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Sample records for 119sb a potent auger

  1. {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.

  2. Pierre Auger--a life in the service of science.

    PubMed

    Persson, L

    1996-01-01

    A short biography of Pierre Auger, the discoverer of the atomic auger electron effect, is given. Professor Auger's outstanding professional career covered physics, nuclear power and space research, organization and administration of research, diplomatic services and pedagogics but also extended into modern biology, humanistic sciences, poetry and arts. Part of a speech in Paris of professor Auger held in 1989 on the theme 'Research and Creativity' at an international symposium on the auger effect is included in this biography as well as one of his poems.

  3. 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.

  4. 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 .

  5. Some performance tests of a microarea AES. [Auger Electron Spectroscopy

    NASA Technical Reports Server (NTRS)

    Todd, G.; Poppa, H.

    1978-01-01

    An Auger electron spectroscopy (AES) system which has a submicron analysis capability is described. The system provides secondary electron imaging, as well as micro- and macro-area AES. The resolution of the secondary electron image of an oxidized Al contact pad on a charge-coupled device chip indicates a primary beam size of about 1000 A. For Auger mapping, a useful resolution of about 4000 A is reported

  6. Thermal swing reactor including a multi-flight auger

    DOEpatents

    Ermanoski, Ivan

    2017-03-07

    A thermal swing reactor including a multi-flight auger and methods for solar thermochemical reactions are disclosed. The reactor includes a multi-flight auger having different helix portions having different pitch. Embodiments of reactors include at least two distinct reactor portions between which there is at least a pressure differential. In embodiments, reactive particles are exchanged between portions during a reaction cycle to thermally reduce the particles at first conditions and oxidize the particles at second conditions to produce chemical work from heat.

  7. 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.

  8. 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.

  9. Production and dosimetric aspects of the potent Auger emitter {sup 58m}Co for targeted radionuclide therapy of small tumors

    SciTech Connect

    Thisgaard, H.; Elema, D.R.; Jensen, M.

    2011-08-15

    Purpose: Based on theoretical calculations, the Auger emitter {sup 58m}Co has been identified as a potent nuclide for targeted radionuclide therapy of small tumors. During the production of this isotope, the coproduction of the long-lived ground state {sup 58g}Co is unfortunately unavoidable, as is ingrowth of the ground state following the isomeric decay of {sup 58m}Co. The impact of {sup 58g}Co as a {beta}{sup +}- and {gamma}-emitting impurity should be included in the dosimetric analysis. The purpose of this study was to investigate this critical part of dosimetry based on experimentally determined production yields of {sup 58m}Co and {sup 58g}Co using a low-energy cyclotron. Also, the cellular S-values for {sup 58m}Co have been calculated and are presented here for the first time. Methods: {sup 58m}Co was produced via the {sup 58}Fe(p,n){sup 58m}Co nuclear reaction on highly enriched {sup 58}Fe metal. In addition, radiochemical separations of produced radio-cobalt from {sup nat}Fe target material were performed. The theoretical subcellular dosimetry calculations for {sup 58m}Co and {sup 58g}Co were performed using the MIRD formalism, and the impact of the increasing ground state impurity on the tumor-to-normal-tissue dose ratios (TND) per disintegration as a function of time after end of bombardment (EOB) was calculated. Results: 192 {+-} 8 MBq of {sup 58m}Co was produced in the irradiation corresponding to a production yield of 10.7 MBq/{mu}Ah. The activity of {sup 58g}Co was measured to be 0.85% {+-} 0.04% of the produced {sup 58m}Co activity at EOB. The radio-cobalt yields in the rapid separations were measured to be >97% with no detectable iron contaminations in the cobalt fractions. Due to the unavoidable coproduction and ingrowth of the long-lived ground state {sup 58g}Co, the TND and the potency of the {sup 58m}Co decrease with time after EOB. If a future treatment with a {sup 58m}Co labeled compound is not initiated before, e.g., 21 h after EOB, the

  10. A compilation of microdosimetry for uniformly distributed Auger emitters used in medicine.

    PubMed

    Chen, Jing

    2008-12-01

    To provide a compilation of microdosimetric characteristics for 12 Auger emitters commonly used in medicine. Monte Carlo electron track structure simulations are performed for 12 Auger emitters. They are (55)Fe, (67)Ga, (99m)Tc, (111)In, (113m)In, (115m)In, (123)I, (125)I, (193m)Pt, (195m)Pt, (201)Tl, and (203)Pb. Proximity functions of 12 Auger emitters are calculated from the simulated track structures and compared with that of gamma rays from (60)Co. Some of those Auger emitters are highly radiotoxic compared to hard gamma rays from (60)Co. The more electrons per decay and the lower electron energies, the more effective an Auger emitter could be. The high radiotoxicity of Auger emitters is due to correlations of low-energy electrons released from decay processes. If these correlations were disregarded, Auger emitters would not differ significantly from other low linear energy transfer (LET) radiation sources. Even in the case of uniform distribution, some of those Auger emitters are highly radiotoxic compared to hard gamma rays. For Auger emitters to bond to radiosensitive sites in cell nucleus, much higher radiation effectiveness could be expected.

  11. Auger electron spectroscopy at high spatial resolution and nA primary beam currents

    NASA Technical Reports Server (NTRS)

    Todd, G.; Poppa, H.; Moorhead, D.; Bales, M.

    1975-01-01

    An experimental Auger microprobe system is described which incorporates a field-emission electron gun and total beam currents in the nanoampere range. The distinguishing characteristics of this system include a large multistation UHV specimen chamber, pulse counting and fully digital Auger signal-processing techniques, and digital referencing methods to eliminate the effects of beam instabilities. Some preliminary results obtained with this system are described, and it is concluded that field-emission electron sources can be used for high-resolution Auger electron spectroscopy with primary-beam spots of less than 100 nm and beam currents of the order of 1 nA.

  12. 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.

  13. A local chemical environment effect in site-specific Auger spectra of ethyl trifluoroacetate.

    PubMed

    Iwayama, H; Sisourat, N; Lablanquie, P; Penent, F; Palaudoux, J; Andric, L; Eland, J H D; Bučar, K; Žitnik, M; Velkov, Y; Hikosaka, Y; Nakano, M; Shigemasa, E

    2013-01-14

    We have investigated a local chemical environment effect on Auger spectra of ethyl trifluoroacetate (C(4)H(5)F(3)O(2)), using multi-electron coincidence spectroscopy and high-resolution electron spectroscopy. Site-specific KVV Auger spectra for each carbon atom, and for the fluorine and oxygen atoms are presented. The extent of hole localization in the final dicationic states was investigated with the help of theoretical calculations based on a two-hole population analysis. The Auger spectra have been simulated using a statistical approach. It is found that all Auger decays populate mainly localized dicationic states, with the two holes located either on the same fluorine atom or on adjacent fluorine atoms. While the decay of the F 1s hole populates exclusively the former states, the latter class of states is also populated by the decay of the C and O 1s holes.

  14. 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.

  15. 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.

  16. Removing Single Limbs Using a Rotary Auger Cutter

    Treesearch

    Nels S. Christopherson

    1984-01-01

    An experiment using auger cutters to remove single limbs from six species showed that torque required depends on species and relative cutter rotation direction and that all species require 2 horsepower or less per inch width of cut using 2 1/2-inch-diameter cutters

  17. Interchannel interference in resonant Auger scattering from fixed-in-space molecules as a technique for structure determination

    SciTech Connect

    Gel'mukhanov, F.; Minkov, I.

    2004-09-01

    A method for structure determination of polyatomic molecules with equivalent atoms is suggested. The method is based on an interference pattern in the resonant Auger scattering process. This pattern is caused by interference of resonant Auger channels corresponding to a core hole localized on different equivalent atoms. The predicted effect can be observed in angular resolved electron-ion coincidence measurements or, alternatively, using the ordinary Auger technique on surface-oriented molecules.

  18. A calculation of backscattering factor database for quantitative analysis by Auger electron spectroscopy

    SciTech Connect

    Zeng, R. G.; Ding, Z. J.; Li, Y. G.; Mao, S. F.

    2008-12-01

    A systematic calculation of the backscattering factor in quantitative analysis by Auger electron spectroscopy has been performed for the primary electron beam of energy from the threshold energy of inner-shell ionization to 30 keV at the incident angle of 0 deg. - 89 deg. and for principal Auger transition and Auger electrons emitted from over 28 pure elements at an emission angle of 0 deg. - 89 deg. by using a Monte Carlo simulation method. The calculation employs a general definition of backscattering factor, Casnati's ionization cross section, up-to-date Monte Carlo model of electron scattering, and a large number of electron trajectories to ensure less statistical error. Both the configuration geometry of concentric hemispherical analyzer and the cylindrical mirror analyzer for Auger electron detection are considered in the calculation. The calculated backscattering factors are found to describe very well an experimental dependence of Auger electron intensity on primary energy and on incident angle for Si, Cu, Ag, and W in literature. The calculated numerical values of backscattering factor are stored in an open and online database at http://micro.ustc.edu.cn/BSFDataBase/BFAES.htm.

  19. Auger electron spectroscopy as a probe of the solution of aqueous ions.

    PubMed

    Pokapanich, Wandared; Bergersen, Henrik; Bradeanu, Ioana L; Marinho, Ricardo R T; Lindblad, Andreas; Legendre, Sebastien; Rosso, Aldana; Svensson, Svante; Björneholm, Olle; Tchaplyguine, Maxim; Ohrwall, Gunnar; Kryzhevoi, Nikolai V; Cederbaum, Lorenz S

    2009-06-03

    Aqueous potassium chloride has been studied by synchrotron-radiation excited core-level photoelectron and Auger electron spectroscopy. In the Auger spectrum of the potassium ion, the main feature comprises the final states where two outer valence holes are localized on potassium. This spectrum exhibits also another feature at a higher kinetic energy which is related to final states where outer valence holes reside on different subunits. Through ab initio calculations for microsolvated clusters, these subunits have been assigned as potassium ions and the surrounding water molecules. The situation is more complicated in the Auger spectrum of the chloride anion. One-center and multicenter final states are present here as well but overlap energetically.

  20. Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values

    NASA Astrophysics Data System (ADS)

    Falzone, Nadia; Lee, Boon Q.; Fernández-Varea, José M.; Kartsonaki, Christiana; Stuchbery, Andrew E.; Kibédi, Tibor; Vallis, Katherine A.

    2017-03-01

    The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely 67Ga, 80mBr, 89Zr, 90Nb, 99mTc, 111In, 117mSn, 119Sb, 123I, 124I, 125I, 135La, 195mPt and 201Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKs using appropriate geometric reduction factors. The number of Auger and Coster–Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKs in the sub-micrometre dimension were quickly diminished in larger dimensions. Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.

  1. Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values.

    PubMed

    Falzone, Nadia; Lee, Boon Q; Fernández-Varea, José M; Kartsonaki, Christiana; Stuchbery, Andrew E; Kibédi, Tibor; Vallis, Katherine A

    2017-03-21

    The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely (67)Ga, (80m)Br, (89)Zr, (90)Nb, (99m)Tc, (111)In, (117m)Sn, (119)Sb, (123)I, (124)I, (125)I, (135)La, (195m)Pt and (201)Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKs using appropriate geometric reduction factors. The number of Auger and Coster-Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKs in the sub-micrometre dimension were quickly diminished in larger dimensions. Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.

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

    PubMed

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

    2016-05-13

    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 CH_{4} 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.

  3. 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.

  4. 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.

  5. Time-domain ab initio study of Auger and phonon-assisted auger processes in a semiconductor quantum dot.

    PubMed

    Hyeon-Deuk, Kim; Prezhdo, Oleg V

    2011-04-13

    We developed time-domain ab initio simulation of Auger phenomena, including multiple exciton generation (MEG) and recombination (MER). It is the first approach describing phonon-assisted processes and early dynamics. MEG starts below the electronic threshold, strongly accelerating with energy. Ligands are particularly important to phonon-assisted MEG, which therefore can be probed with infrared spectroscopy. Short-time gaussian component gives 5-10% of MEG, justifying rate theories that assume exponential dynamics. MER is preceded by electron-phonon relaxation to low energies.

  6. Tank 241-SY-103 auger samples, risers 7A, 14B and 22A

    SciTech Connect

    Bell, K.E.

    1994-12-12

    Preliminary differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) data were reported in a letter from K.L. Kocher, WHC, to G.D. Johnson; et. al, WHC, ``40 Day Deliverable for Tank 241-SY-103``, dated July 14, 1994. This report is the final report for the Sy-1-3 auger sample characterization effort; some of the data reported earlier may have changed. A copy of the hot cell work plan, chain of custody forms, extruded segment description sheets, and photographs of the extruded augers were also included in the cited letter. The final DSC, TGA, total organic carbon (TOC), and total inorganic carbon (TIC) data, and the DSC and TGA scans and analytical cards, are reported here.

  7. QS-21: a potent vaccine adjuvant

    USDA-ARS?s Scientific Manuscript database

    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...

  8. 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.

  9. Measurements of Auger Electron Diffraction Using a 180° Deflection Toroidal Analyzer

    NASA Astrophysics Data System (ADS)

    Shiraki, Susumu; Ishii, Hideshi; Nihei, Yoshimasa; Owari, Masanori

    A 180° deflection toroidal analyzer is a novel electron spectrometer, which allows the simultaneous registration of the wide range of polar angles in a given azimuth of the sample. Therefore, measurements of photo- and Auger electron intensities over π steradians can be performed rapidly by azimuthal rotation of the sample. Using this analyzer, two-dimensional patterns of electron-beam-excited O KVV and Mg KVV Auger electron diffraction (AED) from a MgO(001) surface were measured in short acquisition times. The AED patterns obtained were compared with theoretical ones calculated by the multiple-scattering scheme. The agreement between experimental and theoretical data was good for both O KVV and Mg KVV transitions.

  10. Adhesion, friction and Auger spectroscopy analysis of a commercial cobalt base aircraft turbine shroud alloy

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1974-01-01

    A commercially used cast cobalt base alloy was investigated as a turbine shroud material which revealed a surface enriched with tungsten and carbon suggesting a surface layer of tungsten carbide. Adhesion and friction of this segregated surface layer are higher than for the bulk cobalt base alloy composition. Auger spectroscopy analysis of the segregation of tungsten in the alloy indicates that it occurs between 850 and 1000 C.

  11. 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.

  12. Auger recombination in sodium iodide

    NASA Astrophysics Data System (ADS)

    McAllister, Andrew; Kioupakis, Emmanouil; Åberg, Daniel; Schleife, André

    2014-03-01

    Scintillators are an important tool used to detect high energy radiation - both in the interest of national security and in medicine. However, scintillator detectors currently suffer from lower energy resolutions than expected from basic counting statistics. This has been attributed to non-proportional light yield compared to incoming radiation, but the specific mechanism for this non-proportionality has not been identified. Auger recombination is a non-radiative process that could be contributing to the non-proportionality of scintillating materials. Auger recombination comes in two types - direct and phonon-assisted. We have used first-principles calculations to study Auger recombination in sodium iodide, a well characterized scintillating material. Our findings indicate that phonon-assisted Auger recombination is stronger in sodium iodide than direct Auger recombination. Computational resources provided by LLNL and NERSC. Funding provided by NA-22.

  13. Direct observation of the double Auger decay of a {ital K} hole

    SciTech Connect

    Hindi, M.M.; Zhu, L.; Avci, R.; Miocinovic, P.M.; Kozub, R.L.; Lapeyre, G.J. |

    1996-06-01

    The double Auger (DA) decay of a {ital K} hole has been observed directly by detecting the two emitted electrons in coincidence. The hole was created in {sup 37}Cl following the electron-capture decay of {sup 37}Ar. The probability of DA decay, per Auger decay, with the two electrons both having an energy greater than 250 eV was found to be 3.7{plus_minus}0.2{percent}. The DA probability was found to decrease exponentially as the energy partitioning between the two electrons changed from the asymmetric case ({ital E}{sub 1}{gt}{ital E}{sub 2}) to the symmetric case ({ital E}{sub 1}{approx_equal}{ital E}{sub 2}). The DA probability accounts for the bulk of the intensity of high charge states previously measured in {sup 37}Cl. {copyright} {ital 1996 The American Physical Society.}

  14. 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.

  15. 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.

  16. High resolution imaging and analysis of grain boundaries in steel using a field emission auger microprobe

    NASA Astrophysics Data System (ADS)

    Walmsley, J. C.; Jones, G.; Lee, B. J.; Wild, R. K.

    1997-02-01

    A standard cast low alloy steel sample, with known levels of grain boundary phosphorus and tin segregation, has been analysed after impact-fracture in a dedicated Auger microprobe. The instrument utilised a thermally assisted, Schottky diode field emission electron source. The examination illustrates the extra information that can be obtained by the high spatial resolution, in both secondary electron imaging and Auger electron spectroscopy and imaging, offered by this kind of source, when compared with more conventional tungsten and lanthanum hexaboride filaments. Cavities, with diameters of less than 1 μm, are observed on a proportion of the grain surfaces. Where cavitation occurs, tin is found to be present within the cavities and phosphorus on the areas of smooth grain boundary surface between them. During previous examinations of the same material, in a number of different laboratories, these features had not been resolved. In addition, elemental Auger mapping and analysis with a spatial resolution down to a few tens of nanometres are demonstrated by elemental imaging and spectroscopy of individual boron nitride particles on the cavitated grain boundary surfaces. It is suggested that, in the material examined, localised creep cavitation occurs during heat treatment. This is driven by residual stresses from the initial solution treatment and water quenching.

  17. Dmt and opioid peptides: a potent alliance.

    PubMed

    Bryant, Sharon D; Jinsmaa, Yunden; Salvadori, Severo; Okada, Yoshio; Lazarus, Lawrence H

    2003-01-01

    The introduction of the Dmt (2',6'-dimethyl-L-tyrosine)-Tic pharmacophore into the design of opioid ligands produced an extraordinary family of potent delta-opioid receptor antagonists and heralded a new phase in opioid research. First reviewed extensively in 1998, the incorporation of Dmt into a diverse group of opioid molecules stimulated the opioid field leading to the development of unique analogues with remarkable properties. This overview will document the crucial role played by this residue in the proliferation of opioid peptides with high receptor affinity (K(i) equal to or less than 1 nM) and potent bioactivity. The discussion will include the metamorphosis between delta-opioid receptor antagonists to delta-agonists based solely on subtle structural changes at the C-terminal region of the Dmt-Tic pharmacophore as well as their behavior in vivo. Dmt may be considered promiscuous due to the acquisition of potent mu-agonism by dermorphin and endomorphin derivatives as well as by a unique class of opioidmimetics containing two Dmt residues separated by alkyl or pyrazinone linkers. Structural studies on the Dmt-Tic compounds were enhanced tremendously by x-ray diffraction data for three potent and biologically diverse Dmt-Tic opioidmimetics that led to the development of pharmacophores for both delta-opioid receptor agonists and antagonists. Molecular modeling studies of other unique Dmt opioid analogues illuminated structural differences between delta- and mu-receptor ligand interactions. The future of these compounds as therapeutic applications for various medical syndromes including the control of cancer-associated pain is only a matter of time and perseverance. Copyright 2003 Wiley Periodicals, Inc.

  18. 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....

  19. 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....

  20. 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....

  1. 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....

  2. Auger North: The Pierre Auger Observatory in the Northern Hemisphere

    SciTech Connect

    Mantsch, Paul M.; /Fermilab

    2009-01-01

    Results from Auger South have settled some fundamental issues about ultra-high energy (UHE) cosmic rays and made clear what is needed now to identify the sources of these particles, to uncover the acceleration process, to establish the particle types, and to test hadronic interaction properties at extreme energies. The cosmic rays above 55 EeV are key. Auger North targets this high energy frontier by increasing the collecting power of the Auger Observatory by a factor of eight for those high energy air showers. Particles above about 40 EeV have been shown to be subject to propagation energy loss, as predicted by Greisen, Zatsepin and Kuzmin (GZK) in 1966. Moreover, it is now evident that there is a detectable flux of particles from extragalactic sources within the GZK sphere. The inhomogeneous distribution of matter in the local universe imprints its anisotropy on the arrival directions of cosmic rays above 55 EeV. The challenge is to collect enough of those arrival directions to identify the class of astrophysical accelerators and measure directly the brightest sources. Auger North will increase the event rate from 25 per year to 200 per year and give the Auger Observatory full sky exposure. The Auger Observatory also has the capability to detect UHE photons and neutrinos from discrete sources or from the decays of GZK pions. With the expanded aperture of Auger North, the detection of GZK photons and neutrinos will provide a complementary perspective of the highest energy phenomena in the contemporary universe. Besides being an observatory for UHE cosmic rays, photons, and neutrinos, the Auger Observatory will serve as a laboratory for the study of hadronic interactions with good statistics over a wide range of center-of-mass energies above what can be reached at the LHC. Auger North will provide statistical power at center-of-mass energies above 250 TeV where the alternative extrapolations of hadronic cross sections diverge. Auger North is ready to go. The

  3. 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.

  4. 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.

  5. Micro-area Auger analysis of a SiC/Ti fibre composite

    NASA Technical Reports Server (NTRS)

    Zironi, E. P.; Poppa, H.

    1981-01-01

    Micro-area Auger electron spectroscopy with a spatial resolution of less than 50 nm has been used to study the concentration of elements across the reaction zone of a W-reinforced SiC fiber in a titanium matrix. Although the elemental concentrations obtained by this technique are affected by the reaction zone morphology to a greater extent than in the case of X-ray microprobe analysis, the proposed technique has the advantage of a much higher spatial resolution and avoids the problems of bulk averaging that characterize the X-ray technique.

  6. Experimental study of underground exploration by auger boring on a Mars rover

    NASA Astrophysics Data System (ADS)

    Kojima, Masaki; Saitou, Kenji; Kaneko, Yutaka; Kawashima, Nobuki

    Results are presented of a system study conducted on the possibility of exploring Mars using a Mars rover; emphasis is focused on the underground exploration of Mars by an auger boring machine. An engineering model was constructed, and a boring test was conducted using simulated Martian soil. It is shown that it is possible to drill soil composed of dust, sand, and gravel measuring 0.007-16 mm in diameter to a depth of 1.5 m. The diffusion of the collected sample can be confined to less than a thickness of 20 cm.

  7. Micro-area Auger analysis of a SiC/Ti fibre composite

    NASA Technical Reports Server (NTRS)

    Zironi, E. P.; Poppa, H.

    1981-01-01

    Micro-area Auger electron spectroscopy with a spatial resolution of less than 50 nm has been used to study the concentration of elements across the reaction zone of a W-reinforced SiC fiber in a titanium matrix. Although the elemental concentrations obtained by this technique are affected by the reaction zone morphology to a greater extent than in the case of X-ray microprobe analysis, the proposed technique has the advantage of a much higher spatial resolution and avoids the problems of bulk averaging that characterize the X-ray technique.

  8. SEARCH FOR A CORRELATION BETWEEN ANTARES NEUTRINOS AND PIERRE AUGER OBSERVATORY UHECRs ARRIVAL DIRECTIONS

    SciTech Connect

    Adrian-Martinez, S.; Ardid, M.; Bou-Cabo, M.; Andre, M.; Anghinolfi, M.; Anton, G.; Anvar, S.; Astraatmadja, T.; Beemster, L. J.; Bogazzi, C.; Bouwhuis, M. C.; Baret, B.; Bouhou, B.; Basa, S.; Biagi, S.; and others

    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 {sup -2} energy spectrum) from all UHECR directions, a 90% CL upper limit on the neutrino flux of 5.0 Multiplication-Sign 10{sup -8} GeV cm{sup -2} s{sup -1} per source is derived.

  9. Auger and carrier-surface phonon interaction processes in graphene on a substrate made of polar materials

    NASA Astrophysics Data System (ADS)

    Mahdouani, M.; Bourguiga, R.

    2017-02-01

    We present a theoretical study of two specific dynamical optical properties, namely Auger and surface electron-phonon interaction processes in monolayer graphene on polar substrates such as SiO2 , HfO2 , SiC and hexagonal BN. Thus the eigenenergies have been derived from the tight-binding Hamiltonian in monolayer graphene. Our results indicate that both Auger and electron-surface phonon interaction processes depend on the polar substrate. Such polar substrates allow for the presence of polar optical phonons localized near the graphene-substrate interface which could be a significant scattering source for graphene carriers across the long-range Fröhlich coupling. Furthermore, the linear, gapless band structure of graphene provides ideal conditions for Auger processes which are Auger recombination (AR) and impact ionization (IMI). These processes are of fundamental interest because they strongly influence the relaxation dynamics of carriers. Likewise, we have investigated the effect of various dielectrics on both Auger and electron-surface phonon scattering rates in single layer graphene by varying the temperature, the charge carrier density and the physical separation between the interface of the dielectric substrate and graphene.

  10. 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

  11. 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.

  12. Highly potent and moderately potent topical steroids are effective in treating phimosis: a prospective randomized study.

    PubMed

    Yang, Stephen Shei Dei; Tsai, Yao Chou; Wu, Chia Chang; Liu, Shih Ping; Wang, Chung Cheng

    2005-04-01

    We report a prospective randomized study comparing the effects of highly potent and moderately potent topical steroids in treating pediatric phimosis. A total of 70 boys 1 to 12 years old with phimosis were randomly assigned to receive topical application of either betamethasone valerate 0.06% (a highly potent steroid) or clobetasone butyrate 0.05% (a moderately potent steroid). Parents of the boys were instructed to retract the foreskin gently without causing pain, and to apply the topical steroids over the stenotic opening of the prepuce twice daily for 4 weeks, then for another 4 weeks if no improvement was achieved. Retractibility of the prepuce was graded from 0 to 5. Response to treatment was arbitrarily defined as improvement in the retractibility score of more than 2 points. Mean treatment and followup periods were 4.3 and 19.1 weeks, respectively. The response rates in boys treated with betamethasone valerate and clobetasone butyrate were 81.3% and 77.4%, respectively (p = 0.63). Mean retractibility score decreased from 3.9 +/- 1.0 to 1.7 +/- 1.1, and 4.2 +/- 1.0 to 1.9 +/- 1.0 in the betamethasone and clobetasone groups, respectively. Both steroids were effective in all age groups. Pretreatment retractibility score did not affect treatment outcomes. No adverse effect was encountered. Highly potent and moderately potent topical steroids are of comparable effectiveness in treating phimosis. A less potent steroid may be considered first to decrease the risk of the potential adverse effects.

  13. A Convenient Formalism for Auger and Autoionization of Overlapping Resonances

    NASA Astrophysics Data System (ADS)

    Tabanli, M. M.; Peacher, J. L.; Madison, D. H.

    2003-05-01

    Following the works of Fano [1], Balashov [2], and Davis and Feldkamp [3], we have developed a general formalism for cross sections near overlapping autoionizing resonances [4]. We show that the effect of the interaction between different resonances can be treated as a correction factor to the isolated resonances treatment of the problem. We present a simple correction factor, which can be calculated using only the energy and the width of the resonances. We have applied our approach to four physically important cases as a representative of two overlapping resonances. Our results indicate that even in the case where the resonances are only somewhat overlapping, the correction factor makes a considerable contribution and the agreement between the relative experimental cross section and the isolated resonances calculation does not necessarily imply that the resonance-resonance interactions are negligible. [1] U. Fano, Phys. Rev. 124,.1866 (1961) [2] V. V. Balashov, S. S. Lipovetsky and V. S. Senashenko, Sov. Phys. JETP 36, 858 (1973) [3] L. C. Davis and L. A. Feldkamp, Phys. Rev B. 15, 2961 (1977) [4] M. M. Tabanli, J. L. Peacher and D. H. Madison, J. Phys. B 36, 217 (2003)

  14. Extended x-ray-absorption fine structure—Auger process for surface structure analysis: Theoretical considerations of a proposed experiment

    PubMed Central

    Landman, Uzi; Adams, David L.

    1976-01-01

    A method for surface structure analysis is proposed. The proposed process combines x-ray photoabsorption and Auger electron emission. The extended x-ray-absorption fine structure, occurring for photon energies above an atomic absorption edge, contains structural information of the microscopic environment due to the coupling of the photoelectron final state with the atomic initial state. Measurement of the variations in the intensity of particular Auger lines, as a function of the incident radiation energy, provides a surface sensitive measure of the photoabsorption cross section in the media. Theoretical considerations of the physical processes underlying the proposed experiment and its feasibility, and a discussion of background contributions are presented. PMID:16592339

  15. Electrical Detection of Quantum Dot Hot Electrons Generated via a Mn(2+)-Enhanced Auger Process.

    PubMed

    Barrows, Charles J; Rinehart, Jeffrey D; Nagaoka, Hirokazu; deQuilettes, Dane W; Salvador, Michael; Chen, Jennifer I L; Ginger, David S; Gamelin, Daniel R

    2017-01-05

    An all-solid-state quantum-dot-based photon-to-current conversion device is demonstrated that selectively detects the generation of hot electrons. Photoexcitation of Mn(2+)-doped CdS quantum dots embedded in the device is followed by efficient picosecond energy transfer to Mn(2+) with a long-lived (millisecond) excited-state lifetime. Electrons injected into the QDs under applied bias then capture this energy via Auger de-excitation, generating hot electrons that possess sufficient energy to escape over a ZnS blocking layer, thereby producing current. This electrically detected hot-electron generation is correlated with a quench in the steady-state Mn(2+) luminescence and the introduction of a new nonradiative excited-state decay process, consistent with electron-dopant Auger cross-relaxation. The device's efficiency at detecting hot-electron generation provides a model platform for the study of hot-electron ionization relevant to the development of novel photodetectors and alternative energy-conversion devices.

  16. The Pierre Auger Observatory

    SciTech Connect

    Hojvat, C.

    1997-03-01

    The Pierre Auger Observatory is an international collaboration for the detailed study of the highest energy cosmic rays. It will operate at two similar sites, one in the northern hemisphere and one in the southern hemisphere. The Observatory is designed to collect a statistically significant data set of events with energies greater than 10{sup 19} eV and with equal exposures for the northern and southern skies.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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%.

  2. 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%.

  3. 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%.

  4. Evaluation and auger analysis of a zinc-dialkyl-dithiophosphate antiwear additive in several diester lubricants

    NASA Technical Reports Server (NTRS)

    Brainard, W. A.; Ferrante, J.

    1979-01-01

    The wear of pure iron in sliding contact with hardened M-2 tool steel was measured for a series of synthetic diester fluids, both with and without a zinc dialkyl dithiophosphate (ZDP) antiwear additive, as test lubricants. Selected wear scars were analyzed by an Auger emission spectroscopy (AES) depth profiling technique in order to assess the surface film elemental composition. The ZDP was an effective antiwear additive for all the diesters except dibutyl oxalate and dibutyl sebacate. The high wear measured for the additive-containing oxalate was related to corrosion; the higher wear measured for the additive-containing sebacate was due to an oxygen interaction. The AES of dibutyl sebacate surfaces run in dry air and in dry nitrogen showed large differences only in the amount of oxygen present. The AES of worn surfaces where the additive was effective showed no zinc, only a little phosphorus, and large amounts of sulfur.

  5. Application of a Novel Multiple-Scattering Approach to Photoelectron Diffraction and Auger Electron Diffraction.

    NASA Astrophysics Data System (ADS)

    Kaduwela, Ajith P.

    We apply a new separable-Green's-function matrix method due to Rehr and Albers (Phys. Rev. B4l (1990) 8139) to a multiple scattering treatment of photoelectron diffraction and Auger electron diffraction. This cluster -based method permits building up successive orders of scattering and judging the approach to convergence in a convenient and time-saving way. We include multiple scattering up to tenth order and can treat photoelectron emission form any initial state (s, p, d, or f) with full final-state interference. This new approach is used to simulate emission from linear and bent chains of atoms, from epitaxial overlayers and multilayer substrates and from atomic and molecular adsorbates, and various conclusions are drawn concerning the range of utility of the method and the geometric structures for which multiple scattering effects must be considered.

  6. A Targeted Search for Point Sources of EeV Photons with the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Aab, A.; Abreu, P.; Aglietta, M.; Samarai, I. Al; Albuquerque, I. F. M.; Allekotte, I.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Anastasi, G. A.; Anchordoqui, L.; Andrada, B.; Andringa, S.; Aramo, C.; Arqueros, F.; Arsene, N.; Asorey, H.; Assis, P.; Aublin, J.; Avila, G.; Badescu, A. M.; Balaceanu, A.; Barreira Luz, R. J.; Beatty, J. J.; Becker, K. H.; Bellido, J. A.; Berat, C.; Bertaina, M. E.; Bertou, X.; Biermann, P. L.; Billoir, P.; Biteau, J.; Blaess, S. G.; Blanco, A.; Blazek, J.; Bleve, C.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Borodai, N.; Botti, A. M.; Brack, J.; Brancus, I.; Bretz, T.; Bridgeman, A.; Briechle, F. L.; Buchholz, P.; Bueno, A.; Buitink, S.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, L.; Cancio, A.; Canfora, F.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Chavez, A. G.; Chinellato, J. A.; Chudoba, J.; Clay, R. W.; Colalillo, R.; Coleman, A.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cooper, M. J.; Coutu, S.; Covault, C. E.; Cronin, J.; D'Amico, S.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Jong, S. J.; De Mauro, G.; de Mello Neto, J. R. T.; De Mitri, I.; de Oliveira, J.; de Souza, V.; Debatin, J.; Deligny, O.; Di Giulio, C.; Di Matteo, A.; Díaz Castro, M. L.; Diogo, F.; Dobrigkeit, C.; D'Olivo, J. C.; Dorosti, Q.; dos Anjos, R. C.; Dova, M. T.; Dundovic, A.; Ebr, J.; Engel, R.; Erdmann, M.; Erfani, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Fick, B.; Figueira, J. M.; Filipčič, A.; Fratu, O.; Freire, M. M.; Fujii, T.; Fuster, A.; Gaior, R.; García, B.; Garcia-Pinto, D.; Gaté, F.; Gemmeke, H.; Gherghel-Lascu, A.; Ghia, P. L.; Giaccari, U.; Giammarchi, M.; Giller, M.; Głas, D.; Glaser, C.; Golup, G.; Gómez Berisso, M.; Gómez Vitale, P. F.; González, N.; Gorgi, A.; Gorham, P.; Grillo, A. F.; Grubb, T. D.; Guarino, F.; Guedes, G. P.; Hampel, M. R.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Heimann, P.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Holt, E.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huege, T.; Hulsman, J.; Insolia, A.; Isar, P. G.; Jandt, I.; Jansen, S.; Johnsen, J. A.; Josebachuili, M.; Kääpä, A.; Kambeitz, O.; Kampert, K. H.; Katkov, I.; Keilhauer, B.; Kemp, E.; Kemp, J.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Krause, R.; Krohm, N.; Kuempel, D.; Kukec Mezek, G.; Kunka, N.; Kuotb Awad, A.; LaHurd, D.; Lauscher, M.; Legumina, R.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; Lopes, L.; López, R.; López Casado, A.; Luce, Q.; Lucero, A.; Malacari, M.; Mallamaci, M.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Mariş, I. C.; Marsella, G.; Martello, D.; Martinez, H.; Martínez Bravo, O.; Masías Meza, J. J.; Mathes, H. J.; Mathys, S.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Mayotte, E.; Mazur, P. O.; Medina, C.; Medina-Tanco, G.; Melo, D.; Menshikov, A.; Micheletti, M. I.; Middendorf, L.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Mockler, D.; Mollerach, S.; Montanet, F.; Morello, C.; Mostafá, M.; Müller, A. L.; Müller, G.; Muller, M. A.; Müller, S.; Mussa, R.; Naranjo, I.; Nellen, L.; Nguyen, P. H.; Niculescu-Oglinzanu, M.; Niechciol, M.; Niemietz, L.; Niggemann, T.; Nitz, D.; Nosek, D.; Novotny, V.; Nožka, H.; Núñez, L. A.; Ochilo, L.; Oikonomou, F.; Olinto, A.; Palatka, M.; Pallotta, J.; Papenbreer, P.; Parente, G.; Parra, A.; Paul, T.; Pech, M.; Pedreira, F.; Pȩkala, J.; Pelayo, R.; Peña-Rodriguez, J.; Pereira, L. A. S.; Perlín, M.; Perrone, L.; Peters, C.; Petrera, S.; Phuntsok, J.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Porowski, C.; Prado, R. R.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Quinn, S.; Ramos-Pollan, R.; Rautenberg, J.; Ravignani, D.; Revenu, B.; Ridky, J.; Risse, M.; Ristori, P.; Rizi, V.; Rodrigues de Carvalho, W.; Rodriguez Fernandez, G.; Rodriguez Rojo, J.; Rogozin, D.; Roncoroni, M. J.; Roth, M.; Roulet, E.; Rovero, A. C.; Ruehl, P.; Saffi, S. J.; Saftoiu, A.; Salamida, F.; Salazar, H.; Saleh, A.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Sanchez-Lucas, P.; Santos, E. M.; Santos, E.; Sarazin, F.; Sarmento, R.; Sarmiento, C. A.; Sato, R.; Schauer, M.; Scherini, V.; Schieler, H.; Schimp, M.; Schmidt, D.; Scholten, O.; Schovánek, P.; Schröder, F. G.; Schulz, A.; Schulz, J.; Schumacher, J.; Sciutto, S. J.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sigl, G.; Silli, G.; Sima, O.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sonntag, S.; Sorokin, J.; Squartini, R.; Stanca, D.; Stanič, S.; Stasielak, J.; Stassi, P.; Strafella, F.; Suarez, F.; Suarez Durán, M.; Sudholz, T.; Suomijärvi, T.; Supanitsky, A. D.; Swain, J.; Szadkowski, Z.; Taboada, A.; Taborda, O. A.; Tapia, A.; Theodoro, V. M.; Timmermans, C.; Todero Peixoto, C. J.; Tomankova, L.; Tomé, B.; Torralba Elipe, G.; Travnicek, P.; Trini, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van Bodegom, P.; van den Berg, A. M.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Varner, G.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Vergara Quispe, I. D.; Verzi, V.; Vicha, J.; Villaseñor, L.; Vorobiov, S.; Wahlberg, H.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weindl, A.; Wiencke, L.; Wilczyński, H.; Winchen, T.; Wirtz, M.; Wittkowski, D.; Wundheiler, B.; Yang, L.; Yelos, D.; Yushkov, A.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zepeda, A.; Zimmermann, B.; Ziolkowski, M.; Zong, Z.; Zuccarello, F.

    2017-03-01

    Simultaneous measurements of air showers with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for EeV photon point sources. Several Galactic and extragalactic candidate objects are grouped in classes to reduce the statistical penalty of many trials from that of a blind search and are analyzed for a significant excess above the background expectation. The presented search does not find any evidence for photon emission at candidate sources, and combined p-values for every class are reported. Particle and energy flux upper limits are given for selected candidate sources. These limits significantly constrain predictions of EeV proton emission models from non-transient Galactic and nearby extragalactic sources, as illustrated for the particular case of the Galactic center region.

  7. A Targeted Search for Point Sources of EeV Photons with the Pierre Auger Observatory

    DOE PAGES

    Aab, A.; Abreu, P.; Aglietta, M.; ...

    2017-03-09

    Simultaneous measurements of air showers with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for EeV photon point sources. Several Galactic and extragalactic candidate objects are grouped in classes to reduce the statistical penalty of many trials from that of a blind search and are analyzed for a significant excess above the background expectation. The presented search does not find any evidence for photon emission at candidate sources, and combined p-values for every class are reported. Particle and energy flux upper limits are given for selected candidate sources. Lastly, these limits significantly constrain predictionsmore » of EeV proton emission models from non-transient Galactic and nearby extragalactic sources, as illustrated for the particular case of the Galactic center region.« less

  8. Recent results on the operation of a Cherenkov detector prototype for the Pierre Auger observatory

    NASA Astrophysics Data System (ADS)

    Alarcón, M.; Medina, M.; Villaseñor, L.; Fernández, A.; Salazar, H.; Valdés-Galicia, J. F.; D'Olivo, J. C.; Nellen, L.; Zepeda, A.

    1999-10-01

    A full-sized water Cherenkov detector (WCD) prototype (cylinder 3.57 m diameter filled with purified water up to a height of 1.2 m) was used to obtain experimental results that validate the concept of remote calibration and monitoring of WCDs based on the use of the natural flux of cosmic ray muons. Two types of events can be used to monitor and to calibrate each of the WCDs: through-going muons (i.e., isolated muons) and decay electrons from muons stopped inside each detector. The different triggers that will be used to obtain these events and the on-line calibration and monitoring histograms are discussed along with the way these data can be used to diagnose component failures of any of the surface stations of the Auger Observatory.

  9. 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.

  10. 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.

  11. Triple targeting of Auger emitters using octreotate conjugated to a DNA-binding ligand and a nuclear localizing signal.

    PubMed

    Violet, John A; Farrugia, Gabriella; Skene, Colin; White, Jonathan; Lobachevsky, Pavel; Martin, Roger

    2016-11-01

    We investigated the effect of incorporation of a nuclear localization signal (NLS) into a conjugate comprising the DNA binding ligand para-iodoHoechst (PIH) and octreotate on its DNA binding and affinity to the somatostatin receptor (SSTR). Confirmation of these properties would support development of similar conjugates labelled with Auger emitters for their potential in Auger endoradiotherapy. We synthesized conjugates of PIH and octreotate (PO) or PIH and NLS (PN) and a conjugate comprising PIH, NLS and octreotate (PNO). DNA-binding characteristics of PIH and conjugates were assessed using synthetic DNA oligonucleotides employing spectrophotometric titration of ligand solutions with DNA. We used membranes from the type 2 SSTR (SSTR2) overexpressing human non-small cell lung cancer cell line A427-7 to investigate the binding affinity of PNO. We demonstrated PN and PNO retain specific high affinity DNA-binding properties observed for PIH, and acquire an additional non-specific binding capacity. No DNA binding was observed for PO. PNO retains its binding affinity for SSTR. The DNA-binding properties of PNO and its affinity for SSTR suggests that it could potentially be used for tumour-specific delivery of PIH labelled with an Auger emitter in SSTR expressing tumours.

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 30 CFR 819.19 - Auger mining: Backfilling and grading.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 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 819.19 - Auger mining: Backfilling and grading.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 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...

  1. 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...

  2. 30 CFR 819.19 - Auger mining: Backfilling and grading.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 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...

  3. 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...

  4. 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...

  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, 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...

  7. 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 §§ 816.41...

  8. 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 §§ 816.41...

  9. 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 §§ 816.41...

  10. 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 §§ 816.41...

  11. 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... 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 §§ 816.41...

  12. 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.

  13. The Pierre Auger Research and Development Array (RDA) in southeastern Colorado - R&D for a giant ground array

    NASA Astrophysics Data System (ADS)

    Sarazin, Fred; Collonges, S.; Courty, B.; Daubenspeck, M.; Gaumé, A.; Génolini, B.; Guglielmi, L.; Hevinga, M. A.; Hodgson, J.; Hollenbeck, J.; Kuhn, K.; Malinowski, M.; Marton, M.; Maskevics, M.; Meyer, H.; Nelson, K.; Rauly, E.; Robinson, S.; Rokos, A.; Solomey, N.; Speelman, C. F.; Thompson, J.; Nguyen Trung, T.; Wolf, O.; Yadon, J.

