Guilbaud, S.; Cubaynes, D.

    2015-07-01

    We have studied photoionization in the inner valence 3 s subshell of K and the spectroscopic properties of the two 3 s-1(1S) and (3S) resulting states. Similar to the Rb and Cs cases, the lifetime widths of the (1S) and (3S) states are found to be markedly different, due to the electron correlation effects. The main part of the study deals with the subsequent Auger decay of the 3 s-1 states, which have the particularity to involve low energy (˜5 eV ) Auger electrons. A magnetic bottle spectrometer with a multicoincidence technique has been used to observe and filter the Auger spectra with respect to the K2 + final state. The evolution of these Auger spectra has been investigated near the ionization threshold. They show strong post-collision interaction (PCI) effects, which are well reproduced by semiclassical and eikonal models. They reveal the importance of the photoelectron-Auger-electron interaction associated with these low energy Auger electrons.

  14. Recent results from the Pierre Auger Observatory

    SciTech Connect

    Gascón, Alberto; Collaboration: Pierre Auger Collaboration

    2014-07-23

    The Pierre Auger Observatory has been designed to investigate the origin and nature of Ultra High Energy Cosmic Rays (UHECR) using a hybrid detection technique. In this contribution we present some of the most recent results of the observatory, namely the upper-end of the spectrum of cosmic rays, state-of-the-art analyses on mass composition, the measurements of the proton-air cross-section, and the number of muons at ground.

  15. The marine cyanobacterial metabolite gallinamide A is a potent and selective inhibitor of human cathepsin L.

    PubMed

    Miller, Bailey; Friedman, Aaron J; Choi, Hyukjae; Hogan, James; McCammon, J Andrew; Hook, Vivian; Gerwick, William H

    2014-01-24

    A number of marine natural products are potent inhibitors of proteases, an important drug target class in human diseases. Hence, marine cyanobacterial extracts were assessed for inhibitory activity to human cathepsin L. Herein, we have shown that gallinamide A potently and selectively inhibits the human cysteine protease cathepsin L. With 30 min of preincubation, gallinamide A displayed an IC50 of 5.0 nM, and kinetic analysis demonstrated an inhibition constant of ki = 9000 ± 260 M(-1) s(-1). Preincubation-dilution and activity-probe experiments revealed an irreversible mode of inhibition, and comparative IC50 values display a 28- to 320-fold greater selectivity toward cathepsin L than closely related human cysteine cathepsin V or B. Molecular docking and molecular dynamics simulations were used to determine the pose of gallinamide in the active site of cathepsin L. These data resulted in the identification of a pose characterized by high stability, a consistent hydrogen bond network, and the reactive Michael acceptor enamide of gallinamide A positioned near the active site cysteine of the protease, leading to a proposed mechanism of covalent inhibition. These data reveal and characterize the novel activity of gallinamide A as a potent inhibitor of human cathepsin L. PMID:24364476

  16. The Marine Cyanobacterial Metabolite Gallinamide A is a Potent and Selective Inhibitor of Human Cathepsin L

    PubMed Central

    Miller, Bailey; Friedman, Aaron J; Choi, Hyukjae; Hogan, James; McCammon, J. Andrew; Hook, Vivian; Gerwick, William H.

    2014-01-01

    A number of marine natural products are potent inhibitors of proteases, an important drug target class in human diseases. Hence, marine cyanobacterial extracts were assessed for inhibitory activity to human cathepsin L. Herein, we have shown that gallinamide A potently and selectively inhibits the human cysteine protease, cathepsin L. With 30 min of preincubation, gallinamide A displayed an IC50 of 5.0 nM, and kinetic analysis demonstrated an inhibition constant of ki = 9000 ± 260 M−1 s−1. Preincubation-dilution and activity-probe experiments revealed an irreversible mode of inhibition, and comparative IC50 values display a 28- to 320- fold greater selectivity toward cathepsin L than closely related human cysteine cathepsins V or B. Molecular docking and molecular dynamics simulations were used to determine the pose of gallinamide in the active site of cathepsin L. These data resulted in the identification of a pose characterized by high stability, a consistent hydrogen bond network, and the reactive Michael acceptor enamide of gallinamide A positioned near the active site cysteine of the protease, leading to a proposed mechanism of covalent inhibition. These data reveal and characterize the novel activity of gallinamide A as a potent inhibitor of human cathepsin L. PMID:24364476

  17. Distributed Computing for the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Chudoba, J.

    2015-12-01

    Pierre Auger Observatory operates the largest system of detectors for ultra-high energy cosmic ray measurements. Comparison of theoretical models of interactions with recorded data requires thousands of computing cores for Monte Carlo simulations. Since 2007 distributed resources connected via EGI grid are successfully used. The first and the second versions of production system based on bash scripts and MySQL database were able to submit jobs to all reliable sites supporting Virtual Organization auger. For many years VO auger belongs to top ten of EGI users based on the total used computing time. Migration of the production system to DIRAC interware started in 2014. Pilot jobs improve efficiency of computing jobs and eliminate problems with small and less reliable sites used for the bulk production. The new system has also possibility to use available resources in clouds. Dirac File Catalog replaced LFC for new files, which are organized in datasets defined via metadata. CVMFS is used for software distribution since 2014. In the presentation we give a comparison of the old and the new production system and report the experience on migrating to the new system.

  18. A Highly Arginolytic Streptococcus Species That Potently Antagonizes Streptococcus mutans.

    PubMed

    Huang, Xuelian; Palmer, Sara R; Ahn, Sang-Joon; Richards, Vincent P; Williams, Matthew L; Nascimento, Marcelle M; Burne, Robert A

    2016-04-01

    The ability of certain oral biofilm bacteria to moderate pH through arginine metabolism by the arginine deiminase system (ADS) is a deterrent to the development of dental caries. Here, we characterize a novel Streptococcus strain, designated strain A12, isolated from supragingival dental plaque of a caries-free individual. A12 not only expressed the ADS pathway at high levels under a variety of conditions but also effectively inhibited growth and two intercellular signaling pathways of the dental caries pathogen Streptococcus mutans. A12 produced copious amounts of H2O2 via the pyruvate oxidase enzyme that were sufficient to arrest the growth of S. mutans. A12 also produced a protease similar to challisin (Sgc) of Streptococcus gordonii that was able to block the competence-stimulating peptide (CSP)-ComDE signaling system, which is essential for bacteriocin production by S. mutans. Wild-type A12, but not an sgc mutant derivative, could protect the sensitive indicator strain Streptococcus sanguinis SK150 from killing by the bacteriocins of S. mutans. A12, but not S. gordonii, could also block the XIP (comX-inducing peptide) signaling pathway, which is the proximal regulator of genetic competence in S. mutans, but Sgc was not required for this activity. The complete genome sequence of A12 was determined, and phylogenomic analyses compared A12 to streptococcal reference genomes. A12 was most similar to Streptococcus australis and Streptococcus parasanguinis but sufficiently different that it may represent a new species. A12-like organisms may play crucial roles in the promotion of stable, health-associated oral biofilm communities by moderating plaque pH and interfering with the growth and virulence of caries pathogens. PMID:26826230

  19. MIT(1), a black mamba toxin with a new and highly potent activity on intestinal contraction.

    PubMed

    Schweitz, H; Pacaud, P; Diochot, S; Moinier, D; Lazdunski, M

    1999-11-19

    Mamba intestinal toxin (MIT(1)) isolated from Dendroaspis polylepis venom is a 81 amino acid polypeptide cross-linked by five disulphide bridges. MIT(1) has a very potent action on guinea-pig intestinal contractility. MIT(1) (1 nM) potently contracts longitudinal ileal muscle and distal colon, and this contraction is equivalent to that of 40 mM K(+). Conversely MIT(1) relaxes proximal colon again as potently as 40 mM K(+). The MIT(1)-induced effects are antagonised by tetrodotoxin (1 microM) in proximal and distal colon but not in longitudinal ileum. The MIT(1)-induced relaxation of the proximal colon is reversibly inhibited by the NO synthase inhibitor L-NAME (200 microM). (125)I-labelled MIT(1) binds with a very high affinity to both ileum and brain membranes (K(d)=1.3 pM and 0.9 pM, and B(max)=30 fmol/mg and 26 fmol/mg, respectively). MIT(1) is a very highly selective toxin for a receptor present both in the CNS and in the smooth muscle and which might be an as yet unidentified K(+) channel. PMID:10567694

  20. Optimization of a series of potent and selective ketone histone deacetylase inhibitors.

    PubMed

    Pescatore, Giovanna; Kinzel, Olaf; Attenni, Barbara; Cecchetti, Ottavia; Fiore, Fabrizio; Fonsi, Massimiliano; Rowley, Michael; Schultz-Fademrecht, Carsten; Serafini, Sergio; Steinkühler, Christian; Jones, Philip

    2008-10-15

    Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in the clinic. Herein we describe the optimization of a series of ketone small molecule HDAC inhibitors leading to potent and selective class I HDAC inhibitors with good dog PK. PMID:18809328

  1. Discovery of a Potent, Dual Serotonin and Norepinephrine Reuptake Inhibitor

    PubMed Central

    2013-01-01

    The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug–drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior. Compound 1 thus represents a potential new probe to explore utility of SNRIs in central nervous system disorders, including chronic pain conditions. PMID:24900709

  2. Nitric oxide as a potent fumigant for postharvest pest control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is a great demand for safe and effective alternative fumigants to replace methyl bromide and other toxic fumigants for pest control. Nitric oxide, a common signal molecule in biological systems, was found to be effective and safe to control insects under ultralow oxygen conditions. Fumigatio...

