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Sample records for katrin jgar aare

  1. The KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Beck, Marcus; Katrin Collaboration

    2010-01-01

    The KArlsruhe TRitium Neutrino mass experiment, KATRIN, aims to search for the mass of the electron neutrino with a sensitivity of 0.2eV/c2 (90% C.L.) and a detection limit of 0.35 eV/c2 (5σ). Both a positive or a negative result will have far reaching implications for cosmology and the standard model of particle physics and will give new input for astroparticle physics and cosmology. The major components of KATRIN are being set up at the Karlsruhe Institut of Technology in Karlsruhe, Germany, and test measurements of the individual components have started. Data taking with tritium is scheduled to start in 2012.

  2. The Katrin Experiment: Status and Outlook

    NASA Astrophysics Data System (ADS)

    Parno, D. S.

    2014-01-01

    The KATRIN experiment, presently under construction in Karlsruhe, Germany, will improve on previous laboratory limits on the neutrino mass by a factor of ten. KATRIN will use a high-activity, gaseous T2 source and a very high-resolution spectrometer to measure the shape of the high-energy tail of the tritium-decay β spectrum. The shape measurement will also be sensitive to new physics, including sterile neutrinos and Lorentz violation. This report summarizes recent progress in the experiment.

  3. Status of the neutrino mass experiment KATRIN

    SciTech Connect

    Bornschein, L.; Bornschein, B.; Sturm, M.; Roellig, M.; Priester, F.

    2015-03-15

    The most sensitive way to determine the neutrino mass scale without further assumptions is to measure the shape of a tritium beta spectrum near its kinematic end-point. Tritium is the nucleus of choice because of its low endpoint energy, superallowed decay and simple atomic structure. Within an international collaboration the Karlsruhe Tritium Neutrino experiment (KATRIN) is currently being built up at KIT. KATRIN will allow a model-independent measurement of the neutrino mass scale with an expected sensitivity of 0.2 eV/c{sup 2} (90% CL). KATRIN will use a source of ultrapure molecular tritium. This contribution presents the status of the KATRIN experiment, thereby focusing on its Calibration and Monitoring System (CMS), which is the last component being subject to research/development. After a brief overview of the KATRIN experiment in Section II the CMS is introduced in Section III. In Section IV the Beta Induced X-Ray Spectroscopy (BIXS) as method of choice to monitor the tritium activity of the KATRIN source is described and first results are presented.

  4. Status of the KATRIN Neutrino Mass Experiment

    NASA Astrophysics Data System (ADS)

    Parno, Diana; Katrin Collaboration

    2015-04-01

    The Karlsruhe Tritium Neutrino experiment (KATRIN), presently under construction in Germany, will probe the absolute mass scale of the neutrino through the kinematics of tritium beta decay, a nearly model-independent approach. To achieve the projected sensitivity of 0.2 eV at the 90% confidence level, KATRIN will use a windowless, gaseous tritium source and a large magnetic adiabatic collimation-electrostatic filter. The collaboration has now completed a second commissioning phase of the spectrometer and detector section, and construction of the tritium sections is proceeding well. We will report on the current status of the experiment and the outlook for data-taking with tritium. US participation in KATRIN is supported by the U.S. Department of Energy Office of Science, Office of Nuclear Physics under Award Number DE-FG02-97ER41020.

  5. KATRIN: Measuring the Mass Scale of Neutrinos

    NASA Astrophysics Data System (ADS)

    Oblath, Noah; Katrin Collaboration

    2011-10-01

    Over the past decade, experiments studying neutrinos from atmospheric, solar, and reactor sources have shown conclusively that neutrinos change flavor and, as a consequence, have a small but finite mass. However, the scale of neutrino masses remains an open question that is of great importance for many areas of physics. The most direct method to measure the neutrino mass scale is still via beta decay. The talk will focus primarily on the status of the KArlsruhe TRItium Neutrino experiment (KATRIN), currently under construction. KATRIN combines an ultra-luminous molecular windowless gaseous tritium source with a high-resolution integrating spectrometer to gain sensitivity to the absolute mass scale of neutrinos. The projected sensitivity of the experiment on the neutrino mass is 0.2 eV at 90% C.L. In this talk I will discuss the status of the KATRIN experiment.

  6. Commissioning Measurements of the KATRIN Main Spectrometer

    NASA Astrophysics Data System (ADS)

    Wierman, Kevin; Katrin Collaboration

    2013-10-01

    Beginning in May 2013, the KArlsruhe TRItium Neutrino experiment (KATRIN) collaboration began measurements to commission the 10-m diameter main spectrometer. KATRIN utilizes the spectrometer to provide magnetic adiabatic collimation and electrostatic filtering designed to analyze the tritium beta decay spectrum for contributions from the neutrino mass. In order to achieve an order-of-magnitude improvement on previous neutrino mass experiments the desired sensitivity of the apparatus must be 200 meV in the decay endpoint region. Goals of the recent measurements include identification and reduction of backgrounds and determination of the spectrometer transfer function. Backgrounds have been probed by utilizing electromagnetic field configurations to explore decays in the spectrometer, Penning traps and field emission. A 148-pixel PIN diode array is employed to detect particles exiting the spectrometer, which permits angular and radial distributions of particles to be analyzed. This has allowed for high precision comparison between measurements and simulations of expected backgrounds to be investigated in order to commission the spectrometer. This work is supported by grants from the DOE Office of Nuclear Physics and the Helmholtz Association.

  7. The Automated Aircraft Rework System (AARS): A system integration approach

    NASA Technical Reports Server (NTRS)

    Benoit, Michael J.

    1994-01-01

    The Mercer Engineering Research Center (MERC), under contract to the United States Air Force (USAF) since 1989, has been actively involved in providing the Warner Robins Air Logistics Center (WR-ALC) with a robotic workcell designed to perform rework automated defastening and hole location/transfer operations on F-15 wings. This paper describes the activities required to develop and implement this workcell, known as the Automated Aircraft Rework System (AARS). AARS is scheduled to be completely installed and in operation at WR-ALC by September 1994.

  8. Electron line shape of the KATRIN monitor spectrometer

    NASA Astrophysics Data System (ADS)

    Slezák, M.; Bauer, S.; Dragoun, O.; Erhard, M.; Schlösser, K.; Špalek, A.; Vénos, D.; Zbořil, M.

    2013-12-01

    Conversion electrons emitted from 83mKr implanted into a solid substrate will serve as a powerful tool for monitoring of the energy scale stability in the KATRIN neutrino experiment. An appropriate description of the conversion line shape is essential to determine the energy of the emitted electrons. It is shown that the Doniach-Šunjić line shape gives a significantly better fit to the conversion electron spectra than the previously used double Voigt model. The electron spectra were obtained with the KATRIN MAC-E filter monitor spectrometer.

  9. Focal-plane detector system for the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Amsbaugh, J. F.; Barrett, J.; Beglarian, A.; Bergmann, T.; Bichsel, H.; Bodine, L. I.; Bonn, J.; Boyd, N. M.; Burritt, T. H.; Chaoui, Z.; Chilingaryan, S.; Corona, T. J.; Doe, P. J.; Dunmore, J. A.; Enomoto, S.; Formaggio, J. A.; Fränkle, F. M.; Furse, D.; Gemmeke, H.; Glück, F.; Harms, F.; Harper, G. C.; Hartmann, J.; Howe, M. A.; Kaboth, A.; Kelsey, J.; Knauer, M.; Kopmann, A.; Leber, M. L.; Martin, E. L.; Middleman, K. J.; Myers, A. W.; Oblath, N. S.; Parno, D. S.; Peterson, D. A.; Petzold, L.; Phillips, D. G.; Renschler, P.; Robertson, R. G. H.; Schwarz, J.; Steidl, M.; Tcherniakhovski, D.; Thümmler, T.; Van Wechel, T. D.; VanDevender, B. A.; Vöcking, S.; Wall, B. L.; Wierman, K. L.; Wilkerson, J. F.; Wüstling, S.

    2015-04-01

    The focal-plane detector system for the KArlsruhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high-vacuum system, a high-vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system. It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.

  10. Characterization of the KATRIN Focal Plane Detector

    NASA Astrophysics Data System (ADS)

    Bodine, Laura; Leber, Michelle; Myers, Allan; Tolich, Kazumi; Vandevender, Brent; Wall, Brandon

    2008-10-01

    The Karlsruhe Tritium Neutrino (KATRIN) Experiment is a next generation tritium beta decay experiment designed to measure directly the electron neutrino mass with a sensitivity of 0.2 eV. In the experiment, electrons from tritium decay of a gaseous source are magnetically guided through analyzing solenoidal retarding electrostatic spectrometers and detected via a focal plane detector. The focal plane detector is a 90mm diameter, 500 micron thick monolithic silicon pin-diode array with 148 pixels. The diode contacts have a titanium nitride overlayer and are connected to preamplifiers via an array of spring-loaded pogo pins. This novel connection scheme minimizes backgrounds from radioactive materials near the detector, facilitates characterization and replacement of the detector wafer, but requires a unique mounting design. The force of the pins strains the silicon, possibly altering the detector properties and performance. Results on the mechanical, thermal and electrical performance of a prototype detector under stress from pogo pin readouts will be presented.

  11. Penning Trap Searches in the KATRIN Main Spectrometer

    NASA Astrophysics Data System (ADS)

    Wierman, Kevin; Katrin Collaboration

    2015-10-01

    The Karlsruhe Tritium Neutrino Experiment (KATRIN) aims to make a precision measurement of the tritium beta decay spectrum with a projected sensitivity to neutrino mass of 200 meV. Meeting this goal requires low backgrounds in the beta decay endpoint region. In KATRIN, spatially confined charged particles represent a potential source of backgrounds and systematic errors. Trapping conditions can occur in KATRIN's 10m diameter main spectrometer due to the high magnetic and electrostatic fields required to momentum analyze the electrons. Backgrounds are generated by trapped particles due to scattering off residual gas in the spectrometer causing negative ions to be accelerated towards KATRIN's detector system. Additionally, systematic errors in the neutrino mass measurement can be caused by the electrostatic field generated by trapped electrons. To search for these conditions, the spectrometer was probed by a monoenergetic electron source to determine trapping probabilities as a function of the applied electric and magnetic fields. We acknowledge the support of the German Helmholtz Association, the German Ministry for Education and Research, the Helmholtz Alliance for Astroparticle Physics, the Grant Agency of the Czech Republic, and the US Department of Energy.

  12. Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.

    PubMed

    Santos, Karine; Preussner, Marco; Heroven, Anna Christina; Weber, Gert

    2015-11-01

    In eukaryotes, the removal of nuclear noncoding sequences (pre-mRNA splicing) is catalyzed by the spliceosome, which consists of five ribonucleoprotein particles (U1, U2, U4, U5 and U6 snRNPs, each with a respective snRNA) and a plethora of protein factors that aid spliceosomal maturation, assembly, activation and disassembly. Recently, the U5 snRNP maturation factor Aar2p from baker's yeast has been characterized structurally and biochemically. Aar2p binds to the RNaseH (RH) and Jab1/MPN domains of the highly conserved U5-specific Prp8p, which forms a framework for the spliceosomal catalytic centre. Thereby, Aar2p sterically excludes Brr2p, a helicase essential for the catalytic activation of the spliceosome, from Prp8p binding. At the same time, Aar2p blocks U4/U6 di-snRNA binding to Prp8p. Aar2p therefore prevents premature spliceosome activation and its functions are regulated by reversible phosphorylation. To date, little is known about the hypothetical human Aar2 (hsAar2) orthologue C20ORF4. This study identifies C20ORF4 (i) as part of the HeLa proteome by Western blotting and (ii) as a true Aar2 orthologue which binds to the RH domain (hsRH) of Prp8 and corroborates an evolutionary link between yeast and human Aar2 function. An elaborate strategy was devised to crystallize hsAar2 in complex with hsRH. The analysis of initial weakly diffracting crystals obtained by in situ proteolysis and homology modelling guided the design of an hsAar2 construct in which an internal loop was replaced by three serines (hsAar2(Δloop)). A complex of hsAar2(Δloop) and hsRH crystallized in space group C2; the crystals diffracted to 2.35 Å resolution and were suitable for structure determination by molecular-replacement approaches. The study presented here suggests a connection between Aar2 and the spliceosome in human cells and paves the way for structural studies of human Aar2. PMID:26527271

  13. FASD -- De Aar mums get beyond the 'tippling point'.

    PubMed

    Bateman, Chris

    2010-11-01

    When most of the low-income folk in the 'ghost train' town of De Aar began remonstrating with any pregnant mother who was boozing, excited campaigners thought they'd broken through the 'tippling point'. However, their research colleagues proved they'd gone even further -- the dedicated local platoon of social workers, nurses, therapists and volunteers had in three short years reduced the prevalence of fetal alcohol spectrum disorder (FASD) by 30%. This is in a town with the worst recorded FASD prevalence in any single community in the world, where 120 out of every 1 000 residents suffer from FASD (12%). PMID:21081033

  14. Environmental gamma radiation in the KATRIN Spectrometer Hall

    NASA Astrophysics Data System (ADS)

    Kippenbrock, Luke; Katrin Collaboration

    2016-03-01

    The KATRIN (KArlsruhe TRItium Neutrino) experiment, presently undergoing final assembly in Germany, will use tritium β-decay to probe the electron antineutrino mass down to a sensitivity of 0.2 eV/c2 (90% confidence level). The experimental apparatus has been designed to limit the effect of known and predicted backgrounds near the beta endpoint energy. However, recent commissioning measurements with the main spectrometer have shown that an elusive background source still remains. In this talk, the interaction of environmental gamma radiation inside the KATRIN main spectrometer is studied as a potential background creation mechanism. Geant4 simulations of the gamma flux, derived from concrete radioassay measurements, are compared with detector background rates collected under multiple gamma radiation conditions. Funded by U.S. Department of Energy, Office of Nuclear Physics under Grant #DE-FG02-97ER41020.

  15. First tritium results of the KATRIN test experiment TRAP

    SciTech Connect

    Eichelhardt, F.; Bornschein, B.; Bornschein, L.; Kazachenko, O.; Kernert, N.; Sturm, M.

    2008-07-15

    The TRAP experiment (Tritium Argon frost Pump) has been built at the Tritium Laboratory Karlsruhe (TLK) as a test rig for the Cryogenic Pumping Section (CPS) of the Karlsruhe Tritium Neutrino Experiment (KATRIN). TRAP employs a heterogeneous layer of pre-condensed argon to adsorb hydrogen isotopes at {approx} 4.2 K This paper presents results obtained in the first three tritium experiments with TRAP. (authors)

  16. Precision high voltage divider for the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Thümmler, Th; Marx, R.; Weinheimer, Ch

    2009-10-01

    The Karlsruhe Tritium Neutrino (KATRIN) experiment aims to determine the absolute mass of the electron antineutrino from a precise measurement of the tritium β-spectrum near its endpoint at 18.6 keV with a sensitivity of 0.2 eV c-2. KATRIN uses an electrostatic retardation spectrometer of MAC-E filter type for which it is crucial to monitor high voltages of up to 35 kV with a precision and long-term stability at the ppm level. Since devices capable of this precision are not commercially available, a new high voltage divider for direct voltages of up to 35 kV has been designed, following the new concept of the standard divider for direct voltages of up to 100 kV developed at the Physikalisch-Technische Bundesanstalt (PTB)PTB is the German National Metrology Institute providing scientific and technical services.. The electrical and mechanical design of the divider, the screening procedure for the selection of the precision resistors, and the results of the investigation and calibration at the PTB are reported here. During the latter, uncertainties at the low ppm level have been deduced for the new divider, thus qualifying it for the precision measurements of the KATRIN experiment.

  17. Adult Attachment Ratings (AAR): an item response theory analysis.

    PubMed

    Pilkonis, Paul A; Kim, Yookyung; Yu, Lan; Morse, Jennifer Q

    2014-01-01

    The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent attachment (excessive dependency, interpersonal ambivalence, and compulsive care-giving), 3 for avoidant attachment (rigid self-control, defensive separation, and emotional detachment), and 1 for secure attachment. The scales include items (ranging from 6-16 in their original form) scored by raters using a 3-point format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce a total score. Item response theory (IRT) analyses were conducted with data from 414 participants recruited from psychiatric outpatient, medical, and community settings to identify the most informative items from each scale. The IRT results allowed us to shorten the scales to 5-item versions that are more precise and easier to rate because of their brevity. In general, the effective range of measurement for the scales was 0 to +2 SDs for each of the attachment constructs; that is, from average to high levels of attachment problems. Evidence for convergent and discriminant validity of the scales was investigated by comparing them with the Experiences of Close Relationships-Revised (ECR-R) scale and the Kobak Attachment Q-sort. The best consensus among self-reports on the ECR-R, informant ratings on the ECR-R, and expert judgments on the Q-sort and the AAR emerged for anxious, ambivalent attachment. Given the good psychometric characteristics of the scale for secure attachment, however, this measure alone might provide a simple alternative to more elaborate procedures for some measurement purposes. Conversion tables are provided for the 7 scales to facilitate transformation from raw scores to IRT-calibrated (theta) scores. PMID:24033268

  18. 76 FR 47612 - AAR Manufacturing, Inc.; Completion of Radiological Survey Activities at CSX Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... NRC informed AAR that radioactive thorium surface and subsurface contamination had been detected at... contamination on the CSXT property would result in doses well below NRC's criteria for unrestricted...

  19. Commissioning of the vacuum system of the KATRIN Main Spectrometer

    NASA Astrophysics Data System (ADS)

    Arenz, M.; Babutzka, M.; Bahr, M.; Barrett, J. P.; Bauer, S.; Beck, M.; Beglarian, A.; Behrens, J.; Bergmann, T.; Besserer, U.; Blümer, J.; Bodine, L. I.; Bokeloh, K.; Bonn, J.; Bornschein, B.; Bornschein, L.; Büsch, S.; Burritt, T. H.; Chilingaryan, S.; Corona, T. J.; De Viveiros, L.; Doe, P. J.; Dragoun, O.; Drexlin, G.; Dyba, S.; Ebenhöch, S.; Eitel, K.; Ellinger, E.; Enomoto, S.; Erhard, M.; Eversheim, D.; Fedkevych, M.; Felden, A.; Fischer, S.; Formaggio, J. A.; Fränkle, F.; Furse, D.; Ghilea, M.; Gil, W.; Glück, F.; Gonzalez Ureña, A.; Görhardt, S.; Groh, S.; Grohmann, S.; Grössle, R.; Gumbsheimer, R.; Hackenjos, M.; Hannen, V.; Harms, F.; Haußmann, N.; Heizmann, F.; Helbing, K.; Herz, W.; Hickford, S.; Hilk, D.; Hillen, B.; Höhn, T.; Holzapfel, B.; Hötzel, M.; Howe, M. A.; Huber, A.; Jansen, A.; Kernert, N.; Kippenbrock, L.; Kleesiek, M.; Klein, M.; Kopmann, A.; Kosmider, A.; Kovalík, A.; Krasch, B.; Kraus, M.; Krause, H.; Krause, M.; Kuckert, L.; Kuffner, B.; La Cascio, L.; Lebeda, O.; Leiber, B.; Letnev, J.; Lobashev, V. M.; Lokhov, A.; Malcherek, E.; Mark, M.; Martin, E. L.; Mertens, S.; Mirz, S.; Monreal, B.; Müller, K.; Neuberger, M.; Neumann, H.; Niemes, S.; Noe, M.; Oblath, N. S.; Off, A.; Ortjohann, H.-W.; Osipowicz, A.; Otten, E.; Parno, D. S.; Plischke, P.; Poon, A. W. P.; Prall, M.; Priester, F.; Ranitzsch, P. C.-O.; Reich, J.; Rest, O.; Robertson, R. G. H.; Röllig, M.; Rosendahl, S.; Rupp, S.; Ryšavý, M.; Schlösser, K.; Schlösser, M.; Schönung, K.; Schrank, M.; Schwarz, J.; Seiler, W.; Seitz-Moskaliuk, H.; Sentkerestiová, J.; Skasyrskaya, A.; Slezák, M.; Špalek, A.; Steidl, M.; Steinbrink, N.; Sturm, M.; Suesser, M.; Telle, H. H.; Thümmler, T.; Titov, N.; Tkachev, I.; Trost, N.; Unru, A.; Valerius, K.; Vénos, D.; Vianden, R.; Vöcking, S.; Wall, B. L.; Wandkowsky, N.; Weber, M.; Weinheimer, C.; Weiss, C.; Welte, S.; Wendel, J.; Wierman, K. L.; Wilkerson, J. F.; Winzen, D.; Wolf, J.; Wüstling, S.; Zacher, M.; Zadoroghny, S.; Zbořil, M.

    2016-04-01

    The KATRIN experiment will probe the neutrino mass by measuring the β-electron energy spectrum near the endpoint of tritium β-decay. An integral energy analysis will be performed by an electro-static spectrometer (``Main Spectrometer''), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m3, and a complex inner electrode system with about 120 000 individual parts. The strong magnetic field that guides the β-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300 °C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10‑11 mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.

  20. Penning discharge in the KATRIN pre-spectrometer

    NASA Astrophysics Data System (ADS)

    Fränkle, F. M.; Glück, F.; Valerius, K.; Bokeloh, K.; Beglarian, A.; Bonn, J.; Bornschein, L.; Drexlin, G.; Habermehl, F.; Leber, M. L.; Osipowicz, A.; Otten, E. W.; Steidl, M.; Thümmler, T.; Weinheimer, C.; Wilkerson, J. F.; Wolf, J.; Zadorozhny, S. V.

    2014-07-01

    The KArlsruhe TRItium Neutrino (KATRIN) experiment is a next-generation, large-scale tritium β-decay experiment to determine the neutrino mass by investigating the kinematics of tritium β-decay with a sensitivity of 200 meV/c2 using the MAC-E filter technique. In order to reach this sensitivity a low background level of 10-2 counts per second (cps) is required. A major background concern in MAC-E filters is the presence of Penning traps. A Penning trap is a special configuration of electromagnetic fields that allows the storage of electrically charged particles. This paper describes the mechanism of Penning discharges and the corresponding measurements performed at the test setup of the KATRIN pre-spectrometer. These investigations led to the conclusion that the observed electric breakdown, strong discharges and extremely large background rates were due to discharges caused by Penning traps located at both ends of the pre-spectrometer. Furthermore, the paper describes the design of a new set of electrodes (modified ground electrodes and new ``anti-Penning'' electrodes) to successfully remove these traps. After the installation of these electrodes in the pre-spectrometer, the measurements confirmed that the strong Penning discharges disappeared. The experience gained from the pre-spectrometer was used to design the electrode system of the main spectrometer. Recent measurements with the main spectrometer showed no indications of Penning trap related backgrounds.

  1. Introduction to direct neutrino mass measurements and KATRIN

    NASA Astrophysics Data System (ADS)

    Thümmler, T.; Katrin Collaboration

    2012-08-01

    The properties of neutrinos and especially their rest mass play an important role at the intersections of cosmology, particle physics and astroparticle physics. At present there are two complementary approaches to address this topic in laboratory experiments. The search for neutrinoless double beta decay probes whether neutrinos are Majorana particles and determines an effective neutrino mass value. On the other hand experiments such as MARE, KATRIN and the recently proposed Project 8 will investigate the spectral shape of β-decay electrons close to their kinematic endpoint in order to determine the neutrino rest mass with a model-independent method. Here, because of neutrino flavour mixing, the neutrino mass appears as an average of all neutrino mass eigenstates contributing to the electron neutrino. The KArlsruhe TRItium Neutrino experiment (KATRIN) is currently the experiment in the most advanced status of commissioning. It combines an ultra-luminous molecular windowless gaseous tritium source with an integrating high-resolution spectrometer of MAC-E filter type. It will investigate the neutrino rest mass with 0.2 eV/c (90% C.L.) sensitivity and allow β spectroscopy close to the T endpoint at 18.6 keV with unprecedented precision.

  2. The small RNA Aar in Acinetobacter baylyi: a putative regulator of amino acid metabolism.

    PubMed

    Schilling, Dominik; Findeiss, Sven; Richter, Andreas S; Taylor, Jennifer A; Gerischer, Ulrike

    2010-09-01

    Small non-coding RNAs (sRNAs) are key players in prokaryotic metabolic circuits, allowing the cell to adapt to changing environmental conditions. Regulatory interference by sRNAs in cellular metabolism is often facilitated by the Sm-like protein Hfq. A search for novel sRNAs in A. baylyi intergenic regions was performed by a biocomputational screening. One candidate, Aar, encoded between trpS and sucD showed Hfq dependency in Northern blot analysis. Aar was expressed strongly during stationary growth phase in minimal medium; in contrast, in complex medium, strongest expression was in the exponential growth phase. Whereas over-expression of Aar in trans did not affect bacterial growth, seven mRNA targets predicted by two in silico approaches were upregulated in stationary growth phase. All seven mRNAs are involved in A. baylyi amino acid metabolism. A putative binding site for Lrp, the global regulator of branched-chain amino acids in E. coli, was observed within the aar gene. Both facts imply an Aar participation in amino acid metabolism. PMID:20559624

  3. Long-term management of AAR-affected structures - An international perspective

    SciTech Connect

    Charlwood, R.G.; Solymar, Z.V.

    1995-12-31

    The objective of the paper is to review international practice and comment on progress made in the long-term management of existing AAR-affected dams and hydroelectric plants. A updated detailed worldwide listing which now includes 104 AAR-affected structures constructed since 1900 will be presented. The listing gives summary data on the year of construction, the year that significant problems were noted, aggregate and cement types, measured expansion rates, test data, time to initial deterioration, duration of reaction, damage to the structures and effects on equipment, and repairs or replacement. A comprehensive bibliography will also be given. Analysis of the database and significant case histories will be used to identify issues affecting dam safety, plant operations, remedial measures and long-term performance of AAR-affected structures. The presentation will be illustrated by several case histories where remedial measures have been implemented.

  4. An angular-selective electron source for the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Beck, M.; Bokeloh, K.; Hein, H.; Bauer, S.; Baumeister, H.; Bonn, J.; Ortjohann, H.-W.; Ostrick, B.; Rosendahl, S.; Streubel, S.; Valerius, K.; Zbořil, M.; Weinheimer, C.

    2014-11-01

    The KATRIN experiment is going to search for the average mass of the electron antineutrino with a sensitivity of 0.2 eV/c2. It uses a retardation spectrometer of MAC-E filter type to accurately measure the shape of the electron spectrum at the endpoint of tritium beta decay. In order to achieve the planned sensitivity the transmission properties of the spectrometer have to be understood with high precision for all initial conditions. For this purpose an electron source has been developed that emits single electrons at adjustable total energy and adjustable emission angle. The emission is pointlike and can be moved across the full flux tube that is imaged onto the detector. Here, we demonstrate that this novel type of electron source can be used to investigate the transmission properties of a MAC-E filter in detail.

  5. Status and commissioning of the Karlsruhe tritium neutrino experiment KATRIN

    NASA Astrophysics Data System (ADS)

    Thuemmler, Thomas; Katrin Collaboration

    2013-10-01

    Neutrino properties, and especially the determination of the neutrino rest mass, play an important role at the intersections of cosmology, particle physics and astroparticle physics. At present there are two complementary approaches to address this topic in laboratory experiments. The search for neutrinoless double β decay probes whether neutrinos are Majorana particles and determines an effective neutrino mass value. Experiments based on single β decay investigate electrons close to their kinematic endpoint in order to determine the neutrino mass by a modelindependent method. The KArlsruhe TRItium Neutrino experiment (KATRIN) is currently the experiment in the most advanced status of commissioning. Applying an ultra-luminous molecular windowless gaseous tritium source and an integrating high-resolution spectrometer of MAC-E filter type, it allows β spectroscopy close to the tritium endpoint with unprecedented precision and will reach a sensitivity of 200 meV/c2 (90% C.L.) on the neutrino mass.

  6. IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.

    PubMed

    Malkani, Niyati; Jansson, Thomas; Gupta, Madhulika B

    2015-09-01

    Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1 hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor + rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and hyperphosphorylation (pSer101/pSer119/pSer169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in response to decreased amino acid availability. PMID:25957086

  7. A broad-band FT-ICR Penning trap system for KATRIN

    NASA Astrophysics Data System (ADS)

    Ubieto-Díaz, M.; Rodríguez, D.; Lukic, S.; Nagy, Sz; Stahl, S.; Blaum, K.

    2009-12-01

    The KArlsruhe TRItium Neutrino experiment KATRIN aims at improving the upper limit of the mass of the electron antineutrino to about 0.2 eV (90% c.l.) by investigating the -decay of tritium gas molecules . The experiment is currently under construction to start first data taking in 2012. One source of systematic uncertainties in the KATRIN experiment is the formation of ion clusters when tritium decays and decay products interact with residual tritium molecules. It is essential to monitor the abundances of these clusters since they have different final state energies than tritium ions. For this purpose, a prototype of a cylindrical Penning trap has been constructed and tested at the Max-Planck-Institute for Nuclear Physics in Heidelberg, which will be installed in the KATRIN beam line. This system employs the technique of Fourier-Transform Ion-Cyclotron-Resonance in order to measure the abundances of the different stored ion species.

  8. Resolving the reactor neutrino anomaly with the KATRIN neutrino experiment

    NASA Astrophysics Data System (ADS)

    Formaggio, J. A.; Barrett, J.

    2011-11-01

    The KArlsruhe TRItium Neutrino experiment (KATRIN) combines an ultra-luminous molecular tritium source with an integrating high-resolution spectrometer to gain sensitivity to the absolute mass scale of neutrinos. The projected sensitivity of the experiment on the electron neutrino mass is 200 meV at 90% C.L. With such unprecedented resolution, the experiment is also sensitive to physics beyond the Standard Model, particularly to the existence of additional sterile neutrinos at the eV mass scale. A recent analysis of available reactor data appears to favor the existence of such a sterile neutrino with a mass splitting of | Δmsterile | 2 ⩾ 1.5eV2 and mixing strength of sin2 2θsterile = 0.17 ± 0.08 at 95% C.L. Upcoming tritium beta decay experiments should be able to rule out or confirm the presence of the new phenomenon for a substantial fraction of the allowed parameter space.

  9. Measurement and reduction of low-level radon background in the KATRIN experiment

    SciTech Connect

    Fränkle, F. M.

    2013-08-08

    The KArlsruhe TRItium Neutrino (KATRIN) experiment is a next generation, model independent, large scale experiment to determine the mass of the electron anti-neutrino by investigating the kinematics of tritium beta decay with a sensitivity of 200 meV/c{sup 2}. The measurement setup consists of a high luminosity windowless gaseous molecular tritium source (WGTS), a differential and cryogenic pumped electron transport and tritium retention section, a tandem spectrometer section (pre-spectrometer and main spectrometer) for energy analysis, followed by a detector system for counting transmitted beta decay electrons. Measurements performed at the KATRIN pre-spectrometer test setup showed that the decay of radon (Rn) atoms in the volume of the KATRIN spectrometers is a major background source. Rn atoms from low-level radon emanation of materials inside the vacuum region of the KATRIN spectrometers are able to penetrate deep into the magnetic flux tube so that the alpha decay of Rn contributes to the background. Of particular importance are electrons emitted in processes accompanying the Rn alpha decay, such as shake-off, internal conversion of excited levels in the Rn daughter atoms and Auger electrons. Lowenergy electrons (< 100 eV) directly contribute to the background in the signal region. High-energy electrons can be stored magnetically inside the volume of the spectrometer and are able to create thousands of secondary electrons via subsequent ionization processes with residual gas molecules. In order to reduce the Rn induced background different active and passive counter measures were developed and tested. This proceeding will give an overview on Rn sources within the KATRIN spectrometer, describes how Rn decays inside the spectrometer produce background events at the detector and presents different counter measures to reduce the Rn induced background.

  10. aarC, an essential gene involved in density-dependent regulation of the 2'-N-acetyltransferase in Providencia stuartii.

    PubMed Central

    Rather, P N; Solinsky, K A; Paradise, M R; Parojcic, M M

    1997-01-01

    The 2'-N-acetyltransferase [AAC(2')-Ia] in Providencia stuartii has a dual function where it is involved in the acetylation of peptidoglycan and certain aminoglycosides. A search for negative regulators of the aac(2')-Ia gene has resulted in the identification of aarC. A missense allele (aarC1) resulted in an 8.9-fold increase in beta-galactosidase accumulation from an aac(2')-lacZ transcriptional fusion. Northern blot analysis demonstrated an increase in aac(2')-Ia mRNA accumulation that was specific to cells at high density. In addition, the aarC1 allele also resulted in a substantial increase in the expression of aarP, a transcriptional activator of the aac(2')-Ia gene. The wild-type aarC gene was isolated by complementation and encodes a predicted protein of 365 amino acids with a molecular mass of 39,815 Da. The predicted AarC protein exhibited 88% amino acid homology to the previously identified GcpE protein of Escherichia coli and 86% homology to a gene product from Haemophilus influenzae. The E. coli gcpE gene was able to functionally complement the aarC1 allele in P. stuartii. The aarC1 allele was identified as a T to G transversion that resulted in a valine to glycine substitution at position 136 in the AarC protein. The aarC gene appears to be essential for cell viability as construction of a disrupted copy (aarC::lacZ) was possible only in cells that carried an episomal copy of aarC or gcpE. PMID:9079912

  11. Amino acid deprivation induces CREBZF/Zhangfei expression via an AARE-like element in the promoter.

    PubMed

    Zhang, Yani; Jin, Yaping; Williams, Tegan A; Burtenshaw, Sally M; Martyn, Amanda C; Lu, Rui

    2010-01-15

    CREBZF (also called ZF or Zhangfei) is a basic region-leucine zipper transcription factor that has been implicated in the herpesvirus infection cycle and related cellular processes. Since ATF4 is known to play a key role in cellular responses to various ER stresses as well as amino acid deprivation, we sought to examine the potential involvement of CREBZF in the amino acid response (AAR). We found that the CREBZF protein was induced by amino acid deprivation in the canine MDCK cells. We subsequently cloned a canine CREBZF promoter region (-1767bp to +1bp) that responds to amino acid limitation. Using deletion mapping and site-directed mutagenesis, we identified a 9-bp sequence 5'-ATTCACTCA-3' in the promoter (-1227 to -1219), deletion of which resulted in a complete loss of inducibility by amino acid deprivation. This sequence is similar to the known amino acid response elements (AAREs) found in other AAR-inducible genes, such as CHOP (C/EBP homologous protein, also known as GADD153). These results suggest that CREBZF may be an amino acid stress sensor. Considering the AARE-like sequence found in CREBZF and other similarities between CREBZF and CHOP, we postulate that CREBZF and CHOP may be two sensors that regulate different yet related signaling pathways governing the AAR. PMID:20026304

  12. Neutrinos secretly converting to lighter particles to please both KATRIN and the cosmos

    NASA Astrophysics Data System (ADS)

    Farzan, Yasaman; Hannestad, Steen

    2016-02-01

    Within the framework of the Standard Model of particle physics and standard cosmology, observations of the Cosmic Microwave Background (CMB) and Baryon Acoustic Oscillations (BAO) set stringent bounds on the sum of the masses of neutrinos. If these bounds are satisfied, the upcoming KATRIN experiment which is designed to probe neutrino mass down to ~ 0.2 eV will observe only a null signal. We show that the bounds can be relaxed by introducing new interactions for the massive active neutrinos, making neutrino masses in the range observable by KATRIN compatible with cosmological bounds. Within this scenario, neutrinos convert to new stable light particles by resonant production of intermediate states around a temperature of T~ keV in the early Universe, leading to a much less pronounced suppression of density fluctuations compared to the standard model.

  13. Electron line shape and transmission function of the KATRIN monitor spectrometer

    NASA Astrophysics Data System (ADS)

    Slezák, M.

    2013-12-01

    Knowledge of the neutrino mass is of particular interest in modern neutrino physics. Besides the neutrinoless double beta decay and cosmological observation information about the neutrino mass is obtained from single beta decay by observing the shape of the electron spectrum near the endpoint. The KATRIN β decay experiment aims to push the limit on the effective electron antineutrino mass down to 0.2 eV/c2. To reach this sensitivity several systematic effects have to be under control. One of them is the fluctuations of the absolute energy scale, which therefore has to be continuously monitored at very high precision. This paper shortly describes KATRIN, the technique for continuous monitoring of the absolute energy scale and recent improvements in analysis of the monitoring data.

  14. Tests of by-pass diodes at cryogenic temperatures for the KATRIN magnets

    SciTech Connect

    Gil, W.; Bolz, H.; Jansen, A.; Müller, K.; Steidl, M.; Hagedorn, D.

    2014-01-27

    The Karlsruhe Tritium Neutrino experiment (KATRIN) requires a series of superconducting solenoid magnets for guiding beta-electrons from the source to the detector. By-pass diodes will operate at liquid helium temperatures to protect the superconducting magnets and bus bars in case of quenches. The operation conditions of the by-pass diodes depend on the different magnet systems of KATRIN. Therefore, different diode stacks are designed with adequate copper heat sinks assuming adiabatic conditions. The by-pass diode stacks have been submitted to cold tests both at liquid nitrogen and liquid helium temperatures for checking operation conditions. This report presents the test set up and first results of the diode characteristics at 300 K and 77 K, as well as of endurance tests of the diode stacks at constant current load at 77 K and 4.2 K.

  15. Electron line shape and transmission function of the KATRIN monitor spectrometer

    SciTech Connect

    Slezák, M.

    2013-12-30

    Knowledge of the neutrino mass is of particular interest in modern neutrino physics. Besides the neutrinoless double beta decay and cosmological observation information about the neutrino mass is obtained from single beta decay by observing the shape of the electron spectrum near the endpoint. The KATRIN β decay experiment aims to push the limit on the effective electron antineutrino mass down to 0.2 eV/c{sup 2}. To reach this sensitivity several systematic effects have to be under control. One of them is the fluctuations of the absolute energy scale, which therefore has to be continuously monitored at very high precision. This paper shortly describes KATRIN, the technique for continuous monitoring of the absolute energy scale and recent improvements in analysis of the monitoring data.

  16. 1450 m^3 at 10^-9 Pa: One of the KATRIN Challenges

    SciTech Connect

    Christian Day; R. Gumbsheimer; W. Herz; J. Wolf; J. Bonn; R. Reid; G.R. Myneni

    2006-11-12

    The KATRIN project is a challenging experiment to measure the mass of the electron neutrino directly with a sensitivity of 0.2 eV. It is a next generation tritium beta-decay experiment scaling up the size and precision of previous experiments by an order of magnitude as well as the intensity of the tritium beta source. Ultrafine spectrometric analysis of the energy distribution of the decay electrons at their very endpoint of 18.57 keV is the key to derive the neutrino mass. This is provided by a high-resolution spectrometer of unique size (10 m in diameter, 22 m in length). To avoid any negative influence from residual gas, the spectrometer vessel is designed to UHV/XHV conditions (an ultimate total pressure of below 10{sup -9} Pa and a wall outgassing rate below 10{sup -13} Pam{sup 3}/scm{sup 2}). The paper shortly describes the experimental idea behind KATRIN. The emphasis will then be given to the pumping concept for how to achieve the target parameters and to the manufacturing of the spectrometer tank. Critical issues will also be discussed (surface treatment, welding, transportation). Finally, a description of the current status and an outlook on the overall KATRIN schedule completes the paper.

  17. A regulatory cascade involving AarG, a putative sensor kinase, controls the expression of the 2'-N-acetyltransferase and an intrinsic multiple antibiotic resistance (Mar) response in Providencia stuartii.

    PubMed

    Rather, P N; Paradise, M R; Parojcic, M M; Patel, S

    1998-06-01

    A recessive mutation, aarG1, has been identified that resulted in an 18-fold increase in the expression of beta-galactosidase from an aac(2')-lacZ fusion. Transcriptional fusions and Northern blot analysis demonstrated that the aarG1 allele also resulted in a large increase in the expression of aarP, a gene encoding a transcriptional activator of aac(2')-Ia. The effects of aarG1 on aac(2')-Ia expression were mediated by aarP-dependent and -independent mechanisms. The aarG1 allele also resulted in a multiple antibiotic resistance (Mar) phenotype, which included increased chloramphenicol, tetracycline and fluoroquinolone resistance. This Mar phenotype also resulted from aarP-dependent and -independent mechanisms. Sequence analysis of the aarG locus revealed the presence of two open reading frames, designated aarR and aarG, organized in tandem. The putative AarR protein displayed 75% amino acid identity to the response regulator PhoP, and the AarG protein displayed 57% amino acid identity to the sensor kinase PhoQ. The aarG1 mutation, a C to T substitution, resulted in a threonine to isoleucine substitution at position 279 (T279I) in the putative sensor kinase. The AarG product was functionally similar to PhoQ, as it was able to restore wild-type levels of maganin resistance to a Salmonella typhimurium phoQ mutant. However, expression of the aarP and aac(2')-Ia genes was not significantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG senses a signal other than divalent cations. PMID:9680222

  18. Use of After Action Reports (AARs) to Promote Organizational and Systems Learning in Emergency Preparedness

    PubMed Central

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D.

    2012-01-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The “lessons-learned” approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the “Lessons Learned Information Sharing (LLIS.gov)” system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strived to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed. PMID:23066408

  19. Use of after action reports (AARs) to promote organizational and systems learning in emergency preparedness.

    PubMed

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D

    2012-08-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The "lessons-learned" approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the "Lessons Learned Information Sharing (LLIS.gov)" system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strove to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed. PMID:23066408

  20. Responses to the AAR-Teagle White Paper: "The Religious Studies Major in a Post-9/11 World"

    ERIC Educational Resources Information Center

    Webster, Jane S.; Buckley, James J.; Jensen, Tim; Floyd-Thomas, Stacey

    2011-01-01

    In October 2008 The American Academy of Religion published the findings of an eighteen month study (conducted with funding from the Teagle Foundation) on "The Religious Studies Major in a Post-9/11 World: New Challenges, New Opportunities." Re-published here, this AAR-Teagle White Paper provides the opportunity for four respondents to raise issues…

  1. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    PubMed

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-01-01

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

  2. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR)

    PubMed Central

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J.; Laclette, Juan P.; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-01-01

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest. PMID:25989346

  3. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  4. Halogen and trace element geochemistry in Mid-Ocean Ridge basalts from the Australian-Antarctic Ridge (AAR)

    NASA Astrophysics Data System (ADS)

    Yang, Y. S.; Seo, J. H.; Park, S. H.; Kim, T.

    2015-12-01

    Australian-Antarctic Ridge (AAR) is an extension of easternmost SE Indian Mid-Ocean Ridge (MOR).We collected volcanic glasses from the "in-axis" of the KR1 and KR2 MOR, and the overlapping zones of the KR1 MOR and the nearby seamounts ("KR1 mixing"). We determined trace and halogen elements in the glasses. Halogen concentrations and its ratios in the glasses are important to understand the mantle metasomatism and volatile recycling. 52 of the collected glasses are "primitive" (higher than 6 wt% MgO), while 3 of them have rather "evolved" composition (MgO wt% of 1.72, 2.95 and 4.15). K2O concentrations and Th/Sc ratios in the glasses show a negative correlation with its MgO concentration. Incompatible element ratios such as La/Sm are rather immobile during a magma differentiation so the ratios are important to understand mantle composition (Hofmann et al. 2003). La/Sm ratios in the glasses are 0.95 ~ 3.28 suggesting that the AAR basalts can be classified into T-MORB and E-MORB (Schilling et al., 1983). La/Sm ratios are well-correlated with incompatible elements such as U, Ba, Nb, and negatively correlated with compatible elements such as Sc, Eu2+, Mg. The AAR glasses contain detectable halogen elements. The "KR1 mixing" glasses in halogen elements are more abundant than "in-axis" the glasses. Cl is the least variable element compared to the other halogens such as Br and I in the AAR. The "KR1 mixing" glasses have the largest variations of Br/Cl ratios compared to the "in-axis" glasses. The Cl/Br and Th/Sc ratios in the "in-axis" glasses and in the "KR1 mixing" glasses show positive and negative correlations, respectively. The Br-rich glasses in the "KR1 mixing" zone might be explained by a recycled Br-rich oceanic slab of paleo-subduction or by a hydrothermal alteration in the AAR. I composition in the glasses does not show a correlation other trace elements. The K/Cl and K/Ti ratios in the AAR glasses are similar to the basalts from the Galapagos Spreading Center

  5. The Front of the Aar Massif: A Crustal-Scale Ramp Anticline?

    NASA Astrophysics Data System (ADS)

    Herwegh, Marco; Mock, Samuel; Wehrens, Philip; Baumberger, Roland; Berger, Alfons; Wangenheim, Cornelia; Glotzbach, Christoph; Kissling, Edi

    2015-04-01

    The front of the Aar Massif (Swiss Central Alps) is characterized by Paleozoic basement rocks exposed at altitudes of more than 4600m above sea level, followed by a steeply north dipping Mesozoic sedimentary cover and overlying Helvetic nappes. The sediments turn into subhorizontal orientations just few kilometers to the N, where the top of the basement is situated at depths of about 7000m below sea level. What is the origin of this vertical jump of about 12000m of the basement rocks over such short horizontal distances? Recent structural investigations at the Basement-Cover contact indicate a complex structural evolution involving reactivation of extensional faults and inversion of half-grabens during early compressional stages. In the internal parts of the Aar Massif a general steepening of the faults resulted with progressive compression. In the northern frontal part, however, a new spaced cleavage evolved, which is dipping with 20-30° to the SE. In places, the new cleavage in the basement rocks is intense and pervasive and correlates with a steepening of the basement-cover contact and its offsets of several tens to hundreds of meters. Hence strain is strongly partitioned in a large number of high strain zones, which cover a cumulative thickness of at least 2000m, eventually even much more considering subsurface continuation. The Mesozoic sediments affected by this large-scale deformation zone are either intensely ductile folded in the case of limestones or faulted and imbricated in the case of dolomites. These differences in deformation style result from the deformation conditions of about < 250-300°C, where calcite still deforms in a ductile manner, while dolomite and crystalline basement preferentially undergo brittle deformation in combination of dissolution-precipitation processes. In a large-scale point of view, we suggest that the high strain domain in the crystalline basement in fact represents a crustal-scale several kilometers wide shear zone, which

  6. Gaseous source of 83mKr conversion electrons for the neutrino experiment KATRIN

    NASA Astrophysics Data System (ADS)

    Vénos, D.; Slezák, M.; Dragoun, O.; Inoyatov, A.; Lebeda, O.; Pulec, Z.; Sentkerestiová, J.; Špalek, A.

    2014-12-01

    The metastable 83mKr with short half-life of 1.83 h is intended as a space distributed source of monoenergetic electrons for energy calibration and systematic studies in the Karlsruhe tritium neutrino experiment (KATRIN). The efficient production of the parent radionuclide 83Rb at cyclotron U-120M was implemented. The release of the 83mKr from zeolite (molecular sieve), in which the parent radionuclide 83Rb (T1/2 = 86.2 d) was trapped, was studied under various conditions using the gamma spectroscopy. Residual gas analysis of ultra high vacuum over the zeolite was performed as well.

  7. Lake Biel Holocene sediment record before and after the Aare river deviation (1878 AD)

    NASA Astrophysics Data System (ADS)

    Jeannet, Alice; Corella, Juan Pablo; Kremer, Katrina; Girardclos, Stéphanie

    2014-05-01

    Lake sediments are excellent archives of environmental and climate changes as well as human impact on lake- and river-systems. Lake Biel is a medium-sized peri-alpine lake in Switzerland, with a maximum depth of 74 m, and lies at an altitude of 429 m a.s.l. Lake Biel, which formed during the Pleistocene by glacial erosion, is part of the Aare river system. Our study focuses on the south-west part of the lake basin where the lake sedimentation was originally (i.e. naturally) mainly controlled by autochthonous sedimentation. This area is currently under a strong influence of water and sediment input from this river catchment since the Aare river deviation through the Hagneck canal in 1878. A 10.05 m long composite sediment sequence, cored from a 52 m water depth in September 2011, was built from two long cores retrieved with the ETH Zurich/Eawag Uwitec system. A radiocarbon age model indicates that the retrieved sedimentary sequence spans the last 7500 years. The upper sediments were correlated to previous short core radionuclide stratigraphy for the 1.5 m upper part (Thevenon et al., 2013). Magnetic susceptibility and density were measured by Geotek MultiSensor Core Logger at 0.5 cm resolution. Granulometry was measured with a CILAS grain sizer every 10 cm, and X-ray fluorescence (XRF) was carried out using an Avaatech core scanner at 1-cm resolution. This technique provides semi-quantitative information of the sediment elemental composition and shows how runoff and river input (Ti, Al, Si) or redox conditions (Fe/Mn) vary through time. Lake Biel sediment record suggests marked environmental changes with runoff decrease linked to climate and vegetation change during Atlantic chronobiozone, as well as a complex climate-human impact during the 'La Tène' and Roman cultural times. The most prominent recorded feature is the 10-times increase of sediment rate that occurred after the Aare river deviation through the Hagneck canal into Lake Biel in 1878. This artificial

  8. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  9. Structural Evolution in the Aar Massif (Central Alps): First attempts of linking the micron- to the kilometer-scale

    NASA Astrophysics Data System (ADS)

    Wehrens, P.; Baumberger, R.; Herwegh, M.

    2012-04-01

    The Aar massif belongs to the external massifs of the Alps and is mainly composed of granitoids and gneisses. Despite numerous detailed studies in the past decades, the overall exhumation history and the associated massif internal deformation (internal strain distribution and its evolution in time, kinematics etc.) are largely unknown at present. In this project, we aim to investigate the role of shear zones in the deformation history at a variety of scales. In this context it is important to understand their microstructural evolution, the involved deformation processes, kinematics and relative ages as well as the associated changes in rheology. A GIS-based remote-sensing structural map, verified by fieldwork, (see Baumberger et al., this volume) served as base for our investigations. Lithological differences between the units (Central Aare granite, ZAGr; Grimsel granodiorte, GrGr and gneisses) cause strain to localize along these contacts. Furthermore, the initial magmatic differentiation in the granitoids locally controls the Alpine deformational overprint because of differences in effective viscosity during solid-state deformation. This behavior is illustrated by the increase of foliation intensity and the number of shear zones per rock volume from ZAGr to GrGr. Preliminary results show that deformation at the N boundary of the Aar massif has to be distinguished from the central and the southern part. In the North steep NE-SW trending foliations and shear zones with subvertical lineations represent the major structures. The shear zones acted both as normal faults and as reverse faults, which mostly used pre-existing lithological boundaries between the different gneiss units. In a later stage, E-W trending shear zones and shear bands with moderate dipping angles cross cut the earlier structures. They always show a top to the North component and might be related to the late north directed movements of the Aar massif. Yet, no absolute age dating has been performed

  10. Simulation of background from low-level tritium and radon emanation in the KATRIN spectrometers

    SciTech Connect

    Leiber, B.; Collaboration: KATRIN Collaboration

    2013-08-08

    The KArlsruhe TRItium Neutrino (KATRIN) experiment is a large-scale experiment for the model independent determination of the mass of electron anti-neutrinos with a sensitivity of 200 meV/c{sup 2}. It investigates the kinematics of electrons from tritium beta decay close to the endpoint of the energy spectrum at 18.6 keV. To achieve a good signal to background ratio at the endpoint, a low background rate below 10{sup −2} counts per second is required. The KATRIN setup thus consists of a high luminosity windowless gaseous tritium source (WGTS), a magnetic electron transport system with differential and cryogenic pumping for tritium retention, and electro-static retarding spectrometers (pre-spectrometer and main spectrometer) for energy analysis, followed by a segmented detector system for counting transmitted beta-electrons. A major source of background comes from magnetically trapped electrons in the main spectrometer (vacuum vessel: 1240 m{sup 3}, 10{sup −11} mbar) produced by nuclear decays in the magnetic flux tube of the spectrometer. Major contributions are expected from short-lived radon isotopes and tritium. Primary electrons, originating from these decays, can be trapped for hours, until having lost almost all their energy through inelastic scattering on residual gas particles. Depending on the initial energy of the primary electron, up to hundreds of low energetic secondary electrons can be produced. Leaving the spectrometer, these electrons will contribute to the background rate. This contribution describes results from simulations for the various background sources. Decays of {sup 219}Rn, emanating from the main vacuum pump, and tritium from the WGTS that reaches the spectrometers are expected to account for most of the background. As a result of the radon alpha decay, electrons are emitted through various processes, such as shake-off, internal conversion and the Auger deexcitations. The corresponding simulations were done using the KASSIOPEIA

  11. High-voltage monitoring with a solenoid retarding spectrometer at the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Erhard, M.; Bauer, S.; Beglarian, A.; Bergmann, T.; Bonn, J.; Drexlin, G.; Goullon, J.; Groh, S.; Glück, F.; Kleesiek, M.; Haußmann, N.; Höhn, T.; Johnston, K.; Kraus, M.; Reich, J.; Rest, O.; Schlösser, K.; Schupp, M.; Slezák, M.; Thümmler, T.; Vénos, D.; Weinheimer, C.; Wüstling, S.; Zbořil, M.

    2014-06-01

    The KATRIN experiment will measure the absolute mass scale of neutrinos with a sensitivity of mν = 200meV/c2 by means of an electrostatic spectrometer set close to the tritium β-decay endpoint at 18.6keV. Fluctuations of the energy scale must be under control within ±60mV (±3ppm). Since a precise voltage measurement in the range of tens of kV is on the edge of current technology, a nuclear standard will be deployed additionally. Parallel to the main spectrometer the same retarding potential will be applied to the monitor spectrometer to measure 17.8-keV K-conversion electrons of 83mKr. This article describes the setup of the monitor spectrometer and presents its first measurement results.

  12. Prototype of an angular-selective photoelectron calibration source for the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Valerius, K.; Hein, H.; Baumeister, H.; Beck, M.; Bokeloh, K.; Bonn, J.; Glück, F.; Ortjohann, H.-W.; Ostrick, B.; Zbořil, M.; Weinheimer, Ch

    2011-01-01

    The method of direct neutrino mass determination based on the kinematics of tritium beta decay, which is adopted by the KATRIN experiment, makes use of a large, high-resolution electrostatic spectrometer with magnetic adiabatic collimation. In order to target a sensitivity on m(ν) of 0.2eV/c2, a detailed understanding of the electromagnetic properties of the electron spectrometer is essential, requiring comprehensive calibration measurements with dedicated electron sources. In this paper we report on a prototype of a photoelectron source providing a narrow energy spread and angular selectivity. Both are key properties for the characterisation of the spectrometer. The angular selectivity is achieved by applying non-parallel strong electric and magnetic fields: Directly after being created, photoelectrons are accelerated rapidly and non-adiabatically by a strong electric field before adiabatic magnetic guiding takes over.

  13. GAMMA DETECTOR RESPONSE/SOIL CONCENTRATION CORRELATION STUDY AT THE AAR MANUFACTURING, INC. SITE, LIVONIA, MICHIGAN

    SciTech Connect

    ALTIC, NICK A

    2013-03-22

    At the NRC's request, ORAU conducted surveys of the AAR Manufacturing site during the period of September 25 through September 27, 2012. The survey activities included walkover surveys and sampling activities. Once the survey team was onsite, the NRC personnel decided to forgo survey activities in the New Addition and the pickling area. Areas of the planned study boundary were inaccessible due to overgrowth/large pieces of concrete covering the soil surface; therefore, the study boundary was redefined. Gamma walkover scans of the site boundary and front yard identified multiple areas of elevated gamma radiation. As a result, two judgmental samples were collected. Sample results were above thorium background levels The answer to the PSQ relating to the relationship between thorium concentration in soil and NaI instrument response is Yes. NaI instrument response can be used as a predictor of Th-232 concentration in the 0 to 1 m layer. An R2 value of 0.79 was determined for the surface soil relationship, thus satisfying the DQOs. Moreover, the regression was cross-checked by comparing the predicted Th-232 soil core concentration to the average Th-232 concentration (Section 5.3.2). Based on the cross-check, the regression equation provides a reasonable estimate for the Th-232 concentration at the judgmental locations. Consideration must be given when applying this equation to other soil areas of the site. If the contamination was heterogeneously distributed, and not distributed in a discrete layer as it was in the study area, then using the regression equation to predict Th-232 concentration would not be applicable.

  14. Internal structure of the Aar Massif: What can we learn in terms of exploration for deep geothermal energy?

    NASA Astrophysics Data System (ADS)

    Herwegh, Marco; Baumberger, Roland; Wehrens, Philip; Schubert, Raphael; Berger, Alfons; Maeder, Urs; Spillmann, Thomas

    2014-05-01

    The successful use of deep geothermal energy requires 3D flow paths, which allow an efficient heat exchange between the surrounding host rocks and the circulating fluids. Recent attempts to exploit this energy resource clearly demonstrate that the new technology is facing sever problems. Some major problems are related to the prediction of permeability, the 3D structure of the flow paths and the mechanical responses during elevated fluid pressures at depths of several kilometers. Although seemingly new in a technical perspective, nature is facing and solving similar problems since the beginning of the Alpine orogeny. Based on detailed studies in the Hasli Valley (Aar Massif) we can demonstrate that deformation and fluid flow are strongly localized along mechanical anisotropies (e.g. lithological variations, brittle and ductile faults). Some of them already evolved during Variscan and post-Variscan times. Interestingly, these inherited structures are reactivated over and over again during the Alpine orogeny. Their reactivation occurred at depths of ~13-15 km with elevated temperatures (400-475°C) and involved both ductile and brittle deformation processes. Brittle deformation in form of hydrofracking was always present due to the circulating fluids. It is this process, which was and still is responsible for seismic activity. With progressive uplift and exhumation of the Aar Massif, ductile deformation structures became replaced by brittle cataclasites and fault gouges during fault activity at shallower crustal levels. Existing hydrotest data from the Grimsel Test Site (Nagra's underground research laboratory) indicate that these brittle successors of the ductile shear zones are domains of enhanced recent fluid percolation. Note that although being exposed today, the continuation of these fault structures are still active at depth in both brittle and ductile deformation modes, a fact that can be inferred from recent uplift rates and the active seismicity. On the

  15. Amino acid racemization analysis (AAR) as a successful tool for dating Holocene coastal sediments: Stratigraphy of a barrier island spit (Southern Sylt/North Sea)

    NASA Astrophysics Data System (ADS)

    Tillmann, Tanja; Ziehe, Daniel

    2014-05-01

    Dating of Holocene sediments in shallow coastal areas of the German North Sea by conventional techniques is commonly problematic. In particular the marine reservoir effect of radiocarbon means that radiocarbon dating cannot be applied to sediments younger than about 400 years. Amino acid racemization dating (AAR) is a viable alternative for dating young sediments. The method is based on the determination of ratios of D and L amino acid enantiomers in organic matrices of biogenic carbonates. In this study we use AAR as a tool for dating Holocene barrier islands sediments. Based on an AAR derived chronological framework we develop a model of barrier spit accretion which describes the interaction between extreme events, fair weather coastal processes and sedimentary development that constrains the major episodes of barrier island evolution. The stratigraphy was defined using ground-penetrating radar (GPR) surveys complemented by sedimentological coring data. The stratigraphy is then conceptualised in a AAR chronostratigraphic framework to define a chronological order and allow the development of a stratigraphic model of the evolution of Southern Sylt. The AAR data provide high temporal resolution and have been used for dating stages of barrier spit accretion. The time lines are marked as storm surge generated erosion unconformities in the stratigraphic profile. Individual shells and shell fragments of Cerastoderma edule, Mya arenaria, Mytilus edulis and Scrobicularia plana have been accumulated by short-term storm events as shell layers associated with the erosion unconformities and have been dated by AAR. Time lines reveal that the barrier spit accretion occurred episodically, and is dependant on the provided rate of sand delivery. The general trend is that sequences young to the. South. The AAR derived time lines have been verified and correlated by historic maps and sea charts. It is apparent that spit enlargement at this site increased significantly during the

  16. Identification of trends and patterns in sediment geochemistry from the Aare delta plain, Swiss Alps.

    NASA Astrophysics Data System (ADS)

    Carvalho, Filipe; Schulte, Lothar

    2015-04-01

    The study of fluvial systems by means of sediment cores is one of the most interesting approaches to understand the spatial and temporal pattern of river dynamics under the influence of different driving forces such as climate variability and human activities. This work focuses on the analysis of the geochemistry of fluvial sediments from the Aare delta plain in the Swiss Alps.The analysis of sediment cores allowed the identification of trends and patterns in sediment geochemistry. It was possible to identify diverse sedimentation phases in the delta plain, marked by differences in sedimentation processes and characterized by decreasing grain size sequences. It is worth mentioning the importance of peat formations in this sedimentary environment, reaching several centimeters thick in some cases. These horizons are normally associated with very low concentrations of chemical elements from the mineral fraction, such as Si, Al, Fe, and K. The general trends in geochemistry indicate the dominance of elements such as Al and Si, which have similar variability in all cores. It is noted that these elements have a reasonably good correlation with grain size and inverse relation with organic matter content. Factor analysis was used to study the geochemical data set of 3 sediment cores. This analysis is based on a statistical description of the variability of the correlated data where a smaller number of not observed variables are obtained (factors). Factor analysis attempts to find joint variation of the data series and presents that response as unobservable latent variables. In this study, factor analysis was conducted with the major chemical elements: Al, Si, P, K, Ca, Ti, Mn, Fe, Cu, Zn, Pb and also the percentage of TOC. Variations of these 12 inorganic and organic elements are reflected in two unobserved variables, factor 1 and factor 2. Factor analysis has enabled the recognition of two clusters: 1) a group of elements that include the TOC and metals, which are

  17. Reactivity of fluoride dentifrices with artificial caries. III. Quantitative aspects of acquired acid resistance (AAR): F uptake, retention, surface hardening and remineralization.

    PubMed

    White, D J

    1991-01-01

    A pH cycling remineralization/dimineralization model has been used to compare remineralization and acid resistance benefits provided by commercial MFP and NaF dentifrices. Test results show that fluoride dentifrice systems were effective in enhancing lesion remineralization and providing acquired acid resistance (AAR) to carious lesions, with AAR benefits considerably greater in magnitude. Fluoride uptake into the carious lesions was associated with remineralization and AAR benefits. Dentifrices containing the highest levels of soluble ionic fluoride were found most effective in this protocol with MFP dentifrices showing significantly less activity. MFP dentifrice efficacy was enhanced slightly in calcium abrasives. The enhanced activity could be explained by increased levels of background ionic fluoride in the formulations. In contrast to the latter effects, a dual-active NaF+MFP dentifrice in a calcium abrasive system exhibited decreased efficacy relative to a silica abrasive formulation due to incompatibility of free fluoride ion. Comparison of analytical techniques for measurement of AAR in shallow lesions demonstrates that surface microhardness methods match radiographic measures and are thus adequate for ICT measurement of cariogenicity and F remineralization. PMID:1812910

  18. Next generation KATRIN high precision voltage divider for voltages up to 65kV

    NASA Astrophysics Data System (ADS)

    Bauer, S.; Berendes, R.; Hochschulz, F.; Ortjohann, H.-W.; Rosendahl, S.; Thümmler, T.; Schmidt, M.; Weinheimer, C.

    2013-10-01

    The KATRIN (KArlsruhe TRItium Neutrino) experiment aims to determine the mass of the electron antineutrino with a sensitivity of 200 meV by precisely measuring the electron spectrum of the tritium beta decay. This will be done by the use of a retarding spectrometer of the MAC-E-Filter type. To achieve the desired sensitivity the stability of the retarding potential of -18.6 kV has to be monitored with a precision of 3 ppm over at least two months. Since this is not feasible with commercial devices, two ppm-class high voltage dividers were developed, following the concept of the standard divider for DC voltages of up to 100 kV of the Physikalisch-Technische Bundesanstalt (PTB). In order to reach such high accuracies different effects have to be considered. The two most important ones are the temperature dependence of resistance and leakage currents, caused by insulators or corona discharges. For the second divider improvements were made concerning the high-precision resistors and the thermal design of the divider. The improved resistors are the result of a cooperation with the manufacturer. The design improvements, the investigation and the selection of the resistors, the built-in ripple probe and the calibrations at PTB will be reported here. The latter demonstrated a stability of about 0.1 ppm/month over a period of two years.

  19. An attempt to validate the ultra-accelerated microbar and the concrete performance test with the degree of AAR-induced damage observed in concrete structures

    SciTech Connect

    Leemann, Andreas; Merz, Christine

    2013-07-15

    There is little knowledge about the relation between AAR-induced damage observed in structures and the expansion potential obtained with accelerated tests. In this study, aggregates used in structures damaged by AAR were tested with the microbar test (MBT/AFNOR XP 18-594) and the concrete performance test (CPT/AFNOR P18-454). After the tests, the samples were examined using optical and scanning electron microscopy. Based on the results, the significance of the microbar test has to be examined very critically. The agreement of measured expansion, reacted rock types and the composition of the reaction products between the on-site concrete and the reproduced concrete subjected to the CPT clearly indicates that the reaction mechanisms in the structure and in the concrete performance test are comparable. As such, the concrete performance test seems to be an appropriate tool to test the potential reactivity of specific concrete mixtures.

  20. A one- and two-dimensional cross-section sensitivity and uncertainty path of the AARE (Advanced Analysis for Reactor Engineering) modular code system

    SciTech Connect

    Davidson, J.W.; Dudziak, D.J.; Higgs, C.E.; Stepanek, J.

    1988-01-01

    AARE, a code package to perform Advanced Analysis for Reactor Engineering, is a linked modular system for fission reactor core and shielding, as well as fusion blanket, analysis. Its cross-section sensitivity and uncertainty path presently includes the cross-section processing and reformatting code TRAMIX, cross-section homogenization and library reformatting code MIXIT, the 1-dimensional transport code ONEDANT, the 2-dimensional transport code TRISM, and the 1- and 2- dimensional cross-section sensitivity and uncertainty code SENSIBL. IN the present work, a short description of the whole AARE system is given, followed by a detailed description of the cross-section sensitivity and uncertainty path. 23 refs., 2 figs.

  1. This NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No. 847) is acting as an in-flight refueling tanker in the study to develop analytical models for an automated aerial refueling system for unmanned vehicles. A 300-gallon aerodynamic pod containing air-refueling equipment is seen beneath the fuselage. The hose and refueling basket are extended during an assessment of their dynamics on the F/A-18A.

  2. Status of the KATRIN Experiment and Prospects to Search for keV-mass Sterile Neutrinos in Tritium β-decay

    NASA Astrophysics Data System (ADS)

    Mertens, Susanne

    In this contribution the current status and future perspectives of the Karlsruhe Tritium Neutrino (KATRIN) Experiment are presented. The prime goal of this single β-decay experiment is to probe the absolute neutrino mass scale with a sensitivity of 200 meV (90% CL). We discuss first results of the recent main spectrometer commissioning measurements, successfully verifying the spectrometer's basic vacuum, transmission and background properties. We also discuss the prospects of making use of the KATRIN tritium source, to search for sterile neutrinos in the multi-keV mass range constituting a classical candidate for Warm Dark Matter. Due to the very high source luminosity, a statistical sensitivity down to active-sterile mixing angles of sin2θ < 1 . 10-7 (90% CL) could be reached.