    2013-06-01

    The Pierre Auger Research and Development Array (RDA) was originally designed to be the precursor of the northern Auger observatory, a hybrid array of 4400 surface detector stations and 39 fluorescence telescopes deployed over 20,000 square kilometers. It is conceived as a test bed aiming at validating an improved and more cost-effective 1-PMT surface detector design and a new peer-to-peer communication system. The array of ten surface detector stations and ten communication-only stations is currently being deployed in southeastern Colorado and will be operated at least until late 2013. It is configured in such a way that it allows testing of a new peer-to-peer communication protocol, as well as a new surface detector electronics design with a larger dynamic range aiming at reducing the distance from the shower core where saturation is observed. All these developments are expected in the short term to improve the performance of the Pierre Auger Observatory and enable future enhancements. In the longer term, it is hoped that some of these new developments may contribute to the design of a next-generation giant ground array.

  14. 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.

  15. Strand breakage by decay of DNA-bound (124)I provides a basis for combined PET imaging and Auger endoradiotherapy.

    PubMed

    Lobachevsky, Pavel; Clark, George R; Pytel, Patrycja D; Leung, Brenda; Skene, Colin; Andrau, Laura; White, Jonathan M; Karagiannis, Tom; Cullinane, Carleen; Lee, Boon Q; Stuchbery, Andrew; Kibedi, Tibor; Hicks, Rodney J; Martin, Roger F

    2016-11-01

    Purpose DNA ligands labelled with (125)I induce cytotoxic DNA double-strand breaks (DSB), suggesting a potential for Auger endoradiotherapy. Since the 60-day half-life of (125)I is suboptimal for therapy, we have investigated another Auger-emitter (124)I, with shorter half-life (4.18 days), and the additional feature of positron-emission, enabling positron emission tomography (PET) imaging. The purpose of this study was to compare the two radionuclides on the basis of DNA DSB per decay. Materials and methods Using a (124)I- (or (125)I)-labelled minor groove binding DNA ligand, we investigated DNA breakage using the plasmid DNA assay. Biodistribution of the conjugate of the labelled ligand with transferrin was investigated in nude mice bearing a K562 human lymphoma xenograft. Results The probability of DSB per decay was 0.58 and 0.85 for (124)I and (125)I, respectively, confirming the therapeutic potential of the former. The crystal structure of the ligand DNA complex shows the iodine atom deep within the minor groove, consistent with the high efficiency of induced damage. Biodistribution studies, including PET imaging, showed distinctive results for the conjugate, compared to the free ligand and transferrin, consistent with receptor-mediated delivery of the ligand. Conclusions Conjugation of (124)I-labelled DNA ligands to tumor targeting peptides provides a feasible strategy for Auger endoradiotherapy, with the advantage of monitoring tumor targeting by PET imaging.

  16. AugerPrime: the upgrade of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Sarazin, Frederic; Pierre Auger Collaboration Collaboration

    2017-01-01

    The nature and origin of ultra-high energy cosmic-rays (UHECRs) remain largely a mystery despite a wealth of new information obtained in recent years at the Pierre Auger Observatory and elsewhere. Mass composition studies performed at Auger appear to challenge the historical view that the UHECR primaries (at least for energies greater than 1019 eV) are all protons, and the observation of a GZK-like flux suppression in the cosmic-ray spectrum is counterbalanced by the absence of point source observations and the relatively weak anisotropy of the UHECR sky. In order to resolve this apparent contradiction, the Pierre Auger collaboration is embarking in an upgrade of the Observatory (``AugerPrime'') with the goal of extending the mass composition measurements beyond the observed flux suppression. In this presentation, the science case for the upgrade and its technical realization will be described and discussed especially with regards to the existence of GZK photons and neutrinos. NSF PHY-1506486.

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

    SciTech Connect

    Nishimura, Shun; Ebitani, Kohki; Miyazato, Akio

    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 H{sub 2}O: 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, {sup 13}C-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.

  18. 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.

  19. 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.

  20. 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.

  1. From The Pierre Auger Observatory to AugerPrime

    NASA Astrophysics Data System (ADS)

    Parra, Alejandra; Martínez Bravo, Oscar; Pierre Auger Collaboration

    2017-06-01

    In the present work we report the principal motivation and reasons for the new stage of the Pierre Auger Observatory, AugerPrime. This upgrade has as its principal goal to clarify the origin of the highest energy cosmic rays through improvement in studies of the mass composition. To accomplished this goal, AugerPrime will use air shower universality, which states that extensive air showers can be completely described by three parameters: the primary energy E 0, the atmospheric shower depth of maximum X max, and the number of muons, Nμ . The Auger Collaboration has planned to complement its surface array (SD), based on water-Cherenkov detectors (WCD) with scintillator detectors, calls SSD (Scintillator Surface Detector). These will be placed at the top of each WCD station. The SSD will allow a shower to shower analysis, instead of the statistical analysis that the Observatory has previously done, to determine the mass composition of the primary particle by the electromagnetic to muonic ratio.

  2. Questions and Answers in Extreme Energy Cosmic Rays - a guide to explore the data set of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Abreu, P.; Andringa, S.; Diogo, F.; Espírito Santo, M. C.; Pierre Auger Collaboration

    2016-04-01

    The Pierre Auger Observatory is the largest extensive air shower detector, covering 3000 km2 in Argentina. The Observatory makes available, for educational and outreach purposes, 1% of its cosmic ray data set, corresponding after 10 years of running to more than 35 000 cosmic ray events. Several different proposals of educational activities have been developed within the collaboration and are available. We will focus on the activity guide we developed with the aim of exploring the rich education and outreach potential of cosmic rays with Portuguese high school students. In this guide we use the Auger public data set as a starting point to introduce open questions on the origin, nature and spectrum of high energy cosmic rays. To address them, the students learn about the air-shower cascade development, data reconstruction and its statistical analysis. The guide has been used both in the context of student summer internships at research labs and directly in schools, under the supervision of trained teachers and in close collaboration with Auger researchers. It is now available in Portuguese, English and Spanish.

  3. 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.

  4. 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.

  5. Proof of principal for staircase auger chip removal theory

    NASA Astrophysics Data System (ADS)

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

    1987-08-01

    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.

  6. 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.

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

    PubMed

    Inhester, L; Burmeister, C F; Groenhof, G; Grubmüller, 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 Schrödinger 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.

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

    NASA Astrophysics Data System (ADS)

    Inhester, Ludger; Burmeister, Carl F.; Groenhof, Gerrit; Grubmueller, Helmut

    2012-06-01

    The high intensity of Free Electron Lasers (FEL) opens up the possibility to perform single-shot molecule scattering experiments. However, even for small molecules radiation damage induced by absorption of intense x-ray radiation is not yet fully understood. 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 MD trajectories photoionization and Auger transition rates were computed based on electronic continuum wavefunctions obtained by explicit integration of the coupled radial Schr"odinger equations. To account for the nuclear dynamics during the core hole lifetime, the calculated electron emission spectra for different molecular geometries were accumulated according to the obtained time-dependent populations. 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 on the electron emission spectra. In addition, the lifetime of the double core ionized water was found to be significantly shorter than half of the single core hole lifetime.

  9. Azachalcones: a new class of potent polyphenol oxidase inhibitors.

    PubMed

    Radhakrishnan, Sini Karanayil; Shimmon, Ronald Gibrial; Conn, Costa; Baker, Anthony T

    2015-04-15

    A library of potent inhibitors of polyphenol oxidase and their structure activity relationships are described. Azachalcone derivatives were synthesized and tested for their tyrosinase inhibitory activity. Their inhibitory activities on mushroom tyrosinase using l-DOPA as a substrate were investigated. Two compounds that are the reduction congeners of the pyridinyl azachalcones strongly inhibited the enzyme activity and were more potent than the positive control kojic acid.

  10. Development of a potent and selective cell penetrant Legumain inhibitor.

    PubMed

    Ness, Kerry A; Eddie, Sharon L; Higgins, Catherine A; Templeman, Amy; D'Costa, Zenobia; Gaddale, Kishore K D; Bouzzaoui, Samira; Jordan, Linda; Janssen, Dominic; Harrison, Timothy; Burkamp, Frank; Young, Andrew; Burden, Roberta; Scott, Christopher J; Mullan, Paul B; Williams, Rich

    2015-12-01

    This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2-P3 linker units and the P3 group SAR which led to the identification of 10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that 10t has activity in both cancer cell viability and colony formation assays.

  11. The Pierre Auger Observatory Upgrade

    NASA Astrophysics Data System (ADS)

    Marsella, Giovanni

    2017-03-01

    It is planned to operate the Pierre Auger Observatory until at least the end of 2024. An upgrade of the experiment has been proposed in order to provide additional measurements to allow one to elucidate the mass composition and the origin of the flux suppression at the highest energies, to search for a flux contribution of protons up to the highest energies and to reach a sensitivity to a contribution as small as 10% in the flux suppression region, to study extensive air showers and hadronic multi-particle production. With operation planned until 2024, event statistics will more than double compared with the existing Auger data set, with the critical added advantage that every event will now have mass information. Obtaining additional composition-sensitive information will not only help to better reconstruct the properties of the primary particles at the highest energies, but also improve the measurements in the energy range just above the ankle. Furthermore, measurements with the new detectors will help to reduce systematic uncertainties related to the modelling hadronic showers and to limitations in the reconstruction algorithms. A description of the principal proposed Auger upgrade will be presented. The Auger upgrade promises high-quality future data, and real scope for new physics.

  12. 33 CFR 147.813 - Auger Tension Leg Platform safety zone.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Auger Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.813 Auger Tension Leg Platform safety zone. (a) Description. The Auger Tension Leg Platform (Auger TLP) is located at position 27°32′45...

  13. 33 CFR 147.813 - Auger Tension Leg Platform safety zone.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Auger Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.813 Auger Tension Leg Platform safety zone. (a) Description. The Auger Tension Leg Platform (Auger TLP) is located at position 27°32′45...

  14. 33 CFR 147.813 - Auger Tension Leg Platform safety zone.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Auger Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.813 Auger Tension Leg Platform safety zone. (a) Description. The Auger Tension Leg Platform (Auger TLP) is located at position 27°32′45...

  15. 33 CFR 147.813 - Auger Tension Leg Platform safety zone.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Auger Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.813 Auger Tension Leg Platform safety zone. (a) Description. The Auger Tension Leg Platform (Auger TLP) is located at position 27°32′45...

  16. 33 CFR 147.813 - Auger Tension Leg Platform safety zone.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Auger Tension Leg Platform safety... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.813 Auger Tension Leg Platform safety zone. (a) Description. The Auger Tension Leg Platform (Auger TLP) is located at position 27°32′45...

  17. 2s photoionization and subsequent Auger cascade in atomic Si

    SciTech Connect

    Partanen, L.; Fritzsche, S.; Jaenkaelae, K.; Huttula, M.; Osmekhin, S.; Aksela, H.; Aksela, S.; Urpelainen, S.

    2010-06-15

    The 2s photoionization and subsequent Auger transition cascade in atomic Si were studied by means of synchrotron-radiation-induced electron spectroscopy. After the 2s photoionization, the core hole states decay predominantly by a two-step Auger transition cascade into the triply ionized [Ne]nl states. The ionization channels of the 2s core-ionized Si{sup +} atoms to Si{sup 3+} ions were observed by measuring the conventional Auger electron spectra of the L{sub 1}-L{sub 2,3}M Coster-Kronig transitions and the L{sub 2,3}M-MMM Auger transitions. The observed L{sub 1}-L{sub 2,3}M and L{sub 2,3}M-MMM Auger spectra were analyzed by means of extensive multiconfiguration Dirac-Fock computations. We found that the electron correlation plays a prominent role in the Auger cascade, especially for the final-step Auger L{sub 2,3}M-MMM spectrum. Additionally, it was seen that the L{sub 2,3}M-MMM Auger spectrum of Si includes more Auger groups than the isoelectronic L{sub 2,3}-MM Auger spectrum of Al. Thus, more information on the intermediate ionic states is obtained if they are produced by Auger cascade rather than by direct photoionization.

  18. The LVV Auger line shape of sulfur on copper studied by Auger photoelectron coincidence spectroscopy.

    PubMed

    Di Filippo, G; Trioni, M I; Fratesi, G; Schumann, F O; Wei, Z; Li, C H; Behnke, L; Patil, S; Kirschner, J; Stefani, G

    2015-03-04

    We have studied the line shapes of Cu(0 0 1)-p (2 × 2)S L2VV and L3VV Auger decay by means of Auger photoelectron coincidence spectroscopy. Measuring the LVV Auger spectrum in coincidence with S 2p1/2 and 2p3/2 photoelectrons respectively, we have been able to separate the two overlapping Auger spectra and determine their intrinsic line shapes. The two Auger transitions, though shifted in energy, display an identical line shape whose main features can be qualitatively understood considering a single particle approximation but are better described within a Cini-Sawatzky (CS) approach. Comparison between the experimental and the CS calculated spectra confirms that a substantial part of the Auger lines (∼20%) can be ascribed to decay events accompanied by the excitation of one additional electron-hole pair in the valence band. For the first time, the locality of the Auger process combined with the surface sensitivity of the APECS technique and its ability to separate overlapping structures are used to study Auger transitions taking place at the the surface states of a S/noble-metal interface.

  19. Deceleration processes of secondary electrons produced by a high-energy Auger electron in a biological context.

    PubMed

    Kai, Takeshi; Yokoya, Akinari; Ukai, Masatoshi; Fujii, Kentaro; Watanabe, Ritsuko

    2016-11-01

    To simulate the deceleration processes of secondary electrons produced by a high-energy Auger electron in water, and particularly to focus on the spatial and temporal distributions of the secondary electron and the collision events (e.g. ionization, electronic excitation, and dissociative electron attachment) that are involved in the multiplication of lesions at sites of DNA damage. We developed a dynamic Monte Carlo code that considers the Coulombic force between an ejected electron and its parent cation produced by the Auger electron in water. Thus our code can simulate some return electrons to the parent cations. Using the code, we calculated to within the order of femtoseconds the temporal evolution of collision events, the mean energy, and the mean traveling distance (including its spatial probability distribution) of the electron at an ejected energy of 20 eV. Some of the decelerating electrons in water in the Coulombic field were attracted to the ionized atoms (cations) by the Coulombic force within hundreds of femtoseconds, although the force did not significantly enhance the number of ionization, electronic excitation, and dissociative electron attachment collision events leading to water radiolysis. The secondary electrons are decelerated in water by the Coulombic force and recombined to the ionized atoms (cations). Furthermore, the some return electrons might be prehydrated in water layer near the parent cation in DNA if the electrons might be emitted from the DNA. The prehydrated electron originated from the return electron might play a significant role in inducing DNA damage.

  20. 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.

  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.

    PubMed

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

    2015-04-01

    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(-9) - 10(-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(4)P and prompt Auger projectile states formed by electron capture in collisions of 25.3 MeV F(7+) with H2 and 12.0 MeV C(4+) with Ne recorded at 0° to the beam direction. These results are important for the accurate evaluation of the 1s2s2p (4)P/(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. Determination of the solid angle and response function of a hemispherical spectrograph with injection lens for Auger electrons emitted from long lived projectile states

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    We present SIMION 8.1 Monte Carlo type simulations of the response function and detection solid angle for long lived Auger states (lifetime τ ˜ 10-9 - 10-5 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 1s2s2p4P and prompt Auger projectile states formed by electron capture in collisions of 25.3 MeV F7+ with H2 and 12.0 MeV C4+ with Ne recorded at 0∘ to the beam direction. These results are important for the accurate evaluation of the 1s2s2p 4P/2P 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.

  3. 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.

  4. 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…

  5. 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…

  6. 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.

  7. 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).

  8. Nanodosimetry of (125)I Auger electrons.

    PubMed

    Bantsar, Aliaksandr; Pszona, Stanislaw

    2012-12-01

    The nanodosimetric description of the radiation action of Auger electrons on nitrogen targets of nanometric size is presented. Experimental microdosimetry at nanometer scale for Auger electrons has been accomplished with the set-up called Jet Counter. This consists of a pulse-operated valve which injects an expanding nitrogen jet into an interaction chamber where a gaseous sensitive volume of cylindrical shape is created. The ionization cluster size distributions (ICSD) created by Auger electrons emitted by (125)I while crossing a nanometer-sized volume have been measured. The ICSD for the sensitive volumes corresponding to 3 and 12 nm in diameter (in unit density 1 g/cm(3)) irradiated by electrons emitted by a (125)I source were collected and compared with the corresponding Monte Carlo (MC) simulation. The preliminary results of the experiments with Auger electrons of (125)I interacting with a nitrogen jet having nanometric size comparable to a deoxyribonucleic acid (DNA) and nucleosome, showing the discrete spectrum of ICSD with extended cluster size, are described. The presented paper describes for the first time the nanodosimetric experiments with Auger electrons emitted by (125)I. A set of the new descriptors of the radiation quality describing the radiation effect at nanometer level is proposed. The ICSD were determined for the first time for an Auger emitter of (125)I.

  9. 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.

  10. Honey: a potent agent for wound healing?

    PubMed

    Lusby, P E; Coombes, A; Wilkinson, J M

    2002-11-01

    Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized. Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. The physicochemical properties (eg, osmotic effects and pH) of honey also aid in its antibacterial actions. Research has also indicated that honey may possess antiinflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey). This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types.

  11. 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.

  12. Alpinia calcarata Roscoe: a potent antiinflammatory agent.

    PubMed

    Arawwawala, L D A M; Arambewela, L S R; Ratnasooriya, W D

    2012-02-15

    Alpinia calcarata Roscoe (Family: Zingiberaceae) rhizomes are often used in Sri Lankan traditional systems of medicine as a remedy for bronchitis, cough, respiratory ailments, diabetics, asthma and arthritis. Generally drugs that are used for arthritis have antinociceptive and antiinflammatory properties. However, validity of the antiinflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the antiinflammatory potential of Alpinia calcarata rhizomes using hot water extract (AWE) and hot ethanolic extract (AEE). The antiinflammatory activity of Alpinia calcarata was evaluated by use of the carrageenan-induced paw oedema model in rats. In addition, the mechanism/s by which Alpinia calcarata is mediated the antinflammatory activity was assessed by determining its effects on (a) membrane stabilizing, (b) antihistamine and (c) prostaglandin synthesis inhibition activity. All the tested doses of AWE and AEE (250, 500, 750, and 1000 mg/kg) produced a significant (P≤0.05) inhibition of the inflammation, most pronounced at 4h after the injection of carrageenan. The antiinflammatory effect induced by 500 mg/kg of AEE was superior than the reference drug, indomethacin at 4h. Inhibition of histamine and prostaglandin synthesis production is probable mechanisms by which Alpinia calcarata mediates its antiinflammatory action. These findings rationalize the traditional usage of Alpinia calcarata as an antiinflammatory agent for the first time. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. 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

  14. Direct measurement of Auger electrons emitted from a semiconductor light-emitting diode under electrical injection: identification of the dominant mechanism for efficiency droop.

    PubMed

    Iveland, Justin; Martinelli, Lucio; Peretti, Jacques; Speck, James S; Weisbuch, Claude

    2013-04-26

    We report on the unambiguous detection of Auger electrons by electron emission spectroscopy from a cesiated InGaN/GaN light-emitting diode under electrical injection. Electron emission spectra were measured as a function of the current injected in the device. The appearance of high energy electron peaks simultaneously with an observed drop in electroluminescence efficiency shows that hot carriers are being generated in the active region (InGaN quantum wells) by an Auger process. A linear correlation was measured between the high energy emitted electron current and the "droop current"--the missing component of the injected current for light emission. We conclude that the droop phenomenon in GaN light-emitting diodes originates from the excitation of Auger processes.

  15. A quantitative study of valence electron transfer in the skutterudite compound CoP(3) by combining x-ray induced Auger and photoelectron spectroscopy.

    PubMed

    Diplas, S; Prytz, O; Karlsen, O B; Watts, J F; Taftø, J

    2007-06-20

    We use the sum of the ionization and Auger energy, the so-called Auger parameter, measured from the x-ray photoelectron spectrum, to study the valence electron distribution in the skutterudite CoP(3). The electron transfer between Co and P was estimated using models relating changes in Auger parameter values to charge transfer. It was found that each P atom gains 0.24 e(-), and considering the unit formula CoP(3) this is equivalent to a donation of 0.72 e(-) per Co atom. This is in agreement with a recent electron energy-loss spectroscopy study, which indicates a charge transfer of 0.77 e(-)/atom from Co to P.

  16. A quantitative study of valence electron transfer in the skutterudite compound CoP3 by combining x-ray induced Auger and photoelectron spectroscopy

    NASA Astrophysics Data System (ADS)

    Diplas, S.; Prytz, Ø.; Karlsen, O. B.; Watts, J. F.; Taftø, J.

    2007-06-01

    We use the sum of the ionization and Auger energy, the so-called Auger parameter, measured from the x-ray photoelectron spectrum, to study the valence electron distribution in the skutterudite CoP3. The electron transfer between Co and P was estimated using models relating changes in Auger parameter values to charge transfer. It was found that each P atom gains 0.24 e-, and considering the unit formula CoP3 this is equivalent to a donation of 0.72 e- per Co atom. This is in agreement with a recent electron energy-loss spectroscopy study, which indicates a charge transfer of 0.77 e-/atom from Co to P.

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

    PubMed

    Hach, V; McDonald, E C

    1971-10-08

    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.

  18. 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.

  19. 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

  20. 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

  1. 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

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

    2014-07-01

    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. Absorbed dose and stopping cross section for the Auger electrons of 5-18 eV emitted by(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. For a single decay of(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(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. 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 dosimetry calculation of such

  2. Laser control over the ultrafast Coulomb explosion of N22 + after Auger decay: A quantum-dynamics investigation

    NASA Astrophysics Data System (ADS)

    Hanna, Athiya Mahmud; Vendrell, Oriol; Ourmazd, Abbas; Santra, Robin

    2017-04-01

    By theoretical calculation, we demonstrate the possibility to control and partially suppress the Coulomb explosion of N2 molecules after core-level photoionization by an x-ray laser and subsequent Auger decay. This is achieved by means of a femtosecond infrared laser pulse interacting with the N22 + dication produced by the x-ray pulse. Suppression of molecular fragmentation requires few-femtosecond IR pulses interacting with the system either during or shortly after the arrival of the x-ray pulse. The IR pulse suppresses fragmentation mostly by optically coupling the electronic routes to ultrafast molecular dissociation with electronic channels able to support long-lived vibrational resonances. The effect is strongly dependent on the orientation of the molecule with respect to the polarization axis of the IR field. Our calculations are motivated by x-ray pump-IR probe experiments performed at an x-ray free-electron laser [J. M. Glownia et al., Opt. Express 18, 17620 (2010), 10.1364/OE.18.017620], where only enhancement of N22 + fragmentation as a function of the pump-probe delay time was reported. The opposite effect reported here becomes apparent when the various electronic channels are considered separately. In practice, this corresponds to a coincident measurement of the energy of the ejected Auger electron.

  3. Influence of defect-impurity complexes on slow positron yield of a tungsten moderator: Positron annihilation, Auger, and SIMS study

    NASA Astrophysics Data System (ADS)

    Amarendra, G.; Rajaraman, R.; Rajagopalan, S.; Suzuki, R.; Ohdaira, T.

    2004-03-01

    Polycrystalline tungsten foil annealed at successively higher temperature up to ˜2300 K has been investigated for slow positron moderation yield. LINAC-based intense positron beam lifetime studies have revealed that reemitted slow positron and positronium fractions gradually improve upon high-temperature annealing. So as to correlate the presence of defects and chemical impurities with the improvement in slow positron yield, positron annihilation, Auger electron spectroscopy, and secondary ion mass spectroscopy (SIMS), studies have been carried out on virgin and high-temperature (˜2300 K) annealed W foils. The positron beam S parameter shows a large value throughout the sample depth corresponding to the virgin sample, while it is lower for annealed samples. This indicates that, as compared to virgin sample, the annealed W sample has a lower concentration of vacancylike defects. Auger studies revealed that in virgin state the surface is fully contaminated with carbon, while the annealed foil shows prominent W peaks. Corroborative SIMS concentration profiles have indicated that the carbon content is much lower in an annealed sample over a large depth region. From these studies, it is concluded that improvement in slow positron yield upon high-temperature annealing is obtained due to the removal of the surface tungsten-carbide layer as well as carbon-vacancy complexes present throughout the sample depth.

  4. Role of Emission Character in Auger Electron Diffraction

    NASA Astrophysics Data System (ADS)

    Idzerda, Y. U.

    A review of the interpretation of the angle-dependent Auger intensity pattern by both Auger electron diffraction (AED), which is concerned with identifying the nearby atomic structure, and angle-resolved Auger electron spectroscopy (ARAES), which is concerned with identifying the character of the emitted electron source function, is presented. The importance of the emission character of the Auger electron (in terms of its angular momentum, l, and its magnetic quantum number, m) in understanding the generation of the AED and ARAES patterns is described. Understanding of how the various direct and secondary mechanisms for the Auger electron generation can affect the populations of these states can also be used to help identify the multiplet structure within the Auger lineshape as well as elucidate the core hole generation process.

  5. 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.

  6. Spin-polarized Auger electrons

    NASA Astrophysics Data System (ADS)

    Merz, H.; Semke, J.

    1990-12-01

    The spin polarization of Auger electrons will be discussed within the standard two-step model of the Auger emission process for different situations: target polarized, projectile polarized, targe and projectile unpolarized. In these three cases different interaction mechanisms are responsible for the polarization of the emitted Auger electrons. The present theoretical and experimental situation will be reviewed.

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

    PubMed

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

    2014-03-24

    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).

  8. Multielectron spectroscopy: the xenon 4d hole double auger decay.

    PubMed

    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.

  9. UNC1062, a new and potent Mer inhibitor.

    PubMed

    Liu, Jing; Zhang, Weihe; Stashko, Michael A; Deryckere, Deborah; Cummings, Christopher T; Hunter, Debra; Yang, Chao; Jayakody, Chatura N; Cheng, Nancy; Simpson, Catherine; Norris-Drouin, Jacqueline; Sather, Susan; Kireev, Dmitri; Janzen, William P; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2013-07-01

    Abnormal activation of Mer kinase has been implicated in the oncogenesis of many human cancers including acute lymphoblastic and myeloid leukemia, non-small cell lung cancer, and glioblastoma. We have discovered a new family of small molecule Mer inhibitors, pyrazolopyrimidine sulfonamides, that potently inhibit the kinase activity of Mer. Importantly, these compounds do not demonstrate significant hERG activity in the PatchXpress assay. Through structure-activity relationship studies, 35 (UNC1062) was identified as a potent (IC50 = 1.1 nM) and selective Mer inhibitor. When applied to live tumor cells, UNC1062 inhibited Mer phosphorylation and colony formation in soft agar. Given the potential of Mer as a therapeutic target, UNC1062 is a promising candidate for further drug development.

  10. UNC1062, a new and potent Mer inhibitor

    PubMed Central

    Liu, Jing; Zhang, Weihe; Stashko, Michael A; DeRyckere, Deborah; Cummings, Christopher T.; Hunter, Debra; Yang, Chao; Jayakody, Chatura N.; Cheng, Nancy; Simpson, Catherine; Norris-Drouin, Jacqueline; Sather, Susan; Kireev, Dmitri; Janzen, William P.; Earp, H Shelton; Graham, Douglas K.; Frye, Stephen V.; Wang, Xiaodong

    2013-01-01

    Abnormal activation of Mer kinase has been implicated in the oncogenesis of many human cancers including acute lymphoblastic and myeloid leukemia, non-small cell lung cancer, and glioblastoma. We have discovered a new family of small molecule Mer inhibitors, pyrazolopyrimidine sulfonamides, that potently inhibit the kinase activity of Mer. Importantly, these compounds do not demonstrate significant hERG activity in the PatchXpress assay. Through structure-activity relationship studies, 35 (UNC1062) was identified as a potent (IC50 = 1.1 nM) and selective Mer inhibitor. When applied to live tumor cells, UNC1062 inhibited Mer phosphorylation and colony formation in soft agar. Given the potential of Mer as a therapeutic target, UNC1062 is a promising candidate for further drug development. PMID:23693152

  11. New methods for image collection and analysis in scanning Auger microscopy

    NASA Astrophysics Data System (ADS)

    Browning, R.

    1985-10-01

    While scanning Auger micrographs are used extensively for illustrating the stoichiometry of complex surfaces and for indicating areas of interest for fine point Auger spectroscopy, there are many problems in the quantification and analysis of Auger images. These problems include multiple contrast mechanisms and the lack of meaningful relationships with other Auger data. Collection of multielemental Auger images allows some new approaches to image analysis and presentation. Information about the distribution and quantity of elemental combinations at a surface are retrievable, and particular combinations of elements can be imaged, such as alloy phases. Results from the precipitate hardened alloy Al-2124 illustrate multispectral Auger imaging.

  12. 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

  13. 2-Aminoresorcinol is a potent alpha-glucosidase inhibitor.

    PubMed

    Gao, Hong; Kawabata, Jun

    2008-01-15

    A series of aminoresorcinols and related compounds were tested for rat intestinal alpha-glucosidase inhibition and these results suggested that the 2-aminoresorcinol moiety of 6-amino-5,7-dihydroxyflavone (2) is important to exert the intestinal alpha-glucosidase inhibitory activity and 2-aminoresorcinol (4), itself, is a potent alpha-glucosidase inhibitor and inhibited sucrose-hydrolyzing activity of rat intestinal alpha-glucosidase uncompetitively.

  14. Auger electron spectroscopy: a rational method for determining thickness of graphene films.

    PubMed

    Xu, Mingsheng; Fujita, Daisuke; Gao, Jianhua; Hanagata, Nobutaka

    2010-05-25

    We report the determination of the thickness of graphene layers by Auger electron spectroscopy (AES). We measure AES spectra of graphenes with different numbers of layers. The AES spectroscopy shows distinct spectrum shape, intensity, and energy characteristics with an increasing number of graphene layers. We also calculate electron inelastic mean free paths for graphene layers directly from these measurements. The method allows unambiguous and high-throughput determination of thickness up to six graphene layers and detection of defect and dopant in graphene films on almost any substrate. The availability of this reliable method will permit direct probing of graphene growth mechanisms and exploration of novel properties of graphenes with different thicknesses on diverse substrates.

  15. Angle Resolved Photoelectron and Auger Electron Diffraction as a Structural Probe for Surfaces, Interfaces, and Epitaxial Films.

    NASA Astrophysics Data System (ADS)

    Li, Hong

    The recently developed techniques of angle-resolved photoelectron and Auger electron diffraction (ARXPD/AED) have shown promise in identifying the structures of epitaxial films. This is due to the realization that electrons scattered by other atoms are enhanced along the forward direction. In this dissertation research, we have further investigated the capabilities of the ARXPD/AED technique. First, the complete polar angle distribution of the Auger electron intensity from Cu(001) was measured from the (100) to the (110) azimuth. The presentation of the ARAED in the form of a contour map clearly shows the relationship of the constructive and destructive interference of electron scattering to the crystallographic index of the crystal. Secondly, the angular distributions of electron emissions with initial states of 3p, 3d, 4d, and the Auger emission with electron kinetic energies ranging from 348 eV to 1477 eV were measured for single crystal Ag(001). The results show that all of these electron emissions have similar electron forward scattering enhancements along the directions of nearest and next nearest neighbour atoms in the crystal. The forward scattering enhancements do not shift as the electron kinectic energy changes. The ARXPD/AED combined with low energy electron diffraction (LEED) has been demonstrated to be a very powerful technique in probing both the long range order and the short range order of the epitaxial films. The epitaxial films studied include Co on Cu(001), Fe on Ag(001), Co on Ag(001), and Co on an ultra-thin film of Fe(001), which was epitaxially grown on Ag(001). We find that up to 20 ML thickness of high quality metastable fcc Co can be stabilized on Cu(001) at room temperature. We have directly verified that the Fe on Ag(001) is bcc. The Co on Ag(001) is neither bcc nor fcc for coverages of less than 3 ML. Thick films of Co on Ag(001) are disordered, of which a very small portion has a local structure of bcc. The bcc Co phases has been

  16. Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase.

    PubMed

    Keung, W M; Vallee, B L

    1993-02-15

    Human mitochondrial aldehyde dehydrogenase (ALDH-I) is potently, reversibly, and selectively inhibited by an isoflavone isolated from Radix puerariae and identified as daidzin, the 7-glucoside of 4',7-dihydroxyisoflavone. Kinetic analysis with formaldehyde as substrate reveals that daidzin inhibits ALDH-I competitively with respect to formaldehyde with a Ki of 40 nM, and uncompetitively with respect to the coenzyme NAD+. The human cytosolic aldehyde dehydrogenase isozyme (ALDH-II) is nearly 3 orders of magnitude less sensitive to daidzin inhibition. Daidzin does not inhibit human class I, II, or III alcohol dehydrogenases, nor does it have any significant effect on biological systems that are known to be affected by other isoflavones. Among more than 40 structurally related compounds surveyed, 12 inhibit ALDH-I, but only prunetin and 5-hydroxydaidzin (genistin) combine high selectivity and potency, although they are 7- to 15-fold less potent than daidzin. Structure-function relationships have established a basis for the design and synthesis of additional ALDH inhibitors that could both be yet more potent and specific.

  17. 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.

  18. Auger electron spectroscopy study of initial stages of oxidation in a copper - 19.6-atomic-percent-aluminum alloy

    NASA Technical Reports Server (NTRS)

    Ferrante, J.

    1973-01-01

    Auger electron spectroscopy was used to examine the initial stages of oxidation of a polycrystalline copper - 19.6 a/o-aluminum alloy. The growth of the 55-eV aluminum oxide peak and the decay of the 59-, 62-, and 937-eV copper peaks were examined as functions of temperature, exposure, and pressure. Pressures ranged from 1x10 to the minus 7th power to 0.0005 torr of O2. Temperatures ranged from room temperature to 700 C. A completely aluminum oxide surface layer was obtained in all cases. Complete disappearance of the underlying 937-eV copper peak was obtained by heating at 700 C in O2 at 0.0005 torr for 1 hr. Temperature studies indicated that thermally activated diffusion was important to the oxidation studies. The initial stages of oxidation followed a logarithmic growth curve.

  19. 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.

  20. 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.

  1. Observation of four-electron Auger processes

    NASA Astrophysics Data System (ADS)

    Müller, A.; Borovik, A., Jr.; Buhr, T.; Hellhund, J.; Holste, K.; Kilcoyne, A. L. D.; Klumpp, S.; Martins, M.; Ricz, S.; Viefhaus, J.; Schippers, S.

    2015-09-01

    Multiple ionization of ions subsequent to absorption of a single photon has been studied employing a photon-ion merged-beam setup at the PETRA III synchrotron radiation facility of DESY in Hamburg. Absolute cross sections for single, double and triple ionization of C+ ions were measured with emphasis on specific well defined terms of K-shell excited C+. In particular, the terms C+ (1s2s22p2 2D,2P) were excited from the ground level of C+. Subsequent autoionization processes resulted in the production of C2+, C3+ and C4+ ions. The associated decay mechanisms are single-Auger, double-Auger and triple-Auger decay. The observation of C4+ products arising from C+(1s2s22p2 2D,2P) unambiguously confirmed the existence of triple-Auger decay, i.e., a process in which 4 electrons interact with one another such that one fills the K-shell vacancy and the others are simultaneously ejected. The experiment yields branching ratios for the Auger decay channels as well as individual decay rates for autoionization and radiative stabilization of the C+(1s2s22p2 2D,2P) terms.

  2. 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.

  3. Discovery of a highly potent series of TLR7 agonists.

    PubMed

    Jones, Peter; Pryde, David C; Tran, Thien-Duc; Adam, Fiona M; Bish, Gerwyn; Calo, Frederick; Ciaramella, Guiseppe; Dixon, Rachel; Duckworth, Jonathan; Fox, David N A; Hay, Duncan A; Hitchin, James; Horscroft, Nigel; Howard, Martin; Laxton, Carl; Parkinson, Tanya; Parsons, Gemma; Proctor, Katie; Smith, Mya C; Smith, Nicholas; Thomas, Amy

    2011-10-01

    The discovery of a series of highly potent and novel TLR7 agonist interferon inducers is described. Structure-activity relationships are presented, along with pharmacokinetic studies of a lead molecule from this series of N9-pyridylmethyl-8-oxo-3-deazapurine analogues. A rationale for the very high potency observed is offered. An investigation of the clearance mechanism of this class of compounds in rat was carried out, resulting in aldehyde oxidase mediated oxidation being identified as a key component of the high clearance observed. A possible solution to this problem is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. A potent alpha-glucosidase inhibitor from Myristica cinnamomea King.

    PubMed

    Sivasothy, Yasodha; Loo, Kong Yong; Leong, Kok Hoong; Litaudon, Marc; Awang, Khalijah

    2016-02-01

    A dimeric acylphenol and a potent α-glucosidase inhibitor, giganteone D (IC50 5.05μM), was isolated and characterized from the bark of Myristica cinnamomea King. The bark also yielded an acylphenol with an unprecedented skeleton for which the name cinnamomeone A (IC50 358.80μM) was proposed. Their structures were established by means of NMR and MS spectrometric analyses. The Lineweaver-Burk plot of giganteone D indicated that it was a mixed-type inhibitor. This is the first report on the α-glucosidase inhibiting potential of acylphenols.

  5. Design and synthesis of a potent histone deacetylase inhibitor.

    PubMed

    Liu, Tao; Kapustin, Galina; Etzkorn, Felicia A

    2007-05-03

    Histone deacetylase (HDAC) inhibitors have potential for cancer therapy. An HDAC inhibitor based on a cyclic peptide mimic of known structure, linked by an aliphatic chain to a hydroxamic acid, was designed and synthesized. The chimeric compound showed potent competitive inhibition of nuclear HDACs, with an IC50 value of 46 nM and a Ki value of 13.7 nM. The designed inhibitor showed 4-fold selectivity for HDAC1 (57 nM) over HDAC8 (231 nM).

  6. 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.

  7. 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

  8. Auger spectrometry of atoms and molecules

    SciTech Connect

    Krause, M.O.

    1994-09-01

    The author discusses the importance of Auger spectrometry at synchrotron radiation centers. First, he explains how a high energy photon source such as the APS (Advanced Photon Source) could be used to help provide missing spectral information about the shell structure of some elements. The missing data occurs mainly at higher energies in the 1--10 keV ranges as for the K-shells of Z = 30 to 60 elements and the L-shells for Z = 30 to 100 elements. He explains how even though Auger electron spectrometry does not depend on synchrotron radiation it can greatly benefit from this variable photon source as it allows one to select the Auger line group that is most suitable for a specific purpose. Most significantly, a continuous photon source becomes indispensable when one is interested in threshold effects. Lastly, he discusses coherence effects between different inner-shell vacancy states by way of some recent work done at Daresbury.

  9. Quantitative Auger analysis of Nb-Ge superconducting alloys

    SciTech Connect

    Buitrago, R.H.

    1980-01-01

    The feasibility of using Auger electron analysis for quantitative analysis was investigated by studying Nb/sub 3/Ge thin-film Auger data with different approaches. A method base on elemental standards gave consistent quantitative values with reported Nb-Ge data. Alloy sputter yields were also calculated and results were consistent with those for pure elements.

  10. Discovery of a Potent and Orally Bioavailable CCR2 and CCR5 Dual Antagonist

    PubMed Central

    2009-01-01

    This report describes the discovery of a potent, orally bioavailable CC chemokine receptor 2 (CCR2) antagonist which, while optimized for CCR2 potency, also had potent CC chemokine receptor 5 (CCR5) activity.

  11. Adrenomedullin - new perspectives of a potent peptide hormone.

    PubMed

    Schönauer, Ria; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2017-07-01

    Adrenomedullin (ADM) is a 52-amino acid multifunctional peptide, which belongs to the calcitonin gene-related peptide (CGRP) superfamily of vasoactive peptide hormones. ADM exhibits a significant vasodilatory potential and plays a key role in various regulatory mechanisms, predominantly in the cardiovascular and lymphatic system. It exerts its effects by activation of the calcitonin receptor-like receptor associated with one of the receptor activity-modifying proteins 2 or 3. ADM was first isolated from human phaeochromocytoma in 1993. Numerous studies revealed a widespread distribution in various tissues and organs, which is reflected by its multiple physiological roles in health and disease. Because of its anti-inflammatory, anti-apoptotic and proliferative properties, ADM exhibits potent protective functions under diverse pathological conditions, but it is also critically involved in tumor progression. ADM has therefore raised great interest in therapeutic applications and several clinical trials already revealed promising results. However, because the receptor activation mode has not yet been fully elucidated, a rational design of potent and selective ligands is still challenging. Detailed information on the binding mode of ADM from a recently reported crystal structure as well as efforts to improve its plasma stability and bioavailability may help to overcome these limitations in the future. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

  12. Experimentally accessible signatures of Auger scattering in graphene

    NASA Astrophysics Data System (ADS)

    Winzer, Torben; Jago, Roland; Malic, Ermin

    2016-12-01

    The gapless and linear electronic band structure of graphene opens up Auger scattering channels bridging the valence and the conduction band and changing the charge carrier density. Here, we reveal experimentally accessible signatures of Auger scattering in optically excited graphene. To be able to focus on signatures of Auger scattering, we apply a low excitation energy, weak pump fluences, and a cryostatic temperature, so that all relevant processes lie energetically below the optical phonon threshold. In this regime, carrier-phonon scattering is strongly suppressed and Coulomb processes govern the carrier dynamics. Depending on the excitation regime, we find an accumulation or depletion of the carrier occupation close to the Dirac point. This reflects well the behavior predicted from Auger-dominated carrier dynamics. Based on this observation, we propose a multicolor pump-probe experiment to uncover the extreme importance of Auger channels for the nonequilibrium dynamics in graphene.

  13. 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.

  14. 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.

  15. Exploring Protonation and Deprotonation Effects with Auger Electron Spectroscopy.

    PubMed

    Kryzhevoi, Nikolai V; Cederbaum, Lorenz S

    2012-09-20

    Auger electron spectroscopy is demonstrated to be a very efficient tool to probe alterations in local chemical environment due to changes in protonation states. We show that electronic and geometric structure changes induced by protonation or deprotonation are well reflected in Auger spectra through characteristic chemical shifts and spectral shape variations. We also present evidence that Auger spectra are sensitive to relative concentrations of compounds in different protonation states. Special attention is paid to the high kinetic energy spectral regions that exhibit remarkable features resulting from core ICD-like transitions in normal species and Auger transitions in deprotonated fragments. The latter contribution was so far ignored when explaining Auger spectra of species embedded in the environment. This contribution should be reconsidered, taking into account the recently discovered possibility of ultrafast dissociation of core-ionized hydrogen-bonded systems in media.

  16. Molecular frame Auger electron energy spectrum from N2

    NASA Astrophysics Data System (ADS)

    Cryan, J. P.; Glownia, J. M.; Andreasson, J.; Belkacem, A.; Berrah, N.; Blaga, C. I.; Bostedt, C.; Bozek, J.; Cherepkov, N. A.; DiMauro, L. F.; Fang, L.; Gessner, O.; Gühr, M.; Hajdu, J.; Hertlein, M. P.; Hoener, M.; Kornilov, O.; Marangos, J. P.; March, A. M.; McFarland, B. K.; Merdji, H.; Messerschmidt, M.; Petrović, V. S.; Raman, C.; Ray, D.; Reis, D. A.; Semenov, S. K.; Trigo, M.; White, J. L.; White, W.; Young, L.; Bucksbaum, P. H.; Coffee, R. N.