  3. Faculty Leadership: A Dynamic, Potent Force for Comprehensive Institutional Development.

    ERIC Educational Resources Information Center

    Franklin, Homer D.; And Others

    Responding to the crisis in leadership at community colleges, scholars and practitioners alike have called for a new style of leadership capable of adapting and responding easily to an uncertain political and social climate. Although community colleges are rooted historically in a hierarchical leadership mode, there seems to be broad consensus…

  4. Binary collision model for neon Auger spectra from neon ion bombardment of the aluminum surface

    NASA Technical Reports Server (NTRS)

    Pepper, S. V.

    1986-01-01

    A model is developed to account for the angle-resolved Auger spectra from neon ion bombardment of the aluminum surface recently obtained by Pepper and Aron. The neon is assumed to be excited in a single asymmetric neon-aluminum-collision and scattered back into the vacuum where it emits an Auger electron. The velocity of the Auger electron acquires a Doppler shift by virtue of the emission from a moving source. The dependence of the Auger peak shape and energy on the incident ion energy, angle of incidence and on the angle of Auger electron emission with respect to the surface is presented. Satisfactory agreement with the angle resolved experimental observations is obtained. The dependence of the angle-integrated Auger yield on the incident ion energy and angle of incidence is also obtained and shown to be in satisfactory agreement with available experimental evidence.

  5. Spermine is a potent modulator of proton transport through LHCII.

    PubMed

    Tsiavos, Theodoros; Ioannidis, Nikolaos E; Tsortos, Achilleas; Gizeli, Electra; Kotzabasis, Kiriakos

    2015-04-01

    The effect of spermine on proton transport across large unilamellar liposomes containing incorporated complexes of the PSII antenna has been studied with the application of a pH-sensitive dye entrapped inside the vesicles. Both monomeric LHCbs and trimeric LHCII increased the permeability of proteoliposomes to protons when in a partly aggregated state within the lipid membrane. We have previously shown that a spermine-induced conformational change in LHCII results in its aggregation and ultimately in the enhancement of excitation energy as heat (qE). In this paper, spermine-induced aggregation of LHCII was found to facilitate proton transport across the proteoliposomes, indicating that a second protective mechanism (other than qE) might exist and might be regulated in vivo by polyamines when photosynthesis is saturated in excess light. PMID:25659334

  6. Methoxetamine--a novel recreational drug with potent hallucinogenic properties.

    PubMed

    Zawilska, Jolanta B

    2014-11-01

    Methoxetamine is one of the constantly growing group of novel psychoactive substances that has emerged in recent years. The compound belongs to the arylcyclohexylamine class, which is used for its recreational and psychedelic effects. Methoxetamine is a structural analogue of ketamine, with a much longer duration of action and intensity of effects, and has been extensively advertised as its 'legal' and 'bladder friendly' alternative. This review surveys the current state of knowledge regarding the metabolism, pharmacology, prevalence and pattern of methoxetamine use, and analytical methods of its detection. Consumption of methoxetamine bears a significant health risk and may even lead to fatal intoxication. A significant amount of research is still needed in order to fully quantify the short- and long-term effects of methoxetamine and its interaction with other drugs of abuse. PMID:25128700

  7. Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity.

    PubMed

    Allemann, Oliver; Brutsch, Manuela; Lukesh, John C; Brody, Daniel M; Boger, Dale L

    2016-07-13

    Many natural products, including vinblastine, have not been easily subjected to simplifications in their structures by synthetic means or modifications by late-stage semisynthetic derivatization in ways that enhance their biological potency. Herein, we detail a synthetic vinblastine that incorporates added benign complexity (ABC), which improves activity 10-fold, and is now accessible as a result of advances in the total synthesis of the natural product. The compound incorporates designed added molecular complexity but no new functional groups and maintains all existing structural and conformational features of the natural product. It constitutes a member of an analogue class presently inaccessible by semisynthetic derivatization of the natural product, by its late-stage functionalization, or by biosynthetic means. Rather, it was accessed by synthetic means, using an appropriately modified powerful penultimate single-step vindoline-catharanthine coupling strategy that proceeds with a higher diastereoselectivity than found for the natural product itself. PMID:27356080

  8. Alstroemeria. A new and potent allergen for florists.

    PubMed

    Adams, R M; Daily, A D; Brancaccio, R R; Dhillon, I P; Gendler, E C

    1990-01-01

    Alstroemeria (Peruvian or Inca lily) has found particular favor because of its beauty and durability. However, it may induce a dermatitis so severe that workers have to change jobs. The dermatitis is chronic, with fissuring at the tips of the fingers bilaterally. Itching is often a less prominent symptom. Preventative measures are of little benefit, and many floral shops are vanishing the plant. PMID:2137401

  9. A Potent Phytotoxic Substance in Aglaia odorata Lour.

    PubMed

    Kato-Noguchi, Hisashi; Suzuki, Masahiko; Noguchi, Kazutaka; Ohno, Osamu; Suenaga, Kiyotake; Laosinwattana, Chamroon

    2016-05-01

    Aglaia odorata Lour. (Meliaceae) was found to have very strong allelopathic activity and a bioherbicide PORGANIC(™) was developed from its leaf extracts. However, the phytotoxic substances causing the strong allelopathic activity of the plants have not yet been determined. Therefore, we investigated allelopathic properties and phytotoxic substances in A. odorata. Aqueous EtOH extracts of A. odorata leaves inhibited root and shoot growth of garden cress (Lepidum sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), ryegrass (Lolium multiflorum), and Echinochloa crus-galli with the extract concentration-dependent manner. The extracts were then purified and a major phytotoxic substance with allelopathic activity was isolated and identified by spectral data as rocaglaol. Rocaglaol inhibited the growth of garden cress and E. crus-galli at concentrations > 0.3 and 0.03 μm, respectively. The concentrations required for 50% inhibition ranged from 0.09 to 2.5 μm. The inhibitory activity of rocaglaol on the weed species, E. crus-galli, was much greater than that of abscisic acid. These results suggest that rocaglaol may be a major contributor to the allelopathic effect of A. odorata and bioherbicide PORGANIC(™) . PMID:27088639

  10. Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2.

    PubMed

    Kokotos, George; Hsu, Yuan-Hao; Burke, John E; Baskakis, Constantinos; Kokotos, Christoforos G; Magrioti, Victoria; Dennis, Edward A

    2010-05-13

    Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one (FKGK18) is the most potent inhibitor of GVIA iPLA(2) (X(I)(50) = 0.0002) ever reported. Being 195 and >455 times more potent for GVIA iPLA(2) than for GIVA cPLA(2) and GV sPLA(2), respectively, makes it a valuable tool to explore the role of GVIA iPLA(2) in cells and in vivo models. 1,1,1,2,2,3,3-Heptafluoro-8-(naphthalene-2-yl)octan-4-one inhibited GVIA iPLA(2) with a X(I)(50) value of 0.001 while inhibiting the other intracellular GIVA cPLA(2) and GV sPLA(2) at least 90 times less potently. Hexa- and octafluoro ketones were also found to be potent inhibitors of GVIA iPLA(2); however, they are not selective. PMID:20369880

  11. Potent and Selective Fluoroketone Inhibitors of Group VIA Calcium-Independent Phospholipase A2

    PubMed Central

    Kokotos, George; Hsu, Yuan-Hao; Burke, John E.; Baskakis, Constantinos; Kokotos, Christoforos G.; Magrioti, Victoria; Dennis, Edward A.

    2010-01-01

    Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA2 inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(naphthalen-2-yl)hexan-2-one (FKGK18) is the most potent inhibitor of GVIA iPLA2 (XI(50) 0.0002) ever reported. Being 195 and >455 times more potent for GVIA iPLA2 than for GIVA cPLA2 and GV sPLA2, respectively, makes it a valuable tool to explore the role of GVIA iPLA2 in cells and in vivo models. 1,1,1,2,2,3,3-Heptafluoro-8-(naphthalene-2-yl) octan-4-one inhibited GVIA iPLA2 with a XI(50) value of 0.001, while inhibiting the other intracellular GIVA cPLA2 and GV sPLA2 at least 90-times less potently. Hexa- and octa-fluoro ketones were also found to be potent inhibitors of GVIA iPLA2; however they are not selective. PMID:20369880

  12. Glucagon-like peptide 1: a potent glycogenic hormone.

    PubMed

    Valverde, I; Morales, M; Clemente, F; López-Delgado, M I; Delgado, E; Perea, A; Villanueva-Peñacarrillo, M L

    1994-08-01

    GLP-1(7-36)amide is an insulinotropic peptide derived from the intestinal post-translational proglucagon process, the release of which is increased mainly after a carbohydrate meal; also, its anti-diabetogenic effect in normal and diabetic states has been reported. In this study, GLP-1(7-36)amide stimulates the formation of glycogen from glucose in isolated rat hepatocytes, such a glycogenic effect being achieved with physiological concentrations of the peptide. The GLP-1(7-36)amide-induced glycogenesis is abolished by glucagon, and it is accompanied by stimulation of the glycogen synthase alpha activity and by a decrease in the basal and glucagon-stimulated cyclic AMP content. These findings could explain, at least in part, the GLP-1(7-36)amide insulin-independent plasma glucose lowering effect. PMID:8050588

  13. Smad4 (DPC4)--a potent tumour suppressor?

    PubMed Central

    Duff, E. K.; Clarke, A. R.