  3. Status of the KATRIN experiment and prospects to search for keV-mass sterile neutrinos in tritium β-decay

    DOE PAGESBeta

    Mertens, Susanne

    2015-03-24

    In this contribution the current status and future perspectives of the Karlsruhe Tritium Neutrino (KATRIN) Experiment are presented. The prime goal of this single β-decay experiment is to probe the absolute neutrino mass scale with a sensitivity of 200 meV (90% CL). We discuss first results of the recent main spectrometer commissioning measurements, successfully verifying the spectrometer’s basic vacuum, transmission and background properties. We also discuss the prospects of making use of the KATRIN tritium source, to search for sterile neutrinos in the multi-keV mass range constituting a classical candidate for Warm Dark Matter. Due to the very high sourcemore » luminosity, a statistical sensitivity down to active-sterile mixing angles of sin² θ < 1 · 10⁻⁷ (90% CL) could be reached.« less

  4. Status of the KATRIN experiment and prospects to search for keV-mass sterile neutrinos in tritium β-decay

    SciTech Connect

    Mertens, Susanne

    2015-03-24

    In this contribution the current status and future perspectives of the Karlsruhe Tritium Neutrino (KATRIN) Experiment are presented. The prime goal of this single β-decay experiment is to probe the absolute neutrino mass scale with a sensitivity of 200 meV (90% CL). We discuss first results of the recent main spectrometer commissioning measurements, successfully verifying the spectrometer’s basic vacuum, transmission and background properties. We also discuss the prospects of making use of the KATRIN tritium source, to search for sterile neutrinos in the multi-keV mass range constituting a classical candidate for Warm Dark Matter. Due to the very high source luminosity, a statistical sensitivity down to active-sterile mixing angles of sin² θ < 1 · 10⁻⁷ (90% CL) could be reached.

  5. An online FT-ICR Penning-trap mass spectrometer for the DPS2-F section of the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Heck, M.; Ascher, P.; Cakirli, R. B.; Golzke, H.; Rodríguez, D.; Stahl, S.; Ubieto-Díaz, M.; Blaum, K.

    2014-09-01

    Two Fourier-transform ion-cyclotron resonance (FT-ICR) Penning-trap mass spectrometers will be installed in the pumping section of the KArlsruhe TRItium Neutrino (KATRIN) experiment. This experiment aims at determining the electron anti-neutrino mass m(νebar) with a sensitivity of 0.2 eV (90% C.L.) by high-resolution tritium β-spectroscopy. The tritium source creates various types of ions, which have to be reduced in order to reach the required low background level. The purpose of the FT-ICR mass spectrometers is the identification of the ion flux components as well as their abundance. Furthermore, the pumping efficiency of the differential pumping section DPS2-F can be determined since these Penning traps will be installed one at the entrance and one at the exit. In this paper the operation of the FT-ICR system is described. Experimental results are presented concerning the cryogenic broad-band amplifier system for the FT-ICR detection as well as the characterisation of the mass spectrometer with respect to, e.g., noise density and detection limit.

  6. MicroRNA-16 is putatively involved in the NF-κB pathway regulation in ulcerative colitis through adenosine A2a receptor (A2aAR) mRNA targeting

    PubMed Central

    Tian, Ting; Zhou, Yu; Feng, Xiao; Ye, Shicai; Wang, Hao; Wu, Weiyun; Tan, Wenkai; Yu, Caiyuan; Hu, Juxiang; Zheng, Rong; Chen, Zonghao; Pei, Xinyu; Luo, Hesheng

    2016-01-01

    MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene expression by targeting the 3′-untranslated region of their target genes. Altered expression of miR-16 is reported in human ulcerative colitis (UC), but its role in the development of the disease remains unclear. Adenosine through adenosine A2a receptor (A2aAR) could inhibit nuclear factor-kappaB (NF-κB) signaling pathway in inflammation. Here we identified overexpression of miR-16 and down-regulation of A2aAR in the colonic mucosa of active UC patients. We demonstrated that miR-16 negatively regulated the expression of the A2aAR at the post-transcriptional level. Furthermore, transfection of miR-16 mimics promoted nuclear translocation of NF-κB p65 protein and expression of pro-inflammatory cytokines, IFN-γ and IL-8 in colonic epithelial cells. Treatment with miR-16 inhibitor could reverse these effects in cells. The A2aAR-mediated effects of miR-16 on the activation of the NF-κB signaling pathway were confirmed by the A2aAR knockdown assay. Our results suggest that miR-16 regulated the immune and inflammatory responses, at least in part, by suppressing the expression of the A2aAR to control the activation of the NF-κB signaling pathway. PMID:27476546

  7. Quantitative assessment of alkali-reactive aggregate mineral content through XRD using polished sections as a supplementary tool to RILEM AAR-1 (petrographic method)

    SciTech Connect

    Castro, Nelia; Sorensen, Bjorn E.; Broekmans, Maarten A.T.M.

    2012-11-15

    The mineral content of 5 aggregate samples from 4 different countries, including reactive and non-reactive aggregate types, was assessed quantitatively by X-ray diffraction (XRD) using polished sections. Additionally, electron probe microanalyzer (EPMA) mapping and cathodoluminescence (CL) were used to characterize the opal-CT identified in one of the aggregate samples. Critical review of results from polished sections against traditionally powdered specimen has demonstrated that for fine-grained rocks without preferred orientation the assessment of mineral content by XRD using polished sections may represent an advantage over traditional powder specimens. Comparison of data on mineral content and silica speciation with expansion data from PARTNER project confirmed that the presence of opal-CT plays an important role in the reactivity of one of the studied aggregates. Used as a complementary tool to RILEM AAR-1, the methodology suggested in this paper has the potential to improve the strength of the petrographic method.

  8. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study.

    PubMed

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-01-01

    BACKGROUND Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. MATERIAL AND METHODS All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. RESULTS A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506-0.6 and 0.539-0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601-0.664 and 0.596-0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627-0.69 and 0.607-0.692, respectively. CONCLUSIONS APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis. PMID:26687574

  9. Alpine re-activation of pre-Alpine structures: details from a large-scale shear zone in the Aar massif (Central Alps)

    NASA Astrophysics Data System (ADS)

    Wehrens, Philip; Baumberger, Roland; Herwegh, Marco

    2013-04-01

    The Aar massif belongs to the external massifs of the Alps and is mainly composed of granitoids and gneisses. Post-Variscan granitoid rocks have intruded old gneisses belonging to the pre-Variscan basement. Despite numerous detailed studies in the past decades, the overall exhumation history and the associated massif internal deformation (internal strain distribution and its evolution in time, kinematics etc.) are largely unknown at present. In this project, we aim to investigate the role of shear zones in the deformation history at a variety of scales. In this context it is important to understand their microstructural evolution, the involved deformation processes, kinematics and relative ages as well as the associated changes in rheology. A detailed study was conducted along a major shear zone located at the southern margin of the Aar massif (running from Furka to Grimsel Pass and Oberaar Glacier), where the Grimsel Granodiorite (GrGr) is juxtapositioned to strongly foliated gneisses. Preliminary results show that a crenulation of these gneisses predates the age of the granitoid intrusion, meaning they must be older than 298 Ma. The crenulation and a related axial plane foliation (145/80°) define mechanical anisotropies within these Pre-Variscan rocks. The intruding granite has exploited these anisotropies a first time during its emplacement in post-Variscan times. The lithological boundary between the intruded GrGr and Pre-Variscan rocks causes strain again to localize during Alpine deformation and results in a 40 m wide large-scale shear zone. The older part of the shear zone shows cm-scale shear zones with vertical lineations shearing off the aforementioned pre-Alpine axial plane foliation. Hence the contact is reactivated, now as Alpine normal/ reverse fault, a second time. Towards the youngest parts of the shear zone the stretching lineation on the shear surfaces turns from vertical towards a subhorizontal position, indicating a change from initial vertical

  10. Growth of exfoliation joints and near-surface stress orientations inferred from fractographic markings observed in the upper Aar valley (Swiss Alps)

    NASA Astrophysics Data System (ADS)

    Ziegler, Martin; Loew, Simon; Bahat, Dov

    2014-06-01

    Granitic rock mass of the upper Aar valley (Grimsel area, Switzerland) contains distinct generations of exfoliation joints, which formed during different stages of the Pleistocene, subparallel to distinct glacial valley palaeotopography. The bulk of exfoliation joints shows prominent, common fractographic features: (1) radial plumose structures with distinct plume axes; (2) arrest marks superimposed by plumose striations; and (3) gradually-developing en échelon fringe cracks. Multiple arrest marks reveal that exfoliation joints formed incrementally and, together with the absence of hackle fringes, suggest stable, i.e., subcritical fracturing conditions. Smooth transitions from plumose structures on the parent plane to en échelon fringe cracks, combined with non-systematic stepping senses of fringe cracks, suggest local (vs. temporal) stress field variations. Assuming that plume axes formed parallel to the maximum principal compressive stress (σ1) enables us to infer near-surface palaeostress orientations and compare them with classical borehole-based in-situ stress data. The majority of plume axes suggest (1) persistently subhorizontal to slightly inclined σ1 orientations at trough valley slopes and (2) near-surface variability of σ1 orientations originating from topographic perturbation caused by glacial valley erosion superimposed on the regional stress field. Our investigations of fracture surface morphologies yield unique insights into exfoliation fracture formation, such as directional trends of fracture propagation and associated palaeostress orientations within Alpine valley slopes.

  11. Stable isotope and Ar/Ar evidence of prolonged multiscale fluid flow during exhumation of orogenic crust: Example from the Mont Blanc and Aar Massifs (NW Alps)

    NASA Astrophysics Data System (ADS)

    Rossi, M.; Rolland, Y.

    2014-09-01

    The spatial and temporal scales and the geometry of fluid pathways in a collisional orogen are investigated using stable isotope analysis (O, C, and H) and 40Ar/39Ar dating of vein minerals formed at circa 11-16 Ma in the Mont Blanc and the Aar External Crystalline Massifs. In both massifs 40Ar/39Ar dating of veins adularia provides evidence for progressive crystallization from 16 to 9 Ma, and mainly at 11-12 Ma following veins opening during shear zone activity. The fluid flow duration thus ranges from 4 to 5 Ma in the two massifs. The δ18O values of vein quartz and calcite are similar to those of undeformed crystalline and sedimentary host rocks, suggesting rock buffering, while carbon isotope ratios of vein calcites fall into three compositional groups. A-type veins have δ13C values that are buffered by the Helvetic metasediments, which suggests that these veins formed in a closed system from a locally derived CO2-rich fluid. The fluid in equilibrium with C-type veins has depleted δ13C values similar to mantle-CO2, while the intermediate δ13C values of B-type veins suggest mixing between the A-type and C-type fluids. These results are in agreement with crustal- to lithosphere-scale upward vertical fluid flow along vertical shear zones related to the strike-slip system bounding the Adriatic block since 16-20 Ma, connecting a deep-seated fluid to some downward flow in the sedimentary cover of External Crystalline Massifs.

  12. Distribution and inferred age of exfoliation joints in the Aar Granite of the central Swiss Alps and relationship to Quaternary landscape evolution

    NASA Astrophysics Data System (ADS)

    Ziegler, Martin; Loew, Simon; Moore, Jeffrey R.

    2013-11-01

    deepest exfoliation joint generation is associated with erosion of the inner glacial troughs of the upper Aar valley, which likely occurred during the mid-Pleistocene Revolution. Our study shows how exfoliation joint episodes can be dated, and, conversely, that better knowledge of the distribution of exfoliation joint sets can reveal unique information about the morphological evolution of an Alpine valley.

  13. The influence of snow cover on alpine floods reconstructed from the analysis of satellite images. The case of the Hasli-Aare river basin, Berner Oberland (1987-2012)

    NASA Astrophysics Data System (ADS)

    Cabrera-Medina, Paula; Schulte, Lothar; Carvalho, Filipe; Peña, Juan Carlos; García, Carles

    2016-04-01

    Regarding the hydrological hazards in the Hasli-Aare river over the last century, instrumental and documentary data show that flood frequency and magnitude increased since 1977. One of the main water inputs contributing to peak discharges is given by the thaw of the stored snow. Therefore, the knowledge of the evolution of snow cover is considered essential for the assessment of alpine floods. Snow cover studies can be made by different approaches such as the analysis of data provided by field work or by nivometeorological stations. However, these methods are usually expensive and do not present adequate spatial or temporal coverage data. For this reason, satellite images with different spatial and temporal resolution are an interesting complementary source for the understanding of the snow cover dynamics. The aim of the paper is to study the influence of snow cover variations during years of severe floods that occurred in the upper Aare basin from 1987 to 2012. Three satellite images have been selected for each of the 9 studied events: 1) maximum snow cover during winter, 2) the last image before the event and 3) the first image after the flood. Each image has been processed with the ArcGIS software applying a statistical method of supervised classification. This image processing allows the spatial quantification of the variation of the snow cover in the Aare headwater catchment. Because the melting of snow cover is related to the changes of weather situations before and during the flood episode, it is important to analyse also the nivometeorological data of stations located in the catchment (snow depth, temperature and precipitation). From these data we determined 4 types of flood, which can be classified according to their nivometeorological variables and synoptic situation (500 hPa geopotential and Sea Level Pressure) into two patterns. The first group of events can be associated to an Atlantic pattern recording decreasing temperatures, moderate to high

  14. Calibration of amino acid racemization (AAR) kinetics in United States mid-Atlantic Coastal Plain Quaternary mollusks using 87Sr/ 86Sr analyses: Evaluation of kinetic models and estimation of regional Late Pleistocene temperature history

    USGS Publications Warehouse

    Wehmiller, J. F.; Harris, W.B.; Boutin, B.S.; Farrell, K.M.

    2012-01-01

    The use of amino acid racemization (AAR) for estimating ages of Quaternary fossils usually requires a combination of kinetic and effective temperature modeling or independent age calibration of analyzed samples. Because of limited availability of calibration samples, age estimates are often based on model extrapolations from single calibration points over wide ranges of D/L values. Here we present paired AAR and 87Sr/ 86Sr results for Pleistocene mollusks from the North Carolina Coastal Plain, USA. 87Sr/ 86Sr age estimates, derived from the lookup table of McArthur et al. [McArthur, J.M., Howarth, R.J., Bailey, T.R., 2001. Strontium isotopic stratigraphy: LOWESS version 3: best fit to the marine Sr-isotopic curve for 0-509 Ma and accompanying Look-up table for deriving numerical age. Journal of Geology 109, 155-169], provide independent age calibration over the full range of amino acid D/L values, thereby allowing comparisons of alternative kinetic models for seven amino acids. The often-used parabolic kinetic model is found to be insufficient to explain the pattern of racemization, although the kinetic pathways for valine racemization and isoleucine epimerization can be closely approximated with this function. Logarithmic and power law regressions more accurately represent the racemization pathways for all amino acids. The reliability of a non-linear model for leucine racemization, developed and refined over the past 20 years, is confirmed by the 87Sr/ 86Sr age results. This age model indicates that the subsurface record (up to 80m thick) of the North Carolina Coastal Plain spans the entire Quaternary, back to ???2.5Ma. The calibrated kinetics derived from this age model yield an estimate of the effective temperature for the study region of 11??2??C., from which we estimate full glacial (Last Glacial Maximum - LGM) temperatures for the region on the order of 7-10??C cooler than present. These temperatures compare favorably with independent paleoclimate information

  15. Stable isotope and Ar/Ar evidence of prolonged multi-scale fluid flow during exhumation of orogenic crust: example from the Mont Blanc and Aar massifs (NW Alps)

    NASA Astrophysics Data System (ADS)

    Rolland, Yann; Rossi, Magali

    2015-04-01

    The spatial and temporal scales and the geometry of fluid pathways in a collisional orogen are investigated using stable isotope analysis (O, C, H) and 40Ar/39Ar dating of vein minerals formed at c. 11-16 Ma in the Mont Blanc and the Aar External Crystalline Massifs. In both massifs 40Ar/39Ar dating of veins adularia provides evidence for progressive crystallization from 16 to 9 Ma, and mainly at 11-12 Ma following veins opening during shear zone activity. The fluid flow duration thus ranges from 4 to 5 Ma in the two massifs. The δ18O values of vein quartz and calcite are similar to those of undeformed crystalline and sedimentary host-rocks, suggesting rock buffering, while carbon isotope ratios of vein calcites fall into three compositional groups. A-type veins have δ13C values that are buffered by the Helvetic metasediments, which suggests that these veins formed in a closed-system from a locally-derived CO2-rich fluid. The fluid in equilibrium with C-type veins has depleted δ13C values similar to mantle-CO2, while the intermediate δ13C values of B-type veins suggest mixing between the A-type and C-type fluids. These results are in agreement with crustal- to lithosphere-scale upward vertical fluid flow along vertical shear zones related to the strike-slip system bounding the Adriatic block since 16-20 Ma, connecting a deep-seated fluid to some downward flow in the sedimentary cover of External Crystalline Massifs.

  16. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part I

    NASA Astrophysics Data System (ADS)

    Wetter, Oliver; Tuttenuj, Daniel

    2016-04-01

    systematically analysed the period from 1446-1542 and could prove a large number of pre-instrumental flood events of river Rhine, Birs, Birsig and Wiese in Basel. All in all the weekly led account books contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results for river Emme and Saane (see Abstract Daniel Tuttenuj), whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs-, Birsig-, Rhine- and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see also Abstract of Daniel Tuttenuj).

  17. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part II.

    NASA Astrophysics Data System (ADS)

    Tuttenuj, Daniel; Wetter, Oliver

    2016-04-01

    contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results of river Emme and Saane, whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs, Birsig, Rhine and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see Abstract Oliver Wetter).

  18. AAR in concrete of Asejire spillway (OYO state - Nigeria)

    SciTech Connect

    Lamaudiere, J.P.; Spaeti, F.

    1995-12-31

    The Asejire dam at Ibadan, Nigeria was constructed in the late sixties for the purpose of providing water for the city of Ibadan (presently about 4,5 million inhabitants). It is located on the Oshun river approximately fifteen miles from the city. In 1982 cracks were observed on the wing walls and although these continued to develop, no attempt was made at that time to investigate their causes and no repair was carried out. In 1989 the SGI ENGINEERING Group of Geneva, Switzerland was appointed as the consultant for the complete refurbishment of the Asejire water scheme. The consortium Degremont-Poat-Clemessy was awarded the contract for the project. The African Development Bank and the Nigerian Government have provided the loan to finance the project.

  19. F/A-18 Automated Aerial Refueling (AAR) Phase 1

    NASA Video Gallery

    Engineers at NASA's Dryden Flight Research Center are evaluating the capability of an F/A-18A aircraft as an in-flight refueling tanker to develop analytical models for an automated aerial refuelin...

  20. The NASA Dryden AAR Project: A Flight Test Approach to an Aerial Refueling System

    NASA Technical Reports Server (NTRS)

    Hansen, Jennifer L.; Murray, James E.; Campos, Norma V.

    2004-01-01

    The integration of uninhabited aerial vehicles (UAVs) into controlled airspace has generated a new era of autonomous technologies and challenges. Autonomous aerial refueling would enable UAVs to travel further distances and loiter for extended periods over time-critical targets. The NASA Dryden Flight Research Center recently has completed a flight research project directed at developing a dynamic hose and drogue system model to support the development of an automated aerial refueling system. A systematic dynamic model of the hose and drogue system would include the effects of various influences on the system, such as flight condition, hose and drogue type, tanker type and weight, receiver type, and tanker and receiver maneuvering. Using two NASA F/A-18 aircraft and a conventional hose and drogue aerial refueling store from the Navy, NASA has obtained flight research data that document the response of the hose and drogue system to these effects. Preliminary results, salient trends, and important lessons are presented.

  1. A Service for Emotion Management: Turkish Version of the Adolescent Anger Rating Scale (AARS)

    ERIC Educational Resources Information Center

    Aslan, A. Esra; Sevincler-Togan, Seyhan

    2009-01-01

    An individual's activities are closely related with his/her communication abilities. One's awareness of his feelings and needs and to what extend he can control such feelings are the key factors which effect communication abilities. Webster (1996) defines anger as, "a strong emotion; a feeling that is oriented toward some real or supposed…

  2. The contribution of quartz and the role of aluminum for understanding the AAR with greywacke

    SciTech Connect

    Huenger, Klaus-Juergen E-mail: huenger@tu-cottbus.de

    2007-08-15

    Precambrian Greywacke from Lower Lusatia (Germany) has been well known as an alkali sensitive aggregate for several years. It can cause considerable damages in concrete buildings due to an Alkali-Aggregate-Reaction. The investigations are focused on quartz as the main releaser of silica, its characterization and its behavior in an alkaline solution. But there are no relations between quartz properties and the alkali sensitivities of greywacke samples. To understand this fact the role of aluminum which greywacke releases in different amounts into the alkaline solution too must be considered. Aluminum affects the silica concentration by three different mechanisms. The result is always a decrease of the silica concentration in the solution caused by an alumino silicate formation. The silica bound by alumino silicate structures can be quantified by {sup 27}Al-NMR-spectroscopy. The expansions of concrete samples can now be described much well as a function of a so called 'free' silica. Based on this results a direct test method for the assessment of the alkali sensitivity of greywackes could be created and suggestions for an inhibition can be given.

  3. Predicting Mothers' Reports of Children's Mental Health Three Years after Hurricane Katrin.

    PubMed

    Lowe, Sarah R; Godoy, Leandra; Rhodes, Jean E; Carter, Alice S

    2013-01-01

    This study explored pathways through which hurricane-related stressors affected the psychological functioning of elementary school aged children who survived Hurricane Katrina. Participants included 184 mothers from the New Orleans area who completed assessments one year pre-disaster (Time 1), and one and three years post-disaster (Time 2 and Time 3, respectively). Mothers rated their children's behavior problems at Time 3 only (n = 251 children; 53.0% male; Mean age: 10.19 years, SD = 1.68 years). A path analytic model indicated that hurricane-related stressors were associated with increased maternal psychological distress and school mobility in the first post-disaster year, which were associated with higher child internalizing and externalizing symptoms three years post-disaster. Mediation analysis indicated that hurricane-related stressors were associated with child symptoms indirectly, through their impact on maternal psychological distress. Findings underscore the importance of interventions that boost maternal and child mental health and support children through post-disaster school transitions. PMID:23471125

  4. AarF Domain Containing Kinase 3 (ADCK3) Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation

    PubMed Central

    Cullen, Jason K.; Abdul Murad, Norazian; Yeo, Abrey; McKenzie, Matthew; Ward, Micheal; Chong, Kok Leong; Schieber, Nicole L.; Parton, Robert G.; Lim, Yi Chieh; Wolvetang, Ernst; Maghzal, Ghassan J.; Stocker, Roland; Lavin, Martin F.

    2016-01-01

    Autosomal recessive ataxias are a clinically diverse group of syndromes that in some cases are caused by mutations in genes with roles in the DNA damage response, transcriptional regulation or mitochondrial function. One of these ataxias, known as Autosomal Recessive Cerebellar Ataxia Type-2 (ARCA-2, also known as SCAR9/COQ10D4; OMIM: #612016), arises due to mutations in the ADCK3 gene. The product of this gene (ADCK3) is an atypical kinase that is thought to play a regulatory role in coenzyme Q10 (CoQ10) biosynthesis. Although much work has been performed on the S. cerevisiae orthologue of ADCK3, the cellular and biochemical role of its mammalian counterpart, and why mutations in this gene lead to human disease is poorly understood. Here, we demonstrate that ADCK3 localises to mitochondrial cristae and is targeted to this organelle via the presence of an N-terminal localisation signal. Consistent with a role in CoQ10 biosynthesis, ADCK3 deficiency decreased cellular CoQ10 content. In addition, endogenous ADCK3 was found to associate in vitro with recombinant Coq3, Coq5, Coq7 and Coq9, components of the CoQ10 biosynthetic machinery. Furthermore, cell lines derived from ARCA-2 patients display signs of oxidative stress, defects in mitochondrial homeostasis and increases in lysosomal content. Together, these data shed light on the possible molecular role of ADCK3 and provide insight into the cellular pathways affected in ARCA-2 patients. PMID:26866375

  5. Validation of 3D Code KATRIN For Fast Neutron Fluence Calculation of VVER-1000 Reactor Pressure Vessel by Ex-Vessel Measurements and Surveillance Specimens Results

    NASA Astrophysics Data System (ADS)

    Dzhalandinov, A.; Tsofin, V.; Kochkin, V.; Panferov, P.; Timofeev, A.; Reshetnikov, A.; Makhotin, D.; Erak, D.; Voloschenko, A.

    2016-02-01

    Usually the synthesis of two-dimensional and one-dimensional discrete ordinate calculations is used to evaluate neutron fluence on VVER-1000 reactor pressure vessel (RPV) for prognosis of radiation embrittlement. But there are some cases when this approach is not applicable. For example the latest projects of VVER-1000 have upgraded surveillance program. Containers with surveillance specimens are located on the inner surface of RPV with fast neutron flux maximum. Therefore, the synthesis approach is not suitable enough for calculation of local disturbance of neutron field in RPV inner surface behind the surveillance specimens because of their complicated and heterogeneous structure. In some cases the VVER-1000 core loading consists of fuel assemblies with different fuel height and the applicability of synthesis approach is also ambiguous for these fuel cycles. Also, the synthesis approach is not enough correct for the neutron fluence estimation at the RPV area above core top. Because of these reasons only the 3D neutron transport codes seem to be satisfactory for calculation of neutron fluence on the VVER-1000 RPV. The direct 3D calculations are also recommended by modern regulations.

  6. 75 FR 38114 - [Docket ID FEMA-2010-0008

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ...) After Action Report (AAR) Improvement Plan (IP). SUMMARY: The Federal Emergency Management Agency (FEMA... SECURITY Federal Emergency Management Agency Agency Information Collection Activities: Submission for OMB...) After Action Report (AAR) Improvement Plan (IP) AGENCY: Federal Emergency Management Agency, DHS....

  7. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying...

  8. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying...

  9. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying...

  10. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment, and car fully conforms to all... Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a report in prescribed form, certifying...

  11. 49 CFR 179.5 - Certificate of construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to the owner and the Executive Director—Tank Car Safety, AAR, certifying that the tank, equipment... each series when submitted to the Executive Director—Tank Car Safety, AAR. (c) If the owner elects to furnish service equipment, the owner shall furnish the Executive Director—Tank Car Safety, AAR, a...

  12. 75 FR 13775 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... (AAR) Improvement Plan (IP) AGENCY: Federal Emergency Management Agency, DHS. ACTION: Notice; 60-day... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP). SUMMARY... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP)....

  13. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning.

    PubMed

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-03-01

    Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning.Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370.Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)-especially rash (59.74%)-were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae.Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is higher with Ultravist

  14. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

    PubMed Central

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Abstract Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning. Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370. Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)—especially rash (59.74%)—were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae. Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is

  15. Second international conference on alkali-aggregate reactions in hydroelectric plants and dams

    SciTech Connect

    1995-12-31

    This document is the report of the Second International Conference on Alkali-Aggregate Reactions in Hydroelectric Plants and Dams. This conference was held in October 1995 in Chattanooga, TN and sponsored by the Tennessee Valley Authority. Thirty five papers were presented, with technical sessions covering: (1) The TVA experience, (2) AAR in Hydroelectric Powerplants, (3) AAR in Dams and Spillways, and (4) Long-term management of AAR. Additionally, there were several workshop sessions.

  16. Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats.

    PubMed

    Pelassa, Ilaria; Fiumara, Ferdinando

    2015-01-01

    Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as "junk" sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in shaping

  17. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  18. The Importance of Admissions Scores and Attendance to First-Year Performance

    ERIC Educational Resources Information Center

    Moore, Randy

    2006-01-01

    The goal of this study was to determine how ACT Aptitude Ratings (AAR, a pre-admission criterion) of first-year students are associated with various aspects of their first-year experiences. AAR scores were only weakly correlated with students' first-semester grade point averages (GPA), as well as their second-semester grades and attendance rates…

  19. High throughput screening and structure-activity relationship study of potential α2A-adrenoceptor agonists by LANCETM cAMP assay.

    PubMed

    Yang, Huan; He, Ling; Yan, Ming; He, Jian-Guo; Yu, Tao

    2013-06-28

    G protein-coupled receptors (GPCRs) are signaling molecules with a wide variety of skills. Members of this large family of membrane protein have been shown to regulate the activities of the different signaling pathways of the ligand specific manner. α2-adrenoceptors (α2-ARs) are one of the GPCRs and the stimulation of them could modulate many classical effects such as hypotension, bradycardia, etc. Recently, α2A-AR is more and more important for its role in the therapeutic applications in central nervous system (CNS) diseases.High throughput screening of α2A-AR agonists was established by LANCETM cAMP assay from a compound library of 80,000 small-molecule compounds to find out potential human α2A-adrenoceptor (α2A-AR) agonists that might have therapeutic effect in CNS diseases. From the preliminary and secondary screening, 37 compounds were identified as α2AAR agonists, and six compounds among them presented more pronounced α2A-AR stimulating activity than guanfacine, a selective α2A-AR agonist. The study provided referred data for the development of potent α2A-AR agonists and suggested that the existence of the parent structure (1, 2, 4-benzothiadiazine 1, 1-dioxide) bodes well for pharmaceutical development of α2A-AR agonists. PMID:23514320

  20. Defining Educational Research: A Perspective of/on Presidential Addresses and the Australian Association for Research in Education

    ERIC Educational Resources Information Center

    Lingard, Bob; Gale, Trevor

    2010-01-01

    This paper is concerned with the definition of the field of educational research and the changing and developing role of the Australian Association for Research in Education (AARE) in representing and constituting this field. The evidence for the argument is derived from AARE Presidential Addresses across its 40-year history. The paper documents…

  1. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: (1) AAR means Association of American Railroads. (2) Approved means approval by the AAR Tank Car... this chapter also apply. (6) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8... (IBR, see § 171.7 of this subchapter). (9) (10) Tank car facility means an entity that...

  2. 76 FR 35026 - Weather Shield Manufacturing, Inc. Corporate Office, Medford, WI; Notice of Amended Negative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... published in the Federal Register on August 2, 2009 (75 FR 45163). AAR 77. The authority for these issuances... Register on September 21, 2009 (75 FR 57519). AAR 120. In response to the Plaintiff's complaint filed with... Employment and Training Administration TA-W-72,673 Weather Shield Manufacturing, Inc. Corporate...

  3. Detector-related backgrounds in the Karlsruhe Tritium Neutrino Experiment

    NASA Astrophysics Data System (ADS)

    Leber, Michelle; Katrin Collaboration

    2011-12-01

    The Karlsruhe Tritium Neutrino Experiment, or KATRIN, is a next generation tritium beta decay experiment to directly measure neutrino mass with an expected sensitivity of 0.2 eV [KATRIN Design Report 2004 see http://www-ik.fzk.de/~katrin/]. Neutrino mass does not fit into the Standard Model, and determining this mass may set the scale of new physics. To achieve this level of sensitivity, backgrounds in the experiment must be minimized. A complete Geant4 [Agostinelli S et al. 2003 Nuclear Instr. Methods A 506 250-303 Allison J et al. 2006 IEEE Transactions on Nuclear Science53 No. 1 270-8] simulation of KATRIN's focal plane detector and surrounding region is being developed. These simulations will help guide the design and selection of shielding and detector construction materials to reduce backgrounds from cosmic rays and natural radioactivity.

  4. Atlantoaxial Rotatory Subluxation after Removal of a Ventriculoperitoneal Shunt in the Supine-Lateral Position.

    PubMed

    Hashide, Shusei; Aihara, Yasuo; Nagahara, Ayumi; Mitsuyama, Tetsuryu; Okada, Yoshikazu

    2015-01-01

    Atlantoaxial rotatory subluxation (AARS) is an uncommon disease with a greater prevalence in children than adults. So far there has only been one report of AARS after surgery related to ventriculoperitoneal (VP) shunting. We present a new case of AARS closed reduction treatment after VP shunt removal in an 8-year-old girl with wound pain on the back of her head and torticollis after surgery. Her head was rotated in the spine-lateral position during surgery. The diagnosis of AARS was established by 3D-computed tomography. The rotatory subluxation was cured after cervical traction therapy. The successful closed reduction was the consequence of early detection and conservative treatment, which are important constituents in the management of AARS. PMID:26202450

  5. Adenosine A2A receptor activation reduces recurrence and mortality from Clostridium difficile infection in mice following vancomycin treatment

    PubMed Central

    2012-01-01

    Background Activation of the A2A adenosine receptor (A2AAR) decreases production of inflammatory cytokines, prevents C. difficile toxin A-induced enteritis and, in combination with antibiotics, increases survival from sepsis in mice. We investigated whether A2AAR activation improves and A2AAR deletion worsens outcomes in a murine model of C. difficile (strain VPI10463) infection (CDI). Methods C57BL/6 mice were pretreated with an antibiotic cocktail prior to infection and then treated with vancomycin with or without an A2AAR agonist. A2AAR-/- and littermate wild-type (WT) mice were similarly infected, and IFNγ and TNFα were measured at peak of and recovery from infection. Results Infected, untreated mice rapidly lost weight, developed diarrhea, and had mortality rates of 50-60%. Infected mice treated with vancomycin had less weight loss and diarrhea during antibiotic treatment but mortality increased to near 100% after discontinuation of antibiotics. Infected mice treated with both vancomycin and an A2AAR agonist, either ATL370 or ATL1222, had minimal weight loss and better long-term survival than mice treated with vancomycin alone. A2AAR KO mice were more susceptible than WT mice to death from CDI. Increases in cecal IFNγ and blood TNFα were pronounced in the absence of A2AARs. Conclusion In a murine model of CDI, vancomycin treatment resulted in reduced weight loss and diarrhea during acute infection, but high recurrence and late-onset death, with overall mortality being worse than untreated infected controls. The administration of vancomycin plus an A2AAR agonist reduced inflammation and improved survival rates, suggesting a possible benefit of A2AAR agonists in the management of CDI to prevent recurrent disease. PMID:23217055

  6. Forebrain pathway for auditory space processing in the barn owl.

    PubMed

    Cohen, Y E; Miller, G L; Knudsen, E I

    1998-02-01

    The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a "top-down" approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completely auditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway. PMID:9463450

  7. The importance of nasal resistance in obstructive sleep apnea syndrome: a study with positional rhinomanometry.

    PubMed

    De Vito, A; Berrettini, S; Carabelli, A; Sellari-Franceschini, S; Bonanni, E; Gori, S; Pasquali, L; Murri, L

    2001-01-01

    The importance of nasal obstruction in the pathogenesis of obstructive sleep apnea syndrome (OSAS) has not yet been totally defined. Numerous studies have reported an association between nasal obstruction and OSAS, but the precise nature of this relationship remains to be clarified. This study was undertaken to evaluate the prevalence of nasal obstruction disorders in a group of OSAS patients. For this purpose, we analyzed the nasal resistance of 36 OSAS patients by performing a traditional basal anterior active rhinomanometry test (AAR) and a positional AAR, with the patient in a supine position. Seven patients had a pathologic nasal resistance in the seated position that increased further in the supine position; 9 patients had normal resistance in the seated position but a pathologic resistance in the supine position. In 20 patients, nasal resistance was normal in both positions. No statistically significant differences in the degree of apnea/hypopnea index (AHI) was found between the 20 patients with normal positional AAR and the 16 with pathologic positional AAR (p = 0.13). Moreover, no statistically significant differences in the degree of AHI was found between the 7 patients with pathologic basal and positional AAR and the 9 patients with normal basal AAR and pathologic positional AAR (p = 0.38). PMID:11868135

  8. ADRA2A is involved in neuro-endocrine regulation of bone resorption

    PubMed Central

    Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

    2015-01-01

    Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

  9. Dual allosteric modulation of opioid antinociceptive potency by α2A-adrenoceptors.

    PubMed

    Chabot-Doré, Anne-Julie; Millecamps, Magali; Naso, Lina; Devost, Dominic; Trieu, Phan; Piltonen, Marjo; Diatchenko, Luda; Fairbanks, Carolyn A; Wilcox, George L; Hébert, Terence E; Stone, Laura S

    2015-12-01

    Opioid and α2-adrenoceptor (AR) agonists are analgesic when administered in the spinal cord and show a clinically beneficial synergistic interaction when co-administered. However, α2-AR antagonists can also inhibit opioid antinociception, suggesting a complex interaction between the two systems. The α2A-AR subtype is necessary for spinal adrenergic analgesia and synergy with opioids for most agonist combinations. Therefore, we investigated whether spinal opioid antinociception and opioid-adrenergic synergy were under allosteric control of the α2A-AR. Drugs were administered intrathecally in wild type (WT) and α2A-knock-out (KO) mice and antinociception was measured using the hot water tail immersion or substance P behavioral assays. The α2A-AR agonist clonidine was less effective in α2A-KO mice in both assays. The absence of the α2A-AR resulted in 10-70-fold increases in the antinociceptive potency of the opioid agonists morphine and DeltII. In contrast, neither morphine nor DeltII synergized with clonidine in α2A-KO mice, indicating that the α2AAR has both positive and negative modulatory effects on opioid antinociception. Depletion of descending adrenergic terminals with 6-OHDA resulted in a significant decrease in morphine efficacy in WT but not in α2A-KO mice, suggesting that endogenous norepinephrine acts through the α2A-AR to facilitate morphine antinociception. Based on these findings, we propose a model whereby ligand-occupied versus ligand-free α2A-AR produce distinct patterns of modulation of opioid receptor activation. In this model, agonist-occupied α2A-ARs potentiate opioid analgesia, while non-occupied α2A-ARs inhibit opioid analgesia. Exploiting such interactions between the two receptors could lead to the development of better pharmacological treatments for pain management. PMID:26254859

  10. Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that selectively activates the MAPK/ERK pathway.

    PubMed

    Copik, Alicja J; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J; Fitch, Bill; Raymond, John R; Ford, Anthony P D W; Button, Donald; Milla, Marcos E

    2015-01-01

    The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e., not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK

  11. Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway

    PubMed Central

    Copik, Alicja. J.; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill; Raymond, John R.; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.

    2015-01-01

    The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK

  12. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  13. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  14. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  15. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  16. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... fusion welded. Head-to-shell joints must be forge welded on class DOT-106A tanks and fusion welded on... AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this subchapter). (b)...

  17. 49 CFR 179.220-26 - Stenciling.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... outer shell, or the jacket if the outer shell is insulated, must be stenciled in compliance with AAR... both sides of the outer shell or jacket near the center in letters and figures at least 11/2...

  18. 49 CFR 179.220-26 - Stenciling.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... jacket if the outer shell is insulated, must be stenciled in compliance with AAR Specifications for Tank... the outer shell or jacket near the center in letters and figures at least 11/2 inches high to...

  19. 75 FR 20036 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... requires that the sound level of locomotive horns manufactured before September 18, 2006, be tested before... been tested. AAR states that there are a number of reasons that the testing has not progressed...

  20. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  1. 49 CFR 179.220-6 - Thickness of plates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... required bursting pressure in psig; S = Minimum tensile strength of plate material in p.s.i. as prescribed... pressure in psig; S = Minimum tensile strength of plate material in psi as prescribed in AAR...

  2. 49 CFR 179.220-6 - Thickness of plates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... required bursting pressure in psig; S = Minimum tensile strength of plate material in p.s.i. as prescribed... pressure in psig; S = Minimum tensile strength of plate material in psi as prescribed in AAR...

  3. 49 CFR 179.220-6 - Thickness of plates.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... required bursting pressure in psig; S = Minimum tensile strength of plate material in p.s.i. as prescribed... pressure in psig; S = Minimum tensile strength of plate material in psi as prescribed in AAR...

  4. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... designs, materials and construction, conversion or alteration of tank car tanks under these...

  5. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... designs, materials and construction, conversion or alteration of tank car tanks under these...

  6. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... designs, materials and construction, conversion or alteration of tank car tanks under these...

  7. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Safety, AAR, for consideration by its Tank Car Committee and other appropriate committees. Approval or... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS... designs, materials and construction, conversion or alteration of tank car tanks under these...

  8. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients.

    PubMed

    Rief, Peter; Pichler, Martin; Raggam, Reinhard; Hafner, Franz; Gerger, Armin; Eller, Philipp; Brodmann, Marianne; Gary, Thomas

    2016-06-01

    The aspartat aminotransferase (AST)/alanin aminotransferase (ALT) (De-Ritis) ratio (AAR) is an easily applicable blood test. An elevated AAR on the one hand has been associated with an increase in nonalcoholic fatty liver disease (NAFLD). NAFLD on the other hand is associated with an increase in cardiovascular disease, all-cause mortality, and diabetes. As the AAR is also elevated in case of muscular damage, we investigated AAR and its association with critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients.In our cross-sectional study, we included 1782 PAOD patients treated at our institution from 2005 to 2010. Patients with chronic alcohol consumption (>20 g/day) were excluded. AAR was calculated and the cohort was categorized into tertiles according to the AAR. An optimal cut-off value for the continuous AAR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non-CLI.In our cohort, occurrence of CLI significantly increased with an elevation in AAR. As an optimal cut-off value, an AAR of 1.67 (sensitivity 34.1%, specificity 81.0%) was identified. Two groups were categorized, 1st group containing 1385 patients (AAR < 1.67) and a 2nd group with 397 patients (AAR > 1.67). CLI was more frequent in AAR > 1.67 patients (166 [41.9%]) compared to AAR < 1.67 patients (329 [23.8%]) (P < 0.001), as was prior myocardial infarction (28 [7.1%] vs 54 [3.9%], P = 0.01). Regarding inflammatory parameters, C-reactive protein (median 8.1 mg/L [2.9-28.23] vs median 4.3 mg/L [2.0-11.5]) and fibrinogen (median 427.5 mg/dL [344.25-530.0] vs 388.0 mg/dL [327.0-493.0]) also significantly differed in the 2 patient groups (both P < 0.001). Finally, an AAR > 1.67 was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] 1.7-2.3) for CLI even after adjustment for other well-established vascular risk factors.An increased AAR is significantly associated with patients

  9. ATF4-dependent Regulation of the JMJD3 Gene during Amino Acid Deprivation Can Be Rescued in Atf4-deficient Cells by Inhibition of Deacetylation*

    PubMed Central

    Shan, Jixiu; Fu, Lingchen; Balasubramanian, Mukundh N.; Anthony, Tracy; Kilberg, Michael S.

    2012-01-01

    Following amino acid deprivation, the amino acid response (AAR) induces transcription from specific genes through a collection of signaling mechanisms, including the GCN2-eIF2-ATF4 pathway. The present report documents that the histone demethylase JMJD3 is an activating transcription factor 4 (ATF4)-dependent target gene. The JMJD3 gene contains two AAR-induced promoter activities and chromatin immunoprecipitation (ChIP) analysis showed that the AAR leads to enhanced ATF4 recruitment to the C/EBP-ATF response element (CARE) upstream of Promoter-1. AAR-induced histone modifications across the JMJD3 gene locus occur upon ATF4 binding. Jmjd3 transcription is not induced in Atf4-knock-out cells, but the AAR-dependent activation was rescued by inhibition of histone deacetylation with trichostatin A (TSA). The TSA rescue of AAR activation in the absence of Atf4 also occurred for the Atf3 and C/EBP homology protein (Chop) genes, but not for the asparagine synthetase gene. ChIP analysis of the Jmjd3, Atf3, and Chop genes in Atf4 knock-out cells documented that activation of the AAR in the presence of TSA led to specific changes in acetylation of histone H4. The results suggest that a primary function of ATF4 is to recruit histone acetyltransferase activity to a sub-set of AAR target genes. Thus, absolute binding of ATF4 to these particular genes is not required and no ATF4 interaction with the general transcription machinery is necessary. The data are consistent with the hypothesis that ATF4 functions as a pioneer factor to alter chromatin structure and thus, enhance transcription in a gene-specific manner. PMID:22955275

  10. α2A adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction

    PubMed Central

    Chen, Yunjia; Peng, Yin; Che, Pulin; Gannon, Mary; Liu, Yin; Li, Ling; Bu, Guojun; van Groen, Thomas; Jiao, Kai; Wang, Qin

    2014-01-01

    Accumulation of amyloid β (Aβ) peptides in the brain is the key pathogenic factor driving Alzheimer’s disease (AD). Endocytic sorting of amyloid precursor protein (APP) mediated by the vacuolar protein sorting (Vps10) family of receptors plays a decisive role in controlling the outcome of APP proteolytic processing and Aβ generation. Here we report for the first time to our knowledge that this process is regulated by a G protein-coupled receptor, the α2A adrenergic receptor (α2AAR). Genetic deficiency of the α2AAR significantly reduces, whereas stimulation of this receptor enhances, Aβ generation and AD-related pathology. Activation of α2AAR signaling disrupts APP interaction with a Vps10 family receptor, sorting-related receptor with A repeat (SorLA), in cells and in the mouse brain. As a consequence, activation of α2AAR reduces Golgi localization of APP and concurrently promotes APP distribution in endosomes and cleavage by β secretase. The α2AAR is a key component of the brain noradrenergic system. Profound noradrenergic dysfunction occurs consistently in patients at the early stages of AD. α2AAR-promoted Aβ generation provides a novel mechanism underlying the connection between noradrenergic dysfunction and AD. Our study also suggests α2AAR as a previously unappreciated therapeutic target for AD. Significantly, pharmacological blockade of the α2AAR by a clinically used antagonist reduces AD-related pathology and ameliorates cognitive deficits in an AD transgenic model, suggesting that repurposing clinical α2AR antagonists would be an effective therapeutic strategy for AD. PMID:25404298

  11. Cluster in the Auroral Acceleration Region

    NASA Technical Reports Server (NTRS)

    Pickett, Jolene S.; Fazakerley, Andrew N.; Marklund, Gorun; Dandouras, Iannis; Christopher, Ivar W.; Kistler, Lynn; Lucek, Elizabeth; Masson, Arnaud; Taylor, Matthew G.; Mutel, Robert L.; Santolik, Ondrej; Bell, Timothy F.; Fung, Shing; Pottelette, Raymond; Hanasz, Jan; Schreiber, Roman; Hull, Arthur J.

    2010-01-01

    Due to a fortuitous evolution of the Cluster orbit, the Cluster spacecraft penetrated for the first time in its mission the heart of Earth's auroral acceleration region (AAR) in December 2009 and January 2010. During this time a special AAR campaign was carried out by the various Cluster instrument teams with special support from ESA and NASA facilities. We present some of the first multi-spacecraft observations of the waves, particles and fields made during that campaign. The Cluster spacecraft configuration during these AAR passages was such that it allowed us to explore the differences in the signatures of waves, particles, and fields on the various spacecraft in ways not possible with single spacecraft. For example, one spacecraft was more poleward than the other three (C2), one was at higher altitude (C1), and one of them (0) followed another (C4) through the AAR on approximately the same track but delayed by three minutes. Their separations were generally on the order of a few thousand km or less and occasionally two of them were lying along the same magnetic field line. We will show some of the first analyses of the data obtained during the AAR campaign, where upward and downward current regions, and the waves specifically associated with those regions, as well as the auroral cavities, were observed similarly and differently on the various spacecraft, helping us to explore the spatial, as well as the temporal, aspects of processes occurring in the AAR.

  12. T2-weighted MRI of post-infarct myocardial edema in mice

    PubMed Central

    Beyers, Ronald J.; Smith, R. Scott; Xu, Yaqin; Piras, Bryan A.; Salerno, Michael; Berr, Stuart S.; Meyer, Craig H.; Kramer, Christopher M.; French, Brent A.; Epstein, Frederick H.

    2011-01-01

    T2-weighted, cardiac magnetic resonance imaging (T2w CMR) can be used to noninvasively detect and quantify the edematous region that corresponds to the area at risk (AAR) following myocardial infarction (MI). Previously, CMR has been used to examine structure and function in mice, expediting the study of genetic manipulations. To date, CMR has not been applied to imaging of post-MI AAR in mice. We developed a whole-heart, T2w CMR sequence to quantify the AAR in mouse models of ischemia and infarction. The ΔB0 and ΔB1 environment around the mouse heart at 7 T were measured, and a T2-preparation sequence suitable for these conditions was developed. Both in vivo T2w and late gadolinium enhanced CMR were performed in mice after 20-minute coronary occlusions, resulting in measurements of AAR size of 32.5 ± 3.1 (mean ± SEM) % LV mass, and MI size of 50.1 ± 6.4% AAR size. Excellent interobserver agreement and agreement with histology were also found. This T2w imaging method for mice may allow for future investigations of genetic manipulations and novel therapies affecting the AAR and salvaged myocardium following reperfused MI. PMID:21630350

  13. Methods for Kinetic and Thermodynamic Analysis of Aminoacyl-tRNA Synthetases

    PubMed Central

    Francklyn, Christopher S.; First, Eric A.; Perona, John J.; Hou, Ya-Ming

    2008-01-01

    The accuracy of protein synthesis relies on the ability of aminoacyl-tRNA synthetases (aaRSs) to discriminate among true and near cognate substrates. To date, analysis of aaRSs function, including identification of residues of aaRS participating in amino acid and tRNA discrimination, has largely relied on the steady state kinetic pyrophosphate exchange and aminoacylation assays. Pre-steady state kinetic studies investigating a more limited set of aaRS systems have also been undertaken to assess the energetic contributions of individual enzyme-substrate interactions, particularly in the adenylation half reaction. More recently, a renewed interest in the use of rapid kinetics approaches for aaRSs has led to their application to several new aaRS systems, resulting in the identification of mechanistic differences that distinguish the two structurally distinct aaRS classes. Here, we review the techniques for thermodynamic and kinetic analysis of aaRS function. Following a brief survey of methods for the preparation of materials and for steady state kinetic analysis, this review will describe pre-steady state kinetic methods employing rapid quench and stopped-flow fluorescence for analysis of the activation and aminoacyl transfer reactions. Application of these methods to any aaRS system allows the investigator to derive detailed kinetic mechanisms for the activation and aminoacyl transfer reactions, permitting issues of substrate specificity, stereochemical mechanism, and inhibitor interaction to be addressed in a rigorous and quantitative fashion. PMID:18241792

  14. A feasibility study evaluating effectiveness of an intervention to implement brief tobacco cessation counseling in community chain pharmacies

    PubMed Central

    Patwardhan, Pallavi D.; Chewning, Betty A.

    2016-01-01

    Objective To test the feasibility of implementing ask-advise-refer (AAR) in representative community chain pharmacies serving low socioeconomic areas, and to assess the effectiveness of a multimodal intervention on short-term implementation of AAR. Design Randomized controlled trial Settings Sixteen community chain pharmacies in South-central Wisconsin Intervention A multimodal intervention including: 1) training to implement AAR, 2) workflow integration recommendations, 3) a cessation poster to create awareness, and 4) a support visit. Main outcome measures Number of patrons asked about their tobacco use, number of tobacco users advised to quit, number of quitline cards given, and number of tobacco users enrolled in the quitline. Results As hypothesized, the multimodal intervention significantly predicted the number of patrons asked (estimate=4.84, incidence rate ratios[IRR]=127.2; p<0.001) tobacco users advised (estimate=2.12, IRR=8.33; p<0.01), quitline cards distributed (estimate=1.04, IRR=2.82; p<0.05), and tobacco users enrolled in the quitline (estimate=2.31, IRR=10.13; p<0.001). Conclusion This trial demonstrates the feasibility of implementing AAR in routine community pharmacy practice. This trial also indicates the short-term effectiveness of the intervention in facilitating AAR, implementation in partnership with other public health services and systems. More research is needed to evaluate the generalizability, effectiveness and sustainability of AAR, including factors influencing adoption and the impact on cessation. PMID:22825231

  15. Altitude Distribution and Position of Auroral Density Cavities in the Auroral Acceleration Region

    NASA Astrophysics Data System (ADS)

    Alm, L.; Li, B.; Marklund, G. T.; Karlsson, T.

    2014-12-01

    We have investigated the statistical distribution of auroral density cavities (ADC) in the auroral acceleration region (AAR) using data from the Cluster satellites. The data was collected from 2002 to 2007, at geocentric altitudes of 3.0-6.5 RE and 60-80 degrees invariant latitude. All time intervals containing upward ion beams events were manually inspected for the presence of inverted-V electrons and the spacecraft potential determined as a proxy for the electron density. The parallel potential drops above and below the satellite was estimated in order to determine the satellite's position relative the AAR. Between 4.0 and 5.5 RE several crossings of the upper edge of the AAR were observed. The maximum rate of occurrence was found between 4.75 and 5.0 RE. Between 3.75 and 6.5 RE many of the events exhibits an ion beam but no inverted-V electrons. This is consistent with the satellite being located inside the flux tube of the AAR but above the AAR. A sharp increase in the occurrence rate of ion beams without inverted-V electrons is found above 5.25 RE. The maximum occurrence rate is found between 6 and 6.5 REwhere none of the events exhibits any inverted-V. The spacecraft potential exhibits a monotonic decrease with the geocentric altitude, though the rate of decrease is very small between 4.5 and 5.75 RE. Above 5.75 RE, where a large number of events do not exhibit any inverted-V electrons, the spacecraft potential exhibits a rapid decrease. This is consistent with entering a distinct region of low electron densities. The observations indicate that the AAR extends considerably higher that the 2.0-3.0 RE which is often cited. The region between 4.5 and 5.75 RE appears to be a transition region based on the behavior of the spacecraft potential and loss of inverted-V electrons. We interpret this as being the upper edge of the AAR. However, the ADC does not appear to be confined by the AAR and will in many cases both extend above the AAR and in many cases become more

  16. Lithological influence of aggregate in the alkali-carbonate reaction

    SciTech Connect

    Lopez-Buendia, A.M. . E-mail: angel.lopez@aidico.es; Climent, V. . E-mail: vcliment@grupogla.com; Verdu, P.

    2006-08-15

    The reactivity of carbonate rock with the alkali content of cement, commonly called alkali-carbonate reaction (ACR), has been investigated. Alkali-silica reaction (ASR) can also contribute in the alkali-aggregate reaction (AAR) in carbonate rock, mainly due to micro- and crypto-crystalline quartz or clay content in carbonate aggregate. Both ACR and ASR can occur in the same system, as has been also evidenced on this paper. Carbonate aggregate samples were selected using lithological reactivity criteria, taking into account the presence of dedolomitization, partial dolomitization, micro- and crypto-crystalline quartz. Selected rocks include calcitic dolostone with chert (CDX), calcitic dolostone with dedolomitization (CDD), limestone with chert (LX), marly calcitic dolostone with partial dolomitization (CD), high-porosity ferric dolostone with clays (FD). To evaluate the reactivity, aggregates were studied using expansion tests following RILEM AAR-2, AAR-5, a modification using LiOH AAR-5Li was also tested. A complementary study was done using petrographic monitoring with polarised light microscopy on aggregates immersed in NaOH and LiOH solutions after different ages. SEM-EDAX has been used to identify the presence of brucite as a product of dedolomitization. An ACR reaction showed shrinkage of the mortar bars in alkaline solutions explained by induced dedolomitization, while an ASR process typically displayed expansion. Neither shrinkage nor expansion was observed when mortar bars were immersed in solutions of lithium hydroxide. Carbonate aggregate classification with AAR pathology risk has been elaborated based on mechanical behaviours by expansion and shrinkage. It is proposed to be used as a petrographic method for AAR diagnosis to complement the RILEM AAR1 specifically for carbonate aggregate. Aggregate materials can be classified as I (non-reactive), II (potentially reactive), and III (probably reactive), considering induced dedolomitization ACR

  17. α2A adrenergic receptors highly expressed in mesoprefrontal dopamine neurons.

    PubMed

    Castelli, M Paola; Spiga, Saturnino; Perra, Andrea; Madeddu, Camilla; Mulas, Giovanna; Ennas, M Grazia; Gessa, Gian Luigi

    2016-09-22

    α2 adrenoreceptors (α2-ARs) play a key role in the control of noradrenaline and dopamine release in the medial prefrontal cortex (mPFC). Here, using UV-laser microdissection-based quantitative mRNA expression in individual neurons we show that in hTH-GFP rats, a transgenic line exhibiting intense and specific fluorescence in dopaminergic (DA) neurons, α2A adrenoreceptor (α2A-AR) mRNA is expressed at high and low levels in DA cells in the ventral tegmental area (VTA) and substantia nigra compacta (SNc), respectively. Confocal microscopy fluorescence immunohistochemistry revealed that α2A-AR immunoreactivity colocalized with tyrosine hydroxylase (TH) in nearly all DA cells in the VTA and SNc, both in hTH-GFP rats and their wild-type Sprague-Dawley (SD) counterparts. α2A-AR immunoreactivity was also found in DA axonal projections to the mPFC and dorsal caudate in the hTH-GFP and in the anterogradely labeled DA axonal projections from VTA to mPFC in SD rats. Importantly, the α2A-AR immunoreactivity localized in the DA cells of VTA and in their fibers in the mPFC was much higher than that in DA cells of SNc and their fibers in dorsal caudate, respectively. The finding that α2A-ARs are highly expressed in the cell bodies and axons of mesoprefrontal dopaminergic neurons provides a morphological basis to the vast functional evidence that somatodendritic and nerve-terminal α2A-AR receptors control dopaminergic activity and dopamine release in the prefrontal cortex. This finding raises the question whether α2A-ARs might function as autoreceptors in the mesoprefrontal dopaminergic neurons, replacing the lack of D2 autoreceptors. PMID:27365174

  18. α(2A) adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction.

    PubMed

    Chen, Yunjia; Peng, Yin; Che, Pulin; Gannon, Mary; Liu, Yin; Li, Ling; Bu, Guojun; van Groen, Thomas; Jiao, Kai; Wang, Qin

    2014-12-01

    Accumulation of amyloid β (Aβ) peptides in the brain is the key pathogenic factor driving Alzheimer's disease (AD). Endocytic sorting of amyloid precursor protein (APP) mediated by the vacuolar protein sorting (Vps10) family of receptors plays a decisive role in controlling the outcome of APP proteolytic processing and Aβ generation. Here we report for the first time to our knowledge that this process is regulated by a G protein-coupled receptor, the α(2A) adrenergic receptor (α(2A)AR). Genetic deficiency of the α(2A)AR significantly reduces, whereas stimulation of this receptor enhances, Aβ generation and AD-related pathology. Activation of α(2A)AR signaling disrupts APP interaction with a Vps10 family receptor, sorting-related receptor with A repeat (SorLA), in cells and in the mouse brain. As a consequence, activation of α(2A)AR reduces Golgi localization of APP and concurrently promotes APP distribution in endosomes and cleavage by β secretase. The α(2A)AR is a key component of the brain noradrenergic system. Profound noradrenergic dysfunction occurs consistently in patients at the early stages of AD. α(2A)AR-promoted Aβ generation provides a novel mechanism underlying the connection between noradrenergic dysfunction and AD. Our study also suggests α(2A)AR as a previously unappreciated therapeutic target for AD. Significantly, pharmacological blockade of the α(2A)AR by a clinically used antagonist reduces AD-related pathology and ameliorates cognitive deficits in an AD transgenic model, suggesting that repurposing clinical α(2A)R antagonists would be an effective therapeutic strategy for AD. PMID:25404298

  19. 76 FR 72713 - Government-Owned Inventions; Availability for Licensing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-25

    ...). Inventors: Katrin D. Mayer, Bruno Bezerril D. Andrade, F. Alan Sher, and Daniel L. Barber (NIAID... inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results...

  20. A GLIMPSE INTO THE EYE OF THE EMERGENCY RESPONSE AT EPA KATRINA AND RITA

    EPA Science Inventory

    This presentation was given at the Texas Environmental Health Association Annual Meeting in Round Rock, TX on October 12, 2005. The keynote address was focused on the conditions after Katrins, organizing response, field response, EPA's role in emergency response, what is EPA doi...

  1. A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation.

    PubMed

    Shan, Jixiu; Balasubramanian, Mukundh N; Donelan, William; Fu, Lingchen; Hayner, Jaclyn; Lopez, Maria-Cecilia; Baker, Henry V; Kilberg, Michael S

    2014-08-29

    Amino acid (AA) limitation in mammalian cells triggers a collection of signaling cascades jointly referred to as the AA response (AAR). In human HepG2 hepatocellular carcinoma, the early growth response 1 (EGR1) gene was induced by either AA deprivation or endoplasmic reticulum stress. AAR-dependent EGR1 activation was discovered to be independent of the well characterized GCN2-ATF4 pathway and instead dependent on MEK-ERK signaling, one of the MAPK pathways. ChIP showed that constitutively bound ELK1 at the EGR1 proximal promoter region was phosphorylated after AAR activation. Increased p-ELK1 binding was associated with increased de novo recruitment of RNA polymerase II to the EGR1 promoter. EGR1 transcription was not induced in HEK293T cells lacking endogenous MEK activity, but overexpression of exogenous constitutively active MEK in HEK293T cells resulted in increased basal and AAR-induced EGR1 expression. ChIP analysis of the human vascular endothelial growth factor A (VEGF-A) gene, a known EGR1-responsive gene, revealed moderate increases in AAR-induced EGR1 binding within the proximal promoter and highly inducible binding to a site within the first intron. Collectively, these data document a novel AA-activated MEK-ERK-ELK1 signaling mechanism. PMID:25028509

  2. MAPK signaling triggers transcriptional induction of cFOS during amino acid limitation of HepG2 cells.

    PubMed

    Shan, Jixiu; Donelan, William; Hayner, Jaclyn N; Zhang, Fan; Dudenhausen, Elizabeth E; Kilberg, Michael S

    2015-03-01

    Amino acid (AA) deprivation in mammalian cells activates a collection of signaling cascades known as the AA response (AAR), which is characterized by transcriptional induction of stress-related genes, including FBJ murine osteosarcoma viral oncogene homolog (cFOS). The present study established that the signaling mechanism underlying the AA-dependent transcriptional regulation of the cFOS gene in HepG2 human hepatocellular carcinoma cells is independent of the classic GCN2-eIF2-ATF4 pathway. Instead, a RAS-RAF-MEK-ERK cascade mediates AAR signaling to the cFOS gene. Increased cFOS transcription is observed from 4-24 h after AAR-activation, exhibiting little or no overlap with the rapid and transient increase triggered by the well-known serum response. Furthermore, serum is not required for the AA-responsiveness of the cFOS gene and no phosphorylation of promoter-bound serum response factor (SRF) is observed. The ERK-phosphorylated transcription factor E-twenty six-like (p-ELK1) is increased in its association with the cFOS promoter after activation of the AAR. This research identified cFOS as a target of the AAR and further highlights the importance of AA-responsive MAPK signaling in HepG2 cells. PMID:25523140

  3. Design, synthesis, and biological evaluation of novel 2-((2-(4-(substituted)phenylpiperazin-1-yl)ethyl)amino)-5'-N-ethylcarboxamidoadenosines as potent and selective agonists of the A2A adenosine receptor.

    PubMed

    Preti, Delia; Baraldi, Pier Giovanni; Saponaro, Giulia; Romagnoli, Romeo; Aghazadeh Tabrizi, Mojgan; Baraldi, Stefania; Cosconati, Sandro; Bruno, Agostino; Novellino, Ettore; Vincenzi, Fabrizio; Ravani, Annalisa; Borea, Pier Andrea; Varani, Katia

    2015-04-01

    Stimulation of A2A adenosine receptors (AR) promotes anti-inflammatory responses in animal models of allergic rhinitis, asthma, chronic obstructive pulmonary disease, and rheumatic diseases. Herein we describe the results of a research program aimed at identifying potent and selective agonists of the A2AAR as potential anti-inflammatory agents. The recent crystallographic analysis of A2AAR agonists and antagonists in complex with the receptor provided key information on the structural determinants leading to receptor activation or blocking. In light of this, we designed a new series of 2-((4-aryl(alkyl)piperazin-1-yl)alkylamino)-5'-N-ethylcarboxamidoadenosines with high A2AAR affinity, activation potency and selectivity obtained by merging distinctive structural elements of known agonists and antagonists of the investigated target. Docking-based SAR optimization allowed us to identify compound 42 as one of the most potent and selective A2A agonist discovered so far (Ki hA2AAR = 4.8 nM, EC50 hA2AAR = 4.9 nM, Ki hA1AR > 10 000 nM, Ki hA3AR = 1487 nM, EC50 hA2BAR > 10 000 nM). PMID:25780876

  4. Energy Budget of Alfven Wave Interactions with the Auroral Acceleration Region

    NASA Astrophysics Data System (ADS)

    Pilipenko, V.; Fedorov, E.; Engebretson, M. J.

    2003-12-01

    Recent Polar satellite observations of intense Alfven ULF bursts over auroral arcs prompted researchers to suggest that ULF wave activity does provide energy to the auroral arc intensification. However, to provide physical grounds for this suggestion, it is important to know possible bounds on the rate of the ULF wave energy transfer into electron acceleration. To estimate the power dissipated in the ionosphere and that transferred into electron acceleration, we consider the interaction of magnetospheric Alfven waves with the auroral ionosphere, comprising the auroral acceleration region (AAR). The AAR is characterized by a mirror resistance to the field-aligned upward current that can provide the potential drop and the acceleration of electrons. Analytical treatment of the interaction of Alfven waves with the combined magnetosphere-AAR-topside ionosphere-E-layer system has been made within the "thin" AAR approximation, which is valid for small-scale disturbances. The input of Alfven waves into the energy balance of the AAR depends critically on their transverse scale. Only waves with scales comparable to the Alfven transit scale, that is kperpendicular to λ A ˜= 1, will provide energy into electron acceleration. This process is expected to be more effective above a conductive ionosphere. These theoretical predictions could be verified with the multi-satellite measurements in the Cluster-2 mission.

  5. Loss-of-Function Alanyl-tRNA Synthetase Mutations Cause an Autosomal-Recessive Early-Onset Epileptic Encephalopathy with Persistent Myelination Defect

    PubMed Central

    Simons, Cas; Griffin, Laurie B.; Helman, Guy; Golas, Gretchen; Pizzino, Amy; Bloom, Miriam; Murphy, Jennifer L.P.; Crawford, Joanna; Evans, Sarah H.; Topper, Scott; Whitehead, Matthew T.; Schreiber, John M.; Chapman, Kimberly A.; Tifft, Cyndi; Lu, Katrina B.; Gamper, Howard; Shigematsu, Megumi; Taft, Ryan J.; Antonellis, Anthony; Hou, Ya-Ming; Vanderver, Adeline

    2015-01-01

    Mutations in genes encoding aminoacyl-tRNA synthetases are known to cause leukodystrophies and genetic leukoencephalopathies—heritable disorders that result in white matter abnormalities in the central nervous system. Here we report three individuals (two siblings and an unrelated individual) with severe infantile epileptic encephalopathy, clubfoot, absent deep tendon reflexes, extrapyramidal symptoms, and persistently deficient myelination on MRI. Analysis by whole exome sequencing identified mutations in the nuclear-encoded alanyl-tRNA synthetase (AARS) in these two unrelated families: the two affected siblings are compound heterozygous for p.Lys81Thr and p.Arg751Gly AARS, and the single affected child is homozygous for p.Arg751Gly AARS. The two identified mutations were found to result in a significant reduction in function. Mutations in AARS were previously associated with an autosomal-dominant inherited form of axonal neuropathy, Charcot-Marie-Tooth disease type 2N (CMT2N). The autosomal-recessive AARS mutations identified in the individuals described here, however, cause a severe infantile epileptic encephalopathy with a central myelin defect and peripheral neuropathy, demonstrating that defects of alanyl-tRNA charging can result in a wide spectrum of disease manifestations. PMID:25817015

  6. Alkali-aggregate reactivity of typical siliceious glass and carbonate rocks in alkali-activated fly ash based geopolymers

    NASA Astrophysics Data System (ADS)

    Lu, Duyou; Liu, Yongdao; Zheng, Yanzeng; Xu, Zhongzi; Shen, Xiaodong

    2013-08-01

    For exploring the behaviour of alkali-aggregate reactivity (AAR) in alkali-activated geopolymeric materials and assessing the procedures for testing AAR in geopolymers, the expansion behaviour of fly ash based geopolymer mortars with pure silica glass and typical carbonate rocks were studied respectively by curing at various conditions, i.e. 23°C and 38°C with relative humidity over 95%, immersed in 1M NaOH solution at 80°C. Results show that, at various curing conditions, neither harmful ASR nor harmful ACR was observed in geopolymers with the criteria specified for OPC system. However, with the change of curing conditions, the geopolymer binder and reactive aggregates may experience different reaction processes leading to quite different dimensional changes, especially with additional alkalis and elevated temperatures. It suggests that high temperature with additional alkali for accelerating AAR in traditional OPC system may not appropriate for assessing the alkali-aggregate reactivity behaviour in geopolymers designed for normal conditions. On the other hand, it is hopeful to control the dimensional change of geopolymer mortar or concrete by selecting the type of aggregates and the appropriate curing conditions, thus changing the harmful AAR in OPC into beneficial AAR in geopolymers and other alkali-activated cementitious systems.