    2012-03-01

    Here we present the first angle-resolved, non-resonant (normal) Auger spectra for impulsively aligned nitrogen molecules. We have measured the angular pattern of Auger electron emission following K-shell photoionization by 1.1 keV photons from the Linac Coherent Light Source (LCLS). Using strong-field-induced molecular alignment to make molecular frame measurements is equally effective for both repulsive and quasi-bound final states. The capability to resolve Auger emission angular distributions in the molecular frame of reference provides a new tool for spectral assignments in congested Auger electron spectra that takes advantage of the symmetries of the final diction states. Based on our experimental results and theoretical predictions, we propose the assignment of the spectral features in the Auger electron spectrum.

  17. A Synthetic Chalcone as a Potent Inducer of Glutathione Biosynthesis

    PubMed Central

    Kachadourian, Remy; Day, Brian J.; Pugazhenti, Subbiah; Franklin, Christopher C.; Genoux-Bastide, Estelle; Mahaffey, Gregory; Gauthier, Charlotte; Di Pietro, Attilio; Boumendjel, Ahcène

    2014-01-01

    Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2′,5′-dihydroxychalcone (2′,5′-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure–activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4′,6′-dimethoxy-2′-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements. PMID:22239485

  18. ATHLETE : Double Auger Anchoring Mechanism

    NASA Technical Reports Server (NTRS)

    Shin, Joseph

    2011-01-01

    The All-Terrain Hex-Legged Extra-Terrestrial Explorer (ATHLETE) is a six-limbed robot designed to support surface explorations on Near Earth Objects, the Moon and Mars. ATHLETE can carry large payloads on its top deck and can carry a fully equipped pressurized habitat in low gravity. The robot has wheels on each of its six articulated limbs, allowing it to actively conform to terrain while driving and to walk when driving is impractical. With the use of a tool adapter, ATHLETE limbs can be equipped with end effectors to support various mission objectives. For work on Near Earth Objects and other microgravity environments, an anchoring mechanism is needed to keep the ATHLETE from floating off the surface. My goal for this spring session at JPL was to design and build a counter rotating, double auger, anchoring mechanism. The mechanism mates to the tool adapter and is driven off the wheel motor. The double auger anchoring mechanism will be tested in a regolith simulant that will determine the uplift capacity of the anchoring mechanism.

  19. ATHLETE : Double Auger Anchoring Mechanism

    NASA Technical Reports Server (NTRS)

    Shin, Joseph

    2011-01-01

    The All-Terrain Hex-Legged Extra-Terrestrial Explorer (ATHLETE) is a six-limbed robot designed to support surface explorations on Near Earth Objects, the Moon and Mars. ATHLETE can carry large payloads on its top deck and can carry a fully equipped pressurized habitat in low gravity. The robot has wheels on each of its six articulated limbs, allowing it to actively conform to terrain while driving and to walk when driving is impractical. With the use of a tool adapter, ATHLETE limbs can be equipped with end effectors to support various mission objectives. For work on Near Earth Objects and other microgravity environments, an anchoring mechanism is needed to keep the ATHLETE from floating off the surface. My goal for this spring session at JPL was to design and build a counter rotating, double auger, anchoring mechanism. The mechanism mates to the tool adapter and is driven off the wheel motor. The double auger anchoring mechanism will be tested in a regolith simulant that will determine the uplift capacity of the anchoring mechanism.

  20. 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

    2010-07-13

    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.

  1. 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.

  2. Deoxygedunin, a Natural Product with Potent Neurotrophic Activity in Mice

    PubMed Central

    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

  3. 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.

  4. 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.

  5. 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.

  6. Angle-resolved electron spectroscopy of laser-assisted Auger decay induced by a few-femtosecond x-ray pulse.

    PubMed

    Meyer, M; Radcliffe, P; Tschentscher, T; Costello, J T; Cavalieri, A L; Grguras, I; Maier, A R; Kienberger, R; Bozek, J; Bostedt, C; Schorb, S; Coffee, R; Messerschmidt, M; Roedig, C; Sistrunk, E; Di Mauro, L F; Doumy, G; Ueda, K; Wada, S; Düsterer, S; Kazansky, A K; Kabachnik, N M

    2012-02-10

    Two-color (x-ray+infrared) electron spectroscopy is used for investigating laser-assisted KLL Auger decay following 1s photoionization of atomic Ne with few-femtosecond x-ray pulses from the Linac Coherent Light Source. In an angle-resolved experiment, the overall width of the laser-modified Auger-electron spectrum and its structure change significantly as a function of the emission angle. The spectra are characterized by a strong intensity variation of the sidebands revealing a gross structure. This variation is caused, as predicted by theory, by the interference of electrons emitted at different times within the duration of one optical cycle of the infrared dressing laser, which almost coincides with the lifetime of the Ne 1s vacancy.

  7. Nicotinamide is a potent inhibitor of proinflammatory cytokines

    PubMed Central

    UNGERSTEDT, J S; BLOMBÄCK, M; SöDERSTRÖM, T

    2003-01-01

    The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1β, IL-6 and TNFα responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4–40 mmol/l nicotinamide or 4–100 µmol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFα, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease. PMID:12519385

  8. Shockley-Read-Hall and Auger non-radiative recombination in GaN based LEDs: A size effect study

    NASA Astrophysics Data System (ADS)

    Olivier, Francois; Daami, Anis; Licitra, Christophe; Templier, Francois

    2017-07-01

    GaN-based micro light-emitting diode (μLED) arrays are very promising devices for display applications. In these arrays, each μLED works as a single pixel of a whole image. The electro-optical performance of these μLEDs is an important subject to study. Here, we investigate the influence of LED size on the radiative and non-radiative recombination. The standard ABC model has been widely used to describe the efficiency of GaN based LEDs. Using this model, we extract A, B, and C coefficients for various LED sizes, showing how the competition between radiative and non-radiative recombination processes varies with the LED geometry. Time-resolved photoluminescence allows us to determine coefficient B, related to radiative recombination. Through current-voltage-luminance characterizations, we determine parameters A and C related to Shockley-Read-Hall and Auger recombination. We find that coefficient A is strongly dependent on LED size, indicating a drastic effect of sidewall defects on the performance of LEDs. On the other hand, coefficient C is independent of LED size. This latter result demonstrates that efficiency droop does not depend on LED size.

  9. X-ray-photoelectron-spectroscopy and Auger-electron-spectroscopy study of ultrathin palladium films on a Pt(111) substrate

    NASA Astrophysics Data System (ADS)

    Han, Moonsup; Mrozek, P.; Wieckowski, A.

    1993-09-01

    We have studied ultrathin palladium films vacuum deposited onto a Pt(111) substrate utilizing Auger-electron spectroscopy (AES), low-energy electron diffraction, and x-ray photoelectron spectroscopy. The AES results fit well to a layer-by-layer growth deposition. Below a coverage of 4 monolayers, the electron-diffraction data only show a (1×1) structure of palladium adatoms on the Pt(111) substrate, supporting the Frank-van der Merve growth mechanism. In contrast to two-dimensional palladium clusters and palladium bimetallic systems, the Pd 3d core-level binding energy of palladium on Pt(111) shifts toward lower binding energy relative to the value of bulk palladium with decreasing palladium overlayer coverage. This negative binding-energy shift of a surface adatom core level results mainly from the initial-state band-narrowing effect predicted by Citrin, Wertheim, and Baer. Also, the absence of the final-state effect after creating a core hole in the Pd/Pt(111) system indicates that efficient screening or very fast relaxation occurs, and that hybridization of the valence bands of the palladium adlayer and the platinum substrate plays an implortant role in the negative surface-atom binding-energy shift of the Pd 3d core level.

  10. Photoelectron and Auger electron diffraction studies of a sulfur-terminated GaAs(001)-(2×6) surface

    NASA Astrophysics Data System (ADS)

    Shimoda, M.; Tsukamoto, S.; Koguchi, N.

    1998-01-01

    Core-level X-ray photoelectron diffraction (XPD) and Auger electron diffraction (AED) have been applied to investigate the sulfur-terminated GaAs(001)-(2×6) surface. No forward scattering peaks were found in the XPD pattern of S 2s emission, indicating that adsorbed S atoms form a single layer on the GaAs substrate. In accordance with the zincblende structure of GaAs, the AED patterns of Ga L 3M 45M 45 and As L 3M 45M 45 emission almost coincide with each other, if one of the emissions is rotated by 90° around the [001] direction. This fact suggests that the diffraction patterns mainly reflect the structure of the bulk GaAs crystal. In order to investigate the surface structure, AED patterns in large polar angles were analyzed with single scattering cluster (SSC) calculations. The best result was obtained with a model cluster where the S-S bond length was set at 0.28 nm, 30% shorter than the corresponding length of the ideal (1×1) structure, and the adsorption height was set at 0.12-0.13 nm, 10% shorter than the ideal interlayer distance of GaAs(001) planes. These values are in good agreement with the results of STM measurements. A modulation of the inter-dimer distance was also found, suggesting the existence of missing dimers.

  11. 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.

  12. Nuclear Excitation via Auger Transitions (NEAT)

    NASA Astrophysics Data System (ADS)

    Ward, Thomas; Emery, Guy; Rasmussen, John; Karwowski, Hugon; Castaneda, Carlos

    2008-10-01

    Triggering (prompt de-excitation) of isomeric states produced in a process of coupling nuclear excitations to atomic shells via Auger transitions (NEAT) is studied. In this resonant process the nuclear transition energy between the two states must be less than the Auger transition energy. This requires the emitted Auger electron energy and the exact on-resonance nuclear excitation share the Auger transition energy. NEAT is compared to other proposed processes of nuclear excitation produced by x-rays (NEET), by electron capture (NEEC) and bound internal conversion (BIC), all of which suffer from off-resonance nuclear excitation except in those accidental cases where the energies may coincide. Estimates of the total resonance strength will be given for the case of ^182mHf which has been extensively studied theoretically. A second case, ^189Os, where NEAT processes may contribute to the nuclear resonance fluorescence (NRF) of the ground state to the 5.8hr isomeric state will also be examined as a good case for experimental verification of the NEAT process.

  13. Energy and angular distributions of electrons emitted by direct double auger decay.

    PubMed

    Viefhaus, Jens; Cvejanović, Slobodan; Langer, Burkhard; Lischke, Toralf; Prümper, Georg; Rolles, Daniel; Golovin, Alexander V; Grum-Grzhimailo, Alexei N; Kabachnik, Nikolai M; Becker, Uwe

    2004-02-27

    We have observed the direct L(2,3)MMM double Auger transition after photoionization of the 2p shell of argon by angle-resolved electron-electron coincidence spectroscopy. The process is responsible for about 20% of the observed Auger electron intensity. In contrast to the normal Auger lines, the spectra in double Auger decay show a continuous intensity distribution. The energy and angular distributions of the emitted electrons allow one to obtain information on the electron correlations giving rise to the double Auger process as well as the symmetry of the associated two-electron continuum state.

  14. 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.

  15. 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.

  16. 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.

  17. Microwave pyrolysis of textile dyeing sludge in a continuously operated auger reactor: Condensates and non-condensable gases.

    PubMed

    Gao, Zuopeng; Zhang, Hedong; Ao, Wenya; Li, Jing; Liu, Guangqing; Chen, Xiaochun; Fu, Jie; Ran, Chunmei; Liu, Yang; Kang, Qinhao; Mao, Xiao; Dai, Jianjun

    2017-09-01

    This paper investigated an auger pyrolyser under microwave irradiation using textile dyeing sludge (DS) as the feedstock. Microwave power, temperature, auger speed, gas velocity and addition of catalysts were studied. In terms of ICP-MS, Cu and As concentrations in condensates, depending on pyrolysis temperatures, exceeded the wastewater discharge standard in China. The condensate and oil yields reached maximum (i.e. 12.86 wt% and 0.84 wt%, respectively) at 650 °C. The content of aromatic compounds in the oil increased as temperature increased, up to 88.38% (GC-MS area) at 750 °C. Heterocyclic aromatic compounds containing nitrogen accounted for 20%-58% of the pyrolysis oil. Addition of catalysts such as CaO and Fe decreased pyrolysis oil yield and increased the content of H2. The H2 content increased from 25.39v% without catalyst to 64.17v% with addition of 30 wt% CaO. The electricity consumption was 0.80-2.64 kWh/kg wet sludge from 450 to 750 °C and auger speed range of 1-9 rpm. Higher auger speeds and lower temperatures led to lower electricity consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Biophysical aspects of Auger processes. American Association of Physicists in Medicine symposium proceedings No. 8

    SciTech Connect

    Howell, R.W.; Narra, V.R.; Rao, D.V. . Dept. of Radiology); Sastry, K.S.R. . Dept. of Physics and Astronomy)

    1992-01-01

    The 2nd International Symposium on Biophysical Aspects of Auger Processes was held in July 1991, at the University of Massachusetts. This conference provided a forum for state-of-the-art information regarding the basic mechanisms of action by which Auger processes effect biological damage, as well as the nature of the radiosensitive targets in the cell nucleus. In addition, new insight into the radiotoxicity of Auger processes arising from photon activation of atoms situated in the DNA were presented. Novel approaches to implement agents radiolabeled with Auger electron emitters for cancer therapy were discussed. The information is organized into three sections: Biological effects of photon induced Auger processes; biological effects of Auger-electron emitting radionuclides; and therapeutic applications of Auger electron emitters. Individual papers have been processed separately for inclusion in the appropriate data bases.

  20. A potent vasoactive cytolysin isolated from Scorpaena plumieri scorpionfish venom.

    PubMed

    Andrich, F; Carnielli, J B T; Cassoli, J S; Lautner, R Q; Santos, R A S; Pimenta, A M C; de Lima, M E; Figueiredo, S G

    2010-09-15

    A new vasoactive cytolytic toxin, referred to as Sp-CTx, has been purified from the venom of the scorpionfish Scorpaena plumieri by a combination of gel filtration and anion exchange chromatographies. An estimation of Sp-CTx native molecular mass, performed by size exclusion chromatography, demonstrated that it is a 121 kDa protein. Further physicochemical studies revealed its glycoproteic nature and dimeric constitution, comprising subunits of approximately 65 kDa (MALDI-TOF-MS). Such protein has proved to possess a potent hemolytic activity on washed rabbit erythrocytes (EC(50) 0.46 nM), whose effect was strongly reduced after treatment with antivenom raised against stonefish venom -Synanceja trachynis (SFAV). This cross-reactivity has been confirmed by western blotting. Like S. plumieri whole venom (100 microg/mL), Sp-CTx (1-50 nM) caused a biphasic response on phenylephrine pre-contracted rat aortic rings, characterized by an endothelium- and dose-dependent relaxation phase followed by a contractile phase. The vasorelaxant activity has been abolished by l-NAME, demonstrating the involvement of nitric oxide on the response. We report here the first isolation of a cytolytic/vasoactive protein from scorpionfish venom and the data provided suggest structural and functional similarities between Sp-CTx and previously published stonefish hemolytic toxins. Copyright 2010 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Haj, Christeene G.; Sumariwalla, Percy F.; Hanuš, Lumír; Kogan, Natalya M.; Yektin, Zhana; Feldmann, Mark

    2015-01-01

    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 Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ9-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 Δ9-THC–like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID:26272937

  2. 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.

  3. 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.

  4. Hemin as a generic and potent protein misfolding inhibitor.

    PubMed

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

    2014-11-14

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

    PubMed Central

    Lee, Sanghyun; Baldridge, Megan T.

    2017-01-01

    Interferon-lambda (IFN-λ) is a recently described cytokine found to be of critical importance in innate immune regulation of intestinal viruses. Endogenous IFN-λ has potent antiviral effects and has been shown to control multiple intestinal viruses and may represent a factor that contributes to human variability in response to infection. Importantly, recombinant IFN-λ has therapeutic potential against enteric viral infections, many of which lack other effective treatments. In this mini-review, we describe recent advances regarding IFN-λ-mediated regulation of enteric viruses with important clinical relevance including rotavirus, reovirus, and norovirus. We also briefly discuss IFN-λ interactions with other cytokines important in the intestine, and how IFN-λ may play a role in regulation of intestinal viruses by the commensal microbiome. Finally, we indicate currently outstanding questions regarding IFN-λ control of enteric infections that remain to be explored to enhance our understanding of this important immune molecule. PMID:28713375

  6. Neutralization mechanism of a highly potent antibody against Zika virus

    PubMed Central

    Zhang, Shuijun; Kostyuchenko, Victor A.; Ng, Thiam-Seng; Lim, Xin-Ni; Ooi, Justin S. G.; Lambert, Sebastian; Tan, Ter Yong; Widman, Douglas G.; Shi, Jian; Baric, Ralph S.; Lok, Shee-Mei

    2016-01-01

    The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event—a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate. PMID:27882950

  7. 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.

  8. 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

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

    PubMed

    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 CCl(4) 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.

  10. Pharmacological profile of TCV-309--a potent PAF antagonist.

    PubMed

    Terashita, Z; Takatani, M; Nishikawa, K

    1992-01-01

    TCV-309 potently and specifically inhibited the diverse biological actions of PAF such as platelet aggregation, hypotension, increased vascular permeability, bronchoconstriction and death. TCV-309 did not cause hemolysis or vascular irritation. TCV-309 showed beneficial effects on experimental endotoxic shock, anaphylactic shock and disseminated intravascular coagulation.

  11. 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.

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

    SciTech Connect

    Abreu, P.; Andringa, S.; Aglietta, M.; Ahlers, M.; Ahn, E.J.; Albuquerque, I.F.M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Castillo, J. Alvarez; Alvarez-Muñiz, J.; Ambrosio, M.; Aramo, C.; Aminaei, A.; Anchordoqui, L.; Antici'c, T.; Arganda, E.; Arqueros, F.; Collaboration: Pierre Auger Collaboration; and others

    2012-04-01

    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 Véron-Cetty Véron 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 49.3 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.

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

    NASA Astrophysics Data System (ADS)

    Pierre Auger Collaboration; Abreu, P.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antici'c, T.; Aramo, C.; Arganda, E.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Bäcker, T.; Badescu, A. M.; Balzer, M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Barroso, S. L. C.; Baughman, B.; Bäuml, J.; Beatty, J. J.; Becker, B. R.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Bohácová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Burton, R. E.; Caballero-Mora, K. S.; Caccianiga, B.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chirinos Diaz, J.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Cordier, A.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; De Donato, C.; de Jong, S. J.; De La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; del Peral, L.; del Río, M.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Fajardo Tapia, I.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Filevich, A.; Filipcic, A.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Gascon, A.; Gemmeke, H.; Ghia, P. L.; Giaccari, U.; Giller, M.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, D.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gouffon, P.; Grashorn, E.; Grebe, S.; Griffith, N.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Guzman, A.; Hague, J. D.; Hansen, P.; Harari, D.; Harmsma, S.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horneffer, A.; Horvath, P.; Hrabovský, M.; Huege, T.; Insolia, A.; Ionita, F.; Italiano, A.; Jarne, C.; Jiraskova, S.; Josebachuili, M.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuehn, F.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; Lachaud, C.; Lauer, R.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Macolino, C.; Maldera, S.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Meurer, C.; Mi'canovi'c, S.; Micheletti, M. I.; Minaya, I. A.; Miramonti, L.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, E.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nhung, P. T.; Niechciol, M.; Niemietz, L.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Nyklicek, M.; Oehlschläger, J.; Olinto, A.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Pekala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrinca, P.; Petrolini, A.; Petrov, Y.; Petrovic, J.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Ponce, V. H.; Pontz, M.; Porcelli, A.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulte, S.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Sima, O.; 'Smiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Srivastava, Y. N.; Stanic, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tapia, A.; Tartare, M.; Taşcău, O.; Tavera Ruiz, C. G.; Tcaciuc, R.; Tegolo, D.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Toma, G.; Tomé, B.; Tonachini, A.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; Varela, E.; Vargas Cárdenas, B.; Vázquez, J. R.; Vázquez, R. A.; Veberic, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Westerhoff, S.; Whelan, B. J.; Widom, A.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.

    2012-04-01

    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 Véron-Cetty Véron 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 49.3 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.

  14. Imipenem: a potent inducer of multidrug resistance in Acinetobacter baumannii.

    PubMed

    Kuo, Han-Yueh; Chang, Kai-Chih; Kuo, Jai-Wei; Yueh, Hui-Wen; Liou, Ming-Li

    2012-01-01

    This study investigated the progression of multidrug resistance upon exposure to imipenem in Acinetobacter baumannii. Eighteen A. baumannii strains, including two reference strains (ATCC 19606 and ATCC 17978), four clinical strains (AB56, AB242, AB273 and AB279) and 12 antibiotic-selected mutant strains, were used in this study. Imipenem-selected mutants were generated from imipenem-susceptible strains (ATCC 19606, ATCC 17978 and AB242) by multistep selection resistance. Amikacin-, ciprofloxacin-, colistin-, meropenem- and ceftazidime-selected mutants were also generated from the two reference strains and were used for comparison. Antibiotic susceptibilities in the absence and presence of the efflux pump inhibitors carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) were examined in the three imipenem-selected mutants and the three clinical multidrug-resistant (MDR) isolates. Expression profiles of the antimicrobial resistance genes in the imipenem-selected mutants and their parental strains were also determined. The results showed that imipenem was more likely, compared with the other antibiotics, to induce a MDR phenotype in the two reference strains. Differences in OXA-51-like carbapenemase, efflux pumps or/and AmpC β-lactamase expression were observed in the three imipenem-selected mutants. Moreover, a reduction in imipenem or amikacin resistance was observed when the imipenem-selected mutants and clinical isolates were exposed to NMP and CCCP. This study concluded that imipenem might be a potent inducer of multidrug resistance in A. baumannii strains. OXA-51-like carbapenemase combined with other resistance mechanisms may contribute to the development of multidrug resistance in A. baumannii. Monitoring the use of carbapenems is required to reduce the spread of MDR A. baumannii in hospitals.

  15. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

    PubMed

    Nadal, Xavier; Del Río, Carmen; Casano, Salvatore; Palomares, Belén; Ferreiro-Vera, Carlos; Navarrete, Carmen; Sánchez-Carnerero, Carolina; Cantarero, Irene; Luz Bellido, M; Meyer, Stefan; Morello, Gaetano; Appendino, Giovanni; Muñoz, Eduardo

    2017-08-29

    Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing, and storage. While the biological effects of decarboxylated cannabinoids such as Δ(9) -tetrahydrocannabinol (Δ(9) -THC) have been extensively investigated, the bioactivity of Δ(9) -THCA is largely unknown, despite its occurrence in different Cannabis preparations. The aim of this study was to determine whether Δ(9) -THCA modulates the PPARγ pathway and has neuroprotective activity EXPERIMENTAL APPROACH: The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ(9) -THCA on mitochondrial biogenesis and PGC-1α expression was investigated in N2a cells. The neuroprotective effect was analysed in STHdh(Q111/Q111) cells expressing a mutated form of the huntingtin protein, and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). In vivo neuroprotective activity of Δ(9) -THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NP). Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ(9) -THCA increases mitochondrial mass in neuroblastoma N2a cells, and prevents cytotoxicity induced by serum deprivation in STHdh(Q111/Q111) cells and by mutHtt-q94 in N2a cells. Δ(9) -THCA, through a PPARγ-dependent pathway, was neuroprotectant in mice intoxicated with 3-NP, improving motor deficits and preventing striatal degeneration. In addition, Δ(9) -THCA attenuated microgliosis, astrogliosis and the upregulation of proinflammatory markers induced by 3-NP. Δ(9) -THCA shows potent neuroprotective activity, worth consideration for the treatment of Huntington´s Disease and possibly other neurodegenerative and neuroinflammatory diseases. This article is protected by copyright. All rights reserved.

  16. 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

  17. 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

    2014-06-06

    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.

  18. A comprehensive study of the vibrationally resolved S 2p(-1) Auger electron spectrum of carbonyl sulfide.

    PubMed

    Sekushin, V; Püttner, R; Fink, R F; Martins, M; Jiang, Y H; Aksela, H; Aksela, S; Kaindl, G

    2012-07-28

    High-resolution normal Auger-electron spectra of carbonyl sulfide subsequent to S 2p(-1) photoionization at photon energies of 200, 220, and 240 eV are reported along with corresponding photoelectron spectra. In addition, theoretical results are presented that take the core-hole orientation of the various spin-orbit-split and molecular-field-split S 2p(-1) states into account. Auger transitions to eight metastable dicationic final states are observed and assigned on the basis of the theoretical results. From Franck-Condon analysis, assuming Morse potentials along the normal coordinates for seven of the observed quasi-stable dicationic final states, information on the potential-energy surfaces is derived and compared with theoretical results from the literature.

  19. 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.

  20. 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.

  1. The Auger spectroscopy of pyrimidine and halogen-substituted pyrimidines.

    PubMed

    Storchi, L; Tarantelli, F; Veronesi, S; Bolognesi, P; Fainelli, E; Avaldi, L

    2008-10-21

    The C 1s and N 1s Auger spectra of pyrimidine, 2-chloropyrimidine, and 5-bromopyrimidine have been measured in an electron impact experiment at 1000 eV. In the case of the halogen-substituted pyrimidines, also the Cl 2p and Br 3d Auger spectra have been recorded. We have thoroughly analyzed and interpreted all the Auger spectra recorded here with the aid of accurate Green's function calculations with a large basis set. The spectra are extremely complex with thousands of states contributing and almost no single-state feature even near the double ionization threshold. Besides reproducing and explaining with great detail nearly all the main spectral features observed, the calculations have successfully unraveled the interplay among the different C 1s core hole chemical shifts in each molecule and how this affects some fingerprinting details in the composite C 1s Auger spectra.

  2. 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.

  3. 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 ...

  4. 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 ...

  5. Auger spectroscopy of Magnox pressure vessel steels

    SciTech Connect

    Fisher, S.; Knowles, G.; Lee, B.

    1999-10-01

    Magnox Electric maintains a significant microstructural program in support of its safety case for operation of its stations with steel pressure vessels. An important part of this program is the characterization of grain boundary chemistry using Auger spectroscopy. Mechanical testing and subsequent examination of surveillance material has shown that some Charpy specimens display a proportion of intergranular fracture and Auger work has linked this to the presence of phosphorus on the grain boundaries. A feature of particular interest in the study of the boundaries is the co-segregation of carbon. The measurement of the true levels of phosphorus and carbon segregation is complicated by the presence of carbon contamination. This paper describes the simple approach used to overcome this problem.

  6. Hydroxychavicol: a potent xanthine oxidase inhibitor obtained from the leaves of betel, Piper betle.

    PubMed

    Murata, Kazuya; Nakao, Kikuyo; Hirata, Noriko; Namba, Kensuke; Nomi, Takao; Kitamura, Yoshihisa; Moriyama, Kenzo; Shintani, Takahiro; Iinuma, Munekazu; Matsuda, Hideaki

    2009-07-01

    The screening of Piperaceous plants for xanthine oxidase inhibitory activity revealed that the extract of the leaves of Piper betle possesses potent activity. Activity-guided purification led us to obtain hydroxychavicol as an active principle. Hydroxychavicol is a more potent xanthine oxidase inhibitor than allopurinol, which is clinically used for the treatment of hyperuricemia.

  7. Auger electron spectroscopy of lunar samples

    NASA Technical Reports Server (NTRS)

    Grant, R. W.; Housley, R. M.; Szalkowski, F. J.; Marcus, H. L.

    1974-01-01

    Auger spectroscopy has been employed to study the surface composition of a number of grains from the submillimeter lunar fines. Some of the problems associated with using this technique for lunar sample analyses are discussed in terms of relevant physical principles. The use of inert gas sputtering to obtain thickness profiles of surface films is shown to be important in this type of investigation. Four anorthite grains from the Apollo 17 fines have been examined for evidence of vapor-deposited surface coatings of micrometeorite impact origin. The results indicate that the thickness of surface deposits, if they exist at all, are orders of magnitude less than expected. Auger analysis of orange glass balls form the 74220,107 fines have established sulfur-rich surface coatings on the order of 30 A in thickness.

  8. The Pierre Auger Cosmic Ray Observatory

    DOE PAGES

    Aab, Alexander

    2015-07-08

    The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above 1017 eV and study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water Cherenkov particle detector stations spread over 3000 km2 overlooked by 24 air fluorescence telescopes. Additionally, three high elevation fluorescence telescopes overlook a 23.5 km2, 61-detector infilled array with 750 m spacing. The Observatory has been in successful operation since completionmore » in 2008 and has recorded data from an exposure exceeding 40,000 km2 sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Observatory.« less

  9. Directional Auger Electron Spectroscopy — Physical Foundations and Applications

    NASA Astrophysics Data System (ADS)

    Mróz, S.

    Experimental data about the dependence of the Auger signal from crystalline samples on the primary beam direction are presented and discussed. It is shown that, for Auger electrons and elastically and inelastically backscattered electrons, maxima of the signal in its dependence on the polar and azimuth angles of the primary beam (in polar and azimuth profiles, respectively) appear when the primary beam is parallel either to one of the close-packed rows of atoms or to one of the densely packed atomic planes in the sample. This indicates that the diffraction of the primary electron beam is responsible for the dependence mentioned above. Mechanisms proposed for simple explanation of this dependence (channeling and forward focusing of primary electrons) are presented and results of their application are discussed. It is shown that both those mechanisms play an important role in the creation of the Auger signal contrast. The possibilities and limitations of the application of polar and azimuth Auger emission profiles in the determination of the surface layer crystalline structure (directional Auger electron spectroscopy — DAES) are presented and discussed. It is shown that the thickness of the investigated surface layer can be decreased up to a few monolayers. Results obtained with DAES are similar to those provided by X-ray photoelectron diffraction (XPD) and Auger electron diffraction (AED), but the DAES experimental equipment is simple and inexpensive and measurements are fast. Finally, experimental systems for DAES are described and examples of DAES applications are presented.

  10. In Vitro Assessment of a Peptide Nucleic Acid (PNA) - Peptide Conjugate Labeled With an Auger-Emitting Radionuclide for Prostate Cell Killing

    DTIC Science & Technology

    2005-02-01

    synthesis of a peptide nucleic acid (PNA) that has an Auger-emitter (1-125) incorporated. By design the PNA will bind with mRNA and DNA associated with...bind with cell surface gastrin -releasing peptide receptors and be internalized (3). Binding with mRNA and nuclear DNA specific to the insulin-like...route proposed to prepare 10 is shown in Figure 1 (compounds 1-10). This synthesis began with the preparation of the base-reactive intermediate 5

  11. Latest results of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Creusot, A.; Pierre Auger Collaboration

    2012-01-01

    The Pierre Auger Observatory measures extensive air showers induced by ultra-high energy cosmic rays using two methods: a sampling of the shower particles at the ground level and the detection of the fluorescence light emitted by the air molecules after the shower crossing. The southern site of the Pierre Auger Observatory is acquiring data since 2004. The first results were published few years ago. This article is dedicated to the presentation of the last results, taking into account the data up to end of March 2009. The energy spectrum, the anisotropies in the arrival directions and the mass composition of the cosmic rays are discussed here as well as the extrapolations of the proton-air cross-section in the hadronic models.

  12. 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.

  13. Recent results from the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Gascón, Alberto; Pierre Auger Collaboration

    2014-07-01

    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.

  14. 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.

  15. First results from the spectral DCT trigger implemented in the Cyclone V Front-End Board used for a detection of very inclined showers in the Pierre Auger surface detector Engineering Array

    SciTech Connect

    Szadkowski, Zbigniew

    2015-07-01

    The paper presents the first results from the trigger based on the Discrete Cosine Transform (DCT) operating in the new Front-End Boards with Cyclone V FPGA deployed in 8 test surface detectors in the Pierre Auger Engineering Array. The patterns of the ADC traces generated by very inclined showers were obtained from the Auger database and from the CORSIKA simulation package supported next by Offline reconstruction Auger platform which gives a predicted digitized signal profiles. Simulations for many variants of the initial angle of shower, initialization depth in the atmosphere, type of particle and its initial energy gave a boundary of the DCT coefficients used next for the on-line pattern recognition in the FPGA. Preliminary results have proven a right approach. We registered several showers triggered by the DCT for 120 MSps and 160 MSps. (authors)

  16. 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.

  17. Normal Auger spectra of iodine in gas phase alkali iodide molecules

    NASA Astrophysics Data System (ADS)

    Hu, Zhengfa; Caló, Antonio; Kukk, Edwin; Aksela, Helena; Aksela, Seppo

    2005-06-01

    Molecular normal Auger electron spectra following the iodine 4d ionization in gas-phase alkali iodides were investigated both experimentally and theoretically. The Auger electron spectra for LiI, NaI and KI were recorded using electron impact, and for RbI by using photo-excitation. These Auger spectra were analyzed in detail and compared to the referenced normal Auger spectra of HI [L. Karlsson, S. Svensson, P. Baltzer, M. Carlsson-Göthe, M.P. Keane, A. Naves de Brito, N. Correia, B. Wannberg, J. Phys. B 22 (1989) 3001]. An energy shift toward higher kinetic energy and a narrowing in linewidth are observed in the Auger spectra series revealing the effect of the changing environment from covalently bonded HI to ionic alkali iodide compounds. The experimental results are also compared with the theoretical ab initio calculations and with the Auger spectra of I -, computed with the multiconfiguration Hartree-Fock (MCHF) method.

  18. A computer controlled chemical bevel etching apparatus: applications to Auger analysis of multi-layered structures

    NASA Astrophysics Data System (ADS)

    El-Gomati, M.; Gelsthorpe, A.; Srnanek, R.; Liday, J.; Vogrincic, P.; Kovac, J.

    1999-04-01

    Analysis of thin layer structures can be achieved by chemically etching a bevel and subsequently analysing the surface. However non-linear bevels often result due to differing etch rates of the materials leading to incorrect analysis results. We report on a computer controlled stepper motor reactor whereby the specimen is lowered into the etchant at a rate which compensates for the different etch rates of the various layers constituting the sample. The apparatus is used to produce linear bevels of various magnifications on GaAs/AlGaAs heterostructures. The etchant of H 3PO 4/H 2O 2/H 2O is used for bevel preparation capped by a water layer to suppress the meniscus. Application of the technique to Multi Quantum Wells (MQW) and Bragg diffraction layers is shown. The depth resolution of the bevelled samples are analysed by AES and a comparison is made to conventional ion sputtering techniques.

  19. Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer

    DTIC Science & Technology

    1999-08-01

    proportion of estrogen receptor-negative and hormone-resistant breast cancers. Our objective is to construct a human epidermal growth factor (hEGF...61 5 INTRODUCTION Overexpression of the epidermal growth factor receptor (EGFR) occurs in a high proportion of estrogen receptor-negative and...Lac Iq promotor induced by isopropyl-b- D -thiogalactopyranoside (IPTG). The DNA sequence of the final hEGF-CH1 construct was confirmed (FUi. 2). BamHJ

  20. Analysis of a measurement scheme for ultrafast hole dynamics by few femtosecond resolution X-ray pump-probe Auger spectroscopy.

    PubMed

    Cooper, Bridgette; Kolorenč, Přemysl; Frasinski, Leszek J; Averbukh, Vitali; Marangos, Jon P

    2014-01-01

    Ultrafast hole dynamics created in molecular systems as a result of sudden ionisation is the focus of much attention in the field of attosecond science. Using the molecule glycine we show through ab initio simulations that the dynamics of a hole, arising from ionisation in the inner valence region, evolves with a timescale appropriate to be measured using X-ray pulses from the current generation of SASE free electron lasers. The examined pump-probe scheme uses X-rays with photon energy below the K edge of carbon (275-280 eV) that will ionise from the inner valence region. A second probe X-ray at the same energy can excite an electron from the core to fill the vacancy in the inner-valence region. The dynamics of the inner valence hole can be tracked by measuring the Auger electrons produced by the subsequent refilling of the core hole as a function of pump-probe delay. We consider the feasibility of the experiment and include numerical simulation to support this analysis. We discuss the potential for all X-ray pump-X-ray probe Auger spectroscopy measurements for tracking hole migration.

  1. 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.

  2. 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.

  3. A study of the effect of molecular and aerosol conditions in the atmosphere on air fluorescence measurements at the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Abraham, J.; Abreu, P.; Aglietta, M.; Aguirre, C.; Ahn, E. J.; Allard, D.; Allekotte, I.; Allen, J.; Alvarez-Muñiz, J.; Ambrosio, M.; Anchordoqui, L.; Andringa, S.; Anzalone, A.; Aramo, C.; Arganda, E.; Arisaka, K.; Arqueros, F.; Asch, T.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avila, G.; Bäcker, T.; Badagnani, D.; Barber, K. B.; Barbosa, A. F.; Barroso, S. L. C.; Baughman, B.; Bauleo, P.; Beatty, J. J.; Beau, T.; Becker, B. R.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanch-Bigas, O.; Blanco, F.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Burton, R. E.; Busca, N. G.; Caballero-Mora, K. S.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cazon, L.; Cester, R.; Chauvin, J.; Chiavassa, A.; Chinellato, J. A.; Chou, A.; Chudoba, J.; Chye, J.; Clay, R. W.; Colombo, E.; Conceição, R.; Contreras, F.; Cook, H.; Coppens, J.; Cordier, A.; Cotti, U.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; De Donato, C.; de Jong, S. J.; De La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; Decerprit, G.; del Peral, L.; Deligny, O.; Della Selva, A.; Delle Fratte, C.; Dembinski, H.; Di Giulio, C.; Diaz, J. C.; Diep, P. N.; Dobrigkeit, C.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; DuVernois, M. A.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferrer, F.; Ferrero, A.; Fick, B.; Filevich, A.; Filipčič, A.; Fleck, I.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fulgione, W.; Gamarra, R. F.; Gambetta, S.; García, B.; García Gámez, D.; Garcia-Pinto, D.; Garrido, X.; Gelmini, G.; Gemmeke, H.; Ghia, P. L.; Giaccari, U.; Giller, M.; Glass, H.; Goggin, L. M.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gonçalves, P.; Gonzalez, D.; Gonzalez, J. G.; Góra, D.; Gorgi, A.; Gouffon, P.; Gozzini, S. R.; Grashorn, E.; Grebe, S.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Gutiérrez, J.; Hague, J. D.; Halenka, V.; Hansen, P.; Harari, D.; Harmsma, S.; Harton, J. L.; Haungs, A.; Healy, M. D.; Hebbeker, T.; Hebrero, G.; Heck, D.; Hojvat, C.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horneffer, A.; Hrabovský, M.; Huege, T.; Hussain, M.; Iarlori, M.; Insolia, A.; Ionita, F.; Italiano, A.; Jiraskova, S.; Kaducak, M.; Kampert, K. H.; Karova, T.; Kasper, P.; Kégl, B.; Keilhauer, B.; Kelley, J.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapik, R.; Knapp, J.; Koang, D.-H.; Krieger, A.; Krömer, O.; Kruppke-Hansen, D.; Kuehn, F.; Kuempel, D.; Kulbartz, K.; Kunka, N.; Kusenko, A.; La Rosa, G.; Lachaud, C.; Lago, B. L.; Lautridou, P.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Lee, J.; Leigui de Oliveira, M. A.; Lemiere, A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martínez Bravo, O.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mazur, P. O.; McEwen, M.; McNeil, R. R.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Meurer, C.; Micheletti, M. I.; Miller, W.; Miramonti, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Morris, C.; Mostafá, M.; Moura, C. A.; Mueller, S.; Muller, M. A.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Newman-Holmes, C.; Nhung, P. T.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Nyklicek, M.; Oehlschläger, J.; Olinto, A.; Oliva, P.; Olmos-Gilbaja, V. M.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parlati, S.; Parsons, R. D.; Pastor, S.; Paul, T.; Pavlidou, V.; Payet, K.; Pech, M.; Peķala, J.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrinca, P.; Petrolini, A.; Petrov, Y.; Petrovic, J.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pimenta, M.; Pirronello, V.; Platino, M.; Ponce, V. H.; Pontz, M.; Privitera, P.; Prouza, M.; Quel, E. J.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Redondo, A.; Revenu, B.; Rezende, F. A. S.; Ridky, J.; Riggi, S.; Risse, M.; Rivière, C.; Rizi, V.; Robledo, C.; Rodriguez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodriguez-Cabo, I.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Salamida, F.; Salazar, H.; Salina, G.; Sánchez, F.; Santander, M.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Schmidt, F.; Schmidt, T.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schroeder, F.; Schulte, S.; Schüssler, F.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Semikoz, D.; Settimo, M.; Shellard, R. C.; Sidelnik, I.; Siffert, B. B.; Sigl, G.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Strazzeri, E.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Tamashiro, A.; Tamburro, A.; Tarutina, T.; Taşcău, O.; Tcaciuc, R.; Tcherniakhovski, D.; Tegolo, D.; Thao, N. T.; Thomas, D.; Ticona, R.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Tomé, B.; Tonachini, A.; Torres, I.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van den Berg, A. M.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Velarde, A.; Venters, T.; Verzi, V.; Videla, M.; Villaseñor, L.; Vorobiov, S.; Voyvodic, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Warner, D.; Watson, A. A.; Westerhoff, S.; Whelan, B. J.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Winchen, T.; Winnick, M. G.; Wu, H.; Wundheiler, B.; Yamamoto, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Ziolkowski, M.; Pierre Auger Collaboration

    2010-03-01

    The air fluorescence detector of the Pierre Auger Observatory is designed to perform calorimetric measurements of extensive air showers created by cosmic rays of above 1018eV. To correct these measurements for the effects introduced by atmospheric fluctuations, the Observatory contains a group of monitoring instruments to record atmospheric conditions across the detector site, an area exceeding 3000 km 2. The atmospheric data are used extensively in the reconstruction of air showers, and are particularly important for the correct determination of shower energies and the depths of shower maxima. This paper contains a summary of the molecular and aerosol conditions measured at the Pierre Auger Observatory since the start of regular operations in 2004, and includes a discussion of the impact of these measurements on air shower reconstructions. Between 1018 and 1020eV, the systematic uncertainties due to all atmospheric effects increase from 4% to 8% in measurements of shower energy, and 4gcm to 8gcm in measurements of the shower maximum.

  4. A beginning investigation into the possible role of cosmic rays in the initiation of lightning discharges at the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Brown, W. C.; Dywer, J. R.; Huangs, A.; Krehbiel, P. R.; Rison, W.; Thomas, R. J.; Edens, H.; Niemitz, L.; Rautenberg, J.

    2012-08-01

    The means by which lightning is initiated inside storms is not yet understood and remains a primary unsolved problem in advancing our understanding of lightning. Due to the inconsistency between the estimated required and measured field strengths in thunderclouds, an increasing amount of research has focused on energetic electron/particle runaway processes as the basic initiating mechanism. An important class of these ideas and models is that the seed energetic electrons for runaway processes are provided by energetic cosmic rays. However, as yet there is little experimental or observational evidence to support or refute this idea. Consequently, we are beginning with a Lightning Mapping Array (LMA) in conjunction with the Pierre Auger Observatory in Argentina. The goal is to determine if discharges are initiated when high energy cosmic ray air showers pass through electrified storms. The planned instrumentation will combine the Pierre Auger Observatory with the LMA. The later will include stations placed to span the observatory to accurately measure the arrival times of impulsive VHF radiation events. These data will provide detailed 3 -dimensional pictures of individual lightning discharges inside storms, The approach of the proposed study is to identify air showers that pass through electrified storms and to look for temporal and spatial correlations with lightning in the storms, paying particular attention to the initial stages of the lightning. The study will be conducted for at least several years to assess fully the possible effects of cosmic rays in initiating lightning.

  5. Monte Carlo-simulated Auger electron spectra for nuclides of radiobiological and medical interest - a validation with noble gas ionization data.