    1998-01-01

    The recently described family of Smad molecules are essential mediators of transforming growth factor beta (TGF-beta) signalling. To date, seven members of this family have been identified, each of which plays a specific and separate role in mediating TGF-beta superfamily gene transcription. At least two different Smads, Smad2 and Smad4 (DPC4), have been implicated in human cancer and appear to have tumour-suppressor functions. Loss of function of Smad4 is most strongly associated with human pancreatic and colorectal malignancy. Furthermore, work from several different groups has suggested associations between Smad4 loss and malignancy in a number of other tissues. Here, we present a review of the current state of the literature implicating the central Smad mediator, Smad4, in the development of cancer. PMID:9862572

  14. Calixtyrosol: a Novel Calixarene Based Potent Radical Scavenger.

    PubMed

    Nasuhi Pur, Fazel; Akbari Dilmaghani, Karim

    2015-01-01

    The oxidative stress causes many diseases in human, therefore antioxidants have a special position in the medicinal chemistry. Tyrosol is an important antioxidant with a plenty of biological properties. There are many strategies such as clustering single drug units in order to develop new drugs. The cluster effect can increase drug effects relative to single drug unit. Calixtyrosol is the novel cluster of tyrosol that shows a more effective antioxidant activity than single tyrosol. In fact, tyrosol can be considered as 1/4 of the cluster. Four hydroxyethyl moieties have been grafted at the upper rim of the calix[4]arene in all-syn orientation, giving novel agent in the field of antioxidant agents. Free radical scavenging tests were determined by the 2, 2-diphenyl-1-picrylhydrazyl radical in methanol for four antioxidants: calixtyrosol, tyrosol, hydroxytyrosol and 3, 5-di-tert-buty l-4-hydroxytoluene to compare their antioxidant activity. Free radical scavenging test showed that calixtyrosol has enhanced antioxidant activity in comparison to the corresponding single tyrosol unit (> 5 fold), it has even more active than the other test antioxidants (2 fold). Presumably, it is attributed to tethering and arraying of four impacted tyrosol units, which make a synergistic effect in interactions with radicals for creating effective radical scavenging activity. This method is in debt of synergistic effect, tethering and arraying of single units in the cluster structure. PMID:26664385

  15. Calixtyrosol: a Novel Calixarene Based Potent Radical Scavenger

    PubMed Central

    Nasuhi Pur, Fazel; Akbari Dilmaghani, Karim

    2015-01-01

    The oxidative stress causes many diseases in human, therefore antioxidants have a special position in the medicinal chemistry. Tyrosol is an important antioxidant with a plenty of biological properties. There are many strategies such as clustering single drug units in order to develop new drugs. The cluster effect can increase drug effects relative to single drug unit. Calixtyrosol is the novel cluster of tyrosol that shows a more effective antioxidant activity than single tyrosol. In fact, tyrosol can be considered as 1/4 of the cluster. Four hydroxyethyl moieties have been grafted at the upper rim of the calix[4]arene in all-syn orientation, giving novel agent in the field of antioxidant agents. Free radical scavenging tests were determined by the 2, 2-diphenyl-1-picrylhydrazyl radical in methanol for four antioxidants: calixtyrosol, tyrosol, hydroxytyrosol and 3, 5-di-tert-buty l-4-hydroxytoluene to compare their antioxidant activity. Free radical scavenging test showed that calixtyrosol has enhanced antioxidant activity in comparison to the corresponding single tyrosol unit (> 5 fold), it has even more active than the other test antioxidants (2 fold). Presumably, it is attributed to tethering and arraying of four impacted tyrosol units, which make a synergistic effect in interactions with radicals for creating effective radical scavenging activity. This method is in debt of synergistic effect, tethering and arraying of single units in the cluster structure. PMID:26664385

  16. Hydrogen sulfide as a potent cardiovascular protective agent.

    PubMed

    Yu, Xiao-Hua; Cui, Li-Bao; Wu, Kai; Zheng, Xi-Long; Cayabyab, Francisco S; Chen, Zhi-Wei; Tang, Chao-Ke

    2014-11-01

    Hydrogen sulfide (H2S) is a well-known toxic gas with the characteristic smell of rotten eggs. It is synthesized endogenously in mammals from the sulfur-containing amino acid l-cysteine by the action of several distinct enzymes: cystathionine-γ-lyase (CSE), cystathionine-ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) along with cysteine aminotransferase (CAT). In particular, CSE is considered to be the major H2S-producing enzyme in the cardiovascular system. As the third gasotransmitter next to nitric oxide (NO) and carbon monoxide (CO), H2S plays an important role in the regulation of vasodilation, angiogenesis, inflammation, oxidative stress and apoptosis. Growing evidence has demonstrated that this gas exerts a significant protective effect against the progression of cardiovascular diseases by a number of mechanisms such as vasorelaxation, inhibition of cardiovascular remodeling and resistance to form foam cells. The aim of this review is to provide an overview of the physiological functions of H2S and its protection against several major cardiovascular diseases, and to explore its potential health and therapeutic benefits. A better understanding will help develop novel H2S-based therapeutic interventions for these diseases. PMID:25058799

  17. Nesfatin-1 as a New Potent Regulator in Reproductive System

    PubMed Central

    Kim, Jinhee; Yang, Hyunwon

    2012-01-01

    Nesfatin-1 is a recently discovered anorexigenic peptide which is distributed in several brain areas implicated in the feeding and metabolic regulation. Recently, it has been reported that nesfatin-1 is expressed not only in brain, but also in peripheral organs such as digestive organs, adipose tissues, heart, and reproductive organs. Nesfatin-1 is markedly expressed in the pancreas, stomach and duodenum. Eventually, the nesfatin-1 expression in the digestive organs may be regulated by nutritional status, which suggests a regulatory role of peripheral nesfatin-1 in energy homeostasis. Nesfatin-1 is also detected in the adipose tissues of humans and rodents, indicating that nesfatin-1 expression in the fat may regulate food intake independently, rather than relying on leptin. In addition, nesfatin-1 is expressed in the heart as a cardiac peptide. It suggests that nesfatin-1 may regulate cardiac function and encourage clinical potential in the presence of nutrition-dependent physio-pathologic cardiovascular diseases. Currently, only a few studies demonstrate that nesfatin-1 is expressed in the reproductive system. However, it is not clear yet what function of nesfatin-1 is in the reproductive organs. Here, we summarize the expression of nesfatin-1 and its roles in brain and peripheral organs and discuss the possible roles of nesfatin-1 expressed in reproductive organs, including testis, epididymis, ovary, and uterus. We come to the conclusion that nesfatin-1 as a local regulator in male and female reproductive organs may regulate the steroidogenesis in the testis and ovary and the physiological activity in epididymis and uterus. PMID:25949098

  18. Peroxiredoxin 6 is a potent cytoprotective enzyme in the epidermis.

    PubMed

    Kümin, Angelika; Huber, Christine; Rülicke, Thomas; Wolf, Eckhard; Werner, Sabine

    2006-10-01

    Peroxiredoxin 6 is an enzyme that detoxifies hydrogen peroxide and various organic peroxides. In previous studies we found strongly increased expression of peroxiredoxin 6 in the hyperproliferative epidermis of wounded and psoriatic skin, suggesting a role of this enzyme in epidermal homeostasis. To address this question, we generated transgenic mice overexpressing peroxiredoxin 6 in the epidermis. Cultured keratinocytes from transgenic mice showed enhanced resistance to the toxicity of various agents that induce oxidative stress. However, overexpression of peroxiredoxin 6 did not affect skin morphogenesis or homeostasis. On skin injury, enhancement of wound closure was observed in aged animals. Most importantly, peroxiredoxin 6 overexpression strongly reduced the number of apoptotic cells after UVA or UVB irradiation. These findings demonstrate that peroxiredoxin 6 protects keratinocytes from cell death induced by reactive oxygen species in vitro and in vivo, suggesting that activation of this enzyme could be a novel strategy for skin protection under stress conditions. PMID:17003478

  19. Draft Genome Sequence of Pedobacter sp. Strain NL19, a Producer of Potent Antibacterial Compounds

    PubMed Central

    2015-01-01

    Here, we report the draft genome sequence of Pedobacter sp. strain NL19. The genome has 5.99 Mbp and a G+C content of 39.0%. NL19 was isolated from sludge from an abandoned uranium mine in the north of Portugal, and it produces potent antibacterials against Gram-positive and Gram-negative bacteria. PMID:25814603

  20. Draft Genome Sequence of Pedobacter sp. Strain NL19, a Producer of Potent Antibacterial Compounds.

    PubMed

    Santos, Tiago; Cruz, Andreia; Caetano, Tânia; Covas, Cláudia; Mendo, Sónia

    2015-01-01

    Here, we report the draft genome sequence of Pedobacter sp. strain NL19. The genome has 5.99 Mbp and a G+C content of 39.0%. NL19 was isolated from sludge from an abandoned uranium mine in the north of Portugal, and it produces potent antibacterials against Gram-positive and Gram-negative bacteria. PMID:25814603

  1. Antitumor agents, 110. Bryophyllin B, a novel potent cytotoxic bufadienolide from Bryophyllum pinnatum.

    PubMed

    Yamagishi, T; Haruna, M; Yan, X Z; Chang, J J; Lee, K H

    1989-01-01

    Bryophyllin B [1], a potent cytotoxic bufadienolide, has been isolated from Bryophyllum pinnatum and its structure confirmed by the use of 2D-nmr techniques and difference nOe method. Transformation of bryotoxin C [2] to 1 with acid is also discussed. PMID:2607348

  2. Emotional lability secondary to the application of a very potent topical corticosteroid

    PubMed Central

    Malladi, Srinivasa Sastry

    2009-01-01

    A 66 yrs old gentleman presented with severe mood changes following application of very potent topical corticosteroid cream, clobetasol propionate, which was prescribed for his recalcitrant eczema. The symptoms disappeared within 24 hours of discontinuation of the cream and he remained mentally well when reviewed after 2 weeks. PMID:19881052

  3. Mangrove forests: a potent nexus of coastal biogeochemical cycling

    NASA Astrophysics Data System (ADS)

    Barr, J. G.; Fuentes, J. D.; Shoemaker, B.; O'Halloran, T. L.; Lin, G., Sr.; Engel, V. C.