  7. A Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase (MEK)-dependent Transcriptional Program Controls Activation of the Early Growth Response 1 (EGR1) Gene during Amino Acid Limitation*

    PubMed Central

    Shan, Jixiu; Balasubramanian, Mukundh N.; Donelan, William; Fu, Lingchen; Hayner, Jaclyn; Lopez, Maria-Cecilia; Baker, Henry V.; Kilberg, Michael S.

    2014-01-01

    Amino acid (AA) limitation in mammalian cells triggers a collection of signaling cascades jointly referred to as the AA response (AAR). In human HepG2 hepatocellular carcinoma, the early growth response 1 (EGR1) gene was induced by either AA deprivation or endoplasmic reticulum stress. AAR-dependent EGR1 activation was discovered to be independent of the well characterized GCN2-ATF4 pathway and instead dependent on MEK-ERK signaling, one of the MAPK pathways. ChIP showed that constitutively bound ELK1 at the EGR1 proximal promoter region was phosphorylated after AAR activation. Increased p-ELK1 binding was associated with increased de novo recruitment of RNA polymerase II to the EGR1 promoter. EGR1 transcription was not induced in HEK293T cells lacking endogenous MEK activity, but overexpression of exogenous constitutively active MEK in HEK293T cells resulted in increased basal and AAR-induced EGR1 expression. ChIP analysis of the human vascular endothelial growth factor A (VEGF-A) gene, a known EGR1-responsive gene, revealed moderate increases in AAR-induced EGR1 binding within the proximal promoter and highly inducible binding to a site within the first intron. Collectively, these data document a novel AA-activated MEK-ERK-ELK1 signaling mechanism. PMID:25028509

  8. Morphometric assessment of the canine hip joint using the acetabular angle of retrotorsion.

    PubMed

    Doskarova, B; Kyllar, M; Paral, V

    2010-01-01

    Morphometric assessment of the canine hip joint using acetabular angle of retrotorsion was used in this study. The aim of our study was to compare the acetabular angle of retrotorsion (AAR) with values of the Norberg angle (NA) and the hip score (HS) in the Leonberger dog breed and to determine the cut-off point of AAR that distinguish between normal and dysplastic hip status on the basis of Fédération Cynologique Internationale (FCI) hip evaluation. Retrospective analysis of NA and AAR was measured from standard ventrodorsal pelvic radiographs with extended femurs in 387 Leonberger dogs (141 males and 246 females) from 18 to 63 months of age, which were then divided into five age-groups. Through analysis of these radiographs, it was determined that the cut-off point for NA was 105°, AAR was 15°, and the acetabular angle of retrotorsion was positively correlated with Norberg angle and negatively correlated with hip score. The results of our study indicate that the acetabular angle of retrotorsion may represent a reliable morphometric assessment tool in evaluating acetabular cup conformation, and values of AAR may help to assess the FCI grade of canine hip dysplasia. PMID:20740259

  9. Stimulation of α(2A)-adrenoceptors promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex.

    PubMed

    Ren, Wen-Wen; Liu, Yue; Li, Bao-Ming

    2012-02-01

    Dendritic spines are tiny protrusions along dendrites that receive excitatory synaptic inputs and compartmentalize postsynaptic responses in the mature brain. It is known that change in spine morphology is associated with brain functions such as learning and memory. α(2A)-Adrenoceptors (α(2A)-ARs) are highly expressed in cortical neurons and play important roles in neuronal differentiation, growth and neurotrophy. However, little is known about the role of α(2A)-ARs in the maturation of dendritic spines. Here, we report that stimulation of α(2A)-ARs promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex of rodents. Our results show that, stimulation of α(2A)-ARs by guanfacine induced significantly more stubby or mushroom spines in cultured mPFC neurons, with an enlargement of the spine head size. In parallel, the expression of PSD95 (a postsynaptic protein) in guanfacine-treated neurons was enhanced, while that of synapsin (a pre-synaptic protein) kept unchanged. These effects of guanfacine were blocked by co-administered yohimbine, a non-selective α(2)-AR antagonist. The present results implicate a prominent role of α(2A)-ARs in regulating the maturation of dendritic spines in the mPFC. PMID:22015717

  10. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect.

    PubMed

    Simons, Cas; Griffin, Laurie B; Helman, Guy; Golas, Gretchen; Pizzino, Amy; Bloom, Miriam; Murphy, Jennifer L P; Crawford, Joanna; Evans, Sarah H; Topper, Scott; Whitehead, Matthew T; Schreiber, John M; Chapman, Kimberly A; Tifft, Cyndi; Lu, Katrina B; Gamper, Howard; Shigematsu, Megumi; Taft, Ryan J; Antonellis, Anthony; Hou, Ya-Ming; Vanderver, Adeline

    2015-04-01

    Mutations in genes encoding aminoacyl-tRNA synthetases are known to cause leukodystrophies and genetic leukoencephalopathies-heritable disorders that result in white matter abnormalities in the central nervous system. Here we report three individuals (two siblings and an unrelated individual) with severe infantile epileptic encephalopathy, clubfoot, absent deep tendon reflexes, extrapyramidal symptoms, and persistently deficient myelination on MRI. Analysis by whole exome sequencing identified mutations in the nuclear-encoded alanyl-tRNA synthetase (AARS) in these two unrelated families: the two affected siblings are compound heterozygous for p.Lys81Thr and p.Arg751Gly AARS, and the single affected child is homozygous for p.Arg751Gly AARS. The two identified mutations were found to result in a significant reduction in function. Mutations in AARS were previously associated with an autosomal-dominant inherited form of axonal neuropathy, Charcot-Marie-Tooth disease type 2N (CMT2N). The autosomal-recessive AARS mutations identified in the individuals described here, however, cause a severe infantile epileptic encephalopathy with a central myelin defect and peripheral neuropathy, demonstrating that defects of alanyl-tRNA charging can result in a wide spectrum of disease manifestations. PMID:25817015

  11. Optimal hierarchies for fuzzy object models

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica M. S.; Udupa, Jayaram K.

    2013-03-01

    In radiologic clinical practice, the analysis underlying image examinations are qualitative, descriptive, and to some extent subjective. Quantitative radiology (QR) is valuable in clinical radiology. Computerized automatic anatomy recognition (AAR) is an essential step toward that goal. AAR is a body-wide organ recognition strategy. The AAR framework is based on fuzzy object models (FOMs) wherein the models for the different objects are encoded in a hierarchy. We investigated ways of optimally designing the hierarchy tree while building the models. The hierarchy among the objects is a core concept of AAR. The parent-offspring relationships have two main purposes in this context: (i) to bring into AAR more understanding and knowledge about the form, geography, and relationships among objects, and (ii) to foster guidance to object recognition and object delineation. In this approach, the relationship among objects is represented by a graph, where the vertices are the objects (organs) and the edges connect all pairs of vertices into a complete graph. Each pair of objects is assigned a weight described by the spatial distance between them, their intensity profile differences, and their correlation in size, all estimated over a population. The optimal hierarchy tree is obtained by the shortest-path algorithm as an optimal spanning tree. To evaluate the optimal hierarchies, we have performed some preliminary tests involving the subsequent recognition step. The body region used for initial investigation was the thorax.

  12. Paraventricular nucleus is involved in the central pathway of adipose afferent reflex in rats.

    PubMed

    Shi, Zhen; Wang, Yuan-Fang; Wang, Gui-Hua; Wu, Yu-Long; Ma, Chun-Lei

    2016-05-01

    Increasing evidence indicates a link between sympathetic nervous system activation and obesity, but the underlying mechanisms remain elusive. The adipose afferent reflex (AAR) is a sympathoexcitatory reflex that is activated by afferent neurotransmission from the white adipose tissue (WAT). This study aimed to investigate whether the hypothalamic paraventricular nucleus (PVH) is an important component of the central neurocircuitry of the AAR. In anesthetized rats, the discharge activity of individual PVH neurons was recorded in vivo. Activation of WAT afferents was initiated by capsaicin injection, and the AAR was evaluated by monitoring renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses. The responses of PVH neurons to activation of WAT afferents were evaluated by c-fos immunoreactivity and the discharge activity of individual PVH neurons, which was recorded using extracellular single-unit recording. After activation of WAT afferents, both individual PVH neuron discharge activity and c-fos immunoreactivity increased. Bilateral selective lesions of the neurons in the PVH with kainic acid abolished the AAR. These results indicate that PVH is an important component of the central neurocircuitry of the AAR. PMID:26963333

  13. Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24

    SciTech Connect

    Nichols, R.C.; Blinder, J.; Pai, S.I.

    1996-08-15

    Protein synthesis is initiated by the attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (aaRS). Five of twenty human aaRS (histidyl-RS, threonyl-RS, alanyl-RS, glycyl-RS, and isoleucyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Autoantibodies to human lysyl-RS, a sixth autoantigenic aminoacyl-RS, were recently identified. The genes for histidyl-RS and threonyl-RS have been localized to chromosome 5, and we recently reported that the genes for alanyl-RS and glycyl-RS localize to chromosomes 16 and 7, respectively. To understand the genesis of autoimmune responses to aaRS better, we have used PCR-based screening of somatic cell hybrid panels and fluorescence in situ hybridization (FISH) to assign the genes for isoleucyl-RS and lysyl-RS. 19 refs., 1 fig.

  14. Finite element analysis of three TVA dams with alkali-aggregate reaction

    SciTech Connect

    Grenoble, B.A.; Meisenheimer, J.K.; Wagner, C.D.; Newell, V.A.

    1995-12-31

    Three large Tennessee Valley Authority (TVA) dams are currently experiencing problems caused by alkali-aggregate reaction (AAR). Since the fall of 1990, engineers in Stone & Webster`s Denver, Colorado office have been working with TVA to evaluate how AAR is affecting the dams and to identify measures for controlling the adverse effects of the concrete growth. This paper provides an overview of how finite element analysis is being used to understand the affects of AAR on these structures and to evaluate alternatives for minimizing the adverse effects of the concrete growth. Work on Hiwassee Dam is essentially complete, while that on the Chickamauga and Fontana Projects is still in progress. Consequently, this paper will focus primarily on Hiwassee Dam. The ongoing work on the other two projects will only be discussed briefly.

  15. Effects of phorbol esters on adrenergic receptors of DDT MF-2 smooth muscle cells

    SciTech Connect

    Cowlen, M.; Toews, M.

    1986-03-05

    Phorbol esters have been reported to induce redistribution or internalization of several types of cell surface receptors, including beta-adrenergic receptors (BAR) in some cells. They investigated the effects of phorbol esters on adrenergic receptor distribution in DDT/sub 1/ MF-2 smooth muscle cells in suspension culture. Exposure of cells to epinephrine, an agonist for both BAR and alpha-1 adrenergic receptors (AAR), led to a shift of about half of BAR from plasma membrane to light vesicle fractions on sucrose density gradient centrifugation. This change correlates with other evidence for internalization or sequestration of BAR away from the cell surface. AAR distribution remained unaltered following agonist treatment. Pretreatment of cells with phorbol 12-myristate 13-acetate, which caused about 80% inhibition of epinephrine-stimulated turnover of inositol phospholipids, did not lead to redistribution of either BAR or AAR.

  16. Excellent amino acid racemization results from Holocene sand dollars

    NASA Astrophysics Data System (ADS)

    Kosnik, M.; Kaufman, D. S.; Kowalewski, M.; Whitacre, K.

    2015-12-01

    Amino acid racemization (AAR) is widely used as a cost-effective method to date molluscs in time-averaging and taphonomic studies, but it has not been attempted for echinoderms despite their paleobiological importance. Here we demonstrate the feasibility of AAR geochronology in Holocene aged Peronella peronii (Echinodermata: Echinoidea) collected from Sydney Harbour (Australia). Using standard HPLC methods we determined the extent of AAR in 74 Peronella tests and performed replicate analyses on 18 tests. We sampled multiple areas of two individuals and identified the outer edge as a good sampling location. Multiple replicate analyses from the outer edge of 18 tests spanning the observed range of D/Ls yielded median coefficients of variation < 4% for Asp, Phe, Ala, and Glu D/L values, which overlaps with the analytical precision. Correlations between D/L values across 155 HPLC injections sampled from 74 individuals are also very high (pearson r2 > 0.95) for these four amino acids. The ages of 11 individuals spanning the observed range of D/L values were determined using 14C analyses, and Bayesian model averaging was used to determine the best AAR age model. The averaged age model was mainly composed of time-dependent reaction kinetics models (TDK, 71%) based on phenylalanine (Phe, 94%). Modelled ages ranged from 14 to 5539 yrs, and the median 95% confidence interval for the 74 analysed individuals is ±28% of the modelled age. In comparison, the median 95% confidence interval for the 11 calibrated 14C ages was ±9% of the median age estimate. Overall Peronella yields exceptionally high-quality AAR D/L values and appears to be an excellent substrate for AAR geochronology. This work opens the way for time-averaging and taphonomic studies of echinoderms similar to those in molluscs.

  17. Geophysical Investigation of Australian-Antarctic Ridge Using High-Resolution Gravity and Bathymetry

    NASA Astrophysics Data System (ADS)

    Kim, S. S.; Lin, J.; Park, S. H.; Choi, H.

    2015-12-01

    Much of the Australian-Antarctic Ridge (AAR) has been remained uncharted until 2011 because of its remoteness and harsh weather conditions. From 2011, the multidisciplinary ridge program initiated by the Korea Polar Research Institute (KOPRI) surveyed the little-explored eastern ends of the AAR to characterize the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. In this study, we present a detailed analysis of a 300-km-long supersegment of the AAR to quantify the spatial variations in ridge morphology and axial and off-axis volcanisms as constrained by high-resolution shipboard bathymetry and gravity. The ridge axis morphology alternates between rift valleys and axial highs within relatively short ridge segments. To obtain a geological proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for neighboring seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle in comparison to the conjugate northern flank. Furthermore, this north-south asymmetry becomes more prominent toward the KR1 supersegment of the AAR. The axial topography of the KR1 supersegment exhibits a sharp transition from axial highs at the western end to rift valleys at the eastern end, with regions of axial highs being associated with more robust magma supply as indicated by more negative RMBA. We also compare and contrast the characteristics of the AAR supersegment with that of other ridges of intermediate spreading rates, including the Juan de Fuca Ridge, Galápagos Spreading Center, and Southeast Indian Ridge west of the Australian-Antarctic Discordance, to investigate the influence of ridge-hotspot interaction on ridge magma supply and tectonics.

  18. Automatic anatomy recognition in post-tonsillectomy MR images of obese children with OSAS

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Odhner, Dewey; Sin, Sanghun; Arens, Raanan

    2015-03-01

    Automatic Anatomy Recognition (AAR) is a recently developed approach for the automatic whole body wide organ segmentation. We previously tested that methodology on image cases with some pathology where the organs were not distorted significantly. In this paper, we present an advancement of AAR to handle organs which may have been modified or resected by surgical intervention. We focus on MRI of the neck in pediatric Obstructive Sleep Apnea Syndrome (OSAS). The proposed method consists of an AAR step followed by support vector machine techniques to detect the presence/absence of organs. The AAR step employs a hierarchical organization of the organs for model building. For each organ, a fuzzy model over a population is built. The model of the body region is then described in terms of the fuzzy models and a host of other descriptors which include parent to offspring relationship estimated over the population. Organs are recognized following the organ hierarchy by using an optimal threshold based search. The SVM step subsequently checks for evidence of the presence of organs. Experimental results show that AAR techniques can be combined with machine learning strategies within the AAR recognition framework for good performance in recognizing missing organs, in our case missing tonsils in post-tonsillectomy images as well as in simulating tonsillectomy images. The previous recognition performance is maintained achieving an organ localization accuracy of within 1 voxel when the organ is actually not removed. To our knowledge, no methods have been reported to date for handling significantly deformed or missing organs, especially in neck MRI.

  19. Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow.

    PubMed

    Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F; McEver, Rodger P

    2015-10-15

    A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID:26355151

  20. Amino acid racemization on planktic foraminifera from the central Arctic Ocean

    NASA Astrophysics Data System (ADS)

    Hanslik, D.; Kaufman, D. S.; Jakobsson, M.

    2009-12-01

    Amino acid racemization (AAR) is the interconversion of amino acids from one chiral form (L - levo) to a mixture of L- and D- (dextro) forms as a function of time and temperature. The extent of AAR in foraminifera shells can be determined by measuring the ratio of D/L amino acids, and can be used as a relative dating method. The technique can also be used to determine numerical ages once the rate of racemization is calibrated for a study area using samples of known ages. In this study sediment cores from the Lomonosov Ridge (88°N) and Morris Jesup Rise (85°N), in the central Arctic Ocean, were analyzed for AAR on monospecific samples of the polar planktic foraminifera Neogloboquadrina pachyderma sinistral. Numerical ages were derived using an equation developed for aspartic and glutamic acids in a previous study on other cores from the Northwind, Mendeleev and Lomonosov ridges, which applies to samples younger than about 150 ka (Kaufman et al., 2008, Paleoceanography 23:PA3224). The calculated AAR ages are in relatively good agreement with 14C ages throughout the range of 14C dating for both of our cores. The core from Morris Jesup Rise includes older sediment beyond the range of 14C dating where ages were inferred from benthic foraminifera events and correlation with other cores with previously published age models. The AAR age for the level of unique occurrence of the benthic foramifera Bulimina aculeata from this core is about 85 ka, which agrees with previous work that assigned this level to MIS 5.1. Beyond about 85 ka, there is a progressively increasing age discrepancy between calculated AAR ages and estimated ages based on benthic foraminifera events. For MIS 5.5, the D/L values for the Epistominella exigua marker are lower in our core than in the cores analyzed by Kaufman et al. (2008). Assuming that this event is a chronostratigraphic marker, then the AAR results suggest that deepwater temperature at our site during MIS 5 was lower than at the other

  1. Data on Arc and Zif268 expression in the brain of the α-2A adrenergic receptor knockout mouse

    PubMed Central

    Sanders, Jeff

    2016-01-01

    The α2-adrenergic receptor (α2-AR) is widely distributed in the brain with distinct roles for α2-AR subtypes (A, B and C). In this article, data are provided on Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 expression in the brain of the α2A-AR knockout (α2A-AR KO) mouse. These data are supplemental to an original research article examining Arc and Zif268 expression in rats injected with the α2-AR antagonist, RX821002 (http://dx.doi.org/10.1016/j.neulet.2015.12.002. [1]). PMID:26952134

  2. Data on Arc and Zif268 expression in the brain of the α-2A adrenergic receptor knockout mouse.

    PubMed

    Sanders, Jeff

    2016-06-01

    The α2-adrenergic receptor (α2-AR) is widely distributed in the brain with distinct roles for α2-AR subtypes (A, B and C). In this article, data are provided on Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 expression in the brain of the α2A-AR knockout (α2A-AR KO) mouse. These data are supplemental to an original research article examining Arc and Zif268 expression in rats injected with the α2-AR antagonist, RX821002 (http://dx.doi.org/10.1016/j.neulet.2015.12.002. [1]). PMID:26952134

  3. Interaction with Caveolin-1 Modulates G Protein Coupling of Mouse β3-Adrenoceptor*

    PubMed Central

    Sato, Masaaki; Hutchinson, Dana S.; Halls, Michelle L.; Furness, Sebastian G. B.; Bengtsson, Tore; Evans, Bronwyn A.; Summers, Roger J.

    2012-01-01

    Caveolins act as scaffold proteins in multiprotein complexes and have been implicated in signaling by G protein-coupled receptors. Studies using knock-out mice suggest that β3-adrenoceptor (β3-AR) signaling is dependent on caveolin-1; however, it is not known whether caveolin-1 is associated with the β3-AR or solely with downstream signaling proteins. We have addressed this question by examining the impact of membrane rafts and caveolin-1 on the differential signaling of mouse β3a- and β3b-AR isoforms that diverge at the distal C terminus. Only the β3b-AR promotes pertussis toxin (PTX)-sensitive cAMP accumulation. When cells expressing the β3a-AR were treated with filipin III to disrupt membrane rafts or transfected with caveolin-1 siRNA, the cyclic AMP response to the β3-AR agonist CL316243 became PTX-sensitive, suggesting Gαi/o coupling. The β3a-AR C terminus, SP384PLNRF389DGY392EGARPF398PT, resembles a caveolin interaction motif. Mutant β3a-ARs (F389A/Y392A/F398A or P384S/F389A) promoted PTX-sensitive cAMP responses, and in situ proximity assays demonstrated an association between caveolin-1 and the wild type β3a-AR but not the mutant receptors. In membrane preparations, the β3b-AR activated Gαo and mediated PTX-sensitive cAMP responses, whereas the β3a-AR did not activate Gαi/o proteins. The endogenous β3a-AR displayed Gαi/o coupling in brown adipocytes from caveolin-1 knock-out mice or in wild type adipocytes treated with filipin III. Our studies indicate that interaction of the β3a-AR with caveolin inhibits coupling to Gαi/o proteins and suggest that signaling is modulated by a raft-enriched complex containing the β3a-AR, caveolin-1, Gαs, and adenylyl cyclase. PMID:22535965

  4. Monte Carlo calculations of the intrinsic detector backgrounds for the Karlsruhe Tritium Neutrino Experiment

    NASA Astrophysics Data System (ADS)

    Leber, Michelle L.

    The Karlsruhe Tritium Neutrino Experiment (KATRIN) aims to measure the absolute neutrino mass, an open question in neutrino physics. KATRIN exploits the fact that the beta-decay spectral shape near the endpoint depends on the neutrino mass. Using a gaseous tritium source and a precise electrostatic spectrometer, KATRIN will measure the integral beta-decay spectrum in a silicon detector. KATRIN strives for a sensitivity of 0.2 eV (90% CL) to the neutrino mass, ten times better than the current limit. A measurement at this level of sensitivity has broad implications for cosmology and particle physics. To maximize sensitivity to the small beta-decay signal, the KATRIN silicon detector must have minimal intrinsic backgrounds. The background goal for the detector is less than 10-3 counts per second (1 mHz) in the region of interest near the 18.6 keV signal. In this dissertation, we present estimates of the detector background rate calculated with a custom Geant4-based Monte Carlo simulation. The simulation includes a detailed description of the detector system and attributes of the intrinsic background sources, natural radioactivity and cosmic rays. We identified the largest background sources, optimized the detector region design to minimize the background rate, and performed measurements to confirm the simulation results. In particular, we have measured the radiation field from radioactivity in all objects in the detector laboratory using a germanium detector. The simulated germanium detector rate agrees within 5% of the measured rate. In addition, various calibration spectra measured with silicon and germanium detectors are within 7% of the simulated spectra. The results from our simulations indicate that we should observe a background of [2.54 +/- 0.11(stat.) +0.36-0.35 (sys.)]mHz at the nominal magnetic field of 3 T and zero post acceleration. The largest background sources are radiation from the laboratory environment and cosmic-ray photons. Utilizing 20 kV of

  5. Chapter K: Progress in the Evaluation of Alkali-Aggregate Reaction in Concrete Construction in the Pacific Northwest, United States and Canada

    USGS Publications Warehouse

    Shrimer, Fred H.

    2005-01-01

    The supply of aggregates suitable for use in construction and maintenance of infrastructure in western North America is a continuing concern to the engineering and resources-management community. Steady population growth throughout the region has fueled demand for high-quality aggregates, in the face of rapid depletion of existing aggregate resources and slow and difficult permitting of new sources of traditional aggregate types. In addition to these challenges, the requirement for aggregates to meet various engineering standards continues to increase. In addition to their physical-mechanical properties, other performance characteristics of construction aggregates specifically depend on their mineralogy and texture. These properties can result in deleterious chemical reactions when aggregate is used in concrete mixes. When this chemical reaction-termed 'alkali-aggregate reaction' (AAR)-occurs, it can pose a major problem for concrete structures, reducing their service life and requiring expensive repair or even replacement of the concrete. AAR is thus to be avoided in order to promote the longevity of concrete structures and to ensure that public moneys invested in infrastructure are well spent. Because the AAR phenomenon is directly related to the mineral composition, texture, and petrogenesis of the rock particles that make up aggregates, an understanding of the relation between the geology and the performance of aggregates in concrete is important. In the Pacific Northwest, some aggregates have a moderate to high AAR potential, but many others have no or only a low AAR potential. Overall, AAR is not as widespread or serious a problem in the Pacific Northwest as in other regions of North America. The identification of reactive aggregates in the Pacific Northwest and the accurate prediction of their behavior in concrete continue to present challenges for the assessment and management of geologic resources to the owners and operators of pits and quarries and to the

  6. LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS

    EPA Science Inventory

    2003 AAR PM Meeting
    Particulate Matter: Atmospheric Sciences,
    Exposure and the Fourth Colloquium on PM and Human Health

    LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, C...

  7. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

  8. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

  9. Personal Epistemology of Urban Elementary School Teachers

    ERIC Educational Resources Information Center

    Pearrow, Melissa; Sanchez, William

    2008-01-01

    Personal epistemology, originating from social construction theory, provides a framework for researchers to understand how individuals view their world. The Attitudes About Reality (AAR) scale is one survey method that qualitatively assesses personal epistemology along the logical positivist and social constructionist continuum; however, the…

  10. 76 FR 40701 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... Star Safire III Forward Looking Infrared Radar Systems, 6 AAR-57(V)3 Common Missile Warning Systems, 6... Signal Detecting Sets, 80 AN/AVS-9 Night Vision Devices, 6 Star Safire III Forward Looking Infrared Radar.... The Star Safire III Electro-Optical System is a long-range, multi-sensor infrared imaging radar...

  11. 77 FR 53184 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    .../INS) with a Selective Availability Anti-spoofing Module (SAASM), AN/AAR-60 Infrared Missile Warning...-60 Infrared Missile Warning and AN/ALE-47 Countermeasures System, Electro-Optical Sensor, SIGINT... with an integrated electro-optical and infrared (EO/IR), Eye-safe Laser Range Finder and Laser...

  12. 77 FR 40023 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... Looking Infrared system. Self Protection systems include the AN/AAR-47 Missile Warning Set, AN/ALQ-144A Infrared Counter Measure System, and the AN/ALE-47chaff and flare decoy dispenser. 2. The MH-60S SEAHAWK... Kit includes the AN/AAS-44 Forward Looking Infrared, external weapons systems (pylons to carry up...

  13. 77 FR 76169 - Quarterly Rail Cost Adjustment Factor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ... Surface Transportation Board Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the AAR's proposed rebasing calculations and the rebased first quarter 2013 rail cost adjustment factor (RCAF)...

  14. [Phytoadaptogens-induced phenomenon similar to ischemic preconditioning].

    PubMed

    Arbuzov, A G; Maslov, L N; Burkova, V N; Krylatov, A V; Konkovskaia, Iu N; Safronov, S M

    2009-04-01

    The course administration (16 mg/kg per os for 5 days) of extracts of Panax ginseng or Rhodiola rosea induced a decrease in the infarction size/the area at risk (IS AAR) ratio during a 45-min local ischemia and a 2-hr reperfusion in artificially ventilated chloralose-anaesthetized rats. Single administration of ginseng or Rhodiola 24 h before ischemia did not affect the IS/AAR ratio. Chronic administration of Extracts of Eleutherococcus senticosus, Leuzea carthamoides and Aralia mandshurica had no effect on the IS/AAR ratio. Pretreatment with extract ofAralia mandshurica prevented appearance of ventricular arrhythmias during first 10 min coronary artery occlusion. Pretreatment with extract of Rhodiola rosea decreased the incidence of ventricular fibrillation during ischemia. Single administration of extracts of Panax ginseng or Rhodiola rosea in a dose of 16 mg/kg had no effect on the IS/AAR ratio. The authors conclude that extracts of ginseng or Rhodiola exhibit a powerful cardioprotective effect. Extract of Aralia exhibit a strong antiarrhythmic effect. Extracts of ginseng and Rhodiola do not mimic phenomena of ischemia preconditioning. PMID:19505042

  15. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... joints must be fusion welded. Head-to-shell joints must be forge welded on class DOT-106A tanks and fusion welded on class DOT-110A tanks. Welding procedures, welders and fabricators must be approved in...) Fusion-welded joints must be in compliance with the requirements of AAR Specifications for Tank...

  16. 76 FR 2719 - Investigations Regarding Certifications of Eligibility To Apply for Worker Adjustment Assistance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ... (Petitioners) Location institution petition 74983 AAR Mobility System (Union). Cadillac, MI 12/13/10 12/07/10.../13/10 74991 Norandex Building Materials Gaylord, MI 12/14/10 12/13/10 Distribution, Inc. (State/ One... Burroughs Payment Systems, Plymouth, MI 12/16/10 12/14/10 Inc. (Union). 75005 Manufacturers...

  17. 75 FR 11992 - Notice of Scheduling of Public Hearing; Association of American Railroads

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... comments and related material by any of the following methods: Internet: http://www.regulations.gov... download on the internet at the docket facility's Web site at http://www.regulations.gov . Anyone is able... FRA-2009-0111. A copy of AAR's full petition is available for review online at...

  18. Early visual experience shapes the representation of auditory space in the forebrain gaze fields of the barn owl.

    PubMed

    Miller, G L; Knudsen, E I

    1999-03-15

    Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain. Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls. This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli. PMID:10066282

  19. 77 FR 58615 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-21

    ... at Class 5 speeds over ``heavy-point'' frog designs conforming to the standards for Class 4 track frogs guard check and face gage dimensions. The heavy-point frog is a unique design, which has a thicker frog point. As proposed in the original waiver petition, AAR states that it offers safety benefits...

  20. 49 CFR 179.16 - Tank-head puncture-resistance systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... head and made from steel having a tensile strength greater than 379.21 N/mm2 (55,000 psi). (2) The design and test requirements of the full-head protection (shields) or full tank-head jackets must meet the impact test requirements in Section 5.3 of the AAR Specifications for Tank Cars (IBR, see §...

  1. 49 CFR 179.16 - Tank-head puncture-resistance systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... head and made from steel having a tensile strength greater than 379.21 N/mm2 (55,000 psi). (2) The design and test requirements of the full-head protection (shields) or full tank-head jackets must meet the impact test requirements in Section 5.3 of the AAR Specifications for Tank Cars (IBR, see §...

  2. 49 CFR 179.16 - Tank-head puncture-resistance systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... head and made from steel having a tensile strength greater than 379.21 N/mm2 (55,000 psi). (2) The design and test requirements of the full-head protection (shields) or full tank-head jackets must meet the impact test requirements in Section 5.3 of the AAR Specifications for Tank Cars (IBR, see §...

  3. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank...

  4. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank...

  5. 49 CFR 179.100-10 - Postweld heat treatment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Postweld heat treatment. 179.100-10 Section 179... Specifications for Pressure Tank Car Tanks (Classes DOT-105, 109, 112, 114 and 120) § 179.100-10 Postweld heat... heat treated as a unit in compliance with the requirements of AAR Specifications for Tank...

  6. Modeling of alkali aggregate reaction effects in concrete dams

    SciTech Connect

    Capra, B.; Bournazel, J.P.; Bourdarot, E.

    1995-12-31

    Alkali Aggregate Reactions (AAR) are difficult to model due to the random distribution of the reactive sites and the imperfect knowledge of these chemical reactions. A new approach, using fracture mechanics and probabilities, capable to describe the anisotropic swelling of a structure is presented.

  7. Abstractions of Awareness: Aware of What?

    NASA Astrophysics Data System (ADS)

    Metaxas, Georgios; Markopoulos, Panos

    This chapter presents FN-AAR, an abstract model of awareness systems. The purpose of the model is to capture in a concise and abstract form essential aspects of awareness systems, many of which have been discussed in design essays or in the context of evaluating specific design solutions.

  8. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

    PubMed Central

    Fang, Pengfei; Guo, Min

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. PMID:26670257

  9. 77 FR 41473 - Proposed Technical Standard Order (TSO)-C126b, 406 MHz Emergency Locator Transmitters (ELT) and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... mounting tray has caused the antenna connection to sever, rendering the ELT ineffective and severely... Aircraft Accident Report AAR-11-03: The antenna cable was severed from the ELT when the ELT slipped out of... NTSB ID WPR10FA273: The antenna cable was severed from the ELT when the ELT slipped out of the hook...

  10. Probing catalytic rate enhancement during intramembrane proteolysis.

    PubMed

    Arutyunova, Elena; Smithers, Cameron C; Corradi, Valentina; Espiritu, Adam C; Young, Howard S; Tieleman, D Peter; Lemieux, M Joanne

    2016-09-01

    Rhomboids are ubiquitous intramembrane serine proteases involved in various signaling pathways. While the high-resolution structures of the Escherichia coli rhomboid GlpG with various inhibitors revealed an active site comprised of a serine-histidine dyad and an extensive oxyanion hole, the molecular details of rhomboid catalysis were unclear because substrates are unknown for most of the family members. Here we used the only known physiological pair of AarA rhomboid with its psTatA substrate to decipher the contribution of catalytically important residues to the reaction rate enhancement. An MD-refined homology model of AarA was used to identify residues important for catalysis. We demonstrated that the AarA active site geometry is strict and intolerant to alterations. We probed the roles of H83 and N87 oxyanion hole residues and determined that substitution of H83 either abolished AarA activity or reduced the transition state stabilization energy (ΔΔG‡) by 3.1 kcal/mol; substitution of N87 decreased ΔΔG‡ by 1.6-3.9 kcal/mol. Substitution M154, a residue conserved in most rhomboids that stabilizes the catalytic general base, to tyrosine, provided insight into the mechanism of nucleophile generation for the catalytic dyad. This study provides a quantitative evaluation of the role of several residues important for hydrolytic efficiency and oxyanion stabilization during intramembrane proteolysis. PMID:27071148

  11. 78 FR 34427 - 2012 Tax Information for Use In The Revenue Shortfall Allocation Method

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ... Surface Transportation Board 2012 Tax Information for Use In The Revenue Shortfall Allocation Method... Shortfall Allocation Method (RSAM). DATES: Comments are due by July 9, 2013. If any comment opposing AAR's... Revenue Shortfall Allocation Method, EP 646 (Sub-No. 2) (STB served Nov. 21, 2008). RSAM is intended...

  12. 76 FR 40448 - 2010 Tax Information for Use in the Revenue Shortfall Allocation Method

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... Surface Transportation Board 2010 Tax Information for Use in the Revenue Shortfall Allocation Method... Allocation Method (RSAM). DATES: Comments are due by August 8, 2011. If any comment opposing AAR's... Shortfall Allocation Method, EP 646 (Sub-No. 2) (STB served Nov. 21, 2008). RSAM is intended to measure...

  13. 49 CFR 179.7 - Quality assurance program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Quality assurance program. 179.7 Section 179.7... Introduction, Approvals and Reports § 179.7 Quality assurance program. (a) At a minimum, each tank car facility shall have a quality assurance program, approved by AAR, that— (1) Ensures the finished product...

  14. 49 CFR 179.3 - Procedure for securing approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Executive Director—Tank Car Safety, AAR, for consideration by its Tank Car Committee and other appropriate... SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR... for approval of designs, materials and construction, conversion or alteration of tank car tanks...

  15. 77 FR 25910 - National Trails System Act and Railroad Rights-of-Way

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... plain language of 16 U.S.C. 1247(d) requires states and political subdivisions, as well as qualified... rules, given the plain language of the statute.\\5\\ \\4\\ See, e.g., Chesapeake R.R.--Certificate of... Willingness. AAR concurs in the Board's view in the NPRM that the plain language of 16 U.S.C....

  16. Effects of Synephrine and B-Phenethylamine on Human a-Adrenoceptor Subtypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synephrine and B-phenethylamine are structurally related to ephedrine. In this study, the effects of synephrine and B-phenethylamine are investigated on a-adrenoceptor (a-AR) subtypes expressed in human embroyonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-no...

  17. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Postweld heat treatment. 179.400-12 Section 179... and 107A) § 179.400-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not... closing seams, must be postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix...

  18. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7...

  19. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7...

  20. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Postweld heat treatment. 179.400-12 Section 179...-12 Postweld heat treatment. (a) Postweld heat treatment of the inner tank is not required. (b) The... postweld heat treated as prescribed in AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7...

  1. Rocket-Based Combined Cycle Engine Concept Development

    NASA Technical Reports Server (NTRS)

    Ratekin, G.; Goldman, Allen; Ortwerth, P.; Weisberg, S.; McArthur, J. Craig (Technical Monitor)

    2001-01-01

    The development of rocket-based combined cycle (RBCC) propulsion systems is part of a 12 year effort under both company funding and contract work. The concept is a fixed geometry integrated rocket, ramjet, scramjet, which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals, seal purge gas, and closeout side attachments. Engine A5 is the current configuration for NASA Marshall Space Flight Center (MSFC) for the ART program. Engine A5 models the complete flight engine flowpath of inlet, isolator, airbreathing combustor, and nozzle. High-performance rocket thrusters are integrated into the engine enabling both low speed air-augmented rocket (AAR) and high speed pure rocket operation. Engine A5 was tested in GASL's new Flight Acceleration Simulation Test (FAST) facility in all four operating modes, AAR, RAM, SCRAM, and Rocket. Additionally, transition from AAR to RAM and RAM to SCRAM was also demonstrated. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. SCRAM and rocket mode performance was above predictions. For the first time, testing also demonstrated transition between operating modes.

  2. 49 CFR 180.515 - Markings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Markings. 180.515 Section 180.515 Transportation... Qualification and Maintenance of Tank Cars § 180.515 Markings. (a) When a tank car passes the required... applicable provisions of Appendix C of the AAR Specifications for Tank Cars (IBR, see § 171.7 of...

  3. 49 CFR 180.515 - Markings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Markings. 180.515 Section 180.515 Transportation... Qualification and Maintenance of Tank Cars § 180.515 Markings. (a) When a tank car passes the required... applicable provisions of Appendix C of the AAR Specifications for Tank Cars (IBR, see § 171.7 of...

  4. A New Key to Scholarly Collaboration?

    ERIC Educational Resources Information Center

    Fitzmier, Jack

    2012-01-01

    The American Academy of Religion, in concert with the Sakai Foundation, has envisioned a scholarly use of the new Sakai Open Academic Environment open-source software. Currently working under the title "Biosphere," the program would put a rich collection of collaborative tools in the hands of AAR members, their colleagues in related scholarly…

  5. 77 FR 34846 - Inspection, Repair, and Maintenance; Driver-Vehicle Inspection Report for Intermodal Equipment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... FR 3316) at http://edocket.access.gpo.gov/2008/pdf/E8-785.pdf . III. Abbreviations AAR Association of....C. 31151(d) and (e)). FMCSA published a final rule on December 17, 2008 (73 FR 76794), implementing... provider's designated agent'' (49 U.S.C. 31151(a)(3)(L)). FMCSA's December 17, 2008 rule (73 FR...

  6. 77 FR 31815 - Hazardous Materials Regulations: Combustible Liquids

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ..., hazardous waste, or a marine pollutant is not subject to HMR in domestic transportation, by highway or rail... the safe transportation of hazardous materials, one of our associated goals is to facilitate... Corporation; Association of American Railroads (AAR); Council on Safe Transportation of Hazardous...

  7. Moving to atomic tritium for neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Kazkaz, Kareem; Project8 Collaboration

    2016-03-01

    For direct measurements of the neutrino mass, the tritium-based experiments Mainz and Troitsk have provided the most sensitive measurements to date, with upper limits near 2200 meV. The KATRIN experiment, beginning its first science run in 2016, also uses tritium as its source and has an anticipated ultimate sensitivity of 200 meV. The largest single systematic effect limiting the mass sensitivity beyond KATRIN is the energy sharing between the emitted beta particle and the resulting T-3He molecule. It therefore behooves all future tritium-based experiments to use atomic, rather than molecular, tritium. In this presentation we will outline experimental considerations of atomic tritium: production, purification, inhibiting recombination, and cooling. We will discuss these considerations within the context of Project8, a tritium-based, cyclotron radiation emission spectroscopy neutrino mass measurement with an ultimate target sensitivity of 50 meV. Prepared by LLNL under Contract DE-AC52-07NA27344.

  8. Performance of a TiN-coated monolithic silicon pin-diode array under mechanical stress

    NASA Astrophysics Data System (ADS)

    VanDevender, B. A.; Bodine, L. I.; Myers, A. W.; Amsbaugh, J. F.; Howe, M. A.; Leber, M. L.; Robertson, R. G. H.; Tolich, K.; Van Wechel, T. D.; Wall, B. L.

    2012-05-01

    The Karlsruhe Tritium Neutrino Experiment (KATRIN) will detect tritium β-decay electrons that pass through its electromagnetic spectrometer with a highly segmented monolithic silicon pin-diode focal-plane detector (FPD). This pin-diode array will be on a single piece of 500-μm-thick silicon, with contact between titanium nitride (TiN)-coated detector pixels and front-end electronics made by spring-loaded pogo pins. The pogo pins will exert a total force of up to 50 N on the detector, deforming it and resulting in mechanical stress up to 50 MPa in the silicon bulk. We have evaluated a prototype pin-diode array with a pogo-pin connection scheme similar to the KATRIN FPD. We find that pogo pins make good electrical contact to TiN and observe no effects on detector resolution or reverse-bias leakage current which can be attributed to mechanical stress.

  9. Testing molecular effects for tritium-based neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Parno, Diana; Bodine, Laura; Robertson, R. G. Hamish

    2015-10-01

    The upcoming KATRIN experiment will use the kinematics of tritium beta decay to probe the neutrino mass. The tritium source is molecular, however, and one of KATRIN's largest expected systematic uncertainties arises from the population of molecular final states following beta decay. To study this uncertainty, the Tritium Recoil-Ion Mass Spectrometer will measure the dissociation probability of the daughter molecule following beta decay, addressing a discrepancy between modern, high-precision theoretical calculations and two mass spectrometry measurements from the 1950s. We will describe the novel measurement technique and the commissioning of the experiment. This research is supported by the U.S. Department of Energy Office of Science, Office of Nuclear Physics under Award Number DE-FG02-97ER41020.

  10. Reproducibility of area at risk assessment in acute myocardial infarction by T1- and T2-mapping sequences in cardiac magnetic resonance imaging in comparison to Tc99m-sestamibi SPECT.

    PubMed

    Langhans, Birgit; Nadjiri, Jonathan; Jähnichen, Christin; Kastrati, Adnan; Martinoff, Stefan; Hadamitzky, Martin

    2014-10-01

    Area at risk (AAR) is an important parameter for the assessment of the salvage area after revascularization in acute myocardial infarction (AMI). By combining AAR assessment by T2-weighted imaging and scar quantification by late gadolinium enhancement imaging cardiovascular magnetic resonance (CMR) offers a promising alternative to the "classical" modality of Tc99m-sestamibi single photon emission tomography (SPECT). Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury, particularly the T1-mapping and T2-mapping, have attracted rising attention. But no direct comparison between the different sequences in the setting of AMI or a validation against SPECT has been reported so far. We analyzed 14 patients undergoing primary coronary revascularization in AMI in whom both a pre-intervention Tc99m-sestamibi-SPECT and CMR imaging at a median of 3.4 (interquartile range 3.3-3.6) days after the acute event were performed. Size of AAR was measured by three different non-contrast CMR techniques on corresponding short axis slices: T2-weighted, fat-suppressed turbospin echo sequence (TSE), T2-mapping from T2-prepared balanced steady state free precession sequences (T2-MAP) and T1-mapping from modified look locker inversion recovery (MOLLI) sequences. For each CMR sequence, the AAR was quantified by appropriate methods (absolute values for mapping sequences, comparison with remote myocardium for other sequences) and correlated with Tc99m-sestamibi-SPECT. All measurements were performed on a 1.5 Tesla scanner. The size of the AAR assessed by CMR was 28.7 ± 20.9 % of left ventricular myocardial volume (%LV) for TSE, 45.8 ± 16.6 %LV for T2-MAP, and 40.1 ± 14.4 %LV for MOLLI. AAR assessed by SPECT measured 41.6 ± 20.7 %LV. Correlation analysis revealed best correlation with SPECT for T2-MAP at a T2-threshold of 60 ms

  11. Direct neutrino mass experiments and exotic charged current interactions

    NASA Astrophysics Data System (ADS)

    Ludl, Patrick Otto; Rodejohann, Werner

    2016-06-01

    We study the effect of exotic charged current interactions on the electron energy spectrum in tritium decay, focussing on the KATRIN experiment and a possible modified setup that has access to the full spectrum. Both sub-eV and keV neutrino masses are considered. We perform a fully relativistic calculation and take all possible new interactions into account, demonstrating the possible sizable distortions in the energy spectrum.

  12. Exact relativistic {beta} decay endpoint spectrum

    SciTech Connect

    Masood, S. S.; Nasri, S.; Schechter, J.; Tortola, M. A.; Valle, J. W. F.

    2007-10-15

    The exact relativistic form for the {beta} decay endpoint spectrum is derived and presented in a simple factorized form. We show that our exact formula can be well approximated to yield the endpoint form used in the fit method of the KATRIN Collaboration. We also discuss the three-neutrino case and how information from neutrino oscillation experiments may be useful in analyzing future {beta} decay endpoint experiments.

  13. Automatic localization of IASLC-defined mediastinal lymph node stations on CT images using fuzzy models

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica M. S.; Beig, Niha G.; Udupa, Jayaram K.; Archer, Steven; Torigian, Drew A.

    2014-03-01

    Lung cancer is associated with the highest cancer mortality rates among men and women in the United States. The accurate and precise identification of the lymph node stations on computed tomography (CT) images is important for staging disease and potentially for prognosticating outcome in patients with lung cancer, as well as for pretreatment planning and response assessment purposes. To facilitate a standard means of referring to lymph nodes, the International Association for the Study of Lung Cancer (IASLC) has recently proposed a definition of the different lymph node stations and zones in the thorax. However, nodal station identification is typically performed manually by visual assessment in clinical radiology. This approach leaves room for error due to the subjective and potentially ambiguous nature of visual interpretation, and is labor intensive. We present a method of automatically recognizing the mediastinal IASLC-defined lymph node stations by modifying a hierarchical fuzzy modeling approach previously developed for body-wide automatic anatomy recognition (AAR) in medical imagery. Our AAR-lymph node (AAR-LN) system follows the AAR methodology and consists of two steps. In the first step, the various lymph node stations are manually delineated on a set of CT images following the IASLC definitions. These delineations are then used to build a fuzzy hierarchical model of the nodal stations which are considered as 3D objects. In the second step, the stations are automatically located on any given CT image of the thorax by using the hierarchical fuzzy model and object recognition algorithms. Based on 23 data sets used for model building, 22 independent data sets for testing, and 10 lymph node stations, a mean localization accuracy of within 1-6 voxels has been achieved by the AAR-LN system.

  14. α2A-Adrenergic Receptors Filter Parabrachial Inputs to the Bed Nucleus of the Stria Terminalis

    PubMed Central

    Flavin, Stephanie A.; Matthews, Robert T.; Wang, Qin; Muly, E. Chris

    2014-01-01

    α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress–reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α2A-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α2A-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α2A-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α2A-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α2A-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. PMID:25009265

  15. α(2A)-adrenergic receptors filter parabrachial inputs to the bed nucleus of the stria terminalis.

    PubMed

    Flavin, Stephanie A; Matthews, Robert T; Wang, Qin; Muly, E Chris; Winder, Danny G

    2014-07-01

    α2-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST α(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain α(2A)-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the α(2A)-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of α(2A)-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that α(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs. PMID:25009265

  16. Plasticity of α2-adrenergic spinal antinociception following nerve injury: selective, bidirectional interaction with the delta opioid receptor.

    PubMed

    Aira, Zigor; Barrenetxea, Teresa; Buesa, Itsaso; Azkue, Jon Jatsu

    2015-01-12

    Interactions of opioid receptors with other receptor families can be made use of to improve analgesia and reduce adverse effects of opioid analgesics. We investigated interactions of the α2-adrenergic receptor (α2AR) with opioid receptors of the mu (MOR) and delta (DOR) types in the spinal dorsal horn in an animal model of neuropathic pain induced by spinal nerve ligation. Nine days after nerve injury, immunoreactivity for the α2AR subtype A (α2AAR) was increased both in tissue homogenates and at pre- and post-synaptic sites in transverse sections. The efficacy of spinally administered α2AAR agonist guanfacine at reducing C-fiber-evoked field potentials was increased in nerve-ligated rats. This reducing effect was impaired by simultaneous administration of DOR antagonist naltrindole, but not MOR antagonist CTOP, suggesting that concurrent DOR activation was required for α2AAR-mediated inhibition. While DOR agonist deltorphin II and MOR agonist DAMGO both effectively depressed C-fiber-evoked spinal field potentials, DOR- but not MOR-mediated depression was enhanced by subclinical guanfacine. In conscious, nerve-ligated rats, chronically administered deltorphin II produced stable thermal and mechanical antinociception over the 9 following days after nerve injury without apparent signs of habituation. Such an effect was dramatically enhanced by co-administration of a low dose of guanfacine, which reversed thermal and mechanical thresholds to levels near those prior to injury. The results suggest that spinal, α2AAR-mediated antinociception is increased after nerve injury and based on DOR co-activation. We demonstrate in vivo that α2AAR/DOR interaction can be exploited to provide effective behavioral antinociception during neuropathic pain. PMID:25446445

  17. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase.

    PubMed

    Murphy, Jesse R; Mullins, Elwood A; Kappock, T Joseph

    2016-01-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. PMID:27242998

  18. Cluster Multi-Point Studies of the Auroral Acceleration Region

    NASA Astrophysics Data System (ADS)

    Marklund, G. T.

    2014-12-01

    Multi-point studies of the auroral acceleration region (AAR) by the Cluster spacecraft has enabled a number of open issues on the auroral acceleration to be addressed and revealed. Data from AAR crossings of Inverted-V aurora, by the C1 and C3 spacecraft at different altitudes, enabled a detailed reconstruction of the acceleration potential and a verification of its stability on a five min time scale. The relative role of quasi-static and Alfvénic acceleration behind aurora are addressed in two event studies. In one of these, the two processes are shown to operate jointly on the plasma population within the polar cap boundary. In the other, the electron energy flux producing multiple arcs within a surge is found to be generally dominated by the quasi-static contribution. Acceleration features and the FAC closure associated with surge-horn aurora crossed by the Cluster fleet were derived in another event study. A study of the density distribution within the auroral cavity, showed for all included events, exponential density decreases, relative to the ambient densities, from the mid to top of the AAR. In another study, cavities were found to extend well beyond the top of the AAR. Finally, statistical high-latitude electric field and plasma density distributions are presented based on 10 years of Cluster data collected between 2 and 4 RE altitudes. Intense electric fields appear in two altitude regimes on the nightside, separated by a gap at 2.8 RE. The upper altitude fields were interpreted to be Alfvénic and the lower altitude fields quasi-static, related to the AAR. The gap in the electric field intensity indicates a partial closure of the potentials in the lower region, with similarities to model results of reflected Alfvén waves and earlier reported observations

  19. A lack of α1A-adrenergic receptor-mediated antidepressant-like effects of S-(+)-niguldipine and B8805-033 in the forced swim test.

    PubMed

    Kreiner, Grzegorz; Roman, Adam; Zelek-Molik, Agnieszka; Kowalska, Marta; Nalepa, Irena

    2016-06-01

    The α1-adrenergic receptors (α1-ARs), which belong to a G protein-coupled receptor family, consist of three highly homologous subtypes known as α1A-ARs, α1B-ARs, and α1D-ARs. Our previous findings suggested that α1A-ARs are an important target for imipramine and electroconvulsive therapy. The current study sought to evaluate whether S-(+)-niguldipine and B8805-033, two selective antagonists of α1A-ARs, can evoke antidepressant-like effects in the forced swim test in rats. Both compounds were administered at three time points (24, 5, and 1 h before testing), and the effects of three doses (2, 5, and 10 mg/kg) of each compound were investigated. S-(+)-Niguldipine produced no antidepressant-like effects other than a 14% reduction in immobility time at the highest dose. Although B8805-033 at a dose of 2 mg/kg did not influence the rats' behavior, higher B8805-033 doses (5 and 10 mg/kg) produced significant reductions in immobility time (approximately 42 and 44% vs. controls, respectively; P<0.01). However, this effect was abolished by the concomitant administration of WAY100135, a serotonin receptor antagonist, suggesting that the observed antidepressant-like effects of B8805-033 are unrelated to α1A-ARs. Nevertheless, given the current dearth of selective α1A-AR agonists, the question of whether this particular subtype could be involved in antidepressant therapy mechanisms remains unresolved. PMID:26588212

  20. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase

    PubMed Central

    Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

    2016-01-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. PMID:27242998

  1. Alfvén: magnetosphere—ionosphere connection explorers

    NASA Astrophysics Data System (ADS)

    Berthomier, M.; Fazakerley, A. N.; Forsyth, C.; Pottelette, R.; Alexandrova, O.; Anastasiadis, A.; Aruliah, A.; Blelly, P.-L.; Briand, C.; Bruno, R.; Canu, P.; Cecconi, B.; Chust, T.; Daglis, I.; Davies, J.; Dunlop, M.; Fontaine, D.; Génot, V.; Gustavsson, B.; Haerendel, G.; Hamrin, M.; Hapgood, M.; Hess, S.; Kataria, D.; Kauristie, K.; Kemble, S.; Khotyaintsev, Y.; Koskinen, H.; Lamy, L.; Lanchester, B.; Louarn, P.; Lucek, E.; Lundin, R.; Maksimovic, M.; Manninen, J.; Marchaudon, A.; Marghitu, O.; Marklund, G.; Milan, S.; Moen, J.; Mottez, F.; Nilsson, H.; Ostgaard, N.; Owen, C. J.; Parrot, M.; Pedersen, A.; Perry, C.; Pinçon, J.-L.; Pitout, F.; Pulkkinen, T.; Rae, I. J.; Rezeau, L.; Roux, A.; Sandahl, I.; Sandberg, I.; Turunen, E.; Vogt, J.; Walsh, A.; Watt, C. E. J.; Wild, J. A.; Yamauchi, M.; Zarka, P.; Zouganelis, I.

    2012-04-01

    The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfvén concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.

  2. Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase

    NASA Astrophysics Data System (ADS)

    Murphy, Jesse; Mullins, Elwood; Kappock, T.

    2016-05-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates less than 3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analogue dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analogue of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.

  3. A randomized controlled trial with a Canadian electronic pill dispenser used to measure and improve medication adherence in patients with schizophrenia

    PubMed Central

    Stip, Emmanuel; Vincent, Philippe D.; Sablier, Juliette; Guevremont, Catherine; Zhornitsky, Simon; Tranulis, Constantin

    2013-01-01

    Objective: Medication adherence is extremely important in preventing relapse and lowering symptoms in schizophrenic patients. However, estimates show that nearly half of these patients have poor adherence. The Brief Adherence Rating Scale (BARS) seems to be the most reliable tool assessing adherence in schizophrenia and shows that the antipsychotic adherence ratio (AAR) is about 49.5% in schizophrenia. The aim of the study was to test if an electronic pill dispenser named DoPill® improved AAR of schizophrenic patients. Furthermore, we compared AAR obtained by the DoPill® and the BARS, in order to verify whether the DoPill® provides reliable assessment of medication adherence. Methods: The DoPill® is a smart pill dispenser that beeps and flashes at the appropriate time of the day. Each of its 28 compartments is covered by a plastic lamina that, when taken off, sends a signal to the pharmacist. Patients were randomized to the DoPill® or treatment as usual groups for 6 weeks. The BARS was used as a reference measure. Results: Forty-six percent of patients were deemed to be non-adherent with antipsychotic medication. The mean AAR was 67% after 6 weeks. DoPill® recorded better AAR than some of those found in the literature and were lower than the BARS estimate we found. Conclusion: These results suggest that DoPill® is a valid tool that provides more reliable and objective data for the clinician about their patient’s adherence, than existing assessment tools like the BARS. Furthermore, the device may help patients successfully manage their medication regimen. PMID:23950746

  4. Biodistribution and Safety Assessment of Bladder Cancer Specific Recombinant Oncolytic Adenovirus in Subcutaneous Xenografts Tumor Model in Nude Mice

    PubMed Central

    Wang, Fang; Wang, Zhiping; Tian, Hongwei; Qi, Meijiao; Zhai, Zhenxing; Li, Shuwen; Li, Renju; Zhang, Hongjuan; Wang, Wenyun; Fu, Shenjun; Lu, Jianzhong; Rodriguez, Ronald; Guo, Yinglu; Zhou, Liqun

    2012-01-01

    Background The previous works about safety evaluation for constructed bladder tissue specific adenovirus are poorly documented. Thus, we investigated the biodistribution and body toxicity of bladder specific oncolytic adenovirus Ad-PSCAE-UPII-E1A (APU-E1A) and Ad-PSCAE-UPII-E1A-AR (APU-E1A-AR), providing meaningful information prior to embarking on human clinical trials. Materials and Method Conditionally replicate recombinant adenovirus (CRADs) APU-E1A, APU-EIA-AR were constructed with bladder tissue specific Uroplakin II (UP II) promoter to induce the expression of Ad5E1A gene and E1A-AR fusing gene, and PSCAE was inserted at upstream of promoter to enhance the function of promoter. Based on the cytopathic and anti-tumor effect of bladder cancer, these CRADs were intratumorally injected into subcutaneous xenografts tumor in nude mice. We then determined the toxicity through general health and behavioral assessment, hepatic and hematological toxicity evaluation, macroscopic and microscopic postmortem analyses. The spread of the transgene E1A of adenovirus was detected with RT-PCR and Western blot. Virus replication and distribution were examined with APU-LUC administration and Luciferase Assay. Results General assessment and body weight of the animals did not reveal any alteration in general behavior. The hematological alterations of groups which were injected with 5×108 pfu or higher dose (5×109 pfu) of APU-E1A and APU-E1A-AR showed no difference in comparison with PBS group, and only slight increased transaminases in contrast to PBS group at 5×109 pfu of APU-E1A and APU-E1A-AR were observed. E1A transgene did not disseminate to organs outside of xenograft tumor. Virus replication was not detected in other organs beside tumor according to Luciferase Assay. Conclusions Our study showed that recombinant adenovirus APU-E1A-AR and APU-E1A appear safe with 5×107 pfu and 5×108 pfu intratumorally injection in mice, without any discernable effects on general health

  5. Modern and Little Ice Age equilibrium-line altitudes on Outlet Valley glaciers from Jostedalsbreen, western Norway: An evaluation of different approaches to their calculation

    SciTech Connect

    Torsnes, I.; Rye, N. ); Nesje, A. )

    1993-05-01

    The modern and Little Ice Age (LIA) equilibrium-line altitude (ELA) of 20 outlet valley glacier from Jostedalsbreen, western Norway, has been calculated using different approaches. Using an accumulation area ratio (AAR) of 0.6 [+-] 0.05 gave a mean little Ice Age ELA depression of 70 m. A method developed by M. Kuhle, taking the influence by topography into account gave a mean ELA depression of 35-255 m, the median elevation of glaciers 115 m, and the toe-to-headwall altitude ration 140 m. Differences in the ELA estimates can be attributed to the differences in topography and morphology of the glaciers. The AAR method appears to provide the most reliable results. This will aid in determining mean global temperatures during the LIA. 34 refs., 9 figs., 5 tabs.

  6. Detection, monitoring and modelling of alkali-aggregate reaction in Kouga Dam (South Africa)

    SciTech Connect

    Elges, H.; Lecocq, P.; Oosthuizen, C.; Geertsema, A.

    1995-12-31

    Kouga Dam (formerly Paul Sauer Dam) is a double curvature arch dam completed in 1969. The aggregates and the cement used for the construction have subsequently been proven to be alkali reactive. The results of the monitoring programme and the alkali-aggregate reaction (AAR) tests as well as the methodology developed to standardise the logging of cores for these investigations are presented. A brief description of the Finite Element Model used to approximate the AAR process in order to determine positions for in-situ stress measurements is also given. The aim with these tests is to refine the model for prediction of the long-term behaviour of the dam and to make an assessment of the possibility of raising the dam.

  7. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications

    NASA Astrophysics Data System (ADS)

    Hendy, Erica J.; Tomiak, Peter J.; Collins, Matthew J.; Hellstrom, John; Tudhope, Alexander W.; Lough, Janice M.; Penkman, Kirsty E. H.

    2012-06-01

    Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed from

  8. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications.

    PubMed

    Hendy, Erica J; Tomiak, Peter J; Collins, Matthew J; Hellstrom, John; Tudhope, Alexander W; Lough, Janice M; Penkman, Kirsty E H

    2012-06-01

    Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA 56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed

  9. Embedded prediction in feature extraction: application to single-trial EEG discrimination.

    PubMed

    Hsu, Wei-Yen

    2013-01-01

    In this study, an analysis system embedding neuron-fuzzy prediction in feature extraction is proposed for brain-computer interface (BCI) applications. Wavelet-fractal features combined with neuro-fuzzy predictions are applied for feature extraction in motor imagery (MI) discrimination. The features are extracted from the electroencephalography (EEG) signals recorded from participants performing left and right MI. Time-series predictions are performed by training 2 adaptive neuro-fuzzy inference systems (ANFIS) for respective left and right MI data. Features are then calculated from the difference in multi-resolution fractal feature vector (MFFV) between the predicted and actual signals through a window of EEG signals. Finally, the support vector machine is used for classification. The proposed method estimates its performance in comparison with the linear adaptive autoregressive (AAR) model and the AAR time-series prediction of 6 participants from 2 data sets. The results indicate that the proposed method is promising in MI classification. PMID:23248335

  10. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase

    PubMed Central

    Keller, Tracy L.; Zocco, Davide; Sundrud, Mark S.; Hendrick, Margaret; Edenius, Maja; Yum, Jina; Kim, Yeon-Jin; Lee, Hak-kyo; Cortese, Joseph F.; Wirth, Dyann; Dignam, John David; Rao, Anjana; Yeo, Chang-Yeol; Mazitschek, Ralph; Whitman, Malcolm

    2011-01-01

    Febrifugine, one of the fifty fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity whilst its molecular target has remained unknown. Febrifugine derivatives have been used to treat malaria, cancer, fibrosis, and inflammatory disease. We recently demonstrated that halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of Th17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response pathway (AAR). Here we show that HF binds glutamyl-prolyl-tRNA synthetase (EPRS) inhibiting prolyl-tRNA synthetase activity; this inhibition is reversed by the addition of exogenous proline or EPRS. We further show that inhibition of EPRS underlies the broad bioactivities of this family of natural products. This work both explains the molecular mechanism of a promising family of therapeutics, and highlights the AAR pathway as an important drug target for promoting inflammatory resolution. PMID:22327401

  11. Naturally occurring aminoacyl-tRNA synthetases editing-domain mutations that cause mistranslation in Mycoplasma parasites

    PubMed Central

    Li, Li; Boniecki, Michal T.; Jaffe, Jacob D.; Imai, Brian S.; Yau, Peter M.; Luthey-Schulten, Zaida A.; Martinis, Susan A.

    2011-01-01

    Mycoplasma parasites escape host immune responses via mechanisms that depend on remarkable phenotypic plasticity. Identification of these mechanisms is of great current interest. The aminoacyl-tRNA synthetases (AARSs) attach amino acids to their cognate tRNAs, but occasionally make errors that substitute closely similar amino acids. AARS editing pathways clear errors to avoid mistranslation during protein synthesis. We show here that AARSs in Mycoplasma parasites have point mutations and deletions in their respective editing domains. The deleterious effect on editing was confirmed with a specific example studied in vitro. In vivo mistranslation was determined by mass spectrometric analysis of proteins produced in the parasite. These mistranslations are uniform cases where the predicted closely similar amino acid replaced the correct one. Thus, natural AARS editing-domain mutations in Mycoplasma parasites cause mistranslation. We raise the possibility that these mutations evolved as a mechanism for antigen diversity to escape host defense systems. PMID:21606343

  12. Cluster Observations of the Auroral Acceleration Region

    NASA Astrophysics Data System (ADS)

    Sadeghi, S.; Marklund, G.; Karlsson, R.; Lindqvist, P.; Li, B.; Nilsson, H.; Marghitu, O.; Fazakerley, A. N.; Lucek, E. A.

    2011-12-01

    We present results from Cluster satellite multi-point event studies from the auroral acceleration region (AAR). Electric potential structures associated with inverted-V aurora are investigated using electric field, magnetic field, ion and electron data from the Cluster spacecraft, crossing the auroral acceleration region (AAR) at different altitudes above the auroral oval. The spatial and temporal development of the acceleration structures is studied, given the magnetic conjunction opportunity and the short time-difference between the Cluster spacecraft crossings. The configuration allowed for estimating the characteristic times of development for the structures and estimating the parallel electric field and potential drop. For one of the negative potential structures, a growth time of 40 s and stability for more than one minute was observed and an average parallel electric field was estimated (~ 0.56 mV/m, between 1.13 and 1.3 RE of altitude).

  13. A 9,000-year-old caribou hunting structure beneath Lake Huron

    PubMed Central

    O’Shea, John M.; Lemke, Ashley K.; Sonnenburg, Elizabeth P.; Reynolds, Robert G.; Abbott, Brian D.

    2014-01-01

    Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. PMID:24778246

  14. A 9,000-year-old caribou hunting structure beneath Lake Huron.

    PubMed

    O'Shea, John M; Lemke, Ashley K; Sonnenburg, Elizabeth P; Reynolds, Robert G; Abbott, Brian D

    2014-05-13

    Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. PMID:24778246

  15. Body-Wide Hierarchical Fuzzy Modeling, Recognition, and Delineation of Anatomy in Medical Images

    PubMed Central

    Udupa, Jayaram K.; Odhner, Dewey; Zhao, Liming; Tong, Yubing; Matsumoto, Monica M.S.; Ciesielski, Krzysztof C.; Falcao, Alexandre X.; Vaideeswaran, Pavithra; Ciesielski, Victoria; Saboury, Babak; Mohammadianrasanani, Syedmehrdad; Sin, Sanghun; Arens, Raanan; Torigian, Drew A.

    2014-01-01

    To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide automatic anatomy recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions – thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) – involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and

  16. Development of an IR stimulator concept for testing IR missile warning systems

    NASA Astrophysics Data System (ADS)

    Robinson, William G.; Farrier, David A.

    1999-07-01

    Missile warning systems (MWS) present unique problems for hardware-in-the-loop testing compared to other sensors found on modern day military aircraft and ground vehicles. End-to- end testing of an IR MWS like the AN/AAR-44 and other IR MWS requires a scene projector or stimulator capable of large intensity dynamic range, moderate temporal response, and a very large field of regard. These requirements dictate a different type of stimulator than is normally used with more conventional IR imaging systems using IR focal plane arrays and relatively narrow fields of view on the order of 10 - 30 degrees. This paper describes an initial design approach for development of an IR stimulator that satisfies the requirements for hardware and software testing of the AN/AAR-44 and other IR MWS equipment.

  17. Life in the slow lane: making hospitals safer, slowly but surely

    PubMed Central

    Walker, Judy; Andrews, Steve; Grewcock, Dave; Halligan, Aidan

    2012-01-01

    Recognition that serious deficiencies in mutual respect and team work were hampering safe and effective patient care led to the creation of the cultural change initiative described here. We feel this has widespread applicability to other healthcare settings. The After Action Review (AAR) concept was adapted for use in the NHS for the first time as it provides a deceptively simple vehicle to structure healthy blame free team interactions with the aim of improving practice and team behaviours. The organizational and psychological barriers to being able to do this in multi-professional teams are accentuated by the hierarchical nature of the clinical context, but this project has begun to make lasting change so that AAR is an approach that is now widely understood and frequently used. PMID:22843646

  18. Low-Torque Seal Development

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Borowski, Richard

    2009-01-01

    The EcoTurn Class K production prototypes have passed all AAR qualification tests and received conditional approval. The accelerated life test on the second set of seals is in progress. Due to the performance of the first set, no problems are expected.The seal has demonstrated superior performance over the HDL seal in the test lab with virtually zero torque and excellent contamination exclusion and grease retention.