    PubMed

    Pomplun, Ekkehard

    2012-01-01

    To further validate Monte Carlo calculation codes simulating cascades of Auger electron transitions in radionuclides that decay by electron capture or internal conversion. In particular, the need for an appropriate kinetic energy determination of the Auger electrons emitted from multiple-ionized atoms as well as the consideration of shake-off electrons would be investigated implicitly. Charge distributions of noble gases after photoionization for different photon energies were calculated and compared with experimental data from the literature. In addition, new electron emission spectra were generated for (99m)Tc and (123)I. By including strict energy book-keeping and allowing shake-off electrons, the agreement between experimentally detected charge distributions and Monte Carlo simulations was very good. On this basis, the number of emitted electrons per decay was found to be between 1 and 17 with a mean of 4.0 for (99m)Tc and between 1 and 26 with a mean of 7.4 for (123)I. Because of the good agreement with the experimental findings, the validation can be considered to be successful.

  6. In situ observation on electron beam induced chemical vapor deposition by Auger electron spectroscopy

    SciTech Connect

    Matsui, S.; Mori, K.

    1987-08-31

    W deposition, using WF/sub 6/ gas source by electron beam induced surface reaction, has been studied by Auger electron spectroscopy. W Auger electron signals have been observed for WF/sub 6/ adlayer by Auger electron spectroscopy. Moreover, initial growth for W deposition has been observed in situ by Auger electron spectroscopy. As a result, it became clear that a growth rate for W deposition is proportional to WF/sub 6/ gas pressure and can be --1 A/min at 2 x 10/sup -7/ Torr.

  7. Relative extent of double and single Auger decay in molecules containing C, N and O atoms.

    PubMed

    Roos, A Hult; Eland, J H D; Andersson, J; Zagorodskikh, S; Singh, R; Squibb, R J; Feifel, R

    2016-09-14

    We show that the proportion of double Auger decay following creation of single 1s core holes in molecules containing C, N and O atoms is greater than usually assumed, amounting to about 10% of single Auger decay in many cases. It varies from molecule to molecule, where the size of the molecule has a positive correlation to the amount of double Auger decay. In neon, examined as a related benchmark, the proportion of double Auger decay is similar to that in methane, and is in the order of 5%.

  8. Normal Auger processes with ultrashort x-ray pulses in neon

    NASA Astrophysics Data System (ADS)

    Sullivan, Raymond; Jia, Junteng; Vázquez-Mayagoitia, Álvaro; Picón, Antonio

    2016-10-01

    Modern x-ray sources enable the production of coherent x-ray pulses with a pulse duration in the same order as the characteristic lifetimes of core-hole states of atoms and molecules. These pulses enable the manipulation of the core-hole population during Auger-decay processes, modifying the line shape of the electron spectra. In this work, we present a theoretical model to study those effects in neon. We identify effects in the Auger-electron-photoelectron coincidence spectrum due to the duration and intensity of the pulses. The normal Auger line shape is recovered in Auger-electron spectra integrated over all photoelectron energies.

  9. Potent anti-muscarinic activity in a novel series of quinuclidine derivatives.

    PubMed

    Starck, Jean-Philippe; Talaga, Patrice; Quéré, Luc; Collart, Philippe; Christophe, Bernard; Lo Brutto, Patrick; Jadot, Sophie; Chimmanamada, Dinesh; Zanda, Matteo; Wagner, Alain; Mioskowski, Charles; Massingham, Roy; Guyaux, Michel

    2006-01-15

    The synthesis and biological evaluation of a novel family of M(3) muscarinic antagonists are described. A systematic modification of the substituents to a novel alkyne-quinuclidine scaffold yielded original compounds displaying potent in vitro anticholinergic properties.

  10. An expedient route to a potent gastrin/CCK-B receptor antagonist (+)-AG-041R.

    PubMed

    Sato, Shigeki; Shibuya, Masatoshi; Kanoh, Naoki; Iwabuchi, Yoshiharu

    2009-10-02

    An enantiocontrolled synthesis of (+)-AG-041R (1), a potent gastrin/CCK-B receptor antagonist, has been achieved employing a chiral rhodium(II)-catalyzed, oxidative intramolecular aza-spiroannulation as the key step.

  11. Lasonolide A, a potent and reversible inducer of chromosome condensation

    PubMed Central

    Zhang, Yong-Wei; Ghosh, Arun K.; Pommier, Yves

    2012-01-01

    Lasonolide A (LSA) is a natural product with high and selective cytotoxicity against mesenchymal cancer cells, including leukemia, melanomas and glioblastomas. Here, we reveal that LSA induces rapid and reversible premature chromosome condensation (PCC) associated with cell detachment, plasma membrane smoothening and actin reorganization. PCC is induced at all phases of the cell cycle in proliferative cells as well as in circulating human lymphocytes in G0. It is independent of Cdk1 signaling, associated with cyclin B downregulation and induced in cells at LSA concentrations that are three orders of magnitude lower than those required to block phosphatases 1 and 2A in vitro. At the epigenetic level, LSA-induced PCC is coupled with histone H3 and H1 hyperphosphorylation and deacetylation. Treatment with SAHA reduced LSA-induced PCC, implicating histone deacetylation as one of the PCC effector mechanisms. In addition, PCC is coupled with topoisomerase II (Top2) and Aurora A hyperphosphorylation and activation. Inhibition of Top2 or Aurora A partially blocked LSA-induced PCC. Our findings demonstrate the profound epigenetic alterations induced by LSA and the potential of LSA as a new cytogenetic tool. Based on the unique cellular effects of LSA, further studies are warranted to uncover the cellular target of lasonolide A (“TOL”). PMID:23159859

  12. 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.

  13. On the equivalent dose for Auger electron emitters.

    PubMed

    Howell, R W; Narra, V R; Sastry, K S; Rao, D V

    1993-04-01

    Radionuclides that emit Auger electrons are widely used in nuclear medicine (e.g., 99mTc, 123I, 201Tl) and biomedical research (e.g., 51Cr, 125I), and they are present in the environment (e.g., 40K, 55Fe). Depending on the subcellular distribution of the radionuclide, the biological effects caused by tissue-incorporated Auger emitters can be as severe as those from high-LET alpha particles. However, the recently adopted recommendations of the International Commission on Radiological Protection (ICRP) provide no guidance with regard to calculating the equivalent dose for these radionuclides. The present work, using spermatogenesis in mouse testis as the experimental model, shows that the lethality of the prolific Auger emitter 125I is linearly dependent on the fraction of the radioactivity in the organ that is bound to DNA. This suggests that the equivalent dose for Auger emitters may have a similar linear dependence. Accordingly, a formalism for calculating the equivalent dose for Auger emitters is advanced within the ICRP framework.

  14. On the Equivalent Dose for Auger Electron Emitters

    PubMed Central

    Howell, Roger W.; Narra, Venkat R.; Sastry, Kandula S. R.; Rao, Dandamudi V.

    2012-01-01

    Radionuclides that emit Auger electrons are widely used in nuclear medicine (e.g., 99mTc, 123I, 201T1) and biomedical research (e.g., 51Cr, 125I), and they are present in the environment (e.g., 40K, 55Fe). Depending on the subcellular distribution of the radionuclide, the biological effects caused by tissue-incorporated Auger emitters can be as severe as those from high-LET α particles. However, the recently adopted recommendations of the International Commission on Radiological Protection (ICRP) provide no guidance with regard to calculating the equivalent dose for these radionuclides. The present work, using spermatogenesis in mouse testis as the experimental model, shows that the lethality of the prolific Auger emitter 125I is linearly dependent on the fraction of the radioactivity in the organ that is bound to DNA. This suggests that the equivalent dose for Auger emitters may have a similar linear dependence. Accordingly, a formalism for calculating the equivalent dose for Auger emitters is advanced within the ICRP framework. PMID:8475256

  15. 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.

  16. Auger recombination in scintillator materials from first principles

    NASA Astrophysics Data System (ADS)

    McAllister, Andrew; Kioupakis, Emmanouil; Åberg, Daniel; Schleife, André

    2015-03-01

    Scintillators convert high energy radiation into lower energy photons which are easier to detect and analyze. One of the uses of these devices is identifying radioactive materials being transported across national borders. However, scintillating materials have a non-proportional light yield in response to incident radiation, which makes this task difficult. One possible cause of the non-proportional light yield is non-radiative Auger recombination. Auger recombination can occur in two ways - direct and phonon-assisted. We have studied both types of Auger recombination from first principles in the common scintillating material sodium iodide. Our results indicate that the phonon-assisted process, assisted primarily by short-range optical phonons, dominates the direct process. The corresponding Auger coefficients are 5 . 6 +/- 0 . 3 ×10-32cm6s-1 for the phonon-assisted process versus 1 . 17 +/- 0 . 01 ×10-33cm6s-1 for the direct process. At higher electronic temperatures the direct Auger recombination rate increases but remains lower than the phonon-assisted rate. This research was supported by the National Science Foundation CAREER award through Grant No. DMR-1254314 and NA-22. Computational Resources provide by LLNL and DOE NERSC Facility.

  17. WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

    SciTech Connect

    Taborda, A; Benabdallah, N; Desbree, A

    2015-06-15

    Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres of unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S

  18. Study of Risetime as a function of the distance to the Shower Core in the Surface Detector (SD) of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Castellanos Valdés, Hernán; Salomé Caballero Mora, Karen

    2017-06-01

    Cosmic Rays (CR) are high energy particles which come from the universe. When one of those particles enters to the earth’s atmosphere it produces an air shower, conformed by secondary particles in which the initial energy is distributed. The Pierre Auger Observatory, located in Argentina, is dedicated to the study of those events. One of the main goals is to find out where those CR are coming from and which kind of chemical composition do they have. In this work we show the status of a study of the risetime (t 1/2) as a function of the distance to the shower core (near to the air shower’s axis) for different zenith angles and energies, obtaining a new variable that will be compared with other variables used by the Observatory. The main objective of this study is to better understand risetime as a mass composition sensitive parameter of CR.

  19. Evaluation of the Dmt-Tic pharmacophore: conversion of a potent delta-opioid receptor antagonist into a potent delta agonist and ligands with mixed properties.

    PubMed

    Balboni, Gianfranco; Guerrini, Remo; Salvadori, Severo; Bianchi, Clementina; Rizzi, Daniela; Bryant, Sharon D; Lazarus, Lawrence H

    2002-01-31

    Analogues of the 2',6'-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore were prepared to test the hypothesis that a "spacer" and a third aromatic center in opioid peptides are required to convert a delta-antagonist into ligands with delta-agonist or with mixed delta-antagonist/mu-agonist properties. Potent delta-agonists and bifunctional compounds with high delta- and mu-opioid receptor affinities were obtained by varying the spacer length [none, NH-CH(2), NH-CH(2)-CH(2), Gly-NH-CH(2)] and C-terminal aromatic nucleus [1H-benzimidazole-2-yl, phenyl (Ph) and benzyl groups]. C-terminal modification primarily affected mu-opioid receptor affinities, which increased maximally 1700-fold relative to the prototype delta-antagonist H-Dmt-Tic-NH(2) and differentially modified bioactivity. In the absence of a spacer (1), the analogue exhibited dual delta-agonism (pEC(50), 7.28) and delta-antagonism (pA(2), 7.90). H-Dmt-Tic-NH-CH(2)-1H-benzimidazole-2-yl (Bid) (2) became a highly potent delta-agonist (pEC(50), 9.90), slightly greater than deltorphin C (pEC(50), 9.56), with mu-agonism (pE(50), 7.57), while H-Dmt-Tic-Gly-NH-CH(2)-Bid (4) retained potent delta-antagonism (pA(2), 9.0) but with an order of magnitude less mu-agonism. Similarly, H-Dmt-Tic-Gly-NH-Ph (5) had nearly equivalent high delta-agonism (pEC(50), 8.52) and mu-agonism (pEC(50), 8.59), while H-Dmt-Tic-Gly-NH-CH(2)-Ph (6) whose spacer was longer by a single methylene group exhibited potent delta-antagonism (pA(2), 9.25) and very high mu-agonism (pEC(50), 8.57). These data confirm that the distance between the Dmt-Tic pharmacophore and a third aromatic nucleus is an important criterion in converting Dmt-Tic from a highly potent delta-antagonist into a potent delta-agonist or into ligands with mixed delta- and mu-opioid properties.

  20. 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.

  1. Radiolabeling and in vitro evaluation of (67)Ga-NOTA-modular nanotransporter--a potential Auger electron emitting EGFR-targeted radiotherapeutic.

    PubMed

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

    2014-07-01

    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 (67)Ga. EGF was the targeting ligand on the MNT, and NOTA was selected for its radiolabeling with (67)Ga. In the radiolabeling study we dealt with the precipitation of MNT (pI 5.7) at the labeling pH (4.5-5.5) of (67)Ga. Cellular and nuclei uptake of (67)Ga-NOTA-MNT by the A431 cell line was determined. Its specific cytotoxicity was compared to that of (67)Ga-EDTA, (67)Ga-NOTA-BSA and (67)Ga-NOTA-hEGF, in A431 and U87MGWTT, cell lines, by clonogenic assay. Dosimetry studies were also performed. (67)Ga-NOTA-MNT was produced with 90% yield and specific activity of 25.6mCi/mg. The in vitro kinetics revealed an increased uptake over 24h. 55% of the internalized radioactivity was detected in the nuclei at 1h. The cytotoxicity of (67)Ga-NOTA-MNT on A431 cell line was 17 and 385-fold higher when compared to non-specific (67)Ga-NOTA-BSA and (67)Ga-EDTA. While its cytotoxic potency was 13 and 72-fold higher when compared to (67)Ga-NOTA-hEGF in the A431 and the U87MGWTT cell lines, respectively, validating its nuclear localization. The absorbed dose, for 63% cell killing, was 8Gy, confirming the high specific index of (67)Ga. These results demonstrate the feasibility of using MNT as a platform for single cell kill targeted radiotherapy by Auger electron emitters. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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

  3. Anomalous Auger intensities for nitrogen explained

    SciTech Connect

    Dawson, P.T.; Chen, Y.

    1995-12-31

    The nitrogen KLL Auger electron intensities from a series of nine interstital nitride films from the Group 4, 5 and 6 elements Ti, V, Cr, Zr, Nb, Mo, Hf, Ta and W, prepared by high temperature reaction with ammonia gas, were found to vary periodically in a manner which could not be interpreted by the usual matrix effects of primary beam back-scattering and inelastic mean free path. In addition to these unexpected trends observed for all nine elements, the extreme members, Ti and W, showed unreasonably anomalous high and low intensities respectively. It is the purpose of this paper to account for these large anomalies. The chemisorption of ground and excited state ammonia on the three low index planes of single crystal tungsten has been investigated. In all cases the extremely low nitrogen KLL Auger electron intensities were no longer observed. The unexpectedly low value previously observed for nitride thin films arises from surface roughness, induced by nucleation and growth of micron-sized nitride particles. Auger electron spectroscopy of nitrogen in titanium is complicated by the total overlap of the nitrogen KLL and titanium LMM peaks at 384 eV. This laboratory has made extensive studies of the titanium-nitrogen system offering a solution to the overlap problem that has become widely accepted as an effective method for nitrogen surface analysis by AES. The procedure involves the assumption that the relative intensity of the 384 and 420 eV Ti peaks does not change on nitriding, and using the observable intensity of the 420 eV peak in the nitride to subtract the Ti contribution from the combined peak at 384 eV. However, the success of this analysis procedure does not require that the relative intensity of the Ti peaks is independent of nitrogen concentration, only that if it varies, it does so linearly. Applying these results to titanium removes the gross anomaly previously reported.

  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. From Auger to AugerPrime: Understanding Ultrahigh-Energy Cosmic Rays

    NASA Astrophysics Data System (ADS)

    Montanet, F.; Pierre Auger Collaboration

    2016-12-01

    Ultrahigh-energy cosmic rays (UHECRs), whose origin is still mysterious, provide a unique probe of the most extreme environments in the universe, of the intergalactic space and of particle physics beyond the reach of terrestrial accelerators. The Pierre Auger Observatory started operating more than a decade ago. Outperforming preceding experiments both in size and in precision, it has boosted forward the field of UHECRs as witnessed by a wealth of results. These include the study of the energy spectrum beyond 1 EeV with its spectral suppression around 40 EeV, of the large-scale anisotropy, of the mass composition, as well as stringent limits on photon and neutrino fluxes. But any harvest of new results also calls for new questions: what is the true nature of the spectral suppression: a propagation effect (so-called Greisen, Zatsepin and Kuz'min or GZK cutoff) or cosmic accelerators running out of steam? What is the composition of UHECRs at the highest energies? In order to answer these questions, the Auger Collaboration is undertaking a major upgrade program of its detectors, the AugerPrime project. The science case and motivations, the technical strategy and the scientific prospects are presented.

  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. High Spatial Resolution Auger Spectroscopy and Nucleation and Growth Studies of SILVER/SILICON(100)

    NASA Astrophysics Data System (ADS)

    Luo, Frank C. H.

    1990-01-01

    The ability to analyse the composition of a sample at high spatial resolution using Auger Electron Spectroscopy is very desirable for both industrial and academic research. The spatial resolution of the traditional Auger instrument is typically limited by the incident beam size to the range of 0.1-1 mum. This dissertation reports the efforts of construction, testing and utilizing a new Auger spectrometer with a nanometer incident probe in a scanning transmission electron microscopy (STEM). In order to use the 100 keV electron beam of the STEM for the Auger experiment, a low energy electron beam deflection system was designed and constructed. The testing of such deflection system and the spectrometer, both in a test chamber with different hardware configuration and in the microscope, was very extensive. Both Auger spectra and images can be obtained in the microscope with excellent energy resolution in a relatively short time. Quantitative analysis of the data showed a spatial resolution of less than 10 nm was achieved with a good collection efficiency. More quantitative work was carried on the Silver/Silicon(100) system as the application of the Auger instrument. Nucleation and growth phenomena of Ag on Si at both room and elevated temperatures was studied with the microscope operating both in Auger and scanning electron microscopy (SEM) mode. Suggestions for the further improvement of the Auger instrument and the Ag/Si(100) case study are made.

  8. Auger recombination in sodium-iodide scintillators from first principles

    SciTech Connect

    McAllister, Andrew; Åberg, Daniel; Schleife, André; Kioupakis, Emmanouil

    2015-04-06

    Scintillator radiation detectors suffer from low energy resolution that has been attributed to non-linear light yield response to the energy of the incident gamma rays. Auger recombination is a key non-radiative recombination channel that scales with the third power of the excitation density and may play a role in the non-proportionality problem of scintillators. In this work, we study direct and phonon-assisted Auger recombination in NaI using first-principles calculations. Our results show that phonon-assisted Auger recombination, mediated primarily by short-range phonon scattering, dominates at room temperature. We discuss our findings in light of the much larger values obtained by numerical fits to z-scan experiments.

  9. Multielectron spectroscopy: Auger decays of the krypton 3d hole

    SciTech Connect

    Palaudoux, J.; Lablanquie, P.; Penent, F.; Andric, L.; Ito, K.; Shigemasa, E.; Eland, J. H. D.; Jonauskas, V.; Kucas, S.; Karazija, R.

    2010-10-15

    The emission of one or two Auger electrons, following Kr 3d inner-shell ionization by synchrotron light, has been investigated both experimentally and theoretically. All electrons emitted in the process are detected in coincidence and analyzed in energy thanks to a magnetic-bottle electron time-of-flight spectrometer. In addition, noncoincident high-resolution electron spectra have been measured to characterize the cascade double-Auger paths more fully. Combination of the two experimental approaches and of our calculations allows a full determination of the decay pathways and branching ratios in the case of Kr 3d single- and double-Auger decays. The Kr{sup 3+} threshold is found at 74.197{+-}0.020 eV.

  10. Multimode resonant Auger scattering from the ethene molecule.

    PubMed

    Liu, Ji-Cai; Nicolas, Christophe; Sun, Yu-Ping; Flammini, Roberto; O'Keeffe, Patrick; Avaldi, Lorenzo; Morin, Paul; Kimberg, Victor; Kosugi, Nobuhiro; Gel'mukhanov, Faris; Miron, Catalin

    2011-05-12

    Resonant Auger spectra of ethene molecule have been measured with vibrational resolution at several excitation energies in the region of the C1s(-1)1b(2g)(π*) resonance. The main features observed in the experiment have been assigned and are accurately interpreted on the basis of ab initio multimode calculations. Theory explains the extended vibrational distribution of the resonant Auger spectra and its evolution as a function of the excitation energy by multimode excitation during the scattering process. As a result, the resonant Auger spectra display two qualitatively different spectral features following the Raman and non-Raman dispersion laws, respectively. Calculations show that two observed thresholds of formation of non-Raman spectral bands are related to the "double-edge" structure of the X-ray absorption spectrum.

  11. Mapping the composition of planetary surfaces by Auger electron spectroscopy

    NASA Technical Reports Server (NTRS)

    Lin, R. P.; Gopalan, R.

    1991-01-01

    The feasibility of AES as a remote-sensing technique to map the composition of the sunlit surfaces of planetary bodies without atmospheres is studied. Solar X-rays eject photoelectrons from the planetary surface. The resulting ions relax by emission of fluorescence X-rays or Auger electrons, with energies characteristic of the element which is ionized. The spectrum of Auger electrons and photoelectrons is computed for a variety of elements and for representative lunar rock types illuminated by soft-X-ray line and continuum emission typical of solar long-lived coronal active regions. The Auger electron lines for O, Si, Mg, Al, Fe, and Ca in lunar rocks stand well above the continuum background from photoelectrons and backscattered interplanetary electrons, with typical line-to-continuum ratios from about 20 to over 1000.

  12. The Pierre Auger Observatory Upgrade - Preliminary Design Report

    SciTech Connect

    Aab, Alexander

    2016-04-12

    The Pierre Auger Observatory has begun a major Upgrade of its already impressive capabilities, with an emphasis on improved mass composition determination using the surface detectors of the Observatory. Known as AugerPrime, the upgrade will include new 4 m2 plastic scintillator detectors on top of all 1660 water-Cherenkov detectors, updated and more flexible surface detector electronics, a large array of buried muon detectors, and an extended duty cycle for operations of the fluorescence detectors. This Preliminary Design Report was produced by the Collaboration in April 2015 as an internal document and information for funding agencies. It outlines the scientific and technical case for AugerPrime. We now release it to the public via the arXiv server. We invite you to review the large number of fundamental results already achieved by the Observatory and our plans for the future.

  13. Auger recombination in sodium-iodide scintillators from first principles

    NASA Astrophysics Data System (ADS)

    McAllister, Andrew; Åberg, Daniel; Schleife, André; Kioupakis, Emmanouil

    2015-04-01

    Scintillator radiation detectors suffer from low energy resolution that has been attributed to non-linear light yield response to the energy of the incident gamma rays. Auger recombination is a key non-radiative recombination channel that scales with the third power of the excitation density and may play a role in the non-proportionality problem of scintillators. In this work, we study direct and phonon-assisted Auger recombination in NaI using first-principles calculations. Our results show that phonon-assisted Auger recombination, mediated primarily by short-range phonon scattering, dominates at room temperature. We discuss our findings in light of the much larger values obtained by numerical fits to z-scan experiments.

  14. Calculation of equivalent dose for Auger electron emitting radionuclides distributed in human organs.

    PubMed

    Goddu, S M; Howell, R W; Rao, D V

    1996-01-01

    Radionuclides that emit Auger electrons can be extremely radiotoxic depending on the subcellular distribution of the radiochemical. Despite this, ICRP 60 provides no guidance in the calculation of equivalent dose H(T) for Auger electrons. The recent report by the American Association of Physicists in Medicine recommends a radiation weighting factor wR of 20 for stochastic effects caused by Auger electrons, along with a method of calculating the equivalent dose that takes into account the subcellular distribution of the radionuclide. In view of these recommendations, it is important to reevaluate equivalent doses from Auger electron emitters. The mean absorbed dose per unit cumulated activity (S-value) from Auger electrons and other radiations is calculated for ninety Auger-electron-emitting radionuclides distributed in human ovaries, testes and liver. Using these S-values, and the formalism given in the recent AAPM report, the dependence of the organ equivalent doses on subcellular distribution of the Auger electron emitters is examined. The results show an increase in the mean equivalent dose for Auger electron emitters when a significant fraction of the organ activity localizes in the DNA.

  15. Nuclear dynamics during the resonant Auger decay of water molecules.

    PubMed

    Eroms, Matthis; Vendrell, Oriol; Jungen, Martin; Meyer, Hans-Dieter; Cederbaum, Lorenz S

    2009-04-21

    The resonant Auger decay of water molecules is investigated. Here, the excitation process, the motion of the nuclei, and the decay of the resonantly excited state take place on the same (femtosecond) time scale. Therefore, a multistep picture is not suitable. Instead, the nuclear wave packet at each instant of time is a result of several competing and interfering contributions. The resonant Auger decay of water is simulated and its dynamics is studied in detail. An analysis of the final vibrational distribution is given. The multiconfiguration time-dependent Hartree method is used to study the intricate multidimensional dynamics. The potential energy surfaces have been calculated using a multireference configuration interaction method.

  16. Studies of liquid metal surfaces using Auger spectroscopy

    NASA Technical Reports Server (NTRS)

    Hardy, S.; Fine, J.

    1982-01-01

    The surface composition of liquid gallium-tin alloys is studied in an Auger electron spectrometer as a function of bulk composition and temperature. The sessile drop samples are cleaned by argon ion bombardment sputtering of the liquid. This technique produces surfaces that are entirely free of impurities within the sensitivity of the spectrometer and remain so for many days. Tin is found to be strongly adsorbed at the liquid-vacuum interface. Surface concentrations based on Auger measurements are found to be in reasonably good agreement with values calculated from surface tension measurements interpreted in terms of a monolayer depth distribution model for the adsorbed tin.

  17. Studies of liquid metal surfaces using Auger spectroscopy

    NASA Technical Reports Server (NTRS)

    Hardy, S.; Fine, J.

    1982-01-01

    The surface composition of liquid gallium-tin alloys is studied in an Auger electron spectrometer as a function of bulk composition and temperature. The sessile drop samples are cleaned by argon ion bombardment sputtering of the liquid. This technique produces surfaces that are entirely free of impurities within the sensitivity of the spectrometer and remain so for many days. Tin is found to be strongly adsorbed at the liquid-vacuum interface. Surface concentrations based on Auger measurements are found to be in reasonably good agreement with values calculated from surface tension measurements interpreted in terms of a monolayer depth distribution model for the adsorbed tin.

  18. Angular correlation between photoelectrons and auger electrons from K-shell ionization of neon.

    PubMed

    Landers, A L; Robicheaux, F; Jahnke, T; Schöffler, M; Osipov, T; Titze, J; Lee, S Y; Adaniya, H; Hertlein, M; Ranitovic, P; Bocharova, I; Akoury, D; Bhandary, A; Weber, Th; Prior, M H; Cocke, C L; Dörner, R; Belkacem, A

    2009-06-05

    We have used cold target recoil ion momentum spectroscopy to study the continuum correlation between the photoelectron of core-photoionized neon and the subsequent Auger electron. We observe a strong angular correlation between the two electrons. Classical trajectory Monte Carlo calculations agree quite well with the photoelectron energy distribution that is shifted due to the potential change associated with Auger decay. However, a striking discrepancy results in the distribution of the relative angle between Auger and photoelectron. The classical model predicts a shift in photoelectron flux away from the Auger emission direction, and the data strikingly reveal that the flux is lost rather than diverted, indicating that the two-step interpretation of photoionization followed by Auger emission is insufficient to fully describe the core-photoionization process.

  19. Angular Correlation between Photoelectrons and Auger Electrons from K-Shell Ionization of Neon

    SciTech Connect

    Landers, A. L.; Robicheaux, F.; Bhandary, A.; Jahnke, T.; Schoeffler, M.; Titze, J.; Akoury, D.; Doerner, R.; Osipov, T.; Lee, S. Y.; Adaniya, H.; Hertlein, M.; Weber, Th.; Prior, M. H.; Belkacem, A.; Ranitovic, P.; Bocharova, I.; Cocke, C. L.

    2009-06-05

    We have used cold target recoil ion momentum spectroscopy to study the continuum correlation between the photoelectron of core-photoionized neon and the subsequent Auger electron. We observe a strong angular correlation between the two electrons. Classical trajectory Monte Carlo calculations agree quite well with the photoelectron energy distribution that is shifted due to the potential change associated with Auger decay. However, a striking discrepancy results in the distribution of the relative angle between Auger and photoelectron. The classical model predicts a shift in photoelectron flux away from the Auger emission direction, and the data strikingly reveal that the flux is lost rather than diverted, indicating that the two-step interpretation of photoionization followed by Auger emission is insufficient to fully describe the core-photoionization process.

  20. Angular Correlation between Photoelectrons and Auger Electrons from K-Shell Ionization of Neon

    NASA Astrophysics Data System (ADS)

    Landers, A. L.; Robicheaux, F.; Jahnke, T.; Schöffler, M.; Osipov, T.; Titze, J.; Lee, S. Y.; Adaniya, H.; Hertlein, M.; Ranitovic, P.; Bocharova, I.; Akoury, D.; Bhandary, A.; Weber, Th.; Prior, M. H.; Cocke, C. L.; Dörner, R.; Belkacem, A.

    2009-06-01

    We have used cold target recoil ion momentum spectroscopy to study the continuum correlation between the photoelectron of core-photoionized neon and the subsequent Auger electron. We observe a strong angular correlation between the two electrons. Classical trajectory Monte Carlo calculations agree quite well with the photoelectron energy distribution that is shifted due to the potential change associated with Auger decay. However, a striking discrepancy results in the distribution of the relative angle between Auger and photoelectron. The classical model predicts a shift in photoelectron flux away from the Auger emission direction, and the data strikingly reveal that the flux is lost rather than diverted, indicating that the two-step interpretation of photoionization followed by Auger emission is insufficient to fully describe the core-photoionization process.

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

    DOE PAGES

    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

  2. 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.

  3. Auger analysis of films formed on metals in sliding contact with halogenated polymers

    NASA Technical Reports Server (NTRS)

    Pepper, S. V.

    1974-01-01

    The use of Auger electron spectroscopy (AES) to search for transferred polymer must contend with the fact that there has been no published work on Auger analysis of polymers. Since this is a new area for AES, the Auger spectra of polymers and of halogenated polymers in particular is discussed. It is shown that the Auger spectra of halogenated polymers have certain characteristics that permit an assessment of whether a polymeric transfer film has been established by sliding contact. The discussion is general and the concepts should be useful in considering the Auger analysis of any polymer. The polymers chosen for this study are the halogenated polymers polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), and polychlorotrifluorethylene (PCTFE).

  4. Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity.

    PubMed

    Tao, Zhi-Fu; Hasvold, Lisa; Wang, Le; Wang, Xilu; Petros, Andrew M; Park, Chang H; Boghaert, Erwin R; Catron, Nathaniel D; Chen, Jun; Colman, Peter M; Czabotar, Peter E; Deshayes, Kurt; Fairbrother, Wayne J; Flygare, John A; Hymowitz, Sarah G; Jin, Sha; Judge, Russell A; Koehler, Michael F T; Kovar, Peter J; Lessene, Guillaume; Mitten, Michael J; Ndubaku, Chudi O; Nimmer, Paul; Purkey, Hans E; Oleksijew, Anatol; Phillips, Darren C; Sleebs, Brad E; Smith, Brian J; Smith, Morey L; Tahir, Stephen K; Watson, Keith G; Xiao, Yu; Xue, John; Zhang, Haichao; Zobel, Kerry; Rosenberg, Saul H; Tse, Chris; Leverson, Joel D; Elmore, Steven W; Souers, Andrew J

    2014-10-09

    A-1155463, a highly potent and selective BCL-XL inhibitor, was discovered through nuclear magnetic resonance (NMR) fragment screening and structure-based design. This compound is substantially more potent against BCL-XL-dependent cell lines relative to our recently reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical liabilities. A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. A-1155463 thus represents an excellent tool molecule for studying BCL-XL biology as well as a productive lead structure for further optimization.

  5. Potent complement C3a receptor agonists derived from oxazole amino acids: Structure-activity relationships.

    PubMed

    Singh, Ranee; Reed, Anthony N; Chu, Peifei; Scully, Conor C G; Yau, Mei-Kwan; Suen, Jacky Y; Durek, Thomas; Reid, Robert C; Fairlie, David P

    2015-12-01

    Potent ligands for the human complement C3a receptor (C3aR) were developed from the almost inactive tripeptide Leu-Ala-Arg corresponding to the three C-terminal residues of the endogenous peptide agonist C3a. The analogous Leu-Ser-Arg was modified by condensing the serine side chain with the leucine carbonyl with elimination of water to form leucine-oxazole-arginine. Subsequent elaboration with a variety of N-terminal amide capping groups produced agonists as potent as human C3a itself in stimulating Ca(2+) release from human macrophages. Structure-activity relationships are discussed.

  6. New potent and selective polyfluoroalkyl ketone inhibitors of GVIA calcium-independent phospholipase A2.

    PubMed

    Magrioti, Victoria; Nikolaou, Aikaterini; Smyrniotou, Annetta; Shah, Ishita; Constantinou-Kokotou, Violetta; Dennis, Edward A; Kokotos, George

    2013-09-15

    Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA2 inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA2 inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA2 inhibitor ever reported with a XI(50) value of 0.0001, and with no significant inhibition against GIVA cPLA2 or GV sPLA2. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA2, GIVA cPLA2, and GV sPLA2. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor

    PubMed Central

    2010-01-01

    During the course of our research efforts to develop a potent and selective γ-secretase inhibitor for the treatment of Alzheimer's disease, we investigated a series of carboxamide-substituted sulfonamides. Optimization based on potency, Notch/amyloid-β precursor protein selectivity, and brain efficacy after oral dosing led to the discovery of 4 (BMS-708163). Compound 4 is a potent inhibitor of γ-secretase (Aβ40 IC50 = 0.30 nM), demonstrating a 193-fold selectivity against Notch. Oral administration of 4 significantly reduced Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs. PMID:24900185

  8. First identification of xanthone sulfonamides as potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.

    PubMed

    Hu, Honggang; Liao, Hongli; Zhang, Jun; Wu, Weifeng; Yan, Jufang; Yan, Yonghong; Zhao, Qingjie; Zou, Yan; Chai, Xiaoyun; Yu, Shichong; Wu, Qiuye

    2010-05-15

    Inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) would be useful anti-atherogenic agents, since an absence of ACAT affects the absorption and transformation of cholesterol, indirectly resulting in the reduction of cholesteryl ester accumulation in blood vessels. This report discloses xanthone sulfonamides as novel class small molecule inhibitors of ACAT. A series of xanthone sulfonamides were synthesized and evaluated to result in the identification of several potent ACAT inhibitors, among which 2n proved to be more potent than the positive control Sandoz58-35. Moreover, a molecular model for the binding between 2n and the active site of ACAT-2 was provided based computational docking results.

  9. Synthesis and antibacterial activity of a novel series of potent DNA gyrase inhibitors. Pyrazole derivatives.

    PubMed

    Tanitame, Akihiko; Oyamada, Yoshihiro; Ofuji, Keiko; Fujimoto, Mika; Iwai, Noritaka; Hiyama, Yoichi; Suzuki, Kenji; Ito, Hideaki; Terauchi, Hideo; Kawasaki, Motoji; Nagai, Kazuo; Wachi, Masaaki; Yamagishi, Jun-ichi

    2004-07-01

    We have previously found that a pyrazole derivative 1 possesses antibacterial activity and inhibitory activity against DNA gyrase and topoisomerase IV. Here, we synthesized new pyrazole derivatives and found that 5-[(E)-2-(5-chloroindol-3-yl)vinyl]pyrazole 16 possesses potent antibacterial activity and selective inhibitory activity against bacterial topoisomerases. Many of the synthesized pyrazole derivatives were potent against clinically isolated quinolone- or coumarin-resistant Gram-positive strains and had minimal inhibitory concentration values against these strains equivalent to those against susceptible strains.

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

    PubMed Central

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

    2016-01-01

    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

  11. 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

    2016-01-29

    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.

  12. Content Analysis: A Potent Tool in the Searcher's Arsenal.

    ERIC Educational Resources Information Center

    Solomon, Marc

    1993-01-01

    Shows how online content analysis can be used to measure the frequencies and contexts of issues that advertisers circulate to major media markets. An example of a study of word strings of advertising slogans, a description of the benchmarks of successful sloganeering, and strategies for planning a study are described. (KRN)

  13. A Potent, Versatile Disulfide-Reducing Agent from Aspartic Acid

    PubMed Central

    2013-01-01

    Dithiothreitol (DTT) is the standard reagent for reducing disulfide bonds between and within biological molecules. At neutral pH, however, >99% of DTT thiol groups are protonated and thus unreactive. Herein, we report on (2S)-2-amino-1,4-dimercaptobutane (dithiobutylamine or DTBA), a dithiol that can be synthesized from l-aspartic acid in a few high-yielding steps that are amenable to a large-scale process. DTBA has thiol pKa values that are ∼1 unit lower than those of DTT and forms a disulfide with a similar E°′ value. DTBA reduces disulfide bonds in both small molecules and proteins faster than does DTT. The amino group of DTBA enables its isolation by cation-exchange and facilitates its conjugation. These attributes indicate that DTBA is a superior reagent for reducing disulfide bonds in aqueous solution. PMID:22353145

  14. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. 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.

  17. 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…

  18. Nobiletin: a citrus flavonoid displaying potent physiological activity.

    PubMed

    Noguchi, Shuji; Atsumi, Haruka; Iwao, Yasunori; Kan, Toshiyuki; Itai, Shigeru

    2016-02-01

    Nobiletin [systematic name: 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-chromen-4-one; C21H22O8] is a flavonoid found in citrus peels, and has been reported to show a wide range of physiological properties, including anti-inflammatory, anticancer and antidementia activities. We have solved the crystal structure of nobiletin, which revealed that the chromene and arene rings of its flavone moiety, as well as the two methoxy groups bound to its arene ring, were coplanar. In contrast, the C atoms of the four methoxy groups bound to the chromene ring are out of the plane, making the molecule conformationally chiral. A comparison of the crystal structures of nobiletin revealed that it could adopt a variety of different conformations through rotation of the covalent bond between the chromene and arene rings, and the orientations of methoxy groups bound to the chromene ring.

  19. National Cost Implications of a Potentional Perchlorate Regulation

    EPA Pesticide Factsheets

    In this study, a screening level cost assessment was conducted to evaluate the national cost implications of five potential regulatory levels for perchlorate in drinking water 4, 6, 12, 18, and 24 ?g/L.

  20. Biological Activities of Fusarochromanone: a Potent Anti-cancer Agent

    DTIC Science & Technology

    2014-09-03

    Univ. of Texas- MD Anderson Cancer Center), MCF-7 (low malignant mammary gland adenocarcinoma), MDA-231 (malignant mammary gland adenocarcinoma), SV...differences between the groups of mice in terms of tumor volume or persisting benign cysts was compared using the Mann–Whitney test and differences...has modest in-vivo activity. In a mouse xenograft skin SCC tumor model, FC101 was well tolerated and non-toxic, but it required a dose of 8 mg/kg/day

  1. 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

  2. [Bryophytes, a potent source of drugs for tomorrow's medicine?].

    PubMed

    Krzaczkowski, Lucie; Wright, Michel; Gairin, Jean Edouard

    2008-11-01

    Although secondary plant metabolites provided numerous leads for the development of a wide array of therapeutic drugs, the discovery of new drugs with novel structures has declined in the past few years. Indeed higher plants have a similar evolutionary history and so produce similar metabolites. Search for novel sources of new therapeutic compounds within unexplored parts of biodiversity is thus an attractive challenge. Bryophytes, a group of small terrestrial plants remain relatively untouched in the drug discovery process whereas some have been used as medicinal plants. Studies of their secondary metabolites are recent but reveal original compounds, some of which not synthesized by higher plants. However investigations often meet difficulties during harvest or isolation of active compounds. In consequence, small quantities of substances obtained may be the main reason for the lack of biological tests. Strategies to overcome those troubles may exist and then lead to innovative medicinal applications.

  3. Synthesis of a potent new antimalarial through natural products conjugation

    PubMed Central

    Bruno, Michela; Trucchi, Beatrice; Monti, Diego; Romeo, Sergio; Kaiser, Marcel; Verotta, Luisella

    2013-01-01

    Three natural products have been assembled to obtain a new antimalarial hit. (+)-Usnic acid was used as scaffold to design and synthesize new products, that were tested on asexual development for P. falciparum and P. berghei. Among them, the ester of (+)-usnic acid-4-aminobutyric acid 14 with dihydroartemisinin shows considerable in vivo antimalarial activity against P. berghei in mice, similar to the synthetic drug artesunate. Compound 14 behaves as a delivery system for dihydroartemisinin and combine the effects of the endoperoxide with the redox properties of the phenolic portions of (+)-usnic acid. PMID:23307699

  4. Fire for Effect: Calling for a More Potent Energy System

    DTIC Science & Technology

    2008-05-22

    Press, 2003 Clausewitz, Carl Von, edited and translated by Michael Howard and Peter Paret, On War. Princeton, NJ: Princeton University Press, 1976...at http://www.cfr.org/publication/14901/robertson.html (accessed 14 February 2008) Sagan , Scott, Christopher Chyba and Hans Blix, “Looking Ahead: A

  5. 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.

  6. 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.

  7. A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost.

    PubMed

    Krupa, Małgorzata; Chodyński, Michał; Ostaszewska, Anna; Cmoch, Piotr; Dams, Iwona

    2017-01-31

    Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.

  8. 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

  9. Resveratrol: cellular actions of a potent natural chemical that confers a diversity of health benefits.

    PubMed

    Marques, Francine Z; Markus, M Andrea; Morris, Brian J

    2009-11-01

    Resveratrol is a polyphenolic flavonoid with potent antioxidant activity. It is found in a diversity of plants, notably berry fruit, and is attracting increased attention due to its health benefits, especially in common age-related diseases such as cancer, type 2 diabetes, cardiovascular disease, and neurological conditions. Resveratrol has positive effects on metabolism and can increase the lifespan of various organisms. Its effects arise from its capacity to interact with multiple molecular targets involved in diverse intracellular pathways. Most well known is the ability of resveratrol to activate sirtuins, a class of NAD(+)-dependent deacetylases that affect multiple transcription factors and other protein targets. More potent sirtuin activators have now been discovered by large-scale screening programs. Resveratrol and the new compounds are the subject of clinical trials to determine their consumer safety and suitability for the prevention and treatment of most common diseases of aging.

  10. Lining material tests for the AUGER PROJECT surface detector

    NASA Astrophysics Data System (ADS)

    Escobar, C. O.; Fauth, A. C.; Guzzo, M. M.; Shibuya, E. H.

    1999-03-01

    We are trying to obtain a suitable material to compose the lining of a water Cerenkov tank for the surface detector. part of a hybrid detector of the Auger Project. Results of tests were compared with DuPont 1073Tyvek TM and obtained a reasonable performance for (PVC+BaSO 4) material.

  11. A Potent Vector: Assessing Chinese Cruise Missile Developments

    DTIC Science & Technology

    2014-01-01

    multiyear comprehensive study of Chinese cruise missiles based exclusively on open sources. More than 1,000 discrete Chinese- language sources were...infrastructure; didactic PLA discussions (Modern Navy and People’s Navy); generalist deliberations on the de- velopment trajectory and operational use of...These Chinese sources were supplemented with a wide variety of English- language sources, including—in descending level of demonstrated author- ity

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

    PubMed

    Arabaci, Betul; Gulcin, Ilhami; Alwasel, Saleh

    2014-07-10

    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.