    2014-12-01

    Mangrove forests cover just 0.1% of the Earth's terrestrial surface, yet they provide a disproportionate source (~10 % globally) of terrestrially derived, refractory dissolved organic carbon to the oceans. Mangrove forests are biogeochemical reactors that convert biomass into dissolved organic and inorganic carbon at unusually high rates, and many studies recognize the value of mangrove ecosystems for the substantial amounts of soil carbon storage they produce. However, questions remain as to how mangrove forest ecosystem services should be valuated and quantified. Therefore, this study addresses several objectives. First, we demonstrate that seasonal and annual net ecosystem carbon exchange in three selected mangrove forests, derived from long-term eddy covariance measurements, represent key quantities in defining the magnitude of biogeochemical cycling and together with other information on carbon cycle parameters serves as a proxy to estimate ecosystem services. Second, we model ecosystem productivity across the mangrove forests of Everglades National Park and southern China by relating net ecosystem exchange values to remote sensing data. Finally, we develop a carbon budget for the mangrove forests in the Everglades National Park for the purposes of demonstrating that these forests and adjacent estuaries are sites of intense biogeochemical cycling. One conclusion from this study is that much of the carbon entering from the atmosphere as net ecosystem exchange (~1000 g C m-2 yr-1) is not retained in the net ecosystem carbon balance. Instead, a substantial fraction of the carbon entering the system as net ecosystem exchange is ultimately exported to the oceans or outgassed as reaction products within the adjacent estuary.

  4. Comprehensive Review on Betulin as a Potent Anticancer Agent

    PubMed Central

    Kiełbus, Michał; Stepulak, Andrzej

    2015-01-01

    Numerous plant-derived substances, and their derivatives, are effective antitumour and chemopreventive agents. Yet, there are also a plethora of tumour types that do not respond, or become resistant, to these natural substances. This requires the discovery of new active compounds. Betulin (BE) is a pentacyclic triterpene and secondary metabolite of plants abundantly found in the outer bark of the birch tree Betulaceae sp. BE displays a broad spectrum of biological and pharmacological properties, among which the anticancer and chemopreventive activity attract most of the attention. In this vein, BE and its natural and synthetic derivatives act specifically on cancer cells with low cytotoxicity towards normal cells. Although the antineoplastic mechanism of action of BE is not well understood yet, several interesting aspects of BE's interactions are coming to light. This review will summarize the anticancer and chemopreventive potential of BE in vitro and in vivo by carefully dissecting and comparing the doses and tumour lines used in previous studies, as well as focusing on mechanisms underlying its activity at cellular and molecular level, and discuss future prospects. PMID:25866796

  5. Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.

    PubMed

    Sheppard, Neil C; Brinckmann, Sarah A; Gartlan, Kate H; Puthia, Manoj; Svanborg, Catharina; Krashias, George; Eisenbarth, Stephanie C; Flavell, Richard A; Sattentau, Quentin J; Wegmann, Frank

    2014-10-01

    Polyethyleneimine (PEI) is an organic polycation used extensively as a gene and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here, we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration and enhanced antigen uptake by antigen-presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome; however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When coformulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased toward a Th1-type immune profile. Taken together, these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens. PMID:24844701

  6. Capsaicin: a potent inhibitor of carbonic anhydrase isoenzymes.

    PubMed

    Arabaci, Betul; Gulcin, Ilhami; Alwasel, Saleh

    2014-01-01

    Carbonic anhydrase (CA, EC 4.2.1.1) is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2) and water (H2O) into a proton (H+) and bicarbonate (HCO3-) ion. On the other hand, capsaicin is the main component in hot chili peppers and is used extensively used in spices, food additives and drugs; it is responsible for their spicy flavor and pungent taste. There are sixteen known CA isoforms in humans. Human CA isoenzymes I, and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of capsaicin against the slow cytosolic isoform hCA I, and the ubiquitous and dominant rapid cytosolic isozymes hCA II were studied. Both CA isozymes were inhibited by capsaicin in the micromolar range. This naturally bioactive compound has a Ki of 696.15 µM against hCA I, and of 208.37 µM against hCA II. PMID:25014536

  7. A new antibiotic with potent activity targets MscL

    PubMed Central

    Iscla, Irene; Wray, Robin; Blount, Paul; Larkins-Ford, Jonah; Conery, Annie L; Ausubel, Frederick M; Ramu, Soumya; Kavanagh, Angela; Huang, Johnny X; Blaskovich, Mark A; Cooper, Matthew A; Obregon-Henao, Andres; Orme, Ian; Tjandra, Edwin S; Stroeher, Uwe H; Brown, Melissa H; Macardle, Cindy; van Holst, Nick; Ling Tong, Chee; Slattery, Ashley D; Gibson, Christopher T; Raston, Colin L; Boulos, Ramiz A

    2015-01-01

    The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections. PMID:25649856

  8. Auranofin is a potent suppressor of osteosarcoma metastasis

    PubMed Central

    Topkas, Eleni; Cai, Na; Cumming, Andrew; Hazar-Rethinam, Mehlika; Gannon, Orla Margaret; Burgess, Melinda; Saunders, Nicholas Andrew; Endo-Munoz, Liliana

    2016-01-01

    Osteosarcoma (OS) accounts for 56% of malignant bone cancers in children and adolescents. Patients with localized disease rarely develop metastasis; however, pulmonary metastasis occurs in approximately 50% of patients and leads to a 5-year survival rate of only 10–20%. Therefore, identifying the genes and pathways involved in metastasis, as new therapeutic targets, is crucial to improve long-term survival of OS patients. Novel markers that define metastatic OS were identified using comparative transcriptomic analyses of two highly metastatic (C1 and C6) and two poorly metastatic clonal variants (C4 and C5) isolated from the metastatic OS cell line, KHOS. Using this approach, we determined that the metastatic phenotype correlated with overexpression of thioredoxin reductase 2 (TXNRD2) or vascular endothelial growth factor (VEGF). Validation in patient biopsies confirmed TXNRD2 and VEGF targets were highly expressed in 29–42% of metastatic OS patient biopsies, with no detectable expression in non-malignant bone or samples from OS patients with localised disease. Auranofin (AF) was used to selectively target and inhibit thioredoxin reductase (TrxR). At low doses, AF was able to inhibit TrxR activity without a significant effect on cell viability whereas at higher doses, AF could induce ROS-dependent apoptosis. AF treatment, in vivo, significantly reduced the development of pulmonary metastasis and we provide evidence that this effect may be due to an AF-dependent increase in cellular ROS. Thus, TXNRD2 may represent a novel druggable target that could be deployed to reduce the development of fatal pulmonary metastases in patients with OS. PMID:26573231

  9. Synthesis of (−)-callicarpenal, a potent arthropod-repellent

    PubMed Central

    Ling, Taotao; Xu, Jing; Smith, Ryan; Ali, Abbas; Cantrell, Charles L.; Theodorakis, Emmanuel A.

    2011-01-01

    Callicarpenal (1), a natural terpenoid isolated from American beautyberry (Callicarpa americana), has shown significant repellent activities against mosquitoes, ticks and imported fire ants. Here we report our efficient synthetic approach to this natural product, and preliminary results of the mosquito biting-deterrent effects of callicarpenal as well as its synthetic precursors and related C8-epimers. The synthetic strategy allows rapid access to various epimers and analogues of the natural product that can be used to explore its structure-activity relationship and optimize its biological properties. PMID:21643472

  10. Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta.

    PubMed

    Gibbons, Simon; Fallah, Fatemeh; Wright, Colin W

    2003-04-01

    The activity of cryptolepine hydrochloride, a salt of the main indoloquinoline alkaloid from the West African medicinal plant Cryptolepis sanguinolenta, was assessed against the fast growing mycobacterial species Mycobacterium fortuitum, which has recently been shown to be of use in the evaluation of antitubercular drugs. The low minimum inhibitory concentration (MIC) of this compound (16 microg/mL) prompted further evaluation against other fast growing mycobacteria namely, M. phlei, M. aurum, M. smegmatis, M. bovis BCG and M. abcessus and the MICs ranged over 2-32 microg/mL for these species. The strong activity of this agent, the need for new antibiotics with activity against Mycobacterium tuberculosis, coupled with the ethnobotanical use of C. sanguinolenta extracts to treat infections, highlight the potential of the cryptolepine template for development of antimycobacterial agents. PMID:12722159

  11. Crystal structure of PTP1B complexed with a potent and selective bidentate inhibitor.

    PubMed

    Sun, Jin-Peng; Fedorov, Alexander A; Lee, Seung-Yub; Guo, Xiao-Ling; Shen, Kui; Lawrence, David S; Almo, Steven C; Zhang, Zhong-Yin

    2003-04-01

    Protein-tyrosine phosphatase 1B (PTP1B) has been implicated as an important regulator in several signaling pathways including those initiated by insulin and leptin. Potent and specific PTP1B inhibitors could serve as useful tools in elucidating the physiological functions of PTP1B and may constitute valuable therapeutics in the treatment of several human diseases. We have determined the crystal structure of PTP1B in complex with compound 2, the most potent and selective PTP1B inhibitor reported to date. The structure at 2.15-A resolution reveals that compound 2 simultaneously binds to the active site and a unique proximal noncatalytic site formed by Lys-41, Arg-47, and Asp-48. The structural data are further corroborated by results from kinetic analyses of the interactions of PTP1B and its site-directed mutants with compound 2 and several of its variants. Although many of the residues important for interactions between PTP1B and compound 2 are not unique to PTP1B, the combinations of all contact residues differ between PTP isozymes, which provide a structural basis for potent and selective PTP1B inhibition. Our data further suggest that potent, yet highly selective, PTP1B inhibitory agents can be acquired by targeting the area defined by residues Lys-41, Arg-47, and Asp-48, in addition to the previously identified second aryl phosphate-binding pocket. PMID:12547827

  12. Silver-Lactoferrin Nanocomplexes as a Potent Antimicrobial Agent.

    PubMed

    Pomastowski, Paweł; Sprynskyy, Myroslav; Žuvela, Petar; Rafińska, Katarzyna; Milanowski, Maciej; Liu, J Jay; Yi, Myunggi; Buszewski, Bogusław