  19. GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment.

    PubMed

    Wilson, Gabriel J; Lennox, Brittany A; She, Pengxiang; Mirek, Emily T; Al Baghdadi, Rana J T; Fusakio, Michael E; Dixon, Joseph L; Henderson, Gregory C; Wek, Ronald C; Anthony, Tracy G

    2015-02-15

    The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis. PMID:25491724

  20. Coniston Dam: The rehabiliation of a 50-year-old concrete dam affected by alkali aggregate reaction

    SciTech Connect

    Read, P.H.; Thomas, M.

    1995-12-31

    This paper discusses the rehabilitation of the Coniston main dam in Ontario, with particular emphasis on the alkali-aggregate reaction (AAR) related aspects of the investigation and the influence of these on the design approach adopted, including measures taken to allow for possible future expansion of the original gravity section concrete. The rehabilitation program was primarily undertaken to increase the stability of the gravity sections and log chute which did not meet current dam safety criteria. However, all parts of the structure were found to be affected by AAR and the downstream face of the gravity sections were severely deteriorated due to the combined effects of AAR and freeze-thaw cycles. Field and laboratory investigations were undertaken to determine the extent of deterioration of the dam structures and to assess the potential for continued deterioration. Based on the findings from these studies, a rehabilitation and upgrade strategy was developed which included removal of badly deteriorated concrete, placement of reinforced concrete liners (upstream and downstream), addition of mass concrete buttresses along the length of the gravity sections, replacement of the deck and epoxy injection of the cracked sluiceway piers. Particular attention was paid to the design of the new concrete mixes (to limit the supply of alkalis to the existing concrete) and to the relief of stress between the original concrete core and new concrete liners. The new gravity section liner was debonded from the core concrete to reduce the transfer of stress due to continued expansion of the core; furthermore, the reinforcement of the liner was designed to resist tensile stresses induced by future expansion. Consideration was also given to minimizing the ingress of water to the dam core in order to reduce the degree of saturation and likelihood of further AAR and freeze-thaw action.

  1. On primordial sense-antisense coding

    PubMed Central

    Rodin, Andrei S.; Rodin, Sergei N.; Carter, Charles W.

    2010-01-01

    The genetic code is implemented by aminoacyl-tRNA synthetases (aaRS). These twenty enzymes are divided into two classes that, despite performing same functions, have nothing common in structure. The mystery of this striking partition of aaRSs might have been concealed in their sterically complementary modes of tRNA recognition that, as we have found recently, protect the tRNAs with complementary anticodons from confusion in translation. This finding implies that, in the beginning, life increased its coding repertoire by the pairs of complementary codons (rather than one-by-one) and used both complementary strands of genes as templates for translation. The class I and class II aaRSs may represent one of the most important examples of such primordial sence-antisence (SAS) coding (Rodin and Ohno, 1995). In this report, we address the issue of SAS coding in a wider scope. We suggest a variety of advantages that such coding would have had in exploring a wider sequence space before translation became highly specific. In particular, we confirm that in Achylia klebsiana a single gene might have originally coded for an HSP70 chaperonin (class II aaRS homolog) and an NAD-specific GDH-like enzyme (class I aaRS homolog) via its sense and antisense strands. Thus, in contrast to the conclusions in (Williams et al., 2009), this could indeed be a “Rosetta stone” (eroded somewhat, though) gene for the SAS origin of the two aaRS classes (Carter and Duax, 2002). PMID:19956936

  2. Alpha1a-Adrenoceptor Genetic Variant Triggers Vascular Smooth Muscle Cell Hyperproliferation and Agonist Induced Hypertrophy via EGFR Transactivation Pathway

    PubMed Central

    Schwinn, Debra A.; Oganesian, Anush

    2015-01-01

    α1a Adrenergic receptors (α1aARs) are the predominant AR subtype in human vascular smooth muscle cells (SMCs). α1aARs in resistance vessels are crucial in the control of blood pressure, yet the impact of naturally occurring human α1aAR genetic variants in cardiovascular disorders remains poorly understood. To this end, we present novel findings demonstrating that 3D cultures of vascular SMCs expressing human α1aAR-247R (247R) genetic variant demonstrate significantly increased SMC contractility compared with cells expressing the α1aAR-WT (WT) receptor. Stable expression of 247R genetic variant also triggers MMP/EGFR-transactivation dependent serum- and agonist-independent (constitutive) hyperproliferation and agonist-dependent hypertrophy of SMCs. Agonist stimulation reduces contractility Using pathway-specific inhibitors we determined that the observed hyperproliferation of 247R-expressing cells is triggered via β-arrestin1/Src/MMP-2/EGFR/ERK-dependent mechanism. MMP-2-specific siRNA inhibited 247R-triggered hyperproliferation indicating MMP-2 involvement in 247R-triggered hyperproliferation in SMCs. β-arrestin1-specific shRNA also inhibited 247R-triggered hyperproliferation but did not affect hypertrophy in 247R-expressing SMCs, indicating that agonist-dependent hypertrophy is independent of β-arrestin1. Our data reveal that in different cardiovascular cells the same human receptor genetic variant can activate alternative modulators of the same signaling pathway. Thus, our findings in SMCs demonstrate that depending on the type of cells expressing the same receptor (or receptor variant), different target-specific inhibitors could be used to modulate aberrant hyperproliferative or hypertrophic pathways in order to restore normal phenotype. PMID:26571308

  3. Body-wide anatomy recognition in PET/CT images

    NASA Astrophysics Data System (ADS)

    Wang, Huiqian; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Zhao, Liming; Torigian, Drew A.

    2015-03-01

    With the rapid growth of positron emission tomography/computed tomography (PET/CT)-based medical applications, body-wide anatomy recognition on whole-body PET/CT images becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem and seldom studied due to unclear anatomy reference frame and low spatial resolution of PET images as well as low contrast and spatial resolution of the associated low-dose CT images. We previously developed an automatic anatomy recognition (AAR) system [15] whose applicability was demonstrated on diagnostic computed tomography (CT) and magnetic resonance (MR) images in different body regions on 35 objects. The aim of the present work is to investigate strategies for adapting the previous AAR system to low-dose CT and PET images toward automated body-wide disease quantification. Our adaptation of the previous AAR methodology to PET/CT images in this paper focuses on 16 objects in three body regions - thorax, abdomen, and pelvis - and consists of the following steps: collecting whole-body PET/CT images from existing patient image databases, delineating all objects in these images, modifying the previous hierarchical models built from diagnostic CT images to account for differences in appearance in low-dose CT and PET images, automatically locating objects in these images following object hierarchy, and evaluating performance. Our preliminary evaluations indicate that the performance of the AAR approach on low-dose CT images achieves object localization accuracy within about 2 voxels, which is comparable to the accuracies achieved on diagnostic contrast-enhanced CT images. Object recognition on low-dose CT images from PET/CT examinations without requiring diagnostic contrast-enhanced CT seems feasible.

  4. 49 CFR 179.220-7 - Materials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... metal (longitudinal) AAR TC 128, Gr. B 81,000 19 ASTM A 516 2, Gr. 70 70,000 20 1 Maximum stresses to be... temper only. 3 Weld filler metal 5556 must not be used. 4 Maximum stresses to be used in calculations. (d... § 171.7 of this subchapter), Type 316L 70,000 30 1 Maximum stresses to be used in calculations....

  5. Role of Adenosine Receptor(s) in the Control of Vascular Tone in the Mouse Pudendal Artery.

    PubMed

    Labazi, Hicham; Tilley, Stephen L; Ledent, Catherine; Mustafa, S Jamal

    2016-03-01

    Activation of adenosine receptors (ARs) has been implicated in the modulation of renal and cardiovascular systems, as well as erectile functions. Recent studies suggest that adenosine-mediated regulation of erectile function is mainly mediated through A2BAR activation. However, no studies have been conducted to determine the contribution of AR subtype in the regulation of the vascular tone of the pudendal artery (PA), the major artery supplying and controlling blood flow to the penis. Our aim was to characterize the contribution of AR subtypes and identify signaling mechanisms involved in adenosine-mediated vascular tone regulation in the PA. We used a DMT wire myograph for muscle tension measurements in isolated PAs from wild-type, A2AAR knockout, A2BAR knockout, and A2A/A2BAR double-knockout mice. Real-time reverse transcription-polymerase chain reaction was used to determine the expression of the AR subtypes. Data from our pharmacologic and genetic approaches suggest that AR activation-mediated vasodilation in the PA is mediated by both the A2AAR and A2BAR, whereas neither the A1AR nor A3AR play a role in vascular tone regulation of the PA. In addition, we showed that A2AAR- and A2BAR-mediated vasorelaxation requires activation of nitric oxide and potassium channels; however, only the A2AAR-mediated response requires protein kinase A activation. Our data are complemented by mRNA expression showing the expression of all AR subtypes with the exception of the A3AR. AR signaling in the PA may play an important role in mediating erection and represent a promising therapeutic option for the treatment of erectile dysfunction. PMID:26718241

  6. Sympathetic activation by chemical stimulation of white adipose tissues in rats.

    PubMed

    Shi, Zhen; Chen, Wei-Wei; Xiong, Xiao-Qing; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-03-01

    Injection of leptin into white adipose tissue (WAT) increases sympathetic outflow. The present study was designed to determine the effects of capsaicin and other chemicals in WAT on the sympathetic outflow and blood pressure and the roles of WAT afferents and hypothalamic paraventricular nucleus (PVN) in the adipose afferent reflex (AAR). The AAR was induced by injection of capsaicin, bradykinin, adenosine, adenosine triphosphate (ATP), or leptin into inguinal WAT (iWAT) or retroperitoneal WAT (rWAT) in anesthetized rats. The iWAT injection of capsaicin increased the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) but not the heart rate. Bradykinin, adenosine, or leptin but not ATP in the iWAT caused similar effects to capsaicin on the RSNA and MAP. Intravenous, intramuscular, or intradermal injection of capsaicin had no significant effects on the RSNA and MAP. The effects of capsaicin in rWAT were similar to that in iWAT on the RSNA and MAP. Furthermore, injection of capsaicin into the iWAT increased the WAT afferent nerve activities, WAT efferent nerve activity, and brown adipose tissue efferent nerve activity. The iWAT denervation or chemical lesion of the PVN neurons with kainic acid abolished the AAR induced by the iWAT injection of capsaicin. These results indicate that the stimulation of iWAT afferents with capsaicin, bradykinin, adenosine, or leptin reflexly increases the RSNA and blood pressure. The iWAT afferents and the PVN are involved in the AAR induced by capsaicin in the iWAT. PMID:22223453

  7. 5'-Substituted Amiloride Derivatives as Allosteric Modulators Binding in the Sodium Ion Pocket of the Adenosine A2A Receptor.

    PubMed

    Massink, Arnault; Louvel, Julien; Adlere, Ilze; van Veen, Corine; Huisman, Berend J H; Dijksteel, Gabrielle S; Guo, Dong; Lenselink, Eelke B; Buckley, Benjamin J; Matthews, Hayden; Ranson, Marie; Kelso, Michael; IJzerman, Adriaan P

    2016-05-26

    The sodium ion site is an allosteric site conserved among many G protein-coupled receptors (GPCRs). Amiloride 1 and 5-(N,N-hexamethylene)amiloride 2 (HMA) supposedly bind in this sodium ion site and can influence orthosteric ligand binding. The availability of a high-resolution X-ray crystal structure of the human adenosine A2A receptor (hA2AAR), in which the allosteric sodium ion site was elucidated, makes it an appropriate model receptor for investigating the allosteric site. In this study, we report the synthesis and evaluation of novel 5'-substituted amiloride derivatives as hA2AAR allosteric antagonists. The potency of the amiloride derivatives was assessed by their ability to displace orthosteric radioligand [(3)H]4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol ([(3)H]ZM-241,385) from both the wild-type and sodium ion site W246A mutant hA2AAR. 4-Ethoxyphenethyl-substituted amiloride 12l was found to be more potent than both amiloride and HMA, and the shift in potency between the wild-type and mutated receptor confirmed its likely binding to the sodium ion site. PMID:27124340

  8. Quantitative normal thoracic anatomy at CT.

    PubMed

    Matsumoto, Monica M S; Udupa, Jayaram K; Tong, Yubing; Saboury, Babak; Torigian, Drew A

    2016-07-01

    Automatic anatomy recognition (AAR) methodologies for a body region require detailed understanding of the morphology, architecture, and geographical layout of the organs within the body region. The aim of this paper was to quantitatively characterize the normal anatomy of the thoracic region for AAR. Contrast-enhanced chest CT images from 41 normal male subjects, each with 11 segmented objects, were considered in this study. The individual objects were quantitatively characterized in terms of their linear size, surface area, volume, shape, CT attenuation properties, inter-object distances, size and shape correlations, size-to-distance correlations, and distance-to-distance correlations. A heat map visualization approach was used for intuitively portraying the associations between parameters. Numerous new observations about object geography and relationships were made. Some objects, such as the pericardial region, vary far less than others in size across subjects. Distance relationships are more consistent when involving an object such as trachea and bronchi than other objects. Considering the inter-object distance, some objects have a more prominent correlation, such as trachea and bronchi, right and left lungs, arterial system, and esophagus. The proposed method provides new, objective, and usable knowledge about anatomy whose utility in building body-wide models toward AAR has been demonstrated in other studies. PMID:27065241

  9. Unusual cause of acute low-back pain: sudden annulus fibrosus rupture.

    PubMed

    Ozer, Ali Fahir; Oktenoglu, Tunc; Sasani, Mehdi; Kaner, Tuncay; Ercelen, Omur; Canbulat, Nazan

    2012-05-01

    Low-back pain is a common problem in neu-rosurgery practice, and an algorithm has been developed for assessing these cases. However, one subgroup of these patients shares several clinical features and these individuals are not easy to categorize and diagnose. We present our observations for 8 of these patients, individuals with low-back pain caused by atypical annulus fibrosus rupture (AAR). The aim of this study is to show the consequences of overlooked annular tears on acute onset of low back pain. Eight patients with acute-onset severe low-back pain were admitted. Physical examinations were normal and each individual was examined neurologically and assessed with neuroradiologic studies [plain x-rays, magnetic resonance imaging (MRI), discography and computed tomography (CT) discography]. AAR was ultimately diagnosed with provocative discography. In all cases, MRI showed a healthy disc or mild degeneration, whereas discography and CT discography demonstrated disc disease. Anterior interbody cage implantation was performed in 3 of the 8 cases and posterior dynamic stabilization was carried out in 3 cases. The other 2 individuals refused surgery, and we were informed that one of them developed disc herniation at the affected level 1 year after our diagnosis. Clinical and radiological outcomes were evaluated. In cases where AAR is suspected, MRI, discography, and CT discography should be performed in addition to routine neuroradiologic studies. PMID:22802990

  10. The Transient Receptor Potential Channel TRPM8 Is Inhibited via the α2A Adrenoreceptor Signaling Pathway*

    PubMed Central

    Bavencoffe, Alexis; Gkika, Dimitra; Kondratskyi, Artem; Beck, Benjamin; Borowiec, Anne-Sophie; Bidaux, Gabriel; Busserolles, Jérôme; Eschalier, Alain; Shuba, Yaroslav; Skryma, Roman; Prevarskaya, Natalia

    2010-01-01

    The transient receptor potential channel melastatin member 8 (TRPM8) is expressed in sensory neurons, where it constitutes the main receptor of environmental innocuous cold (10–25 °C). Among several types of G protein-coupled receptors expressed in sensory neurons, Gi-coupled α2A-adrenoreceptor (α2A-AR), is known to be involved in thermoregulation; however, the underlying molecular mechanisms remain poorly understood. Here we demonstrated that stimulation of α2A-AR inhibited TRPM8 in sensory neurons from rat dorsal root ganglia (DRG). In addition, using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the Gi protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. We therefore propose that inhibition of TRPM8 through the α2A-AR signaling cascade could constitute a new mechanism of modulation of thermosensation in both physiological and pathological conditions. PMID:20110357

  11. Searching for novel ATF4 target genes in human hepatoma cells by microarray analysis.

    PubMed

    Maruyama, Ryuto; Shimizu, Makoto; Ishijima, Tomoko; Nakai, Yuji; Inoue, Jun; Sato, Ryuichiro

    2016-06-01

    Activating transcription factor 4 (ATF4) is a transcription factor with an important biological activity. ATF4 is induced by various stresses, such as endoplasmic reticulum stress, through the phosphorylation of eukaryotic translation initiation factor 2α. ATF4 is also involved in lipid metabolism. In the present study, we performed a microarray experiment to identify new ATF4 target genes, particularly those involved in lipid metabolism, and identified C12orf39, CSTA, and CALCB as novel ATF4 target genes. An amino acid response element (AARE) as an ATF4-binding site is present in the promoter regions of these genes. In a detailed analysis using luciferase assay, we showed that ATF4 activated C12orf39 promoter activity and that this activation was diminished by deletion or mutation of the AARE sequence in the promoter region. Our results suggest that C12orf39, CSTA, and CALCB are novel ATF4 target genes and that C12orf39 promoter activity is activated by ATF4 through AARE. PMID:26967115

  12. A Modified Johnson-Cook Constitutive Equation to Predict Hot Deformation Behavior of Ti-6Al-4V Alloy

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Zhai, Peng; Li, Fuguo; Yang, Jie

    2014-09-01

    A modified Johnson-Cook constitutive equation of Ti-6Al-4V alloy is proposed based on hot compression tests performed in the temperature range of 1073-1323 K and strain rate 0.001-1 s-1. The experimental stress-strain data were employed to develop the modified Johnson-Cook constitutive equation of different phase regimes (α + β and β phase). The predicted flow stresses using the developed equation were compared with experimental data. Correlation coefficient (R) and average absolute relative error (AARE) were introduced to verify the validity of the constitutive equation. The values of R and AARE for α + β phase were 0.990 and 7.81%, respectively. And in β phase region, the values of R and AARE were 0.985 and 10.36%, respectively. Meanwhile, the accuracy, the number of material constants involved, and the computational time required of the constitutive equation were evaluated by comparing with a strain-compensated Arrhenius-type constitutive equation. The results indicate that accuracy of modified Johnson-Cook constitutive equation is higher than that of compensated Arrhenius-type model at α + β phase, while lower at single β phase region. Meanwhile, the time required for evaluating the material constants of modified Johnson-Cook constitutive equation is much shorter than that of the strain-compensated Arrhenius type ones.

  13. A Modified Johnson-Cook Constitutive Equation to Predict Hot Deformation Behavior of Ti-6Al-4V Alloy

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Zhai, Peng; Li, Fuguo; Yang, Jie

    2015-01-01

    A modified Johnson-Cook constitutive equation of Ti-6Al-4V alloy is proposed based on hot compression tests performed in the temperature range of 1073-1323 K and strain rate 0.001-1 s-1. The experimental stress-strain data were employed to develop the modified Johnson-Cook constitutive equation of different phase regimes (α + β and β phase). The predicted flow stresses using the developed equation were compared with experimental data. Correlation coefficient ( R) and average absolute relative error (AARE) were introduced to verify the validity of the constitutive equation. The values of R and AARE for α + β phase were 0.990 and 7.81%, respectively. And in β phase region, the values of R and AARE were 0.985 and 10.36%, respectively. Meanwhile, the accuracy, the number of material constants involved, and the computational time required of the constitutive equation were evaluated by comparing with a strain-compensated Arrhenius-type constitutive equation. The results indicate that accuracy of modified Johnson-Cook constitutive equation is higher than that of compensated Arrhenius-type model at α + β phase, while lower at single β phase region. Meanwhile, the time required for evaluating the material constants of modified Johnson-Cook constitutive equation is much shorter than that of the strain-compensated Arrhenius type ones.

  14. The aminoacyl-tRNA synthetases of Drosophila melanogaster

    PubMed Central

    Lu, Jiongming; Marygold, Steven J; Gharib, Walid H; Suter, Beat

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. Drosophila has become a preferred system to model human diseases caused by mutations in aaRS genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of aaRS genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on Drosophila aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field. PMID:26761199

  15. A Modified Constitutive Equation for Aluminum Alloy Reinforced by Silicon Carbide Particles at Elevated Temperature

    NASA Astrophysics Data System (ADS)

    Yang, Yajing; Li, Fuguo; Yuan, Zhanwei; Qiao, Huijuan

    2013-09-01

    In this paper, the constitutive relationship of an aluminum alloy reinforced by silicon carbide particles is investigated using a new method of double multivariate nonlinear regression (DMNR) in which the strain, strain rate, deformation temperature, and the interaction effect among the strain, strain rate, and deformation temperature are considered. The experimental true stress-strain data were obtained by isothermal hot compression tests on a Gleeble-3500 thermo-mechanical simulator in the temperature range of 623-773 K and the strain rate range of 0.001-10 s-1. The experiments showed that the material-softening behavior changed with the strain rate, and it changed from dynamic recovery to dynamic recrystallization with an increase in the strain rate. A new constitutive equation has been established by the DMNR; the correlation coefficient ( R) and average absolute relative error (AARE) of this model are 0.98 and 7.8%, respectively. To improve the accuracy of the model, separate constitutive relationships were obtained according to the softening behavior. At strain rates of 0.001, 0.01, 0.1, and 1 s-1, the R and AARE are 0.9865 and 6.0%, respectively; at strain rates of 5 and 10 s-1, the R and AARE are 0.9860 and 3.0%, respectively. The DMNR gives an accurate and precise evaluation of the flow stress for the aluminum alloy reinforced by silicon carbide particles.

  16. The aminoacyl-tRNA synthetases of Drosophila melanogaster.

    PubMed

    Lu, Jiongming; Marygold, Steven J; Gharib, Walid H; Suter, Beat

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. Drosophila has become a preferred system to model human diseases caused by mutations in aaRS genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of aaRS genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on Drosophila aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field. PMID:26761199

  17. Yohimbine impairs extinction of cocaine-conditioned place preference in an alpha2-adrenergic receptor independent process.

    PubMed

    Davis, Adeola R; Shields, Angela D; Brigman, Jonathan L; Norcross, Maxine; McElligott, Zoe A; Holmes, Andrew; Winder, Danny G

    2008-09-01

    Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to addiction treatment. Data suggest a major role for the noradrenergic system in extinction of fear-based learning. Employing both pharmacological and genetic approaches, we investigated the role of the alpha(2)-adrenergic receptor (alpha(2)-AR) in extinction of cocaine-conditioned place preference (CPP) and glutamatergic transmission in the bed nucleus of the stria terminalis (BNST). We found that pre-extinction systemic treatment with the alpha(2)-AR antagonist yohimbine impaired cocaine CPP extinction in C57BL/6J mice, an effect that was not mimicked by the more selective alpha(2)-AR antagonist, atipamezole. Moreover, alpha(2A)-AR knockout mice exhibited similar cocaine CPP extinction and exacerbated extinction impairing effects of yohimbine. Using acute brain slices and electrophysiological approaches, we found that yohimbine produces a slowly evolving depression of glutamatergic transmission in the BNST that was not mimicked by atipamezole. Further, this action was extant in slices from alpha(2A)-AR knockout mice. Our data strongly suggest that extinction-modifying effects of yohimbine are unlikely to be due to actions at alpha(2A)-ARs. PMID:18772254

  18. Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate.

    PubMed Central

    Arnez, J G; Harris, D C; Mitschler, A; Rees, B; Francklyn, C S; Moras, D

    1995-01-01

    The crystal structure at 2.6 A of the histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate has been determined. The enzyme is a homodimer with a molecular weight of 94 kDa and belongs to the class II of aminoacyl-tRNA synthetases (aaRS). The asymmetric unit is composed of two homodimers. Each monomer consists of two domains. The N-terminal catalytic core domain contains a six-stranded antiparallel beta-sheet sitting on two alpha-helices, which can be superposed with the catalytic domains of yeast AspRS, and GlyRS and SerRS from Thermus thermophilus with a root-mean-square difference on the C alpha atoms of 1.7-1.9 A. The active sites of all four monomers are occupied by histidyl-adenylate, which apparently forms during crystallization. The 100 residue C-terminal alpha/beta domain resembles half of a beta-barrel, and provides an independent domain oriented to contact the anticodon stem and part of the anticodon loop of tRNA(His). The modular domain organization of histidyl-tRNA synthetase reiterates a repeated theme in aaRS, and its structure should provide insight into the ability of certain aaRS to aminoacylate minihelices and other non-tRNA molecules. Images PMID:7556055

  19. Rocketdyne RBCC Engine Concept Development

    NASA Technical Reports Server (NTRS)

    Ratckin, G.; Goldman, A.; Ortwerth, P.; Weisberg, S.

    1999-01-01

    Boeing Rocketdyne is pursuing the development of Rocket Based Combined Cycle (RBCC), propulsion systems as demonstrated by significant contract work in the hypersonic arena (ART, NASP, SCT, system studies) and over 12 years of steady company discretionary investment. The Rocketdyne concept is a fixed geometry integrated rocket, ramjet, scramjet which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals. seal purge gas, and closeout side attachments. Rocketdyne's experimental RBCC engine (Engine A5) was constructed under contract with the NASA Marshall Space Flight Center. Engine A5 models the complete flight engine flowpath consisting of an inlet, isolator, airbreathing combustor and nozzle. High performance rocket thrusters are integrated into the engine to enable both air-augmented rocket (AAR) and pure rocket operation. Engine A5 was tested in CASL's new FAST facility as an air-augmented rocket, a ramjet and a pure rocket. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. Rocket mode performance was above predictions. For the first time. testing also demonstrated transition from AAR operation to ramjet operation. This baseline configuration has also been shown, in previous testing, to perform well in the scramjet mode.

  20. Plasma Levels of Dimethylarginines in Preterm Very Low Birth Weight Neonates: Its Relation with Perinatal Factors and Short-Term Outcome

    PubMed Central

    Moonen, Rob M.; Huizing, Maurice J.; Cavallaro, Giacomo; González-Luis, Gema E.; Bas-Suárez, Pilar; Bakker, Jaap A.; Villamor, Eduardo

    2014-01-01

    Endogenously produced inhibitors of nitric oxide (NO) synthase, in particular asymmetric dimethylarginine (ADMA), are currently considered of importance in various disease states characterized by reduced NO availability. We investigated the association between plasma levels of ADMA, symmetric dimethylarginine (SDMA), l-arginine, and citrulline and perinatal factors and outcome in 130 preterm (gestational age ≤30 weeks) very low birth weight (VLBW, <1500 g) infants. Plasma samples were collected 6–12 h after birth. We did not find significant correlations between ADMA, SDMA, l-arginine, and citrulline levels and gestational age or birth weight. However, the arginine:ADMA ratio (AAR, a better indicator of NO availability than either arginine or ADMA separately) was positively correlated with gestational age. ADMA and arginine levels were not significantly different between males and females but males showed a negative correlation between ADMA levels and gestational age. Perinatal factors such as preeclampsia, chrorioamnionitis, prolonged rupture of membranes, or form of delivery did not significantly alter dimethylarginine levels or AAR. In contrast, the AAR was significantly reduced in the infants with respiratory distress, mechanical ventilation, and systemic hypotension Therefore, our data suggest that altered NO availability may play a role in the respiratory and cardiovascular adaptation in preterm VLBW infants. PMID:25546385

  1. Hyrdo-Quebec`s experience using deep slot cutting to rehabilitate concrete gravity dams affected by alkali-aggregate reaction

    SciTech Connect

    Veilleux, M.

    1995-12-31

    In recent years, Hydro-Qu{acute e}bec has cut vertical slots in concrete dams to solve structural problems stemming from aging of concrete subject to thermal cycles and alkali-aggregate reaction (AAR). In most cases, the structural disorders caused large cracks and permanent displacement. This paper describes Hydro-Qu{acute e}bec`s experience using a new slot-cutting and sealing technology to rehabilitate concrete gravity dams affected by AAR, among them rehabilitation of the Paugan (1991), La Tuque (1992-1993), Rapides Farmers (1993-1994) and Chelsea (1994) hydroelectric developments. The aim of this technology is to relieve internal stress and to create an effective expansion joint which can accommodate reversible and irreversible displacement induced by thermal cycles as well as permanent movement due to chemical concrete swelling caused by AAR. This method of rehabilitation is generally used in conjunction with grouting and drainage work and sometimes with post-tensioned anchor rods or cables.

  2. Structural Basis of Brr2-Prp8 Interactions and Implications for U5 snRNP Biogenesis and the Spliceosome Active Site

    PubMed Central

    Nguyen, Thi Hoang Duong; Li, Jade; Galej, Wojciech P.; Oshikane, Hiroyuki; Newman, Andrew J.; Nagai, Kiyoshi

    2013-01-01

    Summary The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Sm proteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP. PMID:23727230

  3. Fluorescence Tomography of Rapamycin-Induced Autophagy and Cardioprotection In Vivo

    PubMed Central

    Chen, Howard H.; Mekkaoui, Choukri; Cho, Hoonsung; Ngoy, Soeun; Marinelli, Brett; Waterman, Peter; Nahrendorf, Matthias; Liao, Ronglih; Josephson, Lee; Sosnovik, David E.

    2013-01-01

    Background Autophagy is a biological process during which cells digest organelles in their cytoplasm and recycle the constituents. The impact of autophagy in the heart, however, remains unclear in part due to the inability to noninvasively image this process in living animals. Methods and Results Here, we report the use of fluorescence molecular tomography (FMT) and a cathepsin activatable fluorochrome to image autophagy in the heart in vivo following ischemia-reperfusion and rapamycin therapy. We show that cathepsin-B activity in the lysosome is upregulated by rapamycin and that this allows the expanded lysosomal compartment in autophagy to be imaged in vivo with FMT. We further demonstrate that the delivery of diagnostic nanoparticles to the lysosome by endocytosis is enhanced during autophagy. The upregulation of autophagy by rapamycin was associated with a 23% reduction (p<0.05) of apoptosis in the area-at-risk (AAR), and a 45% reduction in final infarct size (19.6 +/− 5.6% of AAR with rapamycin versus 35.9 +/− 9.1% of AAR without rapamycin, p<0.05). Conclusions The ability to perform noninvasive tomographic imaging of autophagy in the heart has the potential to provide valuable insights into the pathophysiology of autophagy, particularly its role in cardiomyocyte salvage. While additional data are needed, our study supports the investigation of rapamycin therapy in patients with acute coronary syndromes. PMID:23537953

  4. Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life

    NASA Astrophysics Data System (ADS)

    Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter

    2011-12-01

    Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

  5. Automated Aerial Refueling Hitches a Ride on AFF

    NASA Technical Reports Server (NTRS)

    Hansen, Jennifer L.; Murray, James E.; Bever, Glenn; Campos, Norma V.; Schkolnik, Gerard

    2007-01-01

    The recent introduction of uninhabited aerial vehicles [UAVs (basically, remotely piloted or autonomous aircraft)] has spawned new developments in autonomous operation and posed new challenges. Automated aerial refueling (AAR) is a capability that will enable UAVs to travel greater distances and loiter longer over targets. NASA Dryden Flight Research Center, in cooperation with the Defense Advanced Research Projects Agency (DARPA), the Naval Air Systems Command (NAVAIR), the Naval Air Force Pacific Fleet, and the Air Force Research Laboratory, rapidly conceived and accomplished an AAR flight research project focused on collecting a unique, high-quality database on the dynamics of the hose and drogue of an aerial refueling system. This flight-derived database would be used to validate mathematical models of the dynamics in support of design and analysis of AAR systems for future UAVs. The project involved the use of two Dryden F/A-18 airplanes and an S-3 hose-drogue refueling store on loan from the Navy. In this year-long project, which was started on October 1, 2002, 583 research maneuvers were completed during 23 flights.

  6. Soft tissue removal by maceration and feeding of Dermestes sp.: impact on morphological and biomolecular analyses of dental tissues in forensic medicine.

    PubMed

    Offele, Daniel; Harbeck, Michaela; Dobberstein, Reimer C; von Wurmb-Schwark, Nicole; Ritz-Timme, Stefanie

    2007-09-01

    Maceration techniques remove soft tissue by the destruction of biomolecules, but the applied techniques may also affect the morphology and the molecular integrity of the hard tissue itself. The impact of seven different techniques for soft tissue removal on morphological and biomolecular parameters of teeth and dental tissues was systematically examined. All methods tested showed significant changes in dental morphology and in the molecular integrity of DNA and the dental proteins, as revealed by aspartic acid racemisation (AAR). In forensic casework this may have severe impacts on the results of morphological methods (e.g. age estimation based on root translucency) and of biomolecular analyses (e.g. age estimation based on AAR and DNA analysis). Therefore, age estimation based on AAR should not be applied to tissue treated in such a manner, and it is recommended that teeth for analysis should be extracted before soft tissue removal. DNA in the hard tissue seems to be less susceptible to soft tissue removal than proteins, and several of the tested maceration techniques appear not to have a damaging effect on DNA. Generally, the indication for soft tissue removal demands a careful case management to avoid methodological collisions. PMID:16983584

  7. Hazmat on the rails: A closer look

    SciTech Connect

    Larson, K.M.

    1996-10-01

    Despite what appears to be a rash of railroad incidents involving hazardous materials, the Association of American Railroads (AAR; Washington, DC) maintains that 1995 was the safest year in railroad history, even though rail freight traffic was at an all-time high. AAR says railroads have an especially good record when it comes to moving hazardous waste. Railroads in 1994 moved more than 1.6 million carloads of hazardous materials, yet only 43 cars released hazardous contents--fewer than one for every 37,000 cars moved, AAR notes. Preliminary figures indicate another 43 cars released hazardous materials in 1995. Not all rail car releases occur as a result of an accident or derailment. Nonaccident releases (NARs) can result from such problems as tank car overfilling, chemical reactions during temperature changes, or loose tank closures. The top 10 hazardous commodities are: sulfuric acid, hydrochloric acid solution, anhydrous ammonia, liquefied petroleum gases, sodium hydroxide solution, flammable liquids not otherwise specified, corrosive liquids not otherwise specified, phosphoric acid, methyl tertiary butyl ether, and methanol.

  8. Using immobilized G-protein coupled receptors to screen bioactive traditional Chinese medicine compounds with multiple targets.

    PubMed

    Zhao, Xinfeng; Li, Qian; Bian, Liujiao; Zheng, Xiaohui; Zheng, Jianbin; Zhang, Youyi; Li, Zijian

    2012-11-01

    Demand on high-throughput methods for multi-target compounds screening continues to increase nowadays due to the decline of new drugs on the market. Two kinds of G-protein-coupled receptors, alpha1-adrenoceptor (α(1A)-AR) and beta2-adrenoceptor (β(2)-AR), were purified and immobilized on the surface of macroporous silica gel to prepare new chromatographic stationary phases. Control drugs (e.g., prazosin, terazosin, salbutamol, and terbutaline) were used to characterize the retention behavior of the obtained α(1A)-AR and β(2)-AR columns. This study also coupled both columns with a six-way switching valve to construct an automatic two-dimensional system for multi-target compounds screening in complex mixtures. Adrenaline hydrochloride was used as a representative drug to evaluate the chromatographic performance of the two dimensional system. The aqueous extracts from Salvia miltiorrhiza and Coptis chinensis were also analyzed by the automatic system. The compounds in S. miltiorrhiza had no binding to both α(1A)-AR and β(2)-AR columns. But berberine, palmatine and jatrorrhizine were screened as the bioactive compounds in C. chinensis, targeting both the receptors. The proposed method is an alternative for recognizing and separating the compounds targeting different proteins from a complex matrix. PMID:22651959

  9. In silico detection of tRNA sequence features characteristic to aminoacyl-tRNA synthetase class membership

    PubMed Central

    Jakó, Éena; Ittzés, Péter; Szenes, Áron; Kun, Ádám; Szathmáry, Eörs; Pál, Gábor

    2007-01-01

    Aminoacyl tRNA synthetases (aaRS) are grouped into Class I and II based on primary and tertiary structure and enzyme properties suggesting two independent phylogenetic lineages. Analogously, tRNA molecules can also form two respective classes, based on the class membership of their corresponding aaRS. Although some aaRS–tRNA interactions are not extremely specific and require editing mechanisms to avoid misaminoacylation, most aaRS–tRNA interactions are rather stereospecific. Thus, class-specific aaRS features could be mirrored by class-specific tRNA features. However, previous investigations failed to detect conserved class-specific nucleotides. Here we introduce a discrete mathematical approach that evaluates not only class-specific ‘strictly present’, but also ‘strictly absent’ nucleotides. The disjoint subsets of these elements compose a unique partition, named extended consensus partition (ECP). By analyzing the ECP for both Class I and II tDNA sets from 50 (13 archaeal, 30 bacterial and 7 eukaryotic) species, we could demonstrate that class-specific tRNA sequence features do exist, although not in terms of strictly conserved nucleotides as it had previously been anticipated. This finding demonstrates that important information was hidden in tRNA sequences inaccessible for traditional statistical methods. The ECP analysis might contribute to the understanding of tRNA evolution and could enrich the sequence analysis tool repertoire. PMID:17704131

  10. A continuous multi-millennial record of surficial bivalve mollusk shells from the São Paulo Bight, Brazilian shelf

    NASA Astrophysics Data System (ADS)

    Dexter, Troy A.; Kaufman, Darrell S.; Krause, Richard A.; Barbour Wood, Susan L.; Simões, Marcello G.; Huntley, John Warren; Yanes, Yurena; Romanek, Christopher S.; Kowalewski, Michał

    2014-03-01

    To evaluate the potential of using surficial shell accumulations for paleoenvironmental studies, an extensive time series of individually dated specimens of the marine infaunal bivalve mollusk Semele casali was assembled using amino acid racemization (AAR) ratios (n = 270) calibrated against radiocarbon ages (n = 32). The shells were collected from surface sediments at multiple sites across a sediment-starved shelf in the shallow sub-tropical São Paulo Bight (São Paulo State, Brazil). The resulting 14C-calibrated AAR time series, one of the largest AAR datasets compiled to date, ranges from modern to 10,307 cal yr BP, is right skewed, and represents a remarkably complete time series: the completeness of the Holocene record is 66% at 250-yr binning resolution and 81% at 500-yr binning resolution. Extensive time-averaging is observed for all sites across the sampled bathymetric range indicating long water depth-invariant survival of carbonate shells at the sediment surface with low net sedimentation rates. Benthic organisms collected from active depositional surfaces can provide multi-millennial time series of biomineral records and serve as a source of geochemical proxy data for reconstructing environmental and climatic trends throughout the Holocene at centennial resolution. Surface sediments can contain time-rich shell accumulations that record the entire Holocene, not just the present.

  11. Surface modification of polypropylene battery separator by direct fluorination with different gas components

    NASA Astrophysics Data System (ADS)

    Li, Baoyin; Gao, Jie; Wang, Xu; Fan, Cong; Wang, Huina; Liu, Xiangyang

    2014-01-01

    Improvement in hydrophilicity of polypropylene (PP) separator and its stability is essential for enhancing the comprehensive performance of battery. In this study, the PP separators were surface modified by direct fluorination with F2/N2 and F2/O2/N2 gas atmosphere. The alkali absorption ratios (AARs) of these two kinds of fluorinated separators are 302.7% and 418.4%, respectively, which is about nine and twelve times than that of the virgin PP separator. At the same time, the AARs of the fluorinated separators stored for 90 days at ambient temperature in air environment still remain. The surface energy of PP separators is increased from 37.8 mN/m to 47.7 mN/m and 48.9 mN/m determined by contact angle measurement after direct fluorination. X-ray photoelectron spectroscopy (XPS) and attenuated total reflection infrared spectroscopy (ATR-FTIR) results indicate that polar groups, such as sbnd Cdbnd O(OH) and sbnd Csbnd Fx, are introduced into the polymeric structures of the two fluorinated separator surfaces. Larger quantity of polar groups, especially sbnd Cdbnd O(OH), are introduced on separator surface by the F2/O2/N2 modified route, which results in the difference of the AARs and behavior of alkali absorption. Scanning electron microscope (SEM) demonstrates that the size and shape of micropores of PP separators remain almost unchanged after direct fluorination.

  12. Influence of steel fibers on the development of alkali-aggregate reaction

    SciTech Connect

    Pires de Carvalho, Maria Rita; Pagan Hasparyk, Nicole

    2010-04-15

    This work presents the results of an experimental research concerning the use of fibers in mortar specimens subjected to alkali-aggregate reaction (AAR). Two types of steel fibers (0.16 mm diameter and 6.0 mm length, and 0.20 mm diameter and 13.0 mm length) were used with fiber volume contents of 1% and 2%. Besides the expansion accelerated tests, compressive tests and flexural tests have also been carried out to display the main mechanical characteristics of the fiber-reinforced mortars after being subjected to AAR. Moreover, the microstructure of the specimens was analyzed by scanning electron microscopy and energy dispersive X-ray. The results shown that the addition of steel fibers reduced the expansion due to AAR for the experimental conditions studied in this paper. The most expressive benefit corresponded to the addition of 13.0 mm fibers in the mixture containing 2% fiber content. This fiber volume content also corresponded to the maximum increment in the mechanical properties compared to the reference mortar, mainly for the post-cracking strength and for the toughness in bending. It was observed that the fibers have a beneficial effect on the material, without compromising its main mechanical properties.

  13. Unique forbidden beta decays and neutrino mass

    NASA Astrophysics Data System (ADS)

    Dvornický, Rastislav; Šimkovic, Fedor

    2015-10-01

    The measurement of the electron energy spectrum in single β decays close to the endpoint provides a direct determination of the neutrino masses. The most sensitive experiments use β decays with low Q value, e.g. KATRIN (tritium) and MARE (rhenium). We present the theoretical spectral shape of electrons emitted in the first, second, and fourth unique forbidden β decays. Our findings show that the Kurie functions for these unique forbidden β transitions are linear in the limit of massless neutrinos like the Kurie function of the allowed β decay of tritium.

  14. Statistical criteria for search of heavy neutrino in tritium spectrum

    NASA Astrophysics Data System (ADS)

    Lokhov, Alexey; Tkachov, Fyodor

    2016-05-01

    The method of quasi-optimal weights is applied to constructing (quasi-)optimal criteria for search of heavy (4th generation) neutrino contribution in experimental β-decay spectra. Various approaches to searching for anomalous contributions in spectra are discussed. In particular the tritium β-decay spectrum (for instance, in Troitsk-v-mass, Mainz Neutrino Mass and KATRIN experiments) is analyzed using the derived special criteria. The power functions constructed for each criteria show the efficiency of the derived quasi-optimal criteria as statistical instruments for detecting the anomalous contributions in the spectra. The overall sensitivity of the criteria is estimated.

  15. Direct Neutrino Mass Searches

    NASA Astrophysics Data System (ADS)

    VanDevender, B. A.

    2009-12-01

    Neutrino flavor oscillation experiments have demonstrated that the three Standard Model neutrino flavor eigenstates are mixed with three mass eigenstates whose mass eigenvalues are nondegenerate. The oscillation experiments measure the differences between the squares of the mass eigenvalues but tell us nothing about their absolute values. The unknown absolute neutrino mass scale has important implications in particle physics and cosmology. Beta decay endpoint measurements are presented as a model-independent method to measure the absolute neutrino mass. The Karlsruhe Tritium Neutrino Experiment (KATRIN) is explored in detail.

  16. Unique forbidden beta decays and neutrino mass

    SciTech Connect

    Dvornický, Rastislav; Šimkovic, Fedor

    2015-10-28

    The measurement of the electron energy spectrum in single β decays close to the endpoint provides a direct determination of the neutrino masses. The most sensitive experiments use β decays with low Q value, e.g. KATRIN (tritium) and MARE (rhenium). We present the theoretical spectral shape of electrons emitted in the first, second, and fourth unique forbidden β decays. Our findings show that the Kurie functions for these unique forbidden β transitions are linear in the limit of massless neutrinos like the Kurie function of the allowed β decay of tritium.

  17. Does a Superswell Exist Between Antarctica and Australia?

    NASA Astrophysics Data System (ADS)

    Park, S. H.; Langmuir, C. H.; Scott, S. R.; Sims, K. W. W.; Lin, J.; Kim, S.; Michael, P. J.; Hahm, D.

    2015-12-01

    The Australian-Antarctic Ridge (AAR) is located between the Australian-Antarctic Discordance (AAD) of the Southeast Indian ridge (SEIR) in the west and Pacific-Antarctic Ridge (PAR) in the east. The AAR has intermediate spreading rate (~70 mm/yr) and consists of a series of 1st order segments bounded by parallel transform faults. KR1, a southernmost segment (63°S) of the AAR, is a 300-km-long super-segment with shallow axial depth (~2000 m). KR1 is bounded by the Macquarie transform fault in the east and the Balleney transform fault in the west, which connects KR1 with KR2 at ~ 200 km north. KR2 is 180 km long with axial depth (~2300 m) deeper than KR1. Both KR1 and KR2 are shallow relative to global mid-ocean ridges. Most of the basaltic rocks from the two segments show enriched geochemical characteristics that differ from both the AAD (Southeast Indian Ridge) and the PAR. La/Sm ratios vary from N-MORB to T-MORB; however, K2O/Nb ratios of all samples are consistently low like OIB. Their Pb isotopes are mostly more radiogenic than the N-MORB samples from PAR (and EPR) and SEIR, with 206Pb/204Pb mostly >18.6. At a given 206Pb/204Pb, their 87Sr/86Sr are higher than the PAR, but lower than the SEIR. The basalts from the two segments are geochemically similar to Cenozoic volcanoes erupted on southeast Australia, Zealandia and northwest Antarctica, suggesting a genetic relationship. According to tectonic reconstruction models, these three continents were originally joined, but separated from each other after ~80 Ma. Notably, the KR1 and KR2 segments are located at the boundary of this continental separation. The ages of Cenozoic volcanoes span from ~ 60 Ma to the recent, and the volcanoes might be related to a plume head that caused the breakup of the continents. Seismic tomography studies show that there is a low velocity zone (LVZ) in the shallow mantle (> 250 km) between Antarctica and Australia where the AAR is located. The AAR would be sampling this LVZ, and this

  18. Absolute neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Wolf, Joachim

    2011-10-01

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2β) searches, single β-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy. Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium β-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope (137Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R&D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2β decay and single β-decay.

  19. Direct neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Thümmler, T.

    2011-07-01

    The determination of the neutrino rest mass plays an important role at the intersections of cosmology, particle physics and astroparticle physics. This topic is currently being addressed by two complementary approaches in laboratory experiments. Neutrinoless double beta decay experiments probe whether neutrinos are Majorana particles and determine an effective neutrino mass value. Single beta decay experiments such as KATRIN and MARE investigate the spectral shape of β-decay electrons close to their kinematic endpoint in order to determine the neutrino rest mass with a model-independent method. Owing to neutrino flavour mixing, the neutrino mass parameter appears as an average of all neutrino mass eigenstates contributing to the electron neutrino. The KArlsruhe TRItium Neutrino experiment (KATRIN) is currently the experiment in the most advanced status of commissioning. Applying an ultra-luminous molecular windowless gaseous tritium source and an integrating high-resolution spectrometer of MAC-E filter type, it allows β-spectroscopy close to the T 2 end-point with unprecedented precision and will reach a sensitivity of 200 meV/ c 2 (90% C.L.) on the neutrino rest mass.

  20. Progress with the MPIK/UW-PTMS in Heidelberg

    NASA Astrophysics Data System (ADS)

    Diehl, Christoph; Blaum, Klaus; Höcker, Martin; Ketter, Jochen; Pinegar, David B.; Streubel, Sebastian; Van Dyck, Robert S.

    2011-07-01

    The precise determination of the 3He/3H mass ratio, and hence the tritium β-decay endpoint energy E 0, is of relevance for the measurement of the electron anti-neutrino mass performed by the Karlsruhe Tritium Neutrino experiment (KATRIN). By determining this ratio to an uncertainty of 1 part in 1011, systematic errors of E 0 can be checked in the data analysis of KATRIN. To reach this precision, a Penning Trap Mass Spectrometer was constructed at the University of Washington and has been transferred to the Max Planck Institute for Nuclear Physics in Heidelberg at the end of 2008. Since then it is called MPIK/UW-PTMS. Special design features are the utilization of an external ion source and a double trap configuration. The external Penning ion source efficiently ionizes the helium and tritium gas and can give superior elimination of unwanted ion species compared to the previously utilized in-trap-ionization by electrons from a field-emission point. The design as a double Penning trap allows a faster measurement procedure. This should help to avoid problems resulting from long-term drifts in the experimental conditions. Additionally, the laboratory in Heidelberg was carefully prepared to have very stable environmental conditions. Experimental challenges and the first Heidelberg results with the new spectrometer are presented.

  1. Absolute neutrino mass measurements

    SciTech Connect

    Wolf, Joachim

    2011-10-06

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2{beta}) searches, single {beta}-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy.Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium {beta}-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope ({sup 137}Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R and D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2{beta} decay and single {beta}-decay.

  2. Role of ω-hydroxylase in adenosine-mediated aortic response through MAP kinase using A2A-receptor knockout mice.

    PubMed

    Ponnoth, Dovenia S; Nayeem, Mohammed A; Kunduri, Swati S; Tilley, Stephen L; Zeldin, Darryl C; Ledent, Catherine; Mustafa, S Jamal

    2012-02-15

    Previously, we have shown that A(2A) adenosine receptor (A(2A)AR) knockout mice (KO) have increased contraction to adenosine. The signaling mechanism(s) for A(2A)AR is still not fully understood. In this study, we hypothesize that, in the absence of A(2A)AR, ω-hydroxylase (Cyp4a) induces vasoconstriction through mitogen-activated protein kinase (MAPK) via upregulation of adenosine A(1) receptor (A(1)AR) and protein kinase C (PKC). Organ bath and Western blot experiments were done using isolated aorta from A(2A)KO and corresponding wild-type (WT) mice. Isolated aortic rings from WT and A(2A)KO mice were precontracted with submaximal dose of phenylephrine (10(-6) M), and concentration responses for selective A(1)AR, A(2A)AR agonists, angiotensin II and cytochrome P-450-epoxygenase, 20-hydroxyeicosatrienoic acid (20-HETE) PKC, PKC-α, and ERK1/2 inhibitors were obtained. 2-p-(2-Carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680, A(2A)AR agonist) induced concentration-dependent relaxation in WT, which was blocked by methylsulfonyl-propargyloxyphenylhexanamide (cytochrome P-450-epoxygenase inhibitor; 10(-5) M) and also with removal of endothelium. A(1) agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA) produced higher contraction in A(2A)KO aorta than WT (49.2 ± 8.5 vs. 27 ± 5.9% at 10(-6) M, P < 0.05). 20-HETE produced higher contraction in A(2A)KO than WT (50.6 ± 8.8 vs. 21.1 ± 3.3% at 10(-7) M, P < 0.05). Contraction to CCPA in WT and A(2A)KO aorta was inhibited by PD-98059 (p42/p44 MAPK inhibitor; 10(-6) M), chelerythrine chloride (nonselective PKC blocker; 10(-6) M), Gö-6976 (selective PKC-α inhibitor; 10(-7) M), and HET0016 (20-HETE inhibitor; 10(-5) M). Also, contraction to 20-HETE in WT and A(2A)KO aorta was inhibited by PD-98059 and Gö-6976. Western blot analysis indicated the upregulation of A(1)AR, Cyp4a, PKC-α, and phosphorylated-ERK1/2 in A(2A)KO compared with WT (P < 0.05), while expression of Cyp2c29 was

  3. Alkane Biosynthesis Genes in Cyanobacteria and Their Transcriptional Organization

    PubMed Central

    Klähn, Stephan; Baumgartner, Desirée; Pfreundt, Ulrike; Voigt, Karsten; Schön, Verena; Steglich, Claudia; Hess, Wolfgang R.

    2014-01-01

    In cyanobacteria, alkanes are synthesized from a fatty acyl-ACP by two enzymes, acyl–acyl carrier protein reductase and aldehyde deformylating oxygenase. Despite the great interest in the exploitation for biofuel production, nothing is known about the transcriptional organization of their genes or the physiological function of alkane synthesis. The comparison of 115 microarray datasets indicates the relatively constitutive expression of aar and ado genes. The analysis of 181 available genomes showed that in 90% of the genomes both genes are present, likely indicating their physiological relevance. In 61% of them they cluster together with genes encoding acetyl-CoA carboxyl transferase and a short-chain dehydrogenase, strengthening the link to fatty acid metabolism and in 76% of the genomes they are located in tandem, suggesting constraints on the gene arrangement. However, contrary to the expectations for an operon, we found in Synechocystis sp. PCC 6803 specific promoters for the two genes, sll0208 (ado) and sll0209 (aar), which give rise to monocistronic transcripts. Moreover, the upstream located ado gene is driven by a proximal as well as a second, distal, promoter, from which a third transcript, the ~160 nt sRNA SyR9 is transcribed. Thus, the transcriptional organization of the alkane biosynthesis genes in Synechocystis sp. PCC 6803 is of substantial complexity. We verified all three promoters to function independently from each other and show a similar promoter arrangement also in the more distant Nodularia spumigena, Trichodesmium erythraeum, Anabaena sp. PCC 7120, Prochlorococcus MIT9313, and MED4. The presence of separate regulatory elements and the dominance of monocistronic mRNAs suggest the possible autonomous regulation of ado and aar. The complex transcriptional organization of the alkane synthesis gene cluster has possible metabolic implications and should be considered when manipulating the expression of these genes in cyanobacteria. PMID

  4. Proteomic-Coupled-Network Analysis of T877A-Androgen Receptor Interactomes Can Predict Clinical Prostate Cancer Outcomes between White (Non-Hispanic) and African-American Groups

    PubMed Central

    Zaman, Naif; Giannopoulos, Paresa N.; Chowdhury, Shafinaz; Bonneil, Eric; Thibault, Pierre; Wang, Edwin; Trifiro, Mark; Paliouras, Miltiadis

    2014-01-01

    The androgen receptor (AR) remains an important contributor to the neoplastic evolution of prostate cancer (CaP). CaP progression is linked to several somatic AR mutational changes that endow upon the AR dramatic gain-of-function properties. One of the most common somatic mutations identified is Thr877-to-Ala (T877A), located in the ligand-binding domain, that results in a receptor capable of promiscuous binding and activation by a variety of steroid hormones and ligands including estrogens, progestins, glucocorticoids, and several anti-androgens. In an attempt to further define somatic mutated AR gain-of-function properties, as a consequence of its promiscuous ligand binding, we undertook a proteomic/network analysis approach to characterize the protein interactome of the mutant T877A-AR in LNCaP cells under eight different ligand-specific treatments (dihydrotestosterone, mibolerone, R1881, testosterone, estradiol, progesterone, dexamethasone, and cyproterone acetate). In extending the analysis of our multi-ligand complexes of the mutant T877A-AR we observed significant enrichment of specific complexes between normal and primary prostatic tumors, which were furthermore correlated with known clinical outcomes. Further analysis of certain mutant T877A-AR complexes showed specific population preferences distinguishing primary prostatic disease between white (non-Hispanic) vs. African-American males. Moreover, these cancer-related AR-protein complexes demonstrated predictive survival outcomes specific to CaP, and not for breast, lung, lymphoma or medulloblastoma cancers. Our study, by coupling data generated by our proteomics to network analysis of clinical samples, has helped to define real and novel biological pathways in complicated gain-of-function AR complex systems. PMID:25409505

  5. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

    PubMed

    Tang, Xiaohu; Keenan, Melissa M; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J Will; Freedland, Stephen J; Murphy, Susan K; Chi, Jen-Tsan

    2015-04-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  6. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    PubMed Central

    2010-01-01

    Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

  7. An Ancestral Tryptophanyl-tRNA Synthetase Precursor Achieves High Catalytic Rate Enhancement without Ordered Ground-State Tertiary Structures.

    PubMed

    Sapienza, Paul J; Li, Li; Williams, Tishan; Lee, Andrew L; Carter, Charles W

    2016-06-17

    Urzymes-short, active core modules derived from enzyme superfamilies-prepared from the two aminoacyl-tRNA synthetase (aaRS) classes contain only the modules shared by all related family members. They have been described as models for ancestral forms. Understanding them currently depends on inferences drawn from the crystal structures of the full-length enzymes. As aaRS Urzymes lack much of the mass of modern aaRS's, retaining only a small portion of the hydrophobic cores of the full-length enzymes, it is desirable to characterize their structures. We report preliminary characterization of (15)N tryptophanyl-tRNA synthetase Urzyme by heteronuclear single quantum coherence (HSQC) NMR spectroscopy supplemented by circular dichroism, thermal melting, and induced fluorescence of bound dye. The limited dispersion of (1)H chemical shifts (0.5 ppm) is inconsistent with a narrow ensemble of well-packed structures in either free or substrate-bound forms, although the number of resonances from the bound state increases, indicating a modest, ligand-dependent gain in structure. Circular dichroism spectroscopy shows the presence of helices and evidence of cold denaturation, and all ligation states induce Sypro Orange fluorescence at ambient temperatures. Although the term "molten globule" is difficult to define precisely, these characteristics are consistent with most such definitions. Active-site titration shows that a majority of molecules retain ∼60% of the transition state stabilization free energy observed in modern synthetases. In contrast to the conventional view that enzymes require stable tertiary structures, we conclude that a highly flexible ground-state ensemble can nevertheless bind tightly to the transition state for amino acid activation. PMID:27008438

  8. Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process

    PubMed Central

    Woese, Carl R.; Olsen, Gary J.; Ibba, Michael; Söll, Dieter

    2000-01-01

    The aminoacyl-tRNA synthetases (AARSs) and their relationship to the genetic code are examined from the evolutionary perspective. Despite a loose correlation between codon assignments and AARS evolutionary relationships, the code is far too highly structured to have been ordered merely through the evolutionary wanderings of these enzymes. Nevertheless, the AARSs are very informative about the evolutionary process. Examination of the phylogenetic trees for each of the AARSs reveals the following. (i) Their evolutionary relationships mostly conform to established organismal phylogeny: a strong distinction exists between bacterial- and archaeal-type AARSs. (ii) Although the evolutionary profiles of the individual AARSs might be expected to be similar in general respects, they are not. It is argued that these differences in profiles reflect the stages in the evolutionary process when the taxonomic distributions of the individual AARSs became fixed, not the nature of the individual enzymes. (iii) Horizontal transfer of AARS genes between Bacteria and Archaea is asymmetric: transfer of archaeal AARSs to the Bacteria is more prevalent than the reverse, which is seen only for the “gemini group.” (iv) The most far-ranging transfers of AARS genes have tended to occur in the distant evolutionary past, before or during formation of the primary organismal domains. These findings are also used to refine the theory that at the evolutionary stage represented by the root of the universal phylogenetic tree, cells were far more primitive than their modern counterparts and thus exchanged genetic material in far less restricted ways, in effect evolving in a communal sense. PMID:10704480

  9. Aminoacylating Urzymes Challenge the RNA World Hypothesis*♦

    PubMed Central

    Li, Li; Francklyn, Christopher; Carter, Charles W.

    2013-01-01

    We describe experimental evidence that ancestral peptide catalysts substantially accelerated development of genetic coding. Structurally invariant 120–130-residue Urzymes (Ur = primitive plus enzyme) derived from Class I and Class II aminoacyl-tRNA synthetases (aaRSs) acylate tRNA far faster than the uncatalyzed rate of nonribosomal peptide bond formation from activated amino acids. These new data allow us to demonstrate statistically indistinguishable catalytic profiles for Class I and II aaRSs in both amino acid activation and tRNA acylation, over a time period extending to well before the assembly of full-length enzymes and even further before the Last Universal Common Ancestor. Both Urzymes also exhibit ∼60% of the contemporary catalytic proficiencies. Moreover, they are linked by ancestral sense/antisense genetic coding, and their evident modularities suggest descent from even simpler ancestral pairs also coded by opposite strands of the same gene. Thus, aaRS Urzymes substantially pre-date modern aaRS but are, nevertheless, highly evolved. Their unexpectedly advanced catalytic repertoires, sense/antisense coding, and ancestral modularities imply considerable prior protein-tRNA co-evolution. Further, unlike ribozymes that motivated the RNA World hypothesis, Class I and II Urzyme·tRNA pairs represent consensus ancestral forms sufficient for codon-directed synthesis of nonrandom peptides. By tracing aaRS catalytic activities back to simpler ancestral peptides, we demonstrate key steps for a simpler and hence more probable peptide·RNA development of rapid coding systems matching amino acids with anticodon trinucleotides. PMID:23867455

  10. Stimulatory effect of isoferulic acid on alpha1A-adrenoceptor to increase glucose uptake into cultured myoblast C2C12 cell of mice.

    PubMed

    Liu, I M; Tsai, C C; Lai, T Y; Cheng, J T

    2001-05-14

    In an attempt to elucidate the effect of isoferulic acid on alpha1-adrenoceptor (AR), the myoblast C2C12 cells of mice were employed to investigate the change of glucose uptake in the present study. Isoferulic acid enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner, which were abolished by pretreatment with prazosin. Effect of isoferulic acid on alpha1-AR was further characterized using the displacement of [3H]YM617 binding in C2C12 cells. The radioactive glucose uptake increasing action of isoferulic acid was abolished by tamsulosin or WB 4101 at concentration sufficient to block alpha1A-adrenoceptor (alpha1A-AR) but it was not modified by chlorethylclonidine (CEC) at the concentration sufficient to abolish alpha1B-AR. An activation of alpha1A-AR by isoferulic acid in C2C12 cells can thus be considered. Pharmacological inhibition of phospholipase C (PLC) by U73312 resulted in a concentration-dependent reduction of isoferulic acid-stimulated glucose uptake in C2C12 cells. This inhibition by U73112 was specific because the inactive congener, U73343, failed to modify the action of isoferulic acid. Also, chelerythrine and GF 109203X diminished the action of isoferulic acid at concentration sufficient to inhibit the activity of protein kinase C (PKC). The obtained data suggest that an activation of alpha1A-AR by isoferulic acid may increase the glucose uptake via PLC-PKC pathway in C2C12 cells. PMID:11474559

  11. [Alpha1-adrenoceptor subtype selectivity and organ specificity of silodosin (KMD-3213)].

    PubMed

    Tatemichi, Satoshi; Kobayashi, Kumi; Maezawa, Ayaka; Kobayashi, Mamoru; Yamazaki, Yoshinobu; Shibata, Nobuo

    2006-03-01

    The selectivity of silodosin (KMD-3213), an antagonist of alpha(1)-adrenoceptor (AR), to the subtypes (alpha(1A)-, alpha(1B)- and alpha(1D)-ARs) was examined by a receptor-binding study and a functional pharmacological study, and we compared its subtype-selectivity with those of other alpha(1)-AR antagonists. In the receptor-binding study, a replacement experiment using [(3)H]-prazosin was conducted using the membrane fraction of mouse-derived LM (tk-) cells in which each of three human alpha(1)-AR subtypes was expressed. In the functional pharmacological study, the following isolated tissues were used as representative organs with high distribution densities of alpha(1)-AR subtypes (alpha(1A)-AR: rabbit prostate, urethra and bladder trigone; alpha(1B)-AR: rat spleen; alpha(1D)-AR: rat thoracic aorta). Using the Magnus method, we studied the inhibitory effect of silodosin on noradrenaline-induced contraction, and compared it with those of tamsulosin hydrochloride, naftopidil and prazosin hydrochloride. Silodosin showed higher selectivity for the alpha(1A)-AR subtype than tamsulosin hydrochloride, naftopidil or prazosin hydrochloride (affinity was highest for tamsulosin hydrochloride, followed by silodosin, prazosin hydrochloride and naftopidil in that order). Silodosin strongly antagonized noradrenaline-induced contractions in rabbit lower urinary tract tissues (including prostate, urethra and bladder trigone, with pA(2) or pKb values of 9.60, 8.71 and 9.35, respectively). On the other hand, the pA(2) values for antagonism of noradrenaline-induced contractions in rat isolated spleen and rat isolated thoracic aorta were 7.15 and 7.88, respectively. Selectivity for lower urinary tract was higher for silodosin than for the other alpha(1)-AR antagonists. Our data suggest that silodosin has a high selectivity for the alpha(1A)-AR subtype and for the lower urinary tract. PMID:16518085

  12. A comparison of the toxinological characteristics of two Cassiopea and Aurelia species.

    PubMed

    Radwan, F F; Burnett, J W; Bloom, D A; Coliano, T; Eldefrawi, M E; Erderly, H; Aurelian, L; Torres, M; Heimer-de la Cotera, E P

    2001-01-01

    A comparison of the toxinological properties of nematocyst venoms from Old and New World Cassiopea and Aurelia species was undertaken. The cnidom of venomous Cassiopea andromeda (Ca) and Aurelia (Aa(RS)) from the Red Sea was identical to that of nonvenomous Bahamian Cassiopea xamancha (Cx) and Chesapeake Bay Aurelia aurita (Aa(CB)), respectively. A clean nematocyst preparation of Ca and both Aurelias could be obtained but algal particles could not be separated completely from the Cx nematocysts. Further purification of all four nematocyst preparations showed significant differences in the action of their protein. Only the Cassiopea had coexisting dermonecrotic and vasopermeability producing properties and Ca's hemolytic activity was associated with mouse lethality. The protein, hemolysin and phospholipase gel filtration eluant curves of Ca venom were similar. Venomous Aa(RS) actively stung lips and contained more potent mouse lethal, demonecrotic, vasopermeability plus hemolytic factors than Aa(CB). Cross reactivity of convalescent human serum obtained from patients stung by Ca and venomous Cx collected in Central America occurred. This was also observed between sera of bathers stung by Aa(RS) and stinging Aurelia which appeared in Florida during the recent El Niño year. IgG was stimulated by several nematocyst proteins since many venom subfractions tested positive at high titers against convalescent sera. T-cell proliferation of mice primed with either Aurelia venom was positive against the homologous preparation with cross reactivity to the heterologous venom. Crude venoms of both Red Sea jellyfish metabolically stimulated cultured human hepatocytes more than their New World counterparts. This data shows that considerable similarities and differences exist in the venoms of these Old and New World Cassiopea and Aurelia medusae with the Eastern species being more potent. PMID:10978742

  13. A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects.

    PubMed

    Wang, Yong; Zhou, Xiao-Long; Ruan, Zhi-Rong; Liu, Ru-Juan; Eriani, Gilbert; Wang, En-Duo

    2016-03-18

    Mitochondria require all translational components, including aminoacyl-tRNA synthetases (aaRSs), to complete organelle protein synthesis. Some aaRS mutations cause mitochondrial disorders, including human mitochondrial threonyl-tRNA synthetase (hmtThrRS) (encoded by TARS2), the P282L mutation of which causes mitochondrial encephalomyopathies. However, its catalytic and structural consequences remain unclear. Herein, we cloned TARS2 and purified the wild-type and P282L mutant hmtThrRS. hmtThrRS misactivates non-cognate Ser and uses post-transfer editing to clear erroneously synthesized products. In vitro and in vivo analyses revealed that the mutation induces a decrease in Thr activation, aminoacylation, and proofreading activities and a change in the protein structure and/or stability, which might cause reduced catalytic efficiency. We also identified a splicing variant of TARS2 mRNA lacking exons 8 and 9, the protein product of which is targeted into mitochondria. In HEK293T cells, the variant does not dimerize and cannot complement the ThrRS knock-out strain in yeast, suggesting that the truncated protein is inactive and might have a non-canonical function, as observed for other aaRS fragments. The present study describes the aminoacylation and editing properties of hmtThrRS, clarifies the molecular consequences of the P282L mutation, and shows that the yeast ThrRS-deletion model is suitable to test pathology-associated point mutations or alternative splicing variants of mammalian aaRS mRNAs. PMID:26811336

  14. Early auditory experience induces frequency-specific, adaptive plasticity in the forebrain gaze fields of the barn owl.