  13. 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

  14. A new antibiotic with potent activity targets MscL.

    PubMed

    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

    2015-07-01

    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.

  15. 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

  16. Antidiabetic Indian Plants: A Good Source of Potent Amylase Inhibitors

    PubMed Central

    Bhat, Menakshi; Zinjarde, Smita S.; Bhargava, Shobha Y.; Kumar, Ameeta Ravi; Joshi, Bimba N.

    2011-01-01

    Diabetes is known as a multifactorial disease. The treatment of diabetes (Type II) is complicated due to the inherent patho-physiological factors related to this disease. One of the complications of diabetes is post-prandial hyperglycemia (PPHG). Glucosidase inhibitors, particularly α-amylase inhibitors are a class of compounds that helps in managing PPHG. Six ethno-botanically known plants having antidiabetic property namely, Azadirachta indica Adr. Juss.; Murraya koenigii (L.) Sprengel; Ocimum tenuflorum (L.) (syn: Sanctum); Syzygium cumini (L.) Skeels (syn: Eugenia jambolana); Linum usitatissimum (L.) and Bougainvillea spectabilis were tested for their ability to inhibit glucosidase activity. The chloroform, methanol and aqueous extracts were prepared sequentially from either leaves or seeds of these plants. It was observed that the chloroform extract of O. tenuflorum; B. spectabilis; M. koenigii and S. cumini have significant α-amylase inhibitory property. Plants extracts were further tested against murine pancreatic, liver and small intestinal crude enzyme preparations for glucosidase inhibitory activity. The three extracts of O. tenuflorum and chloroform extract of M. koenigi showed good inhibition of murine pancreatic and intestinal glucosidases as compared with acarbose, a known glucosidase inhibitor. PMID:18955350

  17. Antidiabetic Indian plants: a good source of potent amylase inhibitors.

    PubMed

    Bhat, Menakshi; Zinjarde, Smita S; Bhargava, Shobha Y; Kumar, Ameeta Ravi; Joshi, Bimba N

    2011-01-01

    Diabetes is known as a multifactorial disease. The treatment of diabetes (Type II) is complicated due to the inherent patho-physiological factors related to this disease. One of the complications of diabetes is post-prandial hyperglycemia (PPHG). Glucosidase inhibitors, particularly α-amylase inhibitors are a class of compounds that helps in managing PPHG. Six ethno-botanically known plants having antidiabetic property namely, Azadirachta indica Adr. Juss.; Murraya koenigii (L.) Sprengel; Ocimum tenuflorum (L.) (syn: Sanctum); Syzygium cumini (L.) Skeels (syn: Eugenia jambolana); Linum usitatissimum (L.) and Bougainvillea spectabilis were tested for their ability to inhibit glucosidase activity. The chloroform, methanol and aqueous extracts were prepared sequentially from either leaves or seeds of these plants. It was observed that the chloroform extract of O. tenuflorum; B. spectabilis; M. koenigii and S. cumini have significant α-amylase inhibitory property. Plants extracts were further tested against murine pancreatic, liver and small intestinal crude enzyme preparations for glucosidase inhibitory activity. The three extracts of O. tenuflorum and chloroform extract of M. koenigi showed good inhibition of murine pancreatic and intestinal glucosidases as compared with acarbose, a known glucosidase inhibitor.

  18. Comprehensive review on betulin as a potent anticancer agent.

    PubMed

    Król, Sylwia Katarzyna; Kiełbus, Michał; Rivero-Müller, Adolfo; 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.

  19. Studies Toward the Pharmacophore of Salvinorin A, a Potent Kappa Opioid Receptor Agonist

    PubMed Central

    Munro, Thomas A.; Rizzacasa, Mark A.; Roth, Bryan L.; Toth, Beth A.; Yan, Feng

    2009-01-01

    Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective kappa opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity, but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors. PMID:15658846

  20. Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist.

    PubMed

    Munro, Thomas A; Rizzacasa, Mark A; Roth, Bryan L; Toth, Beth A; Yan, Feng

    2005-01-27

    Salvinorin A (1), from the sage Salvia divinorum, is a potent and selective kappa opioid receptor (KOR) agonist. We screened other salvinorins and derivatives for binding affinity and functional activity at opioid receptors. Our results suggest that the methyl ester and furan ring are required for activity but that the lactone and ketone functionalities are not. Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors.

  1. 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

  2. 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

  3. A potent acetylcholinesterase inhibitor from Pancratium illyricum L.

    PubMed

    Iannello, Carmelina; Pigni, Natalia Belèn; Antognoni, Fabiana; Poli, Ferruccio; Maxia, Andrea; de Andrade, Jean Paulo; Bastida, Jaume

    2014-01-01

    Plants belonging to the Amaryllidaceae contain an exclusive group of alkaloids, known as sources of important biological activities. In the present work, Pancratium illyricum L., a species belonging to this family and endemic of Sardinia (Italy), was investigated for its alkaloid content. Fresh bulbs and leaves were processed separately. Standard extraction and purification procedures were applied to obtain fractions and compounds for GC-MS and NMR analysis. In addition to eight already known alkaloids (1-8), 11α-hydroxy-O-methylleucotamine (9) was isolated for the first time and its structure completely determined by one and two-dimensional (1)H and (13)C NMR spectroscopy. This new galanthamine-type compound exhibited a pronounced in vitro acetylcholinesterase (AChE) inhibitory activity (IC50=3.5±1.1 μM) in comparison to the reference standard galanthamine hydrobromide (IC50=1.5±0.2 μM). Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Domoic acid is a potent neurotoxin to neonatal rats.

    PubMed

    Xi, D; Peng, Y G; Ramsdell, J S

    1997-01-01

    Domoic acid induces a time-dependent neuroexcitotoxic effect in neonatal rats characterized by hyperactivity, stereotypic scratching, convulsions, and death with observable behaviors occurring at exposures 40 times lower by body weight in neonates than reported in adults. Low doses of domoic acid (0.1 mg/kg) induced c-fos in the central nervous system which was inhibited in part by 2-amino-5-phosphonovaleric acid, an NMDA receptor antagonist. Domoic acid caused no evidence of structural alteration in the brain of neonates as assessed by Nissel staining and cupric silver histochemistry. Domoic acid induced reproducible behavioral effects at doses as low as 0.05 mg/kg and induced seizures doses as low as 0.2 mg/kg. Determination of serum domoic acid levels after 60 min exposure indicated that serum levels of domoic acid in the neonates corresponded closely to the serum levels that induce similar symptoms in adult rats and mice. We conclude that neonatal rats are highly sensitive to the neuroexcitatory and lethal effects of domoic acid and that the increased sensitivity results from higher than expected serum levels of domoic acid. These findings are consistent with other findings that reduced serum clearance of domoic acid is a predisposing factor to domoic acid toxicity.

  5. Suaveolic Acid: A Potent Phytotoxic Substance of Hyptis suaveolens

    PubMed Central

    Islam, A. K. M. Mominul; Ohno, Osamu; Suenaga, Kiyotake; Kato-Noguchi, Hisashi

    2014-01-01

    Hyptis suaveolens (Lamiaceae) is an exotic invasive plant in many countries. Earlier studies reported that the aqueous, methanol, and aqueous methanol extract of H. suaveolens and its residues have phytotoxic properties. However, to date, the phytotoxic substances of this plant have not been reported. Therefore, the objectives of this study were isolation and identification of phytotoxic substances of H. suaveolens. Aqueous methanol extract of this plant was purified by several chromatographic runs through bioassay guided fractionation using garden cress (Lepidium sativum) as a test plant. Final purification of a phytotoxic substance was achieved by reverse phase HPLC and characterized as 14α-hydroxy-13β-abiet-8-en-18-oic acid (suaveolic acid) by high-resolution ESI-MS, 1H-,13C-NMR, CD, and specific rotation. Suaveolic acid inhibited the shoot growth of garden cress, lettuce (Lactuca sativa), Italian ryegrass (Lolium multiflorum), and barnyard grass (Echinochloa crus-galli) at concentrations greater than 30 µM. Root growth of all but lettuce was also inhibited at concentrations greater than 30 µM. The inhibitory activities were concentration dependent. Concentrations required for 50% growth inhibition of suaveolic acid for those test plant species were ranged from 76 to 1155 µM. Therefore, suaveolic acid is phytotoxic and may be responsible for the phytotoxicity of H. suaveolens plant extracts. PMID:25405221

  6. Selenocyanates and diselenides: a new class of potent antileishmanial agents.

    PubMed

    Plano, Daniel; Baquedano, Ylenia; Moreno-Mateos, David; Font, María; Jiménez-Ruiz, Antonio; Palop, Juan Antonio; Sanmartín, Carmen

    2011-08-01

    Thirty five selenocyanate and diselenide compounds were subjected to in vitro screening against Leishmania infantum promastigotes and the most active ones were also tested in an axenic amastigote model. In order to establish the selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines. Thirteen derivatives exhibit better IC(50) values than miltefosine and edelfosine. Bis(4-aminophenyl)diselenide exhibits the best activity when assayed in infected macrophages and one of the lowest cytotoxic activities against the human cell lines tested, with SI values of 32 and 24 against Jurkat and THP-1 cells, respectively. This compound thus represents a new lead for further studies aimed at establishing its mechanism of action. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  7. Nanomedicine as a potent strategy in melanoma tumor microenvironment.

    PubMed

    Pautu, Vincent; Leonetti, Daniela; Lepeltier, Elise; Clere, Nicolas; Passirani, Catherine

    2017-02-20

    Melanoma originated from melanocytes is the most aggressive type of skin cancer. Despite considerable progresses in clinical treatment with the discovery of BRAF or MEK inhibitors and monoclonal antibodies, the durability of response to treatment is often limited to the development of acquired resistance and systemic toxicity. The limited success of conventional treatment highlights the importance of understanding the role of melanoma tumor microenvironment in tumor developement and drug resistance. Nanoparticles represent a promising strategy for the development of new cancer treatments able to improve the bioavailability of drugs and increase their penetration by targeting specifically tumors cells and/or tumor environment. In this review, we will discuss the main influence of tumor microenvironment in melanoma growth and treatment outcome. Furthermore, third generation loaded nanotechnologies represent an exciting tool for detection, treatment, and escape from possible mechanism of resistance mediated by tumor microenvironment, and will be highlighted in this review.

  8. CGS 8216: receptor binding characteristics of a potent benzodiazepine antagonist.

    PubMed

    Czernik, A J; Petrack, B; Kalinsky, H J; Psychoyos, S; Cash, W D; Tsai, C; Rinehart, R K; Granat, F R; Lovell, R A; Brundish, D E; Wade, R

    1982-01-25

    CGS 8216 is a novel nonbenzodiazepine that inhibited 3H-flunitrazepam (3H-FLU) binding to rat synaptosomal membranes in vitro at subnanomolar concentrations. It prevented the in vivo labeling of brain benzodiazepine receptors by 3H-FLU with the same potency as diazepam when given orally to mice. Pharmacologic tests showed that it was devoid of benzodiazepine-like activity but it antagonized the actions of diazepam in these tests. It did not interact with alpha- or beta- adrenergic, H1-histaminergic or GABA receptors but it inhibited adenosine-activation of cyclic AMP formation. Studies with 3H-CGS 8216 demonstrated that it bound specifically and with high affinity to rat forebrain membranes and was displaced by drugs with an order of potencies similar to that observed when 3H-diazepam and 3H-FLU were used as radioligands. The regional distribution of 3H-CGS 8216 binding sites in the brain was also similar to that of 3H-FLU. Dissociation of 3H-CGS 8216 binding was slow at 0 degrees C but increased with temperature and was almost complete within 1 min at 37 degrees C. Scatchard analyses were linear, yielding KD values of 0.044, 0.11 and 0.18 nM at 0, 25 and 37 degrees C, respectively; the Bmax value did not change appreciably with temperature and was approximately 1000 fmoles/mg protein. Using 3H-FLU, the value for Bmax as well as for the KD increased with temperature. The total number of binding sites determined for 3H-FLU was greater than that for 3H-CGS 8216 at each temperature. CGS 8216 exhibited mixed-type inhibition of 3H-FLU binding. GABA did not stimulate 3H-CGS 8216 binding whereas it enhanced 3H-FLU binding. CGS 8216 may be a useful ligand for probing the antagonist properties of the benzodiazepine receptor and is likely to exhibit interesting therapeutic effects.

  9. 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.

  10. The Antibiotic Micrococcin Is a Potent Inhibitor of Growth and Protein Synthesis in the Malaria Parasite

    PubMed Central

    Rogers, M. John; Cundliffe, Eric; McCutchan, Thomas F.

    1998-01-01

    The antibiotic micrococcin is a potent growth inhibitor of the human malaria parasite Plasmodium falciparum, with a 50% inhibitory concentration of 35 nM. This is comparable to or less than the corresponding levels of commonly used antimalarial drugs. Micrococcin, like thiostrepton, putatively targets protein synthesis in the plastid-like organelle of the parasite. PMID:9517961

  11. Discovery of a highly potent series of oxazole-based phosphodiesterase 4 inhibitors.

    PubMed

    Kuang, Rongze; Shue, Ho-Jane; Blythin, David J; Shih, Neng-Yang; Gu, Danlin; Chen, Xiao; Schwerdt, John; Lin, Ling; Ting, Pauline C; Zhu, Xiaohong; Aslanian, Robert; Piwinski, John J; Xiao, Li; Prelusky, Daniel; Wu, Ping; Zhang, Ji; Zhang, Xiang; Celly, Chander S; Minnicozzi, Michael; Billah, Motasim; Wang, Peng

    2007-09-15

    Substituted quinolyl oxazoles were discovered as a novel and highly potent series of phosphodiesterase 4 (PDE4) inhibitors. Structure-activity relationship studies revealed that the oxazole core, with 4-carboxamide and 5-aminomethyl groups, is a novel PDE4 inhibitory pharmacophore. Selectivity profiles and in vivo biological activity are also reported.

  12. CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability.

    PubMed

    Elzein, Elfatih; Ibrahim, Prabha; Koltun, Dmitry O; Rehder, Ken; Shenk, Kevin D; Marquart, Timothy A; Jiang, Bob; Li, Xiaofen; Natero, Reina; Li, Yuan; Nguyen, Marie; Kerwar, Suresh; Chu, Nancy; Soohoo, Daniel; Hao, Jia; Maydanik, Victoria Y; Lustig, David A; Zeng, Dewan; Leung, Kwan; Zablocki, Jeff A

    2004-12-20

    New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50=380 nM rat mitochondria) with favorable PK properties (F=93%, t(1/2)=13.6h, dog).

  13. The antibiotic micrococcin is a potent inhibitor of growth and protein synthesis in the malaria parasite.

    PubMed

    Rogers, M J; Cundliffe, E; McCutchan, T F

    1998-03-01

    The antibiotic micrococcin is a potent growth inhibitor of the human malaria parasite Plasmodium falciparum, with a 50% inhibitory concentration of 35 nM. This is comparable to or less than the corresponding levels of commonly used antimalarial drugs. Micrococcin, like thiostrepton, putatively targets protein synthesis in the plastid-like organelle of the parasite.

  14. 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.

  15. Auger tension leg platform: Conquering the deepwater Gulf of Mexico

    SciTech Connect

    Bourgeois, T.M.

    1994-12-31

    Conquering the ultra-deepwater Gulf of Mexico (GOM) is among the greatest challenges facing the oil and gas industry today. Explorationists have found significant quantities of hydrocarbons in the ultra-deep GOM. Since Shell Offshore Inc. (Shell) has over one-third of the deepwater GOM acreage under lease today, development of this vast new oil and gas reservoir represents a major opportunity. Shell`s Auger field, located in Garden Banks 426, was discovered in 1987 in 2,860 feet of water. This discovery kicked off a project of mammoth proportions for Shell and the industry. Shell designed and built a Tension Leg Platform (TLP) and related drilling and producing facilities for the major discovery at Prospect Auger. A TLP is a floating structure which is tethered to the seafloor. This $1.2 billion development is located in a world record shattering water depth of 2,860 feet. Integrating the complexities of this floating structure with the challenges of the subsurface makes Auger the most complex project ever undertaken by Shell`s Production Department. The Auger Project, which was conceived in 1989, is now installed within three months of the original target and $100 million under the original estimate. This is a significant success for Shell and the industry in the deepwater GOM as it opens the ultra-deepwater GOM frontier as an energy source to fuel America for decades to come.

  16. Observation of suppressed Auger mechanism in type-I quantum well structures with delocalized electron-hole wavefunctions

    SciTech Connect

    Hassani Nia, Iman; Fathipour, Vala; Mohseni, Hooman

    2015-08-15

    We report the first observation of non-threshold Auger mechanism for a quantum well structure with Type-I band alignment. Excitation-dependent photoluminescence measurements were used to extract the Auger recombination coefficients from 77 K up to room temperature. The results verify the role of interface mediated momentum exchange as well as suppression of Auger recombination for delocalized electron-hole wavefunctions.

  17. Psymberin, a potent sponge-derived cytotoxin from Psammocinia distantly related to the pederin family.

    PubMed

    Cichewicz, Robert H; Valeriote, Frederick A; Crews, Phillip

    2004-06-10

    [structure: see text] Bioassay-guided fractionation of the sponge Psammocinia sp. afforded psymberin (1) possessing 5S,8S,9S,11R,13R,15S,16R,17R stereochemistry. Psymberin exhibits structural similarities to the pederin family metabolites. The potent cytotoxicty and unique structural features of 1 make it a promising lead for therapeutic development.

  18. Suppression of auger recombination in ""giant"" core/shell nanocrystals

    SciTech Connect

    Garcia Santamaria, Florencio; Vela, Javier; Schaller, Richard D; Hollingsworth, Jennifer A; Klimov, Victor I; Chen, Yongfen

    2009-01-01

    Many potential applications of semiconductor nanocrystals are hindered by nonradiative Auger recombination wherein the electron-hole (exciton) recombination energy is transferred to a third charge carrier. This process severely limits the lifetime and bandwidth of optical gain, leads to large nonradiative losses in light emitting diodes and photovoltaic cells, and is believed to be responsible for intermittency ('blinking') of emission from single nanocrystals. The development of nanostructures in which Auger recombination is suppressed has been a longstanding goal in colloidal nanocrystal research. Here, we demonstrate that such suppression is possible using so-called 'giant' nanocrystals that consist of a small CdSe core and a thick CdS shell. These nanostructures exhibit a very long biexciton lifetime ({approx}10 ns) that is likely dominated by radiative decay instead of non-radiative Auger recombination. As a result of suppressed Auger recombination, even high-order multiexcitons exhibit high emission efficiencies, which allows us to demonstrate optical amplification with an extraordinarily large bandwidth (>500 me V) and record low excitation thresholds.

  19. The Pierre Auger Observatory status and latest results

    NASA Astrophysics Data System (ADS)

    Berat, Corinne

    2017-03-01

    The Pierre Auger Observatory, in Argentina, is the present flagship experiment studying ultrahigh-energy cosmic rays (UHECRs). Facing the challenge due to low cosmic-ray flux at the highest energies, the Observatory has been taking data for more than a decade, reaching an exposure of over 50 000 km2 sr yr. The combination of a large surface detector array and fluorescence telescopes provides a substantial improvement in energy calibration and extensive air shower measurements, resulting in data of unprecedented quality. Moreover, the installation of a denser subarray has allowed extending the sensitivity to lower energies. Altogether, this contributes to provide important information on key questions in the UHECR field in the energy range from 0.1 EeV up to 100 EeV. A review of main results from the Pierre Auger Observatory is presented with a particular focus on the energy spectrum measurements, the mass composition studies, the arrival directions analyses, the search for neutral cosmic messengers, and the investigation of high-energy hadronic interactions. Despite this large amount of valuable results, the understanding of the nature of UHECRs and of their origin remains an open science case that the Auger collaboration is planning to address with the AugerPrime project to upgrade the Observatory.

  20. 45 Day safety screen results for Tank 241-C-108 -- Augers 94-012, 94-014 and 94-015

    SciTech Connect

    Rice, A.D.

    1995-01-31

    Three auger samples from Tank C-108 (on the Ferrocyanide Watch List) were received by the 222-S laboratories. These samples underwent safety screening analysis (DSC, TGA, and Alpha Total) in accordance with reference below. No results exceeded the notification criteria. Due to the calculated depth of sludge at riser 7, two augers were used to sample the sludge. The first (94-AUG-012) was a ten inch auger, the second (94-AUG-014) was a 20 inch auger. One 20 inch auger (94-AUG-015) was used to sample the tank C-108 contents at riser 4. Results are compiled in this report.

  1. Ultrafast X-ray Auger probing of photoexcited molecular dynamics

    DOE PAGES

    McFarland, B. K.; Farrell, J. P.; Miyabe, S.; ...

    2014-06-23

    Here, molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation—X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towardsmore » high kinetic energies, resulting from a particular C–O bond stretch in the ππ* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the nπ* state.« less

  2. Ultrafast X-ray Auger probing of photoexcited molecular dynamics

    SciTech Connect

    McFarland, B. K.; Farrell, J. P.; Miyabe, S.; Tarantelli, F.; Aguilar, A.; Berrah, N.; Bostedt, C.; Bozek, J. D.; Bucksbaum, P. H.; Castagna, J. C.; Coffee, R. N.; Cryan, J. P.; Fang, L.; Feifel, R.; Gaffney, K. J.; Glownia, J. M.; Martinez, T. J.; Mucke, M.; Murphy, B.; Natan, A.; Osipov, T.; Petrović, V. S.; Schorb, S.; Schultz, Th.; Spector, L. S.; Swiggers, M.; Tenney, I.; Wang, S.; White, J. L.; White, W.; Gühr, M.

    2014-06-23

    Here, molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation—X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towards high kinetic energies, resulting from a particular C–O bond stretch in the ππ* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the nπ* state.

  3. Pristine SiC Candidates: Spectral Imaging and Auger Investigations

    NASA Astrophysics Data System (ADS)

    Croat, T. K.; Lebsack, E.; Bernatowicz, T. J.

    2010-03-01

    We describe a new spectral imaging method to locate pristine SiCs (those prepared without acid dissolution) from within Murchison matrix material. We present images,X-ray and Auger electron spectra from pristine SiCs, which show carbonaceous surface coatings.

  4. Highly potent stem cells from full-term amniotic fluid: A realistic perspective.

    PubMed

    Hamid, Adila A; Joharry, Muhammad Khair; Mun-Fun, Hoo; Hamzah, Siti Nurusaadah; Rejali, Zulida; Yazid, Mohd Nazri; Karuppiah, Thilakavathy; Nordin, Norshariza

    2017-03-01

    Amniotic fluid (AF) is now known to harbor highly potent stem cells, making it an excellent source for cell therapy. However, most of the stem cells isolated are from AF of mid-term pregnancies in which the collection procedure involves an invasive technique termed amniocentesis. This has limited the access in getting the fluid as the technique imposes certain level of risks to the mother as well as to the fetus. Alternatively, getting AF from full-term pregnancies or during deliveries would be a better resolution. Unfortunately, very few studies have isolated stem cells from AF at this stage of gestation, the fluid that is merely discarded. The question remains whether full-term AF harbors stem cells of similar potency as of the stem cells of mid-term AF. Here, we aim to review the prospect of having this type of stem cells by first looking at the origin and contents of AF particularly during different gestation period. We will then discuss the possibility that the AF, at full term, contains a population of highly potent stem cells. These stem cells are distinct from, and probably more potent than the AF mesenchymal stem cells (AF-MSCs) isolated from full-term AF. By comparing the studies on stem cells isolated from mid-term versus full-term AF from various species, we intend to address the prospect of having highly potent amniotic fluid stem cells from AF of full-term pregnancies in human and animals.

  5. X-ray excited Auger transitions of Pu compounds

    SciTech Connect

    Nelson, Art J. Grant, William K.; Stanford, Jeff A.; Siekhaus, Wigbert J.; Allen, Patrick G.; McLean, William

    2015-05-15

    X-ray excited Pu core–valence–valence and core–core–valence Auger line-shapes were used in combination with the Pu 4f photoelectron peaks to characterize differences in the oxidation state and local electronic structure for Pu compounds. The evolution of the Pu 4f core-level chemical shift as a function of sputtering depth profiling and hydrogen exposure at ambient temperature was quantified. The combination of the core–valence–valence Auger peak energies with the associated chemical shift of the Pu 4f photoelectron line defines the Auger parameter and results in a reliable method for definitively determining oxidation states independent of binding energy calibration. Results show that PuO{sub 2}, Pu{sub 2}O{sub 3}, PuH{sub 2.7}, and Pu have definitive Auger line-shapes. These data were used to produce a chemical state (Wagner) plot for select plutonium oxides. This Wagner plot allowed us to distinguish between the trivalent hydride and the trivalent oxide, which cannot be differentiated by the Pu 4f binding energy alone.

  6. Cosmic ray composition studies with the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Boncioli, Denise

    2014-04-01

    The Pierre Auger Observatory in Argentina is the largest cosmic ray detector array ever built. Although the construction was completed in 2008, the Observatory has been taking data continuously since January 2004. Its main goal is to measure ultra high energy cosmic rays (UHECRs, energy above 1018 eV) with unprecedented statistics and precision. Measurements of the energy spectrum, chemical composition (including neutrinos and photons) and arrival directions of UHECRs can provide hints for understanding their origin, propagation and interactions. The fluorescence detector of the Pierre Auger Observatory measures the atmospheric depth, Xmax, where the longitudinal profile of a high energy air shower reaches its maximum. This is sensitive to the nuclear mass composition of the cosmic ray and to the characteristics of the hadronic interactions at very high energy. Due to its hybrid design, the Pierre Auger Observatory also provides independent experimental observables obtained from the surface detector for the study of the shower development. A selection of the Pierre Auger Observatory results on the study of the UHECRs will be presented, focusing on composition results. In particular, the measurements and the different roles of the observables with respect to mass composition will be discussed.

  7. ET-22CONVECTION-ENHANCED DELIVERY OF THE AUGER-ELECTRON-EMITTER 125I-UdR: A HIGHLY EFFICIENT THERAPY IN AN ORTHOTOPIC GLIOBLASTOMA XENOGRAFT MODEL

    PubMed Central

    Halle, Bo; Thisgaard, Helge; Aaberg-Jessen, Charlotte; Olsen, Birgitte; Dam, Johan; Langkjær, Niels; Munthe, Sune; Någren, Kjell; Høilund-Carlsen, Poul Flemming; Kristensen, Bjarne

    2014-01-01

    BACKGROUND: Glioblastomas (GBMs), the most common and malignant primary brain tumors, always recur after standard treatment. In order to develop more efficient therapies, we tested a novel therapeutic approach using the radioactive Auger-electron-emitter (AEE) [125I]5-Iodo-2'-deoxyuridine (125I-UdR). This drug incorporates into DNA of dividing cells and upon decay emission of Auger-electrons causes clusters of double strand breaks leading to cell death. METHODS: In vitro, cells from two GBM spheroid cultures (T78 & T87) were exposed to either 125I-UdR or 127I-UdR (non-radioactive analogue) and tumor cell viability and migration were measured. In vivo, nude rats were implanted orthotopically with T87 cells and after tumor formation micro infusion pumps were implanted enabling direct intratumoral convection-enhanced delivery (CED). Animals were divided into three groups (I-III). Group I (n = 8) was treated with 127I-UdR by CED, group II (n = 7) with neoadjuvant methotrexate (MTX) + 125I-UdR by CED and group III with neoadjuvant MTX + 125I-UdR by CED and concomitant systemic temozolomide (TMZ). Rats were followed for 180 days post-treatment with repeated [11C]methylaminoisobutyric acid ([11C]MeAIB) positron emission tomography scans and blood sampling. Single photon emission computed tomography/computed tomography (SPECT/CT) scans were performed to evaluate 125I-UdR distribution. Additionally, post-mortem histological examination of brain, liver, kidneys and thyroid gland was performed. RESULTS: In vitro, 125I-UdR significantly decreased GBM cell viability and migration. In group I, no animals (8/8) survived longer than 23 days after treatment start. In group II, 4/7 animals survived the entire observation period of 180 days. In group III, all animals (8/8) survived the entire observation period. SPECT/CT showed a widespread intracerebral distribution of 125I-UdR, while blood samples and post-mortem histology revealed no signs of dose-limiting adverse effects

  8. Metastable states in NO2+ probed with Auger spectroscopy.

    PubMed

    Püttner, R; Sekushin, V; Fukuzawa, H; Uhlíková, T; Špirko, V; Asahina, T; Kuze, N; Kato, H; Hoshino, M; Tanaka, H; Thomas, T D; Kukk, E; Tamenori, Y; Kaindl, G; Ueda, K

    2011-11-07

    High-resolution N 1s and O 1s photoelectron spectra (PES) of NO are presented together with spectra of the subsequent Auger decay. The PES are analyzed by taking spin-orbit splitting of the (2)Π ground state into account providing detailed information on equilibrium distances, vibrational energies, and lifetime widths of the core-ionized states. In the Auger electron spectra (AES) transitions to five metastable dicationic final states are observed, with two of them previously unobserved. A Franck-Condon analysis of the vibrational progressions belonging to these transitions provides detailed information on the potential-energy curves of the dicationic final states as well as on the relative Auger rates. The present calculations of the potential-energy curves of NO(2+) agree well with the experimental results and allow an assignment of the two hitherto unresolved Auger transitions to excited states of NO(2+), C(2)Σ(+)and c(4)Π. This journal is © the Owner Societies 2011

  9. Localized versus delocalized excitations just above the 3d threshold in krypton clusters studied by Auger electron spectroscopy.

    PubMed

    Tchaplyguine, M; Kivimäki, A; Peredkov, S; Sorensen, S L; Ohrwall, G; Schulz, J; Lundwall, M; Rander, T; Lindblad, A; Rosso, A; Svensson, S; Mårtensson, N; Björneholm, O

    2007-09-28

    We present Auger spectroscopy studies of large krypton clusters excited by soft x-ray photons with energies on and just above the 3d(52) ionization threshold. The deexcitation spectra contain new features as compared to the spectra measured both below and far above threshold. Possible origins of these extra features, which stay at constant kinetic energies, are discussed: (1) normal Auger process with a postcollision interaction induced energy shift, (2) recapture of photoelectrons into high Rydberg orbitals after Auger decay, and (3) excitation into the conduction band (or "internal" ionization) followed by Auger decay. The first two schemes are ruled out, hence internal ionization remains the most probable explanation.

  10. First test results from the Front-End Board with Cyclone V as a test high-resolution platform for the Auger-Beyond-2015 Front End Electronics

    SciTech Connect

    Szadkowski, Zbigniew

    2015-07-01

    The paper presents the first results from the Front- End Board (FEB) with the biggest Cyclone{sup R} V E FPGA 5CEFA9F31I7N, supporting 8 channels sampled up to 250 MSps at 14-bit resolution. Considered sampling for the SD is 120 MSps, however, the FEB has been developed with external anti-aliasing filters to keep a maximal flexibility. Six channels are targeted to the SD, two the rest for other experiments like: Auger Engineering Radio Array and additional muon counters. More channels and higher sampling generate larger size of registered events. We used the standard radio channel for a radio transmission from the detectors to the Central Data Acquisition Station (CDAS) to avoid at present a significant modification of a software in both sides: the detector and the CDAS (planned in a future for a final design). Seven FEBs have been deployed in the test detectors on a dedicated Engineering Array in a hexagon. Several variants of the FPGA code were tested for 120, 160, 200 and even 240 MSps DAQ. Tests confirmed a stability and reliability of the FEB design in real pampas conditions with more than 40 deg. C daily temperature variation and a strong sun exposition with a limited power budget only from a single solar panel. (authors)

  11. Auger electron spectroscopy study of reactor walls in transition from an O{sub 2} to a Cl{sub 2} plasma

    SciTech Connect

    Guha, Joydeep; Donnelly, Vincent M.

    2009-05-15

    In plasma etching processes, the reactor wall conditions can change over time due to a number of intentional and unintentional reasons, leading to a variability in the radical number densities in the plasma, caused by changes in the probabilities for reactions such as recombination at the walls. This leads to loss of reproducibility in the etching process. Here the authors isolated one such effect in which the feed gas was changed in the absence of a substrate. The transient surface composition of an anodized aluminum surface was determined for inductively coupled plasmas as the gas was switched from Cl{sub 2} to O{sub 2} and vice versa. The study was carried out with the spinning wall method and Auger electron spectroscopy. When the surface was first conditioned in an O{sub 2} plasma and then exposed to Cl{sub 2} plasmas, a rapid uptake of Cl was found in the first tens of seconds, followed by a slow approach to a steady-state value within {approx}5 min of plasma exposure. Conversely, when the surface was exposed to a Cl{sub 2} plasma for a long time and then switched to an O{sub 2} plasma, the anodized aluminum surface underwent a rapid dechlorination in the first few seconds and then a slow approach to steady state over {approx}3 min. Throughout these treatments, the coverages of Si (from erosion of the quartz discharge tube) and O were nearly constant.

  12. Effect of Auger Recombination on Lasing in Heterostructured Quantum Dots with Engineered Core/Shell Interfaces.

    PubMed

    Park, Young-Shin; Bae, Wan Ki; Baker, Thomas; Lim, Jaehoon; Klimov, Victor I

    2015-11-11

    Nanocrystal quantum dots (QDs) are attractive materials for applications as laser media because of their bright, size-tunable emission and the flexibility afforded by colloidal synthesis. Nonradiative Auger recombination, however, hampers optical amplification in QDs by rapidly depleting the population of gain-active multiexciton states. In order to elucidate the role of Auger recombination in QD lasing and isolate its influence from other factors that might affect optical gain, we study two types of CdSe/CdS core/shell QDs with the same core radii and the same total sizes but different properties of the core/shell interface ("sharp" vs "smooth"). These samples exhibit distinctly different biexciton Auger lifetimes but are otherwise virtually identical. The suppression of Auger recombination in the sample with a smooth (alloyed) interface results in a notable improvement in the optical gain performance manifested in the reduction of the threshold for amplified spontaneous emission and the ability to produce dual-color lasing involving both the band-edge (1S) and the higher-energy (1P) electronic states. We develop a model, which explicitly accounts for the multiexciton nature of optical gain in QDs, and use it to analyze the competition between stimulated emission from multiexcitons and their decay via Auger recombination. These studies re-emphasize the importance of Auger recombination control for the realization of real-life QD-based lasing technologies and offer practical strategies for suppression of Auger recombination via "interface engineering" in core/shell structures.

  13. Nanodosimetry of Auger electrons: A case study from the decay of 125I and 0-18-eV electron stopping cross sections of cytosine

    NASA Astrophysics Data System (ADS)

    Michaud, M.; Bazin, M.; Sanche, L.

    2013-03-01

    Radiopharmaceuticals emitting Auger electrons are often injected into patients undergoing cancer treatment with targeted radionuclide therapy (TRT). In this type of radiotherapy, the radiation source is radial and most of the emitted primary particles are low-energy electrons (LEEs) having kinetic energies distributed mostly from zero to a few hundred electron volts with very short ranges in biological media. These LEEs generate a high density of energy deposits and clustered damage, thus offering a relative biological effectiveness comparable to that of alpha particles. In this paper, we present a simple model and corresponding measurements to assess the energy deposited near the site of the radiopharmaceuticals in TRT. As an example, a calculation is performed for the decay of a single 125I radionuclide surrounded by a 1-nm-radius spherical shell of cytosine molecules using the energy spectrum of LEEs emitted by 125I along with their stopping cross sections between 0 and 18 eV. The dose absorbed by the cytosine shell, which occupies a volume of 4 nm3, is extremely high. It amounts to 79 kGy per decay of which 3%, 39%, and 58% is attributed to vibrational excitations, electronic excitations, and ionization processes, respectively.

  14. An experimental comparison of the K- and L-Auger electron spectra generated in the decays of 140Nd and 111In.

    PubMed

    Yakushev, E A; Kovalík, A; Filosofov, D V; Korolev, N A; Lebedev, N A; Lubashevski, A V; Rösch, F; Novgorodov, A F

    2005-03-01

    The low-energy electron spectra generated in the decay of 140Nd have been measured using a combined electrostatic spectrometer adjusted to the 4, 7, and 35 eV instrumental resolution. In order to estimate the therapeutic potential of low-energy electrons associated with the decay of 140Nd, similar experiments have been performed with 111In. Relative Auger electron intensity ratios per decay are: 111In(K-Auger)/140Nd(K-Auger)=1.47(12), 111In(L-Auger) /140Nd(L-Auger)=1.1(4), and 111In(L-Auger [2.8-7 keV])/140Nd(L-Auger [2.8-7 keV])=0.24(11). The obtained K-Auger group intensity ratios have been compared with results of calculations. The good agreement found for the experimental and estimated values indicates that such information can be also derived using available nuclear and atomic data. The relative intensity of L-Auger electrons emitted within the 2.8-7 keV interval is higher for 140Nd by a factor of about 4 compared to 111In. As the L-Auger emission is dominating relative to that of the K-Auger group, this implicates that any potential endotherapeutic strategy using 140Nd-labelled targeting vectors requires a maximum accumulation of the endoradiotherapeutical close to the cell nucleus or the DNA of the tumour cell.

  15. The change of the LMM auger spectra in 3d-metals due to oxidation and its correlation with the change of the atomic magnetic moment.

    PubMed

    Zheltysheva, Olga R; Surnin, Dmitry V; Guy, Dmitry E; Gil'mutdinov, Faat Z; Ruts, Yuri V; Grebennikov, Vladimir I

    2005-12-01

    The surfaces of crystalline samples of 3d-metals (Mn, Fe, Co, Ni, and Cu) and their stoichiometric oxides have been studied by Auger spectroscopy. A correlation between the change in the LVV (L-inner level-valence-valence electron transition) Auger intensities and the change of the squares of the corresponding atomic-magnetic moments has been observed. This is because of the complicated nature of the Auger process. That is, the Auger electron emission is a result of the inner atomic level excitation by electron impact and Auger annihilation of the inner-level hole. Therefore, the Auger process has been considered a second-order process, and spin polarization of the valence states has been taken into account for the LMM (L-inner level-M-inner level-M-inner level electron transition) Auger spectra of 3d-metals.

  16. Ratioed scatter diagrams - An erotetic method for phase identification on complex surfaces using scanning Auger microscopy

    NASA Technical Reports Server (NTRS)

    Browning, R.

    1984-01-01

    By ratioing multiple Auger intensities and plotting a two-dimensional occupational scatter diagram while digitally scanning across an area, the number and elemental association of surface phases can be determined. This can prove a useful tool in scanning Auger microscopic analysis of complex materials. The technique is illustrated by results from an anomalous region on the reaction zone of a SiC/Ti-6Al-4V metal matrix composite material. The anomalous region is shown to be a single phase associated with sulphur and phosphorus impurities. Imaging of a selected phase from the ratioed scatter diagram is possible and may be a useful technique for presenting multiple scanning Auger images.

  17. Dynamics of Intraband and Interband Auger Processes in Colloidal Core-Shell Quantum Dots.

    PubMed

    Rabouw, Freddy T; Vaxenburg, Roman; Bakulin, Artem A; van Dijk-Moes, Relinde J A; Bakker, Huib J; Rodina, Anna; Lifshitz, Efrat; L Efros, Alexander; Koenderink, A Femius; Vanmaekelbergh, Daniël

    2015-10-27

    Conventional colloidal quantum dots (QDs) suffer from rapid energy losses by nonradiative (Auger) processes, leading to sub-ns lifetimes in all excited states but the lowest-energy single exciton. Suppression of interband Auger decay, such as biexciton Auger recombination, has been achieved with the design of heterostructured core-shell QDs. Auger-like processes are also believed to be responsible for rapid intraband hot-electron cooling in QDs. However, the simultaneous effect of shell growth on interband Auger recombination and intraband hot-electron cooling has not been addressed. Here we investigate how the growth of a CdS shell affects these two relaxation processes in CdSe/CdS core-shell QDs. Using a combination of ultrafast pump-push-probe spectroscopy on the QD ensemble and analysis of the photon statistics from single QDs, we find that Auger losses in the biexciton state are suppressed with increasing shell thickness, while hot-electron cooling remains unaffected. Calculations conducted within an eight-band k·p model confirm the experimental dependence of the biexciton Auger decay on the shell thickness, and provide insights into the factors determining the cooling rate of hot carriers.

  18. Surface-site-selective study of valence electronic states of a clean Si(111)-7x7 surface using Si L{sub 23}VV Auger electron and Si 2p photoelectron coincidence measurements

    SciTech Connect

    Kakiuchi, Takuhiro; Tahara, Masashi; Nagaoka, Shin-ichi; Hashimoto, Shogo; Fujita, Narihiko; Tanaka, Masatoshi; Mase, Kazuhiko

    2011-01-15

    Valence electronic states of a clean Si(111)-7x7 surface are investigated in a surface-site-selective way using high-resolution coincidence measurements of Si pVV Auger electrons and Si 2p photoelectrons. The Si L{sub 23}VV Auger electron spectra measured in coincidence with energy-selected Si 2p photoelectrons show that the valence band at the highest density of states in the vicinity of the rest atoms is shifted by {approx}0.95 eV toward the Fermi level (E{sub F}) relative to that in the vicinity of the pedestal atoms (atoms directly bonded to the adatoms). The valence-band maximum in the vicinity of the rest atoms, on the other hand, is shown to be shifted by {approx}0.53 eV toward E{sub F} relative to that in the vicinity of the pedestal atoms. The Si 2p photoelectron spectra of Si(111)-7x7 measured in coincidence with energy-selected Si L{sub 23}VV Auger electrons identify the topmost surface components, and suggest that the dimers and the rest atoms are negatively charged while the pedestal atoms are positively charged. Furthermore, the Si 2p-Si L{sub 23}VV photoelectron Auger coincidence spectroscopy directly verifies that the adatom Si 2p component (usually denoted by C{sub 3}) is correlated with the surface state just below E{sub F} (usually denoted by S{sub 1}), as has been observed in previous angle-resolved photoelectron spectroscopy studies.

  19. 30 CFR 77.1500 - Auger mining; planning.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Auger mining; planning. 77.1500 Section 77.1500... MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Auger Mining § 77.1500 Auger mining; planning. Auger mining shall be planned and conducted by the operator to...

  20. 30 CFR 77.1500 - Auger mining; planning.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Auger mining; planning. 77.1500 Section 77.1500... MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Auger Mining § 77.1500 Auger mining; planning. Auger mining shall be planned and conducted by the operator to...

  1. 30 CFR 77.1500 - Auger mining; planning.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Auger mining; planning. 77.1500 Section 77.1500... MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Auger Mining § 77.1500 Auger mining; planning. Auger mining shall be planned and conducted by the operator to...

  2. 30 CFR 77.1500 - Auger mining; planning.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Auger mining; planning. 77.1500 Section 77.1500... MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Auger Mining § 77.1500 Auger mining; planning. Auger mining shall be planned and conducted by the operator to...

  3. 30 CFR 77.1500 - Auger mining; planning.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Auger mining; planning. 77.1500 Section 77.1500... MANDATORY SAFETY STANDARDS, SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND COAL MINES Auger Mining § 77.1500 Auger mining; planning. Auger mining shall be planned and conducted by the operator to...

  4. The Pierre Auger Observatory status and the AugerPrime upgrade program

    NASA Astrophysics Data System (ADS)

    Martello, Daniele

    2017-06-01

    The nature and the origin of ultra-high energy cosmic rays (UHECRs), above 1017 eV, are still unknown. The Pierre Auger Observatory with its huge exposure provides us with a large set of high quality data. The analysis of these data has led to major breakthroughs in the last decade, but a coherent interpretation is still missing. To answer the open questions the Observatory has started a major upgrade, with an emphasis on improved mass composition determination using the surface detectors. The latest results and the planned detector upgrade will be presented. The expected performance and the improved physics sensitivity of the Observatory will be discussed.