    2016-06-29

    The process of silver immobilization onto and/or into bovine lactoferrin (LTF), the physicochemical properties of bovine lactoferrin and obtained silver-lactoferrin complexes, as well as antibacterial activity of silver-lactoferrin complexes were investigated in this work. Kinetic study of the silver immobilization into lactoferrin was carried out using batch sorption techniques. Spectrometric (MALDI-TOF/TOF-MS, ICP-MS), spectroscopic (FTIR, SERS), electron microscopic (TEM) and electrophoretic (I-DE) techniques, as well as zeta potential measurements, were applied for characterization of LTF and binding nature of silver in Ag-LTF complexes. On the basis of the results of the kinetics study, it was established that the silver binding to LTF is a heterogeneous process involving two main stages: (i) internal diffusion and sorption onto external surface of lactoferrin globules; and (ii) internal diffusion and binding into lactoferrin globule structure. Spectroscopic techniques combined with TEM analysis confirmed the binding process. Molecular dynamics (MD) analysis was carried out in order to simulate the mechanism of the binding process, and locate potential binding sites, as well as complement the experimental findings. Quantum mechanics (QM) simulations were performed utilizing density functional theory (DFT) in order to support the reduction mechanism of silver ions to elemental silver. Antimicrobial activity of synthesized lactoferrin complexes against selected clinical bacteria was confirmed using flow cytometry and antibiograms. PMID:27263865

  13. A novel formulation of veggies with potent liver detoxifying activity.

    PubMed

    Jain, Mohit M; Kumari, Nirmala; Rai, Geeta

    2015-01-01

    LXR (encoded by NR1H2 and 3) and FXR (known as bile acid receptor) encoded by NR1H4 (nuclear receptor subfamily 1, group H and member 4) are nuclear receptors in humans and are important regulators of bile acid production, cholesterol, fatty acid and glucose homeostasis hence responsible for liver detoxification. Several strategies for drug design with numerous ligands for this target have failed owing to the inability of the ligand to access the target/receptor or their early metabolisation. In this work, we have evaluated FXR and LXR structure bound with agonist and compared the binding energy affinity of active ligands present in live green-real veggies with reference drugs (ligands) present in the market. A high throughput screening combined with molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions, log P values and percentage of human oral absorption value led to the identification of two compounds present in live green-real veggies with strong potential for liver detoxification. PMID:25869321

  14. Triblock Conjugates: Identification of a Highly Potent Antiinflammatory Agent.

    PubMed

    Singh, Palwinder; Kaur, Jagroop; Singh, Gurjit; Bhatti, Rajbir

    2015-08-13

    Rationally designed conjugates of chrysin, indole, and barbituric acid were synthesized and screened for their antiinflammatory activities through in vitro and in vivo experiments. Improved over the previously reported chrysin-indole-pyrazole conjugates and also in comparison to the chrysin, indole, and barbituric acid based COX-2 inhibitors, the new compounds have displayed significantly better IC50 for COX-2 and some of them also exhibited inhibition of 5-LOX enzyme. For one of the test compounds, IC50 for COX-2 and 5-LOX was 1 and 1.5 nM, respectively. Investigations of Swiss Albino mice through capsaicin induced paw lickings and dextran induced inflammation showed that these compounds possess appreciable analgesic and antiinflammatory activities. Ki, Ka, and ΔG for the enzyme-compound interaction were calculated and found to be in agreement with the biological data. The experimental results were supported by the molecular docking studies of the compounds in the active site of COX-2 and 5-LOX. Overall, a highly promising antiinflammatory agent was identified. PMID:26204057

  15. Method to measure gas levels during auger mining of coal. Information circular/1994

    SciTech Connect

    Volkwein, J.C.; Prokop, A.D.

    1994-01-01

    The U.S. Bureau of Mines has developed a method to measure methane and other gases during the auger mining of coal. An intrinsically safe commercial gas detector with a built-in data logger was mounted in the center of the hollow conveying auger. A sample head through the wall of the auger conducted a gas sample to the detector. Results showed that gas levels can be monitored on a continuous basis during the auger mining of coal and the data retrieved upon completion of the hole.

  16. Synthesis and biological evaluation of a potent salicylihalamide A lactam analogue.

    PubMed

    Balan, Dan; Burns, Christopher J; Fisk, Nicholas G; Hügel, Helmut; Huang, David C S; Segal, David; White, Charlotte; Wagler, Jörg; Rizzacasa, Mark A

    2012-10-28

    The first synthesis of a lactam analogue of salicylihalamide A (1) is reported. A key step in the approach was a photochemical acylation coupling between amine 10 and dioxinone 9 to form the amide 19. Acetylation followed by RCM with Grubbs 1st generation catalyst gave the desired E-lactam 23 (E : Z ratio 87 : 13) as the major compound. Conversion of macrolactam 23 into the vinyl iodide 26 followed by Cu catalysed cross coupling with the diene amide 7 gave aza-salicylihalamide analogue 3 in good yield. This compound demonstrated potent activity against several human leukaemia cell lines. PMID:22964776

  17. Multiple cell upset cross-section modeling: A possible interpretation for the role of the ion energy-loss straggling and Auger recombination

    NASA Astrophysics Data System (ADS)

    Zebrev, G. I.; Zemtsov, K. S.

    2016-08-01

    We found that the energy deposition fluctuations in the sensitive volumes may cause the multiple cell upset (MCU) multiplicity scatter in the nanoscale (with feature sizes less than 100 nm) memories. A microdosimetric model of the MCU cross-section dependence on LET is proposed. It was shown that ideally a staircase-shaped cross-section vs LET curve spreads due to the energy-loss straggling impact into a quasi-linear dependence with a slope depending on the memory cell area, the cell critical energy and efficiency of charge collection. This paper also presents a new model of the Auger recombination as a limiting process of the electron-hole charge yield, especially at the high-LET ion impact. A modified form of the MCU cross-section vs LET data interpolation is proposed, discussed and validated.

  18. Synthesis of the cyanobacterial metabolite nostodione A, structural studies and potent antiparasitic activity against Toxoplasma gondii.

    PubMed

    McNulty, James; Keskar, Kunal; Jenkins, Hilary A; Werstiuk, Nick H; Bordón, Claudia; Yolken, Robert; Jones-Brando, Lorraine

    2015-10-21

    A total synthesis of the cyanobacterial natural product nostodione A is reported involving a convergent, diversity-oriented route, enabling the assembly of a mini-library of structural analogues. The first single crystal X-ray structural determination on a member of this series is reported along with SAR studies identifying potent inhibitors of invasion and replication of the parasitic protozoan Toxoplasma gondii. PMID:26291306

  19. Total synthesis of neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata.

    PubMed

    Xie, Wei-Jia; Tanabe, Genzoh; Tsutsui, Nozomi; Wu, Xiao-Ming; Muraoka, Osamu

    2013-11-01

    Neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata, was synthesized through a key coupling reaction between a perbenzylated thiosugar and an appropriately protected perseitol triflate derived from D-mannose. This key step was found to be quite temperature dependent, and a simultaneous cyclization of the triflate leading to a characteristic 2,4,7-trioxabicyclo[4.2.1]nonane system was detected. PMID:24345510

  20. Discovery and characterization of a potent and selective EP4 receptor antagonist.

    PubMed

    Schiffler, Matthew A; Chandrasekhar, Srinivasan; Fisher, Matthew J; Harvey, Anita; Kuklish, Steven L; Wang, Xu-Shan; Warshawsky, Alan M; York, Jeremy S; Yu, Xiao-Peng

    2015-08-15

    EP4 is a prostaglandin E2 receptor that is a target for potential anti-nociceptive therapy. Described herein is a class of amphoteric EP4 antagonists which reverses PGE2-induced suppression of TNFα production in human whole blood. From this class, a potent and highly bioavailable compound (6) has been selected for potential clinical studies. EP4 binding and functional data, selectivity, and pharmacokinetic properties of this compound are included. PMID:26091726

  1. Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action.

    PubMed

    Royo, Santiago; Rodríguez, Santiago; Schirmeister, Tanja; Kesselring, Jochen; Kaiser, Marcel; González, Florenci V

    2015-09-01

    Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nM and kinact /Ki =1.6×10(6)  M(-1)  s(-1) against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition kinetics data, supported by docking studies, suggest a dual mode of action via attack of cysteine thiolate at two reactive positions. PMID:26179752

  2. A boronic acid chalcone analog of combretastatin A-4 as a potent anti-proliferation agent

    PubMed Central

    Kong, Yali; Wang, Kan; Edler, Michael C.; Hamel, Ernest; Mooberry, Susan L.; Paige, Mikell A.; Brown, Milton L.

    2010-01-01

    Chalcones represent a class of natural products that inhibits tubulin assembly. In this study we designed and synthesized boronic acid analogs of chalcones in an effort to compare biological activities with combretastatin A-4, a potent inhibitor of tubulin polymerization. Systematic evaluation of the positional effects of the carbonyl moiety towards inhibition of tubulin polymerization, cancer cell proliferation and angiogenesis revealed that placement of the carbonyl adjacent to the trimethoxybenzene A-ring resulted in more active compounds than when the carbonyl group was placed adjacent to the C-ring. Our study identified a boronic acid chalcone with inhibition towards 16 human cancer cell lines in the 10–200 nM range, and another three cell lines with GI50-values below 10 nM. Furthermore, this drug has significant anti-angiogenesis effects demonstrated by HUVEC tube formation and aortic ring assay. PMID:20006519

  3. Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor

    PubMed Central

    2015-01-01

    The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels of selectivity across the kinome. Herein we report our structure-based optimization strategy of a dibenzodiazepine hit 1, discovered in a fragment-based screen, yielding highly potent and selective inhibitors of PAK1 such as 2 and 3. Compound 2 was cocrystallized with PAK1 to confirm binding to an allosteric site and to reveal novel key interactions. Compound 3 modulated PAK1 at the cellular level and due to its selectivity enabled valuable research to interrogate biological functions of the PAK1 kinase. PMID:26191365

  4. Synthesis and neurite growth evaluation of new analogues of honokiol, a neolignan with potent neurotrophic activity.

    PubMed

    Praveen Kumar, Vemula; Gajendra Reddy, R; Vo, Duc Duy; Chakravarty, Sumana; Chandrasekhar, Srivari; Grée, René

    2012-02-01

    A versatile synthetic route is reported towards the preparation of new analogues for potent neurotrophic agent biaryl-type lignan honokiol. A focused 24-membered library of derivatives containing five different groups at 5'-position of honokiol has been prepared in fair to good overall yields. Compared to the natural product, or to analogues with a short alkyl chain in this position, these new derivatives have lost most of the neurotrophic activity. PMID:22209461

  5. Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine Transporter.