    PubMed

    Miller, G L; Knudsen, E I

    2001-05-01

    Binaural acoustic cues such as interaural time and level differences (ITDs and ILDs) are used by many species to determine the locations of sound sources. The relationship between cue values and locations in space is frequency dependent and varies from individual to individual. In the current study, we tested the capacity of neurons in the forebrain localization pathway of the barn owl to adjust their tuning for binaural cues in a frequency-dependent manner in response to auditory experience. Auditory experience was altered by raising young owls with a passive acoustic filtering device that caused frequency-dependent changes in ITD and ILD. Extracellular recordings were made in normal and device-reared owls to characterize frequency-specific ITD and ILD tuning in the auditory archistriatum (AAr), an output structure of the forebrain localization pathway. In device-reared owls, individual sites in the AAr exhibited highly abnormal, frequency-dependent variations in ITD tuning, and across the population of sampled sites, there were frequency-dependent shifts in the representation of ITD. These changes were in a direction that compensated for the acoustic effects of the device on ITD and therefore tended to restore a normal representation of auditory space. Although ILD tuning was degraded relative to normal at many sites in the AAr of device-reared owls, the representation of frequency-specific ILDs across the population of sampled sites was shifted in the adaptive direction. These results demonstrate that early auditory experience shapes the representation of binaural cues in the forebrain localization pathway in an adaptive, frequency-dependent manner. PMID:11353033

  15. Distribution within the barn owl's inferior colliculus of neurons projecting to the optic tectum and thalamus.

    PubMed

    Arthur, Ben J

    2005-11-01

    Behavioral studies in barn owls indicate that both the optic tectum (OT) and the auditory arcopallium (AAr) mediate sound localization through the presence of neurons that respond only when sound comes from a circumscribed direction in space. The early stages of the computations leading to these so-called space-specific neurons are shared in a common brainstem pathway, which then splits at the level of the inferior colliculus (IC) such that the last computational stage is thought to be duplicated. The study presented here addresses whether the space-specific neurons in OT and AAr are indeed partially independent of each other by using anatomical methods more precise than those used in previous studies. Specifically, projection neurons in IC were retrogradely labelled with injections of fluorescein- and rhodamine-conjugated dextran amines into OT and nucleus ovoidalis (OV), the thalamic nucleus leading to AAr. By labelling the OT-projecting and OV-projecting neurons in the same owl, it was confirmed that neurons in IC project to either OV or OT but not both. However, although a segregation was generally observed between the medially positioned OV-projecting neurons and the laterally positioned OT-projecting neurons, there was also a slight overlap between the two populations. Moreover, electrolytic lesions demarcating physiological tuning properties indicate that many OV-projecting neurons are within the area containing space-specific neurons. These results highlight the need for more detailed studies elucidating the microcircuitry and corresponding physiology of IC, such as have been done in the cortices of the mammalian cerebellum and cerebrum. PMID:16175562

  16. A large family of anti-activators accompanying XylS/AraC family regulatory proteins.

    PubMed

    Santiago, Araceli E; Yan, Michael B; Tran, Minh; Wright, Nathan; Luzader, Deborah H; Kendall, Melissa M; Ruiz-Perez, Fernando; Nataro, James P

    2016-07-01

    AraC Negative Regulators (ANR) suppress virulence genes by directly down-regulating AraC/XylS members in Gram-negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR-activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC-like member AggR. ANR-AggR binding disrupted AggR dimerization and prevented AggR-DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α-helices. Site-directed mutagenesis studies suggest that at least predicted α-helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners. PMID:27038276

  17. Reversible Unfolding of Rhomboid Intramembrane Proteases.

    PubMed

    Panigrahi, Rashmi; Arutyunova, Elena; Panwar, Pankaj; Gimpl, Katharina; Keller, Sandro; Lemieux, M Joanne

    2016-03-29

    Denaturant-induced unfolding of helical membrane proteins provides insights into their mechanism of folding and domain organization, which take place in the chemically heterogeneous, anisotropic environment of a lipid membrane. Rhomboid proteases are intramembrane proteases that play key roles in various diseases. Crystal structures have revealed a compact helical bundle with a buried active site, which requires conformational changes for the cleavage of transmembrane substrates. A dimeric form of the rhomboid protease has been shown to be important for activity. In this study, we examine the mechanism of refolding for two distinct rhomboids to gain insight into their secondary structure-activity relationships. Although helicity is largely abolished in the unfolded states of both proteins, unfolding is completely reversible for HiGlpG but only partially reversible for PsAarA. Refolding of both proteins results in reassociation of the dimer, with a 90% regain of catalytic activity for HiGlpG but only a 70% regain for PsAarA. For both proteins, a broad, gradual transition from the native, folded state to the denatured, partly unfolded state was revealed with the aid of circular dichroism spectroscopy as a function of denaturant concentration, thus arguing against a classical two-state model as found for many globular soluble proteins. Thermal denaturation has irreversible destabilizing effects on both proteins, yet reveals important functional details regarding substrate accessibility to the buried active site. This concerted biophysical and functional analysis demonstrates that HiGlpG, with a simple six-transmembrane-segment organization, is more robust than PsAarA, which has seven predicted transmembrane segments, thus rendering HiGlpG amenable to in vitro studies of membrane-protein folding. PMID:27028647

  18. New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle

    PubMed Central

    Evans, Ann E.; Tripathi, Abhishek; LaPorte, Heather M.; Brueggemann, Lioubov I.; Singh, Abhay Kumar; Albee, Lauren J.; Byron, Kenneth L.; Tarasova, Nadya I.; Volkman, Brian F.; Cho, Thomas Yoonsang; Gaponenko, Vadim; Majetschak, Matthias

    2016-01-01

    Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α1A/B-AR heteromers are important for α1-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca2+-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α1A-AR heteromers are important for intrinsic α1-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC. PMID:27331810

  19. Understanding and identifying amino acid repeats.

    PubMed

    Luo, Hong; Nijveen, Harm

    2014-07-01

    Amino acid repeats (AARs) are abundant in protein sequences. They have particular roles in protein function and evolution. Simple repeat patterns generated by DNA slippage tend to introduce length variations and point mutations in repeat regions. Loss of normal and gain of abnormal function owing to their variable length are potential risks leading to diseases. Repeats with complex patterns mostly refer to the functional domain repeats, such as the well-known leucine-rich repeat and WD repeat, which are frequently involved in protein–protein interaction. They are mainly derived from internal gene duplication events and stabilized by ‘gate-keeper’ residues, which play crucial roles in preventing inter-domain aggregation. AARs are widely distributed in different proteomes across a variety of taxonomic ranges, and especially abundant in eukaryotic proteins. However, their specific evolutionary and functional scenarios are still poorly understood. Identifying AARs in protein sequences is the first step for the further investigation of their biological function and evolutionary mechanism. In principle, this is an NP-hard problem, as most of the repeat fragments are shaped by a series of sophisticated evolutionary events and become latent periodical patterns. It is not possible to define a uniform criterion for detecting and verifying various repeat patterns. Instead, different algorithms based on different strategies have been developed to cope with different repeat patterns. In this review, we attempt to describe the amino acid repeat-detection algorithms currently available and compare their strategies based on an in-depth analysis of the biological significance of protein repeats. PMID:23418055

  20. Prediction of esophageal varices and variceal hemorrhage in patients with acute upper gastrointestinal bleeding.

    PubMed

    Rockey, Don C; Elliott, Alan; Lyles, Thomas

    2016-03-01

    In patients with upper gastrointestinal bleeding (UGIB), identifying those with esophageal variceal hemorrhage prior to endoscopy would be clinically useful. This retrospective study of a large cohort of patients with UGIB used logistic regression analyses to evaluate the platelet count, aspartate aminotransferase (AST) to platelet ratio index (APRI), AST to alanine aminotransferase (ALT) ratio (AAR) and Lok index (all non-invasive blood markers) as predictors of variceal bleeding in (1) all patients with UGIB and (2) patients with cirrhosis and UGIB. 2233 patients admitted for UGIB were identified; 1034 patients had cirrhosis (46%) and of these, 555 patients (54%) had acute UGIB due to esophageal varices. In all patients with UGIB, the platelet count (cut-off 122,000/mm(3)), APRI (cut-off 5.1), AAR (cut-off 2.8) and Lok index (cut-off 0.9) had area under the curve (AUC)s of 0.80 0.82, 0.64, and 0.80, respectively, for predicting the presence of varices prior to endoscopy. To predict varices as the culprit of bleeding, the platelet count (cut-off 69,000), APRI (cut-off 2.6), AAR (cut-off 2.5) and Lok Index (0.90) had AUCs of 0.76, 0.77, 0.57 and 0.73, respectively. Finally, in patients with cirrhosis and UGIB, logistic regression was unable to identify optimal cut-off values useful for predicting varices as the culprit bleeding lesion for any of the non-invasive markers studied. For all patients with UGIB, non-invasive markers appear to differentiate patients with varices from those without varices and to identify those with a variceal culprit lesion. However, these markers could not distinguish between a variceal culprit and other lesions in patients with cirrhosis. PMID:26912006

  1. New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle.

    PubMed

    Evans, Ann E; Tripathi, Abhishek; LaPorte, Heather M; Brueggemann, Lioubov I; Singh, Abhay Kumar; Albee, Lauren J; Byron, Kenneth L; Tarasova, Nadya I; Volkman, Brian F; Cho, Thomas Yoonsang; Gaponenko, Vadim; Majetschak, Matthias

    2016-01-01

    Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α1A/B-AR heteromers are important for α₁-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca(2+)-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α1A-AR heteromers are important for intrinsic α₁-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC. PMID:27331810

  2. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis

    PubMed Central

    Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan

    2015-01-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  3. Intracellular Adenosine Inhibits IgE-Dependent Degranulation of Human Skin Mast Cells

    PubMed Central

    Gomez, Gregorio; Nardone, Vincent; Lotfi-Emran, Sahar; Zhao, Wei; Schwartz, Lawrence B.

    2015-01-01

    Purpose Adenosine (ADO) can enhance and inhibit mast cell degranulation. Potentiation of degranulation occurs at relatively low concentrations of ADO (10−6–10−5 M) through triggering of A3AR, whereas, inhibition occurs at higher concentrations of ADO reportedly through triggering of A2aAR. However, the discrepancy in the concentration of ADO that inhibits degranulation and that required to trigger ADORs suggests a different mechanism. The purpose of this study is to determine the mechanism by which ADO inhibits human mast cell degranulation. Methods We compare the effectiveness of A2aAR specific antagonist ZM241385 and equilibrative nucleoside transporter inhibitors Dipyridamole and NBMPR in preventing ADO-mediated inhibition of FcεRI-induced degranulation of human skin mast cells (hSMCs). Western blotting is done to analyze the effect of ADO on FcεRI-induced Syk phosphorylation. Results Dipyridamole and NBMPR completely and dose-dependently prevented ADO from inhibiting FcεRI-induced degranulation in all hSMC preparations. In contrast, ZM241385 at 10−5 M was effective in only 3 of 10 hSMC preparations. Moreover, NBMPR was effective even in those hSMC preparations not responsive to ZM241385. ADO inhibited degranulation induced by FcεRI crosslinking, but not that induced by complement component 5a (C5a), Substance P or calcium ionophore. Accordingly, ADO significantly attenuated FcεRI-induced phosphorylation of Syk at the critical activating tyrosine (Y525). Conclusion Blocking the influx of ADO, but not A2aAR signals, is necessary and sufficient to prevent ADO from inhibiting FcεRI-induced mast cell degranulation. Thus, ADO specifically inhibits FcεRI-induced degranulation of hSMCs primarily by an intracellular mechanism that requires its influx via equilibrative nucleoside transporter 1 (ENT1). PMID:24122028

  4. [Adenosine A2A receptor as a drug target for treatment of sepsis].

    PubMed

    Sivak, K V; Vasin, A V; Egorov, V V; Tsevtkov, V B; Kuzmich, N N; Savina, V A; Kiselev, O I

    2016-01-01

    Sepsis is a generalized infection accompanied by response of the body that manifests in a clinical and laboratory syndrome, namely, in the systemic inflammatory response syndrome (SIRS) from the organism to the infection. Although sepsis is a widespread and life-threatening disease, the assortment of drugs for its treatment is mostly limited by antibiotics. Therefore, the search for new cellular targets for drug therapy of sepsis is an urgent task of modern medicine and pharmacology. One of the most promising targets is the adenosine A(2A) receptor (A(2A)AR). The activation of this receptor, which is mediated by extracellular adenosine, manifests in almost all types of immune cells (lymphocytes, monocytes, macrophages, and dendritic cells) and results in reducing the severity of inflammation and reperfusion injury in various tissues. The activation of adenosine A(2A) receptor inhibits the proliferation of T cells and production of proinflammatory cytokines, which contributes to the activation of the synthesis of anti-inflammatory cytokines, thereby suppressing the systemic response. For this reason, various selective A(2A)AR agonists and antagonists may be considered to be drug candidates for sepsis pharmacotherapy. Nevertheless, they remain only efficient ligands and objects of pre-clinical and clinical trials. This review examines the molecular mechanisms of inflammatory response in sepsis and the structure and functions of A(2A)AR and its role in the pathogenesis of sepsis, as well as examples of using agonists and antagonists of this receptor for the treatment of SIRS and sepsis. PMID:27239843

  5. The Roles of Compensatory Evolution and Constraint in Aminoacyl tRNA Synthetase Evolution

    PubMed Central

    Adrion, Jeffrey R.; White, P. Signe; Montooth, Kristi L.

    2016-01-01

    Mitochondrial protein translation requires interactions between transfer RNAs encoded by the mitochondrial genome (mt-tRNAs) and mitochondrial aminoacyl tRNA synthetase proteins (mt-aaRS) encoded by the nuclear genome. It has been argued that animal mt-tRNAs have higher deleterious substitution rates relative to their nuclear-encoded counterparts, the cytoplasmic tRNAs (cyt-tRNAs). This dynamic predicts elevated rates of compensatory evolution of mt-aaRS that interact with mt-tRNAs, relative to aaRS that interact with cyt-tRNAs (cyt-aaRS). We find that mt-aaRS do evolve at significantly higher rates (exemplified by higher dN and dN/dS) relative to cyt-aaRS, across mammals, birds, and Drosophila. While this pattern supports a model of compensatory evolution, the level at which a gene is expressed is a more general predictor of protein evolutionary rate. We find that gene expression level explains 10–56% of the variance in aaRS dN/dS, and that cyt-aaRS are more highly expressed in addition to having lower dN/dS values relative to mt-aaRS, consistent with more highly expressed genes being more evolutionarily constrained. Furthermore, we find no evidence of positive selection acting on either class of aaRS protein, as would be expected under a model of compensatory evolution. Nevertheless, the signature of faster mt-aaRS evolution persists in mammalian, but not bird or Drosophila, lineages after controlling for gene expression, suggesting some additional effect of compensatory evolution for mammalian mt-aaRS. We conclude that gene expression is the strongest factor governing differential amino acid substitution rates in proteins interacting with mitochondrial versus cytoplasmic factors, with important differences in mt-aaRS molecular evolution among taxonomic groups. PMID:26416980

  6. Inhibition of α2A-Adrenoceptors Ameliorates Dextran Sulfate Sodium-Induced Acute Intestinal Inflammation in Mice.

    PubMed

    Zádori, Zoltán S; Tóth, Viktória E; Fehér, Ágnes; Al-Khrasani, Mahmoud; Puskár, Zita; Kozsurek, Márk; Timár, Júlia; Tábi, Tamás; Helyes, Zsuzsanna; Hein, Lutz; Holzer, Peter; Gyires, Klára

    2016-09-01

    It has been hypothesized that α2-adrenoceptors (α2-ARs) may be involved in the pathomechanism of colitis; however, the results are conflicting because both aggravation and amelioration of colonic inflammation have been described in response to α2-AR agonists. Therefore, we aimed to analyze the role of α2-ARs in acute murine colitis. The experiments were carried out in wild-type, α2A-, α2B-, and α2C-AR knockout (KO) C57BL/6 mice. Colitis was induced by dextran sulfate sodium (DSS, 2%); alpha2-AR ligands were injected i.p. The severity of colitis was determined both macroscopically and histologically. Colonic myeloperoxidase (MPO) and cytokine levels were measured by enzyme-linked immunosorbent assay and proteome profiler array, respectively. The nonselective α2-AR agonist clonidine induced a modest aggravation of DSS-induced colitis. It accelerated the disease development and markedly enhanced the weight loss of animals, but did not influence the colon shortening, tissue MPO levels, or histologic score. Clonidine induced similar changes in α2B- and α2C-AR KO mice, whereas it failed to affect the disease activity index scores and caused only minor weight loss in α2A-AR KO animals. In contrast, selective inhibition of α2A-ARs by BRL 44408 significantly delayed the development of colitis; reduced the colonic levels of MPO and chemokine (C-C motif) ligand 3, chemokine (C-X-C motif) ligand 2 (CXCL2), CXCL13, and granulocyte-colony stimulating factor; and elevated that of tissue inhibitor of metalloproteinases-1. In this work, we report that activation of α2-ARs aggravates murine colitis, an effect mediated by the α2A-AR subtype, and selective inhibition of these receptors reduces the severity of gut inflammation. PMID:27418171

  7. Command Center Training Tool (C2T2)

    NASA Technical Reports Server (NTRS)

    Jones, Phillip; Drucker, Nich; Mathews, Reejo; Stanton, Laura; Merkle, Ed

    2012-01-01

    This abstract presents the training approach taken to create a management-centered, experiential learning solution for the Virginia Port Authority's Port Command Center. The resultant tool, called the Command Center Training Tool (C2T2), follows a holistic approach integrated across the training management cycle and within a single environment. The approach allows a single training manager to progress from training design through execution and AAR. The approach starts with modeling the training organization, identifying the organizational elements and their individual and collective performance requirements, including organizational-specific performance scoring ontologies. Next, the developer specifies conditions, the problems, and constructs that compose exercises and drive experiential learning. These conditions are defined by incidents, which denote a single, multi-media datum, and scenarios, which are stories told by incidents. To these layered, modular components, previously developed meta-data is attached, including associated performance requirements. The components are then stored in a searchable library An event developer can create a training event by searching the library based on metadata and then selecting and loading the resultant modular pieces. This loading process brings into the training event all the previously associated task and teamwork material as well as AAR preparation materials. The approach includes tools within an integrated management environment that places these materials at the fingertips of the event facilitator such that, in real time, the facilitator can track training audience performance and resultantly modify the training event. The approach also supports the concentrated knowledge management requirements for rapid preparation of an extensive AAR. This approach supports the integrated training cycle and allows a management-based perspective and advanced tools, through which a complex, thorough training event can be developed.

  8. Overdeepened glacigenic landforms in Lake Thun (Switzerland) revealed by a multichannel reflection seismic survey

    NASA Astrophysics Data System (ADS)

    Fabbri, Stefano; Herwegh, Marco; Schlunegger, Fritz; Hübscher, Christian; Weiss, Benedikt J.; Schmelzbach, Cédric; Horstmeyer, Heinrich; Buechi, Marius W.; Anselmetti, Flavio S.

    2016-04-01

    Recently acquired high-resolution multibeam bathymetry, in combination with a 2D multichannel reflection seismic campaign on perialpine Lake Thun (Switzerland) reveals new insights into the diverse geometry of the lake basin and a so far unknown subaquatic moraine crest with unprecedented clarity. These new data will improve our comprehension concerning the retreat phases of the Aare glacier, the morphology of its proximal deposits and the facies architecture of the subglacial units. The overdeepened basin of Lake Thun was formed by a combination of tectonically predefined weak zones and glacial erosion during the last glacial periods. The new data indicate that below the outermost edge of a morphologically distinct platform in the south eastern part of the lake basin, a ridge structure marked by strong reflection amplitudes occurs. This structure is interpreted as a subaquatic terminal moraine crest, most likely created by a slightly advancing or stagnant grounded Aare glacier during its major retreating phase. The terminal moraine smoothly transforms downstream into well distinguishable foresets with internally recognisable layering, which dip steeply towards the deepest part of the basin, eventually transforming into bottomsets. This depositional sequence formed by the fore- and bottomsets represents ˜50% of the overall sediment volume that fills the basin and was deposited while the glacier was stagnant, interpreted to represent a rather short period of time of a few hundreds of years. This sequence is overlain by lacustrine deposits formed by late-glacial and Holocene laminated muds comprising intercalated turbidites (Wirth et al. 2011). Little is known about the exact timing and behaviour of retreating glaciers between their recessional phase from the Alpine foreland to the deglaciation of the inner-Alpine ice cap, mostly due to the lack of well-developed moraines that indicate glacial stabilization or slight readvance. Findings from pollen analyses by

  9. Spatial and temporal modelling of fluvial aggradation in the Hasli Valley (Swiss Alps) during the last 1300 years

    NASA Astrophysics Data System (ADS)

    Llorca, Jaime; Schulte, Lothar; Carvalho, Filipe

    2016-04-01

    The Haslital delta (upper Aare River catchment, Bernese Alps) progradated into the Lake Brienz after the retreat of the Aare Glacier (post-LGM). Present delta plain geomorphology and spatial distribution of sedimentary facies result from historical fluvial dynamics and aggradation. Over centuries, local communities have struggled to control the Aare floods and to mitigate their effects on the floodplain (by means of raising artificial levees, channelizing the course, creating an underground drainage network, constructing dams at the basin headwaters). This study focuses on the spatial and temporal evolution of sediment dynamics of the floodplain by analyzing fluvial sedimentary records . The internal variability of lithostratigraphic sequences is a key issue to understand hydrological processes in the basin under the effect of environmental and anthropogenic changes of the past. The floodplain lithostratigraphy was reconstructed by coring alongside four cross-sections; each one is composed of more than 25 shallow boreholes (2 m deep) and two long drillings (variable depth, up to 9 m). The chronostratigraphical models were obtained by AMS 14C dating, and information of paleofloods and channel migration were reconstructed from historical sources (Schulte et al., 2015). The identification of different sedimentary facies, associated with the fluvial architecture structures, provides information on variations of vertical and lateral accretion processes (Houben, 2007). The location and geometry of buried channel-levee facies (gravel and coarse sand layers) indicate a significant mobility of the riverbed of the Hasli-Aare river, following an oscillatory pattern during the last millennia. Furthermore, fine sedimentary deposits and peat layers represent the existence of stable areas where floods have a low incidence. Once the different types of deposits were identified, aggradation rates were estimated in order to determine the spatial variability of the accumulation

  10. Testing of the Strutjet RBCC Engine

    NASA Technical Reports Server (NTRS)

    Bulman, Mel; Neill, Todd; Yam, Clement

    1999-01-01

    The testing of the Strutjet Rocket-Based Combined Cycle (RBCC) engine is described in this presentation. Since 1996 Aerojet has conducted thousands of tests on its Strutjet RBCC Engine. The Strutjet is specifically designed as an RBCC engine. The tests included: (1) Inlet, (2) Rocket Checkouts, (3) Direct Connect Mach 6 and 8, and (4) Freejet M = 0, 2.4, 4.1. The modes tested include: (1) Air Augmented Rocket (AAR), (2) Ramjet (3) Scramjet (4) Scram/Rocket (5) Ascent/Rocket. The Strutjet RBCC engine has been tested across the complete airbreathing trajectory. The presentation shows the results of the tests, through diagrams, charts and pictures.

  11. Might adrenergic alpha2C-agonists/alpha2A-antagonists become novel therapeutic tools for pain treatment with morphine?

    PubMed

    Cardinaletti, Claudia; Mattioli, Laura; Ghelfi, Francesca; Del Bello, Fabio; Giannella, Mario; Bruzzone, Ariana; Paris, Hervé; Perfumi, Marina; Piergentili, Alessandro; Quaglia, Wilma; Pigini, Maria

    2009-11-26

    The imidazoline nucleus linked in position 2 via an oxyethylene bridge to a phenyl ring carrying an ortho substituent of moderate steric bulk provided alpha(2)-adrenergic (AR) ligands endowed with significant alpha(2C)-agonism/alpha(2A)-antagonism. Similar behavior was displayed by cirazoline (12). For their positive morphine analgesia modulation (due to alpha(2C)-AR stimulation) and sedation overcoming (due to alpha(2A)-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine. PMID:19886609

  12. Amelie: A Recombinant Computing Framework for Ambient Awareness

    NASA Astrophysics Data System (ADS)

    Metaxas, Georgios; Markopoulos, Panos; Aarts, Emile

    This paper presents Amelie, a service oriented framework that supports the implementation of awareness systems. Amelie adopts the tenets of Recombinant computing to address an important non-functional requirement for Ambient Intelligence software, namely the heterogeneous combination of services and components. Amelie is founded upon FN-AAR an abstract model of Awareness Systems which enables the immediate expression and implementation of socially salient requirements, such as symmetry and social translucence. We discuss the framework and show how system behaviours can be specified using the Awareness Mark-up Language AML.

  13. Equilibrium Line Altitude fluctuations at HualcaHualca volcano (southern Peru).

    NASA Astrophysics Data System (ADS)

    Alcalá, Jesus; Palacios, David; Juan Zamorano, Jose

    2015-04-01

    Interest in Andean glaciers has substantially increased during the last decades, due to its high sensitivity to climate fluctuations. In this sense, Equilibrium Line Altitude (ELA) is a reliable indicator of climate variability that has been frequently used to reconstruct palaeoenvironmental conditions at different temporal and spatial scales. However, the number of sites with ELA reconstructions is still insufficient to determine patterns in tropical climate or estimations of atmospheric cooling since the Last Glacial Maximum. The main purpose of this study is to contribute in resolving tropical climate evolution through ELA calculations on HualcaHualca (15° 43' S; 71° 52' W; 6,025 masl), a large andesitic stratovolcano located in the south-western Peruvian Andes approximately 70 km north-west of Arequipa. We applied Terminus Headwall Altitude Ratio (THAR) with 0.2; 0.4; 0.5; 0.57 ratios, Accumulation Area Ratio (AAR) and Accumulation Area Balance Ratio (AABR) methods in four valleys of HualcaHualca volcano: Huayuray (north side), Pujro Huayjo (southwest side), Mollebaya (east side) and Mucurca (west side). To estimate ELA depression, we calculated the difference between the ELA on 1955 with its position in the Maximum Glacier Extent (MGE), Tardiglacial phases, little Ice Age (LIA) and 2000. Paleotemperature reconstructions derived from vertical temperature gradient 6.5° C / 1 km, based on GODDARD global observation system considered the most appropriate model for arid Andes. During MGE, the ELA was located between 5,005 (AABR) and 5,215 (AAR 0.67) masl. But in 1955, ELA rose to 5,685 (AABR) - 5,775 (AAR 0.67) masl. The ELA depression between those two phases is 560 - 680 m that implies a temperature decrease of 3.5° - 4.4° C. The experimental process based in the use and contrast of different ELA reconstruction techniques applied in this study suggests that THAR (0.57), AAR (0.67) or AABR are the most consistent procedures for HualcaHualca glaciers, while

  14. Quantifying the Area-at-Risk in Reperfused STEMI Patients Using Hybrid Cardiac PET-MR Imaging

    PubMed Central

    Bulluck, Heerajnarain; White, Steven K.; Fröhlich, Georg M.; Casson, Steven G.; O’Meara, Celia; Newton, Ayla; Nicholas, Jennifer; Weale, Peter; Wan, Simon M.Y.; Sirker, Alex; Moon, James C.; Yellon, Derek M.; Groves, Ashley; Menezes, Leon; Hausenloy, Derek J

    2016-01-01

    Background Hybrid Positron Emission Tomography and Magnetic Resonance (PET-MR) allows the advantages of MR in tissue characterizing the myocardium to be combined with the unique metabolic insights of PET. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area-at-risk (AAR) delineated by T2-mapping in ST-segment elevation myocardial infarction (STEMI) patients. Methods and Results Hybrid PET-MR using 18F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 STEMI patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (LGE) (37.2±11.6% versus 22.3±11.7%; P<0.001), and closely matched the AAR by T2-mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R 0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared to the acute scans (19.5 [6.3-31.8]% versus 44.0 [21.3-55.3]%, P=0.002), and closely correlated with the areas of LGE (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of LGE and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. Conclusions Hybrid PET-MR in the reperfused STEMI patient showed reduced myocardial glucose uptake within the AAR and closely matched the AAR delineated by T2-mapping. FDG uptake, as well as transmural extent of LGE acutely can identify viable myocardial segments. PMID:26926269

  15. Mutual design: Overhead transmission lines and railroad facilities: Susceptibility program: Final report

    SciTech Connect

    Frazier, M.J.; Little, D.R.

    1989-07-01

    The sharing of common corridors by electric power transmission lines and railroad facilities can result in the coupling of unwanted electromagnetic energy from the power lines into nearby railroad systems. The coupling can result in voltage being induced onto the railroad system conductors that may compromise the inherent safety and reliability of the railroad signalling system. This broad-scoped research program, which is co-sponsored by EPRI and the AAR, is addressing the problem from two directions. This two volume report describes a Phase 1 effort to develop the methods and techniques for quantifying the signal system response to interference. 54 figs., 7 tabs.

  16. Learning to smell danger: acquired associative representation of threat in the olfactory cortex

    PubMed Central

    Li, Wen

    2014-01-01

    Neuroscience research over the past few decades has reached a strong consensus that the amygdala plays a key role in emotion processing. However, many questions remain unanswered, especially concerning emotion perception. Based on mnemonic theories of olfactory perception and in light of the highly associative nature of olfactory cortical processing, here I propose a sensory cortical model of olfactory threat perception (i.e., sensory-cortex-based threat perception): the olfactory cortex stores threat codes as acquired associative representations (AARs) formed via aversive life experiences, thereby enabling encoding of threat cues during sensory processing. Rodent and human research in olfactory aversive conditioning was reviewed, indicating learning-induced plasticity in the amygdala and the olfactory piriform cortex. In addition, as aversive learning becomes consolidated in the amygdala, the associative olfactory (piriform) cortex may undergo (long-term) plastic changes, resulting in modified neural response patterns that underpin threat AARs. This proposal thus brings forward a sensory cortical pathway to threat processing (in addition to amygdala-based processes), potentially accounting for an alternative mechanism underlying the pathophysiology of anxiety and depression. PMID:24778610

  17. Sediment accumulation, stratigraphic order, and the extent of time-averaging in lagoonal sediments: a comparison of 210Pb and 14C/amino acid racemization chronologies

    NASA Astrophysics Data System (ADS)

    Kosnik, Matthew A.; Hua, Quan; Kaufman, Darrell S.; Zawadzki, Atun

    2015-03-01

    Carbon-14 calibrated amino acid racemization (14C/AAR) data and lead-210 (210Pb) data are used to examine sediment accumulation rates, stratigraphic order, and the extent of time-averaging in sediments collected from the One Tree Reef lagoon (southern Great Barrier Reef, Australia). The top meter of lagoonal sediment preserves a stratigraphically ordered deposit spanning the last 600 yrs. Despite different assumptions, the 210Pb and 14C/AAR chronologies are remarkably similar indicating consistency in sedimentary processes across sediment grain sizes spanning more than three orders of magnitude (0.1-10 mm). Estimates of long-term sediment accumulation rates range from 2.2 to 1.2 mm yr-1. Molluscan time-averaging in the taphonomically active zone is 19 yrs, whereas below the depth of final burial (~15 cm), it is ~110 yrs/5 cm layer. While not a high-resolution paleontological record, this reef lagoon sediment is suitable for paleoecological studies spanning the period of Western colonization and development. This sedimentary deposit, and others like it, should be useful, albeit not ideal, for quantifying anthropogenic impacts on coral reef systems.

  18. A Comparative Study on Improved Arrhenius-Type and Artificial Neural Network Models to Predict High-Temperature Flow Behaviors in 20MnNiMo Alloy

    PubMed Central

    Yu, Chun-tang; Liu, Ying-ying; Xia, Yu-feng

    2014-01-01

    The stress-strain data of 20MnNiMo alloy were collected from a series of hot compressions on Gleeble-1500 thermal-mechanical simulator in the temperature range of 1173∼1473 K and strain rate range of 0.01∼10 s−1. Based on the experimental data, the improved Arrhenius-type constitutive model and the artificial neural network (ANN) model were established to predict the high temperature flow stress of as-cast 20MnNiMo alloy. The accuracy and reliability of the improved Arrhenius-type model and the trained ANN model were further evaluated in terms of the correlation coefficient (R), the average absolute relative error (AARE), and the relative error (η). For the former, R and AARE were found to be 0.9954 and 5.26%, respectively, while, for the latter, 0.9997 and 1.02%, respectively. The relative errors (η) of the improved Arrhenius-type model and the ANN model were, respectively, in the range of −39.99%∼35.05% and −3.77%∼16.74%. As for the former, only 16.3% of the test data set possesses η-values within ±1%, while, as for the latter, more than 79% possesses. The results indicate that the ANN model presents a higher predictable ability than the improved Arrhenius-type constitutive model. PMID:24688358

  19. 3D automatic anatomy recognition based on iterative graph-cut-ASM

    NASA Astrophysics Data System (ADS)

    Chen, Xinjian; Udupa, Jayaram K.; Bagci, Ulas; Alavi, Abass; Torigian, Drew A.

    2010-02-01

    We call the computerized assistive process of recognizing, delineating, and quantifying organs and tissue regions in medical imaging, occurring automatically during clinical image interpretation, automatic anatomy recognition (AAR). The AAR system we are developing includes five main parts: model building, object recognition, object delineation, pathology detection, and organ system quantification. In this paper, we focus on the delineation part. For the modeling part, we employ the active shape model (ASM) strategy. For recognition and delineation, we integrate several hybrid strategies of combining purely image based methods with ASM. In this paper, an iterative Graph-Cut ASM (IGCASM) method is proposed for object delineation. An algorithm called GC-ASM was presented at this symposium last year for object delineation in 2D images which attempted to combine synergistically ASM and GC. Here, we extend this method to 3D medical image delineation. The IGCASM method effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. We propose a new GC cost function, which effectively integrates the specific image information with the ASM shape model information. The proposed methods are tested on a clinical abdominal CT data set. The preliminary results show that: (a) it is feasible to explicitly bring prior 3D statistical shape information into the GC framework; (b) the 3D IGCASM delineation method improves on ASM and GC and can provide practical operational time on clinical images.

  20. Learning to smell danger: acquired associative representation of threat in the olfactory cortex.

    PubMed

    Li, Wen

    2014-01-01

    Neuroscience research over the past few decades has reached a strong consensus that the amygdala plays a key role in emotion processing. However, many questions remain unanswered, especially concerning emotion perception. Based on mnemonic theories of olfactory perception and in light of the highly associative nature of olfactory cortical processing, here I propose a sensory cortical model of olfactory threat perception (i.e., sensory-cortex-based threat perception): the olfactory cortex stores threat codes as acquired associative representations (AARs) formed via aversive life experiences, thereby enabling encoding of threat cues during sensory processing. Rodent and human research in olfactory aversive conditioning was reviewed, indicating learning-induced plasticity in the amygdala and the olfactory piriform cortex. In addition, as aversive learning becomes consolidated in the amygdala, the associative olfactory (piriform) cortex may undergo (long-term) plastic changes, resulting in modified neural response patterns that underpin threat AARs. This proposal thus brings forward a sensory cortical pathway to threat processing (in addition to amygdala-based processes), potentially accounting for an alternative mechanism underlying the pathophysiology of anxiety and depression. PMID:24778610

  1. Battlefield Documentation of Tactical Combat Casualty Care in Afghanistan.

    PubMed

    Robinson, John B; Smith, Michael P; Gross, Kirby R; Sauer, Samual W; Geracci, James J; Day, Charlie D; Kotwal, Russ S

    2016-01-01

    Performance improvement is reliant on information and data, as you cannot improve what you do not measure. The US military went to war in 2001 without an integrated trauma care system to collect and analyze combat casualty care data. By 2006, the conflict in Afghanistan began appreciating the capture and consolidation of hospital care documentation into the Department of Defense Trauma Registry. In contrast, a paucity of documentation has existed for prehospital or tactical combat casualty care (TCCC). Using the 75th Ranger casualty documentation model established in 2005, the Joint Trauma System developed a casualty data collection system for prehospital care using the TCCC Card, the TCCC After Action Report (AAR), and the Prehospital Trauma Registry. In 2013, this system was mandated for use by US forces in Afghanistan. The Joint Trauma System also created and deployed a prehospital team to be an integral part of the Joint Theater Trauma System in Afghanistan. This prehospital team provided prehospital training and facilitated prehospital data capture. Described and analyzed in this report are prehospital data captured in Afghanistan from 2013 to 2014 using the TCCC Card and the TCCC AAR. PMID:27215873

  2. Adding intelligent services to an object oriented system

    NASA Technical Reports Server (NTRS)

    Robideaux, Bret R.; Metzler, Theodore A.

    1994-01-01

    As today's software becomes increasingly complex, the need grows for intelligence of one sort or another to becomes part of the application, often an intelligence that does not readily fit the paradigm of one's software development. There are many methods of developing software, but at this time, the most promising is the object oriented (OO) method. This method involves an analysis to abstract the problem into separate 'objects' that are unique in the data that describe them and the behavior that they exhibit, and eventually to convert this analysis into computer code using a programming language that was designed (or retrofitted) for OO implementation. This paper discusses the creation of three different applications that are analyzed, designed, and programmed using the Shlaer/Mellor method of OO development and C++ as the programming language. All three, however, require the use of an expert system to provide an intelligence that C++ (or any other 'traditional' language) is not directly suited to supply. The flexibility of CLIPS permitted us to make modifications to it that allow seamless integration with any of our applications that require an expert system. We illustrate this integration with the following applications: (1) an after action review (AAR) station that assists a reviewer in watching a simulated tank battle and developing an AAR to critique the performance of the participants in the battle; (2) an embedded training system and over-the-shoulder coach for howitzer crewmen; and (3) a system to identify various chemical compounds from their infrared absorption spectra.

  3. Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective α1A-Adrenoceptor Antagonists.

    PubMed

    Zhao, Fei; Li, Jing; Chen, Ying; Tian, Yanxin; Wu, Chenglin; Xie, Yanan; Zhou, Yu; Wang, Jiang; Xie, Xin; Liu, Hong

    2016-04-28

    A series of indoline and indole derivatives were designed, synthesized, and evaluated as selective α1A-adrenergic receptor (α1A-AR) antagonists for the treatment of benign prostatic hyperplasia (BPH). In this study, two highly selective and potent α1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM, α1B/α1A = 640.1, α1D/α1A = 408.2) and (R)-23l (IC50 = 1.9 nM, α1B/α1A = 1506, α1D/α1A = 249.6), which exhibited similar activities and better selectivities in cell-based calcium assays as compared with the marketed drug silodosin (IC50 = 1.9 nM, α1B/α1A = 285.9, α1D/α1A = 14.4), were identified. In the functional assays with isolated rat tissues, compounds (R)-14r and (R)-23l also showed high potency and uroselectivity. Most importantly, (R)-14r and (R)-23l can significantly decrease the micturition frequency and increase the mean voided volume of the BPH rats in a dose-dependent manner, making them worthy of further investigation for the development of anti-BPH agents. PMID:27031406

  4. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins

    SciTech Connect

    Sung, Uhna; Jennings, Jennifer L.; Link, Andrew J.; Blakely, Randy D.; E-mail: andy.blakely@vanderbilt.edu

    2005-08-05

    The norepinephrine transporter (NET) terminates noradrenergic signals by clearing released NE at synapses. NET regulation by receptors and intracellular signaling pathways is supported by a growing list of associated proteins including syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and Hic-5. In the present study, we sought evidence for additional partnerships by mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our initial proteomic analyses reveal multiple peptides derived from hNET, peptides arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from 14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co-immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via a fusion pull-down approach, implicating specifically the hNET NH{sub 2}-terminus for interactions. The transporter complexes described likely support mechanisms regulating transporter activity, localization, and trafficking.

  5. The crystal structure of yeast mitochondrial ThrRS in complex with the canonical threonine tRNA.

    PubMed

    Holman, Kaitlyn M; Wu, Jiang; Ling, Jiqiang; Simonović, Miljan

    2016-02-18

    In mitochondria of Saccharomyces cerevisiae, a single aminoacyl-tRNA synthetase (aaRS), MST1, aminoacylates two isoacceptor tRNAs, tRNA1(Thr) and tRNA2(Thr), that harbor anticodon loops of different size and sequence. As a result of this promiscuity, reassignment of the CUN codon box from leucine to threonine is facilitated. However, the mechanism by which a single aaRS binds distinct anticodon loops with high specificity is not well understood. Herein, we present the crystal structure of MST1 in complex with the canonical tRNA2(Thr) and non-hydrolyzable analog of threonyl adenylate. Our structure reveals that the dimeric arrangement of MST1 is essential for binding the 5'-phosphate, the second base pair of the acceptor stem, the first two base pairs of the anticodon stem and the first nucleotide of the variable arm. Further, in contrast to the bacterial ortholog that 'reads' the entire anticodon sequence, MST1 recognizes bases in the second and third position and the nucleotide upstream of the anticodon sequence. We speculate that a flexible loop linking strands β4 and β5 may be allosteric regulator that establishes cross-subunit communication between the aminoacylation and tRNA-binding sites. We also propose that structural features of the anticodon-binding domain in MST1 permit binding of the enlarged anticodon loop of tRNA1(Thr). PMID:26704982

  6. Cardiorespiratory responses and reduced apneic time to cold-water face immersion after high intensity exercise.

    PubMed

    Konstantinidou, Sylvia; Soultanakis, Helen

    2016-01-01

    Apnea after exercise may evoke a neurally mediated conflict that may affect apneic time and create a cardiovascular strain. The physiological responses, induced by apnea with face immersion in cold water (10 °C), after a 3-min exercise bout, at 85% of VO2max,were examined in 10 swimmers. A pre-selected 40-s apnea, completed after rest (AAR), could not be met after exercise (AAE), and was terminated with an agonal gasp reflex, and a reduction of apneic time, by 75%. Bradycardia was evident with immersion after both, 40-s of AAR and after AAE (P<0.05). The dramatic elevation of, systolic pressure and pulse pressure, after AAE, were indicative of cardiovascular stress. Blood pressure after exercise without apnea was not equally elevated. The activation of neurally opposing functions as those elicited by the diving reflex after high intensity exercise may create an autonomic conflict possibly related to oxygen-conserving reflexes stimulated by the trigeminal nerve, and those elicited by exercise. PMID:26343750

  7. Representative rainfall thresholds for flash floods in the Cali river watershed, Colombia

    NASA Astrophysics Data System (ADS)

    Ávila, A. D.; Carvajal, Y. E.; Justino, F.

    2015-06-01

    In the 21st century, societies face a significant increase in the number of extreme hydrometeorological events associated with climate variability (CV) and/or climate change (CC). Research has recently focused on establishing adaptation and mitigation measures to counteract the effects of CV and CC, especially those associated with precipitation, such as flash floods and flooding. In this study, 27 floods, listed in the historical database of natural disasters (DesInventar), occurring between 1980 and 2012, were analyzed. Using the daily hydrometeorological data, representative rainfall thresholds were defined to predict flash floods in the hydrographic basin of the Cali River, Colombia. Antecedent rainfall (AR), or short-term rain (1, 3, 5 and 7 days), and accumulated antecedent rainfall (AAR), or long-term rain (5, 7, 10, 15, 20, 25, 30, 60 and 90 days), levels were defined. The analysis showed that the greatest determinant for the occurrence of floods is AAR, with thresholds greater than 73, 95, 124, 170, 218 and 273 mm, for 5, 7, 10, 15, 20 and 25 days, respectively. Additionally, the data showed that, historically, the greatest number of flash floods (81.7 %) occurred in the Cali River basin in the months of April, May, and June.

  8. Validation of Arabic and English versions of the ARSMA-II Acculturation Rating Scale.

    PubMed

    Jadalla, Ahlam; Lee, Jerry

    2015-02-01

    To translate and adapt the Acculturation Rating Scale of Mexican-Americans II (ARSMA-II) for Arab Americans. A multistage translation process followed by a pilot and a large study. The translated and adapted versions, Acculturation Rating Scale for Arabic Americans-II Arabic and English (ARSAA-IIA, ARSAA-IIE), were validated in a sample of 297 Arab Americans. Factor analyses with principal axis factoring extractions and direct oblimin rotations were used to identify the underlying structure of ARSAA-II. Factor analysis confirmed the underlying structure of ARSAA-II and produced two interpretable factors labeled as 'Attraction to American Culture' (AAmC) and 'Attraction to Arabic Culture' (AArC). The Cronbach's alphas of AAmC and AArC were .89 and .85 respectively. Findings support ARSAA-II A & E to assess acculturation among Arab Americans. The emergent factors of ARSAA-II support the theoretical structure of the original ARSMA-II tool and show high internal consistency. PMID:23934518

  9. Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa, Mojave Desert, California: A comparison of the applicability of radiocarbon, luminescence, terrestrial cosmogenic nuclide, electron spin resonance, U-series and amino acid racemization methods

    USGS Publications Warehouse

    Owen, L.A.; Bright, Jordon; Finkel, R.C.; Jaiswal, M.K.; Kaufman, D.S.; Mahan, S.; Radtke, U.; Schneider, J.S.; Sharp, W.; Singhvi, A.K.; Warren, C.N.

    2007-01-01

    A Late Quaternary spit-shoreline complex on the northern shore of Pleistocene Lake Mojave of southeastern California, USA was studied with the goal of comparing accelerator mass spectrometry (AMS) radiocarbon, luminescence, electron spin resonance (ESR), terrestrial cosmogenic radionuclide (TCN) surface exposure, amino acid racemization (AAR) and U-series dating methods. The pattern of ages obtained by the different methods illustrates the complexity of processes acting in the lakeshore environment and highlights the utility of a multi-method approach. TCN surface exposure ages (mostly ???20-30 ka) record the initial erosion of shoreline benches, whereas radiocarbon ages on shells (determined in this and previous studies) within the spit, supported by AAR data, record its construction at fluctuating lake levels from ???16 to 10 ka. Luminescence ages on spit sediment (???6-7 ka) and ESR ages on spit shells (???4 ka) are anomalously young relative to radiocarbon ages of shells within the same deposits. The significance of the surprisingly young luminescence ages is not clear. The younger ESR ages could be a consequence of post-mortem enrichment of U in the shells. High concentrations of detrital thorium in tufa coating spit gravels inhibited the use of single-sample U-series dating. Detailed comparisons such as this provide one of the few means of assessing the accuracy of Quaternary dating techniques. More such comparisons are needed. ?? 2007 Elsevier Ltd and INQUA.

  10. A Characterization of Hot Flow Behaviors Involving Different Softening Mechanisms by ANN for As-Forged Ti-10V-2Fe-3Al Alloy

    NASA Astrophysics Data System (ADS)

    Quan, Guo-zheng; Zou, Zhen-yu; Wen, Hai-rong; Pu, Shi-ao; Lv, Wen-quan

    2015-11-01

    The isothermal compressions of as-forged Ti-10V-2Fe-3Al alloy at the deformation temperature range of 948-1,123 K and the strain rates in the range of 0.001-10 s-1 with a height reduction of 60% were conducted on a Gleeble-3500 thermo-mechanical simulator. The flow behaviors show nonlinear sensitivity to strain, strain rate and temperature. Based on the experimental data, an artificial neural network (ANN) with back-propagation algorithm was developed to deal with the complex deformation behavior characteristics. In the present ANN model, strain, strain rate and temperature were taken as inputs, and flow stress as output. A comparative study on the constitutive relationships based on regression and ANN methods was conducted. According to the predicted and experimental results, the predictabilities of the two models have been evaluated in terms of correlation coefficient (R) and average absolute relative error (AARE). The R-value and the AARE-value at strain of 0.5 from the ANN model is 0.9998 and 0.572%, respectively, better than 0.9902 and 6.583% from the regression model. The predicted strain-stress curves outside of experimental conditions indicate similar characteristics with experimental curves. The results have sufficiently articulated that the well-trained ANN model with back-propagation algorithm has excellent capability to deal with the complex flow behaviors of as-forged Ti-10V-2Fe-3Al alloy.

  11. Hot compression deformation behavior and a modified physically-based constitutive model of Cu-6 %Ag alloy

    NASA Astrophysics Data System (ADS)

    Meng, Lie; Wang, Menghan; Liu, Xiao; Wang, Fenglin

    2016-04-01

    In order to reveal the flow characteristics of Cu-6 %Ag alloy on the condition of hot deformation, the isothermal compression experiments are carried out at the temperatures of 973-1123 K under strain rates of 0.01-10 s-1. The effects of deformation condition on the hot compression deformation behavior are investigated. The low instability strain (ɛ i) behavior at high strain rate (10 s-1) is discussed in this paper. According to the experiment results and analyses, the deformation twinning and inhomogeneous grains are thought to be the possible reasons for low strain cracking. Then, a modified physically based constitutive model is established. The strain for maximum softening rate (\\varepsilon_{ *} ) is quoted in the constitutive equation which is proved that there is a nearly linear relationship between { ln }\\varepsilon_{ *} and { ln }Z . What's more, the correlation coefficient (R) and the average absolute relative error (AARE) are used to evaluate the accuracy of the established constitutive model. The values of R and AARE are 0.99612 and 3.47 %, respectively, which show that the modified constitutive model can exactly reveal the flow stress of Cu-6 %Ag alloy.

  12. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification

    NASA Astrophysics Data System (ADS)

    Kadir, K.; Gao, H.; Payne, A.; Soraghan, J.; Berry, C.

    2012-10-01

    In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm2 between individual investigator one (IV1) and LSM, and -122 mm2 between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients.

  13. A Constitutive Model of 6111-T4 Aluminum Alloy Sheet Based on the Warm Tensile Test

    NASA Astrophysics Data System (ADS)

    Hua, Lin; Meng, Fanzhi; Song, Yanli; Liu, Jianing; Qin, Xunpeng; Suo, Lianbing

    2014-03-01

    As main light-weight material, aluminum alloy sheets have been widely applied to produce auto body panels. In order to predict the formability and springback of aluminum alloy sheets, a precise constitutive model is a necessity. In this article, a series of warm tensile tests were conducted on Gleeble-1500D thermal mechanical simulator for 6111-T4 aluminum alloy sheets. The corresponding strain rate ranged from 0.015 to 1.5 s-1, and the temperature ranged from 25 to 350 °C. The relationship between the temperature, the strain rate, and the flow stress were discussed. A constitutive model based on the updated Fields-Backofen equation was established to describe the flow behavior of 6111-T4 aluminum alloy during the warm tensile tests. Subsequently, the average absolute relative error (AARE) was introduced to verify the predictability of the constitutive model. The value of AARE at the uniform plastic deformation stage was calculated to be 1.677%, which demonstrates that the predicted flow stress values were in accordance with the experimental ones. The constitutive model was validated by the fact that the simulated results of the warm tensile tests coincided with the experimental ones.

  14. Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs.

    PubMed

    Godinic-Mikulcic, Vlatka; Jaric, Jelena; Greber, Basil J; Franke, Vedran; Hodnik, Vesna; Anderluh, Gregor; Ban, Nenad; Weygand-Durasevic, Ivana

    2014-04-01

    Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal protein synthesis. Previous studies have suggested a link between tRNA aminoacylation and high-molecular-weight cellular complexes such as the cytoskeleton or ribosomes. However, the structural basis of these interactions and potential mechanistic implications are not well understood. To biochemically characterize these interactions we have used a system of two interacting archaeal aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS. More specifically, we have shown by thermophoresis and surface plasmon resonance that these two aaRSs bind to the large ribosomal subunit with micromolar affinities. We have identified the L7/L12 stalk and the proteins located near the stalk base as the main sites for aaRS binding. Finally, we have performed a bioinformatics analysis of synonymous codons in the Methanothermobacter thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs may be recharged by aaRSs bound to the ribosome and reused at the next occurrence of a codon encoding the same amino acid. These results suggest a mechanism of tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture the tRNAs released from the preceding ribosome in polysomes. PMID:24569352

  15. Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs

    PubMed Central

    Godinic-Mikulcic, Vlatka; Jaric, Jelena; Greber, Basil J.; Franke, Vedran; Hodnik, Vesna; Anderluh, Gregor; Ban, Nenad; Weygand-Durasevic, Ivana

    2014-01-01

    Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal protein synthesis. Previous studies have suggested a link between tRNA aminoacylation and high-molecular-weight cellular complexes such as the cytoskeleton or ribosomes. However, the structural basis of these interactions and potential mechanistic implications are not well understood. To biochemically characterize these interactions we have used a system of two interacting archaeal aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS. More specifically, we have shown by thermophoresis and surface plasmon resonance that these two aaRSs bind to the large ribosomal subunit with micromolar affinities. We have identified the L7/L12 stalk and the proteins located near the stalk base as the main sites for aaRS binding. Finally, we have performed a bioinformatics analysis of synonymous codons in the Methanothermobacter thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs may be recharged by aaRSs bound to the ribosome and reused at the next occurrence of a codon encoding the same amino acid. These results suggest a mechanism of tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture the tRNAs released from the preceding ribosome in polysomes. PMID:24569352

  16. Amino acid racemization dating of marine shells: A mound of possibilities.

    PubMed

    Demarchi, Beatrice; Williams, Matt G; Milner, Nicky; Russell, Nicola; Bailey, Geoff; Penkman, Kirsty

    2011-07-01

    Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization (AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscan species. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins (by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea. Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world. PMID:21776187

  17. Amino acid racemization dating of marine shells: A mound of possibilities

    PubMed Central

    Demarchi, Beatrice; Williams, Matt G.; Milner, Nicky; Russell, Nicola; Bailey, Geoff; Penkman, Kirsty

    2011-01-01

    Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization (AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscan species. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins (by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea. Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world. PMID:21776187

  18. Recent Updates on DTD (D-Tyr-tRNATyr Deacylase): An Enzyme Essential for Fidelity and Quality of Protein Synthesis

    PubMed Central

    Bhatt, Tarun K.; Soni, Rani; Sharma, Drista

    2016-01-01

    During protein synthesis, there are several checkpoints in the cell to ensure that the information encoded within genetic material is decoded correctly. Charging of tRNA with its cognate amino acid is one of the important steps in protein synthesis and is carried out by aminoacyl-tRNA synthetase (aaRS) with great accuracy. However, due to presence of D-amino acids in the cell, sometimes aaRS charges tRNA with D-amino acids resulting in the hampering of protein translational process, which is lethal to the cell. Every species has some mechanism in order to prevent the formation of D-amino acid-tRNA complex, for instance DTD (D-Tyr-tRNA deacylase) is an enzyme responsible for the cleavage of ester bond formed between D-amino acid and tRNA leading to error free translation process. In this review, structure, function, and enzymatic mechanism of DTD are discussed. The role of DTD as a drug target is also considered. PMID:27200345

  19. Constitutive Equations and Flow Behavior of an As-Extruded AZ31 Magnesium Alloy Under Large Strain Condition

    NASA Astrophysics Data System (ADS)

    Dong, Yuanyuan; Zhang, Cunsheng; Lu, Xing; Wang, Cuixue; Zhao, Guoqun

    2016-06-01

    A reasonable constitutive model is the key to achieving the accurate numerical simulation of magnesium alloy extrusion process. Based on the hot compression tests of the as-extruded AZ31 magnesium alloy, the strain-compensated Arrhenius equation, the constitutive equation taking into account dynamic recovery (DRV) and dynamic recrystallization (DRX), and the modified Fields-Backofen equation (FB) are established to describe the deformation behavior of this alloy under large strain condition (strain level greater than 1.0) and wide strain rate range (0.01 to 10 s-1), respectively. Then material parameters in each constitutive model are determined by linear fitting method. The comparison of these three kinds of equations shows that the strain-compensated Arrhenius model provides the best prediction of flow stress, and the calculated value of correlation coefficient ( R) is the highest as 0.9945 and the average absolute relative error (AARE) is the lowest as 3.11%. The constitutive equation with DRV + DRX can also predict flow stress accurately, and its values of R and AARE are 0.9920 and 4.41%, respectively. However, compared to the other two constitutive equations, the modified FB equation does not give good description of hot deformation behavior for this magnesium alloy. Finally, the advantages and drawbacks of these three kinds of constitutive models are discussed and compared. Therefore, this work could provide theoretical guidelines for investigating hot deformation behavior of wrought magnesium alloys and determining the appropriate extrusion process parameters under large strain condition.

  20. MIST, a Novel Approach to Reveal Hidden Substrate Specificity in Aminoacyl-tRNA Synthetases

    PubMed Central

    Eriani, Gilbert; Karam, Joseph; Jacinto, Jomel; Morris Richard, Erin; Geslain, Renaud

    2015-01-01

    Aminoacyl-tRNA synthetases (AARSs) constitute a family of RNA-binding proteins, that participate in the translation of the genetic code, by covalently linking amino acids to appropriate tRNAs. Due to their fundamental importance for cell life, AARSs are likely to be one of the most ancient families of enzymes and have therefore been characterized extensively. Paradoxically, little is known about their capacity to discriminate tRNAs mainly because of the practical challenges that represent precise and systematic tRNA identification. This work describes a new technical and conceptual approach named MIST (Microarray Identification of Shifted tRNAs) designed to study the formation of tRNA/AARS complexes independently from the aminoacylation reaction. MIST combines electrophoretic mobility shift assays with microarray analyses. Although MIST is a non-cellular assay, it fully integrates the notion of tRNA competition. In this study we focus on yeast cytoplasmic Arginyl-tRNA synthetase (yArgRS) and investigate in depth its ability to discriminate cellular tRNAs. We report that yArgRS in submicromolar concentrations binds cognate and non-cognate tRNAs with a wide range of apparent affinities. In particular, we demonstrate that yArgRS binds preferentially to type II tRNAs but does not support their misaminoacylation. Our results reveal important new trends in tRNA/AARS complex formation and potential deep physiological implications. PMID:26067673

  1. Development and validation of a predictive model for the influences of selected product and process variables on ascorbic acid degradation in simulated fruit juice.

    PubMed

    Gabriel, Alonzo A; Cayabyab, Jochelle Elysse C; Tan, Athalie Kaye L; Corook, Mark Lester F; Ables, Errol John O; Tiangson-Bayaga, Cecile Leah P

    2015-06-15

    A predictive response surface model for the influences of product (soluble solids and titratable acidity) and process (temperature and heating time) parameters on the degradation of ascorbic acid (AA) in heated simulated fruit juices (SFJs) was established. Physicochemical property ranges of freshly squeezed and processed juices, and a previously established decimal reduction times of Escherichiacoli O157:H7 at different heating temperatures were used in establishing a Central Composite Design of Experiment that determined the combinations of product and process variable used in the model building. Only the individual linear effects of temperature and heating time significantly (P<0.05) affected AA reduction (%AAr). Validating systems either over- or underestimated actual %AAr with bias factors 0.80-1.20. However, all validating systems still resulted in acceptable predictive efficacy, with accuracy factor 1.00-1.26. The model may be useful in establishing unique process schedules for specific products, for the simultaneous control and improvement of food safety and quality. PMID:25660889

  2. Constitutive Equations and Flow Behavior of an As-Extruded AZ31 Magnesium Alloy Under Large Strain Condition

    NASA Astrophysics Data System (ADS)

    Dong, Yuanyuan; Zhang, Cunsheng; Lu, Xing; Wang, Cuixue; Zhao, Guoqun

    2016-05-01

    A reasonable constitutive model is the key to achieving the accurate numerical simulation of magnesium alloy extrusion process. Based on the hot compression tests of the as-extruded AZ31 magnesium alloy, the strain-compensated Arrhenius equation, the constitutive equation taking into account dynamic recovery (DRV) and dynamic recrystallization (DRX), and the modified Fields-Backofen equation (FB) are established to describe the deformation behavior of this alloy under large strain condition (strain level greater than 1.0) and wide strain rate range (0.01 to 10 s-1), respectively. Then material parameters in each constitutive model are determined by linear fitting method. The comparison of these three kinds of equations shows that the strain-compensated Arrhenius model provides the best prediction of flow stress, and the calculated value of correlation coefficient (R) is the highest as 0.9945 and the average absolute relative error (AARE) is the lowest as 3.11%. The constitutive equation with DRV + DRX can also predict flow stress accurately, and its values of R and AARE are 0.9920 and 4.41%, respectively. However, compared to the other two constitutive equations, the modified FB equation does not give good description of hot deformation behavior for this magnesium alloy. Finally, the advantages and drawbacks of these three kinds of constitutive models are discussed and compared. Therefore, this work could provide theoretical guidelines for investigating hot deformation behavior of wrought magnesium alloys and determining the appropriate extrusion process parameters under large strain condition.

  3. Bicalutamide-activated oncolytic adenovirus for the adjuvant therapy of high-risk prostate cancer.

    PubMed

    Johnson, T J; Höti, N; Liu, C; Chowdhury, W H; Li, Y; Zhang, Y; Lupold, S E; Deweese, T; Rodriguez, R

    2013-07-01

    Conditionally replicating adenoviruses (CRAds) utilize tissue-specific promoters to control the expression of the early genes, E1A and E1B, to preferentially replicate and lyse tumor cells (oncolysis). Previous CRAds used in prostate cancer (PCa) gene therapy require androgens to activate prostate-specific promoters and induce viral replication. Unfortunately, these CRAds have reduced activity in patients on androgen-suppressive therapy. We describe a novel prostate-specific CRAd generated by fusing the E1A gene to the androgen receptor (AR) cDNA with a point mutation in codon 685 (C685Y). The E1A-AR fusion neutralizes the previously described mutual inhibition of E1A and AR, and the C685Y point mutation alters specificity of steroid ligand binding to the AR, such that both androgens and nonsteroidal anti-androgens can activate viral replication. We demonstrate that the mutated E1A-AR retained the ability to function in regulating AR-responsive genes and E1A-responsive viral genes. In combination therapy of virus, bicalutamide (anti-androgen) and radiation, a profound impact on cell death by viral oncolysis was seen both in vitro and tumor xenografts. To our knowledge, this is the first gene therapy engineered to be enhanced by anti-androgens and a particularly attractive adjuvant strategy for intensity-modulated radiation therapy of high-risk PCas. PMID:23764901

  4. Bicalutamide Activated Oncolytic Adenovirus for the Adjuvant Therapy of High Risk Prostate Cancer

    PubMed Central

    Johnson, Tamara Jane; Hoti, Naser Uddin; Liu, Chunyan; Chowdhury, Wasim H.; Li, Ying; Zhang, Yonggang; Lupold, Shawn E.; DeWeese, Theodore; Rodriguez, Ronald

    2013-01-01

    Conditionally replicating adenoviruses (CRAds) utilize tissue specific promoters to control the expression of the early genes, E1A and E1B, to preferentially replicate and lyse tumor cells (oncolysis). Previous CRAds used in prostate cancer gene therapy require androgens to activate prostate specific promoters and induce viral replication. Unfortunately, these CRAds have reduced activity in patients on androgen suppressive therapy. We describe a novel prostate specific CRAd generated by fusing the E1A gene to the androgen receptor (AR) cDNA with a point mutation in codon 685 (C685Y). The E1A-AR fusion neutralizes the previously described mutual inhibition of E1A & AR, and the C685Y point mutation alters specificity of steroid ligand binding to the AR, such that both androgens and non-steroidal anti-androgens can activate viral replication. We demonstrate that the mutated E1A-AR retained the ability to function in regulating AR responsive genes and E1A responsive viral genes. In combination therapy of virus, bicalutamide (anti-androgen) and radiation, a profound impact on cell death by viral oncolysis was seen both in vitro and tumor xenografts. To our knowledge, this is the first gene therapy engineered to be enhanced by anti-androgens, and a particularly attractive adjuvant strategy for intensity modulated radiation therapy (IMRT) of high-risk prostate cancers. PMID:23764901

  5. Descriptive Epidemiology of Musculoskeletal Injuries and Concussions in the National Football League, 2012-2014

    PubMed Central

    Lawrence, David W.; Hutchison, Michael G.; Comper, Paul

    2015-01-01

    Background: The risk of all-cause injury and concussion associated with football is significant. The National Football League (NFL) has implemented changes to increase player safety warranting investigation into the incidence and patterns of injury. Purpose: To document the incidence and patterns of all-cause injury and concussions in the NFL. Study Design: Descriptive epidemiology study. Methods: Injury data were collected prospectively from official NFL injury reports over 2 regular seasons from 2012 to 2014, with identification of injury incidence rates and patterns. Concussion rate ratios were calculated using previously reported NFL rates. Results: A total of 4284 injuries were identified, including 301 concussions. The all-cause injury rate was 395.8 per 1000 athletes at risk (AAR) and concussion incidence was 27.8 per 1000 AAR. Only 2.3% of team games were injury free. Wide receivers, tight ends, and defensive backs had the highest incidence of injury and concussion. Concussion incidence was 1.61-fold higher in 2012 to 2014 compared with 2002 to 2007. The knee was injured most frequently, followed by the ankle, hamstring, shoulder, and head. Conclusion: The incidence of all-cause injury and concussion in the NFL is significant. Concussion injury rates are higher than previous reports, potentially reflecting an improvement in recognition and awareness. Injury prevention efforts should continue to reduce the prevalence of injury associated with football. PMID:26675321

  6. The Alfvén mission concept

    NASA Astrophysics Data System (ADS)

    Berthomier, M.; Fazakerley, A. N.

    2014-12-01

    The Alfvén mission is a candidate to the 2014 ESA Call for M-class science missions. Its main scientific objective is to elucidate the universal physical processes at work in the Auroral Acceleration Region (AAR). The AAR is a unique laboratory for investigating strongly magnetized plasmas at an interface where ideal magneto-hydrodynamics does not apply. The Alfvén mission will investigate fundamental and multi-scale physical processes that govern what Nobel Prize laureate Hannes Alfvén named the Plasma Universe. The mission concept is designed to teach us where and how the particles that create the aurorae are accelerated, how they emit radiation, and to elucidate the ion heating and outflow processes which are slowly removing the Earth's atmosphere. The only way to distinguish between the models describing acceleration processes at the heart of Magnetosphere-Ionosphere (MI) coupling is to combine high-time resolution in situ measurements (as pioneered by the FAST mission), multi-point measurements (as pioneered by CLUSTER), and auroral arc imaging in one mission. Taking advantage of the existing dense network of ground based observatories the Alfvén mission will also allow a major breakthrough in our understanding of solar terrestrial relationships by providing key experimental measurements to large scale models of MI electrodynamics.

  7. Direct dating of human fossils.

    PubMed

    Grün, Rainer

    2006-01-01

    The methods that can be used for the direct dating of human remains comprise of radiocarbon, U-series, electron spin resonance (ESR), and amino acid racemization (AAR). This review gives an introduction to these methods in the context of dating human bones and teeth. Recent advances in ultrafiltration techniques have expanded the dating range of radiocarbon. It now seems feasible to reliably date bones up to 55,000 years. New developments in laser ablation mass spectrometry permit the in situ analysis of U-series isotopes, thus providing a rapid and virtually non-destructive dating method back to about 300,000 years. This is of particular importance when used in conjunction with non-destructive ESR analysis. New approaches in AAR analysis may lead to a renaissance of this method. The potential and present limitations of these direct dating techniques are discussed for sites relevant to the reconstruction of modern human evolution, including Florisbad, Border Cave, Tabun, Skhul, Qafzeh, Vindija, Banyoles, and Lake Mungo. PMID:17103430

  8. Niemeyer Virus: A New Mimivirus Group A Isolate Harboring a Set of Duplicated Aminoacyl-tRNA Synthetase Genes

    PubMed Central

    Boratto, Paulo V. M.; Arantes, Thalita S.; Silva, Lorena C. F.; Assis, Felipe L.; Kroon, Erna G.; La Scola, Bernard; Abrahão, Jônatas S.