  5. Analysis of switchgrass-derived bio-oil and associated aqueous phase generated in a semi-pilot scale auger pyrolyzer

    SciTech Connect

    Ren, Shoujie; Ye, X. Philip; Borole, Abhijeet P.; Kim, Pyoungchung; Labbé, Ncole

    2016-03-30

    To efficiently utilize water-soluble compounds in bio-oil and evaluate the potential effects of these compounds on processes such as microbial electrolysis, our study investigated the physico-chemical properties of bio-oil and the associated aqueous phase generated from switchgrass using a semi-pilot scale auger pyrolyzer. Combining separation and detection strategies with organic solvent extraction, an array of analytical instruments and methods were used to identify and quantify the chemical constituents. Separation of an aqueous phase from crude bio-oil was achieved by adding water (water: crude bio-oil at 4:1 in weight), which resulted in a partition of 61 wt.% of the organic compounds into a bio-oil aqueous phase (BOAP). GC/MS analysis for BOAP identified over 40 compounds of which 16 were quantified. Acetic acid, propionic acid, and levoglucosan are the major components in BOAP. In addition, a significant portion of chemicals that have the potential to be upgraded to hydrocarbon fuels were extracted to BOAP (77 wt.% of the alcohols, 61 wt.% of the furans, and 52 wt.% of the phenolic compounds in crude bio-oil). Valorization of the BOAP may require conversion methods capable of accommodating a very broad substrate specificity. Ultimately, a better separation strategy is needed to selectively remove the acidic and polar components from crude bio-oil to improve economic feasibility of biorefinery operations.

  6. Analysis of switchgrass-derived bio-oil and associated aqueous phase generated in a semi-pilot scale auger pyrolyzer

    DOE PAGES

    Ren, Shoujie; Ye, X. Philip; Borole, Abhijeet P.; ...

    2016-03-30

    To efficiently utilize water-soluble compounds in bio-oil and evaluate the potential effects of these compounds on processes such as microbial electrolysis, our study investigated the physico-chemical properties of bio-oil and the associated aqueous phase generated from switchgrass using a semi-pilot scale auger pyrolyzer. Combining separation and detection strategies with organic solvent extraction, an array of analytical instruments and methods were used to identify and quantify the chemical constituents. Separation of an aqueous phase from crude bio-oil was achieved by adding water (water: crude bio-oil at 4:1 in weight), which resulted in a partition of 61 wt.% of the organic compoundsmore » into a bio-oil aqueous phase (BOAP). GC/MS analysis for BOAP identified over 40 compounds of which 16 were quantified. Acetic acid, propionic acid, and levoglucosan are the major components in BOAP. In addition, a significant portion of chemicals that have the potential to be upgraded to hydrocarbon fuels were extracted to BOAP (77 wt.% of the alcohols, 61 wt.% of the furans, and 52 wt.% of the phenolic compounds in crude bio-oil). Valorization of the BOAP may require conversion methods capable of accommodating a very broad substrate specificity. Ultimately, a better separation strategy is needed to selectively remove the acidic and polar components from crude bio-oil to improve economic feasibility of biorefinery operations.« less

  7. Incident-beam effects in electron-stimulated Auger-electron diffraction

    NASA Astrophysics Data System (ADS)

    Gao, Y.; Cao, Jianming

    1991-04-01

    We have examined incident-beam effects in electron-stimulated Auger-electron diffraction (AED) on a cleaved GaAs(110) surface. The results indicate that incident-beam diffraction is significant in an AED experiment, and that the dissipative nature of the incident beam in contributing to the Auger process must be accounted for. We have developed a qualitative model that describes the trend of the polar-angle dependence of the Auger intensity for both the incident and exit beams. In calculating the diffraction features, we used a zeroth-order approximation to simulate the dissipation of the incident beam, which is found to adequately describe the experimental data.

  8. Results of a self-triggered prototype system for radio-detection of extensive air showers at the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Abreu, P.; Acounis, S.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Alves Batista, R.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Anti&cbreve; i'c, T.; Aramo, C.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenir, M.; Avila, G.; Badescu, A. M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Baughman, B.; Bäuml, J.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blaess, S. G.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Buchholz, P.; Bueno, A.; Buroker, L.; Burton, R. E.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, B.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Cester, R.; Charrier, D.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chirinos Diaz, J.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Cocciolo, G.; Colalillo, R.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Coutu, S.; Covault, C. E.; Criss, A.; Cronin, J.; Curutiu, J.; Dallier, R.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; De Donato, C.; de Jong, S. J.; De La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; del Peral, L.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Fang, K.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fliescher, S.; Fox, B.; Fracchiolla, C. E.; Fraenkel, E. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Garçon, T.; Garilli, G.; Gascon Bravo, A.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Gitto, J.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gorham, P.; Gouffon, P.; Grashorn, E.; Grebe, S.; Griffith, N.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huber, D.; Huege, T.; Insolia, A.; Ionita, F.; Jansen, S.; Jarne, C.; Jiraskova, S.; Josebachuili, M.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Katkov, I.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; LaHurd, D.; Latronico, L.; Lauer, R.; Lauscher, M.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Malacari, M.; Maldera, S.; Maller, J.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Martraire, D.; Masías Meza, J. J.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mayotte, E.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Messina, S.; Meurer, C.; Meyhandan, R.; Mi'canovi'c, S.; Micheletti, M. I.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nhung, P. T.; Niechciol, M.; Niemietz, L.; Nierstenhoefer, N.; Niggemann, T.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Olinto, A.; Oliveira, M.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Pȩkala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrolini, A.; Petrov, Y.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Ponce, V. H.; Pontz, M.; Porcelli, A.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rivière, C.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez Cabo, I.; Rodriguez Fernandez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saffi, S. J.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulz, J.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Sima, O.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Srivastava, Y. N.; Stanic, S.; Stapleton, J.; Stasielak, J.; Stassi, P.; Stephan, M.; Straub, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tapia, A.; Tartare, M.; Taşcău, O.; Tcaciuc, R.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tkaczyj, W.; Todero Peixoto, C. J.; Toma, G.; Tomankova, L.; Tomé, B.; Tonachini, A.; Torralba Elipe, G.; Torres Machado, D.; Travnicek, P.; Tridapalli, D. B.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van den Berg, A. M.; van Velzen, S.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Varner, G.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Westerhoff, S.; Whelan, B. J.; Widom, A.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano Garcia, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhou, J.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.

    2012-11-01

    We describe the experimental setup and the results of RAuger, a small radio-antenna array, consisting of three fully autonomous and self-triggered radio-detection stations, installed close to the center of the Surface Detector (SD) of the Pierre Auger Observatory in Argentina. The setup has been designed for the detection of the electric field strength of air showers initiated by ultra-high energy cosmic rays, without using an auxiliary trigger from another detection system. Installed in December 2006, RAuger was terminated in May 2010 after 65 registered coincidences with the SD. The sky map in local angular coordinates (i.e., zenith and azimuth angles) of these events reveals a strong azimuthal asymmetry which is in agreement with a mechanism dominated by a geomagnetic emission process. The correlation between the electric field and the energy of the primary cosmic ray is presented for the first time, in an energy range covering two orders of magnitude between 0.1 EeV and 10 EeV. It is demonstrated that this setup is relatively more sensitive to inclined showers, with respect to the SD. In addition to these results, which underline the potential of the radio-detection technique, important information about the general behavior of self-triggering radio-detection systems has been obtained. In particular, we will discuss radio self-triggering under varying local electric-field conditions.

  9. Temperature effects on Li4Ti5O12 electrode/electrolyte interfaces at the first cycle: A X-ray Photoelectron Spectroscopy and Scanning Auger Microscopy study

    NASA Astrophysics Data System (ADS)

    Gieu, J.-B.; Courrèges, C.; El Ouatani, L.; Tessier, C.; Martinez, H.

    2016-06-01

    Li4Ti5O12-based negative electrodes for Lithium-ion batteries are of interest because of the high reversibility of Li+ insertion/extraction. In this study, the surface of cycled electrodes is analysed by X-ray Photoelectron Spectroscopy (XPS) and Scanning Auger Microscopy (SAM) to investigate the effects of cycling temperature (room temperature, 60 °C and 85 °C) upon the solid electrolyte interphase (SEI) formation, which plays a major role in batteries electrochemical performances. Half-cells, with a vinylene carbonate containing electrolyte, are galvanostatically cycled at different steps of the first cycle: the mid-plateau during the first discharge, the end of the first discharge at 1.2 V and the end of the first charge at 2.0 V. XPS analysis evidences that higher temperatures promote the formation of a thicker SEI, which can explain the increase of the irreversible capacity with temperature. SAM mappings (allowing high spatial resolution ∼10-100 nm) evidence that this SEI homogeneously covers the electrode surface, regardless of the cycling temperature. During charge, the SEI is partially dissolved at room temperature, more slightly at 60 °C whereas at 85 °C, no clear evidence of layer thinning is observed. The SEI chemical composition is also investigated and reveals a majority of organic species and an increasing proportion of LiF with the temperature.

  10. Influence of the "surface effect" on the segregation parameters of S in Fe(100): A multi-scale modelling and Auger Electron Spectroscopy study

    NASA Astrophysics Data System (ADS)

    Barnard, P. E.; Terblans, J. J.; Swart, H. C.

    2015-12-01

    The article takes a new look at the process of atomic segregation by considering the influence of surface relaxation on the segregation parameters; the activation energy (Q), segregation energy (ΔG), interaction parameter (Ω) and the pre-exponential factor (D0). Computational modelling, namely Density Functional Theory (DFT) and the Modified Darken Model (MDM) in conjunction with Auger Electron Spectroscopy (AES) was utilized to study the variation of the segregation parameters for S in the surface region of Fe(100). Results indicate a variation in each of the segregation parameters as a function of the atomic layer under consideration. Values of the segregation parameters varied more dramatically as the surface layer is approached, with atomic layer 2 having the largest deviations in comparison to the bulk values. This atomic layer had the highest Q value and formed the rate limiting step for the segregation of S towards the Fe(100) surface. It was found that the segregation process is influenced by two sets of segregation parameters, those of the surface region formed by atomic layer 2, and those in the bulk material. This article is the first to conduct a full scale investigation on the influence of surface relaxation on segregation and labelled it the "surface effect".

  11. Analysis of passivated A-286 stainless steel surfaces for mass spectrometer inlet systems by Auger electron and X-ray photoelectron spectroscopy and scanning electron microscopy

    DOE PAGES

    Ajo, Henry; Blankenship, Donnie; Clark, Elliot

    2014-07-25

    In this study, various commercially available surface treatments are being explored for use on stainless steel components in mass spectrometer inlet systems. Type A-286 stainless steel coupons, approximately 12.5 mm in diameter and 3 mm thick, were passivated with one of five different surface treatments; an untreated coupon served as a control. The surface and near-surface microstructure and chemistry of the coupons were investigated using sputter depth profiling using Auger electron spectroscopy, x-ray photoelectron spectroscopy, and scanning electron microscopy (SEM). All the surface treatments studied appeared to change the surface morphology dramatically, as evidenced by lack of tool marks onmore » the treated samples in SEM images. In terms of the passivation treatment, Vendors A-D appeared to have oxide layers that were very similar in thickness to each other (0.7–0.9 nm thick), as well as to the untreated samples (the untreated sample oxide layers appeared to be somewhat larger). Vendor E’s silicon coating appears to be on the order of 200 nm thick.« less

  12. Analysis of passivated A-286 stainless steel surfaces for mass spectrometer inlet systems by Auger electron and X-ray photoelectron spectroscopy and scanning electron microscopy

    SciTech Connect

    Ajo, Henry; Blankenship, Donnie; Clark, Elliot

    2014-07-25

    In this study, various commercially available surface treatments are being explored for use on stainless steel components in mass spectrometer inlet systems. Type A-286 stainless steel coupons, approximately 12.5 mm in diameter and 3 mm thick, were passivated with one of five different surface treatments; an untreated coupon served as a control. The surface and near-surface microstructure and chemistry of the coupons were investigated using sputter depth profiling using Auger electron spectroscopy, x-ray photoelectron spectroscopy, and scanning electron microscopy (SEM). All the surface treatments studied appeared to change the surface morphology dramatically, as evidenced by lack of tool marks on the treated samples in SEM images. In terms of the passivation treatment, Vendors A-D appeared to have oxide layers that were very similar in thickness to each other (0.7–0.9 nm thick), as well as to the untreated samples (the untreated sample oxide layers appeared to be somewhat larger). Vendor E’s silicon coating appears to be on the order of 200 nm thick.

  13. 3,4-Disubstituted indole acylsulfonamides: a novel series of potent and selective human EP3 receptor antagonists.

    PubMed

    Zhou, Nian; Zeller, Wayne; Krohn, Michael; Anderson, Herb; Zhang, Jun; Onua, Emmanuel; Kiselyov, Alex S; Ramirez, Jose; Halldorsdottir, Gułrún; Andrésson, Thornorkell; Gurney, Mark E; Singh, Jasbir

    2009-01-01

    A series of potent and selective EP(3) receptor antagonists are described. Utilizing a pharmacophore model developed for the EP(3) receptor, a series of 3,4-disubstituted indoles were shown to be high affinity ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors and are potent antagonists in functional assays.

  14. Ultrafast and band-selective Auger recombination in InGaN quantum wells

    SciTech Connect

    Williams, Kristopher W.; Monahan, Nicholas R.; Zhu, X.-Y. E-mail: mhcrawf@sandia.gov; Koleske, Daniel D.; Crawford, Mary H. E-mail: mhcrawf@sandia.gov

    2016-04-04

    In InGaN quantum well based light-emitting diodes, Auger recombination is believed to limit the quantum efficiency at high injection currents. Here, we report the direct observation of carrier loss from Auger recombination on a sub-picosecond timescale in a single InGaN quantum well using time-resolved photoemission. Selective excitations of different valence sub-bands reveal that the Auger rate constant decreases by two orders of magnitude as the effective hole mass decreases, confirming the critical role of momentum conservation.

  15. Chemical effects of F KVV Auger spectra induced by photon impact

    NASA Astrophysics Data System (ADS)

    Uda, M.; Maeda, K.; Koyama, A.; Sasa, Y.

    1984-03-01

    F KVV Auger emissions were measured with NaF, MgF2, A1F3, and Teflon [(CF2)n], which were induced by photoionization. Chemical effects were reflected in line broadening and change in intensity ratios of the spectra emitted from singly and doubly ionized initial states, |K1L0> and |K1L1>. Reduction in Auger peak intensities which originated from |K1L1> is in the order of the covalencies of the fluorides or the natural widths of F L shells. This is caused by the refilling of a F L-shell vacancy by one of the ligand electrons prior to Auger emission.

  16. Identifying clouds over the Pierre Auger Observatory using infrared satellite data

    NASA Astrophysics Data System (ADS)

    Abreu, P.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Alves Batista, R.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antičić, T.; Aramo, C.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Badescu, A. M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Baughman, B.; Bäuml, J.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Buchholz, P.; Bueno, A.; Buroker, L.; Burton, R. E.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, B.; Caccianiga, L.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Cester, R.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chirinos, J.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Cocciolo, G.; Colalillo, R.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coutu, S.; Covault, C. E.; Criss, A.; Cronin, J.; Curutiu, A.; Dallier, R.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; de Jong, S. J.; De La Vega, G.; de Mello, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; del Peral, L.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Diaz, J. C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Fang, K.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fliescher, S.; Fox, B. D.; Fracchiolla, C. E.; Fraenkel, E. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Garilli, G.; Gascon Bravo, A.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Gitto, J.; Glaser, C.; Glass, H.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gorham, P.; Gouffon, P.; Grebe, S.; Griffith, N.; Grillo, A. F.; Grubb, T. D.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huber, D.; Huege, T.; Insolia, A.; Jansen, S.; Jarne, C.; Jiraskova, S.; Josebachuili, M.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Katkov, I.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Krause, R.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; LaHurd, D.; Latronico, L.; Lauer, R.; Lauscher, M.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Malacari, M.; Maldera, S.; Maller, J.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Mariş, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Martraire, D.; Masías Meza, J. J.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mayotte, E.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Messina, S.; Meyhandan, R.; Mićanović, S.; Micheletti, M. I.; Middendorf, L.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nhung, P. T.; Niechciol, M.; Niemietz, L.; Nierstenhoefer, N.; Niggemann, T.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Olinto, A.; Oliveira, M.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Peķala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrolini, A.; Petrov, Y.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Ponce, V. H.; Pontz, M.; Porcelli, A.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez Cabo, I.; Rodriguez Fernandez, G.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saffi, S. J.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F. G.; Schulz, J.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Sima, O.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Srivastava, Y. N.; Stanič, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Straub, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tapia, A.; Tartare, M.; Taşcău, O.; Tcaciuc, R.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Toma, G.; Tomankova, L.; Tomé, B.; Tonachini, A.; Torralba Elipe, G.; Torres Machado, D.; Travnicek, P.; Tridapalli, D. B.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van den Berg, A. M.; van Velzen, S.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Varner, G.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Westerhoff, S.; Whelan, B. J.; Widom, A.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano Garcia, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhou, J.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.

    2013-12-01

    We describe a new method of identifying night-time clouds over the Pierre Auger Observatory using infrared data from the Imager instruments on the GOES-12 and GOES-13 satellites. We compare cloud identifications resulting from our method to those obtained by the Central Laser Facility of the Auger Observatory. Using our new method we can now develop cloud probability maps for the 3000 km2 of the Pierre Auger Observatory twice per hour with a spatial resolution of ˜2.4 km by ˜5.5 km. Our method could also be applied to monitor cloud cover for other ground-based observatories and for space-based observatories.

  17. Auger electron intensity variations in oxygen-exposed large grain polycrystalline silver

    NASA Technical Reports Server (NTRS)

    Lee, W. S.; Outlaw, R. A.; Hoflund, G. B.; Davidson, M. R.

    1989-01-01

    Auger electron spectroscopic studies of the grains in oxygen-charged polycrystal-line silver show significant intensity variations as a function of crystallographic orientation. These intensity variations were observed by studies of the Auger images and line scans of the different grains (randomly selected) for each silver transition energy. The results can be attributed to the diffraction of the ejected Auger electrons and interpreted by corresponding changes in the electron mean-free path for inelastic scattering and by oxygen atom accumulation in the subsurface. The subsurface (second layer) octahedral sites increased in size because of surface relaxation and serve as a stable reservoir for the dissolved oxygen.

  18. Identifying clouds over the Pierre Auger Observatory using infrared satellite data

    SciTech Connect

    Abreu, Pedro; et al.,

    2013-12-01

    We describe a new method of identifying night-time clouds over the Pierre Auger Observatory using infrared data from the Imager instruments on the GOES-12 and GOES-13 satellites. We compare cloud identifications resulting from our method to those obtained by the Central Laser Facility of the Auger Observatory. Using our new method we can now develop cloud probability maps for the 3000 km^2 of the Pierre Auger Observatory twice per hour with a spatial resolution of ~2.4 km by ~5.5 km. Our method could also be applied to monitor cloud cover for other ground-based observatories and for space-based observatories.

  19. Discovery and gram-scale synthesis of BMS-593214, a potent, selective FVIIa inhibitor

    SciTech Connect

    Priestley, E. Scott; De Lucca, Indawati; Zhou, Jinglan; Zhou, Jiacheng; Saiah, Eddine; Stanton, Robert; Robinson, Leslie; Luettgen, Joseph M.; Wei, Anzhi; Wen, Xiao; Knabb, Robert M.; Wong, Pancras C.; Wexler, Ruth R.

    2013-02-14

    A 6-amidinotetrahydroquinoline screening hit was driven to a structurally novel, potent, and selective FVIIa inhibitor through a combination of library synthesis and rational design. An efficient gram-scale synthesis of the active enantiomer BMS-593214 was developed, which required significant optimization of the key Povarov annulation. Importantly, BMS-593214 showed antithrombotic efficacy in a rabbit arterial thrombosis model. A crystal structure of BMS-593214 bound to FVIIa highlights key contacts with Asp 189, Lys 192, and the S2 pocket.

  20. Latest results from the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Dembinski, Hans P.; Pierre Auger Collaboration

    2012-02-01

    The Pierre Auger Observatory, located in the Province of Mendoza, Argentina, is the World's largest detector for cosmic rays at ultra-high energies. In its seven years of operation it has collected an exposure of more than 20000 km2 sr yr, larger than all previous experiments combined. Its original design, optimized for the energy range 1018 eV to 1020 eV, is currently enhanced to cover energies down to almost 1017 eV. We give an overview of the latest results with a focus on the prospect to study nuclear interactions with cosmic rays and conclude with a brief outlook on developments and extensions of the observatory. Full author list

  1. Electrode surface studies by LEED-Auger

    NASA Technical Reports Server (NTRS)

    Ogrady, W. E.; Woo, M. Y. C.; Hagans, P. L.; Yeager, E.

    1977-01-01

    The role the electronic and geometric structures of the metal surface play in electrochemical surface reactions remains as yet an unknown factor. In order to investigate these surface contributions to electrochemical reactions, a low-energy-electron diffraction (LEED) and an Auger electron spectrometer (AES) have been combined with an electrochemical thin-layer cell. The surface to be studied electrochemically is first characterized by LEED-AES and then transferred into a second chamber where it becomes part of the electrochemical thin-layer cell. Electrochemical reactions are then run on this surface. The sample may then be transferred back to the LEED-AES chamber for further characterization. Data on Pt (111) will be presented.

  2. Auger analysis of silver-glass interfaces

    NASA Astrophysics Data System (ADS)

    Bastasz, R.

    1980-09-01

    Moderate annealing in vacuum of evaporated silver films on float glass (used as mirrors in solar energy concentrators) was found to have little effect on either the composition at the silver/glass interface or the profile of the boundary region. The interface remained free of any contaminants that could be detected by Auger spectroscopy. Limited diffusion of silver with glass components was observed, but the process resulted in only slight broadening of the interface during short annealing treatments and could be described by a diffusion coefficient of less than 1 x 10 to the -15th sq cm/s at 200 C. It is concluded that moderate annealing in the absence of contamination does not significantly alter the characteristics of a silver/glass interface.

  3. Site-selected Auger electron spectroscopy of N2O.

    PubMed

    Bolognesi, Paola; Coreno, Marcello; Avaldi, Lorenzo; Storchi, Loriano; Tarantelli, Francesco

    2006-08-07

    The N 1s Auger spectra for the two nonequivalent N atoms in N2O have been measured via Auger electron-photoelectron coincidence spectroscopy. The site-selected Auger spectra are compared with the normal Auger spectrum and with accurate theoretical calculations accounting for the effects of the dynamics of the nuclei on the energy and linewidth of the Auger bands. Such effects are found to be crucial factors in determining the different band shapes in the site-selected spectra.

  4. Current Status of the Pierre Auger Project

    NASA Astrophysics Data System (ADS)

    Etchegoyen, A.

    The Pierre Auger Project aims at building two Observatories in order to study ultra high energy cosmic rays, situated in both northern and southern hemispheres. In 2000 started the construction of the austral observatory. Prior to this, in 1995, the international collaboration was formed encompassing 200 scientists and technicians from institutions in 16 countries. The Auger Project is a basic science enterprise which studies the highest energies known in nature ( 1020 eV) , which are cosmic rays coming from the outer space arriving to the earth surface with at a very reduced flow. This is the reason for constructing a giant observatory spanning an area of 3000 km2 in the department of Malargüe and San Rafael, in the Province of Mendoza. Other distinctive feature, besides the exceptional size of the Observatory, is its hybrid nature: it is constituted by 24 fluorescence detector telescopes .and 1600 surface detectors. As such, it will provide a large number of events with less systematic detection uncertainties. The construction of the Observatory is quite advanced and the buildings at the Central Station in Malargüe city are already operational. So are the telescope buildings at Cerros Los Leones and Coihueco, two telescopes, 32 surface detectors, the telecommunication and data adquisión systems. From the scientific point of view the most important issue was the first detection of an hybrid event (a cosmic ray detected by both telescope and the surface detectors), on January 2002. It confirmed the equipment operates with the design parameters. Twenty hybrid events/month were detected with energies typically below 1019 eV.

  5. Generation of pure spin currents via Auger recombination in quantum wells with Rashba splitting

    SciTech Connect

    Afanasiev, A. N. Greshnov, A. A. Greshnov, A. A.

    2015-10-15

    We propose a nonoptical mechanism for generating spin current via Auger recombination in semiconductor quantum wells (QWs) with spin–orbit splitting associated with structural QW asymmetry. It is shown that Auger recombination in narrow-bandgap semiconductors makes it possible to produce spin currents that exceed those that are obtained in the case of intraband as well as interband optical excitation. Analysis shows that the interference term in the expression for the Auger-recombination rate is responsible for the generation of spin currents.

  6. 45-Day deliverable for Tank 241-BX-105 Auger samples, risers 2 and 6

    SciTech Connect

    Bell, K.E.

    1994-11-16

    Two auger samples from single-shell tank 241-BX-105 (BX-105) were extruded, broken down, and analyzed for DSC, TGA, and total alpha as prescribed. Analytical results were tracked and reported using the laboratory information management system known as LabCore. This is the final report for the fiscal year 1995 BX-105 auger sample characterization effort. Included are copies of the differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA) scans as requested. Also included is a copy of any immediate notification documentation, chain of custody forms, the hot cell work plan, extruded segment [auger] description sheets, and total alpha data.

  7. K-shell Auger lifetime variation in doubly ionized Ne and first row hydrides

    SciTech Connect

    Kolorenc, Premysl; Averbukh, Vitali

    2011-10-07

    We consider 1s Auger decay in doubly (core-core and core-valence) ionized Ne and in the isoelectronic first row element hydrides. We show theoretically that the presence of the spectator inner valence vacancy leads to Auger lifetime variation of up to about a factor of 2, relative to the Auger lifetimes in the singly ionized species. The origin of this effect is traced to spin selection rules. Implications on the modelling of the radiation damage in strong x-ray fields are discussed.

  8. Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A

    PubMed Central

    Lu, Yingying; Dong, Shichen; Hao, Baixia; Li, Chang; Zhu, Kaiyuan; Guo, Wenjing; Wang, Qian; Cheung, King-Ho; Wong, Connie WM; Wu, Wu-Tian; Markus, Huss; Yue, Jianbo

    2014-01-01

    Autophagy is a catabolic lysosomal degradation process essential for cellular homeostasis and cell survival. Dysfunctional autophagy has been associated with a wide range of human diseases, e.g., cancer and neurodegenerative diseases. A large number of small molecules that modulate autophagy have been widely used to dissect this process and some of them, e.g., chloroquine (CQ), might be ultimately applied to treat a variety of autophagy-associated human diseases. Here we found that vacuolin-1 potently and reversibly inhibited the fusion between autophagosomes and lysosomes in mammalian cells, thereby inducing the accumulation of autophagosomes. Interestingly, vacuolin-1 was less toxic but at least 10-fold more potent in inhibiting autophagy compared with CQ. Vacuolin-1 treatment also blocked the fusion between endosomes and lysosomes, resulting in a defect in general endosomal-lysosomal degradation. Treatment of cells with vacuolin-1 alkalinized lysosomal pH and decreased lysosomal Ca2+ content. Besides marginally inhibiting vacuolar ATPase activity, vacuolin-1 treatment markedly activated RAB5A GTPase activity. Expression of a dominant negative mutant of RAB5A or RAB5A knockdown significantly inhibited vacuolin-1-induced autophagosome-lysosome fusion blockage, whereas expression of a constitutive active form of RAB5A suppressed autophagosome-lysosome fusion. These data suggest that vacuolin-1 activates RAB5A to block autophagosome-lysosome fusion. Vacuolin-1 and its analogs present a novel class of drug that can potently and reversibly modulate autophagy. PMID:25483964

  9. A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent Hormonal Therapies

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0275 TITLE: A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent...TYPE Annual 3. DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Changing Landscape of Advanced Prostate Cancer...not curative, and all patients ultimately develop resistance. Therefore, the clinical and molecular landscape of advanced prostate cancer is changing

  10. 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

  11. A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

    PubMed Central

    Zhao, Ji-An; Sang, Mei-Xiang; Geng, Cui-Zhi; Wang, Shi-Jie; Shan, Bao-En

    2016-01-01

    Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta-1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK-HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN-bearing non-treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR. PMID:27895800

  12. Survey of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Dova, T.; Pierre Auger Observatory Collaboration

    The question of the origin and nature of cosmic ray particles with energies exceeding the predicted GZK spectral cutoff is one of the present great challenges of astroparticle physics. The Pierre Auger Observatory (PAO), currently under construction in Province of Mendoza, Argentina, is a broadly based international effort to explore the upper-end of the cosmic ray energy spectrum. The PAO is the first experiment designed to work in a hybrid detection mode. The combination of two complementary detection techniques -water Cerenkov tank arrays overlooked by atmospheric fluorescence detectorsto observe extensive air showers guarantees high-quality and statistically significant data. An updated overview of the science prospects for the PAO is presented. The concept of the experiment as well as the current status is described. 1 Physics motivation for the Pierre Auger Observatory The puzzle set by the existence of cosmic rays with energies above 1020 eV (Lawrence et al., 1991; Hayashida et al., 1994; Bird et al., 1995; Abu-Zayyad et al, 1999), which may be an indication of new physics or exotic particles, is at present one of the hot topics in high energy astroparticle physics. The underlying problem in trying to explain the origin of these extremely high energy cosmic rays (EHECR) is the well-known GZK (Greisen-Zatsepin-Kuzmin) effect: if the cosmic rays are extragalactic in origin, then a sharp cutoff at around several times 1019 eV in the observed spectrum is expected due to energy degradation of the cosmic ray particles through interaction with photons of the microwave background radiation (Greisen, 1965; Zatsepin and Kuzmin, 1966). This process limits the distance of the sources of particles with energies above 1020 eV to less than 100 Mpc from the Earth (Aharonian and Cronin, 1994; Puget et al., 1976; Stecker and Salomon, 1999; Berezinsky, 1970; Protheroe and Biermann, 1996). Since the energy loss mechanism depends on

  13. 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.

  14. "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.

  15. O-(Triazolyl)methyl carbamates as a novel and potent class of FAAH inhibitors

    PubMed Central

    Colombano, Giampiero; Albani, Clara; Ottonello, Giuliana; Ribeiro, Alison; Scarpelli, Rita; Tarozzo, Glauco; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele; Bandiera, Tiziano

    2015-01-01

    Inhibition of fatty acid amide hydrolase (FAAH) activity is under investigation as a valuable strategy for the treatment of several disorders, including pain and drug addiction. A number of potent FAAH inhibitors belonging to different chemical classes have been disclosed. O-aryl carbamates are one of the most representative families. In the search for novel FAAH inhibitors, we synthesized a series of O-(1,2,3-triazol-4-yl)methyl carbamate derivatives exploiting the copper-catalyzed [3 + 2] cycloaddition reaction between azides and alkynes (click chemistry). We explored structure-activity relationships within this new class of compounds and identified potent inhibitors of both rat and human FAAH with IC50 values in the single-digit nanomolar range. PMID:25338703

  16. Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site

    PubMed Central

    Pan, Chang; Liu, Hong-Da; Gong, Zheng; Yu, Xiao; Hou, Xu-Ben; Xie, Di-Dong; Zhu, Xi-Bin; Li, Hao-Wen; Tang, Jun-Yi; Xu, Yun-Fei; Yu, Jia-Qi; Zhang, Lian-Ying; Fang, Hao; Xiao, Kun-Hong; Chen, Yu-Guo; Wang, Jiang-Yun; Pang, Qi; Chen, Wei; Sun, Jin-Peng

    2013-01-01

    The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases. Kinetic studies revealed that cadmium inhibits PPM phosphatases through the M1 metal ion binding site. In particular, the negative charged D441 in PPM1G specific recognized cadmium. Our results suggest that cadmium is likely a potent inhibitor of most PPM family members except for PHLPPs. Furthermore, we demonstrated that cadmium inhibits PPM1A-regulated MAPK signaling and PPM1G-regulated AKT signaling potently in vivo. Cadmium reversed PPM1A-induced cell cycle arrest and cadmium insensitive PPM1A mutant rescued cadmium induced cell death. Taken together, these findings provide a better understanding of the effects of the toxicity of cadmium in the contexts of human physiology and pathology. PMID:23903585

  17. Cadmium is a potent inhibitor of PPM phosphatases and targets the M1 binding site.

    PubMed

    Pan, Chang; Liu, Hong-Da; Gong, Zheng; Yu, Xiao; Hou, Xu-Ben; Xie, Di-Dong; Zhu, Xi-Bin; Li, Hao-Wen; Tang, Jun-Yi; Xu, Yun-Fei; Yu, Jia-Qi; Zhang, Lian-Ying; Fang, Hao; Xiao, Kun-Hong; Chen, Yu-Guo; Wang, Jiang-Yun; Pang, Qi; Chen, Wei; Sun, Jin-Peng

    2013-01-01

    The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases. Kinetic studies revealed that cadmium inhibits PPM phosphatases through the M1 metal ion binding site. In particular, the negative charged D441 in PPM1G specific recognized cadmium. Our results suggest that cadmium is likely a potent inhibitor of most PPM family members except for PHLPPs. Furthermore, we demonstrated that cadmium inhibits PPM1A-regulated MAPK signaling and PPM1G-regulated AKT signaling potently in vivo. Cadmium reversed PPM1A-induced cell cycle arrest and cadmium insensitive PPM1A mutant rescued cadmium induced cell death. Taken together, these findings provide a better understanding of the effects of the toxicity of cadmium in the contexts of human physiology and pathology.

  18. Metofluthrin: a potent new synthetic pyrethroid with high vapor activity against mosquitoes.

    PubMed

    Ujihara, Kazuya; Mori, Tatsuya; Iwasaki, Tomonori; Sugano, Masayo; Shono, Yoshinori; Matsuo, Noritada

    2004-01-01

    (1R)-trans-Norchrysanthemic acid fluorobenzyl esters are synthesized and their structure-activity relationships are discussed. These esters show outstanding insecticidal activity against mosquitoes. In particular, the 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl analog (metofluthrin) exhibits the highest potency, being approximately forty times as potent as d-allethrin in a mosquito coil formulation when tested against southern house mosquitoes (Culex quinquefasciatus). Metofluthrin also exhibits a significant vapor action at room temperature.

  19. Comment on 'Hunting long-lived gluinos at the Pierre Auger Observatory'

    SciTech Connect

    Kopenkin, V.; Fujimoto, Y.; Sinzi, T.

    2008-06-15

    A Comment on the article by Anchordoqui et al. 'Hunting long-lived gluinos at the Pierre Auger Observatory' [L. A. Anchordoqui, A. Delgado, C. A. Garcia Canal, and S. J. Sciutto, Phys. Rev. D 77, 023009 (2008)].

  20. Potent antitumor activity of a urokinase-activated engineered anthrax toxin

    NASA Astrophysics Data System (ADS)

    Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

    2003-01-01

    The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

  1. A Synthetic 7,8-Dihydroxyflavone Derivative Promotes Neurogenesis and Exhibits Potent Antidepressant Effect

    PubMed Central

    Liu, Xia; Chan, Chi-Bun; Jang, Sung-Wuk; Pradoldej, Sompol; Huang, Junjian; He, Kunyan; Phun, Lien H.; France, Stefan; Xiao, Ge; Jia, Yonghui; Luo, Hongbo R.; Ye, Keqiang

    2011-01-01

    7,8-Dihydroxyflavone is a recently identified small molecular tropomyosin-receptor-kinase B (TrkB) agonist. Our preliminary structural activity relationship (SAR) study showed that the 7,8-dihydroxy groups are essential for the agonistic effect. To improve the lead compound's agonistic activity, we have conducted an extensive SAR study and synthesized numerous derivatives. We have successfully identified 4'-dimethylamino-7,8-dihydroxyflavone that displays higher TrkB agonistic activity than the lead. This novel compound also exhibits a more robust and longer TrkB activation effect in animals. Consequently, this new compound reveals more potent anti-apoptotic activity. Interestingly, chronic oral administration of 4'-dimethylamino-7,8-dihydroxyflavone and its lead strongly promotes neurogenesis in dentate gyrus and demonstrates marked antidepressant effects. Hence, our data support that the synthetic 4'-dimethylamino-7,8-dihydroxyflavone and its lead both are orally bioavailable TrkB agonists and possess potent antidepressant effects. PMID:21073191

  2. A-ring modified betulinic acid derivatives as potent cancer preventive agents.

    PubMed

    Hung, Hsin-Yi; Nakagawa-Goto, Kyoko; Tokuda, Harukuni; Iida, Akira; Suzuki, Nobutaka; Bori, Ibrahim D; Qian, Keduo; Lee, Kuo-Hsiung

    2014-02-01

    Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1×10(3) mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5×10(2), 1×10(2), and 1×10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.

  3. Combretastatin linked 1,3,4-oxadiazole conjugates as a Potent Tubulin Polymerization inhibitors.

    PubMed

    Kamal, Ahmed; Srikanth, P S; Vishnuvardhan, M V P S; Kumar, G Bharath; Suresh Babu, Korrapati; Hussaini, S M Ali; Kapure, Jeevak Sopanrao; Alarifi, Abdullah

    2016-04-01

    A new class of combretastatin linked 1,3,4-oxadiazoles were designed, synthesized and screened for their cytotoxic activity against five human cancer cell lines such as HeLa, DU-145, A549, MDA-MB-231 and B16. These compounds showed significant cytotoxicity with IC50 values in the range 0.118-54.32μM. Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line. Flow cytometric analysis revealed that these compounds arrested the cell cycle in G2/M phase. Moreover, the tubulin polymerization assay and immunofluorescence analysis indicate that 5m exhibits potent inhibitory effect on the tubulin assembly. Further, DNA fragmentation and Hoecst staining assays confirm that 5m induces apoptosis. Molecular docking studies and competitive binding assay indicated that 5m effectively bind at the colchicine binding site of the tubulin.

  4. 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

  5. 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

  6. UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor.

    PubMed

    Zhang, Weihe; DeRyckere, Deborah; Hunter, Debra; Liu, Jing; Stashko, Michael A; Minson, Katherine A; Cummings, Christopher T; Lee, Minjung; Glaros, Trevor G; Newton, Dianne L; Sather, Susan; Zhang, Dehui; Kireev, Dmitri; Janzen, William P; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2014-08-28

    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.

  7. The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A.

    PubMed

    Li, M; Makkinje, A; Damuni, Z

    1996-05-10

    Two potent heat-stable protein phosphatase 2A (PP2A) inhibitor proteins designated I1PP2A and I2PP2A have been purified to apparent homogeneity from extracts of bovine kidney (Li, M., Guo, H., and Damuni, Z. (1995) Biochemistry 34, 1988-1996). N-terminal and internal amino acid sequencing indicated that I2PP2A was a truncated form of SET, a largely nuclear protein that is fused to nucleoporin Nup214 in acute non-lymphocytic myeloid leukemia. Experiments using purified preparations of recombinant human SET confirmed that this protein inhibited PP2A. Half-maximal inhibition of the phosphatase occurred at about 2 nM SET. By contrast, SET (up to 20 nM) did not affect the activities of purified preparations of protein phosphatases 1, 2B, and 2C. The results indicate that SET is a potent and specific inhibitor of PP2A and suggest that impaired regulation of PP2A may contribute to acute myeloid leukemogenesis.

  8. Identification of a potent microbial lipid antigen for diverse Natural Killer T cells1

    PubMed Central

    Wolf, Benjamin J.; Tatituri, Raju V. V.; Almeida, Catarina F.; Le Nours, Jérôme; Bhowruth, Veemal; Johnson, Darryl; Uldrich, Adam P.; Hsu, Fong-Fu; Brigl, Manfred; Besra, Gurdyal S.; Rossjohn, Jamie; Godfrey, Dale I.; Brenner, Michael B.

    2016-01-01

    Invariant Natural Killer T (iNKT) cells are a well-characterized CD1d-restricted T cell subset. The availability of potent antigens and tetramers for iNKT cells has allowed this population to be extensively studied and has revealed their central roles in infection, autoimmunity, and tumor immunity. In contrast, diverse Natural Killer T (dNKT) cells are poorly understood because the lipid antigens they recognize are largely unknown. We sought to identify dNKT cell lipid antigen(s) by interrogating a panel of dNKT mouse cell hybridomas with lipid extracts from the pathogen Listeria monocytogenes. We identified Listeria phosphatidylglycerol (PG) as a microbial antigen that was significantly more potent than a previously characterized dNKT cell antigen, mammalian PG. Further, while mammalian PG loaded CD1d tetramers did not stain dNKT cells, the Listeria-derived PG loaded tetramers did. The structure of Listeria PG was distinct from mammalian PG since it contained shorter, fully-saturated anteiso fatty acid lipid tails. CD1d binding lipid displacement studies revealed that the microbial PG antigen binds significantly better to CD1d than counterparts with the same headgroup. These data reveal a highly-potent microbial lipid antigen for a subset of dNKT cells and provide an explanation for its increased antigen potency compared to the mammalian counterpart. PMID:26254340

  9. Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist

    PubMed Central

    Cascio, MG; Gauson, LA; Stevenson, LA; Ross, RA; Pertwee, RG

    2010-01-01

    Background and purpose: Cannabis is the source of at least seventy phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [35S]GTPγS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [3H]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent α2-adrenoceptor agonist (EC50= 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent KB= 51.9 nM). At 10 µM, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be α2-adrenoceptor-mediated (EC50= 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate α2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [35S]GTPγS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain. PMID:20002104

  10. Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist.

    PubMed

    Cascio, M G; Gauson, L A; Stevenson, L A; Ross, R A; Pertwee, R G

    2010-01-01

    Cannabis is the source of at least seventy phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Delta(9)-tetrahydrocannabinol, cannabidiol and Delta(9)-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. The [(35)S]GTPgammaS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [(3)H]CP55940 from mouse CB(1) and human CB(2) cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. In the brain membrane experiments, cannabigerol behaved as a potent alpha(2)-adrenoceptor agonist (EC(50)= 0.2 nM) and antagonized the 5-HT(1A) receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent K(B)= 51.9 nM). At 10 microM, it also behaved as a CB(1) receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be alpha(2)-adrenoceptor-mediated (EC(50)= 72.8 nM) and displayed significant affinity for mouse CB(1) and human CB(2) receptors. This investigation has provided the first evidence that cannabigerol can activate alpha(2)-adrenoceptors, bind to cannabinoid CB(1) and CB(2) receptors and block CB(1) and 5-HT(1A) receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [(35)S]GTPgammaS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain.

  11. 1,3,4-Thiadiazoles: a potent multi targeted pharmacological scaffold.

    PubMed

    Haider, Saqlain; Alam, Mohammad Sarwar; Hamid, Hinna

    2015-03-06

    Despite a significant work on thiadiazoles, continuous efforts are still being made to identify novel heterocyclic compounds with potent biological activities. This review may help the medicinal chemists to develop new leads possessing 1,3,4-thiadiazole nucleus with higher efficacy and reduced side effects. This review throws light on the detailed synthetic approaches which have been used for the synthesis of thiadiazoles. This has been followed by the in depth analysis of the thiadiazoles with respect to their medicinal significance.