    PubMed

    Gavrin, Lori K; Mahaney, Paige E; Jenkins, Douglas; Nogle, Lisa M; Mugford, Cheryl A; Huselton, Christine; Leiter, Jennifer; Johnston, Grace H; Bray, Jenifer A; Burroughs, Kevin D; Cosmi, Scott A; Alfinito, Peter; Ho, Douglas M; Deecher, Darlene C; Trybulski, Eugene J

    2010-06-10

    The potency and selectivity of a series of 1-{(1S)-2-[amino]-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol analogues are described. These compounds were prepared to improve in vitro metabolic stability and achieve brain penetration. Compound 13 (WAY-260022, NRI-022) was found to be a potent inhibitor of norepinephrine reuptake and demonstrated excellent selectivity over the serotonin and dopamine transporters. Additionally, 13 exhibited oral efficacy in a rat model of thermoregulatory dysfunction. PMID:24900182

  6. Discovery of WAY-260022, a Potent and Selective Inhibitor of the Norepinephrine Transporter

    PubMed Central

    2010-01-01

    The potency and selectivity of a series of 1-{(1S)-2-[amino]-1-[3-(trifluoromethoxy)phenyl]ethyl}cyclohexanol analogues are described. These compounds were prepared to improve in vitro metabolic stability and achieve brain penetration. Compound 13 (WAY-260022, NRI-022) was found to be a potent inhibitor of norepinephrine reuptake and demonstrated excellent selectivity over the serotonin and dopamine transporters. Additionally, 13 exhibited oral efficacy in a rat model of thermoregulatory dysfunction. PMID:24900182

  7. A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain

    SciTech Connect

    Wojcik, John; Hantschel, Oliver; Grebien, Florian; Kaupe, Ines; Bennett, Keiryn L.; Barkinge, John; Jones, Richard B.; Koide, Akiko; Superti-Furga, Giulio; Koide, Shohei

    2010-09-02

    Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody mimic (or 'monobody'), termed HA4, that bound to the Abelson (Abl) kinase SH2 domain with low nanomolar affinity. SH2 protein microarray analysis and MS of intracellular HA4 interactors showed HA4's specificity, and a crystal structure revealed how this specificity is achieved. HA4 disrupted intramolecular interactions of Abl involving the SH2 domain and potently activated the kinase in vitro. Within cells, HA4 inhibited processive phosphorylation activity of Abl and also inhibited STAT5 activation. This work provides a design guideline for highly specific and potent inhibitors of a protein interaction domain and shows their utility in mechanistic and cellular investigations.

  8. "Appearance potent"? A content analysis of UK gay and straight men's magazines.

    PubMed

    Jankowski, Glen S; Fawkner, Helen; Slater, Amy; Tiggemann, Marika

    2014-09-01

    With little actual appraisal, a more 'appearance potent' (i.e., a reverence for appearance ideals) subculture has been used to explain gay men's greater body dissatisfaction in comparison to straight men's. This study sought to assess the respective appearance potency of each subculture by a content analysis of 32 issues of the most read gay (Attitude, Gay Times) and straight men's magazines (Men's Health, FHM) in the UK. Images of men and women were coded for their physical characteristics, objectification and nudity, as were the number of appearance adverts and articles. The gay men's magazines featured more images of men that were appearance ideal, nude and sexualized than the straight men's magazines. The converse was true for the images of women and appearance adverts. Although more research is needed to understand the effect of this content on the viewer, the findings are consistent with a more appearance potent gay male subculture. PMID:25129685

  9. A proposed physical model for the impregnated tungsten cathode based on Auger surface studies of the Ba-O-W system

    NASA Technical Reports Server (NTRS)

    Forman, R.

    1979-01-01

    Auger spectra and work function measurements are used to study the surface reactions between tungsten surface and adsorbed layers of barium, and barium and oxygen. The barium on an impregnated tungsten cathod seems to be an intermediate state, probably a coadsorbed barium-oxygen layer on tungsten. A slightly revised version of the previously suggested (1976) impregnated tungsten cathode model is proposed. This revised model assumes that the cathode surface during life has an adsorbed surface layer of a monolayer or less of both barium and oxygen on the surface. At end of life, steep drop in electron emission and resultant cathode failure occur. Recent NASA life test results on TWT type tubes are reported and explained by the proposed model.

  10. A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis.

    PubMed

    Bold, Guido; Schnell, Christian; Furet, Pascal; McSheehy, Paul; Brüggen, Josef; Mestan, Jürgen; Manley, Paul W; Drückes, Peter; Burglin, Marion; Dürler, Ursula; Loretan, Jacqueline; Reuter, Robert; Wartmann, Markus; Theuer, Andreas; Bauer-Probst, Beatrice; Martiny-Baron, Georg; Allegrini, Peter; Goepfert, Arnaud; Wood, Jeanette; Littlewood-Evans, Amanda

    2016-01-14

    This paper describes the identification of 6-(pyrimidin-4-yloxy)-naphthalene-1-carboxamides as a new class of potent and selective human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitors. In biochemical and cellular assays, the compounds exhibit single-digit nanomolar potency toward VEGFR2. Compounds of this series show good exposure in rodents when dosed orally. They potently inhibit VEGF-driven angiogenesis in a chamber model and rodent tumor models at daily doses of less than 3 mg/kg by targeting the tumor vasculature as demonstrated by ELISA for TIE-2 in lysates or by immunohistochemical analysis. This novel series of compounds shows a potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role. PMID:26629594

  11. Preparation and evaluation of tributyrin emulsion as a potent anti-cancer agent against melanoma.

    PubMed

    Kang, Sung Nam; Lee, Eunmyong; Lee, Mi-Kyung; Lim, Soo-Jeong

    2011-02-01

    Histone deacetylase inhibitors such as butyrate are known to exhibit anti-cancer activities in a wide range of cancer including melanoma. In spite of these potencies, butyrate is not practically used for cancer treatment due to its rapid metabolism and very short plasma half-life. Tributyrin, a triglyceride analog of butyrate, can act as a pro-drug of butyrate after being cleaved by intracellular enzymes. The present study sought to investigate a possibility to develop tributyrin emulsion as a potent anti-cancer agent against melanoma. Mixture of Tween80 and 1, 2-dimyristoyl-sn-glycero-3-phosphocholine as a surfactant to disperse tributyrin produced homogeneous emulsions with nanometer sizes, even without a harsh homogenization procedure. Tributyrin emulsion was more potent than butyrate in inhibiting the growth of B16-F10 melanoma cells. Accumulation of cells at sub G(0)/G(1) phase and the DNA fragmentation induced by tributyrin emulsion treatment revealed that tributyrin emulsion inhibited the growth of B16-F10 cells by inducing apoptosis. Treatment with tributyrin emulsion suppressed the colony formation of melanoma cells in a dose-dependent manner. Furthermore, after intraperitoneal administration into mice, tributyrin emulsion inhibited the formation of tumor colonies in the lung following intravenous injection of melanoma cells. Taken together, our data suggests that tributyrin emulsion may be developed as a potent anti-cancer agent against melanoma. PMID:20946006

  12. Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application.

    PubMed

    Cozza, Giorgio; Bonvini, Paolo; Zorzi, Elisa; Poletto, Giorgia; Pagano, Mario A; Sarno, Stefania; Donella-Deana, Arianna; Zagotto, Giuseppe; Rosolen, Angelo; Pinna, Lorenzo A; Meggio, Flavio; Moro, Stefano

    2006-04-20

    Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Using a virtual screening approach, we have identified the ellagic acid, a naturally occurring tannic acid derivative, as a novel potent CK2 inhibitor. At present, ellagic acid represents the most potent known CK2 inhibitor (K(i) = 20 nM). PMID:16610779

  13. Radiolabeling and in vitro evaluation of 67Ga-NOTA-modular nanotransporter – A potential Auger electron emitting EGFR-targeted radiotherapeutic

    PubMed Central

    Koumarianou, Eftychia; Slastnikova, Tatiana A.; Pruszynski, Marek; Rosenkranz, Andrey A.; Vaidyanathan, Ganesan; Sobolev, Alexander S.; Zalutsky, Michael R.