    2015-01-01

    It is well recognized that gene duplication/acquisition is a key factor for molecular evolution, being directly related to the emergence of new genetic variants. The importance of such phenomena can also be expanded to the viral world, with impacts on viral fitness and environmental adaptations. In this work we describe the isolation and characterization of Niemeyer virus, a new mimivirus isolate obtained from water samples of an urban lake in Brazil. Genomic data showed that Niemeyer harbors duplicated copies of three of its four aminoacyl-tRNA synthetase genes (cysteinyl, methionyl, and tyrosyl RS). Gene expression analysis showed that such duplications allowed significantly increased expression of methionyl and tyrosyl aaRS mRNA by Niemeyer in comparison to APMV. Remarkably, phylogenetic data revealed that Niemeyer duplicated gene pairs are different, each one clustering with a different group of mimivirus strains. Taken together, our results raise new questions about the origins and selective pressures involving events of aaRS gain and loss among mimiviruses. PMID:26635738

  9. The physiological target for LeuRS translational quality control is norvaline

    PubMed Central

    Cvetesic, Nevena; Palencia, Andrés; Halasz, Ivan; Cusack, Stephen; Gruic-Sovulj, Ita

    2014-01-01

    The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNAs. Here, we show that the editing activity of Escherichia coli leucyl-tRNA synthetase (EcLeuRS) is not required to prevent incorrect isoleucine incorporation. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline. This conclusion follows from a reassessment of the discriminatory power of LeuRS against isoleucine and the demonstration that a LeuRS editing-deficient E. coli strain grows normally in high concentrations of isoleucine but not under oxygen deprivation conditions when norvaline accumulates to substantial levels. Thus, AARS-based translational quality control is a key feature for bacterial adaptive response to oxygen deprivation. The non-essential role for editing under normal bacterial growth has important implications for the development of resistance to antimicrobial agents targeting the LeuRS editing site. PMID:24935946

  10. Electron swarm coefficients in 1,1,1,2 tetrafluoroethane (R134a) and its mixtures with Ar

    NASA Astrophysics Data System (ADS)

    de Urquijo, J.; Juárez, A. M.; Basurto, E.; Hernández-Ávila, J. L.

    2009-02-01

    Using a pulsed Townsend technique, we have measured the drift velocity, the longitudinal diffusion coefficient and the effective ionisation coefficient of electrons in R134a and R134a-Ar over a wide range of the density-reduced electric field intensity, E/N. Regarding the measurement of the electron drift velocities and of the effective ionization coefficients, we have covered a wider range than that hitherto achieved for pure R134a. Both the electron drift velocity and the effective ionisation coefficient have been found in very good agreement with those published in the literature, covering a shorter range of E/N. On the other hand, the swarm coefficients on R134a-Ar are, to the best of our knowledge, the first to be published. It is hoped that these data will be of interest for the test/derivation of electron collision cross sections for this important hydrofluorocarbon gas, which is nowadays of great use in gaseous detectors.

  11. Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials

    NASA Astrophysics Data System (ADS)

    Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe

    2004-09-01

    We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity.

  12. Supercomputing Sheds Light on the Dark Universe

    SciTech Connect

    Salman Habib

    2012-11-15

    At Argonne National Laboratory, scientists are using supercomputers to shed light on one of the great mysteries in science today, the Dark Universe. With Mira, a petascale supercomputer at the Argonne Leadership Computing Facility, a team led by physicists Salman Habib and Katrin Heitmann will run the largest, most complex simulation of the universe ever attempted. By contrasting the results from Mira with state-of-the-art telescope surveys, the scientists hope to gain new insights into the distribution of matter in the universe, advancing future investigations of dark energy and dark matter into a new realm. The team's research was named a finalist for the 2012 Gordon Bell Prize, an award recognizing outstanding achievement in high-performance computing.

  13. Prospects for cosmic neutrino detection in tritium experiments in the case of hierarchical neutrino masses

    SciTech Connect

    Blennow, Mattias

    2008-06-01

    We discuss the effects of neutrino mixing and the neutrino mass hierarchy when considering the capture of the cosmic neutrino background (CNB) on radioactive nuclei. The implications of mixing and hierarchy at future generations of tritium decay experiments are considered. We find that the CNB should be detectable at these experiments provided that the resolution for the kinetic energy of the outgoing electron can be pushed to a few 0.01 eV for the scenario with inverted neutrino mass hierarchy, about an order of magnitude better than that of the upcoming KATRIN experiment. Another order of magnitude improvement is needed in the case of normal neutrino mass hierarchy. We also note that mixing effects generally make the prospects for CNB detection worse due to an increased maximum energy of the normal beta decay background.

  14. Kamstrup's wow-effect: re-examined and expanded

    NASA Astrophysics Data System (ADS)

    King, Elizabeth M.; Dickmann, Ellyn M.; Johnson, Barbara Z.

    2016-03-01

    This review examines Anna Katrine Kamstrup's article "The wow-effect in science teacher education; technology; sociomateriality." In the discussion below we explore three key areas of her ethnographic research. First, we reconsider Kamstrup's article through the lens of technology as a pedagogical choice and philosophy. This is followed by our discussion of aspects of her study within the context of a basic understanding that entry-level pre-service teachers need to fully understand both the process of learning and scientific principles as these are important foundational factors in determining whether or not the wow-effect will occur as expected. Finally, our review team presents multiple areas in Kamstrup's article as potential points for further elaboration.

  15. Changes to Irradiation Conditions of VVER-1000 Surveillance Specimens Resulting from Fuel Assemblies with Greater Fuel Height

    NASA Astrophysics Data System (ADS)

    Panferov, Pavel; Kochkin, Viacheslav; Erak, Dmitry; Makhotin, Denis; Reshetnikov, Alexandr; Timofeev, Andrey

    2016-02-01

    The goal of the work was to obtain experimental data on the influence of newtype fuel assemblies with higher fuel rods on the irradiation conditions of surveillance specimens installed on the baffe of VVER-1000. For this purpose, two surveillance sets with container assemblies of the same design irradiated in reactors with different fuel assemblies in the core were investigated. Measurements of neutron dosimeters from these sets and retrospective measurements of 54Mn activity accumulated in each irradiated specimen allow a detailed distribution of the fast neutron flux in the containers to be obtained. Neutron calculations have been done using 3D discrete ordinate code KATRIN. On the basis of the obtained results, a change of the lead factor due to newtype fuel assemblies was evaluated for all types of VVER-1000 container assemblies.

  16. Absolute mass of neutrinos and the first unique forbidden {beta} decay of {sup 187}Re

    SciTech Connect

    Dvornicky, Rastislav; Simkovic, Fedor; Muto, Kazuo; Faessler, Amand

    2011-04-15

    The planned rhenium {beta}-decay experiment, called the ''Microcalorimeter Arrays for a Rhenium Experiment'' (MARE), might probe the absolute mass scale of neutrinos with the same sensitivity as the Karlsruhe tritium neutrino mass (KATRIN) experiment, which will take commissioning data in 2011 and will proceed for 5 years. We present the energy distribution of emitted electrons for the first unique forbidden {beta} decay of {sup 187}Re. It is found that the p-wave emission of electron dominates over the s wave. By assuming mixing of three neutrinos, the Kurie function for the rhenium {beta} decay is derived. It is shown that the Kurie plot near the end point is within a good accuracy linear in the limit of massless neutrinos like the Kurie plot of the superallowed {beta} decay of {sup 3}H.

  17. Investigation of durability of optical coatings in highly purified tritium gas

    SciTech Connect

    Fischer, S.; Schoenung, K.; Bornschein, B.; Rolli, R.; Schaefer, V.; Sturm, M.

    2015-03-15

    Anti-reflection coated windows are part of Raman spectroscopy systems for tritium analytics in the KATRIN experiment and fusion-related applications. Damages of such windows were observed after three months of expo-sure to highly purified tritium gas in the LOOPINO facility. In this work, the origin of the damages was investigated, identified and eliminated. Coating samples manufactured by various physical vapor deposition methods have been tested for durability by exposure to pure tritium gas and subsequent visual inspection. Electron beam deposited coatings showed indications for damage after 17 days of tritium exposure in contrast to samples manufactured by ion assisted deposition or sputtering. An improved coating layout of the sample cell is presented for reliable long-term monitoring of tritium gas using Raman spectroscopy. (authors)

  18. Post service examination of turbomolecular pumps after stress testing with Kg-scale tritium throughput

    SciTech Connect

    Priester, F.; Roelling, M.

    2015-03-15

    Turbomolecular pumps (TMP) will be used with large amounts of tritium in future fusion machines like ITER, DEMO and in the KATRIN Experiment. In this work, a stress test of a large, magnetically levitated TMP (Leybold MAG W2800) with a tritium throughput of 1.1 kg over 384 days of operation was performed at TLK. After this, the pump was dismantled and the tritium uptake in several parts was deter-mined. Especially the non-metallic parts of the pump have absorbed large amounts of tritium and are most likely responsible for the observed pollution of the process gas. The total tritium uptake of the TMP was estimated with 0.1-1.1 TBq. No radiation-induced damages were found on the inner parts of the pump. The TMP showed no signs of functional limitations during the 384 days of operation. (authors)

  19. SDAV Viz July Progress Update: LANL

    SciTech Connect

    Sewell, Christopher Meyer

    2012-07-30

    SDAV Viz July Progress Update: (1) VPIC (Vector Particle in Cell) Kinetic Plasma Simulation Code - (a) Implemented first version of an in-situ adapter based on Paraview CoProcessing Library, (b) Three pipelines: vtkDataSetMapper, vtkContourFilter, vtkPistonContour, (c) Next, resolve issue at boundaries of processor domains; add more advanced viz/analysis pipelines; (2) Halo finding/merger trees - (a) Summer student Wathsala W. from University of Utah is working on data-parallel halo finder algorithm using PISTON, (b) Timo Bremer (LLNL), Valerio Pascucci (Utah), George Zagaris (Kitware), and LANL people are interested in using merger trees for tracking the evolution of halos in cosmo simulations; discussed possible overlap with work by Salman Habib and Katrin Heitmann (Argonne) during their visit to LANL 7/11; (3) PISTON integration in ParaView - Now available from ParaView github.

  20. The Absolute Mass of Neutrino and the First Unique Forbidden β-DECAY of 187Re

    NASA Astrophysics Data System (ADS)

    Dvornický, Rastislav; Šimkovic, Fedor; Muto, Kazuo

    2011-10-01

    The planned rhenium β-decay experiment MARE might probe the absolute mass scale of neutrinos with the same sensitivity as the tritium β-decay experiment KATRIN, which will start data taking in 2011 and will proceed for five years. We present the energy distribution of emitted electrons for the first unique forbidden β-decay of 187Re. It is found that the p-wave emission of electron dominates over the s-wave. By assuming mixing of three neutrinos the Kurie function for the rhenium β-decay is derived. It is shown that the Kurie plot near the endpoint is within a good accuracy linear in the limit of massless neutrinos like the Kurie plot of the superallowed βof 3H.

  1. Upper Bound of 0.28 eV on Neutrino Masses from the Largest Photometric Redshift Survey

    SciTech Connect

    Thomas, Shaun A.; Abdalla, Filipe B.; Lahav, Ofer

    2010-07-16

    We present a new limit of (95% CL) on the sum of the neutrino masses assuming a flat {Lambda}CDM cosmology. This relaxes slightly to and when quasinonlinear scales are removed and w{ne}-1, respectively. These are derived from a new photometric catalogue of over 700 000 luminous red galaxies (MegaZ DR7) with a volume of 3.3 (Gpc h{sup -1}){sup 3} and redshift range 0.45KATRIN, are unlikely to obtain a detection.

  2. Anharmonicity of internal atomic oscillation and effective antineutrino mass evaluation from gaseous molecular tritium β-decay

    NASA Astrophysics Data System (ADS)

    Lokhov, Alexey V.; Titov, Nikita A.

    2016-07-01

    Data analysis of the next-generation effective antineutrino mass measurement experiment KATRIN requires reliable knowledge of systematic corrections. In particular, the width of the daughter molecular ion excitation spectrum rovibrational band should be known with better than 1% precision. Very precise ab initio quantum calculations exist, and we compare them with the well-known tritium molecule parameters within the framework of a phenomenological model. The rovibrational band width with accuracy of a few percent is interpreted as a result of the zero-point atomic oscillation in the harmonic potential. The Morse interatomic potential is used to investigate the impact of anharmonic atomic oscillations. The calculated corrections cannot account for the difference between the ab initio quantum calculations and the phenomenological model.

  3. Pharmacological analysis of the novel, selective alpha1-adrenoceptor antagonist, KMD-3213, and its suitability as a tritiated radioligand.

    PubMed

    Murata, S; Taniguchi, T; Muramatsu, I

    1999-05-01

    Pharmacological profiles of tritiated KMD-3213, a new antagonist of alpha1-adrenoceptor (AR), were examined in recombinant and native alpha1-AR, and compared with those of prazosin (PZ) and tamsulosin (YM-617). In saturation experiments, [3H]-KMD (10-2000 pM) showed high affinity for alpha1a-AR (pK(D) = 10.5). However, no significant binding to alpha1b-AR and insufficient/unsaturated binding to alpha1d-AR were observed at concentrations up to 2000 pM. In contrast, [3H]-PZ and [3H]-YM bound to all subtypes with high affinity (pK(D)>9). In competition experiments, KMD-3213 also had higher affinity for alpha1a-AR than for other two subtypes; pKi = 10.4, 8.1 and 8.6 for alpha1a-, alpha1b- and alpha1d-AR, respectively. [3H]-KMD also bound to the native alpha1A-AR (rat submaxillary gland) with high affinity, but not to alpha1B-AR (rat liver). In rat kidney which expresses alpha1A- and alpha1B-AR, [3H]-KMD and [3H]-PZ bound to a single high-affinity site (pK(D) = 10.8 and 10.1, respectively) with distinct amount of binding sites (Bmax = 159 and 267 fmol mg(-1) protein, respectively). [3H]-PZ binding sites consisted of low- and high-affinity sites for KMD-3213 (pKi = 7.6 and 10.7, respectively), for WB4101 (pK = 8.1 and 10.0) and for YM-617 (pKi = 8.7 and 10.8). The proportion of the high affinity site was approximately 60% in these drugs which was compatible to the ratio between Bmax of [3H]-KMD and [3H]-PZ. [3H]-KMD binding sites consisted of a single site for these drugs with affinities which were similar to those of the high affinity sites in [3H]-PZ binding. In functional experiments, KMD-3213 antagonized the contractile responses to NS-49 or noradrenaline (NA) with higher affinity in functional alpha1A- (rat caudal artery, pA2= 10.0 against NS-49) and alpha1L-AR (dog mesenteric artery, pA2 = 9.9 against NA) than in alpha1B- (dog carotid artery, pA2 = 7.7 against NA) and alpha1D-AR (rat thoracic aorta, pA2 = 8.3 against NA). These results confirm the alpha1A-AR

  4. Pharmacological analysis of the novel, selective α1-adrenoceptor antagonist, KMD-3213, and its suitability as a tritiated radioligand

    PubMed Central

    Murata, Satoshi; Taniguchi, Takanobu; Muramatsu, Ikunobu

    1999-01-01

    Pharmacological profiles of tritiated KMD-3213, a new antagonist of α1-adrenoceptor (AR), were examined in recombinant and native α1-AR, and compared with those of prazosin (PZ) and tamsulosin (YM-617). In saturation experiments, [3H]-KMD (10–2000 pM) showed high affinity for α1a-AR (pKD=10.5). However, no significant binding to α1b-AR and insufficient/unsaturated binding to α1d-AR were observed at concentrations up to 2000 pM. In contrast, [3H]-PZ and [3H]-YM bound to all subtypes with high affinity (pKD>9). In competition experiments, KMD-3213 also had higher affinity for α1a-AR than for other two subtypes; pKi=10.4, 8.1 and 8.6 for α1a-, α1b- and α1d-AR, respectively. [3H]-KMD also bound to the native α1A-AR (rat submaxillary gland) with high affinity, but not to α1B-AR (rat liver). In rat kidney which expresses α1A- and α1B-AR, [3H]-KMD and [3H]-PZ bound to a single high-affinity site (pKD=10.8 and 10.1, respectively) with distinct amount of binding sites (Bmax=159 and 267 fmol mg−1 protein, respectively). [3H]-PZ binding sites consisted of low- and high-affinity sites for KMD-3213 (pKi=7.6 and 10.7, respectively), for WB4101 (pKi=8.1 and 10.0) and for YM-617 (pKi=8.7 and 10.8). The proportion of the high affinity site was approximately 60% in these drugs which was compatible to the ratio between Bmax of [3H]-KMD and [3H]-PZ. [3H]-KMD binding sites consisted of a single site for these drugs with affinities which were similar to those of the high affinity sites in [3H]-PZ binding. In functional experiments, KMD-3213 antagonized the contractile responses to NS-49 or noradrenaline (NA) with higher affinity in functional α1A- (rat caudal artery, pA2=10.0 against NS-49) and α1L-AR (dog mesenteric artery, pA2=9.9 against NA) than in α1B- (dog carotid artery, pA2=7.7 against NA) and α1D-AR (rat thoracic aorta, pA2=8.3 against NA). These results confirm the α1A-AR selectivity and high affinity of KMD-3213, and indicate that [3H]-KMD can

  5. A 2600-year history of floods in the Bernese Alps, Switzerland: frequencies, mechanisms and climate forcing

    NASA Astrophysics Data System (ADS)

    Schulte, L.; Peña, J. C.; Carvalho, F.; Schmidt, T.; Julià, R.; Llorca, J.; Veit, H.

    2015-07-01

    A 2600-year long composite palaeoflood record is reconstructed from high-resolution delta plain sediments of the Hasli-Aare floodplain on the northern slope of the Swiss Alps. Natural proxies compiled from sedimentary, geochemical and geomorphological data were calibrated by textual and factual sources and instrumental data. No fewer than 12 of the 14 historically recorded extreme events between 1480 and the termination of the Hasli-Aare river channel correction in 1875 were also identified by coarse-grained flood layers, log(Zr / Ti) peaks and factor 1 anomalies. Geomorphological, historical and instrumental data provide evidence for flood damage intensities and discharge estimations of severe and catastrophic historical floods. Spectral analysis of the geochemical and documentary flood series and several climate proxies (TSI, δ18O, tree-rings, NAO, SNAO) identify similar periodicities of around 60, 80, 100, 120 and 200 years during the last millennia, indicating the influence of the North Atlantic circulation and solar forcing on alpine flood dynamics. The composite floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (from the medium high catchment area) match those of total solar irradiance maxima, suggesting reduced flood activity during warmer climate pulses. Aggradation with multiple sets of flood layers with increased contribution of siliciclasts from the highest catchment area (plutonic bedrock) (e.g. 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) occurred predominantly during periods with reduced solar irradiance, lower δ18O anomalies, cooler summer temperatures and phases of drier spring climate in the Alps. Increased water storage by glaciers, snow cover and snow patches susceptible to melting processes associated with rainfall episodes and abrupt rises in temperature substantially increased surface runoff on slopes and discharges of alpine rivers. This interpretation is in

  6. Identification of the α1L-adrenoceptor in rat cerebral cortex and possible relationship between α1L- and α1A-adrenoceptors

    PubMed Central

    Morishima, S; Suzuki, F; Yoshiki, H; Md Anisuzzaman, A S; Sathi, Z S; Tanaka, T; Muramatsu, I

    2008-01-01

    Background and purpose: In addition to α1A, α1B and α1D-adrenoceptors (ARs), putative α1L-ARs with a low affinity for prazosin have been proposed. The purpose of the present study was to identify the α1A-AR and clarify its pharmacological profile using a radioligand binding assay. Experimental approach: Binding experiments with [3H]-silodosin and [3H]-prazosin were performed in intact tissue segments and crude membrane preparations of rat cerebral cortex. Intact tissue binding assays were also conducted in rat tail artery. Key results: [3H]-silodosin at subnanomolar concentrations specifically bound to intact tissue segments and membrane preparations of rat cerebral cortex at the same density (approximately 150 fmol mg−1 total tissue protein). The binding sites in intact segments consisted of α1A and α1L-ARs that had different affinities for prazosin, while the binding sites in membranes showed an α1A-AR-like profile having single high affinity for prazosin. [3H]-prazosin also bound at subnanomolar concentrations to α1A and α1B-ARs but not α1L-ARs in cerebral cortex; the binding densities being approximately 200 and 290 fmol mg−1 protein in the segments and the membranes, respectively. In the segments of tail artery, [3H]-silodosin only recognized α1A-ARs, whereas [3H]-prazosin bound to α1A and α1B-ARs. Conclusions and implications: The present study clearly reveals the presence of α1L-ARs as a pharmacologically distinct entity from α1A and α1B-ARs in intact tissue segments of rat cerebral cortex but not tail artery. However, the α1L-ARs disappeared after tissue homogenization, suggesting their decomposition and/or their pharmacological profile changes to that of α1A-ARs. PMID:18223667

  7. CYP-epoxygenases contribute to A2A receptor-mediated aortic relaxation via sarcolemmal KATP channels.

    PubMed

    Ponnoth, Dovenia S; Nayeem, Mohammed A; Tilley, Stephen L; Ledent, Catherine; Jamal Mustafa, S

    2012-11-15

    Previously, we have shown that A(2A) adenosine receptor (A(2A)AR) mediates aortic relaxation via cytochrome P-450 (CYP)-epoxygenases. However, the signaling mechanism is not understood properly. We hypothesized that ATP-sensitive K(+) (K(ATP)) channels play an important role in A(2A)AR-mediated relaxation. Organ bath and Western blot experiments were done using isolated aorta from A(2A)KO and corresponding wild-type (WT) mice. Aortic rings from WT and A(2A) knockout (KO) mice were precontracted with submaximal dose of phenylephrine (PE, 10(-6) M), and concentration-response curves for pinacidil, cromakalim (nonselective K(ATP) openers), and diazoxide (mitochondrial K(ATP) opener) were obtained. Diazoxide did not have any relaxation effect on PE-precontracted tissues, whereas relaxation to pinacidil (48.09 ± 5.23% in WT vs. 25.41 ± 2.73% in A(2A)KO; P < 0.05) and cromakalim (51.19 ± 2.05% in WT vs. 38.50 ± 2.26% in A(2A)KO; P < 0.05) was higher in WT than A(2A)KO aorta. This suggested the involvement of sarcolemmal rather than mitochondrial K(ATP) channels. Endothelium removal, treatment with SCH 58651 (A(2A)AR antagonist; 10(-6) M), N(G)-nitro-l-arginine methyl ester (l-NAME, nitric oxide synthase inhibitor) and methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH, CYP-epoxygenases inhibitor; 10(-5) M) significantly reduced pinacidil-induced relaxation in WT compared with controls, whereas these treatments did not have any effect in A(2A)KO aorta. Glibenclamide (K(ATP) channel inhibitor, 10(-5) M) blocked 2-p-(2-carboxyethyl)phenethylamino-5'N-ethylcarboxamido adenosine hydrochloride (CGS 21680, A(2A)AR agonist)-induced relaxation in WT and changed 5'-N-ethylcarboxamide (NECA) (nonselective adenosine analog)-induced response to higher contraction in WT and A(2A)KO. 5-Hydroxydecanoate (5-HD, mitochondrial K(ATP) channel inhibitor, 10(-4) M) had no effect on CGS 21680-mediated response in WT aorta. Our data suggest that A(2A)AR-mediated vasorelaxation occurs

  8. D-Dimer Levels Predict Myocardial Injury in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study

    PubMed Central

    Song, Young Bin; Lima, Joao A. C.; Guallar, Eliseo; Choe, Yeon Hyeon; Hwang, Jin Kyung; Kim, Eun Kyoung; Yang, Jeong Hoon; Hahn, Joo-Yong; Choi, Seung-Hyuk; Lee, Sang-Chol; Lee, Sang Hoon; Gwon, Hyeon-Cheol

    2016-01-01

    Objectives Elevated D-dimer levels on admission predict prognosis in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but the association of D-dimer levels with structural markers of myocardial injury in these patients is unknown. Methods We performed cardiac magnetic resonance (CMR) imaging in 208 patients treated with primary PCI for STEMI. CMR was performed a median of 3 days after the index procedure. Of the 208 patients studied, 75 patients had D-dimer levels above the normal range on admission (>0.5 μg/mL; high D-dimer group) while 133 had normal levels (≤0.5 μg/mL; low D-dimer group). The primary outcome was myocardial infarct size assessed by CMR. Secondary outcomes included area at risk (AAR), microvascular obstruction (MVO) area, and myocardial salvage index (MSI). Results In CMR analysis, myocardial infarct size was larger in the high D-dimer group than in the low D-dimer group (22.3% [16.2–30.5] versus 18.8% [10.7–26.7]; p = 0.02). Compared to the low D-dimer group, the high D-dimer group also had a larger AAR (38.1% [31.7–46.9] versus 35.8% [24.2–45.3]; p = 0.04) and a smaller MSI (37.7 [28.2–46.9] versus 47.1 [33.2–57.0]; p = 0.01). In multivariate analysis, high D-dimer levels were significantly associated with larger myocardial infarct (OR 2.59; 95% CI 1.37–4.87; p<0.01) and lower MSI (OR 2.62; 95% CI 1.44–4.78; p<0.01). Conclusions In STEMI patients undergoing primary PCI, high D-dimer levels on admission were associated with a larger myocardial infarct size, a greater extent of AAR, and lower MSI, as assessed by CMR data. Elevated initial D-dimer level may be a marker of advanced myocardial injury in patients treated with primary PCI for STEMI. PMID:27513758

  9. The Diagnostic Accuracy and Clinical Utility of Three Noninvasive Models for Predicting Liver Fibrosis in Patients with HBV Infection

    PubMed Central

    Zhang, Zhiqiao; Wang, Gongsui; Kang, Kaifu; Wu, Guobiao; Wang, Peng

    2016-01-01

    Aim To evaluate the diagnostic accuracy and clinical utility of the fibrosis index based on the four factors (FIB-4), aspartate aminotransferase -to-platelet ratio index (APRI), and aspartate aminotransferase–alanine aminotransferase ratio index (AAR) for predicting liver fibrosis in patients with HBV infection. Methods From January 2006 to December 2010,a total of 1543 consecutive chronic hepatitis B(CHB) patients who underwent liver biopsies were enrolled. FIB-4,APRI, and AAR were calculated.The areas under the receiver-operating characteristic curves (AUROCs) were calculated to assess the diagnostic accuracy of these models.The AUROCs of these models were compared by DeLong’s test.For further comparisons in different studies,the AUROCs were adjusted to conduct Adjusted AUROCs(ADjAUROCs) according to the prevalence of fibrosis stages using the difference between advanced and nonadvanced fibrosis (DANA). Results For prediction of significant fibrosis,severe fibrosis,and cirrhosis,the AUROCs of FIB-4 were 0.646(ADjAUROC 0.717),0.670(ADjAUROC 0.741), and 0.715(ADjAUROC 0.786) respectively;whereas it were 0.656(ADjAUROC 0.727),0.653(ADjAUROC 0.724) and 0.639(ADjAUROC 0.710) for APRI, 0.498(ADjAUROC 0.569),0.548(ADjAUROC 0.619) and 0.573(ADjAUROC 0.644) for AAR. The further comparisons demonstrated that there were no significant differences of AUROCs between FIB-4 and APRI in predicting significant and severe fibrosis(P > 0.05),while FIB-4 was superior to APRI in predicting cirrhosis(P < 0.001). Further subgroup analysis demonstrated that the diagnostic accuracy of FIB-4 and APRI in patients with normal alanine aminotransferase(ALT) were higher than that in patients with elevated ALT. Conclusions The results demonstrated that FIB-4 and APRI are useful for diagnosis of fibrosis. FIB-4 and APRI have similar diagnostic accuracy in predicting significant and severe fibrosis,while FIB-4 is superior to APRI in predicting cirrhosis. The clinical utility of FIB-4 and APRI

  10. How logical reasoning ability and empirical knowledge interact in the process of solving problems about light and vision among Taiwanese secondary school students

    NASA Astrophysics Data System (ADS)

    Liao, Shih-Chieh

    Piagetian scholars argue that the effect of problem content, e.g., empirical knowledge, should decrease with age. Indeed, they believe that the empirical knowledge cannot affect human problem-solving after individuals approach the formal operation stage. In arguing this point, this study uses an A-AR model to address how empirical knowledge affects the problem-solving process among Taiwanese secondary students. The A-AR model is borrowed from mathematics and the symbols, A, A, and R, represent Assumption, Answering, and Reasoning, respectively. Similar to solving mathematics problems, the A-AR model problems require participants to use the given assumptions by logical reasoning in order to respond to the problems. In this situation, the effect of empirical knowledge on problem-solving is easy to detect. There are three results about human problem-solving found in this study. First, the empirical knowledge still affects human problem-solving at the formal operation stage. Not like the Piagetian scholars' assumption: the effect of empirical knowledge is decreasing with age, this study finds that the effect of empirical knowledge is S-shape. The S-shape is a result of academic training. Second, the academic training, major, shapes human problem-solving strategies. For instance, the 12th grade science students' problem-solving strategy is based on logical reasoning ability by the given assumptions and the same grade social science students' strategy is according of their empirical knowledge. Third, the interference of logical reasoning ability and empirical knowledge is a predictor of the empirical knowledge effect on human problem-solving. The relation between the empirical knowledge and interference can be characterized as: the more negative interference the participants have, the more of the empirical knowledge effect they will have in the next year. This study does not agree with the Piagetian theory about human problem-solving: the effect of empirical knowledge

  11. A 2600 year history of floods in the Bernese Alps, Switzerland: frequencies, mechanisms and climate forcing

    NASA Astrophysics Data System (ADS)

    Schulte, L.; Peña, J. C.; Carvalho, F.; Schmidt, T.; Julià, R.; Llorca, J.; Veit, H.

    2015-03-01

    A 2600 yr long composite palaeoflood record is reconstructed from high-resolution delta plain sediments of the Hasli-Aare floodplain on the northern slope of the Swiss Alps. Natural proxies compiled from sedimentary, geochemical and geomorphological data were calibrated by textual and factual sources and instrumental data. No fewer than 12 of the 14 historically recorded extreme events between 1480 and the termination of the Hasli-Aare Correction in 1875 were also identified by coarse-grained flood layers, log(Zr/Ti) peaks and Factor 1 anomalies. Geomorphological, historical and instrumental data provide evidence for flood damage intensities and discharge estimations of severe and catastrophic historical floods. Spectral analysis of the geochemical and documentary flood series and several climate proxies (TSI, δ18O, tree-rings, NAO, SNAO) identify similar periodicities of around 60, 80, 100, 120 and 200 years during the last millennia, indicating the influence of the North Atlantic circulation and solar forcing on alpine flood dynamics. The composite floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (from the medium high catchment area) match those of Total Solar Irradiance maxima, suggesting reduced flood activity during warmer climate pulses. Aggradation of clusters of flood layers with increased contribution of siliciclasts from the highest catchment area (plutonic bedrock) (e.g., 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) occurred predominantly during periods with reduced solar irradiance, lower δ18O anomalies, cooler summer temperatures and phases of drier spring climate in the Alps. Increased water storage by glaciers, snow cover and snow patches susceptible to melting processes associated with rainfall episodes and abrupt rises in temperature substantially increased surface run-off on slopes and discharges of alpine rivers. This interpretation is in agreement with the findings

  12. Quantification of the cumulative effects of river training works on the basin scale with 2D flood modelling

    NASA Astrophysics Data System (ADS)

    Zischg, Andreas Paul; Felder, Guido; WWeingartner, Rolf

    2015-04-01

    The catchment of the river Aare upstream of Bern, Switzerland, with an area of approx. 3000 km2 is a complex network of sub-catchments with different runoff characteristics; it also includes two larger lakes. Most of the rivers were regulated in the 18th century. An important regulation, however, was realised as early as in the 17th century. For this catchment, the worst case flood event was identified and its consequences were analysed. Beside the hydro-meteorological characteristics, an important basis to model the worst case flood is to understand the non-linear effects of flood retention in the valley bottom and in the lakes. The aim of this study was to compare these effects based on both the current river network and the historic one prior to the main river training works. This allows to quantify the human impacts. Methodologically, we set up a coupled 2D flood model representing the floodplains of the river Aare as well as of the tributaries Lombach, Lütschine, Zulg, Rotache, Chise and Guerbe. The flood simulation was made in 2D with the software BASEMENT-ETH (Vetsch et al. 2014). The model was calibrated by means of reproducing the large floods in August 2005 and the bankfull discharge for all river reaches. The model computes the discharge at the outlet of the Aare catchment at Bern by routing all discharges from the sub-catchments through the river reaches and their floodplains. With this, the modulation of the input hydrographs by widespread floodings in the floodplains can be quantified. The same configuration was applied on the basis of reconstructed digital terrain models representing the landscape and the river network before the first significant river training works had been realised. This terrain model was reconstructed by georeferencing and digitalizing historic maps and cross-sections combined with the mapping of the geomorphologic evidences of former river structures in non-modified areas. The latter mapping procedure was facilitated by the

  13. Mass spectrometry-based ligand binding assays on adenosine A1 and A2A receptors.

    PubMed

    Massink, A; Holzheimer, M; Hölscher, A; Louvel, J; Guo, D; Spijksma, G; Hankemeier, T; IJzerman, A P

    2015-12-01

    Conventional methods to measure ligand-receptor binding parameters typically require radiolabeled ligands as probes. Despite the robustness of radioligand binding assays, they carry inherent disadvantages in terms of safety precautions, expensive synthesis, special lab requirements, and waste disposal. Mass spectrometry (MS) is a method that can selectively detect ligands without the need of a label. The sensitivity of MS equipment increases progressively, and currently, it is possible to detect low ligand quantities that are usually found in ligand binding assays. We developed a label-free MS ligand binding (MS binding) assay on the adenosine A(1) and A(2A) receptors (A(1)AR and A(2A)AR), which are well-characterized members of the class A G protein-coupled receptor (GPCR) family. Radioligand binding assays for both receptors are well established, and ample data is available to compare and evaluate the performance of an MS binding assay. 1,3-Dipropyl-8-cyclopentyl-xanthine (DPCPX) and 4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazin-5-yl)amino)ethyl)phenol (ZM-241,385) are high-affinity ligands selective for the A(1)AR and A(2A)AR, respectively. To proof the feasibility of MS binding on the A(1)AR and A(2A)AR, we first developed an MS detection method for unlabeled DPCPX and ZM-241,385. To serve as internal standards, both compounds were also deuterium-labeled. Subsequently, we investigated whether the two unlabeled compounds could substitute for their radiolabeled counterparts as marker ligands in binding experiments, including saturation, displacement, dissociation, and competition association assays. Furthermore, we investigated the accuracy of these assays if the use of internal standards was excluded. The results demonstrate the feasibility of the MS binding assay, even in the absence of a deuterium-labeled internal standard, and provide great promise for the further development of label-free assays based on MS for other GPCRs. PMID

  14. High Temperature Calcination - MACT Upgrade Equipment Pilot Plant Test

    SciTech Connect

    Richard D. Boardman; B. H. O'Brien; N. R. Soelberg; S. O. Bates; R. A. Wood; C. St. Michel

    2004-02-01

    About one million gallons of acidic, hazardous, and radioactive sodium-bearing waste are stored in stainless steel tanks at the Idaho Nuclear Technology and Engineering Center (INTEC), which is a major operating facility of the Idaho National Engineering and Environmental Laboratory. Calcination at high-temperature conditions (600 C, with alumina nitrate and calcium nitrate chemical addition to the feed) is one of four options currently being considered by the Department of Energy for treatment of the remaining tank wastes. If calcination is selected for future processing of the sodium-bearing waste, it will be necessary to install new off-gas control equipment in the New Waste Calcining Facility (NWCF) to comply with the Maximum Achievable Control Technology (MACT) standards for hazardous waste combustors and incinerators. This will require, as a minimum, installing a carbon bed to reduce mercury emissions from their current level of up to 7,500 to <45 {micro}g/dscm, and a staged combustor to reduce unburned kerosene fuel in the off-gas discharge to <100 ppm CO and <10 ppm hydrocarbons. The staged combustor will also reduce NOx concentrations of about 35,000 ppm by 90-95%. A pilot-plant calcination test was completed in a newly constructed 15-cm diameter calciner vessel. The pilot-plant facility was equipped with a prototype MACT off-gas control system, including a highly efficient cyclone separator and off-gas quench/venturi scrubber for particulate removal, a staged combustor for unburned hydrocarbon and NOx destruction, and a packed activated carbon bed for mercury removal and residual chloride capture. Pilot-plant testing was performed during a 50-hour system operability test January 14-16, followed by a 100-hour high-temperature calcination pilot-plant calcination run January 19-23. Two flowsheet blends were tested: a 50-hour test with an aluminum-to-alkali metal molar ratio (AAR) of 2.25, and a 50-hour test with an AAR of 1.75. Results of the testing

  15. Glacier Changes in the Cordillera Blanca, Peru, Derived From SPOT5 Imagery, GIS and Field- Based Measurements

    NASA Astrophysics Data System (ADS)

    Racoviteanu, A.; Arnaud, Y.; Williams, M. W.; Singh Khalsa, S.

    2007-12-01

    There is urgency in deriving an extensive dataset for deriving glacier changes within the Cordillera Blanca, Peru, in a cost-effective and timely manner. Rapid glacial retreat during the last decades in this area poses a threat for water resources, hydroelectric power and local traditions. While there is some information on decadal changes in glacier extents, there still remains a paucity of mass balance measurements and glacier parameters such as hypsometry, size distribution and termini elevations. Here we investigate decadal changes in glacier parameters for Cordillera Blanca of Peru using data from Système Probatoire d'Observation de la Terre (SPOT) sensor, an old glacier inventory from 1970 aerial photography, field-based mass balance measurements and meteorological observations. Here we focus on: constructing a geospatial glacier inventory from 2003 SPOT scenes; mass balance estimations using remote sensing and field data; frequency distribution of glacier area; changes in termini elevations; hypsometry changes over time; glacier topography (slope, aspect, length/width ratio); AAR vs. mass balance for Artesonraju and Yanamarey benchmark glaciers; precipitation and temperature trends in the region. Over the last 25 years, mean temperatures increases of 0.09 deg.C/yr were greater at lower elevation than the 0.01 deg.C/yr at higher elevations, with little change in precipitation. Comparison of the new SPOT-based glacier inventory with the 1970 inventory shows that glaciers in Cordillera Blanca retreated at a rate of 0.6% per year over the last three decades, with no significant differences in the rate of area loss between E and W side. At lower elevations there is an upward shift of glacier termini along with a decrease in glacier area. Small glaciers are losing more area than large glaciers. Based on the relationship between specific mass balance (bn) and accumulation area ratio (AAR) for the two benchmark glaciers, we predicted a steady-state equilibrium line

  16. Transfer Relations Between Landscape Functions - The Hydrological Point of View

    NASA Astrophysics Data System (ADS)

    Fohrer, N.; Lenhart, T.; Eckhardt, K.; Frede, H.-G.

    EC market policies and regional subsidy programs have an enormous impact on local land use. This has far reaching consequences on various landscape functions. In the joint research project SFB299 at the Giessen University the effect of land use options on economic, ecological and hydrological landscape functions are under investigation. The continuous time step model SWAT-G (Eckhardt et al., 2000; Arnold et al., 1998) is employed to characterize the influence of land use patterns on hydrological processes. The model was calibrated and validated employing a split sample approach. For two mesoscale watersheds (Aar, 60 km2; Dietzhölze, 81 km2) located in the Lahn-Dill- Bergland, Germany, different land use scenarios were analyzed with regard to their hydrological impact. Additionally the effect of land use change was analyzed with an ecological and an agro-economic model. The impact of the stepwise changing land use was expressed as trade off relations between different landscape functions.

  17. Fuzzy object modeling

    NASA Astrophysics Data System (ADS)

    Udupa, Jayaram K.; Odhner, Dewey; Falcao, Alexandre X.; Ciesielski, Krzysztof C.; Miranda, Paulo A. V.; Vaideeswaran, Pavithra; Mishra, Shipra; Grevera, George J.; Saboury, Babak; Torigian, Drew A.

    2011-03-01

    To make Quantitative Radiology (QR) a reality in routine clinical practice, computerized automatic anatomy recognition (AAR) becomes essential. As part of this larger goal, we present in this paper a novel fuzzy strategy for building bodywide group-wise anatomic models. They have the potential to handle uncertainties and variability in anatomy naturally and to be integrated with the fuzzy connectedness framework for image segmentation. Our approach is to build a family of models, called the Virtual Quantitative Human, representing normal adult subjects at a chosen resolution of the population variables (gender, age). Models are represented hierarchically, the descendents representing organs contained in parent organs. Based on an index of fuzziness of the models, 32 thorax data sets, and 10 organs defined in them, we found that the hierarchical approach to modeling can effectively handle the non-linear relationships in position, scale, and orientation that exist among organs in different patients.

  18. Contest of Web-Based Geospatial Applications for Students and Young Scientists

    NASA Astrophysics Data System (ADS)

    Tsai, F.; Cho, K.

    2016-06-01

    The Asian Association on Remote Sensing (AARS) organizes a web contest (WEBCON) of photogrammetry, remote sensing and spatial information sciences in the annual meeting of Asian Conference on Remote Sensing (ACRS) every year. The purpose of WEBCON is to promote the development of web and other forms of internet services of the internet related to geo-information sciences and to attract more students and young scientists participating in the related fields of study and applications. Since 2011, WEBCON has become one of the major events in ACRS and successfully increased the interest in the research, development and applications of photogrammetry, remote sensing and spatial information sciences among students and young scientist. The success of WEBCON is an excellent example of promoting the profession of spatial information to young people.

  19. Roles of endothelial nitric oxide synthase (eNOS) and mitochondrial permeability transition pore (MPTP) in epoxyeicosatrienoic acid (EET)-induced cardioprotection against infarction in intact rat hearts.

    PubMed

    Gross, Garrett J; Hsu, Anna; Pfeiffer, Adam W; Nithipatikom, Kasem

    2013-06-01

    We previously demonstrated that 11,12 and 14,15-epoxeicosatrienoic acids (EETs) produce cardioprotection against ischemia-reperfusion injury in dogs and rats. Several signaling mechanisms have been implicated in the cardioprotective actions of the EETs; however, their mechanisms remain largely elusive. Since nitric oxide (NO) plays a significant role in cardioprotection and EETs have been demonstrated to induce NO production in various tissues, we hypothesized that NO is involved in mediating the EET actions in cardioprotection. To test this hypothesis, we used an in vivo rat model of infarction in which intact rat hearts were subjected to 30-min occlusion of the left coronary artery and 2-hr reperfusion. 11,12-EET or 14,15-EET (2.5mg/kg) administered 10min prior to the occlusion reduced infarct size, expressed as a percentage of the AAR (IS/AAR), from 63.9±0.8% (control) to 45.3±1.2% and 45.5±1.7%, respectively. A nonselective nitric oxide synthase (NOS) inhibitor, L-NAME (1.0mg/kg) or a selective endothelial NOS inhibitor, L-NIO (0.30mg/kg) alone did not affect IS/AAR but they completely abolished the cardioprotective effects of the EETs. On the other hand, a selective neuronal NOS inhibitor, nNOS I (0.03mg/kg) and a selective inducible NOS inhibitor, 1400W (0.10mg/kg) did not affect IS/AAR or block the cardioprotective effects of the EETs. Administration of 11,12-EET (2.5mg/kg) to the rats also transiently increased the plasma NO concentration. 14,15-EET (10μM) induced the phosphorylation of eNOS (Ser(1177)) as well as a transient increase of NO production in rat cardiomyoblast cell line (H9c2 cells). When 11,12-EET or 14,15-EET was administered at 5min prior to reperfusion, infarct size was also reduced to 42.8±2.2% and 42.6±1.9%, respectively. Interestingly, L-NAME (1.0mg/kg) and a mitochondrial KATP channel blocker, 5-HD (10mg/kg) did not abolish while a sarcolemmal KATP channel blocker, HMR 1098 (6.0mg/kg) and a mitochondrial permeability transition

  20. The glaciers of Sierra Segundera (Zamora, NW Spain) during their Maximum Ice Extent: area, volume, Glacial Equilibrium Line Altitude and paleo-climatic implications

    NASA Astrophysics Data System (ADS)

    María Fernández, Jose; Ubeda, Jose; Palacios, David

    2015-04-01

    The aim of this paper is to reconstruct the Quaternary glaciers which formed the eastern sector of the Sierra Segundera ice-cap (NW Iberian Peninsula) during its Maximum Ice Extent (MIE) local phase (33 ka) in a surface area of 165 km2, to estimate the ice volumes and Equilibrium Line Altitudes (ELAs). The study area presents a wide altimetric range of approx. 1200 m, from the Tera glacier front to the Peña Trevinca (42°14'33'' N, 6°47'46'' W; 2127 m) and Peña Negra (42°14'58'' N, 6°47'39'' W; 2121 m) horns, covering a wide plateau at an altitude of over 1700 m. The reconstruction of the MIE paleoglaciers used a combination of various tools: a rheological numerical model which describes the ice flow, GIS and geomorphological field work to validate the results. The model used here allowed the reconstruction of the surface topography of the paleoglacial ice, even though there is no existing geomorphologic evidence to reveal the thickness of the ice at that time. The GIS enabled the creation of Digital Elevation Models (DEMs) and the estimation of thicknesses and volumes. The reconstructed topography and the delimitation of the geomorphologic features were used to estimate the ELA using the following methods: Area x Altitude Balance Ratio (AABR), Accumulation Area Ratio (AAR), Terminus Headwall Altitude Ratio (THAR) and Maximum Elevation of Lateral Moraines (MELM). The DEM reconstructed for the surface of the paleoglaciers obtained an estimated maximum ice thickness of over 450 m during the MIE, and a total ice volume of 2.63 x 10(10)m3 for the eastern half of the ice-cap. When estimating the paleo-ELAs, the AABR and AAR methods obtain more logical values. The AABR method obtains BR=1, which questions the BR=2 assumed as representative for medium latitude glaciers with oceanic influence; the paleo-ELA AABR was 1739 m. Applying the AAR method with the ratio 0.65 gives the result 1735 m. The THAR and MELM methods give values of 1637 m and 1651 m respectively for

  1. Strutjet RBCC Engine Performance

    NASA Technical Reports Server (NTRS)

    Bulman, Mel; Neill, Todd; Yam, Clement

    1999-01-01

    In the past two years Strutjet Rocket Based Combined Cycle (RBCC) engine has been tested extensively under the Advanced Reusable Technology (ART) contract from NASA MSFC. RBCC Engines combine the high thrust to weight of the rocket with the high efficiency of the ramjet engine. This propulsion system has the potential to reduce the cost of launching payloads to orbit by up to a factor of 100. In the ART program we have conducted over 100 hot fire tests. The propellants have been hydrogen and oxygen. The Modes tested have included the Air Augmented Rocket (AAR) from M = 0 to 2.4, the Ramjet at M = 2.4 & 6, Scramjet at M = 6 & 8, Scram/Rocket at Mach 8 and Ascent Rocket in Vacuum. This invited paper will present an overview of these test results and plans for future development of this propulsion cycle.

  2. How to predict Italy L'Aquila M6.3 earthquake

    NASA Astrophysics Data System (ADS)

    Guo, Guangmeng

    2016-04-01

    According to the satellite cloud anomaly appeared over eastern Italy on 21-23 April 2012, we predicted the M6.0 quake occurred in north Italy successfully. Here checked the satellite images in 2011-2013 in Italy, and 21 cloud anomalies were found. Their possible correlation with earthquakes bigger than M4.7 which located in Italy main fault systems was statistically examined by assuming various lead times. The result shows that when the leading time interval is set to 23≤ΔT≤45 days, 8 of the 10 quakes were preceded by cloud anomalies. Poisson random test shows that AAR (anomaly appearance rate) and EOR (EQ occurrence rate) is much higher than the values by chance. This study proved the relation between cloud anomaly and earthquake in Italy. With this method, we found that L'Aquila earthquake can also be predicted according to cloud anomaly.

  3. Determination of Constitutive Equation for Thermo-mechanical Processing of INCONEL 718 Through Double Multivariate Nonlinear Regression Analysis

    NASA Astrophysics Data System (ADS)

    Hussain, Mirza Zahid; Li, Fuguo; Wang, Jing; Yuan, Zhanwei; Li, Pan; Wu, Tao

    2015-07-01

    The present study comprises the determination of constitutive relationship for thermo-mechanical processing of INCONEL 718 through double multivariate nonlinear regression, a newly developed approach which not only considers the effect of strain, strain rate, and temperature on flow stress but also explains the interaction effect of these thermo-mechanical parameters on flow behavior of the alloy. Hot isothermal compression experiments were performed on Gleeble-3500 thermo-mechanical testing machine in the temperature range of 1153 to 1333 K within the strain rate range of 0.001 to 10 s-1. The deformation behavior of INCONEL 718 is analyzed and summarized by establishing the high temperature deformation constitutive equation. The calculated correlation coefficient ( R) and average absolute relative error ( AARE) underline the precision of proposed constitutive model.

  4. Prediction of Weather Impacted Airport Capacity using Ensemble Learning

    NASA Technical Reports Server (NTRS)

    Wang, Yao Xun

    2011-01-01

    Ensemble learning with the Bagging Decision Tree (BDT) model was used to assess the impact of weather on airport capacities at selected high-demand airports in the United States. The ensemble bagging decision tree models were developed and validated using the Federal Aviation Administration (FAA) Aviation System Performance Metrics (ASPM) data and weather forecast at these airports. The study examines the performance of BDT, along with traditional single Support Vector Machines (SVM), for airport runway configuration selection and airport arrival rates (AAR) prediction during weather impacts. Testing of these models was accomplished using observed weather, weather forecast, and airport operation information at the chosen airports. The experimental results show that ensemble methods are more accurate than a single SVM classifier. The airport capacity ensemble method presented here can be used as a decision support model that supports air traffic flow management to meet the weather impacted airport capacity in order to reduce costs and increase safety.

  5. Synthesis and structure-activity relationships of novel arylpiperazines as potent antagonists of α1-adrenoceptor.

    PubMed

    Silva, Renata Oliveira; de Oliveira, Andressa Souza; Nunes Lemes, Laís Flávia; de Camargo Nascente, Luciana; Coelho do Nascimento Nogueira, Patrícia; Silveira, Edilberto R; Brand, Guilherme D; Vistoli, Giulio; Cilia, Antonio; Poggesi, Elena; Buccioni, Michela; Marucci, Gabriella; Bolognesi, Maria Laura; Romeiro, Luiz Antonio Soares

    2016-10-21

    Arylpiperazines 2-11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Modifications at the 1,3-benzodioxole and phenyl phamacophoric units resulted in the identification of a number of potent compounds (moderately selective with respect to the α1b-AR), in binding experiments. Notably, compound 7 (LDT451) showed a subnanomolar pKi of 9.41 towards α1a-AR. An encouragingly lower α1B-potency was a general trend for all the series of compounds, which showed α1A/D over α1B selectivity in functional assays. If adequately optimized, such peculiar selectivity could have relevance for a potential LUTS/BPH therapeutic application. PMID:27448917

  6. Synthesis, structure-affinity relationships, and molecular modeling studies of novel pyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists.

    PubMed

    Lenzi, Ombretta; Colotta, Vittoria; Catarzi, Daniela; Varano, Flavia; Squarcialupi, Lucia; Filacchioni, Guido; Varani, Katia; Vincenzi, Fabrizio; Borea, Pier Andrea; Dal Ben, Diego; Lambertucci, Catia; Cristalli, Gloria

    2011-06-15

    This paper reports the study of new 2-phenyl- and 2-methylpyrazolo[3,4-c]quinolin-4-ones (series A) and 4-amines (series B), designed as adenosine receptor (AR) antagonists. The synthesized compounds bear at the 6-position various groups, with different lipophilicity and steric hindrance, that were thought to increase human A(1) and A(2A) AR affinities and selectivities, with respect to those of the parent 6-unsubstituted compounds. In series A, this modification was not tolerated since it reduced AR affinity, while in series B it shifted the binding towards the hA(1) subtype. To rationalize the observed structure-affinity relationships, molecular docking studies at A(2A)AR-based homology models of the A(1) and A(3) ARs and at the A(2A)AR crystal structure were carried out. PMID:21616671

  7. ERP and Adaptive Autoregressive identification with spectral power decomposition to study rapid auditory processing in infants.

    PubMed

    Piazza, C; Cantiani, C; Tacchino, G; Molteni, M; Reni, G; Bianchi, A M

    2014-01-01

    The ability to process rapidly-occurring auditory stimuli plays an important role in the mechanisms of language acquisition. For this reason, the research community has begun to investigate infant auditory processing, particularly using the Event Related Potentials (ERP) technique. In this paper we approach this issue by means of time domain and time-frequency domain analysis. For the latter, we propose the use of Adaptive Autoregressive (AAR) identification with spectral power decomposition. Results show EEG delta-theta oscillation enhancement related to the processing of acoustic frequency and duration changes, suggesting that, as expected, power modulation encodes rapid auditory processing (RAP) in infants and that the time-frequency analysis method proposed is able to identify this modulation. PMID:25571014

  8. Anal carcinoma and HIV infection: is it time for screening?

    PubMed

    Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M

    2014-03-01

    A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented? PMID:24139082

  9. Peripatetic Highlights in Bern

    NASA Astrophysics Data System (ADS)

    Hentschel, Ann M.

    The capital city of the Swiss Canton of Bern and of the Swiss Confederation is nestled in a narrow loop of the Aare river, at the foot of the Alps. The old town, founded around 1191, is well preserved despite a devastating fire in 1405.** Major industries of the region developed under the constraints of modest domestic markets, high transportation costs, and protectionist legislation across national borders. Switzerland thus found its niche in higher-end markets, such as chocolate making, engine building, instruments, fine textiles, and chemicals or pharmaceuticals. My tour past historically significant scientific sites in Bern will use the local legacy of its most illustrious residents, Albert Einstein (1879-1955), who lived there from 1902-1909, and Fritz Houtermans (1903-1966), who lived there from 1952-1966, as its guiding thread through the old town and the university district. Place names in italics mark stops along the tour.

  10. Fuzzylot: a novel self-organising fuzzy-neural rule-based pilot system for automated vehicles.

    PubMed

    Pasquier, M; Quek, C; Toh, M

    2001-10-01

    This paper presents part of our research work concerned with the realisation of an Intelligent Vehicle and the technologies required for its routing, navigation, and control. An automated driver prototype has been developed using a self-organising fuzzy rule-based system (POPFNN-CRI(S)) to model and subsequently emulate human driving expertise. The ability of fuzzy logic to represent vague information using linguistic variables makes it a powerful tool to develop rule-based control systems when an exact working model is not available, as is the case of any vehicle-driving task. Designing a fuzzy system, however, is a complex endeavour, due to the need to define the variables and their associated fuzzy sets, and determine a suitable rule base. Many efforts have thus been devoted to automating this process, yielding the development of learning and optimisation techniques. One of them is the family of POP-FNNs, or Pseudo-Outer Product Fuzzy Neural Networks (TVR, AARS(S), AARS(NS), CRI, Yager). These generic self-organising neural networks developed at the Intelligent Systems Laboratory (ISL/NTU) are based on formal fuzzy mathematical theory and are able to objectively extract a fuzzy rule base from training data. In this application, a driving simulator has been developed, that integrates a detailed model of the car dynamics, complete with engine characteristics and environmental parameters, and an OpenGL-based 3D-simulation interface coupled with driving wheel and accelerator/ brake pedals. The simulator has been used on various road scenarios to record from a human pilot driving data consisting of steering and speed control actions associated to road features. Specifically, the POPFNN-CRI(S) system is used to cluster the data and extract a fuzzy rule base modelling the human driving behaviour. Finally, the effectiveness of the generated rule base has been validated using the simulator in autopilot mode. PMID:11681754

  11. North Cascade Glacier Annual Mass Balance Record Analysis 1984-2013

    NASA Astrophysics Data System (ADS)

    Pelto, M. S.

    2014-12-01

    The North Cascade Glacier Climate Project (NCGCP) was founded in 1983 to monitor 10 glaciers throughout the range and identify their response to climate change. The annual observations include mass balance, terminus behavior, glacier surface area and accumulation area ratio (AAR). Annual mass balance (Ba) measurements have been continued on the 8 original glaciers that still exist. Two glaciers have disappeared: the Lewis Glacier and Spider Glacier. In 1990, Easton Glacier and Sholes Glacier were added to the annual balance program to offset the loss. One other glacier Foss Glacier has declined to the extent that continued measurement will likely not be possible. Here we examine the 30 year long Ba time series from this project. All of the data have been reported to the World Glacier Monitoring Service (WGMS). This comparatively long record from glaciers in one region conducted by the same research program using the same methods offers some useful comparative data. Degree day factors for melt of 4.3 mm w.e.°C-1d-1 for snow and 6.6 mm w.e.°C-1d-1 for ice has been determined from 412 days of ablation observation. The variation in the AAR for equilibrium Ba is small ranging from 60 to 67. The mean annual balance of the glaciers from 1984-2013 is -0.45 ma-1, ranging from -0.31 to -0.57 ma-1 for individual glacier's. The correlation coefficient of Ba is above 0.80 between all glaciers including the USGS benchmark glacier, South Cascade Glacier. This indicates that the response is to regional climate change, not local factors. The mean annual balance of -0.45 ma-1 is close to the WGMS global average for this period -0.50 ma-1. The cumulative loss of 13.5 m w.e. and 15 m of ice thickness represents more than 20% of the volume of the glaciers.

  12. Upregulation of Phosphodiesterase type 5 in the Hyperplastic Prostate

    PubMed Central

    Zhang, Wenhao; Zang, Ning; Jiang, Yaoming; Chen, Ping; Wang, Xinghuan; Zhang, Xinhua

    2015-01-01

    Both erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) are common in the aging male. Numerous clinical trials have demonstrated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5-Is) for treating LUTS/BPH with/without ED. However, the influence of BPH on prostatic PDE5 expression has never been studied. A testosterone-induced rat model of BPH was developed and human hyperplastic prostate specimens were harvested during cystoprostatectomy. PDE5, nNOS, eNOS and α1-adrenoreceptor subtypes (α1aARs, α1bARs and α1dARs) were determined with real-time RT-PCR for rat tissues whilst PDE5 and α1-adrenoreceptor subtypes were determined in human samples. PDE5 was further analyzed with Western-blot and histological examination. Serum testosterone was measured with ELISA. The rat BPH model was validated as having a significantly enlarged prostate. PDE5 localized mainly in fibromuscular stroma in prostate. Our data showed a significant and previously undocumented upregulation of PDE5 in both rat and human BPH, along with increased expression of nNOS and α1dARs for rat tissues and α1aARs for human BPH. The upregulation of PDE5 in the hyperplastic prostate could explain the mechanism and contribute to the high effectiveness of PDE5-Is for treating LUTS/BPH. Fibromuscular stroma could be the main target for PDE5-Is within prostate. PMID:26657792

  13. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) is a pro-survival, endoplasmic reticulum (ER) stress response gene involved in tumor cell adaptation to nutrient availability.

    PubMed

    Méndez-Lucas, Andrés; Hyroššová, Petra; Novellasdemunt, Laura; Viñals, Francesc; Perales, Jose C

    2014-08-01

    Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), encoded by the nuclear PCK2 gene, links TCA cycle intermediates and glycolytic pools through the conversion of mitochondrial oxaloacetate into phosphoenolpyruvate. In the liver PEPCK-M adjoins its profusely studied cytosolic isoform (PEPCK-C) potentiating gluconeogenesis and TCA flux. However, PEPCK-M is present in a variety of non-gluconeogenic tissues, including tumors of several origins. Despite its potential relevance to cancer metabolism, the mechanisms responsible for PCK2 gene regulation have not been elucidated. The present study demonstrates PEPCK-M overexpression in tumorigenic cells as well as the mechanism for the modulation of PCK2 abundance under several stress conditions. Amino acid limitation and ER stress inducers, conditions that activate the amino acid response (AAR) and the unfolded protein response (UPR), stimulate PCK2 gene transcription. Both the AAR and UPR lead to increased synthesis of ATF4, which mediates PCK2 transcriptional up-regulation through its binding to a putative ATF/CRE composite site within the PCK2 promoter functioning as an amino acid response element. In addition, activation of the GCN2-eIF2α-ATF4 and PERK-eIF2α-ATF4 signaling pathways are responsible for increased PEPCK-M levels. Finally, PEPCK-M knockdown using either siRNA or shRNA were sufficient to reduce MCF7 mammary carcinoma cell growth and increase cell death under glutamine deprivation or ER stress conditions. Our data demonstrate that this enzyme has a critical role in the survival program initiated upon stress and shed light on an unexpected and important role of mitochondrial PEPCK in cancer metabolism. PMID:24973213

  14. Influence of granitoid textural parameters on sediment composition: Implications for sediment generation

    NASA Astrophysics Data System (ADS)

    Caracciolo, L.; Tolosana-Delgado, R.; Le Pera, E.; von Eynatten, H.; Arribas, J.; Tarquini, S.

    2012-12-01

    The aim of this study is to determine and characterise the control exerted by parent rock texture on sand composition as a function of grain size. The sands investigated were generated from granitoid parent rocks by the Rhone, Damma and Sidelen glaciers, which drain the Aar Massif in the Central Alps (Switzerland), and were deposited in glacial and fluvio-glacial settings. Mechanical erosion, comminution (crystal breakdown and abrasion) and hydraulic sorting are the most important processes controlling the generation of sediments in this environment, whereas chemical and/or biochemical weathering plays a negligible role. By using a GIS-based Microscopic Information System (MIS), five samples from the glacier-drained portions of the Aar basement have been analysed to determine textural parameters such as modal composition, crystal size distribution and mineral interfaces (types and lengths). Petrographic data of analysed sands include traditional point counts (Gazzi-Dickinson method, minimum of 300 points) as well as textural counts to determine interface types, frequency, and polycrystallinity in phaneritic rock fragments. According to Pettijohn's classification, grain-size dependent compositions vary from feldspathic litharenite (0φ fraction) via lithic arkose (1φ and 2φ) to arkose (3φ and 4φ). Compositional differences among our data set were compared to modern plutoniclastic sands from the Iberian Massif (Spain) and the St. Gabriel Mts. (California, USA), which allowed us to assess the role exerted by glaciers in generating sediments. By combining data from the MIS with those from petrographic analysis, we outlined the evolution of mineral interfaces from the parent rocks to the sediments.

  15. G protein-coupled receptors, an unexploited animal toxin targets: Exploration of green mamba venom for novel drug candidates active against adrenoceptors.

    PubMed

    Maïga, Arhamatoulaye; Mourier, Gilles; Quinton, Loïc; Rouget, Céline; Gales, Céline; Denis, Colette; Lluel, Philippe; Sénard, Jean-Michel; Palea, Stefano; Servent, Denis; Gilles, Nicolas

    2012-03-15

    At a time when pharmaceutical companies are having trouble finding new low MW drugs and when biologics are becoming more common, animal venoms could constitute an underexploited source of novel drug candidates. We looked for identifying novel animal toxins active against G protein-coupled receptors (GPCR), the most frequently exploited class of treatment targets, with the aim to develop novel research tools and drug candidates. Screening of green mamba (Dendroaspis angusticeps) venom against adrenoceptors identified two novel venom peptides. ρ-Da1a shown an affinity of 0.35 nM for the α1a-AR while ρ-Da1b displayed affinities between 14 and 73 nM for the three α2-ARs. These two venom peptides have sequences similar to those of muscarinic toxins and belong to the three-finger-fold protein family. α1a-AR is the primary target for the treatment of prostate hypertrophy. In vitro and in vivo tests demonstrated that ρ-Da1a reduced prostatic muscle tone as efficiently as tamsulosin (an antagonist presently used), but with fewer cardiovascular side effects. α2-ARs are the prototype of GPCRs not currently used as treatment targets due to a lack of specific ligands. Blockage of these receptors increases intestinal motility, which may be compromised by abdominal surgery and reduces orthosteric hypotension. In vitro and in vivo tests demonstrated that ρ-Da1b antagonizes α2-ARs in smooth muscles and increased heart rate and blood catecholamine concentrations. These results highlight possible exploitation of ρ-Da1a and ρ-Da1b in important pathologies. PMID:21419153

  16. A simple, flexible and high-throughput cloning system for plant genome editing via CRISPR-Cas system.

    PubMed

    Kim, Hyeran; Kim, Sang-Tae; Ryu, Jahee; Choi, Min Kyung; Kweon, Jiyeon; Kang, Beum-Chang; Ahn, Hyo-Min; Bae, Suji; Kim, Jungeun; Kim, Jin-Soo; Kim, Sang-Gyu

    2016-08-01

    CRISPR-Cas9 system is now widely used to edit a target genome in animals and plants. Cas9 protein derived from Streptococcus pyogenes (SpCas9) cleaves double-stranded DNA targeted by a chimeric single-guide RNA (sgRNA). For plant genome editing, Agrobacterium-mediated T-DNA transformation has been broadly used to express Cas9 proteins and sgRNAs under the control of CaMV 35S and U6/U3 promoter, respectively. We here developed a simple and high-throughput binary vector system to clone a 19-20 bp of sgRNA, which binds to the reverse complement of a target locus, in a large T-DNA binary vector containing an SpCas9 expressing cassette. Two-step cloning procedures: (1) annealing two target-specific oligonucleotides with overhangs specific to the AarI restriction enzyme site of the binary vector; and (2) ligating the annealed oligonucleotides into the two AarI sites of the vector, facilitate the high-throughput production of the positive clones. In addition, Cas9-coding sequence and U6/U3 promoter can be easily exchanged via the Gateway(TM) system and unique EcoRI/XhoI sites on the vector, respectively. We examined the mutation ratio and patterns when we transformed these constructs into Arabidopsis thaliana and a wild tobacco, Nicotiana attenuata. Our vector system will be useful to generate targeted large-scale knock-out lines of model as well as non-model plant. PMID:26946469

  17. Microphysiometric analysis of human α1a-adrenoceptor expressed in Chinese hamster ovary cells

    PubMed Central

    Taniguchi, Takanobu; Inagaki, Rika; Murata, Satoshi; Akiba, Isamu; Muramatsu, Ikunobu

    1999-01-01

    The human recombinant α1a-adrenoceptor (AR) has been stably expressed in Chinese hamster ovary cells. Four stable clones, aH4, aH5, aH6 and aH7, expressing 30, 370, 940 and 2900 fmol AR mg−1 protein, respectively, have been employed to characterize this AR subtype using radioligand binding and microphysiometry to measure extracellular acidification rates.Noradrenaline (NA) gave concentration-dependent responses in microphysiometry with increasing extracellular acidification rates. The potency of NA increased as the receptor density increased; pEC50 values of NA for the clones aH4, aH5, aH6 and aH7 were 6.9, 7.5, 7.8 and 8.1, respectively. This increase of potency according to receptor density indicates the presence of spare receptor for NA. Methoxamine, phenylephrine, oxymetazoline and clonidine also gave concentration-dependent responses with various intrinsic activities.Antagonists shifted concentration-response curves for NA rightward in a concentration-dependent manner. Schild analysis revealed that the affinity profile of this AR subtype to antagonists in the clone aH7 had a typical pattern for the α1a-AR; high affinity for prazosin and WB 4101, and low affinity for BMY7378 (pA2=9.5, 9.8 and 7.3, respectively). This profile is similar in the case of the clone aH4. These affinities were in good agreement with those obtained in binding experiments.These results have demonstrated that (1) classical receptor theory can be applied in microphysiometry, and (2) microphysiometry is a useful tool to investigate the pharmacological characterization of α1a-AR. PMID:10433504

  18. Modeling debris-covered glaciers: response to steady debris deposition

    NASA Astrophysics Data System (ADS)

    Anderson, Leif S.; Anderson, Robert S.