  12. 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

  13. A Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3)**

    PubMed Central

    Kaniskan, H. Ümit; Szewczyk, Magdalena M.; Yu, Zhengtian; Eram, Mohammad S.; Yang, Xiaobao; Schmidt, Keith; Luo, Xiao; Dai, Miao; He, Feng; Zang, Irene; Lin, Ying; Kennedy, Steven; Li, Fengling; Dobrovetsky, Elena; Dong, Aiping; Smil, David; Min, Sun-Joon; Landon, Melissa; Lin-Jones, Jennifer; Huang, Xi-Ping; Roth, Bryan L.; Schapira, Matthieu; Atadja, Peter; Barsyte-Lovejoy, Dalia; Arrowsmith, Cheryl H.; Brown, Peter J.; Zhao, Kehao; Jin, Jian; Vedadi, Masoud

    2015-01-01

    PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is essential for maturation of ribosomes, may have a role in lipogenesis, and is implicated in several diseases. A potent, selective, and cell- active PRMT3 inhibitor would be a valuable tool for further investigating PRMT3 biology. Here we report the discovery of the first PRMT3 chemical probe, SGC707, by structure-based optimization of the allosteric PRMT3 inhibitors we reported previously, and thorough characterization of this probe in biochemical, biophysical, and cellular assays. SGC707 is a potent PRMT3 inhibitor (IC50 = 31 ± 2 nm, KD = 53 ± 2 nm) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non-epigenetic targets). The mechanism of action studies and crystal structure of the PRMT3-SGC707 complex confirm the allosteric inhibition mode. Importantly, SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies. This well- characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease. PMID:25728001

  14. The preclinical biology of a new potent and selective progestin: trimegestone.

    PubMed

    Winneker, Richard C; Bitran, Daniel; Zhang, Zhiming

    2003-11-01

    Trimegestone (TMG) is a 19-norpregnane progestin being developed, in combination with an estrogen, for the treatment of postmenopausal symptoms. TMG binds to the human progesterone receptor with an affinity greater than medroxyprogesterone acetate (MPA), norethindrone (NET), and levonorgestrel (LNG). In contrast, TMG binds with low affinity to the androgen, glucocorticoid and mineralocorticoid receptor and has no measurable affinity for the estrogen receptor. Compared to other progestins, TMG demonstrates an improved separation of its PR affinity from its affinity to other classical steroid hormone receptors. In vivo, TMG has potent progestin activity. For example, TMG produces glandular differentiation of the uterine endometrium in rabbits and is about 30 and 60 times more potent than MPA and NET, respectively. In the rat, TMG maintains pregnancy, induces deciduoma formation, inhibits ovulation and has uterine anti-estrogenic activity. With respect to these endpoints, TMG appears to be more potent and selective on uterine epithelial responses than other classical progestin responses. In vivo, TMG does not have significant androgenic, glucocorticoid, anti-glucocorticoid or mineralocorticoid activity but does have anti-mineralocorticoid activity and modest anti-androgenic effects. This overall profile is qualitatively similar to progesterone. When TMG is administered chronically, it antagonizes the effect of estradiol on the uterus but does not antagonize the beneficial bone sparing activity of estradiol. In rat studies evaluating CNS GABAA receptor modulatory activity, TMG is less active on this likely undesirable endpoint than progesterone and norethindrone acetate, which may translate into fewer mood-related side effects. The results indicate that TMG is a potent and selective progestin with a preclinical profile well suited for hormone replacement therapy.

  15. Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors.

    PubMed

    Wang, Qi-Qin; Cheng, Ning; Zheng, Xiao-Wei; Peng, Sheng-Ming; Zou, Xiao-Qing

    2013-07-15

    Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC50 values ranging from (0.099±0.008) μM to (2.833±0.102) μM. O(7)-Nitrooxyethyl-O(3'),O(4')-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50=(0.099±0.008) μM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications.

  16. Adenosine Receptor Prodrugs: Synthesis and Biological Activity of Derivatives of Potent, A1-Selective Agonists

    PubMed Central

    Maillrad, Michel C.; Nikodijević, Olga; LaNoue, Kathryn F.; Berkich, Deborah; Xiao-duo, JI; Bartus, Raymond

    2012-01-01

    5′-Ester derivatives of the potent adenosine agonists N6-[4-[[[[4-[[[(2-acetylaminoethyl)amino] carbonyl] methyl] anilino] carbonyl] methyl] phenyl] adenosine (N-AcADAC; 1) and N6-cyclopentyladenosine (CPA; 2) were prepared as prodrugs. Both alkyl esters or carbonates (designed to enter the brain by virtue of increased lipophilicity) and 1,4-dihydro-1-methyl-3- [(pyridinylcarbonyl)oxy] esters designed to concentrate in the brain by virtue of a redox delivery system were synthesized. In the 5′-blocked form, the adenosine agonists displayed highly diminished affinity for rat brain A1-adenosine receptors in binding assays. The dihydropyridine prodrug 29 was active in an assay of locomotor depression in mice, in which adenosine agonists are highly depressant. The behavior depression was not reversible by peripheral administration of a non-central nervous system active adenosine antagonist. In an assay of the peripheral action of adenosine (i.e., the inhibition of lipolysis in rats), the parent compounds were highly potent and the dihydropyridine prodrug was much less potent. PMID:8138909

  17. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.

    PubMed

    Chen, D Z; Patel, D V; Hackbarth, C J; Wang, W; Dreyer, G; Young, D C; Margolis, P S; Wu, C; Ni, Z J; Trias, J; White, R J; Yuan, Z

    2000-02-15

    Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

  18. A Class of 5-Nitro-2-furancarboxylamides with Potent Trypanocidal Activity against Trypanosoma brucei in Vitro

    PubMed Central

    2013-01-01

    Recently, the World Health Organization approved the nifurtimox–eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, ∼1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness. PMID:23281892

  19. Insight on hole-hole interaction and magnetic order from dichroic auger-photoelectron coincidence spectra.

    PubMed

    Cini, M; Perfetto, E; Gotter, R; Offi, F; Ruocco, A; Stefani, G

    2011-11-18

    The absence of sharp structures in the Auger line shapes of partially filled bands has severely limited the use of electron spectroscopy in magnetic crystals and other correlated materials. By a novel interplay of experimental and theoretical techniques we achieve a combined understanding of the photoelectron, Auger, and Auger-photoelectron coincidence spectra (APECS) of the antiferromagnetic CoO. A recently discovered dichroic effect in angle resolved (DEAR) APECS reveals a complex pattern in the Auger line shape, which is here explained in detail, labeling the final states by their total spin. Since the dichroic effect exists in the antiferromagnetic state but vanishes at the Néel temperature, the DEAR-APECS technique detects the phase transition from its local effects, thus providing a unique tool to observe and understand magnetic correlations where the usual methods are not applicable.

  20. Low-energy Auger electron diffraction: influence of multiple scattering and angular momentum

    NASA Astrophysics Data System (ADS)

    Chassé, A.; Niebergall, L.; Kucherenko, Yu.

    2002-04-01

    The angular dependence of Auger electrons excited from single-crystal surfaces is treated theoretically within a multiple-scattering cluster model taking into account the full Auger transition matrix elements. In particular the model has been used to discuss the influence of multiple scattering and angular momentum of the Auger electron wave on Auger electron diffraction (AED) patterns in the region of low kinetic energies. Theoretical results of AED patterns are shown and discussed in detail for Cu(0 0 1) and Ni(0 0 1) surfaces, respectively. Even though Cu and Ni are very similar in their electronic and scattering properties recently strong differences have been found in AED patterns measured in the low-energy region. It is shown that the differences may be caused to superposition of different electron diffraction effects in an energy-integrated experiment. A good agreement between available experimental and theoretical results has been achieved.

  1. Overcoming Auger recombination in nanocrystal quantum dot laser using spontaneous emission enhancement.

    PubMed

    Gupta, Shilpi; Waks, Edo

    2014-02-10

    We propose a method to overcome Auger recombination in nanocrystal quantum dot lasers using cavity-enhanced spontaneous emission. We derive a numerical model for a laser composed of nanocrystal quantum dots coupled to optical nanocavities with small mode-volume. Using this model, we demonstrate that spontaneous emission enhancement of the biexciton transition lowers the lasing threshold by reducing the effect of Auger recombination. We analyze a photonic crystal nanobeam cavity laser as a realistic device structure that implements the proposed approach.

  2. Auger electron angular distribution of double core-hole states in the molecular reference frame.

    PubMed

    Cryan, James P; Glownia, J M; Andreasson, J; Belkacem, A; Berrah, N; Blaga, C I; Bostedt, C; Bozek, J; Buth, C; DiMauro, L F; Fang, L; Gessner, O; Guehr, M; Hajdu, J; Hertlein, M P; Hoener, M; Kornilov, O; Marangos, J P; March, A M; McFarland, B K; Merdji, H; Petrović, V S; Raman, C; Ray, D; Reis, D; Tarantelli, F; Trigo, M; White, J L; White, W; Young, L; Bucksbaum, P H; Coffee, R N

    2010-08-20

    The Linac Coherent Light Source free electron laser is a source of high brightness x rays, 2×10(11) photons in a ∼5 fs pulse, that can be focused to produce double core vacancies through rapid sequential ionization. This enables double core vacancy Auger electron spectroscopy, an entirely new way to study femtosecond chemical dynamics with Auger electrons that probe the local valence structure of molecules near a specific atomic core. Using 1.1 keV photons for sequential x-ray ionization of impulsively aligned molecular nitrogen, we observed a rich single-site double core vacancy Auger electron spectrum near 413 eV, in good agreement with ab initio calculations, and we measured the corresponding Auger electron angle dependence in the molecular frame.

  3. Auger Electron Angular Distribution of Double Core-Hole States in the Molecular Reference Frame

    NASA Astrophysics Data System (ADS)

    Cryan, James P.; Glownia, J. M.; Andreasson, J.; Belkacem, A.; Berrah, N.; Blaga, C. I.; Bostedt, C.; Bozek, J.; Buth, C.; Dimauro, L. F.; Fang, L.; Gessner, O.; Guehr, M.; Hajdu, J.; Hertlein, M. P.; Hoener, M.; Kornilov, O.; Marangos, J. P.; March, A. M.; McFarland, B. K.; Merdji, H.; Petrović, V. S.; Raman, C.; Ray, D.; Reis, D.; Tarantelli, F.; Trigo, M.; White, J. L.; White, W.; Young, L.; Bucksbaum, P. H.; Coffee, R. N.

    2010-08-01

    The Linac Coherent Light Source free electron laser is a source of high brightness x rays, 2×1011 photons in a ˜5fs pulse, that can be focused to produce double core vacancies through rapid sequential ionization. This enables double core vacancy Auger electron spectroscopy, an entirely new way to study femtosecond chemical dynamics with Auger electrons that probe the local valence structure of molecules near a specific atomic core. Using 1.1 keV photons for sequential x-ray ionization of impulsively aligned molecular nitrogen, we observed a rich single-site double core vacancy Auger electron spectrum near 413 eV, in good agreement with ab initio calculations, and we measured the corresponding Auger electron angle dependence in the molecular frame.

  4. Auger electron diffraction in thin CoO films on Au(1 1 1)

    NASA Astrophysics Data System (ADS)

    Chassé, A.; Niebergall, L.; Heiler, M.; Neddermeyer, H.; Schindler, K.-M.

    The local structure of thin CoO films grown on a single crystal Au(1 1 1) surface has been studied by Auger electron diffraction (AED). Therefore, the angular dependence of the Auger electron intensity of Co-LMM and O-KLL Auger electrons was recorded in the total half-space above the film. Such 2 π-scans immediately reflect the symmetry of the surface and the local structure of the film. The experimental data are compared to multiple-scattering cluster calculations, where both the influence of multiple-scattering effects and effects of Auger transition matrix elements have been investigated. We have found that the AED patterns of a CoO film in forward-scattering conditions do not always provide straightforward information on the local structure of the film, whereas the multiple-scattering approximation applied gives very good agreement between experimental and theoretical results.

  5. Auger contributions to electron impact ionization of Li-like ions

    NASA Astrophysics Data System (ADS)

    Hahn, Yukap

    1980-07-01

    Electron impact ionization by a two-step process of inner-shell excitation followed by an Auger emission is estimated for the Li-like Oxygen and Fe ions. Result for the O 5+ is in good agreement with a recent experiment by Crandall et al. for incident energies above the twice of threshold energy. The Auger cross section is very much reduced in the case of Fe 23+ because of a large fluorescence yield.

  6. Single, double, and triple Auger decays from 1s shake-up states of the oxygen molecule.

    PubMed

    Kaneyasu, T; Odagiri, T; Nakagawa, M; Mashiko, R; Tanaka, H; Adachi, J; Hikosaka, Y

    2017-09-14

    The single, double, and triple Auger decays from the 1s shake-up states of O2 have been studied using a multi-electron coincidence method. Efficient populations of two-hole final states are observed in single Auger decays of the π-π* shake-up states, which is understood as a characteristic property of the Auger transitions from shake-up states of an open-shell molecule. The O2(3+) populations formed by double Auger decays show similar profiles for both the O1s(-1) and shake-up states, which is due to the contributions from cascade double Auger processes. While the cascade contributions to the double Auger decays increase with the initial shake-up energy, the probability of direct double Auger processes remains unchanged between the O1s(-1) and shake-up states, which implies a weak influence of the excited electron on the double Auger emission that originates from the electron correlation effect.

  7. Single, double, and triple Auger decays from 1s shake-up states of the oxygen molecule

    NASA Astrophysics Data System (ADS)

    Kaneyasu, T.; Odagiri, T.; Nakagawa, M.; Mashiko, R.; Tanaka, H.; Adachi, J.; Hikosaka, Y.

    2017-09-01

    The single, double, and triple Auger decays from the 1s shake-up states of O2 have been studied using a multi-electron coincidence method. Efficient populations of two-hole final states are observed in single Auger decays of the π-π* shake-up states, which is understood as a characteristic property of the Auger transitions from shake-up states of an open-shell molecule. The O23+ populations formed by double Auger decays show similar profiles for both the O1s-1 and shake-up states, which is due to the contributions from cascade double Auger processes. While the cascade contributions to the double Auger decays increase with the initial shake-up energy, the probability of direct double Auger processes remains unchanged between the O1s-1 and shake-up states, which implies a weak influence of the excited electron on the double Auger emission that originates from the electron correlation effect.

  8. A method for establishing constraints on galactic magnetic field models using ultra high energy cosmic rays and results from the data of the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Sutherland, Michael Stephen

    2010-12-01

    The Galactic magnetic field is poorly understood. Essentially the only reliable measurements of its properties are the local orientation and field strength. Its behavior at galactic scales is unknown. Historically, magnetic field measurements have been performed using radio astronomy techniques which are sensitive to certain regions of the Galaxy and rely upon models of the distribution of gas and dust within the disk. However, the deflection of trajectories of ultra high energy cosmic rays arriving from extragalactic sources depends only on the properties of the magnetic field. In this work, a method is developed for determining acceptable global models of the Galactic magnetic field by backtracking cosmic rays through the field model. This method constrains the parameter space of magnetic field models by comparing a test statistic between backtracked cosmic rays and isotropic expectations for assumed cosmic ray source and composition hypotheses. Constraints on Galactic magnetic field models are established using data from the southern site of the Pierre Auger Observatory under various source distribution and cosmic ray composition hypotheses. Field models possessing structure similar to the stellar spiral arms are found to be inconsistent with hypotheses of an iron cosmic ray composition and sources selected from catalogs tracing the local matter distribution in the universe. These field models are consistent with hypothesis combinations of proton composition and sources tracing the local matter distribution. In particular, strong constraints are found on the parameter space of bisymmetric magnetic field models scanned under hypotheses of proton composition and sources selected from the 2MRS-VS, Swift 39-month, and VCV catalogs. Assuming that the Galactic magnetic field is well-described by a bisymmetric model under these hypotheses, the magnetic field strength near the Sun is less than 3-4 muG and magnetic pitch angle is less than -8°. These results comprise

  9. Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor.

    PubMed

    Salamoun, Joseph M; McQueeney, Kelley E; Patil, Kalyani; Geib, Steven J; Sharlow, Elizabeth R; Lazo, John S; Wipf, Peter

    2016-07-06

    The phosphatase PTP4A3 is an attractive anticancer target, but knowledge of its exact role in cells remains incomplete. A potent, structurally novel inhibitor of the PTP4A family was obtained by photooxygenation of a less active, electron-rich thienopyridone (1). Iminothienopyridinedione 13 displays increased solution stability and is readily obtained by two new synthetic routes that converge in the preparation of 1. The late-stage photooxygenation of 1 to give 13 in high yield highlights the potential of this reaction to modify the structure and properties of a biological lead compound and generate value for expanding the scope of an SAR investigation. Analog 13 should become a valuable tool for further exploration of the role of PTP4A3 in tumor progression.

  10. Auger Prime the new stage of the Pierre Auger Observatory, using Universality

    NASA Astrophysics Data System (ADS)

    Parra, Alejandra; Martínez, Oscar; Salazar, Humberto

    2016-10-01

    The Pierre Auger Observatory is currently in an update stage denominated AugerPrime. The Observatory will have scintillator detectors on top of each of the surface stations (WCD). The main goal of AugerPrime is to improve the studies on mass composition for ultra high energy cosmic rays, for this purpose AugerPrime will use Universality. The model will parameterize the signal in four principal components, the objective is an adequate discrimination of the muonic and electromagnetic components. We are interested in the discrimination of these two components using simulations. To do that, we are working with OfflineTrunk (the official software of the Collaboration). Our work is focused on the development of some modules for analysis and study of the signal from AugerPrime.

  11. Development of Atmospheric Monitoring System for Auger North

    NASA Astrophysics Data System (ADS)

    Claus, John; Allen, Clint; Botts, Adam; Carande, Bryce; Calhoun, Mike; Emmert, Lucas; Hamilton, Levi; Heid, T. J.; Koop, John; Morgan, Sarah; Robinson, Shay; Sherman, John; Wiencke, Lawrence

    2009-10-01

    The Pierre Auger Northern Fluorescence Detector will measure air-showers over distances of 40 km. Vertical Aerosol profile of the atmosphere at the Pierre Auger Northern site will be measured using the side-scatter method over the 40 km baseline. An atmospheric monitoring telescope (AMT) will use a 3.5 m^2 mirror optimized for UV reflection to focus light from a laser onto a cluster of phototmultiplier tubes. The AMT has been built and final testing and modifications are being carried out before its installation later this year. A remotely programmed, 355 nm YAG laser with a final beam energy of 5 mJ is being used. The automation of the laser and the AMT is controlled via a single board computer (SBC). This talk will present an overview of this R&D program.

  12. Yucasin is a potent inhibitor of YUCCA, a key enzyme in auxin biosynthesis.

    PubMed

    Nishimura, Takeshi; Hayashi, Ken-Ichiro; Suzuki, Hiromi; Gyohda, Atsuko; Takaoka, Chihiro; Sakaguchi, Yusuke; Matsumoto, Sachiko; Kasahara, Hiroyuki; Sakai, Tatsuya; Kato, Jun-Ichi; Kamiya, Yuji; Koshiba, Tomokazu

    2014-02-01

    Indole-3-acetic acid (IAA), an auxin plant hormone, is biosynthesized from tryptophan. The indole-3-pyruvic acid (IPyA) pathway, involving the tryptophan aminotransferase TAA1 and YUCCA (YUC) enzymes, was recently found to be a major IAA biosynthetic pathway in Arabidopsis. TAA1 catalyzes the conversion of tryptophan to IPyA, and YUC produces IAA from IPyA. Using a chemical biology approach with maize coleoptiles, we identified 5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol (yucasin) as a potent inhibitor of IAA biosynthesis in YUC-expressing coleoptile tips. Enzymatic analysis of recombinant AtYUC1-His suggested that yucasin strongly inhibited YUC1-His activity against the substrate IPyA in a competitive manner. Phenotypic analysis of Arabidopsis YUC1 over-expression lines (35S::YUC1) demonstrated that yucasin acts in IAA biosynthesis catalyzed by YUC. In addition, 35S::YUC1 seedlings showed resistance to yucasin in terms of root growth. A loss-of-function mutant of TAA1, sav3-2, was hypersensitive to yucasin in terms of root growth and hypocotyl elongation of etiolated seedlings. Yucasin combined with the TAA1 inhibitor l-kynurenine acted additively in Arabidopsis seedlings, producing a phenotype similar to yucasin-treated sav3-2 seedlings, indicating the importance of IAA biosynthesis via the IPyA pathway in root growth and leaf vascular development. The present study showed that yucasin is a potent inhibitor of YUC enzymes that offers an effective tool for analyzing the contribution of IAA biosynthesis via the IPyA pathway to plant development and physiological processes.

  13. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.

    PubMed

    Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Wang, Junzhi; Fry, Elizabeth E; Stuart, David I; Rao, Zihe

    2017-01-24

    Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

  14. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site

    PubMed Central

    Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S.; Wang, Junzhi; Fry, Elizabeth E.; Stuart, David I.; Rao, Zihe

    2017-01-01

    Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention. PMID:28074040

  15. Pyrazolo-Pyrimidines: A Novel Heterocyclic Scaffold for Potent and Selective p38alpha Inhibitors

    SciTech Connect

    Das,J.; Moquin, R.; Pitt, S.; Zhang, R.; Shen, D.; McIntyre, K.; Gillooly, K.; Doweyko, A.; Sack, J.; et al

    2008-01-01

    The synthesis and structure-activity relationships (SAR) of p38a MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38a MAP kinase with excellent cellular potency toward the inhibition of TNFa production. Compound 2x was highly efficacious in vivo in inhibiting TNFa production in an acute murine model of TNFa production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38a is also disclosed.

  16. Auger recombination in long-wave infrared InAs/InAsSb type-II superlattices

    SciTech Connect

    Olson, B. V.; Grein, C. H.; Kim, J. K.; Kadlec, E. A.; Klem, J. F.; Hawkins, S. D.; Shaner, E. A.

    2015-12-29

    The Auger lifetime is a critical intrinsic parameter for infrared photodetectors as it determines the longest potential minority carrier lifetime and consequently the fundamental limitations to their performance. Here, Auger recombination is characterized in a long-wave infrared InAs/InAsSb type-II superlattice. Auger coefficients as small as 7.1×10–26 cm6/s are experimentally measured using carrier lifetime data at temperatures in the range of 20 K–80 K. The data are compared to Auger-1 coefficients predicted using a 14-band K•p electronic structure model and to coefficients calculated for HgCdTe of the same bandgap. In conclusion, the experimental superlattice Auger coefficients are found to be an order-of-magnitude smaller than HgCdTe.

  17. Auger recombination in long-wave infrared InAs/InAsSb type-II superlattices

    DOE PAGES

    Olson, B. V.; Grein, C. H.; Kim, J. K.; ...

    2015-12-29

    The Auger lifetime is a critical intrinsic parameter for infrared photodetectors as it determines the longest potential minority carrier lifetime and consequently the fundamental limitations to their performance. Here, Auger recombination is characterized in a long-wave infrared InAs/InAsSb type-II superlattice. Auger coefficients as small as 7.1×10–26 cm6/s are experimentally measured using carrier lifetime data at temperatures in the range of 20 K–80 K. The data are compared to Auger-1 coefficients predicted using a 14-band K•p electronic structure model and to coefficients calculated for HgCdTe of the same bandgap. In conclusion, the experimental superlattice Auger coefficients are found to be anmore » order-of-magnitude smaller than HgCdTe.« less

  18. Relativistic Radiative and Auger Rates for Fe XXIV

    NASA Technical Reports Server (NTRS)

    Bautista, M. A.; Mendoza, C.; Kallman, T. R.; Palmeri, P.; White, Nicholas E. (Technical Monitor)

    2002-01-01

    As part of a project to compute improved atomic data for the spectral modeling of iron K lines, we report extensive calculations and comparisons of radiative and Auger rates for transitions involving the K-vacancy states in Fe XXIV. By making use of several computational codes, a detailed study is carried out of orbital representation, configuration interaction, relativistic corrections, cancellation effects, and fine tuning. It is shown that a formal treatment of the Breit interaction is essential to render the important magnetic correlations that take part in the decay pathways of this ion. As a result, the accuracy of the present A-values is firmly ranked at better than 10% while that of the Auger rates at only 15%.

  19. Total synthesis of SR 121463 A, a highly potent and selective vasopressin v(2) receptor antagonist.

    PubMed

    Venkatesan, H; Davis, M C; Altas, Y; Snyder, J P; Liotta, D C

    2001-06-01

    SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of the vasopressin V(2) receptor subtype and, thus, a candidate for control of the clinically debilitating condition of hyponatremia and its associated syndromes. In the present work, we present a novel and stereoselective synthesis that stems from the preparation of three key intermediates: the substituted benzenesulfonyl chloride 2, the N-protected oxindole 3, and protected dibromide 4. The synthesis of 1 has been achieved in good overall yield, each step proceeding in greater than 80% yield. In addition, intermediate 2 and the syn isomer of 1 were prepared with complete control of stereochemistry. The latter reduction appears to proceed by lithium cation mediated chelation control. Molecular mechanics calculations with the MM3* and MMFF force fields underscore geometric and energetic aspects of the reaction.

  20. A PEGylated bovine hemoglobin as a potent hemoglobin-based oxygen carrier.

    PubMed

    Wang, Ying; Wang, Linli; Yu, Weili; Gao, Dawei; You, Guoxing; Li, Penglong; Zhang, Shan; Zhang, Jun; Hu, Tao; Zhao, Lian; Zhou, Hong

    2017-01-01

    Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been used as blood substitutes in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent HBOC, the PEGylated Hb has received much attention for its oxygen delivery and plasma expanding ability. Two PEGylated Hbs, Euro-Hb, and MP4 have been developed for clinical trials, using human adult hemoglobin (HbA) as the original substrate. However, HbA was obtained from outdated human blood and its quantity available from this source may not be sufficient for mass production of PEGylated HbA. In contrast, bovine Hb (bHb) has no quantity constraints for its ample resource. Thus, bHb is of potential to function as an alternative substrate to obtain a PEGylated bHb (bHb-PEG). bHb-PEG was prepared under the same reaction condition as HbA-PEG, using maleimide chemistry. The structural, functional, solution and physiological properties of bHb-PEG were determined and compared with those of HbA-PEG. bHb-PEG showed higher hydrodynamic volume, colloidal osmotic pressure, viscosity and P50 than HbA-PEG. The high P50 of bHb can partially compensate the PEGylation-induced perturbation in the R to T state transition of HbA. bHb-PEG was non-vasoactive and could efficiently recover the mean arterial pressure of mice suffering from hemorrhagic shock. Thus, bHb-PEG is expected to function as a potent HBOC for its high oxygen delivery and strong plasma expanding ability. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:252-260, 2017.

  1. Identification of a resveratrol tetramer as a potent inhibitor of hepatitis C virus helicase

    PubMed Central

    Lee, Sungjin; Yoon, Kee Dong; Lee, Myungeun; Cho, Yoojin; Choi, Gahee; Jang, Hongje; Kim, BeomSeok; Jung, Da‐Hee; Oh, Jin‐Gyo; Kim, Geon‐Woo; Oh, Jong‐Won; Jeong, Yong‐Joo; Kwon, Ho Jeong; Bae, Soo Kyung; Min, Dal‐Hee; Windisch, Marc P

    2015-01-01

    Background and Purpose Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti‐HCV activity and have elucidated its mode of antiviral action. Experimental Approach Luciferase reporter and real‐time RT‐PCR assays were used to measure HCV replication. Western blot, fluorescence‐labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism. Key Results A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B‐resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations. Conclusion and Implications Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products. PMID:26445091

  2. Spectrum of energy depositions in the Auger Water Cherenkov Detector

    NASA Astrophysics Data System (ADS)

    Salazar, Humberto

    1999-08-01

    The measured spectrum of energy depositions in a Water Cherenkov Detector (WCD) prototype for the Pierre Auger Observatory is presented. A WCD (area 10 m2 )is located in the Puebla University campus at a depth of 800 g/cm2 (2200 m above sea level). Differential and integral spectra in a wide energy deposition range (0.5 - 150 of vertical equivalent muons) are presented. The problem of the WCD "self calibration" procedure (by rate of the muon events) is discussed. The characteristic change of the slopes of the differential spectrum at the transition from single muon signals to EAS signals is also discussed. The measured energy deposition spectrum at extreme signals is used to estimate the linearity of the response of the WCD PMTs. Key words: Auger array, water Cherenkov detector, extensive air showers

  3. Auger eectron spectroscopy study of the {ZrO }/{W(100) } system at high temperature

    NASA Astrophysics Data System (ADS)

    Lee, S. C.; Irokawa, Y.; Inoue, M.; Shimizu, R.

    1996-09-01

    To study the role of oxygen in the mechanism of lowering the work function in the oxygen-processed {Zr}/{W(100) } system, Auger spectrum shape analysis was performed at high temperature after oxygen processing, according to the conventional treatment for activation processing of a {Zr-O }/{W(100) } thermal field emitter (TFE). For this we prepared O/Zr(≈1/2 ML)/M(100) and O/Zr(≈1 ML/W(100) to examine whether or not the oxygen adsorption on the {Zr}/{W(100) } results in any variation in the Auger spectrum of Zr as a result of the chemical effect caused by ZrO bonding. Auger electron spectroscopy (AES) of these samples reveals a tiny peak near 130 eV, which is thought to represent ZrO bonding. Careful re-examination of the Zr Auger spectra from {ZrO }/{W(100) } at ≈1700 K has led to the conclusion that this tiny peak at 130 eV did appear in the Auger spectrum reported in the previous paper. It has also been found from the analysis of the oxygen Auger spectrum that WO x is partially formed in a W(100) substrate.

  4. The hybrid performance of the Pierre Auger Observatory

    SciTech Connect

    Mostafa, Miguel, A.; /New Mexico U.

    2005-08-01

    The Pierre Auger Observatory detects ultra-high energy cosmic rays by implementing two complementary air-shower techniques. The combination of a large ground array and fluorescence detectors, known as the hybrid concept, means that a rich variety of measurements can be made on a single shower, providing much improved information over what is possible with either detector alone. In this paper the hybrid reconstruction approach and its performance are described.

  5. Comment on mesic-atom Auger-rate calculation

    NASA Astrophysics Data System (ADS)

    Altman, A.; Fried, Z.

    1983-07-01

    Auger rates for a mesic atom consisting of a lithium nucleus and two electrons are presented. It is shown that the results are sensitive to the screening of the initial and final state of the ejected electron by the spectator electron. These results are compared to transition rates one would obtain by following the procedure used by Burbridge and de Borde, which neglect screening of one electron by the others. Our results show a 40% reduction in transition rates.

  6. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

    PubMed Central

    Dubreuil, Patrice; Letard, Sébastien; Ciufolini, Marco; Gros, Laurent; Humbert, Martine; Castéran, Nathalie; Borge, Laurence; Hajem, Bérengère; Lermet, Anne; Sippl, Wolfgang; Voisset, Edwige; Arock, Michel; Auclair, Christian; Leventhal, Phillip S.; Mansfield, Colin D.; Moussy, Alain; Hermine, Olivier

    2009-01-01

    Background The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. Methodology/Principal Findings In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200±40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50 of 150±80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. Conclusions Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity. PMID:19789626

  7. MONNA, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1.

    PubMed

    Oh, Soo-Jin; Hwang, Seok Jin; Jung, Jonghoon; Yu, Kuai; Kim, Jeongyeon; Choi, Jung Yoon; Hartzell, H Criss; Roh, Eun Joo; Lee, C Justin

    2013-11-01

    Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a --NO₂ group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC₅₀ < 10 μM. The most potent blocker, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid (MONNA), had an IC₅₀ of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10∼30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.

  8. A Highly Potent and Selective Caspase 1 Inhibitor that Utilizes a Key 3-Cyanopropanoic Acid Moiety

    PubMed Central

    Boxer, Matthew B.; Quinn, Amy M.; Shen, Min; Jadhav, Ajit; Leister, William; Simeonov, Anton; Auld, Douglas S.; Thomas, Craig J.

    2011-01-01

    Herein we examine the potential of a nitrile-containing proprionic acid moiety as an electrophile for covalent attack by the active site cysteine residue of caspase 1. The syntheses of several cyanopropanate containing small molecules based upon the optimized peptidic scaffold of the prodrug VX-765 were accomplished and found to be potent inhibitors of caspase 1 (IC50s ≤ 1 nM). Examination of these novel small molecules versus a caspase panel demonstrated an impressive degree of selectivity for caspase 1 inhibition. Assessment of hydrolytic stability and selected ADME properties highlighted these agents as potentially useful tools for studying caspase 1 down-regulation in various settings including in vivo analyses. PMID:20229566

  9. Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist.

    PubMed

    Feng, Song; Yang, Minmin; Zhang, Zhenshan; Wang, Zhanguo; Hong, Di; Richter, Hans; Benson, Gregory Martin; Bleicher, Konrad; Grether, Uwe; Martin, Rainer E; Plancher, Jean-Marc; Kuhn, Bernd; Rudolph, Markus Georg; Chen, Li

    2009-05-01

    According to the docking studies and the analysis of a co-crystal structure of GW4064 with FXR, a series of 3-aryl heterocyclic isoxazole analogs were designed and synthesized. N-Oxide pyridine analog (7b) was identified as a promising FXR agonist with potent binding affinity and good efficacy, supporting our hypothesis that through an additional hydrogen bond interaction between the pyridine substituent of isoxazole analogs and Tyr373 and Ser336 of FXR, binding affinity and functional activity could be improved.

  10. A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent Hormonal Therapies

    DTIC Science & Technology

    2016-10-01

    1 AWARD NUMBER: W81XWH-13-1-0275 TITLE: A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent...TYPE Annual 3. DATES COVERED 30Sep2015 - 29Sep2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0275 A Changing Landscape of Advanced...The mutational landscape of CRPC-NE was similar to CRPC-Adeno (Figure 1c), but also consistent with published studies of CRPC-NE including

  11. Model for Osteosarcoma-9 as a potent factor in cell survival and resistance to apoptosis.

    PubMed

    Vourvouhaki, Ekaterini; Carvalho, Carla; Aguiar, Paulo

    2007-07-01

    In this paper we use a simple model to explore the function of the gene Osteosarcoma-9 (OS-9). We are particularly interested in understanding the role of this gene as a potent anti-apoptotic factor. The theoretical description is constrained by experimental data from induction of apoptosis in cells where OS-9 is overexpressed. The data available suggest that OS-9 promotes cell viability and confers resistance to apoptosis, potentially implicating OS-9 in the survival of cancer cells. Three different apoptosis-inducing mechanisms were tested and are modeled here. A more complex and realistic model is also discussed.

  12. Stereoselective synthesis of protectin D1: A potent anti-inflammatory and proresolving lipid mediator

    PubMed Central

    Aursnes, M.; Tungen, J. E.; Vik, A.; Dalli, J.; Hansen, T. V.

    2014-01-01

    A convergent stereoselective synthesis of the potent anti-inflammatory, proresolving and neuroprotective lipid mediator protectin D1 (2) has been achieved in 15% yield over eight steps. The key features were a stereocontrolled Evans-aldol reaction with Nagao’s chiral auxiliary and a highly selective Lindlar reduction of internal alkyne 23, allowing the sensitive conjugated E,E,Z-triene to be introduced late in the preparation of 2. The UV and LC/MS-MS data of synthetic protectin D1 (2) matched those obtained from endogenously produced material PMID:24253202

  13. Model for Osteosarcoma-9 as a potent factor in cell survival and resistance to apoptosis

    NASA Astrophysics Data System (ADS)

    Vourvouhaki, Ekaterini; Carvalho, Carla; Aguiar, Paulo

    2007-07-01

    In this paper we use a simple model to explore the function of the gene Osteosarcoma-9 (OS-9). We are particularly interested in understanding the role of this gene as a potent anti-apoptotic factor. The theoretical description is constrained by experimental data from induction of apoptosis in cells where OS-9 is overexpressed. The data available suggest that OS-9 promotes cell viability and confers resistance to apoptosis, potentially implicating OS-9 in the survival of cancer cells. Three different apoptosis-inducing mechanisms were tested and are modeled here. A more complex and realistic model is also discussed.

  14. Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics.

    PubMed

    Le, V H; Inai, M; Williams, R M; Kan, T

    2015-02-01

    The ecteinascidin family comprises a number of biologically active compounds, containing two to three tetrahydroisoquinoline subunits. Although isolated from marine tunicates, these compounds share a common pentacyclic core with several antimicrobial compounds found in terrestrial bacteria. Among the tetrahydroisoquinoline natural products, ecteinascidin 743 (Et-743) stands out as the most potent antitumor antibiotics that it is recently approved for treatment of a number of soft tissue sarcomas. In this article, we will review the backgrounds, the mechanism of action, the biosynthesis, and the synthetic studies of Et-743. Also, the development of Et-743 as an antitumor drug is discussed.

  15. Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases

    PubMed Central

    Farnsworth, Aaron; Brown, Earl G.; Van Domselaar, Gary; He, Runtao; Li, Xuguang

    2009-01-01

    Background Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. Methodology/Principal Findings We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus. Conclusions/Significance Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride. PMID:20020057

  16. 6-Methoxypurine arabinoside as a selective and potent inhibitor of varicella-zoster virus.

    PubMed Central

    Averett, D R; Koszalka, G W; Fyfe, J A; Roberts, G B; Purifoy, D J; Krenitsky, T A

    1991-01-01

    Seven 6-alkoxypurine arabinosides were synthesized and evaluated for in vitro activity against varicella-zoster virus (VZV). The simplest of the series, 6-methoxypurine arabinoside (ara-M), was the most potent, with 50% inhibitory concentrations ranging from 0.5 to 3 microM against eight strains of VZV. This activity was selective. The ability of ara-M to inhibit the growth of a variety of human cell lines was at least 30-fold less (50% effective concentration, greater than 100 microM) than its ability to inhibit the virus. Enzyme studies suggested the molecular basis for these results. Of the seven 6-alkoxypurine arabinosides, ara-M was the most efficient substrate for VZV-encoded thymidine kinase as well as the most potent antiviral agent. In contrast, it was not detectably phosphorylated by any of the three major mammalian nucleoside kinases. Upon direct comparison, ara-M was appreciably more potent against VZV than either acyclovir or adenine arabinoside (ara-A). However, in the presence of an adenosine deaminase inhibitor, the arabinosides of adenine and 6-methoxypurine were equipotent but not equally selective; the adenine congener had a much less favorable in vitro chemotherapeutic index. Again, this result correlated with data from enzyme studies in that ara-A, unlike ara-M, was a substrate for two mammalian nucleoside kinases. Unlike acyclovir and ara-A, ara-M had no appreciable activity against other viruses of the herpes group. The potency and selectivity of ara-M as an anti-VZV agent in vitro justify its further study. PMID:1649571

  17. Discovery of a Selective Inhibitor of Oncogenic B-Raf Kinase With Potent Antimelanoma Activity

    SciTech Connect

    Tsai, J.; Lee, J.T.; Wang, W.; Zhang, J.; Cho, H.; Mamo, S.; Bremer, R.; Gillette, S.; Kong, J.; Haass, N.K.; Sproesser, K.; Li, L.; Smalley, K.S.M.; Fong, D.; Zhu, Y.-L.; Marimuthu, A.; Nguyen, H.; Lam, B.; Liu, J.; Cheung, I.; Rice, J.

    2009-05-26

    BRAF{sup V600E} is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting 'active' protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf{sup V600E} with an IC{sub 50} of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf{sup V600E} kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf{sup V600E}-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf{sup V600E}-positive cells. In B-Raf{sup V600E}-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf{sup V600E}-driven tumors.

  18. Atmospheric aerosol monitoring at the Pierre Auger Observatory

    SciTech Connect

    Cester, R.; Chiosso, M.; Chirin, J.; Clay, R.; Dawson, B.; Fick, B.; Filipcic, A.; Garcia, B.; Grillo, A.; Horvat, M.; Iarlori, M.; Malek, M.; Matthews, J.; Matthews, J.A.J.; Melo, D.; Meyhandan, R.; Mostafa, M.; Mussa, R.; Prouza, M.; Raefert, B.; Rizi, V.

    2005-07-01

    For a ground based cosmic-ray observatory the atmosphere is an integral part of the detector. Air fluorescence detectors (FDs) are particularly sensitive to the presence of aerosols in the atmosphere. These aerosols, consisting mainly of clouds and dust, can strongly affect the propagation of fluorescence and Cherenkov light from cosmic-ray induced extensive air showers. The Pierre Auger Observatory has a comprehensive program to monitor the aerosols within the atmospheric volume of the detector. In this paper the aerosol parameters that affect FD reconstruction will be discussed. The aerosol monitoring systems that have been deployed at the Pierre Auger Observatory will be briefly described along with some measurements from these systems.

  19. Some strategies for quantitative scanning Auger electron microscopy

    NASA Technical Reports Server (NTRS)

    Browning, R.; Peacock, D. C.; Prutton, M.

    1985-01-01

    The general applicability of power law forms of the background in electron spectra is pointed out and exploited for background removal from under Auger peaks. This form of B(E) is found to be extremely sensitive to instrumental alignment and to fault-free construction - an observation which can be used to set up analyser configurations in an accurate way. Also, differences between N(E) and B(E) can be used to derive a spectrometer transmission function T(E). The questions of information density in an energy-analysing spatially-resolving instrument are addressed after reliable instrumental characterization has been established. Strategies involving ratio histograms, showing the population distribution of the ratio of a pair of Auger peak heights, composition scatter diagrams and windowed imaging are discussed and illustrated.

  20. Some strategies for quantitative scanning Auger electron microscopy

    NASA Technical Reports Server (NTRS)

    Browning, R.; Peacock, D. C.; Prutton, M.

    1985-01-01

    The general applicability of power law forms of the background in electron spectra is pointed out and exploited for background removal from under Auger peaks. This form of B(E) is found to be extremely sensitive to instrumental alignment and to fault-free construction - an observation which can be used to set up analyser configurations in an accurate way. Also, differences between N(E) and B(E) can be used to derive a spectrometer transmission function T(E). The questions of information density in an energy-analysing spatially-resolving instrument are addressed after reliable instrumental characterization has been established. Strategies involving ratio histograms, showing the population distribution of the ratio of a pair of Auger peak heights, composition scatter diagrams and windowed imaging are discussed and illustrated.

  1. Nitridation of silicon /111/ - Auger and LEED results

    NASA Technical Reports Server (NTRS)

    Delord, J. F.; Schrott, A. G.; Fain, S. C., Jr.

    1980-01-01

    Clean silicon (111) (7x7) surfaces at up to 1050 C have been reacted with nitrogen ions and neutrals produced by a low energy ion gun. The LEED patterns observed are similar to those previously reported for reaction of silicon (111) (7x7) with NH3. The nitrogen KLL peak exhibits no shift or change in shape with nitride growth. At the same time the magnitude of the elemental silicon LVV peak at 92 eV decreases progressively as a new peak at 84 eV increases. The position of both peaks appears to be independent of the degree of nitridation. Since the Auger spectra are free of oxygen and other impurities, these features can be attributed only to silicon, nitrogen, and their reaction products. Characteristic features of the Auger spectra are related to LEED observations and to the growth of microcrystals of Si3N4.

  2. Path-reversed Auger electron and photoelectron diffraction

    SciTech Connect

    Pauli, M. D.; Saldin, D. K.

    2001-08-15

    We propose a method for the computer simulation of Auger electron and photoelectron diffraction patterns by evaluating the amplitude of propagation paths from the detector to the electron-emitting source, justified by Helmholtz's reciprocity principle. The method offers significant computational advantages over previous schemes, and suggests an easy extension to enable the calculation of a structure-perturbation tensor for rapid crystallographic parameter variation.