    2014-01-01

    Introduction Modular nanotransporters (MNTs) are vehicles designed to transport drugs from the cell surface via receptor-mediated endocytosis and endosomal escape to nucleus. Hence their conjugation to Auger electron emitters, can cause severe cell killing, by nuclear localization. Herein we evaluate the use of MNT as a platform for targeted radiotherapy with 67Ga. Methods EGF was the targeting ligand on the MNT, and NOTA was selected for its radiolabeling with 67Ga. In the radiolabeling study we dealt with the precipitation of MNT (pI 5.7) at the labeling pH (4.5–5.5) of 67Ga. Cellular and nuclei uptake of 67Ga-NOTA-MNT by the A431 cell line was determined. Its specific cytotoxicity was compared to that of 67Ga-EDTA, 67Ga-NOTA-BSA and 67Ga-NOTA-hEGF, in A431 and U87MGWTT, cell lines, by clonogenic assay. Dosimetry studies were also performed. Results 67Ga-NOTA-MNT was produced with 90% yield and specific activity of 25.6 mCi/mg. The in vitro kinetics revealed an increased uptake over 24 h. 55% of the internalized radioactivity was detected in the nuclei at 1 h. The cytotoxicity of 67Ga-NOTA-MNT on A431 cell line was 17 and 385-fold higher when compared to non-specific 67Ga-NOTA-BSA and 67Ga-EDTA. While its cytotoxic potency was 13 and 72 – fold higher when compared to 67Ga-NOTA-hEGF in the A431 and the U87MGWTT cell lines, respectively, validating its nuclear localization. The absorbed dose, for 63% cell killing, was 9 Gy, confirms the high specific index of 67Ga. Conclusion These results demonstrate the feasibility of using MNT as a platform for single cell kill targeted radiotherapy by Auger electron emitters. PMID:24776093

  14. Discovery of DS-1558: A Potent and Orally Bioavailable GPR40 Agonist

    PubMed Central

    2015-01-01

    GPR40 is a G protein-coupled receptor that is predominantly expressed in pancreatic β-cells. GPR40 agonists stimulate insulin secretion in the presence of high glucose concentration. On the basis of this mechanism, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia. The improvement of in vitro activity and metabolic stability of compound 1 led to the discovery of 13, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid, as a potent and orally available GPR40 agonist. Compound 13 (DS-1558) was found to have potent glucose lowering effects during an oral glucose tolerance test in ZDF rats. PMID:25815144

  15. UNC2025, a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

    PubMed Central

    2015-01-01

    We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined. PMID:25068800

  16. Education and Outreach for the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Snow, G.

    The scale and scope of the physics studied at the Auger Observatory offer significant opportunities for original outreach work. Education, outreach and public relations of the Auger collaboration are coordinated in a separate task whose goals are to encourage and support a wide range of education and outreach efforts that link schools and the public with the Auger scientists and the science of cosmic rays, particle physics, and associated technologies. The presentation will focus on the impact of the collaboration in Mendoza Province, Argentina, as: the Auger Visitor Center in Malargüe that has hosted over 25,000 visitors since 2001, the Auger Celebration and a collaboration-sponsored science fair held on the Observatory campus in November 2005, the opening of the James Cronin School in Malargüe in November 2006, public lectures, school visits, and courses for science teachers. As the collaboration prepares its northern hemisphere site proposal, plans for an enhanced outreach program are being developed in parallel and will be described.

  17. Potent Inhibitors of Pro-Inflammatory Cytokine Production Produced by a Marine-Derived Bacterium

    PubMed Central

    Strangman, Wendy K.; Kwon, Hak Cheol; Broide, David; Jensen, Paul R.; Fenical, William

    2009-01-01

    Cytokines produced through the Antigen Presenting Cell (APC)–T-cell interaction play a key role in the activation of the allergic asthmatic response. Evaluating small molecules that inhibit the production of these pro-inflammatory proteins is therefore important for the discovery of novel chemical structures with potential anti-asthma activity. We adapted a mouse splenocyte cytokine assay to screen a library of 2,500 marine microbial extracts for their ability to inhibit TH2 cytokine release and identified potent activity in a marine-derived strain CNQ431, identified as a Streptomyces species. Bioactivity guided fractionation of the organic extract of this strain led to the isolation of ten new 9-membered bis-lactones, splenocins A-J (1–10). The new compounds display potent biological activities, comparable to that of the corticosteroid dexamethasone, with IC50 values from 2–50 nanomolar in the splenocyte cytokine assay. This study provides the foundation for the optimization of these potent anti-inflammatory compounds for development in the treatment of asthma. PMID:19323483

  18. Direct and inverse auger processes in InAs nanocrystals: can the decay signature of a trion be mistaken for carrier multiplication?

    PubMed

    Califano, Marco

    2009-09-22

    A complete and detailed theoretical investigation of the main processes involved in the controversial detection and quantification of carrier multiplication (CM) is presented, providing a coherent and comprehensive picture of excited state relaxation in InAs nanocrystals (NCs). The observed rise and decay times of the 1S transient bleach are reproduced, in the framework of the Auger model, using an atomistic semiempirical pseudopotential method, achieving excellent agreement with experiment. The CM time constants for small core-only and core/shell nanocrystals are obtained as a function of the excitation energy, assuming an impact-ionization-like process. The resulting lifetimes at energies close to the observed CM onset are consistent with the upper limits deduced experimentally from PbSe and CdSe samples. Most interestingly, as the Auger recombination lifetimes calculated for charged excitons are found to be of a similar order of magnitude to those computed for biexcitons, both species are expected to exhibit the fast decay component in NC population dynamics so far attributed exclusively to the presence of biexcitons and therefore identified as the signature of CM occurrence in high-energy low-pump-fluence spectroscopic studies. However, the ratio between trions and biexcitons time constants is found to be larger than the typical experimental accuracy. It is therefore concluded that, in InAs NCs, it should be experimentally possible to discriminate between the two species and that the origin of the observed discrepancies in CM yields is unlikely to lay in the presence of charged excitons. PMID:19689121

  19. The Pierre Auger Project: an overview

    NASA Astrophysics Data System (ADS)

    Mantsch, Paul M.

    2003-02-01

    The Southern Hemisphere site of the Pierre Auger Observatory is now under construction in Argentina by a collaboration of 50 institutions in 16 countries. The objective of the Auger Project is to make a high statistics measurement of cosmic rays above 1019 eV. The observatory will record extensive air showers induced by these cosmic rays incident on the atmosphere. The measurement will include energy, direction and composition of the primary particles. The engineering phase is now complete and full construction has begun. The search for the source of the highest energy cosmic rays is one of the most interesting problems in astrophysics. Following the discovery of the cosmic microwave background, Greisen and, independently, Zatsepin and Kuzmin realized hat this background radiation would make space opaque to cosmic rays of very high energy. Nevertheless over the past 30 years several tens of events were recorded with energies above the Greisen, Zatsepin, Kuzmin (GZK) cutoff (about 5×1019 eV) including a number above 1020 eV. These events present a conundrum. Because of the GZK cut off these super high-energy events must come from nearby, less than about 50 Mpc. In addition the cosmic acceleration mechanism for achieving these energies is very difficult to conceive. Yet, even though particles of these energies are only slightly deflected by galactic and extragalactic magnetic fields, none clearly points back to a source sufficiently violent to a be a candidate source. The Auger Observatory finished its engineering development phase at the end of 2001. The "Engineering Array" consists of 40 surface particle detector stations and two prototype air fluorescence telescopes. The Observatory, when complete, will have a 1600 detector surface array covering 3000 km**2 overlooked by 24 fluorescence telescopes. The Engineering Array has demonstrated that all of the detector systems perform as well or better than expected. Recently the Observatory has recorded a number of

  20. A Potent and Highly Efficacious Bcl-2/Bcl-xL Inhibitor

    PubMed Central

    McEachern, Donna; Yang, Chao-Yie; Meagher, Jennifer; Stuckey, Jeanne; Wang, Shaomeng

    2013-01-01

    Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with Ki values of < 1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete and durable tumor regression in vivo at a well-tolerated dose-schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date. PMID:23448298

  1. Auger recombination in InN from first principles

    NASA Astrophysics Data System (ADS)

    McAllister, Andrew; Kioupakis, Emmanouil

    Group-III Nitride materials are used in numerous electronic and optoelectronic devices including solid-state lighting, energy conversion, sensor technologies, and high-power electronics. Indium nitride in particular is interesting for fast electronics and optoelectronics in the infrared. Auger recombination is a non-radiative carrier recombination process that would limit the efficiency of these devices. The small band gap (0.7 eV) and the high intrinsic free-electron concentrations in InN possibly make Auger recombination particularly important in this material. We used first-principles computational methods to determine the Auger recombination rates in InN. Our results suggest that direct Auger recombination is dominant in this material and that phonon-assisted Auger processes are not as important as in wider-gap nitrides such as GaN. This research was supported by the National Science Foundation CAREER award through Grant No. DMR-1254314. Computational resources were provided by the DOE NERSC facility.

  2. Antiviral properties of palinavir, a potent inhibitor of the human immunodeficiency virus type 1 protease.

    PubMed Central

    Lamarre, D; Croteau, G; Wardrop, E; Bourgon, L; Thibeault, D; Clouette, C; Vaillancourt, M; Cohen, E; Pargellis, C; Yoakim, C; Anderson, P C

    1997-01-01

    Palinavir is a potent inhibitor of the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) proteases. Replication of laboratory strains (HIV-1, HIV-2, and simian immunodeficiency virus) and HIV-1 clinical isolates is inhibited by palinavir with 50% effective concentrations ranging from 0.5 to 30 nM. The average cytotoxic concentration of palinavir (35 microM) in the various target cells indicates a favorable therapeutic index. Potent antiviral activity is retained with increased doses of virus and with clinical isolates resistant to zidovudine (AZT), didanosine (ddI), or nevirapine. Combinations of palinavir with either AZT, ddI, or nevirapine demonstrate synergy or additivity in the inhibition of HIV-1 replication. Palinavir retains anti-HIV-1 activity when administered postinfection until times subsequent to the reverse transcription step. In chronically infected CR-10 cells, palinavir blocks Gag precursor polyprotein processing completely, reducing greater than 99% of infectious particle production. The results indicate that the antiviral activity of palinavir is specific to inhibition of the viral protease and occurs at a late stage in the replicative cycle of HIV-1. On the basis of the potent in vitro activity, low-level cytotoxicity, and other data, palinavir was selected for in-depth preclinical evaluation. PMID:9145853

  3. Secretome Identifies Tenascin-X as a Potent Marker of Ovarian Cancer

    PubMed Central

    Kramer, Marianne; Pierredon, Sandra; Ribaux, Pascale; Tille, Jean-Christophe; Cohen, Marie

    2015-01-01

    CA-125 has been a valuable marker for the follow-up of ovarian cancer patients but it is not sensitive enough to be used as diagnostic marker. We had already used secretomic methods to identify proteins differentially secreted by serous ovarian cancer cells compared to healthy ovarian cells. Here, we evaluated the secretion of these proteins by ovarian cancer cells during the follow-up of one patient. Proteins that correlated with CA-125 levels were screened using serum samples from ovarian cancer patients as well as benign and healthy controls. Tenascin-X secretion was shown to correlate with CA-125 value in the initial case study. The immunohistochemical detection of increased amount of tenascin-X in ovarian cancer tissues compared to healthy tissues confirms the potent interest in tenascin-X as marker. We then quantified the tenascin-X level in serum of patients and identified tenascin-X as potent marker for ovarian cancer, showing that secretomic analysis is suitable for the identification of protein biomarkers when combined with protein immunoassay. Using this method, we determined tenascin-X as a new potent marker for serous ovarian cancer. PMID:26090390

  4. Auger tension leg platform cathodic protection system

    SciTech Connect

    Goolsby, A.D.; Smith, J.D.