    2016-05-01

    Debris-covered glaciers are common in rapidly eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. If continuous debris cover is present, ablation rates can be significantly reduced leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2-D long-valley numerical glacier model that includes englacial and supraglacial debris advection. We ran 120 simulations on a linear bed profile in which a hypothetical steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier terminus. Our model and parameter selections can produce 2-fold increases in glacier length. Debris flux onto the glacier and the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris-related variables are held constant. Debris deposited near the equilibrium-line altitude re-emerges high in the ablation zone and therefore impacts melt rate over a greater fraction of the glacier surface. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to initial debris-free glaciers. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). Our simulations reproduce the "general trends" between debris cover, AARs, and glacier surface velocity patterns from modern debris-covered glaciers. We provide a quantitative, theoretical foundation to interpret the effect of debris cover on the moraine record, and to assess the effects of climate change on debris-covered glaciers.

  19. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment

    SciTech Connect

    Ling, Jiqiang; Peterson, Kaitlyn M.; Simonovic, Ivana; Cho, Chris; Soll, Dieter; Simonovic, Miljan

    2014-03-12

    Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular ?? with a threonine (Thr) anticodon, MST1 also recognizes an unusual ??, which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employs distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for ?? recognition, whereas the anticodon sequence is essential for aminoacylation of ??. The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate ??, reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix {alpha}11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria.

  20. Chemistry of Hydrothermal Plumes at 159°E on the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Hahm, D.; Baker, E. T.; Rhee, T. S.; Lupton, J. E.; Resing, J. A.; Park, S. H.

    2014-12-01

    The Australian-Antarctic Ridge (AAR) is one of the largest unexplored regions of the global mid-ocean ridge system. In the present contribution, we present the geochemistry of the hydrothermal plumes over the KR1, an AAR segment at 159ºE and 62ºS. In 2011, we collected 48 Miniature Autonomous Plume Recorder profiles, measuring optical back scatter and oxidation-reduction potential, and identified the area between 158.5 and 159ºE as the densest concentration of active hydrothermal sites. In order to further characterize the chemistry of the hydrothermal plumes over the area, named 'Mujin', we conducted intensive vertical and tow-yo CTD casts in 2013. The maximum concentrations of the chemical tracers 3He, CH4, H2, and dissolved Mn, were 7.47 fmol/kg, 19.6 nmol/kg, 8.8 nmol/kg, 94.3 nmol/L, respectively. The CH4/3He (1 -10) and CH4/Mn (0.01 - 0.2) ratios were significantly lower than many ultra-mafic hosted systems, which are often found in slow spreading ridges. The lower ratios are consistent with a basaltic-hosted system, typical of the intermediate spreading rate of 6.8 cm/yr of KR1. Additionally, some of the plume samples collected around 158.6 and 158.8ºE exhibited slightly higher ratios of H2/3He than the others. Assuming that H2 is produced from the reduction of water by reduced iron compounds in the rock, the higher ratios suggest that those plumes are supported by a younger hydrothermal system, which may have experienced a recent eruption.

  1. First hydrothermal discoveries on the Australian-Antarctic Ridge: Discharge sites, plume chemistry, and vent organisms

    NASA Astrophysics Data System (ADS)

    Hahm, Doshik; Baker, Edward T.; Siek Rhee, Tae; Won, Yong-Jin; Resing, Joseph A.; Lupton, John E.; Lee, Won-Kyung; Kim, Minjeong; Park, Sung-Hyun

    2015-09-01

    The Australian-Antarctic Ridge (AAR) is one of the largest unexplored regions of the global mid-ocean ridge system. Here, we report a multiyear effort to locate and characterize hydrothermal activity on two first-order segments of the AAR: KR1 and KR2. To locate vent sites on each segment, we used profiles collected by Miniature Autonomous Plume Recorders on rock corers during R/V Araon cruises in March and December of 2011. Optical and oxidation-reduction-potential anomalies indicate multiple active sites on both segments. Seven profiles on KR2 found 3 sites, each separated by ˜25 km. Forty profiles on KR1 identified 17 sites, some within a few kilometer of each other. The spatial density of hydrothermal activity along KR1 and KR2 (plume incidence of 0.34) is consistent with the global trend for a spreading rate of ˜70 mm/yr. The densest area of hydrothermal activity, named "Mujin," occurred along the 20 km-long inflated section near the segment center of KR1. Continuous plume surveys conducted in January-February of 2013 on R/V Araon found CH4/3He (1 - 15 × 106) and CH4/Mn (0.01-0.5) ratios in the plume samples, consistent with a basaltic-hosted system and typical of ridges with intermediate spreading rates. Additionally, some of the plume samples exhibited slightly higher ratios of H2/3He and Fe/Mn than others, suggesting that those plumes are supported by a younger hydrothermal system that may have experienced a recent eruption. The Mujin-field was populated by Kiwa crabs and seven-armed Paulasterias starfish previously recorded on the East Scotia Ridge, raising the possibility of circum-Antarctic biogeographic connections of vent fauna.

  2. L-arginine recognition by yeast arginyl-tRNA synthetase.

    PubMed Central

    Cavarelli, J; Delagoutte, B; Eriani, G; Gangloff, J; Moras, D

    1998-01-01

    The crystal structure of arginyl-tRNA synthetase (ArgRS) from Saccharomyces cerevisiae, a class I aminoacyl-tRNA synthetase (aaRS), with L-arginine bound to the active site has been solved at 2.75 A resolution and refined to a crystallographic R-factor of 19.7%. ArgRS is composed predominantly of alpha-helices and can be divided into five domains, including the class I-specific active site. The N-terminal domain shows striking similarity to some completely unrelated proteins and defines a module which should participate in specific tRNA recognition. The C-terminal domain, which is the putative anticodon-binding module, displays an all-alpha-helix fold highly similar to that of Escherichia coli methionyl-tRNA synthetase. While ArgRS requires tRNAArg for the first step of the aminoacylation reaction, the results show that its presence is not a prerequisite for L-arginine binding. All H-bond-forming capability of L-arginine is used by the protein for the specific recognition. The guanidinium group forms two salt bridge interactions with two acidic residues, and one H-bond with a tyrosine residue; these three residues are strictly conserved in all ArgRS sequences. This tyrosine is also conserved in other class I aaRS active sites but plays several functional roles. The ArgRS structure allows the definition of a new framework for sequence alignments and subclass definition in class I aaRSs. PMID:9736621

  3. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart

    PubMed Central

    Thomas, R. Croft; Singh, Abhishek; Cowley, Patrick; Myagmar, Bat-Erdene; Montgomery, Megan D.; Swigart, Philip M.; De Marco, Teresa; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    Background Translation of preclinical findings could benefit from a simple, reproducible, high throughput human model to study myocardial signaling. Alpha-1A-adrenergic receptors (ARs) are expressed at very low levels in the human heart, and it is unknown if they function. Objectives To develop a high throughput human myocardial slice culture model, and to test the hypothesis that alpha-1A- ARs are functional in the human heart. Methods Cores of LV free wall 8 mm diameter were taken from 52 hearts (18 failing and 34 nonfailing). Slices 250 μm thick were cut with a Krumdieck apparatus and cultured using a rotating incubation unit. Results About 60 slices were cut from each LV core, and a typical study could use 96 slices. Myocyte morphology was maintained, and diffusion into the slice center was rapid. Slice viability was stable for at least 3 days in culture by ATP and MTT assays. The beta-AR agonist isoproterenol stimulated phospholamban phosphorylation, and the alpha-1A-AR agonist A61603 stimulated ERK phosphorylation, with nanomolar EC50 values in slices from both failing and nonfailing hearts. Strips cut from the slices were used to quantify activation of contraction by isoproterenol, A61603, and phenylephrine. The slices supported transduction by adenovirus. Conclusions We have developed a simple, high throughput LV myocardial slice culture model to study signaling in the human heart. This model can be useful for translational studies, and we show for the first time that the alpha-1A-AR is functional in signaling and contraction in the human heart. PMID:27453955

  4. Localization of two human autoantigen genes by PCR screening and in situ hybridization-glycyl-tRNA synthetase locates to 7p15 and Alanyl-tRNA synthetase locates to 16q22

    SciTech Connect

    Nichols, R.C.; Pai, S.I.; Liu, P.; Ge, Q.; Targoff, I.N.

    1995-11-01

    Aminoacyl-tRNA synthetases (aminoacyl-RS) catalyze the attachment of an amino acid to its cognate tRNA. Five of 20 human aminoacyl-RS (histidyl-RS, threonyl-RS, isoleucyl-RS, glycyl-RS, and alanyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis (PM/DM; 9). A sixth autoantigenic amino-acyl-RS, lysyl-RS, was recently reported. The genes for histidyl-RS and threonyl-RS have been assigned to chromosome 5, as have the genes for leucyl-RS and arginyl-RS. Six other aminoacyl-RS (glutamyl-prolyl-RS, valyl-RS, cysteinyl-RS, methionyl-RS, tryptophanyl-RS, and asparaginyl-RS) were assigned to chromosomes 1, 6, 11, 12, 14, and 18, respectively. The reason for a preponderance of aminoacyl-RS genes on chromosome 5 is unknown, but it has been suggested that regulatory relatedness might be a factor. Recently the entire or partial cDNA sequences for two autoantigenic aminoacyl-RS genes, glycyl-RS (gene symbol GARS; 4) and alanyl-RS (gene symbol AARS; 1), were reported. To understand further the genesis of autoimmune responses to aminoacyl-RS and to determine whether genes for autoantigenic aminoacyl-RS colocalize to chromosome 5, we have determined the chromosomal site of the GARS and AARS genes by PCR-based screening of somatic cell hybrid panels and by fluorescence in situ hybridization (FISH) analysis. 10 refs., 1 fig.

  5. Exome Sequencing Identifies Mitochondrial Alanyl-tRNA Synthetase Mutations in Infantile Mitochondrial Cardiomyopathy

    PubMed Central

    Götz, Alexandra; Tyynismaa, Henna; Euro, Liliya; Ellonen, Pekka; Hyötyläinen, Tuulia; Ojala, Tiina; Hämäläinen, Riikka H.; Tommiska, Johanna; Raivio, Taneli; Oresic, Matej; Karikoski, Riitta; Tammela, Outi; Simola, Kalle O.J.; Paetau, Anders; Tyni, Tiina; Suomalainen, Anu

    2011-01-01

    Infantile cardiomyopathies are devastating fatal disorders of the neonatal period or the first year of life. Mitochondrial dysfunction is a common cause of this group of diseases, but the underlying gene defects have been characterized in only a minority of cases, because tissue specificity of the manifestation hampers functional cloning and the heterogeneity of causative factors hinders collection of informative family materials. We sequenced the exome of a patient who died at the age of 10 months of hypertrophic mitochondrial cardiomyopathy with combined cardiac respiratory chain complex I and IV deficiency. Rigorous data analysis allowed us to identify a homozygous missense mutation in AARS2, which we showed to encode the mitochondrial alanyl-tRNA synthetase (mtAlaRS). Two siblings from another family, both of whom died perinatally of hypertrophic cardiomyopathy, had the same mutation, compound heterozygous with another missense mutation. Protein structure modeling of mtAlaRS suggested that one of the mutations affected a unique tRNA recognition site in the editing domain, leading to incorrect tRNA aminoacylation, whereas the second mutation severely disturbed the catalytic function, preventing tRNA aminoacylation. We show here that mutations in AARS2 cause perinatal or infantile cardiomyopathy with near-total combined mitochondrial respiratory chain deficiency in the heart. Our results indicate that exome sequencing is a powerful tool for identifying mutations in single patients and allows recognition of the genetic background in single-gene disorders of variable clinical manifestation and tissue-specific disease. Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure. PMID:21549344

  6. Cell-surface targeting of α2-adrenergic receptors — Inhibition by a transport deficient mutant through dimerization

    PubMed Central

    Zhou, Fuguo; Filipeanu, Catalin M.; Duvernay, Matthew T.; Wu, Guangyu

    2009-01-01

    We previously demonstrated that the α2B-adrenergic receptor mutant, in which the F(x)6IL motif in the membrane-proximal carboxyl terminus were mutated to alanines (α2B-ARm), is deficient in export from the endoplasmic reticulum (ER). In this report, we determined if α2B-ARm could modulate transport from the ER to the cell surface and signaling of its wild-type counterpart. Transient expression of α2B-ARm in HEK293T cells markedly inhibited cell-surface expression of wild-type α2B-AR, as measured by radioligand binding. Subcellular localization demonstrated that α2B-ARm trapped α2B-AR in the ER. The α2B-AR was shown to form homodimers and heterodimers with α2B-ARm as measured by co-immunoprecipitation of the receptors tagged with green fluorescent protein and hemagglutinin epitopes. In addition to α2B-AR, the transport of α2A-AR and α2C-AR to the cell surface was also inhibited by α2B-ARm. Furthermore, transient expression of α2B-ARm significantly reduced cell-surface expression of endogenous α2-AR in NG108-15 and HT29 cells. Consistent with its effect on α2-AR cell-surface expression, α2B-ARm attenuated α2A-AR- and α2B-AR-mediated ERK1/2 activation. These data demonstrated that the ER-retained mutant α2B-ARm conferred a dominant negative effect on the cell-surface expression of wild-type α2-AR, which is likely mediated through heterodimerization. These data indicate a crucial role of ER export in the regulation of cell-surface targeting and signaling of G protein-coupled receptors. PMID:15961277

  7. A Transform-Based Feature Extraction Approach for Motor Imagery Tasks Classification

    PubMed Central

    Khorshidtalab, Aida; Mesbah, Mostefa; Salami, Momoh J. E.

    2015-01-01

    In this paper, we present a new motor imagery classification method in the context of electroencephalography (EEG)-based brain–computer interface (BCI). This method uses a signal-dependent orthogonal transform, referred to as linear prediction singular value decomposition (LP-SVD), for feature extraction. The transform defines the mapping as the left singular vectors of the LP coefficient filter impulse response matrix. Using a logistic tree-based model classifier; the extracted features are classified into one of four motor imagery movements. The proposed approach was first benchmarked against two related state-of-the-art feature extraction approaches, namely, discrete cosine transform (DCT) and adaptive autoregressive (AAR)-based methods. By achieving an accuracy of 67.35%, the LP-SVD approach outperformed the other approaches by large margins (25% compared with DCT and 6 % compared with AAR-based methods). To further improve the discriminatory capability of the extracted features and reduce the computational complexity, we enlarged the extracted feature subset by incorporating two extra features, namely, Q- and the Hotelling’s \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$T^{2}$ \\end{document} statistics of the transformed EEG and introduced a new EEG channel selection method. The performance of the EEG classification based on the expanded feature set and channel selection method was compared with that of a number of the state-of-the-art classification methods previously reported with the BCI IIIa competition data set. Our method came second with an average accuracy of 81.38%. PMID:27170898

  8. Mechanisms Underlying Activation of α1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions

    PubMed Central

    Bragiel, Aneta M.; Wang, Di; Pieczonka, Tomasz D.; Shono, Masayuki; Ishikawa, Yasuko

    2016-01-01

    Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α1-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La3+, implying the participation of store-operated Ca2+ channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La3+, suggesting the involvement of extracellular Ca2+ entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca2+/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca2+ entry. PMID:27367668

  9. Hot Deformation Behavior and Flow Stress Prediction of TC4-DT Alloy in Single-Phase Region and Dual-Phase Regions

    NASA Astrophysics Data System (ADS)

    Liu, Jianglin; Zeng, Weidong; Zhu, Yanchun; Yu, Hanqing; Zhao, Yongqing

    2015-05-01

    Isothermal compression tests of TC4-DT titanium alloy at the deformation temperature ranging from 1181 to 1341 K covering α + β phase field and β-phase field, the strain rate ranging from 0.01 to 10.0 s-1 and the height reduction of 70% were conducted on a Gleeble-3500 thermo-mechanical simulator. The experimental true stress-true strain data were employed to develop the strain-compensated Arrhenius-type flow stress model and artificial neural network (ANN) model; the predictability of two models was quantified in terms of correlation coefficient ( R) and average absolute relative error (AARE). The R and AARE for the Arrhenius-type flow stress model were 0.9952 and 5.78%, which were poorer linear relation and more deviation than 0.9997 and 1.04% for the feed-forward back-propagation ANN model, respectively. The results indicated that the trained ANN model was more efficient and accurate in predicting the flow behavior for TC4-DT titanium alloy at elevated temperature deformation than the strain-compensated Arrhenius-type constitutive equations. The constitutive relationship compensating strain could track the experimental data across the whole hot working domain other than that at high strain rates (≥1 s-1). The microstructure analysis illustrated that the deformation mechanisms existed at low strain rates (≤0.1 s-1), where dynamic recrystallization occurred, were far different from that at high strain rates (≥1 s-1) that presented bands of flow localization and cracking along grain boundary.

  10. Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements

    NASA Astrophysics Data System (ADS)

    Forsyth, C.; Fazakerley, A. N.; Walsh, A. P.; Watt, C. E.; Garza, K.; Owen, C. J.; Constantinescu, D. O.; Dandouras, I. S.; Fornacon, K.; Lucek, E. A.; Marklund, G. T.; Sadeghi, S. S.; Khotyaintsev, Y. V.; Masson, A.; Doss, N.

    2013-12-01

    Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modelling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations.

  11. Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements

    NASA Astrophysics Data System (ADS)

    Forsyth, C.; Fazakerley, A. N.; Walsh, A. P.; Watt, C. E. J.; Garza, K. J.; Owen, C. J.; Constantinescu, D.; Dandouras, I.; FornaçOn, K.-H.; Lucek, E.; Marklund, G. T.; Sadeghi, S. S.; Khotyaintsev, Y.; Masson, A.; Doss, N.

    2012-12-01

    Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modeling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations.

  12. Simulated performance of biomass gasification based combined power and refrigeration plant for community scale application

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, S.; Mondal, P.; Ghosh, S.

    2016-07-01

    Thermal performance analysis and sizing of a biomass gasification based combined power and refrigeration plant (CPR) is reported in this study. The plant is capable of producing 100 kWe of electrical output while simultaneously producing a refrigeration effect, varying from 28-68 ton of refrigeration (TR). The topping gas turbine cycle is an indirectly heated all-air cycle. A combustor heat exchanger duplex (CHX) unit burns producer gas and transfer heat to air. This arrangement avoids complex gas cleaning requirements for the biomass-derived producer gas. The exhaust air of the topping GT is utilized to run a bottoming ammonia absorption refrigeration (AAR) cycle via a heat recovery steam generator (HRSG), steam produced in the HRSG supplying heat to the generator of the refrigeration cycle. Effects of major operating parameters like topping cycle pressure ratio (rp) and turbine inlet temperature (TIT) on the energetic performance of the plant are studied. Energetic performance of the plant is evaluated via energy efficiency, required biomass consumption and fuel energy savings ratio (FESR). The FESR calculation method is significant for indicating the savings in fuel of a combined power and process heat plant instead of separate plants for power and process heat. The study reveals that, topping cycle attains maximum power efficiency of 30%in pressure ratio range of 8-10. Up to a certain value of pressure ratio the required air flow rate through the GT unit decreases with increase in pressure ratio and then increases with further increase in pressure ratio. The capacity of refrigeration of the AAR unit initially decreases up to a certain value of topping GT cycle pressure ratio and then increases with further increase in pressure ratio. The FESR is found to be maximized at a pressure ratio of 9 (when TIT=1100°C), the maximum value being 53%. The FESR is higher for higher TIT. The heat exchanger sizing is also influenced by the topping cycle pressure ratio and GT-TIT.

  13. Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo.

    PubMed

    Motoki, Atsuko; Merkel, Matthias J; Packwood, William H; Cao, Zhiping; Liu, Lijuan; Iliff, Jeffrey; Alkayed, Nabil J; Van Winkle, Donna M

    2008-11-01

    Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL\\6J wild-type or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury. PMID:18835921

  14. Optimisation of a system for the co-translational incorporation of a keto amino acid and its application to a tumour-specific Anticalin.

    PubMed

    Reichert, Andreas J; Poxleitner, Gabriele; Dauner, Martin; Skerra, Arne

    2015-12-01

    The bioorthogonal keto group has attracted interest for the site-specific chemical conjugation of recombinant proteins under mild conditions, e.g. with aminooxy-functionalised fluorescent probes, radiometal chelates, toxins or polymers. However, the cotranslational incorporation of the corresponding non-canonical amino acid p-acetyl-L-phenylalanine (Apa) into proteins expressed in Escherichia coli by means of amber suppression using a previously described system with a mutated tRNA and an engineered tyrosyl-tRNA synthetase from Methanococcus jannaschii shows limited efficiency and considerable promiscuity towards endogenous amino acids. Employing a one-plasmid system that encodes all three components required for selection, i.e. the modified aminoacyl-tRNA synthetase (aaRS), the cognate amber suppressor tRNA and the enhanced green fluorescent protein equipped with an amber stop codon and serving as reporter, we have generated an Apa-specific aaRS&tRNA pair with considerably improved efficiency (17-fold increased expression) and also fidelity (6-fold). To this end, both the aaRS and the tRNA were subjected to doped random mutagenesis and selection in altogether four evolutionary cycles using fluorescence-activated bacterial cell sorting as well as automated screening of microcultures. The resulting aaRS&tRNA pair was applied to the functionalisation of an Anticalin with specificity towards oncofetal fibronectin by introducing a keto group at a permissible site for subsequent conjugation with a fluorescent dye, thus allowing visualisation of this tumour target under the microscope. PMID:26405058

  15. Fat segmentation on chest CT images via fuzzy models

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Wu, Caiyun; Pednekar, Gargi; Subramanian, Janani Rajan; Lederer, David J.; Christie, Jason; Torigian, Drew A.

    2016-03-01

    Quantification of fat throughout the body is vital for the study of many diseases. In the thorax, it is important for lung transplant candidates since obesity and being underweight are contraindications to lung transplantation given their associations with increased mortality. Common approaches for thoracic fat segmentation are all interactive in nature, requiring significant manual effort to draw the interfaces between fat and muscle with low efficiency and questionable repeatability. The goal of this paper is to explore a practical way for the segmentation of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) components of chest fat based on a recently developed body-wide automatic anatomy recognition (AAR) methodology. The AAR approach involves 3 main steps: building a fuzzy anatomy model of the body region involving all its major representative objects, recognizing objects in any given test image, and delineating the objects. We made several modifications to these steps to develop an effective solution to delineate SAT/VAT components of fat. Two new objects representing interfaces of SAT and VAT regions with other tissues, SatIn and VatIn are defined, rather than using directly the SAT and VAT components as objects for constructing the models. A hierarchical arrangement of these new and other reference objects is built to facilitate their recognition in the hierarchical order. Subsequently, accurate delineations of the SAT/VAT components are derived from these objects. Unenhanced CT images from 40 lung transplant candidates were utilized in experimentally evaluating this new strategy. Mean object location error achieved was about 2 voxels and delineation error in terms of false positive and false negative volume fractions were, respectively, 0.07 and 0.1 for SAT and 0.04 and 0.2 for VAT.

  16. The Alfvén Mission for the ESA M5 Call: Mission Concept

    NASA Astrophysics Data System (ADS)

    Fazakerley, Andrew; Berthomier, Matthieu; Pottelette, Raymond; Forsyth, Colin

    2016-04-01

    This poster will present the proposed Alfvén mission concept and is complemented by a presentation of the mission scientific goals planned for the ST1.5 session. The Alfvén mission has the scientific objective of studying particle acceleration and other forms of electromagnetic energy conversion in a collisionless low beta plasma. The mission is proposed to operate in the Earth's Auroral Acceleration Region (AAR), the most accessible laboratory for investigating plasmas at an interface where ideal magneto-hydrodynamics does not apply. Alfvén is designed to answer questions about where and how the particles that create the aurorae are accelerated, how and why they emit auroral kilometric radiation, what creates and maintains large scale electric fields aligned with the magnetic field, and to elucidate the ion outflow processes which are slowly removing the Earth's atmosphere. The mission will provide the required coordinated two-spacecraft observations within the AAR several times a day. From well designed separations along or across the magnetic field lines, using a comprehensive suite of inter-calibrated particles and field instruments, it will measure the parallel electric fields, variations in particle flux, and wave energy that will answer open questions on energy conversion. It will use onboard auroral imagers to determine how this energy conversion occurs in the regional context and, together with its orbit design, this makes the mission ideally suited to resolving spatio-temporal ambiguities that have plagued previous auroral satellite studies. The spacecraft observations will be complemented by coordinated observations with the existing dense network of ground based observatories, for more detailed ionospheric and auroral information when Alfvén overflights occur.

  17. Lightweight deformable mirrors for future space telescopes

    NASA Astrophysics Data System (ADS)

    Patterson, Keith

    This thesis presents a concept for ultra-lightweight deformable mirrors based on a thin substrate of optical surface quality coated with continuous active piezopolymer layers that provide modes of actuation and shape correction. This concept eliminates any kind of stiff backing structure for the mirror surface and exploits micro-fabrication technologies to provide a tight integration of the active materials into the mirror structure, to avoid actuator print-through effects. Proof-of-concept, 10-cm-diameter mirrors with a low areal density of about 0.5 kg/m2 have been designed, built and tested to measure their shape-correction performance and verify the models used for design. The low cost manufacturing scheme uses replication techniques, and strives for minimizing residual stresses that deviate the optical figure from the master mandrel. It does not require precision tolerancing, is lightweight, and is therefore potentially scalable to larger diameters for use in large, modular space telescopes. Other potential applications for such a laminate could include ground-based mirrors for solar energy collection, adaptive optics for atmospheric turbulence, laser communications, and other shape control applications. The immediate application for these mirrors is for the Autonomous Assembly and Reconfiguration of a Space Telescope (AAReST) mission, which is a university mission under development by Caltech, the University of Surrey, and JPL. The design concept, fabrication methodology, material behaviors and measurements, mirror modeling, mounting and control electronics design, shape control experiments, predictive performance analysis, and remaining challenges are presented herein. The experiments have validated numerical models of the mirror, and the mirror models have been used within a model of the telescope in order to predict the optical performance. A demonstration of this mirror concept, along with other new telescope technologies, is planned to take place during

  18. Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice.

    PubMed

    Eckle, Tobias; Grenz, Almut; Köhler, David; Redel, Andreas; Falk, Melanie; Rolauffs, Bernd; Osswald, Hartmut; Kehl, Franz; Eltzschig, Holger K

    2006-11-01

    Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of transgenic mice seems critical. Due to technical difficulty associated with performing cardiac IP in mice, we developed an in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion. This technique has the major advantage of eliminating the necessity of intermittently occluding the coronary artery with a knotted suture. To systematically evaluate this model, we first demonstrated correlation of ischemia times (10-60 min) with infarct sizes [3.5 +/- 1.3 to 42 +/- 5.2% area at risk (AAR), Evan's blue/triphenyltetrazolium chloride staining]. IP (4 x 5 min) and cold ischemia (27 degrees C) reduced infarct size by 69 +/- 6.7% and 84 +/- 4.2%, respectively (n = 6, P < 0.01). In contrast, lower numbers of IP cycles did not alter infarct size. However, infarct sizes were distinctively different in mice from different genetic backgrounds. In addition to infarct staining, we tested cardiac troponin I (cTnI) as marker of myocardial infarction in this model. In fact, plasma levels of cTnI were significantly lower in IP-treated mice and closely correlated with infarct sizes (R(2) = 0.8). To demonstrate transcriptional consequences of cardiac IP, we isolated total RNA from the AAR and showed repression of the equilibrative nucleoside transporters 1-4 by IP in this model. Taken together, this study demonstrates highly reproducible infarct sizes and cardiac protection by IP, thus minimizing the variability associated with knot-based coronary occlusion models. Further studies on cardiac IP using transgenic mice may consider this technique. PMID:16766632

  19. Neural network classification of autoregressive features from electroencephalogram signals for brain computer interface design

    NASA Astrophysics Data System (ADS)

    Huan, Nai-Jen; Palaniappan, Ramaswamy

    2004-09-01

    In this paper, we have designed a two-state brain-computer interface (BCI) using neural network (NN) classification of autoregressive (AR) features from electroencephalogram (EEG) signals extracted during mental tasks. The main purpose of the study is to use Keirn and Aunon's data to investigate the performance of different mental task combinations and different AR features for BCI design for individual subjects. In the experimental study, EEG signals from five mental tasks were recorded from four subjects. Different combinations of two mental tasks were studied for each subject. Six different feature extraction methods were used to extract the features from the EEG signals: AR coefficients computed with Burg's algorithm, AR coefficients computed with a least-squares (LS) algorithm and adaptive autoregressive (AAR) coefficients computed with a least-mean-square (LMS) algorithm. All the methods used order six applied to 125 data points and these three methods were repeated with the same data but with segmentation into five segments in increments of 25 data points. The multilayer perceptron NN trained by the back-propagation algorithm (MLP-BP) and linear discriminant analysis (LDA) were used to classify the computed features into different categories that represent the mental tasks. We compared the classification performances among the six different feature extraction methods. The results showed that sixth-order AR coefficients with the LS algorithm without segmentation gave the best performance (93.10%) using MLP-BP and (97.00%) using LDA. The results also showed that the segmentation and AAR methods are not suitable for this set of EEG signals. We conclude that, for different subjects, the best mental task combinations are different and proper selection of mental tasks and feature extraction methods are essential for the BCI design.

  20. Modeling debris-covered glaciers: extension due to steady debris input

    NASA Astrophysics Data System (ADS)

    Anderson, L. S.; Anderson, R. S.

    2015-11-01

    Debris-covered glaciers are common in rapidly-eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. If continuous debris cover is present, mass balance gradients can be reduced leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2-D long-valley numerical glacier model that includes englacial and supraglacial advection. We ran 120 simulations in which a steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier. Our model and parameter selections produce two-fold increases in glacier length. Debris flux onto the glacier and the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris related variables are held constant. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to initial debris-free glaciers. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). The model reproduces first-order relationships between debris cover, AARs, and glacier surface velocities from glaciers in High Asia. We provide a quantitative, theoretical foundation to interpret the effect of debris cover on the moraine record, and to assess the effects of climate change on debris-covered glaciers.

  1. Structure of Leishmania major Methionyl-tRNA Synthetase in Complex with Intermediate Products Methionyladenylate and Pyrophosphate

    PubMed Central

    Larson, Eric T.; Kim, Jessica E.; Zucker, Frank H.; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J.; Verlinde, Christophe L.M.J.; Fan, Erkang; Buckner, Frederick S.; Van Voorhis, Wesley C.; Merritt, Ethan A.; Hol, Wim G.J.

    2011-01-01

    Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg2+ ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of E. coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNAMet complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme. PMID:21144880

  2. Seemingly irrational driving behavior model: The effect of habit strength and anticipated affective reactions.

    PubMed

    Chung, Yi-Shih

    2015-09-01

    An increasing amount of evidence suggests that aberrant driving behaviors are not entirely rational. On the basis of the dual-process theory, this study postulates that drivers may learn to perform irrational aberrant driving behaviors, and these behaviors could be derived either from a deliberate or an intuitive decision-making approach. Accordingly, a seemingly irrational driving behavior model is proposed; in this model, the theory of planned behavior (TPB) was adopted to represent the deliberate decision-making mechanism, and habit strength was incorporated to reflect the intuitive decision process. A multiple trivariate mediation structure was designed to reflect the process through which driving behaviors are learned. Anticipated affective reactions (AARs) were further included to examine the effect of affect on aberrant driving behaviors. Considering the example of speeding behaviors, this study developed scales and conducted a two-wave survey of students in two departments at a university in Northern Taiwan. The analysis results show that habit strength consists of multiple aspects, and frequency of past behavior cannot be a complete repository for accumulating habit strength. Habit strength appeared to be a crucial mediator between intention antecedents (e.g., attitude) and the intention itself. Including habit strength in the TPB model enhanced the explained variance of speeding intention by 26.7%. In addition, AARs were different from attitudes; particularly, young drivers tended to perform speeding behaviors to reduce negative feelings such as regret. The proposed model provides an effective alternative approach for investigating aberrant driving behaviors; corresponding countermeasures are discussed. PMID:26056969

  3. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

    NASA Astrophysics Data System (ADS)

    Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffrey S.; Nekola, Jeffrey C.; Wiles, Gregory C.

    2013-07-01

    Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this 'limestone problem' and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

  4. Sedimentary records of trace elements from large European lakes (Switzerland) document historic to recent freshwater pollution and climate-induced runoff variations

    NASA Astrophysics Data System (ADS)

    Thevenon, F.; Wirth, S. B.; Fujak, M.; Poté, J.; Thierry, A.; Chiaradia, M.; Girardclos, S.

    2011-12-01

    Continuous sedimentary records of anthropogenic and natural trace elements determined by ICPMS, from 5 large and deep perialpine lakes from Central Europe (Switzerland), evidence the environmental impacts of industrial fossil fuel pollution. In fact, the greatest increase in heavy metal pollution was registered at all the studied sites following the European industrial revolution of ca. AD 1800; with the highest values during the middle part of the 20th century. On a regional scale, anthropogenic heavy metal input subsequently stopped increasing thanks to remediation strategies such as the implementation of wastewater treatment plants (WWTPs). On the other hand, the discharge of industrial treated wastewaters into Vidy Bay of Lake Geneva during the second part of the 20th century involved the sedimentation of highly contaminated sediments in the area surrounding the WWTP outlet pipe discharge; less than 4 km from the main supply of drinking water of Lausanne (127'000 hab.). Microbial analyses furthermore reveal i) high increase in bacterial densities following the lake eutrophication in the 1970s, and that ii) the related sediments can be considered as a reservoir of antibiotic resistant bacteria/genes (of human origin). We finally compare instrumental hydrological data over the last century with variations of lithogenic trace elements (e.g., titanium) as registered in three large lakes (Brienz, Thun and Bienne) connected by the River Aar. This task allows to better constraining the runoff variations on a regional scale over the last decades for the the River Aar, and its possible increase under warming climate conditions in the European Alps.

  5. Role of extracellular cysteine residues in the adenosine A2A receptor.

    PubMed

    De Filippo, Elisabetta; Namasivayam, Vigneshwaran; Zappe, Lukas; El-Tayeb, Ali; Schiedel, Anke C; Müller, Christa E

    2016-06-01

    The G protein-coupled A2A adenosine receptor represents an important drug target. Crystal structures and modeling studies indicated that three disulfide bonds are formed between ECL1 and ECL2 (I, Cys71(2.69)-Cys159(45.43); II, Cys74(3.22)-Cys146(45.30), and III, Cys77(3.25)-Cys166(45.50)). However, the A2BAR subtype appears to require only disulfide bond III for proper function. In this study, each of the three disulfide bonds in the A2AAR was disrupted by mutation of one of the cysteine residues to serine. The mutant receptors were stably expressed in Chinese hamster ovary cells and analyzed in cyclic adenosine monophosphate (cAMP) accumulation and radioligand binding studies using structurally diverse agonists: adenosine, NECA, CGS21680, and PSB-15826. Results were rationalized by molecular modeling. The observed effects were dependent on the investigated agonist. Loss of disulfide bond I led to a widening of the orthosteric binding pocket resulting in a strong reduction in the potency of adenosine, but not of NECA or 2-substituted nucleosides. Disruption of disulfide bond II led to a significant reduction in the agonists' efficacy indicating its importance for receptor activation. Disulfide bond III disruption reduced potency and affinity of the small adenosine agonists and NECA, but not of the larger 2-substituted agonists. While all the three disulfide bonds were essential for high potency or efficacy of adenosine, structural modification of the nucleoside could rescue affinity or efficacy at the mutant receptors. At present, it cannot be excluded that formation of the extracellular disulfide bonds in the A2AAR is dynamic. This might add another level of G protein-coupled receptor (GPCR) modulation, in particular for the cysteine-rich A2A and A2BARs. PMID:26969588

  6. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

    USGS Publications Warehouse

    Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffery S.; Nekola, Jeffery C.; Wiles, Gregory C.

    2013-01-01

    Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this ‘limestone problem’ and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

  7. K-Ar dating of synkinematic clay gouges from Neoalpine faults of the Central, Western and Eastern Alps

    NASA Astrophysics Data System (ADS)

    Pleuger, Jan; Mancktelow, Neil; Zwingmann, Horst; Manser, Monika

    2012-07-01

    With ongoing Alpine convergence and deformation during exhumation there is a general progression from ductile to brittle behaviour on the Periadriatic Fault and kinematically related faults farther north (e.g. the Simplon-Rhone Fault and a diffuse, discontinuous zone of generally dextral strike-slip movement on the southern boundary of the Aar massif). K-Ar dating of fine grained illite from clay fault gouges provides a reliable method for establishing the maximum age of this transition to brittle faulting and, for short-lived faults, the approximate time of faulting itself. The new results establish that brittle faulting on the northeastern segment of the Canavese Fault (i.e. the part of the Periadriatic Fault southwest of Lago Maggiore) occurred around 20 Ma, with south-side-up kinematics. A K-Ar age of ca. 17 Ma for the crosscutting Giudicarie Fault in the Eastern Alps is effectively identical with an already published pseudotachylyte age and places a lower limit on major and continuous strike slip movements of the Periadriatic Fault. The age of brittle faulting farther north, on the southern border of the Aar Massif, is from 13.6 ± 0.3 to 8.3 ± 1.1 Ma, consistent with the younger cooling and exhumation in this area. The dominantly dextral brittle faulting becoming younger to the north reflects the continued indentation and anticlockwise rotation of Adria as Alpine units become exhumed and progressively welded to the southern block. In contrast to the Eastern Alps, there is no field evidence for (westward) lateral extrusion of Alpine units relative to Adria and the European foreland.

  8. Evidence of Early Holocene Glacial Advances in Southern South America from Cosmogenic Surface Exposure Dating

    NASA Astrophysics Data System (ADS)

    Douglass, D. C.; Singer, B. S.; Kaplan, M. R.; Ackert, R. P.; Mickelson, D. M.; Caffee, M. W.

    2004-12-01

    10Be and 36Cl cosmogenic nuclide surface exposure dating of erratic boulders reveal two glacier advances in southern South America (46°S) during the Early Holocene. Seven of ten boulders from the outer moraine yield a weighted mean of 8.5±0.7 ka and five of six boulders from the inner moraine yield a weighted mean age of 6.2±0.8 ka (2σ uncertainties). The four outliers are anomalously old (interpreted to contain inherited cosmogenic isotopes from prior exposure) and are identified on the basis of Chi-Squared statistics and bi-modal probability distribution curves. These glacial advances are likely the result of a northward migration of the southern westerlies causing an increase in precipitation and/or a decrease in temperature at this latitude. Reconstructions of equilibrium line altitudes (ELA) at the times of moraine deposition based on Accumulation Area Rations (AARs) are about 300 m lower than modern. This ELA depression is not particularly sensitive to the AAR used, and corresponds to conditions 2.4° C cooler (if no change in precipitation), or 1000 mm/a wetter (if no change in temperature) than the modern climate. The older advance precedes the currently accepted initiation of Holocene glacial activity in southern South America by about 3000 years, and appears to be temporally synchronous with the "8.2 ka event" recorded in Greenland and many other parts of the world. The younger advance is slightly older than, but indistinguishable from, documented neoglacial advances and climate changes in southern South America and four other continents. If there are causal links between these temporally synchronous, globally distributed events, then millennial scale climate changes appear to involve reorganization of global weather systems (such as migration of the southern westerlies), or may be externally forced (e.g. solar variability).

  9. High magnitude and rapid incision from river capture: Rhine River, Switzerland

    NASA Astrophysics Data System (ADS)

    Yanites, Brian J.; Ehlers, Todd A.; Becker, Jens K.; Schnellmann, Michael; Heuberger, Stefan

    2013-06-01

    Landscape evolution is controlled by the development and organization of drainage basins. As a landscape evolves, drainage reorganization events can occur via river capture or piracy, whereby one river basin grows at the expense of another. The river downstream of a capture location will generate a transient topographic response as the added water discharge increases sediment transport and erosion efficiency. This erosional response will propagate upstream through both the captured and original river basins. Here we focus on quantifying the impact of drainage reorganization along the Rhine/Aare River system (~45,000 km2) during the late Pliocene/early Pleistocene, where gravel remnants indicate total incision of ~650 m during the last ~4.2 Myr in the region of the recent Aare-Rhine confluence. We develop a numerical model of drainage capture to quantify the range of possible magnitudes of erosion and the transient river response resulting from the reorganization of the Rhine River. The model accounts for both fluvial incision and sediment transport. Our model estimates 400-800 m of river elevation change (lowering profiles) during the last ~4 Myr due to river capture events, providing an important component to the recent exhumation budget of the Swiss Alpine Foreland. The model indicates a rapid response to capture events (re-equilibration timescale of ~1 Myr). The predicted incision magnitudes are consistent with incision measured from the elevation of Pliocene and early Pleistocene river gravels, suggesting that across northern Switzerland, a significant amount of incision can be explained by drainage reorganization.

  10. Gαi2-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart

    PubMed Central

    Waterson, Rachael E.; Thompson, Corbin G.; Mabe, Nathaniel W.; Kaur, Kuljeet; Talbot, Jeffery N.; Neubig, Richard R.; Rorabaugh, Boyd R.

    2011-01-01

    Aims Regulator of G protein signalling (RGS) proteins act as molecular ‘off switches’ that terminate G protein signalling by catalyzing the hydrolysis of Gα-bound GTP to GDP. Many different Gαi-coupled receptors have been implicated in the cardioprotective effects of ischaemic preconditioning. However, the role of RGS proteins in modulating cardioprotection has not been previously investigated. We used mice that were homozygous (GS/GS) or heterozygous (GS/+) for a mutation in Gαi2 rendering it RGS-insensitive (G184S) to determine whether interactions between endogenous RGS proteins and Gαi2 modulate Gαi-mediated protection from ischaemic injury. Methods and results Langendorff-perfused mouse hearts were subjected to 30 min global ischaemia and 2 h reperfusion. Infarcts in GS/GS (14.5% of area at risk) and GS/+ (22.6% of AAR) hearts were significantly smaller than those of +/+ hearts (37.2% of AAR) and recovery of contractile function was significantly enhanced in GS/GS and GS/+ hearts compared with +/+ hearts. The cardioprotective phenotype was not reversed by wortmannin or U0126 but was reversed by 5-hydroxydecanoic acid and HMR 1098, indicating that RGS-insensitive Gαi2 protects the heart through a mechanism that requires functional ATP-dependent potassium channels but does not require acute activation of extracellular-regulated kinase or Akt signalling pathways. Conclusions This is the first study to demonstrate that Gαi2-mediated cardioprotection is suppressed by RGS proteins. These data suggest that RGS proteins may provide novel therapeutic targets to protect the heart from ischaemic injury. PMID:21349876

  11. Plio-Pleistocene evolution of the north Alpine drainage system: new constraints from detrital thermochronology of foreland deposits

    NASA Astrophysics Data System (ADS)

    Reiter, Wolfgang; Elfert, Simon; Glotzbach, Christoph; Spiegel, Cornelia

    2015-04-01

    The evolution of drainage systems in and around active orogens may be strongly affected by climatic or tectonic processes. Information on the drainage evolution is stored in the sediments of the foreland depocentres. We investigated the provenance of two key deposits adjacent to the Central Alps, the Pliocene Sundgau gravels and the Pleistocene Höhere Deckenschotter by applying detrital thermochronology. Combined with provenance information from Rhine Graben deposits, we propose a reconstruction of the north Alpine drainage system since the middle Pliocene and discuss potential controlling mechanisms. Our data show that the Rhine Graben received detritus from the Alpine realm already during the Pliocene, indicating two different river systems—the proto-Rhine and the Aare-Doubs—draining the Alpine realm toward the North Sea and Mediterranean Sea. The investigated sediments contain detritus from two central Alpine sources, one showing a regional exhumational equilibrium and the other characterized by increasing exhumation rates. Discharge of the latter source ceased after ~2 Ma, reflecting a northward shift of the main Alpine drainage divide. Between ~2.0 and 1.2 Ma, the drainage system was affected by a major change, which we explain as resulting from a change in the Alpine stress field leading to tectonic exhumation and topography reduction in the area of the southern Aar massif. Generally, it seems that between ~4 and 1.2 Ma, the drainage system was mainly controlled by tectonic processes, despite first glaciations that already affected the north-Alpine foreland by ~2 Ma. The drainage system only seems to have reacted to the late Cenozoic climate changes after ~1.2 Ma, i.e., at the time of the most intense Alpine glaciation. At that time, the course of the Rhine River shifted toward the area of the Hegau volcanics, and the size of the Rhine River catchment became strongly reduced.

  12. T3 enhances Ang2 in rat aorta in myocardial I/R: comparison with left ventricle.

    PubMed

    Sabatino, Laura; Kusmic, Claudia; Nicolini, Giuseppina; Amato, Rosario; Casini, Giovanni; Iervasi, Giorgio; Balzan, Silvana

    2016-10-01

    Angiogenesis is important for recovery after tissue damage in myocardial ischemia/reperfusion, and tri-iodothyronine (T3) has documented effects on angiogenesis. The angiopoietins 1/2 and tyrosine kinase receptor represent an essential system in angiogenesis controlling endothelial cell survival and vascular maturation. Recently, in a 3-day ischemia/reperfusion rat model, the infusion of a low dose of T3 improved the post-ischemic recovery of cardiac function.Adopting this model, our study aimed to investigate the effects of T3 on the capillary index and the expression of angiogenic genes as the angiopoietins 1/2 and tyrosine kinase receptor system, in the thoracic aorta and in the left ventricle. In the thoracic aorta, T3 infusion significantly improved the angiogenic sprouting and angiopoietin 2 expression. Instead, Sham-T3 group did not show any significant increment of capillary density and angiopoietin 2 expression. In the area at risk (AAR) of the left ventricle, T3 infusion did not increase capillary density but restored levels of angiopoietin 1, which were reduced in I/R group. Angiopoietin 2 levels were similar to Sham group and unchanged by T3 administration. In the remote zone, T3 induced a significant increment of both angiopoietin 1/2. In conclusion, T3 infusion induced a different response of angiopoietin 1/2 between the ventricle (the AAR and the remote zone) and the thoracic aorta, probably reflecting the different action of angiopoietin 1/2 in cardiomyocytes and endothelial cells. Overall, these data suggest a new aspect of T3-mediated cardioprotection through angiogenesis. PMID:27444191

  13. Changes In Adrenoreceptors In The Prefrontal Cortex Of Subjects With Dementia: Evidence Of Compensatory Changes

    PubMed Central

    Szot, Patricia; White, Sylvia S.; Greenup, J. Lynne; Leverenz, James B.; Peskind, Elaine R.; Raskind, Murray A.

    2012-01-01

    In Alzheimer’s disease (AD) there is a significant loss of locus coeruleus (LC) noradrenergic neurons. However, recent work has shown the surviving noradrenergic neurons to display many compensatory changes, including axonal sprouting to the hippocampus. The prefrontal cortex (PFC) is a forebrain region that is affected in dementia, and receives innervation from the LC noradrenergic neurons. Reduced PFC function can reduce cognition and disrupt behavior. Because the PFC is an important area in AD, we determined if noradrenergic innervation from the LC noradrenergic neurons is maintained and if adrenoreceptors are altered postsynaptically. Presynaptic PFC α2-adrenoreceptor (AR) binding site density, as determined by 3H-RX821002, suggests that axons from surviving noradrenergic neurons in the LC are sprouting to the PFC of subjects with dementia. Changes in postsynaptic α1-AR in the PFC of subjects with dementia indicate normal to elevated levels of binding sites. Expression of α1-AR subtypes (α1A- and α1D-AR) and α2C-AR subtype mRNA in the PFC of subjects with dementia is similar to what was observed in the hippocampus with one exception, the expression of α1A-AR mRNA. The expression of the α1A-AR mRNA subtype is significantly reduced in specific layers of the PFC in subjects with dementia. The loss of α1A-, α1D- and α2C-AR mRNA subtype expression in the PFC may be attributed to neuronal loss observed in dementia. These changes in postsynaptic AR would suggest a reduced function of the PFC. Consequence of this reduced function of the PFC in dementia is still unknown but it may affect memory and behavior. PMID:17324522

  14. Changes in adrenoreceptors in the prefrontal cortex of subjects with dementia: evidence of compensatory changes.

    PubMed

    Szot, P; White, S S; Greenup, J L; Leverenz, J B; Peskind, E R; Raskind, M A

    2007-04-25

    In Alzheimer's disease (AD) there is a significant loss of locus coeruleus (LC) noradrenergic neurons. However, recent work has shown the surviving noradrenergic neurons to display many compensatory changes, including axonal sprouting to the hippocampus. The prefrontal cortex (PFC) is a forebrain region that is affected in dementia, and receives innervation from the LC noradrenergic neurons. Reduced PFC function can reduce cognition and disrupt behavior. Because the PFC is an important area in AD, we determined if noradrenergic innervation from the LC noradrenergic neurons is maintained and if adrenoreceptors are altered postsynaptically. Presynaptic PFC alpha2-adrenoreceptor (AR) binding site density, as determined by 3H-RX821002, suggests that axons from surviving noradrenergic neurons in the LC are sprouting to the PFC of subjects with dementia. Changes in postsynaptic alpha1-AR in the PFC of subjects with dementia indicate normal to elevated levels of binding sites. Expression of alpha1-AR subtypes (alpha1A- and alpha1D-AR) and alpha2C-AR subtype mRNA in the PFC of subjects with dementia is similar to what was observed in the hippocampus with one exception, the expression of alpha1A-AR mRNA. The expression of the alpha1A-AR mRNA subtype is significantly reduced in specific layers of the PFC in subjects with dementia. The loss of alpha1A-, alpha1D- and alpha2C-AR mRNA subtype expression in the PFC may be attributed to neuronal loss observed in dementia. These changes in postsynaptic AR would suggest a reduced function of the PFC. Consequence of this reduced function of the PFC in dementia is still unknown but it may affect memory and behavior. PMID:17324522

  15. Optimal Duration of Coronary Ligation and Reperfusion for Reperfusion Injury Study in a Rat Model

    PubMed Central

    Chang, Shih-Tai; Chu, Chi-Ming; Yang, Teng-Yao; Hung, Li-Man; Pan, Kuo-Li; Cherng, Wen-Jin

    2016-01-01

    Background Reperfusion injury (RI) has an important impact on the clinical prognosis for patients with acute myocardial injury who had their coronary blood flow reestablished. However, no studies to date have investigated the timeframe of coronary occlusion and reperfusion effects on RI. Methods A total of 100 rats were divided into 4 groups based on the coronary ligation period: 30, 60, 120, and 180 min, and each group was further divided into 5 subgroups with different reperfusion periods: 0, 30, 60, 120, and 180 min. R0 was the baseline of each subgroup. All animals received the same protocols for designed ligation and reperfusion periods. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to distinguish different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The differences of the ratios of the necrotic area to AAR between each subgroup and baseline were further averaged to calculate an overall value of each heart. Results The relative RI percentages showed significant differences (0.8 ± 2.3%, 4.9 ± 3.3%, 10.8 ± 3.1%, and 20.3 ± 3.6% respectively, p < 0.001) at different time points of reperfusion but not at different time points of ligation (p = 0.593). The effects of different time courses in RI showed that the L120R180 group (43.4 ± 2.3%) had the highest RI difference with the baseline group. Conclusions Maximal RI occurred at the timeframe of L120R180 in our animal model. This result may be utilized to assess the substantial benefits of RI therapies in an experimental rat model setting. PMID:27471363

  16. Recognition of upper airway and surrounding structures at MRI in pediatric PCOS and OSAS

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, J. K.; Odhner, D.; Sin, Sanghun; Arens, Raanan

    2013-03-01

    Obstructive Sleep Apnea Syndrome (OSAS) is common in obese children with risk being 4.5 fold compared to normal control subjects. Polycystic Ovary Syndrome (PCOS) has recently been shown to be associated with OSAS that may further lead to significant cardiovascular and neuro-cognitive deficits. We are investigating image-based biomarkers to understand the architectural and dynamic changes in the upper airway and the surrounding hard and soft tissue structures via MRI in obese teenage children to study OSAS. At the previous SPIE conferences, we presented methods underlying Fuzzy Object Models (FOMs) for Automatic Anatomy Recognition (AAR) based on CT images of the thorax and the abdomen. The purpose of this paper is to demonstrate that the AAR approach is applicable to a different body region and image modality combination, namely in the study of upper airway structures via MRI. FOMs were built hierarchically, the smaller sub-objects forming the offspring of larger parent objects. FOMs encode the uncertainty and variability present in the form and relationships among the objects over a study population. Totally 11 basic objects (17 including composite) were modeled. Automatic recognition for the best pose of FOMs in a given image was implemented by using four methods - a one-shot method that does not require search, another three searching methods that include Fisher Linear Discriminate (FLD), a b-scale energy optimization strategy, and optimum threshold recognition method. In all, 30 multi-fold cross validation experiments based on 15 patient MRI data sets were carried out to assess the accuracy of recognition. The results indicate that the objects can be recognized with an average location error of less than 5 mm or 2-3 voxels. Then the iterative relative fuzzy connectedness (IRFC) algorithm was adopted for delineation of the target organs based on the recognized results. The delineation results showed an overall FP and TP volume fraction of 0.02 and 0.93.

  17. A New Species of the Genus Kiwa (Decapoda: Anomura) from the Hydrothermal Vent of the Australia-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Won, Y. J.; Lee, S. H.; Lee, W. K.

    2014-12-01

    Due to extreme weather conditions and remoteness to access, the great part of the Southern Ocean remains to be explored. Therefore, little is known about the Circum-Antarctic Ridge (CAR) system and its hydrothermal vent ecosystem underlying the Southern Ocean. We report the first discovery of a new deep-sea hydrothermal vent field and a new anomuran species from the Australia-Antarctic Ridge (AAR), the highest latitude (62°S; 158°E) explored in the Southern Ocean up to date. At this site, a new anomuran species which belongs to the genus Kiwa known as 'yeti crabs' was found. Morphologically, this species has characteristics of the genus Kiwa, including fifth pereopod inserted below sterna plastron, third sternite strongly produced anteriorly, and eyes extremely reduced. However, the new species differs from the other known species of Kiwa, K. hirsuta and K. puravida, showing relatively short rostrum and slender dactylus on second to fourth pereopods. Phylogenetic analysis using DNA sequences of eight genetic loci also supported the result of morphological analysis, confirming this species as a new Kiwa species, Kiwa n. sp. In addition, phylogenetic tree revealed the evolutionary relationship among the Kiwa species, presenting the Kiwa n. sp. as the sister species to K. puravida which inhabits the methane cold seep on the Pacific continental slope off Costa Rica. Considering the geography and the physicochemical environment, this unlikely result casts a mystery to be solved through further taxon sampling particularly from as-yet-unexplored vents and seeps. Discovery of the hydrothermal vent and Kiwa n. sp. from the AAR segment is significant because this site is located in the high latitude of the southern hemisphere and it is the region affected by the Antarctic Circumpolar Current (ACC). Future research on the relation of Kiwa n. sp. and the other Kiwa species affected by the ACC will provide an idea about the biogeography and the evolutionary connections of the

  18. GPCR Ligand Dendrimer (GLiDe) Conjugates: Adenosine Receptor Interactions of a Series of Multivalent Xanthine Antagonists

    PubMed Central

    Kecskés, Angela; Tosh, Dilip K.; Wei, Qiang; Gao, Zhan-Guo; Jacobson, Kenneth A.

    2011-01-01

    Previously, G protein–coupled receptor (GPCR) agonists were tethered from polyamidoamine (PAMAM) dendrimers to provide high receptor affinity and selectivity. Here we prepared GPCR Ligand Dendrimer (GLiDe) conjugates from a potent adenosine receptor (AR) antagonist; such agents are of interest for treating Parkinson’s disease, asthma, and other conditions. Xanthine amine congener (XAC) was appended with an alkyne group on an extended C8 substituent for coupling by Cu(I)-catalyzed click chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. These conjugates also contained triazole-linked PEG groups (8 or 22 moieties per 64 terminal positions) for increasing water-solubility and optionally prosthetic groups for spectroscopic characterization and affinity labeling. Human AR binding affinity increased progressively with the degree of xanthine substitution to reach Ki values in the nM range. The order of affinity of each conjugate was hA2AAR > hA3AR > hA1AR, while the corresponding monomer was ranked hA2AAR > hA1AR ≥ hA3AR. The antagonist activity of the most potent conjugate 14 (34 xanthines per dendrimer) was examined at the Gi-coupled A1AR. Conjugate 14 at 100 nM right-shifted the AR agonist concentration-response curve in a cyclic AMP functional assay in a parallel manner, but at 10 nM (lower than its Ki value) it significantly suppressed the maximal agonist effect in calcium mobilization. This is the first systematic probing of a potent AR antagonist tethered on a dendrimer and its activity as a function of variable loading. PMID:21539392

  19. Dating and biogeographical patterns in the sea slug genus Acanthodoris Gray, 1850 (Mollusca, Gastropoda, Nudibranchia).

    PubMed

    Hallas, Joshua M; Simison, W Brian; Gosliner, Terrence M

    2016-04-01

    Recent studies investigating vicariance and dispersal have been focused on correlating major geological events with instances of taxonomic expansion by incorporating the fossil record with molecular clock analyses. However, this approach becomes problematic for soft-bodied organisms that are poorly represented in the fossil record. Here, we estimate the phylogenetic relationships of the nudibranch genus Acanthodoris Gray, 1850 using three molecular markers (16S, COI, H3), and then test two alternative geologically calibrated molecular clock scenarios in BEAST and their effect on ancestral area reconstruction (AAR) estimates employed in LAGRANGE. The global temperate distribution of Acanthodoris spans multiple geological barriers, including the Bering Strait (∼5.32 Mya) and the Baja Peninsula (∼5.5 Mya), both of which are used in our dating estimates. The expansion of the Atlantic Ocean (∼95-105 Mya) is also used to calibrate the relationship between A. falklandica Eliot, 1905 and A. planca Fahey and Valdés, 2005, which are distributed in southern Chile and South Africa respectively. Phylogenetic analyses recovered strong biogeographical signal and recovered two major clades representing northern and southern hemispheric distributions of Acanthodoris. When all three geological events are applied to the calibration analyses, the age for Acanthodoris is estimated to be mid-Cretaceous. When the expansion of the Atlantic Ocean is excluded from our analyses, however, Acanthodoris is estimated to be much younger, with a divergence time estimate during the Miocene. Regardless of divergence estimates, our AAR suggests that Acanthodoris may have origins in the Atlantic Ocean with the Atlantic acting as a dispersal point to the northeastern Pacific. These results suggest that Acanthodoris exhibits a rare instance of western trans-arctic expansion. This study also shows that northeast Pacific specimens of A. pilosa should be regarded as A. atrogriseata and that A

  20. Effects of a Mask on Breathing Impairment During a Fencing Assault: A Case Series Study

    PubMed Central

    Passali, Desiderio; Cambi, Jacopo; Salerni, Lorenzo; Stortini, Giancarlo; Bellussi, Luisa Maria; Passali, Francesco Maria

    2015-01-01

    Background: Fencers often complain of progressive difficulty in breathing during matches, which is generally attributed to restricted air, light and heat circulation from wearing a mask. Physiologically, the nasal structure generates airflow resistance that can reach -50% of the total respiratory resistance. Objectives: This study aims to investigate the presence of nasal obstruction in fencers and the relationship with the use of mask. Materials and Methods: An observational study on 40 fencers (18 males, 22 females) was conducted. Fencers perform a usual assault, wearing the mask and standardized physical exercises (running, sprints and obstacles) without the mask. ENT examination with a nasal flexible fiberscope, Anterior Active Rhinomanometry (AAR) and Peak Nasal Inspiratory Flow (PNIF) measurement before and after physical activity with or without the mask was recorded. Results: Before physical exercise, the total nasal airway resistance mean value for AAR was 0.33 ± 0.17 Pa/cm3/s at 150 Pa. After a match with the mask, the mean value was 0.28 ± 0.16 Pa/cm3/s. After normal physical exercises without mask, the mean value was 0.24 ± 0.15 Pa/cm3/s. Using t tests, statistically significant difference between nasal resistance before and after physical activity (P < 0.05) was observed, but no significant difference in nasal resistance between the basal value and that taken after a match wearing the masks (P = 0.1265). PNIF values significantly increase with exercise (P < 0.05). Conclusions: Our study shows that wearing the mask causes increased breathing impairment in fencers, when compared with similar physical activity without the mask. PMID:26448845

  1. The effects of automated artifact removal algorithms on electroencephalography-based Alzheimer's disease diagnosis

    PubMed Central

    Cassani, Raymundo; Falk, Tiago H.; Fraga, Francisco J.; Kanda, Paulo A. M.; Anghinah, Renato

    2014-01-01

    Over the last decade, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG signals, however, are susceptible to several artifacts, such as ocular, muscular, movement, and environmental. To overcome this limitation, existing diagnostic systems commonly depend on experienced clinicians to manually select artifact-free epochs from the collected multi-channel EEG data. Manual selection, however, is a tedious and time-consuming process, rendering the diagnostic system “semi-automated.” Notwithstanding, a number of EEG artifact removal algorithms have been proposed in the literature. The (dis)advantages of using such algorithms in automated AD diagnostic systems, however, have not been documented; this paper aims to fill this gap. Here, we investigate the effects of three state-of-the-art automated artifact removal (AAR) algorithms (both alone and in combination with each other) on AD diagnostic systems based on four different classes of EEG features, namely, spectral, amplitude modulation rate of change, coherence, and phase. The three AAR algorithms tested are statistical artifact rejection (SAR), blind source separation based on second order blind identification and canonical correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component analysis (wICA). Experimental results based on 20-channel resting-awake EEG data collected from 59 participants (20 patients with mild AD, 15 with moderate-to-severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone outperforming other enhancement algorithm combinations across three tasks: diagnosis (control vs. mild vs. moderate), early detection (control vs. mild), and disease progression (mild vs. moderate), thus opening the doors for fully-automated systems that can assist clinicians with early detection of AD, as well as disease severity progression assessment. PMID:24723886

  2. Progress at the Penning Trap Mass Spectrometer ``THe-Trap''

    NASA Astrophysics Data System (ADS)

    Hoecker, Martin; Eronen, Tommi; Ketter, Jochen; Streubel, Sebastian; Blaum, Klaus; van Dyck, Robert S.

    2012-03-01

    In 2008, the ``University of Washington Penning-Trap Mass Spectrometer'' (UW-PTMS), originally designed and built by the Van Dyck group, was moved to the Max-Planck-Insitute for Nuclear Physics in Heidelberg, Germany. It was set up in a dedicated laboratory that meets both the radiation-safety requirements, and the environment-stabilization demands for a high-precision measurement of the tritium/helium-3 mass ratio. Our goal is to measure this mass ratio with a relative uncertainty of 10-11, which would be more than an order of magnitude better than the previous best measurement. It would decrease the uncertainty in the tritium beta decay Q-value (an important parameter in the ongoing search for the neutrino mass by experiments such as KATRIN) by the same factor. In order to emphasize the specialization of our experiment with regard to Tritium and ^3Helium, it was renamed to ``THe-Trap''. THe-Trap features a double Penning-trap for rapid ion exchange, an external ion source to minimize trap contamination, a novel Zener-based voltage source, and active as well as passive stabilization of temperature, pressure and the magnetic field of the superconducting magnet. An overview of the project and a report on the recent progress will be given.

  3. Dead layer on silicon p-i-n diode charged-particle detectors

    SciTech Connect

    Wall, B. L.; Amsbaugh, John F.; Beglarian, A.; Bergmann, T.; Bichsel, H. C.; Bodine, L. I.; Boyd, N. M.; Burritt, Tom H.; Chaoui, Z.; Corona, T. J.; Doe, Peter J.; Enomoto, S.; Harms, F.; Harper, Gregory; Howe, M. A.; Martin, E. L.; Parno, D. S.; Peterson, David; Petzold, Linda; Renschler, R.; Robertson, R. G. H.; Schwarz, J.; Steidl, M.; Van Wechel, T. D.; VanDevender, Brent A.; Wustling, S.; Wierman, K. J.; Wilkerson, J. F.

    2014-04-21

    Abstract Semiconductor detectors in general have a dead layer at their surfaces that is either a result of natural or induced passivation, or is formed during the process of making a contact. Charged particles passing through this region produce ionization that is incompletely collected and recorded, which leads to departures from the ideal in both energy deposition and resolution. The silicon p-i-n diode used in the KATRIN neutrinomass experiment has such a dead layer. We have constructed a detailed Monte Carlo model for the passage of electrons from vacuum into a silicon detector, and compared the measured energy spectra to the predicted ones for a range of energies from 12 to 20 keV. The comparison provides experimental evidence that a substantial fraction of the ionization produced in the "dead" layer evidently escapes by discussion, with 46% being collected in the depletion zone and the balance being neutralized at the contact or by bulk recombination. The most elementary model of a thinner dead layer from which no charge is collected is strongly disfavored.

  4. Direct nuclear probes of neutrino mass

    NASA Astrophysics Data System (ADS)

    Parno, Diana

    2016-03-01

    Neutrinos have non-zero mass, as demonstrated by an extensive experimental program in neutrino oscillations. The absolute mass scale of neutrinos, however, remains elusive. In this talk, I will review past and future laboratory-based efforts to measure the neutrino mass directly, with minimal model dependence, through the endpoint kinematics of nuclear beta decays. The KATRIN collaboration expects to begin taking data on tritium within the next year; the Project 8 collaboration has recently demonstrated an important proof-of-principle milestone for a new tritium-based concept; and three collaborations---ECHo, HOLMES, and NuMECS---are making substantial progress toward a competitive holmium-based measurement. I will discuss some of the technical and scientific challenges faced by each approach, and give an update on the current status of the field. I gratefully acknowledge support from the U.S. Department of Energy Office of Science, Office of Nuclear Physics under Award Number DE-FG02-97ER41020.

  5. Probing the Absolute Mass Scale of Neutrinos

    SciTech Connect

    Prof. Joseph A. Formaggio

    2011-10-12

    The experimental efforts of the Neutrino Physics Group at MIT center primarily around the exploration of neutrino mass and its significance within the context of nuclear physics, particle physics, and cosmology. The group has played a prominent role in the Sudbury Neutrino Observatory, a neutrino experiment dedicated to measure neutrino oscillations from 8B neutrinos created in the sun. The group is now focusing its efforts in the measurement of the neutrino mass directly via the use of tritium beta decay. The MIT group has primary responsibilities in the Karlsruhe Tritium Neutrino mass experiment, expected to begin data taking by 2013. Specifically, the MIT group is responsible for the design and development of the global Monte Carlo framework to be used by the KATRIN collaboration, as well as responsibilities directly associated with the construction of the focal plane detector. In addition, the MIT group is sponsoring a new research endeavor for neutrino mass measurements, known as Project 8, to push beyond the limitations of current neutrino mass experiments.

  6. Towards high-precision measurement of the Tritium - He-3 mass difference

    NASA Astrophysics Data System (ADS)

    Shi, Wei; Redshaw, Matthew; Victoria, Juliette; Myers, Edmund

    2004-05-01

    An independent measurement of the mass difference of ^3He-^3T provides an important check of systematic errors in tritium beta-decay experiments that set limits to the electron anti-neutrino mass [1]. Using the precision Penning trap system developed at MIT but recently relocated to Florida State University [2], and the simultaneous two-ion cyclotron frequency measurement technique recently developed at MIT [3], we aim to measure this mass difference to better than 30 meV/c^2, more than an order of magnitude improvement over previous measurements [4,5]. Problems being addressed include producing single T^+ ions in the trap without spoiling the vacuum with ^3He, and the extension of the MIT techniques to ions of lighter mass. [1] KATRIN: http://iklau1.fzk.de/tritium [2] See abstract by Redshaw et al. [3] S. Rainville, J.K. Thompson, and D.E. Pritchard, Science 303, 334 (2004). [4] R.S. Van Dyck, D.L. Farnham, and P.B. Schwinberg, PRL 70, 2888 (1993). [5] G. Audi, A.H. Wapstra, and C. Thibault, Nuclear Physics A729, 337 (2003).