  3. Status and first results of the "Pierre Auger" observatory

    NASA Astrophysics Data System (ADS)

    Arqueros, F.

    The southern Pierre Auger Cosmic Ray Observatory located at Malargue Mendoza Argentina is even before completion the largest cosmic ray detector in operation It consists of a huge surface array for the detection of the air-shower tail and a fluo-rescence detector for the observation of the shower development Since January 2004 the Observatory is collecting data at increasing rate The capabilities of this hybrid detector and the first results will be summarized

  4. A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts

    PubMed Central

    Swarnkar, Gaurav; Sharan, Kunal; Siddiqui, Jawed A; Mishra, Jay Sharan; Khan, Kainat; Khan, Mohd Parvez; Gupta, Varsha; Rawat, Preeti; Maurya, Rakesh; Dwivedi, Anil K; Sanyal, Sabyasachi; Chattopadhyay, Naibedya

    2012-01-01

    BACKGROUND AND PURPOSE Naringenin and its derivatives have been assessed in bone health for their oestrogen-‘like’ effects but low bioavailability impedes clinical potential. This study was aimed at finding a potent form of naringenin with osteogenic action. EXPERIMENTAL APPROACH Osteoblast cultures were harvested from mouse calvaria to study differentiation by naringenin, isosakuranetin, poncirin, phloretin and naringenin-6-C-glucoside (NCG). Balb/cByJ ovariectomized (OVx) mice without or with osteopenia were given naringenin, NCG, 17β-oestradiol (E2) or parathyroid hormone (PTH). Efficacy was evaluated by bone microarchitecture using microcomputed tomography and determination of new bone formation by fluorescent labelling of bone. Plasma levels of NCG and naringenin were determined by HPLC. KEY RESULTS NCG stimulated osteoblast differentiation more potently than naringenin, while isosakuranetin, poncirin or phloretin had no effect. NCG had better oral bioavailability than naringenin. NCG increased the mRNA levels of oestrogen receptors (ERs) and bone morphogenetic protein (an ER responsive gene) in vivo, more than naringenin. In OVx mice, NCG treatment in a preventive protocol increased bone formation rate (BFR) and improved trabecular microarchitecture more than naringenin or E2. In osteopenic mice, NCG but not naringenin, in a therapeutic protocol, increased BFR and improved trabecular microarchitecture, comparable with effects of PTH treatment. Stimulatory effects of NCG on osteoblasts were abolished by an ER antagonist. NCG transactivated ERβ but not ERα. NCG exhibited no uterine oestrogenicity unlike naringenin. CONCLUSIONS AND IMPLICATIONS NCG is a potent derivative of naringenin that has bone anabolic action through the activation of osteoblast ERs and exhibited substantial oral bioavailability. PMID:21864313

  5. A potent novel anti-HIV protein from the cultured cyanobacterium Scytonema varium.

    PubMed

    Bokesch, Heidi R; O'Keefe, Barry R; McKee, Tawnya C; Pannell, Lewis K; Patterson, Gregory M L; Gardella, Roberta S; Sowder, Raymond C; Turpin, Jim; Watson, Karen; Buckheit, Robert W; Boyd, Michael R

    2003-03-11

    A new anti-HIV protein, scytovirin, was isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium. The protein displayed potent anticytopathic activity against laboratory strains and primary isolates of HIV-1 with EC50 values ranging from 0.3 to 22 nM. Scytovirin binds to viral coat proteins gp120, gp160, and gp41 but not to cellular receptor CD4 or other tested proteins. This unique protein consists of a single 95-amino acid chain with significant internal sequence duplication and 10 cysteines forming five intrachain disulfide bonds.

  6. In Situ Click Chemistry for the Identification of a Potent D-Amino Acid Oxidase Inhibitor.

    PubMed

    Toguchi, Shohei; Hirose, Tomoyasu; Yorita, Kazuko; Fukui, Kiyoshi; Sharpless, K Barry; Ōmura, Satoshi; Sunazuka, Toshiaki

    2016-07-01

    In situ click chemistry is a target-guided synthesis approach for discovering novel lead compounds by assembling organic azides and alkynes into triazoles inside the affinity site of target biogenic molecules such as proteins. We report in situ click chemistry screening with human D-amino acid oxidase (hDAO), which led to the identification of a more potent hDAO inhibitor. The hDAO inhibitors have chemotherapeutic potential as antipsychotic agents. The new inhibitor displayed competitive inhibition of hDAO and showed significantly increased inhibitory activity against hDAO compared with that of an anchor molecule of in situ click chemistry.

  7. A new potent inhibitor of horse liver alcohol dehydrogenase: p-methylbenzyl hydroperoxide.

    PubMed

    Skurský, L; Khan, A N; Saleem, M N; al-Tamer, Y Y

    1992-04-01

    A product of p-xylene auto-oxidation, p-methylbenzyl hydroperoxide, acts as a very strong reversible inhibitor of the ethanol dehydrogenating activity of horse liver alcohol dehydrogenase. Concentrations of hydroperoxide as low as that of the enzyme active site (about 10(-8) mol.dm-3) in the assay depresses the activity by 50%. Somewhat less potent is benzyl hydroperoxide (derived from toluene) while the (secondary) hydroperoxide derived from ethylbenzene and tert.butyl hydroperoxide and cumyl hydroperoxide do not inhibit HLAD appreciably.

  8. HIV Integrase Inhibitors with Nucleobase Scaffolds: Discovery of a Highly Potent anti-HIV Agent

    PubMed Central

    Nair, Vasu; Chi, Guochen; Ptak, Roger; Neamati, Nouri

    2008-01-01

    HIV integrase is essential for HIV replication. However, there are currently no integrase inhibitors in clinical use for AIDS. We have discovered a conceptually new β-diketo acid that is a powerful inhibitor of both the 3′-processing and strand transfer steps of HIV-1 integrase. The in vitro anti-HIV data of this inhibitor were remarkable as exemplified by its highly potent antiviral therapeutic efficacy against HIVTEKI and HIV-1NL4-3 replication in PBMC (TI >4,000 and >10,000, respectively). PMID:16420027

  9. Ramsey interferometry for resonant Auger decay through core-excited states

    NASA Astrophysics Data System (ADS)

    Chatterjee, Souvik; Nakajima, Takashi

    2016-08-01

    We theoretically investigate the electron dynamics in Ne atoms involving core-excited states through the Ramsey scheme with a pair of time-delayed x-ray pulses. Irradiation of Ne atoms by the ˜1 femtosecond x-ray pulse simultaneously populates two core-excited states, and an identical but time-delayed x-ray pulse probes the dynamics of the core-excited electron wave packet which is subject to the resonant Auger decay. The energy-integrated total Auger electron yield and energy-resolved Auger electron spectra in the time domain show periodic structures due to the temporal evolution of the wave packet, from which we can obtain the counterpart in the frequency domain through the Fourier transformation. The Auger electron energy spectra in the time as well as frequency domains show the interference patterns between the two Auger electron wave packets released into the continuum from the superposition of two core-excited states at different times. These spectra are important to clarify the individual contribution of the different Auger decay channels upon core excitation by the x-ray pulse.

  10. Photonic crystal enhancement of auger-suppressed infrared photodetectors

    NASA Astrophysics Data System (ADS)

    Djurić, Zoran; Jakšić, Zoran; Ehrfeld, Wolfgang; Schmidt, Andreas; Matić, Milan; Popović, Mirjana

    2001-04-01

    We examine theoretically and experimentally the possibilities to reach room-temperature background-limited operation of narrow-bandgap compound semiconductor photodetectors in (3-14) micrometer infrared wavelength range. To this purpose we consider the combination of non-equilibrium Auger suppression with photonic crystal enhancement (PCE). This means that Auger generation-recombination processes are suppressed utilizing exclusion, extraction or magnetoconcentration effects or their combination. The residual radiative recombination is removed by immersing the detector active area into a photonic crystal and using the benefits of re-absorption (photon recycling) to effectively increase the radiative lifetime. In this manner the total generation-recombination noise is strongly quenched in sufficiently defect-free device materials. It is concluded that the operation of thus enhanced photonic detectors could even approach signal fluctuation limit.

  11. Study of the Auger line shape of polyethylene and diamond

    NASA Technical Reports Server (NTRS)

    Dayan, M.; Pepper, S. V.

    1984-01-01

    The KVV Auger electron line shapes of carbon in polyethylene and diamond have been studied. The spectra were obtained in derivative form by electron beam excitation. They were treated by background subtraction, integration and deconvolution to produce the intrinsic Auger line shape. Electron energy loss spectra provided the response function in the deconvolution procedure. The line shape from polyethylene is compared with spectra from linear alkanes and with a previous spectrum of Kelber et al. Both spectra are compared with the self-convolution of their full valence band densities of states and of their p-projected densities. The experimental spectra could not be understood in terms of existing theories. This is so even when correlation effects are qualitatively taken into account account to the theories of Cini and Sawatzky and Lenselink.

  12. Muricholic bile acids are potent regulators of bile acid synthesis via a positive feedback mechanism.

    PubMed

    Hu, X; Bonde, Y; Eggertsen, G; Rudling, M

    2014-01-01

    Bile acid (BA) synthesis is regulated by negative feedback end-product inhibition, initiated by farnesoid X receptors (FXRs) in liver and gut. Studies on cholic acid (CA)-free Cyp8b1(-/-) mice have concluded that CA is a potent suppressor of BA synthesis. Cyp8b1(-/-) mice have increased BA synthesis and an enlarged BA pool, a phenotype shared with bile-duct-ligated, antibiotics-administered and with germ-free mice. Studies on such mice have concluded BA synthesis is induced due to reduced hormonal signalling by fibroblast growth factor (FGF)15 from intestine to liver. A mutual finding in these models is that potent FXR-agonistic BAs are reduced. We hypothesized that the absence of the potent FXR agonist deoxycholic acid (DCA) may be important for the induction of BA synthesis in these situations. Two of these models were investigated, antibiotic treatment and Cyp8b1(-/-) mice and their combination. Secondary BA formation was inhibited by ampicillin (AMP) given to wild-type and Cyp8b1(-/-) mice. We then administered CA, chenodeoxycholic acid (CDCA) or DCA to AMP-treated Cyp8b1(-/-) mice. Our data show that the phenotype of AMP-treated wild-type mice resembles that of Cyp8b1(-/-) mice with fourfold induced Cyp7a1 expression, increased intestinal apical sodium-dependent BA transporter expression and increased hepatic BA levels. We also show that reductions in the FXR-agonistic BAs CDCA, CA, DCA or lithocholic acid cannot explain this phenotype; instead, it is likely due to increases in levels of α- and β-muricholic BAs and ursodeoxycholic acid, three FXR-antagonistic BAs. Our findings reveal a potent positive feedback mechanism for regulation of BA synthesis in mice that appears to be sufficient without endocrine effects of FGF15 on Cyp7a1. This mechanism will be fundamental in understanding BA metabolism in both mice and humans. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  13. The Past, Present, and Future of Auger Lineshape Analysis

    DTIC Science & Technology

    1991-01-01

    Availability Codei Avail and/or Dist Special Technical Report No. 55 Wf The Past, Present, And Future of Auger Lineshape Analysis By DAVID E. RAMAKER Prepared...interaction on the 0 atom. Values from 4 to 14 have been reported (see reference Ramhtsc2 for a summary of the theoretical and experimental estimates). The 0...public releas \\ ,, distributibin unlimited ) 4 4. PERFORMING ORGANIZATION REPORT NUMBERCS) S. MONITORING- ORGANIZATION REPOR T NUMBER(S) - Technical

  14. Mechanical testing - In situ fracture device for Auger electron spectroscopy

    NASA Technical Reports Server (NTRS)

    Moorhead, R. D.

    1976-01-01

    An in situ fracture device for Auger spectroscopy is described. The device is designed to handle small tensile specimens or small double-cantilever beam specimens and is fully instrumented with load and displacement transducers so that quantitative stress-strain measurements can be made directly. Some initial test results for specimens made from 4130 and 1020 steel are presented. Results indicate that impurity segregation at interfaces other than grain boundary may play a significant role in the mechanism of ductile fracture.

  15. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases.

    PubMed

    Bettayeb, K; Oumata, N; Echalier, A; Ferandin, Y; Endicott, J A; Galons, H; Meijer, L

    2008-10-02

    Among the ten pharmacological inhibitors of cyclin-dependent kinases (CDKs) currently in clinical trials, the purine roscovitine (CYC202, Seliciclib) is undergoing phase 2 trials against non-small-cell lung and nasopharyngeal cancers. An extensive medicinal chemistry study, designed to generate more potent analogues of roscovitine, led to the identification of an optimal substitution at the N6 position (compound CR8). An extensive selectivity study (108 kinases) highlights the exquisite selectivity of CR8 for CDK1/2/3/5/7/9. CR8 was 2- to 4-fold more potent than (R)-roscovitine at inhibiting these kinases. Cocrystal structures of (R)-CR8 and (R)-roscovitine with pCDK2/cyclin A showed that both inhibitors adopt essentially identical positions. The cellular effects of CR8 and (R)-roscovitine were investigated in human neuroblastoma SH-SY5Y cells. CR8 inhibited the phosphorylation of CDK1 and 9 substrates, with a 25-50 times higher potency compared to (R)-roscovitine. CR8 was consistently more potent than (R)-roscovitine at inducing apoptotic cell death parameters: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium reduction (40-fold), lactate dehydrogenase release (35-fold), caspases activation (68-fold) and poly-(ADP-ribose)polymerase cleavage (50-fold). This improved cell death-inducing activity of CR8 over (R)-roscovitine was observed in 25 different cell lines. Altogether these results show that second-generation analogues of (R)-roscovitine can be designed with improved antitumor potential.

  16. A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of β-Secretase

    PubMed Central

    2012-01-01

    β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Aβ40 levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor. PMID:24900403

  17. New anabaenopeptins, potent carboxypeptidase-A inhibitors from the cyanobacterium Aphanizomenon flos-aquae.

    PubMed

    Murakami, M; Suzuki, S; Itou, Y; Kodani, S; Ishida, K

    2000-09-01

    Anabaenopeptins I (1) and J (2), two new ureido bond-containing cyclic peptides, were isolated from the cultured cyanobacterium Aphanizomenon flos-aquae (NIES-81) as potent carboxypeptidase-A (CPA) inhibitors. The gross structures of 1 and 2 were established by spectroscopic analysis, including the 2D NMR techniques. The absolute configurations of 1 and 2 were determined by spectral and chemical methods. Anabaenopeptins I and J inhibited CPA with IC(50) values of 5.2 and 7.6 ng/mL, respectively.

  18. 8-hydroxydihydrochelerythrine and 8-hydroxydihydrosanguinarine with a potent acetylcholinesterase inhibitory activity from Chelidonium majus L.

    PubMed

    Cho, Kyung-Mi; Yoo, Ick-Dong; Kim, Won-Gon

    2006-11-01

    Ethanol extract of the aerial portion of Chelidonium majus L. inhibited acetylcholinesterase (AChE) activity without a significant inhibition of butyrylcholinesterase (BuChE). Using mass spectrometry and NMR studies, three active constituents were isolated and identified: 8-hydroxydihydrochelerythrine (1), 8-hydroxydihydrosanguinarine (2), and berberine (3). Compounds 1-3 showed potent inhibitory activity against AChE, with IC50 (microM) values of 0.61-1.85. Compound 1 exhibited competitive and selective inhibition for AChE.

  19. Atmospheric monitoring and model applications at the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Keilhauer, Bianca

    2015-03-01

    The Pierre Auger Observatory detects high-energy cosmic rays with energies above ˜1017 eV. It is built as a multi-hybrid detector measuring extensive air showers with different techniques. For the reconstruction of extensive air showers, the atmospheric conditions at the site of the Observatory have to be known quite well. This is particularly true for reconstructions based on data obtained by the fluorescence technique. For these data, not only the weather conditions near ground are relevant, most important are altitude-dependent atmospheric profiles. The Pierre Auger Observatory has set up a dedicated atmospheric monitoring programme at the site in the Mendoza province, Argentina. Beyond this, exploratory studies were performed in Colorado, USA, for possible installations in the northern hemisphere. In recent years, the atmospheric monitoring programme at the Pierre Auger Observatory was supplemented by applying data from atmospheric models. Both GDAS and HYSPLIT are developments by the US weather department NOAA and the data are freely available. GDAS is a global model of the atmospheric state parameters on a 1 degree geographical grid, based on real-time measurements and numeric weather predictions, providing a full altitude-dependent data set every 3 hours. HYSPLIT is a powerful tool to track the movement of air masses at various heights, and with it the aerosols. Combining local measurements of the atmospheric state variables and aerosol scattering with the given model data, advanced studies about atmospheric conditions can be performed and high precision air shower reconstructions are achieved.

  20. Resonant Auger decay driving intermolecular Coulombic decay in molecular dimers.

    PubMed

    Trinter, F; Schöffler, M S; Kim, H-K; Sturm, F P; Cole, K; Neumann, N; Vredenborg, A; Williams, J; Bocharova, I; Guillemin, R; Simon, M; Belkacem, A; Landers, A L; Weber, Th; Schmidt-Böcking, H; Dörner, R; Jahnke, T

    2014-01-30

    In 1997, it was predicted that an electronically excited atom or molecule placed in a loosely bound chemical system (such as a hydrogen-bonded or van-der-Waals-bonded cluster) could efficiently decay by transferring its excess energy to a neighbouring species that would then emit a low-energy electron. This intermolecular Coulombic decay (ICD) process has since been shown to be a common phenomenon, raising questions about its role in DNA damage induced by ionizing radiation, in which low-energy electrons are known to play an important part. It was recently suggested that ICD can be triggered efficiently and site-selectively by resonantly core-exciting a target atom, which then transforms through Auger decay into an ionic species with sufficiently high excitation energy to permit ICD to occur. Here we show experimentally that resonant Auger decay can indeed trigger ICD in dimers of both molecular nitrogen and carbon monoxide. By using ion and electron momentum spectroscopy to measure simultaneously the charged species created in the resonant-Auger-driven ICD cascade, we find that ICD occurs in less time than the 20 femtoseconds it would take for individual molecules to undergo dissociation. Our experimental confirmation of this process and its efficiency may trigger renewed efforts to develop resonant X-ray excitation schemes for more localized and targeted cancer radiation therapy.

  1. Laser enabled Auger decay in argon atoms and dimers

    NASA Astrophysics Data System (ADS)

    Ranitovic, Predrag; Tong, Xiao-Min; Hogle, Craig W.; Toshima, N.; Murnane, M. M.; Kapteyn, H. C.

    2011-05-01

    In rare-gas atoms, Auger decay in which an inner-valence shell ns hole is filled is normally not energetically allowed. However, in the presence of a strong laser field, a new laser-enabled Auger decay channel can open up to increase the double-ionization yield. This process is efficient at high laser intensities, and an ns hole can be filled within a few femtoseconds of its creation. This novel laser-enabled Auger decay (LEAD) process is of fundamental importance for controlling electron dynamics in atoms, molecules, and materials. We then use LEAD to investigate charge transfer in a Coulomb exploding Ar dimer. We can selectively double-ionize either the Ar dimer (threshold ~ 36 eV) or Ar atoms (threshold ~ 43.5 eV) using combined laser (1.5 eV) and XUV photons (36 eV) in a time-resolved fashion, and then comparing the kinetic energy releases. The Ar dimer can be double ionized when the 3s hole is filled by a 3p electron from either one of the two Ar atoms through LEAD. Theoretical calculation will support data taken using COLTRIMS and HHG.

  2. In vivo pharmacological characterisation of bilastine, a potent and selective histamine H1 receptor antagonist.

    PubMed

    Corcóstegui, Reyes; Labeaga, Luis; Innerárity, Ana; Berisa, Agustín; Orjales, Aurelio

    2006-01-01

    We set out to establish the in vivo histamine H(1) receptor antagonistic (antihistaminic) and antiallergic properties of bilastine. In vivo antihistaminic activity experiments consisted of measurement of: inhibition of increase in capillary permeability and reduction in microvascular extravasation and bronchospasm in rats and guinea pigs induced by histamine and other inflammatory mediators; and protection against lethality induced by histamine and other inflammatory mediators in rats. In vivo antiallergic activity experiments consisted of measurement of passive and active cutaneous anaphylactic reactions as well as type III and type IV allergic reactions in sensitised rodents. In the in vivo antihistaminic activity experiments, bilastine was shown to have a positive effect, similar to that of cetirizine and more potent than that of fexofenadine. The results of the in vivo antiallergic activity experiments showed that the properties of bilastine in this setting are similar to those observed for cetirizine and superior to fexofenadine in the model of passive cutaneous anaphylactic reaction. When active cutaneous anaphylactic reaction experiments were conducted, bilastine showed significant activity, less potent than that observed with cetirizine but superior to that of fexofenadine. Evaluation of the type III allergic reaction showed that of the antihistamines only bilastine was able to inhibit oedema in sensitised mice, although its effect in this respect was much less potent than that observed with dexamethasone. In terms of the type IV allergic reaction, neither bilastine, cetirizine nor fexofenadine significantly modified the effect caused by oxazolone. The results of our in vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastine possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

  3. Potent Selective Inhibition of Monoamine Oxidase A by Alternariol Monomethyl Ether Isolated from Alternaria brassicae.

    PubMed

    Lee, Hyun Woo; Kim, Yeon Ji; Nam, Sang-Jip; Kim, Hoon

    2017-02-28

    Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated from Alternaria brassicae along with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an IC50 value of 1.71 µM; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with a Ki value of 0.34 µM. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson's disease, and Alzheimer's disease.

  4. GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2).

    PubMed

    Crawford, Terry D; Audia, James E; Bellon, Steve; Burdick, Daniel J; Bommi-Reddy, Archana; Côté, Alexandre; Cummings, Richard T; Duplessis, Martin; Flynn, E Megan; Hewitt, Michael; Huang, Hon-Ren; Jayaram, Hariharan; Jiang, Ying; Joshi, Shivangi; Kiefer, James R; Murray, Jeremy; Nasveschuk, Christopher G; Neiss, Arianne; Pardo, Eneida; Romero, F Anthony; Sandy, Peter; Sims, Robert J; Tang, Yong; Taylor, Alexander M; Tsui, Vickie; Wang, Jian; Wang, Shumei; Wang, Yongyun; Xu, Zhaowu; Zawadzke, Laura; Zhu, Xiaoqin; Albrecht, Brian K; Magnuson, Steven R; Cochran, Andrea G

    2017-07-13

    The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

  5. Aromatic lipoxin A4 and lipoxin B4 analogues display potent biological activities.

    PubMed

    O'Sullivan, Timothy P; Vallin, Karl S A; Shah, Syed Tasadaque Ali; Fakhry, Jérôme; Maderna, Paola; Scannell, Michael; Sampaio, Andre L F; Perretti, Mauro; Godson, Catherine; Guiry, Patrick J

    2007-11-29

    Lipoxins are a group of biologically active eicosanoids typically formed by transcellular lipoxygenase activity. Lipoxin A4 (LXA4) and Lipoxin B4 (LXB4) biosynthesis has been detected in a variety of inflammatory conditions. The native lipoxins LXA4 and LXB4 demonstrate potent antiinflammatory and proresolution bioactions. However, their therapeutic potential is compromised by rapid metabolic inactivation by PG dehydrogenase-mediated oxidation and reduction. Here we report on the stereoselective synthesis of aromatic LXA4 and LXB4 analogues by employing Sharpless epoxidation, Pd-mediated Heck coupling, and diastereoselective reduction as the key transformations. Subsequent biological testing has shown that these analogues display potent biological activities. Phagocytic clearance of apoptotic leukocytes plays a critical role in the resolution of inflammation. Both LXA4 analogues (1R)-3a and (1S)-3a were found to stimulate a significant increase in phagocytosis of apoptotic polymorphonuclear leukocytes (PMN) by macrophages, with comparable efficacy to the effect of native LXA4, albeit greater potency, while the LXB4 analogue also stimulated phagocytosis with a maximum effect observed at 10-11 M. LX-stimulated phagocytosis was associated with rearrangement of the actin cytoskeleton consistent with that reported for native lipoxins. Using zymosan-induced peritonitis as a murine model of acute inflammation (1R)-3a significantly reduced PMN accumulation.

  6. Basic Tetrapeptides as Potent Intracellular Inhibitors of Type A Botulinum Neurotoxin Protease Activity*

    PubMed Central

    Hale, Martha; Oyler, George; Swaminathan, Subramanyam; Ahmed, S. Ashraf

    2011-01-01

    Botulinum neurotoxins (BoNT) are the most potent of all toxins that cause flaccid muscle paralysis leading to death. They are also potential biothreat agents. A systematic investigation of various short peptide inhibitors of the BoNT protease domain with a 17-residue peptide substrate led to arginine-arginine-glycine-cysteine having a basic tetrapeptide structure as the most potent inhibitor. When assayed in the presence of dithiothreitol (DTT), the inhibitory effect was drastically reduced. Replacing the terminal cysteine with one hydrophobic residue eliminated the DTT effect but with two hydrophobic residues made the pentapeptide a poor inhibitor. Replacing the first arginine with cysteine or adding an additional cysteine at the N terminus did not improve inhibition. When assessed using mouse brain lysates, the tetrapeptides also inhibited BoNT/A cleavage of the endogenous SNAP-25. The peptides penetrated the neuronal cell lines, N2A and BE(2)-M17, without adversely affecting metabolic functions as measured by ATP production and P-38 phosphorylation. Biological activity of the peptides persisted within cultured chick motor neurons and rat and mouse cerebellar neurons for more than 40 h and inhibited BoNT/A protease action inside the neurons in a dose- and time-dependent fashion. Our results define a tetrapeptide as the smallest peptide inhibitor in the backdrop of a large substrate protein of 200+ amino acids having multiple interaction regions with its cognate enzyme. The inhibitors should also be valuable candidates for drug development. PMID:20961849

  7. Basis Tetrapeptides as Potent Intracellular Inhibitors of type A Botulinum Neurotoxin Protease Activity

    SciTech Connect

    Hale, M.; Swaminathan, S.; Oyler, G.; Ahmed, S. A.

    2011-01-21

    Botulinum neurotoxins (BoNT) are the most potent of all toxins that cause flaccid muscle paralysis leading to death. They are also potential biothreat agents. A systematic investigation of various short peptide inhibitors of the BoNT protease domain with a 17-residue peptide substrate led to arginine-arginine-glycine-cysteine having a basic tetrapeptide structure as the most potent inhibitor. When assayed in the presence of dithiothreitol (DTT), the inhibitory effect was drastically reduced. Replacing the terminal cysteine with one hydrophobic residue eliminated the DTT effect but with two hydrophobic residues made the pentapeptide a poor inhibitor. Replacing the first arginine with cysteine or adding an additional cysteine at the N terminus did not improve inhibition. When assessed using mouse brain lysates, the tetrapeptides also inhibited BoNT/A cleavage of the endogenous SNAP-25. The peptides penetrated the neuronal cell lines, N2A and BE(2)-M17, without adversely affecting metabolic functions as measured by ATP production and P-38 phosphorylation. Biological activity of the peptides persisted within cultured chick motor neurons and rat and mouse cerebellar neurons for more than 40 h and inhibited BoNT/A protease action inside the neurons in a dose- and time-dependent fashion. Our results define a tetrapeptide as the smallest peptide inhibitor in the backdrop of a large substrate protein of 200+ amino acids having multiple interaction regions with its cognate enzyme. The inhibitors should also be valuable candidates for drug development.

  8. A Nonpolycationic Fully Proteinaceous Multiagent System for Potent Targeted Delivery of siRNA

    PubMed Central

    Liu, David V; Yang, Nicole J; Wittrup, K Dane

    2014-01-01

    Protein-based methods of targeted short-interfering RNA (siRNA) delivery have the potential to solve some of the problems faced by nanoparticle-based methods, such as poor pharmacokinetics and biodistribution, low tumor penetration, and polydispersity. However, protein-based targeted delivery has been limited to fusion proteins with polycationic peptides as siRNA carriers, whose high charge density in some cases results in undesirable biophysical and in vivo properties. Here, we present a fully proteinaceous, multiagent approach for targeted siRNA delivery to epidermal growth factor receptor (EGFR), using a nonpolycationic carrier for siRNA. Each agent contributes a fundamentally different mechanism of action that work together for potent targeted RNA interference. The first agent is an EGFR-targeted fusion protein that uses a double-stranded RNA-binding domain as a nonpolycationic siRNA carrier. This double-stranded RNA-binding domain fusion protein can deliver siRNA to the endosomes of an EGFR-expressing cell line. A second agent delivers the cholesterol-dependent cytolysin, perfringolysin O, in a targeted manner, which enhances the endosomal escape of siRNA and induces gene silencing. A third agent that clusters EGFR increases gene-silencing potency and decreases cytolysin toxicity. Altogether, this system is potent, with only 16 nmol/l siRNA required for gene silencing and a therapeutic window that spans two orders of magnitude of targeted cytolysin concentrations. PMID:24825362

  9. In silico design, synthesis and evaluation of 3'-O-benzylated analogs of salacinol, a potent α-glucosidase inhibitor isolated from an Ayurvedic traditional medicine "Salacia".

    PubMed

    Tanabe, Genzoh; Nakamura, Shinya; Tsutsui, Nozomi; Balakishan, Gorre; Xie, Weijia; Tsuchiya, Satoshi; Akaki, Junji; Morikawa, Toshio; Ninomiya, Kiyofumi; Nakanishi, Isao; Yoshikawa, Masayuki; Muraoka, Osamu

    2012-09-07

    With the aid of an in silico method, α-glucosidase inhibitors with far more potent activities than salacinol (1), a potent natural α-glucosidase inhibitor isolated from an Ayurvedic traditional medicine Salacia reticulata, have been developed.

  10. Auger investigation of annealing processes in MOS technology

    NASA Astrophysics Data System (ADS)

    Jost, S. R.

    Thin oxides of SiO2 on clean Si surfaces were studied by Auger electron spectroscopy to determine the effects of various annealing processes on the Si/SiO2 interface. A defect peak was observed in the Auger spectrum near 83 eV that is theoretically associated with dangling Si bonds at the interface which are caused by lattice mismatch between Si and SiO2. Exposure to hydrogen significantly reduced the magnitude of this Auger peak which corresponds to the reduction in interface-state density in MOS structures following a low temperature forming gas anneal. Subsequent heat treatment in ultrahigh vacuum resulted in the return of the defect peak in the spectrum showing the reversibility of the role of hydrogen in interface state passivation. Nitrogen, argon, and vacuum high temperature anneals were also investigated, and it was found that nitrogen anneals seem to be more effective in the reduction of interface-state density, although a mechanism for its effectiveness could not be determined.

  11. Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template.

    PubMed

    Woo, L W Lawrence; Jackson, Toby; Putey, Aurélien; Cozier, Gyles; Leonard, Philip; Acharya, K Ravi; Chander, Surinder K; Purohit, Atul; Reed, Michael J; Potter, Barry V L

    2010-03-11

    Single agents against multiple drug targets are of increasing interest. Hormone-dependent breast cancer (HDBC) may be more effectively treated by dual inhibition of aromatase and steroid sulfatase (STS). The aromatase inhibitory pharmacophore was thus introduced into a known biphenyl STS inhibitor to give a series of novel dual aromatase-sulfatase inhibitors (DASIs). Several compounds are good aromatase or STS inhibitors and DASI 20 (IC(50): aromatase, 2.0 nM; STS, 35 nM) and its chlorinated congener 23 (IC(50): aromatase, 0.5 nM; STS, 5.5 nM) are examples that show exceptional dual potency in JEG-3 cells. Both biphenyls share a para-sulfamate-containing ring B and a ring A, which contains a triazol-1-ylmethyl meta to the biphenyl bridge and para to a nitrile. At 1 mg/kg po, 20 and 23 reduced plasma estradiol levels strongly and inhibited liver STS activity potently in vivo. 23 is nonestrogenic and potently inhibits carbonic anhydrase II (IC(50) 86 nM). A complex was crystallized and its structure was solved by X-ray crystallography. This class of DASI should encourage further development toward multitargeted therapeutic intervention in HDBC.

  12. Discovery of Potent Cyclophilin Inhibitors Based on the Structural Simplification of Sanglifehrin A.

    PubMed

    Steadman, Victoria A; Pettit, Simon B; Poullennec, Karine G; Lazarides, Linos; Keats, Andrew J; Dean, David K; Stanway, Steven J; Austin, Carol A; Sanvoisin, Jonathan A; Watt, Gregory M; Fliri, Hans G; Liclican, Albert C; Jin, Debi; Wong, Melanie H; Leavitt, Stephanie A; Lee, Yu-Jen; Tian, Yang; Frey, Christian R; Appleby, Todd C; Schmitz, Uli; Jansa, Petr; Mackman, Richard L; Schultz, Brian E

    2017-02-09

    Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but the generation of potent, drug-like molecules through chemical synthesis has been challenging. In this study, a set of macrocyclic cyclophilin inhibitors was synthesized based on the core structure of the natural product sanglifehrin A. Initial compound optimization identified the valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in the sanglifehrin core, stereocenters at C14 and C15, and the hydroxyl group of the m-tyrosine (m-Tyr) residue as key contributors to compound potency. Replacing the C18-C21 diene unit of sanglifehrin with a styryl group led to potent compounds that displayed a novel binding mode in which the styrene moiety engaged in a π-stacking interaction with Arg55 of cyclophilin A (Cyp A), and the m-Tyr residue was displaced into solvent. This observation allowed further simplifications of the scaffold to generate new lead compounds in the search for orally bioavailable cyclophilin inhibitors.

  13. Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable Anticoagulant.

    PubMed

    Soule, Erin E; Bompiani, Kristin M; Woodruff, Rebecca S; Sullenger, Bruce A

    2016-02-01

    Potent and rapid-onset anticoagulation is required for several clinical settings, including cardiopulmonary bypass surgery. In addition, because anticoagulation is associated with increased bleeding following surgery, the ability to rapidly reverse such robust anticoagulation is also important. Previously, we observed that no single aptamer was as potent as heparin for anticoagulating blood. However, we discovered that combinations of two aptamers were as potent as heparin. Herein, we sought to combine two individual anticoagulant aptamers into a single bivalent RNA molecule in an effort to generate a single molecule that retained the potent anticoagulant activity of the combination of individual aptamers. We created four bivalent aptamers that can inhibit Factor X/Xa and prothrombin/thrombin and anticoagulate plasma, as well as the combination of individual aptamers. Detailed characterization of the shortest bivalent aptamer indicates that each aptamer retains full binding and functional activity when presented in the bivalent context. Finally, reversal of this bivalent aptamer with a single antidote was explored, and anticoagulant activity could be rapidly turned off in a dose-dependent manner. These studies demonstrate that bivalent anticoagulant aptamers represent a novel and potent approach to actively and reversibly control coagulation.

  14. Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable Anticoagulant

    PubMed Central

    Soule, Erin E.; Bompiani, Kristin M.; Woodruff, Rebecca S.

    2016-01-01

    Potent and rapid-onset anticoagulation is required for several clinical settings, including cardiopulmonary bypass surgery. In addition, because anticoagulation is associated with increased bleeding following surgery, the ability to rapidly reverse such robust anticoagulation is also important. Previously, we observed that no single aptamer was as potent as heparin for anticoagulating blood. However, we discovered that combinations of two aptamers were as potent as heparin. Herein, we sought to combine two individual anticoagulant aptamers into a single bivalent RNA molecule in an effort to generate a single molecule that retained the potent anticoagulant activity of the combination of individual aptamers. We created four bivalent aptamers that can inhibit Factor X/Xa and prothrombin/thrombin and anticoagulate plasma, as well as the combination of individual aptamers. Detailed characterization of the shortest bivalent aptamer indicates that each aptamer retains full binding and functional activity when presented in the bivalent context. Finally, reversal of this bivalent aptamer with a single antidote was explored, and anticoagulant activity could be rapidly turned off in a dose-dependent manner. These studies demonstrate that bivalent anticoagulant aptamers represent a novel and potent approach to actively and reversibly control coagulation. PMID:26584417

  15. Resonant Auger Effect at High X-Ray Intensity

    SciTech Connect

    Rohringer, N; Santra, R

    2008-03-27

    The resonant Auger effect of atomic neon exposed to high-intensity x-ray radiation in resonance with the 1s {yields} 3p transition is discussed. High intensity here means that the x-ray peak intensity is sufficient ({approx} 10{sup 18} W/cm{sup 2}) to induce Rabi oscillations between the neon ground state and the 1s{sup -1}3p ({sup 1}P) state within the relaxation lifetime of the inner-shell vacancy. For the numerical analysis presented, an effective two-level model, including a description of the resonant Auger decay process, is employed. Both coherent and chaotic x-ray pulses are treated. The latter are used to simulate radiation from x-ray free-electron lasers based on the principle of self-amplified spontaneous emission. Observing x-ray-driven atomic population dynamics in the time domain is challenging for chaotic pulse ensembles. A more practical option for experiments using x-ray free-electron lasers is to measure the line profiles in the kinetic energy distribution of the resonant Auger electron. This provides information on both atomic population dynamics and x-ray pulse properties.

  16. CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo.

    PubMed

    Hjarnaa, P J; Jonsson, E; Latini, S; Dhar, S; Larsson, R; Bramm, E; Skov, T; Binderup, L

    1999-11-15

    A new class of recently discovered antineoplastic agents, the pyridyl cyanoguanidines, exert a potent antitumor activity in rodents after oral administration. Optimization in vitro and in vivo has resulted in the selection of the lead candidate CHS 828 (N-(6-chlorophenoxyhexyl)-N'cyano-N"-4-pyridylguanidine). CHS 828 was found to exert potent cytotoxic effects in human breast and lung cancer cell lines, with lesser effects on normal fibroblasts and endothelial cells. In a study using a panel of cell lines with different resistance patterns, the effects of CHS 828 showed a low correlation with the activity patterns of known anticancer agents, and no sensitivity to known mechanisms of multidrug resistance was observed. In nude mice bearing human tumor xenografts, CHS 828, at doses from 20 to 50 mg/kg/day p.o., inhibited the growth of MCF-7 breast cancer tumors and caused regression of NYH small cell lung cancer tumors. Oral administration of CHS 828 once weekly improved efficacy without increasing toxicity. CHS 828 was found to compare favorably with established chemotherapeutic agents such as cyclophosphamide, etoposide, methotrexate, and paclitaxel. In mice with NYH tumors, long-term survival (>6 months) was observed after treatment with CHS 828 was stopped. In conclusion, CHS 828 is an effective new antitumor agent, with a potentially new mechanism of action. CHS 828 is presently being tested in Phase I clinical trials in collaboration with the European Organization for Research and Treatment of Cancer.

  17. Observation of the Auger resonant Raman effect

    SciTech Connect

    Brown, G.S.; Chen, M.H.; Crasemann, B.; Ice, G.E.

    1980-11-01

    Monochromatized synchrotron radiation near the photoionization threshold was used to produce the (2p/sub 3/2/) vacancy state in atomic Xe. Deexcitation of the state through L/sub 3/-M/sub 4/M/sub 5/(/sup 1/G/sub 4/) Auger-electron emission was measured. The 5d spectator-electron Auger satellite was observed. The satellite energy exhibits linear dispersion. The observed width of the /sup 1/G diagram line decreases by approx. 40% when the exciting photon energy reaches the vicinity of the Xe L/sub 3/ binding energy. This radiationless process can thus be construed as the Auger analog of the x-ray resonant Raman effect. The /sup 1/G diagram line is shifted by -+3 eV due to post-collision interaction; this shift varies with excitation energy.

  18. Identification of a potent immunostimulatory oligodeoxynucleotide from Streptococcus thermophilus lacZ.

    PubMed

    Shimosato, Takeshi; Tohno, Masanori; Sato, Takashi; Nishimura, Junko; Kawai, Yasushi; Saito, Tadao; Kitazawa, Haruki

    2009-10-01

    Immunostimulatory sequences of oligodeoxynucleotides (ODNs), such as CpG ODNs, are potent stimulators of innate immunity. Here, we identified a strong immunostimulatory CpG ODN, which we named MsST, from the lac Z gene of Streptococcus (S.) thermophilus ATCC19258, and we evaluated its immune functions. In in vitro studies, MsST had a similar ability as the murine prototype CpG ODN 1555 to induce inflammatory cytokine production and cell proliferation. In mouse splenocytes, MsST increased the number of CD80+CD11c+and CD86+CD11c+ dendritic cells and CD4+CD25+ regulatory T cells. We also analyzed the effects of MsST on the expression of regulatory cytokines by real-time quantitative PCR. MsST was more potent at inducing interleukin-10 expression than the ODN control 1612, indicating that MsST can augment the regulatory T cell response via Toll-like receptor 9, which plays an important role in suppressing T helper type 2 responses. These results suggest that S. thermophilus, whose genes include a strong Immunostimulatory sequence-ODN, is a good candidate for a starter culture to develop new physiologically functional foods and feeds.

  19. Rice Bran Protein as a Potent Source of Antimelanogenic Peptides with Tyrosinase Inhibitory Activity.

    PubMed

    Ochiai, Akihito; Tanaka, Seiya; Tanaka, Takaaki; Taniguchi, Masayuki

    2016-10-28

    Rice (Oryza sativa) is consumed as a staple food globally, and rice bran, the byproduct, is an unused biomass that is ultimately discarded as waste. Thus, in the present study, a technique for producing tyrosinase inhibitory peptides from rice bran protein (RBP) was developed. Simultaneous treatment of RBP with chymotrypsin and trypsin produced numerous peptides. Subsequently, six tyrosinase inhibitory peptides were isolated from the hydrolysate fractions in a multistep purification protocol, and their amino acid sequences were determined. Three of these peptides had a C-terminal tyrosine residue and exhibited significant inhibitory effects against tyrosinase-mediated monophenolase reactions. Furthermore, peptide CT-2 (Leu-Gln-Pro-Ser-His-Tyr) potently inhibited melanogenesis in mouse B16 melanoma cells without causing cytotoxicity, suggesting the potential of CT-2 as an agent for melanin-related skin disorder treatment. The present data indicate that RBP is a potent source of tyrosinase inhibitory peptides and that simultaneous treatment of RBP with chymotrypsin and trypsin efficiently produces these peptides.

  20. Climbazole is a new potent inducer of rat hepatic cytochrome P450.

    PubMed

    Kobayashi, Y; Suzuki, M; Ohshiro, N; Sunagawa, T; Sasaki, T; Tokuyama, S; Yamamoto, T; Yoshida, T

    2001-08-01

    We examined the effect of climbazole on the induction of rat hepatic microsomal cytochrome P450 (P450), and compared the induction potency with other N-substituted azole drugs such as clorimazole. We found that climbazole is found to be a potent inducer of rat hepatic microsomal P450 as clorimazole. Induced level of P450 by climbazole was almost similar in extent to clorimazole when compared with other imidazole drugs in a dose- and time-dependent manner. Parallel to the increase in P450, climbazole increased aminopyrine and erythromycin N-demethylase, ethoxycoumarin O-deethylase, and androstenedione 16 beta- and 15 alpha/6 beta hydroxylase activities; however, clorimazole did not induce aminopyrine N-demethylase activity irrespective of its marked increase in P450 content. Immunoblot analyses revealed that climbazole induced CYP2B1, 3A2 and 4A1. The present findings indicate that climbazole is a new potent inducer of hepatic microsomal P450 and drug-metabolizing enzymes like clorimazole, but it may have some differential mechanism(s) for these enzymes' induction in rat liver.