    1995-11-01

    In 1986, Shell began investigating corrosion control systems for a generic 3,000 ft. water depth Tension Leg Platform (TLP) type structure to be located in the north-central Gulf of Mexico. In 1987, the 2,850 ft. deep Garden Banks block 426 ``Auger`` location was chosen for the first TLP, and the detailed design process began in earnest. During late 1993 and early 1994, the Auger hull was mated with the other components at its permanent site, and first oil and gas production began April 15, 1994. This paper describes the corrosion control design for the exterior submerged and buried steel surfaces of the 2,850 ft. (869 m) water depth Auger Tension Leg Platform structure. Each major type of component (hull, subsea marine wellhead/guidebase, tendon foundation template, tendon, and production riser) has its own combination of coating system and cathodic protection system designed for a thirty five year lifetime. Cathodic protection (CP) is achieved using a variety of sacrificial anode alloys and geometries (e.g. bracelet, flush-mount, and standoff anodes). Anode and cathode CP design parameters for each component depend upon water depth, and were developed using field test data, laboratory studies, field measurements on existing structures, and available literature information. CP design was performed using design spreadsheets constructed for each component, which optimized anode geometries. Extensive quality assurance efforts were part of the anode procurement process, to ensure performance for the intended life of the corrosion-control systems. Results of early in-service CP surveys of the tendons and guidebases are presented, showing the successful achievement of cathodic protection against seawater corrosion. Corrosion control of one additional system, the eight point lateral mooring system, is not addressed here.

  5. Molecular cascade Auger decays following Si KL23L23 Auger transitions in SiCl4

    NASA Astrophysics Data System (ADS)

    Suzuki, I. H.; Bandoh, Y.; Mochizuki, T.; Fukuzawa, H.; Tachibana, T.; Yamada, S.; Takanashi, T.; Ueda, K.; Tamenori, Y.; Nagaoka, S.

    2016-08-01

    Cascade Si LVV Auger electron spectra at the photoexcitation of the Si 1s electron in a SiCl4 molecule have been measured using an electron spectrometer combined with monochromatized undulator radiation. In the instance of the resonant excitation of the Si 1s electron into the vacant molecular orbital a peak with high yield is observed at about 106 eV, an energy considerably higher than the energies of the normal LVV Auger electron. This peak is presumed to originate from the participator decay from the state with two 2p holes and one excited electron into the state with one 2p hole and one valence hole. Following the normal KL23L23 Auger transition, the cascade spectrum shows several peak structures, e.g. 63 eV, 76 eV and 91 eV. The peak at 91 eV is probably assigned to the second step Auger decay into states having a 2p hole together with two valence holes. These findings are similar to experimental results of SiF4. The former two peaks (63 eV and 76 eV) are ascribed to Auger transitions of Si atomic ions produced through molecular ion dissociation after the first step cascade decays, although the peak heights of atomic ions are lower than those of SiF4.

  6. Auger spectroscopy of fracture surfaces of ceramics

    NASA Technical Reports Server (NTRS)

    Marcus, H. L.; Harris, J. M.; Szalkowski, F. J.

    1974-01-01

    Results of Auger electron spectroscopy (AES) studies of fracture surfaces in a series of ceramic materials, including Al2O3, MgO, and Si3N4, which were formed using different processing techniques. AES on the fractured surface of a lunar sample is also discussed. Scanning electron micrograph fractography is used to relate the surface chemistry to the failure mode. Combined argon ion sputtering and AES studies demonstrate the local variations in chemistry near the fracture surface. The problems associated with doing AES in insulators are also discussed, and the experimental techniques directed toward solving them are described.

  7. Absolute calibration of the Auger fluorescence detectors

    SciTech Connect

    Bauleo, P.; Brack, J.; Garrard, L.; Harton, J.; Knapik, R.; Meyhandan, R.; Rovero, A.C.; Tamashiro, A.; Warner, D.

    2005-07-01

    Absolute calibration of the Pierre Auger Observatory fluorescence detectors uses a light source at the telescope aperture. The technique accounts for the combined effects of all detector components in a single measurement. The calibrated 2.5 m diameter light source fills the aperture, providing uniform illumination to each pixel. The known flux from the light source and the response of the acquisition system give the required calibration for each pixel. In the lab, light source uniformity is studied using CCD images and the intensity is measured relative to NIST-calibrated photodiodes. Overall uncertainties are presently 12%, and are dominated by systematics.

  8. A Search for Ultra-High Energy Neutrinos in Highly Inclined Events at the Pierre Auger Observatory

    DOE PAGESBeta

    Abreu, P

    2011-12-30

    The Surface Detector of the Pierre Auger Observatory is sensitive to neutrinos of all flavors above 0.1 EeV. These interact through charged and neutral currents in the atmosphere giving rise to extensive air showers. When interacting deeply in the atmosphere at nearly horizontal incidence, neutrinos can be distinguished from regular hadronic cosmic rays by the broad time structure of their shower signals in the water-Cherenkov detectors. In this paper we present for the first time an analysis based on down-going neutrinos. We describe the search procedure, the possible sources of background, the method to compute the exposure and the associatedmore » systematic uncertainties. No candidate neutrinos have been found in data collected from 1 January 2004 to 31 May 2010. Assuming an E-2 differential energy spectrum the limit on the single-flavor neutrino is E2dN/dE < 1.74 x 10-7 GeV cm-2s-1sr-1 at 90% C.L. in the energy range 1 x 1017eV < E < 1 x 1020 eV.« less

  9. A Search for Ultra-High Energy Neutrinos in Highly Inclined Events at the Pierre Auger Observatory

    SciTech Connect

    Abreu, P

    2011-12-30

    The Surface Detector of the Pierre Auger Observatory is sensitive to neutrinos of all flavors above 0.1 EeV. These interact through charged and neutral currents in the atmosphere giving rise to extensive air showers. When interacting deeply in the atmosphere at nearly horizontal incidence, neutrinos can be distinguished from regular hadronic cosmic rays by the broad time structure of their shower signals in the water-Cherenkov detectors. In this paper we present for the first time an analysis based on down-going neutrinos. We describe the search procedure, the possible sources of background, the method to compute the exposure and the associated systematic uncertainties. No candidate neutrinos have been found in data collected from 1 January 2004 to 31 May 2010. Assuming an E-2 differential energy spectrum the limit on the single-flavor neutrino is E2dN/dE < 1.74 x 10-7 GeV cm-2s-1sr-1 at 90% C.L. in the energy range 1 x 1017eV < E < 1 x 1020 eV.

  10. The discovery of a selective and potent A2a agonist with extended lung retention

    PubMed Central

    Åstrand, Annika B M; Lamm Bergström, Eva; Zhang, Hui; Börjesson, Lena; Söderdahl, Therese; Wingren, Cecilia; Jansson, Anne-Helene; Smailagic, Amir; Johansson, Camilla; Bladh, Håkan; Shamovsky, Igor; Tunek, Anders; Drmota, Tomas

    2015-01-01

    Although the anti-inflammatory role of the A2a receptor is well established, controversy remains with regard to the therapeutic value for A2a agonists in treatment of inflammatory lung diseases, also as a result of unwanted A2a-mediated cardiovascular effects. In this paper, we describe the discovery and characterization of a new, potent and selective A2a agonist (compound 2) with prolonged lung retention and limited systemic exposure following local administration. To support the lead optimization chemistry program with compound selection and profiling, multiple in vitro and in vivo assays were used, characterizing compound properties, pharmacodynamics (PD), and drug concentrations. Particularly, pharmacokinetic-PD modeling was applied to quantify the effects on the cardiovascular system, and an investigative toxicology study in rats was performed to explore potential myocardial toxicities. Compound 2, in comparison to a reference A2a agonist, UK-432,097, demonstrated higher solubility, lower lipophilicity, lower plasma protein binding, high rat lung retention (28% remaining after 24 h), and was efficacious in a lung inflammatory rat model following intratracheal dosing. Despite these properties, compound 2 did not provide a sufficient therapeutic index, that is, separation of local anti-inflammatory efficacy in the lung from systemic side effects in the cardiovascular system. The plasma concentration that resulted in induction of hypotension (half maximal effective concentration; EC50 0.5 nmol/L) correlated to the in vitro A2a potency (rIC50 0.6 nmol/L). Histopathological lesions in the heart were observed at a dose level which is threefold above the efficacious dose level in the inflammatory rat lung model. In conclusion, compound 2 is a highly potent and selective A2a agonist with significant lung retention after intratracheal administration. Despite its local anti-inflammatory efficacy in rat lung, small margins to the cardiovascular effects suggested