  7. Advanced data extraction infrastructure: Web based system for management of time series data

    NASA Astrophysics Data System (ADS)

    Chilingaryan, S.; Beglarian, A.; Kopmann, A.; Vöcking, S.

    2010-04-01

    During operation of high energy physics experiments a big amount of slow control data is recorded. It is necessary to examine all collected data checking the integrity and validity of measurements. With growing maturity of AJAX technologies it becomes possible to construct sophisticated interfaces using web technologies only. Our solution for handling time series, generally slow control data, has a modular architecture: backend system for data analysis and preparation, a web service interface for data access and a fast AJAX web display. In order to provide fast interactive access the time series are aggregated over time slices of few predefined lengths. The aggregated values are stored in the temporary caching database and, then, are used to create generalizing data plots. These plots may include indication of data quality and are generated within few hundreds of milliseconds even if very high data rates are involved. The extensible export subsystem provides data in multiple formats including CSV, Excel, ROOT, and TDMS. The search engine can be used to find periods of time where indications of selected sensors are falling into the specified ranges. Utilization of the caching database allows performing most of such lookups within a second. Based on this functionality a web interface facilitating fast (Google-maps style) navigation through the data has been implemented. The solution is at the moment used by several slow control systems at Test Facility for Fusion Magnets (TOSKA) and Karlsruhe Tritium Neutrino (KATRIN).

  8. Light sterile neutrino sensitivity of 163Ho experiments

    NASA Astrophysics Data System (ADS)

    Gastaldo, L.; Giunti, C.; Zavanin, E. M.

    2016-06-01

    We explore the sensitivity of 163Ho electron capture experiments to neutrino masses in the standard framework of three-neutrino mixing and in the framework of 3+1 neutrino mixing with a sterile neutrino which mixes with the three standard active neutrinos, as indicated by the anomalies found in short-baseline neutrino oscillations experiments. We calculate the sensitivity to neutrino masses and mixing for different values of the energy resolution of the detectors, of the unresolved pileup fraction and of the total statistics of events, considering the expected values of these parameters in the two planned stages of the ECHo project (ECHo-1k and ECHo-1M). We show that an extension of the ECHo-1M experiment with the possibility to collect 1016 events will be competitive with the KATRIN experiment. This statistics will allow to explore part of the 3+1 mixing parameter space indicated by the global analysis of short-baseline neutrino oscillation experiments. In order to cover all the allowed region, a statistics of about 1017 events will be needed.

  9. Upper bound of 0.28 eV on neutrino masses from the largest photometric redshift survey.

    PubMed

    Thomas, Shaun A; Abdalla, Filipe B; Lahav, Ofer

    2010-07-16

    We present a new limit of ∑m(v) ≤ 0.28 (95% CL) on the sum of the neutrino masses assuming a flat ΛCDM cosmology. This relaxes slightly to ∑m(ν) ≤ 0.34 and ∑m(v) ≤ 0.47 when quasinonlinear scales are removed and w≠ -1, respectively. These are derived from a new photometric catalogue of over 700,000 luminous red galaxies (MegaZ DR7) with a volume of 3.3  (Gpc h(-1))(3) and redshift range 0.45 < z < 0.65. The data are combined with WMAP 5-year CMB, baryon acoustic oscillations, supernovae, and a Hubble Space Telescope prior on h. When combined with WMAP these data are as constraining as adding all supernovae and baryon oscillation data available. The upper limit is one of the tightest constraints on the neutrino from cosmology or particle physics. Further, if these bounds hold, they all predict that current-to-next generation neutrino experiments, such as KATRIN, are unlikely to obtain a detection. PMID:20867754

  10. Assessment of molecular effects on neutrino mass measurements from tritium β decay

    NASA Astrophysics Data System (ADS)

    Bodine, L. I.; Parno, D. Â. S.; Robertson, R. Â. G. Â. H.

    2015-03-01

    The β decay of molecular tritium currently provides the highest sensitivity in laboratory-based neutrino mass measurements. The upcoming Karlsruhe Tritium Neutrino (KATRIN) experiment will improve the sensitivity to 0.2 eV, making a percent-level quantitative understanding of molecular effects essential. The modern theoretical calculations available for neutrino mass experiments agree with spectroscopic data. Moreover, when neutrino mass experiments performed in the 1980s with gaseous tritium are reevaluated using these modern calculations, the extracted neutrino mass squared values are consistent with zero instead of being significantly negative. However, the calculated molecular final-state branching ratios are in conflict with dissociation experiments performed in the 1950s. We reexamine the theory of the final-state spectrum of molecular-tritium decay and its effect on the determination of the neutrino mass, with an emphasis on the role of the vibrational- and rotational-state distribution in the ground electronic state. General features can be reproduced quantitatively from considerations of kinematics and zero-point motion. We summarize the status of validation efforts and suggest means for resolving the apparent discrepancy in dissociation rates.

  11. High-accuracy mass spectrometry for fundamental studies.

    PubMed

    Kluge, H-Jürgen

    2010-01-01

    Mass spectrometry for fundamental studies in metrology and atomic, nuclear and particle physics requires extreme sensitivity and efficiency as well as ultimate resolving power and accuracy. An overview will be given on the global status of high-accuracy mass spectrometry for fundamental physics and metrology. Three quite different examples of modern mass spectrometric experiments in physics are presented: (i) the retardation spectrometer KATRIN at the Forschungszentrum Karlsruhe, employing electrostatic filtering in combination with magnetic-adiabatic collimation-the biggest mass spectrometer for determining the smallest mass, i.e. the mass of the electron anti-neutrino, (ii) the Experimental Cooler-Storage Ring at GSI-a mass spectrometer of medium size, relative to other accelerators, for determining medium-heavy masses and (iii) the Penning trap facility, SHIPTRAP, at GSI-the smallest mass spectrometer for determining the heaviest masses, those of super-heavy elements. Finally, a short view into the future will address the GSI project HITRAP at GSI for fundamental studies with highly-charged ions. PMID:20530821

  12. On the Proof of Dark Matter, the Law of Gravity, and the Mass of Neutrinos

    NASA Astrophysics Data System (ADS)

    Angus, Garry W.; Shan, Huan Yuan; Zhao, Hong Sheng; Famaey, Benoit

    2007-01-01

    We develop a new method to predict the density associated with weak-lensing maps of (un)relaxed clusters in a range of theories interpolating between general relativity (GR) and modified Newtonian dynamics (MOND). We apply it to fit the lensing map of the Bullet merging cluster 1E 0657-56, in order to constrain more robustly the nature and amount of collisionless matter in clusters beyond the usual assumption of spherical equilibrium (Pointecouteau & Silk) and the validity of GR on cluster scales (Clowe et al.). Strengthening the proposal of previous authors, we show that the Bullet Cluster is dominated by a collisionless-most probably nonbaryonic-component in GR as well as in MOND, a result consistent with the dynamics of many X-ray clusters. Our findings add to the number of known pathologies for a purely baryonic MOND, including its inability to fit the latest data from the Wilkinson Microwave Anisotropy Probe. A plausible resolution of all these issues and standard issues of cold dark matter (CDM) with galaxy rotation curves is the ``marriage'' of MOND with ordinary hot neutrinos of 2 eV. This prediction is just within the GR-independent maximum of neutrino mass from current β-decay experiments and will be falsifiable by the Karlsruhe Tritium Neutrino (KATRIN) experiment by 2009. Issues of consistency with strong-lensing arcs and the large relative velocity of the two clusters comprising the Bullet Cluster are also addressed.

  13. Forbidden unique beta-decays and neutrino mass

    SciTech Connect

    Dvornický, Rastislav; Šimkovic, Fedor

    2013-12-30

    The measurement of the electron spectrum in beta-decays provides a robust direct determination of the values of neutrino masses. The planned rhenium beta-decay experiment, called the “Microcalorimeter Arrays for a Rhenium Experiment” (MARE), might probe the absolute mass scale of neutrinos with the same sensitivity as the Karlsruhe tritium neutrino mass (KATRIN) experiment, which is expected to collect data in a near future. In this contribution we discuss the spectrum of emitted electrons close to the end point in the case of the first unique forbidden beta-decay of {sup 79}Se, {sup 107}Pd and {sup 187}Re. It is found that the p{sub 3/2}-wave emission dominates over the s{sub 1/2}-wave. It is shown that the Kurie plot near the end point is within a good accuracy linear in the limit of massless neutrinos like the Kurie plot of the superallowed beta-decay of {sup 3}H.

  14. Suitability of alkaline leaching and etching experiments in the quantification of ASR potential of quartz-rich rocks

    NASA Astrophysics Data System (ADS)

    Kuchařová, Aneta; Šachlová, Šárka; Pertold, Zdeněk; Přikryl, Richard

    2015-04-01

    Three groups of methods are conventionally applied in the assessment of the susceptibility of aggregates used in concrete to be affected by alkali-silica reaction (ASR). The most frequently employed expansion tests (accelerated mortar bar test and concrete prism test, e.g. ASTM C1260, RILEM AAR2, RILEM AAR4.1) quantify ASR potential of aggregates according to the expansion values of mortar bars (resp. concrete prisms) measured after certain testing time period. Petrographic methods are based on the quantification of alkali-reactive phases by polarizing microscopy (e.g. RILEM AAR1). Chemical methods quantify ASR potential according to the amount of Si4+ dissolved into alkaline solution combined with the reduction of alkalinity of the solution (e.g. ASTM C289). The current study focused on the comparison of three approaches: the alkaline etching of polished rock sections and standard chemical method (following ASTM C289) with the measuring of expansion values of mortar bars (following ASTM C1260). Various types of quartz and amorphous SiO2 used for the experiments were separated from rock samples of orthoquartzite, quartz meta-greywacke, pegmatite, phyllite, chert, and flint. Polished rock sections (resp. crushed fraction 0.125/0.250) were used and subjected to leaching in 1M NaOH solution at 80°C for 14 days (resp. 24 hours). After alkaline etching in alkaline solution, the rock sections were analyzed by scanning electron microscopy combined with energy dispersive spectrometer. Representative areas were documented in back scattered electron images and quantified using fully-automatic petrographic image analysis. ASR potential of the polished rock sections was evaluated by the vol. % of area affected by alkaline etching. ASR potential of crushed aggregate was estimated by measurements of Si4+ dissolved into the solution versus the reduction of alkalinity of the solution (following ASTM C289). Classification according to the ASTM C289 indicated three of investigated

  15. Changes in fluid composition in metamorphic veins along a cross section through the Central Alps, Switzerland

    NASA Astrophysics Data System (ADS)

    Martinek, K.; Wagner, T.; Wälle, M.; Heinrich, C. A.

    2012-04-01

    The classical Alpine fissure veins are large cavities lined by occasionally giant quartz crystals and many other euhedral mineral assemblages. They occur in regionally metamorphosed terranes in the upper crust and record important information about the composition and evolution of metamorphic fluids, and fluid sources and mass transfer during crustal fluid-rock interaction (Oliver & Bons, 2001). Detailed fluid inclusion studies of Alpine veins along a cross section through the Central Alps have established that the fluid composition shows a distinct evolution with increasing metamorphic grade, where consecutive zones are dominated by (1) heavier hydrocarbons, (2) CH4, (3) H2O-NaCl, and (4) H2O-CO2-NaCl (Mullis et al., 1994). This study addresses the chemical evolution of fluids in Alpine fissure veins in the Central Swiss Alps by integrating field work, fluid inclusion studies (microthermometry and LA-ICPMS microanalysis of individual fluid inclusions), and geochemical modeling. The field locations were selected along a cross section through the Central Alps that covers different lithologies and metamorphic conditions. This includes vein systems in the Aar massif (Gauli glacier, Gerstenegg vein in the Grimsel power station, Tiefen glacier), the Nufenen and Griess pass, the Bedretto valley, the Cavagnoli region and a tunnel near Faido. Fluid inclusion studies have been completed for the localities in the Aar massif, the Cavagnoli region and the Faido tunnel. It was possible to analyze a considerable number of elements with LA-ICPMS, including Na, K, Rb, Cs, Li, Ca, Mg, Sr, Ba, Mn, B, As, Sb, S, Pb and Zn. The fluid inclusions from the Aar massif are low-salinity aqueous two-phase, whereas the Cavagnoli and Faido samples dominantly contain aqueous-carbonic fluid inclusions. While the Gauli samples contain fluid inclusions with 4.5-5.0 wt% equivalent (eqv.) NaCl, those from the Gerstenegg and Tiefen glacier have a considerably higher salinity of around 10-11 wt% eqv

  16. Rock Magnetic Fabrics, Paleomagnetic Vectors, and Rock Magnetic Cyclostratigraphy of the Marcellus FM, Sunbury PA

    NASA Astrophysics Data System (ADS)

    Minguez, D. A.; Kodama, K. P.

    2013-12-01

    We present the preliminary results of a multi-faceted rock magnetic study conducted on 195 samples from the Oatka Creek member of the Marcellus formation, where it has been extracted from the subsurface as a drill core near Sunbury, PA. Samples were oriented based on bedding attitude observed within the core and were removed from the core at a spacing of ≈0.25 meters starting from the base (depth ≈ 500 meters) and spanning 51 meters of stratigraphic section. The results of measurements of the anisotropy of magnetic susceptibility (AMS) consistently demonstrate a nearly triaxial fabric with maximum principal axes clustering east-west and horizontal in geographic coordinates, nearly parallel to the direction of bedding strike. AMS minimum principal axes cluster near the pole to the bedding plane. Anisotropy of anhysteretic remanence (AAR) applied with a 100 mT peak field and a 97 μT bias field in 9 orientations demonstrates a markedly different fabric, with maximum principal axis clustering north-south and horizontal in geographic coordinates. Minimum principal axes of AAR cluster steeply (~60-70 degrees) to the west. The discrepancy between AAR and AMS fabrics likely indicates the AMS is dominated by paramagnetic clays, and thus may be interpreted as an east-west intersection lineation of clay particles dipping gently north or south. Paleomagnetic directions obtained using Alternating Field (AF) demagnetization in 5 mT steps up to 110 mT demonstrates a high coercivity remanence (>35 mT) with a south and shallow direction (D= 183.4 I=-14.7). This result is consistent with previous studies of the Marcellus formation and the Devonian Catskill red beds. Thermal demagnetization experiments demonstrate a similar magnetization removed by temperatures between 250 and 350 degrees Celsius, however, continued heating results in the acquisition of strong, inconsistent magnetizations likely the result of oxidizing iron sulfides. Thermal demagnetization of orthogonal partial

  17. The history of Cesium-137 liquid emissions by Mühleberg Nuclear Power Plant (Switzerland) is recorded in Lake Biel sediments

    NASA Astrophysics Data System (ADS)

    Girardclos, Stéphanie; Faessler, Jérôme; Loizeau, Jean-Luc; Zehringer, Markus

    2014-05-01

    Lake sediments record changes happening in their upstream river catchment and regional environment which includes traces of artificial radionuclides emissions deriving from human activities. 137Cs emissions started worldwide in the early 1950's and peaked in 1963-64 due to nuclear bomb tests in the high atmosphere. A second 137Cs activity peak, due to the 1986 Chernobyl catastrophe is recorded in sediment archives from central Europe. These two events (1963/64 and 1986) serve routinely as time markers for recent lake records. Nuclear Power Plants (NPPs) are often constructed along river course for cooling purposes. Since 1972, Mühleberg NPP (central Switzerland) lies 18 km upstream Lake Biel and releases radioactive liquid emissions into the Aare river which adds to the diffuse - above mentioned - radioactive pollution, as revealed by Albrecht et al. (1995; 1998) and recently confirmed by Thevenon et al. (2013) from Lake Biel sediments. The water of Lake Biel is used as drinking water for ca. 60'000 inhabitants and its outflowing water is further used by downstream cities lying on the Aare-Rhine course such as Basel (200'000 inhab.) In this study, the 137Cs activity curve of a 90-cm-long sediment core (BIE10-8), retrieved in April 2010 from the central Lake Biel basin at ca. 50 m depth, and measured by gamma ray spectrometry using high resolution germanium detectors, confirms previous work and reveals a new peak for the year 1998-2000, as observed by Thevenon et al. (2013). This peak is most certainly due to Mühleberg NPP as shown by the good correlation with declared 137Cs liquid emissions indicating a significant increase in 1998-99. Decay corrected activity data, converted into 137Cs fluxes, point to water pollution by Mühleberg NPP in 1975-1985 as being similar to those linked to the catastrophic events in 1963-64 and 1986 (about 75%). As former study showed that Lake Biel sediments scavenge only a portion of the total radionuclide in water, i.e. 30-55% for

  18. Metasomatism in the Chain of Ponds K-feldspars: Reassessing Discrete Domain 39Ar-40Ar Modelling

    NASA Astrophysics Data System (ADS)

    Villa, I. M.; Chafe, A. N.; Hanchar, J. M.; Wirth, R.

    2012-12-01

    The post-crystallization petrology of K-feldspar (Kfs) is mostly controlled by fluids. Accordingly, [1] documented that successive mineral generations in Kfs grains of the Aar metagranite can be concordantly identified by both cathodoluminescence (CL) and back-scattered electron (BSE) imaging, elemental, and multi-isotope techniques. Imaging microstructures is a particularly powerful tool appreciated by many U-Pb geochronologists, and its use in 39Ar-40Ar dating is beginning to show beneficial progress [2]. However, a dissenting reviewer of [1] argued that the Aar sample was not typical of "orthodox" Kfs and the results could not be generalized to all Kfs [3]. On a different front, [4] demonstrated that the mathematical modeling that assumed Fickian diffusion in discrete domains, defined once and for all by [5], lacked internal consistency on several counts. As Chain of Ponds Pluton (CPP) Kfs sample MH-10 played a foundational role in the development of the mathematical model by [5], we decided to obtain direct evidence whether the numerous internal inconsistencies of the model are due to the previously undescribed petrological history of MH-10. We collected sample JH-02-01 on the same CPP outcrop as MH-10 [6]. All age spectra of different sieve fractions of the Kfs separate, both handpicked and unpicked, show a staircase shape. The Arrhenius diagram of apparent diffusivity agrees with the original MH-10 [5] and shows the same apparent r/r0 behavior. However, Arrhenius trajectories for all size fractions are parallel to each other and self-similar, as predicted by [4], instead of being joined at low temperature ("small domains") and diverging only at high T ("largest domain"), as would be implicit in the model by [5]. The CL and BSE images demonstrate several successive Kfs generations of diverse luminescence and chemical and isotopic properties. Microchemical analyses document patchy Ba enrichment, a tell-tale fingerprint of deuteric fluid interaction and

  19. Comparative Analysis of the Cardioprotective Properties of Opioid Receptor Agonists in a Rat Model of Myocardial Infarction

    PubMed Central

    Maslov, Leonid N.; Lishmanov, Yury B.; Oeltgen, Peter R.; Barzakh, Eva I.; Krylatov, Andrey V.; Naryzhnaya, Natalia V.; Pei, Jian-Ming; Brown, Stephen A.

    2010-01-01

    Objectives This study was conducted to test the hypothesis that opioid receptor (OR) mediated cardioprotection is agonist-specific when administered prior to coronary artery occlusion and reperfusion in a rat model. Methods Anesthetized open-chest male Wistar rats were subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. Opioid agonists were infused 15 minutes prior to coronary artery occlusion. Two control groups and 15 opioid treated groups were studied. Controls were infused with either saline alone (n = 16) or dimethyl sulfoxide (DMSO) plus hydroxypropyl-β-cyclodextrin in saline (n = 19). The μ selective agonist DAMGO was infused at either 150 nmol/kg (n = 15) or 1500 nmol/kg (n = 14), and Dermorphin-H was infused at 150 nmol/kg (n = 14). The δ1 selective agonist D-Pen2,5 Enkephalin (DPDPE) was infused at 150 nmol/kg (n = 16) or 1500 nmol/kg (n = 14). The δ2 selective agonists Deltorphin II (n = 16), Deltorphin-Dvariant (n = 15) and Deltorphin-E (n = 14) were infused at 150 nmol/kg. The selective κ1 opioid agonist U-50488 was infused at 240 nmol/kg (n = 14), 1500 nmol/kg (n = 14), and 2,400 nmol/kg (n = 14). The selective κ2 opioid agonist GR-89696 was infused at 150 nmol/kg (n = 14) and 1500 nmol/kg (n = 15). Orphinan FQ (Nociceptin), also referred to as OR Ligand1 (ORL1), was infused at 220 nmol/kg (n = 15) and 1500 nmol/kg (n = 15). The infarct size/area at risk (IS/AAR) ratio was determined after reperfusion by negative staining with patent blue violet dye. Hemodynamic parameters including heart rate, mean arterial blood pressure (MAP), and rate pressure product (RPP) were determined. Results Pretreatment with the δ2 OR agonist Deltorphin II (150 nmol/kg) significantly reduced the IS/AAR ratio, while Deltorphin-Dvariant and Deltorphin-E did not exhibit an infarct sparing effect at that treatment dose. Activation of δ1 OR by DPDPE, κ1 OR by U-50488, κ2 OR by U-50488, μ OR by DAMGO, Dermophin-H, and Nociceptin had

  20. Frequencies, mechanisms and climate forcing of paleofloods in the Bernese Alps (Switzerland) inferred from natural, historical, and instrumental time series

    NASA Astrophysics Data System (ADS)

    Schulte, Lothar; Peña, Juan Carlos; Carvalho, Filipe; Julià, Ramon; Gómez-Bolea, Antonio; Burjachs, Francesc; Llorca, Jaime; Rubio, Patricio; Veit, Heinz

    2015-04-01

    The aim of this contribution is the reconstruction of a 2600-yr long flood series generated from high-resolution deltaplain sediments of the Hasli-Aare and Lütschine delta, which reproduces the fluvial dynamic and related mechanisms, including trends, clusters and gaps of floods in alpine catchments. Paleofloods frequencies were reconstructed from geoarchives particularly by sedimentary, geochemical (XRF-core scan, conventional XRF, LOI and grain size), mineralogical, geomorphological, pollen and lichenometric records. An important issue is the question if these paleofloods can be calibrated (exact dating) by data series from historical sources (textual and factual) and by instrumental data. Not less than 12 of 14 severe and catastrophic events before the termination of the River Aare Correction in 1867, are detected during the last 700 years also by coarse-grained flood layers, ln(Zr/Ti) peaks and Factor 1 scores. Spectral analysis of the geochemical and pollen time series and climate proxies (δ14C, TSI, δ18O isotopes from the Greenland ice, temperatures and precipitation reconstruction from tree-rings, NAO, SNAO) evidence similar periodicities of 60, 85, 105, 120 and 200 yrs during the two last Millennia. Thus, the mechanisms of the flood processes are strongly influenced by the North Atlantic dynamics and solar forcing. The composite 2600-yr sedimentary floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (medium high catchment area) match very clearly to maxima of Total Solar Irradiance (Steinhilber et al., 2009) pointing to reduced flood activity during warmer climate pulses. The aggradation of the paleoflood clusters (e.g. 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) with contribution of siliciclasts from highest catchment area (plutonic bedrock) occurred predominantly during periods with cooler summer temperature, reduced solar irradiance and phases of drier spring climate (B

  1. Revised Macquarie-Antarctic plate motion during the last 6 Ma using magnetic anomalies of Australian-Antarctic Ridge near 156°-161°E

    NASA Astrophysics Data System (ADS)

    Choi, H.; Kim, S. S.; Park, S. H.

    2015-12-01

    The longest segment of Australian-Antarctic Ridge (AAR), located near 156°-161°E, is the tectonic boundary between the Australian and the Antarctic plates, and meets the Macquarie Triple Junction of Australian-Antarctic-Pacific plates at the eastern end of the segment. In 2011 and 2013, the multidisciplinary mid-ocean ridge program of Korea Polar Research Institute (KOPRI) conducted a series of geological, geochemical, geophysical, and hydrothermal studies at the segment. Especially, in order to determine the detailed location of the ridge axis, a number of short magnetic cross lines were observed in 2013. In 2015, we additionally collected the magnetic data and the high-resolution shipboard bathymetric data for two 400-km long lines across the ridge segment. Here we utilize the observed magnetic data to estimate spreading rates and its temporal changes along the ridge segment. The half-spreading rates computed using MODMAG with our magnetic data range mostly between 28~34 mm/yr. The southern flank of this ridge segment, which has been added to the Antarctic plate as a trailing side between the Australian and the Antarctic plate, tends to have faster spreading rates compared to the northern flank. According to the previous studies, the Macquarie plate, which is regarded as the intra-plate inside the Australian plate and bounded by the northern flank of the ridge segment in this study, has been rotated relative to the Antarctic plate since about 6 Ma. We revised rotation poles between the Macquarie-Antarctic plates for the chron C2Ay (2.58 Ma), chron C3Ay (6.04 Ma) and the other ages additionally, using Hellinger. In this study, we employed the observed magnetic data with additional constraints from the available shipboard measurements. The synthetic flow-line of Balleny Fracture Zone is used as an input to Hellinger, because the region between the Tasman Fracture Zone and the Macquarie Triple Junction is supposed to be included to the Macquarie plate. We examine

  2. Ground state of bilayer hα-silica: mechanical and electronic properties.

    PubMed

    Han, Yang; Hu, Ming

    2015-12-18

    The family of two-dimensional (2D) crystals was recently joined by silica, one of the most abundant resources on earth. So far two different polymorphs of this material, namely a tetrahedra-shaped monolayer and a fully saturated bilayer structure, have been synthesized on various metal substrates and their fascinating properties enable 2D silica to hold promise in nanoelectronic device applications. In this paper a new ground state of bilayer-AAr-stacking hα-silica-has been discovered by first principles calculations. The new structure is featured with a formation of Si-Si bonds between all sp(3) hybridized SiO3 triangular pyramids, lying respectively in different silica layers, with an intrinsic rotational angle of about 12.5° along the out-of-plane Si-Si bond. Due to the doubled number of Si-Si bonds in the new structure, the system energy is lowered by nearly three times more than that reported recently in literature (0.8 eV) (Özçelik et al 2014 Phys. Rev. Lett. 112 246803), when compared with the single layer hα-silica. A mechanical property investigation shows that the AAr-stacking bilayer hα-silica possesses high in-plane stiffness and a negative Poisson's ratio, which stems from the intrinsic rotational angle of the SiO3 triangular pyramids. Strikingly, the negative Poisson's ratio evolves into positive at a critical tensile strain ϵ ≈ 1.2%. Such negative-to-positive evolvement is associated with the adaptation of the rotational angle to the applied strain and the structure transition into the nearby valley of the energy landscape. The detailed transition process has been thoroughly analyzed. The electronic properties of the new ground state are also calculated, along with their response to the external strain. Our new ground state structure introduces a new member to the family of 2D bilayer silica materials and is expected to facilitate experimental studies identifying the related structures and exploring further physical and chemical properties

  3. Zooplankton Growth, Respiration and Grazing on the Australian Margins of the Tropical Indian and Pacific Oceans

    PubMed Central

    McKinnon, A. David; Doyle, Jason; Duggan, Samantha; Logan, Murray; Lønborg, Christian; Brinkman, Richard

    2015-01-01

    The specific activity of aminoacyl-tRNA synthetases (spAARS), an index of growth rate, and of the electron transport system (spETS), an index of respiration, was measured in three size fractions (73–150 μm, >150 μm and >350 μm) of zooplankton during five cruises to tropical coastal waters of the Kimberley coast (North West Australia) and four cruises to waters of the Great Barrier Reef (GBR; North East Australia). The N-specific biomass of plankton was 3–4-fold higher in the Kimberley than on the GBR in all 3 size classes: Kimberley 1.27, 3.63, 1.94 mg m-3; GBR 0.36, 0.88 and 0.58 mg m-3 in the 73–150 μm, >150 μm and >350 μm size classes, respectively. Similarly, spAARS activity in the Kimberley was greater than that of the GBR: 88.4, 132.2, and 147.6 nmol PPi hr-1 mg protein -1 in the Kimberley compared with 71.7, 82.0 and 83.8 nmol PPi hr-1 mg protein -1 in the GBR, for the 73–150 μm, >150 μm and >350 μm size classes, respectively. Specific ETS activity showed similar differences in scale between the two coasts: 184.6, 148.8 and 92.2 μL O2 hr-1 mg protein-1 in the Kimberley, against 86.5, 88.3 and 71.3 μL O2 hr-1 mg protein-1 in the GBR. On the basis of these measurements, we calculated that >150 μm zooplankton grazing accounted for 7% of primary production in the Kimberley and 8% in GBR waters. Area-specific respiration by >73 μm zooplankton was 7-fold higher in the Kimberley than on the GBR and production by >150 μm zooplankton was of the order of 278 mg C m-2 d-1 in the Kimberley and 42 mg C m-2 d-1 on the GBR. We hypothesize that the much stronger physical forcing on the North West shelf is the principal driver of higher rates in the west than in the east of the continent. PMID:26469275

  4. In vitro alpha1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel alpha1A-adrenoceptor selective antagonists.

    PubMed

    Williams, T J; Blue, D R; Daniels, D V; Davis, B; Elworthy, T; Gever, J R; Kava, M S; Morgans, D; Padilla, F; Tassa, S; Vimont, R L; Chapple, C R; Chess-Williams, R; Eglen, R M; Clarke, D E; Ford, A P

    1999-05-01

    It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia. PMID:10369480

  5. In vitro α1-adrenoceptor pharmacology of Ro 70-0004 and RS-100329, novel α1A-adrenoceptor selective antagonists

    PubMed Central

    Williams, T J; Blue, D R; Daniels, D V; Davis, B; Elworthy, T; Gever, J R; Kava, M S; Morgans, D; Padilla, F; Tassa, S; Vimont, R L; Chapple, C R; Chess-Williams, R; Eglen, R M; Clarke, D E; Ford, A P D W

    1999-01-01

    It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the α1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms.The present study describes the α1-adrenoceptor (α1-AR) subtype selectivities of two novel α1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned α1A-, α1B- and α1D-AR showed nanomolar affinity and significant α1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the α1B- and α1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity.Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing α1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively).The α1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a ‘uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia. PMID:10369480

  6. The response of debris-covered glaciers to climate change: A numerical modeling approach

    NASA Astrophysics Data System (ADS)

    Anderson, Leif S.; Anderson, Robert S.

    2016-04-01

    Debris-covered glaciers are common in rapidly-eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. Continuous debris cover can therefore reduce the mass balance gradient in the ablation zone, leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2D long-valley numerical glacier model that includes deposition of debris on the glacier surface, and both englacial and supraglacial debris advection. We ran 120 simulations in which a steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to new steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier. The debris flux onto the glacier surface, and the details of the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris-related variables are held constant. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to debris-free glaciers forced by the same climate. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). The model reproduces first-order relationships between debris cover, AARs, and glacier surface velocities reported from glaciers in High Asia. We also explore the response of debris-covered glaciers to increases in the equilibrium-line altitude (climate warming). We highlight the conditions required to generate a low surface velocity 'dead' ice terminal reach during a warming climate, and the associated increase of fractional glacier surface debris. We also compare our debris-covered glacier climate response results with data from glaciers in High Asia. Our model provides a quantitative, theoretical

  7. An Interglacial Polar Bear and an Early Weichselian Glaciation at Poolepynten, Western Svalbard

    NASA Astrophysics Data System (ADS)

    Ingolfsson, O.; Alexanderson, H.

    2012-12-01

    Recent discovery of a subfossil polar bear (Ursus maritimus) jawbone in the Poolepynten coastal cliff sequence, western Svalbard (Ingolfsson & Wiig, 2009), and its implications for the natural history of the polar bear (Lindqvist et al. 2010; Miller et al. 2012), motivated an effort to better constrain the environmental history and age envelope of the Poolepynten sediment sequence, particularly the lithostratigraphy of the coastal cliffs with emphasis on re-dating the sequence using the optically stimulated luminescence (OSL) dating technique. We report a revised lithostratigraphy and nine new OSL ages. It is concluded that the Poolepynten sequence holds evidence of four regional glaciation events, recorded in the strata as erosional unconformities and/or glacial deposits followed by shallow-marine deposition signifying transgressions and subsequent glacio-isostatic rebound and regression. Our OSL ages refine previous age determinations (14C and IRSL) and support the interpretation that the subfossil polar bear jawbone is of last interglacial (Eemian) age (Alexanderson et al. in press). References: Alexanderson, H., Ingolfsson, O., Murray, A.S. & Dudek, J. in press. An Interglacial Polar Bear and an Early Weichselian Glaciation at Poolepynten, Western Svalbard. Boreas 00, 000-000. Ingolfsson, O. & Wiig, O. 2009. Late Pleistocene fossil find in Svalbard: the oldest remains of a polar bear (Ursus maritimus Phipps, 1744) ever discovered. Polar Research 28, 455-466. Lindqvist, C., Schuster, S. C., Sun, Y., Talbot, S. L., Qi, J., Ratan, A., Tomsho, L. P., Kasson, L., Zeyl, E., Aars, J., Miller, W., Ingólfsson, Ó., Bachmann, L. & Wiig, Ø. 2010. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear. Proceedings of the National Academy of Sciences 107, 5053-5057. Miller, W., Schuster, S. C., Welch, A. J., Ratan, A., Bedoya-Reina, O. C., Zhao, F., Kim, H. L., Burhans, R.C., Drautz, D.I., Wittekindt, N.E., Tomsho, L.P., Ibarra-Laclette, E

  8. Motor unit potential morphology differences in individuals with non-specific arm pain and lateral epicondylitis

    PubMed Central

    Calder, Kristina M; Stashuk, Daniel W; McLean, Linda

    2008-01-01

    Background The pathophysiology of non-specific arm pain (NSAP) is unclear and the diagnosis is made by excluding other specific upper limb pathologies, such as lateral epicondylitis or cervical radiculopathy. The purpose of this study was to determine: (i) if the quantitative parameters related to motor unit potential morphology and/or motor unit firing patterns derived from electromyographic (EMG) signals detected from an affected muscle of patients with NSAP are different from those detected in the same muscle of individuals with lateral epicondylitis (LE) and/or control subjects and (ii) if the quantitative EMG parameters suggest that the underlying pathophysiology in NSAP is either myopathic or neuropathic in nature. Methods Sixteen subjects with NSAP, 11 subjects with LE, eight subjects deemed to be at-risk for developing a repetitive strain injury, and 37 control subjects participated. A quantitative electromyography evaluation was completed using decomposition-based quantitative electromyography (DQEMG). Needle- and surface-detected EMG signals were collected during low-level isometric contractions of the extensor carpi radialis brevis (ECRB) muscle. DQEMG was used to extract needle-detected motor unit potential trains (MUPTs), and needle-detected motor unit potential (MUP) and surface detected motor unit potential (SMUP) morphology and motor unit (MU) firing rates were compared among the four groups using one-way analysis of variance (ANOVA). Post hoc analyses were performed using Tukey's pairwise comparisons. Results Significant group differences were found for all MUP variables and for MU firing rate (p < 0.006). The post-hoc analyses revealed that patients with NSAP had smaller MUP amplitude and SMUP amplitude and area compared to the control and LE groups (p < 0.006). MUP duration and AAR values were significantly larger in the NSAP, LE and at-risk groups compared to the control group (p < 0.006); while MUP amplitude, duration and AAR values were

  9. Monitoring temporal variations in water resources across the Arabian Peninsula and identification of their controlling factors

    NASA Astrophysics Data System (ADS)

    Ahmed, M.; Sultan, M.; Othman, A.

    2015-12-01

    Assessment, monitoring, and development of the fresh water resources in the Arabian Peninsula (AP) are critical for the sustenance of the AP's growing population and water consumption. Monthly (01/2003-12/2013) Gravity Recovery and Climate Experiment (GRACE) data along with other relevant climatic, geologic, hydrogeologic, and remote sensing datasets were used to monitor the spatiotemporal variability in the AP's water resources and to investigate the causes of those variations. Four regions were selected; in our selection, we tried to cover major aquifers, follow political boundaries, and exceed GRACE footprint (~0.20×106 km2) to minimize uncertainties. The selected regions are: (1) Northern Saudi Arabia and Jordan (area: 0.53×106 km2), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis (area: 0.97×106 km2), (3) Yemen (area: 0.45×106 km2), and (4) Oman (area: 0.32×106 km2). Results indicate: (1) Northern Saudi Arabia and Jordan area is experiencing large depletions (-8.76±0.94 mm/yr; -4.68±0.50 km3/yr) in GRACE-derived terrestrial water storage (TWS) that is largely related to groundwater extraction as well as decrease in rainfall rates throughout the investigated period compared to the preceding period (average annual rainfall [AAR]: 2003-2013: 58 mm; 1979-2002: 103 mm), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis area is experiencing a moderate depletion (-2.73±1.0 mm/yr; -2.63±0.96 km3/yr) in TWS that might be related to groundwater/oil extraction as well as a moderate decrease in rainfall rates (AAR: 2003-2013: 61 mm; 1979-2002: 82 mm), (3) Yemen is experiencing a slight depletion (-0.82±0.30 mm/yr; -0.36±0.13 km3/yr) in TWS that might be related groundwater extraction, and (4) Oman is experiencing slight increase (+0.78±0.30 mm/yr; +0.25±0.09 km3/yr) in TWS that might be related an increase in rainfall rates. Our preliminary results are being further examined by: (1) extracting temporal variations in groundwater storage by

  10. Interpretation of fluid inclusions in quartz deformed by weak ductile shearing: Reconstruction of differential stress magnitudes and pre-deformation fluid properties

    NASA Astrophysics Data System (ADS)

    Diamond, Larryn W.; Tarantola, Alexandre

    2015-05-01

    A well developed theoretical framework is available in which paleofluid properties, such as chemical composition and density, can be reconstructed from fluid inclusions in minerals that have undergone no ductile deformation. The present study extends this framework to encompass fluid inclusions hosted by quartz that has undergone weak ductile deformation following fluid entrapment. Recent experiments have shown that such deformation causes inclusions to become dismembered into clusters of irregularly shaped relict inclusions surrounded by planar arrays of tiny, new-formed (neonate) inclusions. Comparison of the experimental samples with a naturally sheared quartz vein from Grimsel Pass, Aar Massif, Central Alps, Switzerland, reveals striking similarities. This strong concordance justifies applying the experimentally derived rules of fluid inclusion behaviour to nature. Thus, planar arrays of dismembered inclusions defining cleavage planes in quartz may be taken as diagnostic of small amounts of intracrystalline strain. Deformed inclusions preserve their pre-deformation concentration ratios of gases to electrolytes, but their H2O contents typically have changed. Morphologically intact inclusions, in contrast, preserve the pre-deformation composition and density of their originally trapped fluid. The orientation of the maximum principal compressive stress (σ1) at the time of shear deformation can be derived from the pole to the cleavage plane within which the dismembered inclusions are aligned. Finally, the density of neonate inclusions is commensurate with the pressure value of σ1 at the temperature and time of deformation. This last rule offers a means to estimate magnitudes of shear stresses from fluid inclusion studies. Application of this new paleopiezometer approach to the Grimsel vein yields a differential stress (σ1-σ3) of ˜ 300 MPa at 390 ± 30 °C during late Miocene NNW-SSE orogenic shortening and regional uplift of the Aar Massif. This differential

  11. Formation mechanisms and near-surface stress orientations derived from fractographic markings on exfoliation joints in the Alps

    NASA Astrophysics Data System (ADS)

    Ziegler, M.; Loew, S.; Bahat, D.

    2013-12-01

    Granitic bedrock of the upper Aar valley (Grimsel area, Swiss Alps) contains four distinct exfoliation joint generations, which formed during different stages of the Pleistocene and occur in an Alpine landscape between inner trough valley bottoms and high mountain crests. Exfoliation joints of this investigation likely formed during the Middle Pleistocene (0.7-0.4 Ma; batch 1) and Upper Pleistocene to Holocene (<0.1 Ma; batch 2), subparallel to distinct glacial valley (palaeo-)topography. Mapping revealed that exfoliation joints of these batches exhibit prominent fracture surface morphologies. The bulk of exfoliation joints of batches 1 and 2 show common, characteristic fractographic features: (1) noncircular, radial plumose structures, (2) arrest marks on parent fracture planes and fringe cracks, and (3) gradually-developing fringe zones of en échelon type (Figure 1). We interpret smooth transitions from plumose structures on the parent plane to en échelon fringe cracks, combined with non-systematic stepping senses of fringe cracks, as local stress field variations (vs. temporal variations) in the vicinity of pre-existing joints and faults. Multiple arrest marks reveal that exfoliation joints in the Grimsel area formed incrementally and, together with absence of hackle fringes, suggest stable fracture conditions. Furthermore, we put special emphasis on surveying the orientations of plumose structure axes. We assume that plumose structure axes formed parallel to the maximum principal (far-field) compressive stress (σ1). This enables us to infer near-surface stress orientations within Alpine slopes. We found a correlation between the orientations of plumose structure axes and slope aspects for batches 1 and 2. Primarily low pitch angles (<~30°) of plumose structure axes suggest persistently subhorizontal to slightly inclined σ1 orientations, i.e. the orientation of σ1 changes together with change in slope aspect. We attribute this surface-near variability of

  12. K-Ar age data of clay fault gouges from some major Neoalpine faults

    NASA Astrophysics Data System (ADS)

    Pleuger, J.; Zwingmann, H.; Mancktelow, N.; Manser, M.

    2012-04-01

    In the Central Alps, the Insubric Phase in the sense of Argand (1916, Eclogae geol. Helv. 14, 145-191) was related to underthrusting of South Alpine units below the Penninic nappes along the Periadriatic Fault. Several other large-scale faults were active during the same, though not always the entire, Oligocene to Miocene time span. These faults form an array interpreted as to result from the partitioning of strain induced by the crustal convergence between the European and Adriatic plates (e.g. Handy et al. 2005, Geol. Soc. Spec. Publ. 243, 249-276). With ongoing Alpine convergence and deformation during exhumation there is a general progression from ductile to brittle behaviour on the Periadriatic Fault and kinematically related faults further north (e.g. the Simplon Rhone Fault and a diffuse, discontinous zone of generally dextral strike-slip movement on the southern boundary of the Aar massif). K-Ar dating of fine grained illite from clay fault gouges provides a reliable method for establishing the approximate time of faulting. New results establish that brittle faulting on the northeastern segment of the Canavese Fault (i.e. the part of the Periadriatic Fault SW of Val d'Ossola) occurred around 20 Ma, with south-side-up kinematics. An age of ca. 17 Ma for the crosscutting Giudicarie Fault in the Eastern Alps is effectively identical with an already published pseudotachylyte age and places a lower limit on major and continuous strike slip movements the Periadriatic Fault. The age of brittle faulting further north, on the southern border of the Aar massif, is from 13.6±0.3 to 8.3±1.1 Ma, consistent with the younger cooling and exhumation in this area. The dominantly dextral brittle faulting becoming younger to the north reflects the continued indentation and anticlockwise rotation of Adria as Alpine units become exhumed and progressively welded to the southern block. In contrast to the eastern Alps, there is no field evidence for (westward) lateral extrusion

  13. Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

    PubMed Central

    2013-01-01

    Background Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial. Methods and outcomes The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6–8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6–8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6–8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6–8 days and six months. Funding, ethics and

  14. Zooplankton Growth, Respiration and Grazing on the Australian Margins of the Tropical Indian and Pacific Oceans.

    PubMed

    McKinnon, A David; Doyle, Jason; Duggan, Samantha; Logan, Murray; Lønborg, Christian; Brinkman, Richard

    2015-01-01

    The specific activity of aminoacyl-tRNA synthetases (spAARS), an index of growth rate, and of the electron transport system (spETS), an index of respiration, was measured in three size fractions (73-150 μm, >150 μm and >350 μm) of zooplankton during five cruises to tropical coastal waters of the Kimberley coast (North West Australia) and four cruises to waters of the Great Barrier Reef (GBR; North East Australia). The N-specific biomass of plankton was 3-4-fold higher in the Kimberley than on the GBR in all 3 size classes: Kimberley 1.27, 3.63, 1.94 mg m-3; GBR 0.36, 0.88 and 0.58 mg m-3 in the 73-150 μm, >150 μm and >350 μm size classes, respectively. Similarly, spAARS activity in the Kimberley was greater than that of the GBR: 88.4, 132.2, and 147.6 nmol PPi hr-1 mg protein -1 in the Kimberley compared with 71.7, 82.0 and 83.8 nmol PPi hr-1 mg protein -1 in the GBR, for the 73-150 μm, >150 μm and >350 μm size classes, respectively. Specific ETS activity showed similar differences in scale between the two coasts: 184.6, 148.8 and 92.2 μL O2 hr-1 mg protein-1 in the Kimberley, against 86.5, 88.3 and 71.3 μL O2 hr-1 mg protein-1 in the GBR. On the basis of these measurements, we calculated that >150 μm zooplankton grazing accounted for 7% of primary production in the Kimberley and 8% in GBR waters. Area-specific respiration by >73 μm zooplankton was 7-fold higher in the Kimberley than on the GBR and production by >150 μm zooplankton was of the order of 278 mg C m-2 d-1 in the Kimberley and 42 mg C m-2 d-1 on the GBR. We hypothesize that the much stronger physical forcing on the North West shelf is the principal driver of higher rates in the west than in the east of the continent. PMID:26469275

  15. Annual and seasonal mass balances of Chhota Shigri Glacier (benchmark glacier, Western Himalaya), India

    NASA Astrophysics Data System (ADS)

    Mandal, Arindan; Ramanathan, Alagappan; Farooq Azam, Mohd; Wagnon, Patrick; Vincent, Christian; Linda, Anurag; Sharma, Parmanand; Angchuk, Thupstan; Bahadur Singh, Virendra; Pottakkal, Jose George; Kumar, Naveen; Soheb, Mohd

    2015-04-01

    Several studies on Himalayan glaciers have been recently initiated as they are of particular interest in terms of future water supply, regional climate change and sea-level rise. In 2002, a long-term monitoring program was initiated on Chhota Shigri Glacier (15.7 square km, 9 km long, 6263-4050 m a.s.l.) located in Lahaul and Spiti Valley, Himachal Pradesh, India. This glacier lies in the monsoon-arid transition zone (western Himalaya) and is a representative glacier in Lahaul and Spiti Valley. While annual mass balances have been measured continuously since 2002 using the glaciological method, seasonal scale observations began in 2009. The annual and seasonal mass balances were then analyzed along with meteorological conditions in order to understand the role of winter and summer balances on annual glacier-wide mass balance of Chhota Shigri glacier. During the period 2002-2013, the glacier experienced a negative glacier-wide mass balance of -0.59±0.40 m w.e. a-1 with a cumulative glaciological mass balance of -6.45 m w.e. Annual glacier-wide mass balances were negative except for four years (2004/05, 2008/09, 2009/10 and 2010/11) where it was generally close to balanced conditions. Equilibrium line altitude (ELA) for steady state condition is calculated as 4950 m a.s.l. corresponding to an accumulation area ratio (AAR) of 62% using annual glacier-wide mass balance, ELA and AAR data between 2002 and 2013. The winter glacier-wide mass balance between 2009 and 2013 ranges from a maximum value of 1.38 m w.e. in 2009/10 to a minimum value of 0.89 in 2012/13 year whereas the summer glacier-wide mass balance varies from the highest value of -0.95 m w.e. in 2010/11 to the lowest value of -1.72 m w.e. in 2011/12 year. The mean vertical mass balance gradient between 2002 and 2013 was 0.66 m w.e. (100 m)-1 quite similar to Alps, Nepalese Himalayas etc. Over debris covered area, the gradients are highly variable with a negative mean value of -2.15 m w.e. (100 m)-1 over 2002

  16. Ground state of bilayer hα-silica: mechanical and electronic properties

    NASA Astrophysics Data System (ADS)

    Han, Yang; Hu, Ming

    2015-12-01

    The family of two-dimensional (2D) crystals was recently joined by silica, one of the most abundant resources on earth. So far two different polymorphs of this material, namely a tetrahedra-shaped monolayer and a fully saturated bilayer structure, have been synthesized on various metal substrates and their fascinating properties enable 2D silica to hold promise in nanoelectronic device applications. In this paper a new ground state of bilayer—AAr-stacking hα-silica—has been discovered by first principles calculations. The new structure is featured with a formation of Si-Si bonds between all sp3 hybridized SiO3 triangular pyramids, lying respectively in different silica layers, with an intrinsic rotational angle of about 12.5° along the out-of-plane Si-Si bond. Due to the doubled number of Si-Si bonds in the new structure, the system energy is lowered by nearly three times more than that reported recently in literature (0.8 eV) (Özçelik et al 2014 Phys. Rev. Lett. 112 246803), when compared with the single layer hα-silica. A mechanical property investigation shows that the AAr-stacking bilayer hα-silica possesses high in-plane stiffness and a negative Poisson’s ratio, which stems from the intrinsic rotational angle of the SiO3 triangular pyramids. Strikingly, the negative Poisson’s ratio evolves into positive at a critical tensile strain ɛ ≈ 1.2%. Such negative-to-positive evolvement is associated with the adaptation of the rotational angle to the applied strain and the structure transition into the nearby valley of the energy landscape. The detailed transition process has been thoroughly analyzed. The electronic properties of the new ground state are also calculated, along with their response to the external strain. Our new ground state structure introduces a new member to the family of 2D bilayer silica materials and is expected to facilitate experimental studies identifying the related structures and exploring further physical and chemical

  17. Intragenic homogenization and multiple copies of prey-wrapping silk genes in Argiope garden spiders

    PubMed Central

    2014-01-01

    Background Spider silks are spectacular examples of phenotypic diversity arising from adaptive molecular evolution. An individual spider can produce an array of specialized silks, with the majority of constituent silk proteins encoded by members of the spidroin gene family. Spidroins are dominated by tandem repeats flanked by short, non-repetitive N- and C-terminal coding regions. The remarkable mechanical properties of spider silks have been largely attributed to the repeat sequences. However, the molecular evolutionary processes acting on spidroin terminal and repetitive regions remain unclear due to a paucity of complete gene sequences and sampling of genetic variation among individuals. To better understand spider silk evolution, we characterize a complete aciniform spidroin gene from an Argiope orb-weaving spider and survey aciniform gene fragments from congeneric individuals. Results We present the complete aciniform spidroin (AcSp1) gene from the silver garden spider Argiope argentata (Aar_AcSp1), and document multiple AcSp1 loci in individual genomes of A. argentata and the congeneric A. trifasciata and A. aurantia. We find that Aar_AcSp1 repeats have >98% pairwise nucleotide identity. By comparing AcSp1 repeat amino acid sequences between Argiope species and with other genera, we identify regions of conservation over vast amounts of evolutionary time. Through a PCR survey of individual A. argentata, A. trifasciata, and A. aurantia genomes, we ascertain that AcSp1 repeats show limited variation between species whereas terminal regions are more divergent. We also find that average dN/dS across codons in the N-terminal, repetitive, and C-terminal encoding regions indicate purifying selection that is strongest in the N-terminal region. Conclusions Using the complete A. argentata AcSp1 gene and spidroin genetic variation between individuals, this study clarifies some of the molecular evolutionary processes underlying the spectacular mechanical attributes of

  18. Reconstructed glacier geometry and inferred Equilibrium Line Altitude changes during the Late Pleistocene deglaciation in the Retezat Mountains, Southern Carpathians

    NASA Astrophysics Data System (ADS)

    Madarász, Balázs; Ruszkiczay-Rüdiger, Zsófia; Kern, Zoltán; Urdea, Petru

    2016-04-01

    Quaternary glaciations had a major imprint on the landscape and topography of the Southern Carpathians. Their transitional position between continental and Mediterranean climate zones arouses special interest concerning the timing and pattern of glaciations in this area. Probably the Retezat Mts hosted the most extended glaciation during the Late Pleistocene within this range. The peak elevations of the study area reach 2500 m asl, and the most extended glaciers descended to 1040 m in the northern and to 1130 m on the southern valleys. Major cirque floors are typically situated at 2000-2100 m asl. Glacial landforms have been mapped in order to reconstruct the past ice bodies and the elevation shifts of the paleo equilibrium line altitudes (ELA) during several deglaciation phases of the Last Glacial Maximum (LGM) and Lateglacial in the Retezat Mts. On the basis of published 10Be exposure age data on the northern valleys of the study area, deglaciation of the Retezat Mts occurred at least in five phases between ~21.0 ka and 13.5 ka [1]. Various methods (THAR, AAR, AABR) have been tested using a GIS tool to estimate the ELA of the reconstructed paleoglaciers [2] and paleo ELAs were calculated for each of the deglaciation phases. Preliminary estimates of regional LGM paleoELA employing the simplest THAR method (with a ratio of 0.5) ranged from ~1670 m during the LGM to ~2210 m for the smallest cirque glacier at 13.5 ka, respectively. The AAR and AABR methods provide somewhat higher ELAs for each phase. The obtained paleoELAs were compared to ELA reconstructions available from other Carpathian ranges and also to the Alps and Dinarides. Our data will contribute to a more accurate ELA distribution during the LGM, which may be indicative of the past state of the climate system (moisture gradient, circulation regimes). Thanks to OTKA PD83610, PD104899; NKM-96/2014, NKM-31/2015; OMAA 90öu17; LP2012-27/2012. References: [1] Ruszkiczay-Rüdiger et al. 2016 Quat. Int. (in

  19. Medicinal chemistry of adenosine, P2Y and P2X receptors.

    PubMed

    Jacobson, Kenneth A; Müller, Christa E

    2016-05-01

    Pharmacological tool compounds are now available to define action at the adenosine (ARs), P2Y and P2X receptors. We present a selection of the most commonly used agents to study purines in the nervous system. Some of these compounds, including A1 and A3 AR agonists, P2Y1R and P2Y12R antagonists, and P2X3, P2X4 and P2X7 antagonists, are potentially of clinical use in treatment of disorders of the nervous system, such as chronic pain, neurodegeneration and brain injury. Agonists of the A2AAR and P2Y2R are already used clinically, P2Y12R antagonists are widely used antithrombotics and an antagonist of the A2AAR is approved in Japan for treating Parkinson's disease. The selectivity defined for some of the previously introduced compounds has been revised with updated pharmacological characterization, for example, various AR agonists and antagonists were deemed A1AR or A3AR selective based on human data, but species differences indicated a reduction in selectivity ratios in other species. Also, many of the P2R ligands still lack bioavailability due to charged groups or hydrolytic (either enzymatic or chemical) instability. X-ray crystallographic structures of AR and P2YRs have shifted the mode of ligand discovery to structure-based approaches rather than previous empirical approaches. The X-ray structures can be utilized either for in silico screening of chemically diverse libraries for the discovery of novel ligands or for enhancement of the properties of known ligands by chemical modification. Although X-ray structures of the zebrafish P2X4R have been reported, there is scant structural information about ligand recognition in these trimeric ion channels. In summary, there are definitive, selective agonists and antagonists for all of the ARs and some of the P2YRs; while the pharmacochemistry of P2XRs is still in nascent stages. The therapeutic potential of selectively modulating these receptors is continuing to gain interest in such fields as cancer, inflammation, pain

  20. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor.

    PubMed

    Newman-Tancredi, Adrian; Cussac, Didier; Audinot, Valérie; Nicolas, Jean-Paul; De Ceuninck, Frédéric; Boutin, Jean-A; Millan, Mark J

    2002-11-01

    The accompanying multivariate analysis of the binding profiles of antiparkinson agents revealed contrasting patterns of affinities at diverse classes of monoaminergic receptor. Herein, we characterized efficacies at human (h)D(2SHORT(S)), hD(2LONG(L)), hD(3), and hD(4.4) receptors and at halpha(2A)-, halpha(2B)-, halpha(2C)-, and halpha(1A)-adrenoceptors (ARs). As determined by guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding, no ligand displayed "full" efficacy relative to dopamine (100%) at all "D(2)-like" sites. However, at hD(2S) receptors quinpirole, pramipexole, ropinirole, quinerolane, pergolide, and cabergoline were as efficacious as dopamine (E(max)100%); TL99, talipexole, and apomorphine were highly efficacious (79-92%); piribedil, lisuride, bromocriptine, and terguride showed intermediate efficacy (40-55%); and roxindole displayed low efficacy (11%). For all drugs, efficacies were lower at hD(2L) receptors, with terguride and roxindole acting as antagonists. At hD(3) receptors, efficacies ranged from 33% (roxindole) to 94% (TL99), whereas, for hD(4) receptors, highest efficacies (approximately 70%) were seen for quinerolane, quinpirole, and TL99, whereas piribedil and terguride behaved as antagonists and bromocriptine was inactive. Although efficacies at hD(2S) versus hD(2L) sites were highly correlated (r = 0.79), they correlated only modestly to hD(3)/hD(4) sites (r = 0.44-0.59). In [(35)S]GTPgammaS studies of halpha(2A)-ARs, TL99 (108%), pramipexole (52%), talipexole (51%), pergolide (31%), apomorphine (16%), and quinerolane (11%) were agonists and ropinirole and roxindole were inactive, whereas piribedil and other agents were antagonists. Similar findings were obtained at halpha(2B)- and halpha(2C)-ARs. Using [(3)H]phosphatidylinositol depletion, roxindole, bromocriptine, lisuride, and terguride displayed potent antagonist properties at halpha(1A)-ARs. In conclusion, antiparkinson agents display diverse agonist and antagonist

  1. Definition and automatic anatomy recognition of lymph node zones in the pelvis on CT images

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Guo, Shuxu; Attor, Rosemary; Reinicke, Danica; Torigian, Drew A.

    2016-03-01

    Currently, unlike IALSC-defined thoracic lymph node zones, no explicitly provided definitions for lymph nodes in other body regions are available. Yet, definitions are critical for standardizing the recognition, delineation, quantification, and reporting of lymphadenopathy in other body regions. Continuing from our previous work in the thorax, this paper proposes a standardized definition of the grouping of pelvic lymph nodes into 10 zones. We subsequently employ our earlier Automatic Anatomy Recognition (AAR) framework designed for body-wide organ modeling, recognition, and delineation to actually implement these zonal definitions where the zones are treated as anatomic objects. First, all 10 zones and key anatomic organs used as anchors are manually delineated under expert supervision for constructing fuzzy anatomy models of the assembly of organs together with the zones. Then, optimal hierarchical arrangement of these objects is constructed for the purpose of achieving the best zonal recognition. For actual localization of the objects, two strategies are used -- optimal thresholded search for organs and one-shot method for the zones where the known relationship of the zones to key organs is exploited. Based on 50 computed tomography (CT) image data sets for the pelvic body region and an equal division into training and test subsets, automatic zonal localization within 1-3 voxels is achieved.

  2. A new paleomagnetic study of the Itararé Group of Brazil: evidence for shallow paleomagnetic inclinations and implications for Pangea reconstructions

    NASA Astrophysics Data System (ADS)

    Bilardello, D.; Raposo, M. B.

    2012-12-01

    When reconstructing the paleogeography of Pangea, paleomagnetic data for the Permo-Carboniferous imposes an overlap between the two major continental blocks, Laurasia and Gondwana, in the traditional A-type assemblage. Sedimentary rocks dominate the Carboniferous apparent polar wander path (APWP) of South America, and the few igneous rocks are probably either remagnetized or have been subjected to tectonic rotations. Recent work by Bilardello and Kodama (2010) has shown how inclination shallowing corrections of Gondwana sedimentary rocks may completely eliminate the continental overlap. Estimated inclination corrections, however, lack a solid base: they are unreliable and should only be performed to verify if a full inclination correction is required. To this extent, we are performing an inclination shallowing study of the Itararé Group of Brazil. The stratigraphy of the Group has been re-interpreted in recent years, and such study will provide new key paleomagnetic poles in Gondwana's Permo-Carboniferous APWP. Anisotropy of anhysteretic remanence (AAR) and of high field isothermal remanence (hf-AIR) are used to perform inclination corrections of magnetite and hematite bearing rocks, respectively. Corrections have already been successfully applied to Carboniferous rocks from North America. Comparing inclination-corrected paleopoles from Laurasia and Gondwana will give a persuasive, quantitative and robust test of the role of inclination shallowing in the Pangea controversy. Preliminary results will be presented.

  3. Two-dimensional cross-section sensitivity and uncertainty analysis of the LBM (Lithium Blanket Module) experiments at LOTUS

    SciTech Connect

    Davidson, J.W.; Dudziak, D.J.; Pelloni, S.; Stepanek, J.

    1988-01-01

    In a recent common Los Alamos/PSI effort, a sensitivity and nuclear data uncertainty path for the modular code system AARE (Advanced Analysis for Reactor Engineering) was developed. This path includes the cross-section code TRAMIX, the one-dimensional finite difference S/sub N/-transport code ONEDANT, the two-dimensional finite element S/sub N/-transport code TRISM, and the one- and two-dimensional sensitivity and nuclear data uncertainty code SENSIBL. Within the framework of the present work a complete set of forward and adjoint two-dimensional TRISM calculations were performed both for the bare, as well as for the Pb- and Be-preceeded, LBM using MATXS8 libraries. Then a two-dimensional sensitivity and uncertainty analysis for all cases was performed. The goal of this analysis was the determination of the uncertainties of a calculated tritium production per source neutron from lithium along the central Li/sub 2/O rod in the LBM. Considered were the contributions from /sup 1/H, /sup 6/Li, /sup 7/Li, /sup 9/Be, /sup nat/C, /sup 14/N, /sup 16/O, /sup 23/Na, /sup 27/Al, /sup nat/Si, /sup nat/Cr, /sup nat/Fe, /sup nat/Ni, and /sup nat/Pb. 22 refs., 1 fig., 3 tabs.

  4. Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis.

    PubMed

    Cosentino, Marco; Zaffaroni, Mauro; Legnaro, Massimiliano; Bombelli, Raffaella; Schembri, Laura; Baroncini, Damiano; Bianchi, Anna; Clerici, Raffaella; Guidotti, Mario; Banfi, Paola; Bono, Giorgio; Marino, Franca

    2016-09-15

    Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients. No information exists so far in CIS subjects. We investigated DR and AR gene expression in peripheral blood mononuclear cells (PBMC) and in CD4+ T effector (Teff) and regulatory (Treg) cells from CIS subjects, and assessed their relationship with MS progression after 12months. Expression of several DR and AR are upregulated in PBMC, Teff and Treg from CIS subjects. DR D3 and α2A-AR mRNA in PBMC, and DR D5 mRNA in Treg correlate with the risk of MS at 12months. Results show the involvement of dopaminergic and adrenergic pathways in CIS as well as in MS pathogenesis, supporting the evaluation of dopaminergic and adrenergic agents in MS. PMID:27609280

  5. Entamoeba lysyl-tRNA Synthetase Contains a Cytokine-Like Domain with Chemokine Activity towards Human Endothelial Cells

    PubMed Central

    Han, Jung Min; Kim, Sunghoon; Celada, Antonio; Ribas de Pouplana, Lluís

    2011-01-01

    Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity. PMID:22140588

  6. A novel autoregulatory loop between the Gcn2-Atf4 pathway and (L)-Proline [corrected] metabolism controls stem cell identity.

    PubMed

    D'Aniello, C; Fico, A; Casalino, L; Guardiola, O; Di Napoli, G; Cermola, F; De Cesare, D; Tatè, R; Cobellis, G; Patriarca, E J; Minchiotti, G

    2015-07-01

    Increasing evidence indicates that metabolism is implicated in the control of stem cell identity. Here, we demonstrate that embryonic stem cell (ESC) behaviour relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2α-Atf4 amino acid starvation response (AAR) pathway that in turn regulates L-Pro biosynthesis. This regulatory loop generates a highly specific intrinsic shortage of L-Pro that restricts proliferation of tightly packed domed-like ESC colonies and safeguards ESC identity. Indeed, alleviation of this nutrient stress condition by exogenously provided L-Pro induces proliferation and modifies the ESC phenotypic and molecular identity towards that of mesenchymal-like, invasive pluripotent stem cells. Either pharmacological inhibition of the prolyl-tRNA synthetase by halofuginone or forced expression of Atf4 antagonises the effects of exogenous L-Pro. Our data provide unprecedented evidence that L-Pro metabolism and the nutrient stress response are functionally integrated to maintain ESC identity. PMID:25857264

  7. Crystallization and preliminary X-ray crystallographic analysis of a bacterial Asn-transamidosome

    PubMed Central

    Suzuki, Tateki; Yamashita, Keitaro; Tanaka, Yoshikazu; Tanaka, Isao; Yao, Min

    2014-01-01

    Most canonical aminoacyl-tRNAs are synthesized directly by their cognate aminoacyl-tRNA synthetases (aaRSs), but glutaminyl-tRNAGln and asparaginyl-tRNAAsn are synthesized indirectly by two-step processes. These processes are catalyzed by the transamidosome, a large ribonucleoprotein particle composed of GatA, GatB, GatC, aaRS and tRNA. In this study, the Asn-transamidosome from Pseudomonas aeruginosa was reconstructed and crystallized by mixing purified GatCAB complex, AspRS and tRNAAsn. The crystal of the Asn-transamidosome belonged to space group P21, with unit-cell parameters a = 93.3, b = 186.0, c = 287.8 Å, β = 93.3°, and diffracted to 3.73 Å resolution. Preliminary X-ray crystallographic analysis showed that the asymmetric unit contained two Asn-transamidosomes, each composed of two GatCABs, one AspRS dimer and two tRNAAsns, indicating that the construction of the current Asn-transamidosome differs from that of Thermus thermophilus. PMID:24915095

  8. The Evolution of Olfactory Gene Families in Drosophila and the Genomic Basis of chemical-Ecological Adaptation in Drosophila suzukii.

    PubMed

    Ramasamy, Sukanya; Ometto, Lino; Crava, Cristina M; Revadi, Santosh; Kaur, Rupinder; Horner, David S; Pisani, Davide; Dekker, Teun; Anfora, Gianfranco; Rota-Stabelli, Omar

    2016-01-01

    How the evolution of olfactory genes correlates with adaption to new ecological niches is still a debated topic. We explored this issue in Drosophila suzukii, an emerging model that reproduces on fresh fruit rather than in fermenting substrates like most other Drosophila We first annotated the repertoire of odorant receptors (ORs), odorant binding proteins (OBPs), and antennal ionotropic receptors (aIRs) in the genomes of two strains of D. suzukii and of its close relative Drosophila biarmipes We then analyzed these genes on the phylogeny of 14 Drosophila species: whereas ORs and OBPs are characterized by higher turnover rates in some lineages including D. suzukii, aIRs are conserved throughout the genus. Drosophila suzukii is further characterized by a non-random distribution of OR turnover on the gene phylogeny, consistent with a change in selective pressures. In D. suzukii, we found duplications and signs of positive selection in ORs with affinity for short-chain esters, and loss of function of ORs with affinity for volatiles produced during fermentation. These receptors-Or85a and Or22a-are characterized by divergent alleles in the European and American genomes, and we hypothesize that they may have been replaced by some of the duplicated ORs in corresponding neurons, a hypothesis reciprocally confirmed by electrophysiological recordings. Our study quantifies the evolution of olfactory genes in Drosophila and reveals an array of genomic events that can be associated with the ecological adaptations of D. suzukii. PMID:27435796

  9. Design Considerations of Istar Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

    NASA Technical Reports Server (NTRS)

    Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

    2002-01-01

    The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system thai: produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

  10. Design Considerations of ISTAR Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

    NASA Technical Reports Server (NTRS)

    Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

    2003-01-01

    The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system that produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

  11. Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

    PubMed

    Seo, K K; Lee, M Y; Lim, S W; Kim, S C

    1999-02-01

    Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. PMID:10102527

  12. Short peptides from leucyl-tRNA synthetase rescue disease-causing mitochondrial tRNA point mutations

    PubMed Central

    Perli, Elena; Fiorillo, Annarita; Giordano, Carla; Pisano, Annalinda; Montanari, Arianna; Grazioli, Paola; Campese, Antonio F.; Di Micco, Patrizio; Tuppen, Helen A.; Genovese, Ilaria; Poser, Elena; Preziuso, Carmela; Taylor, Robert W.; Morea, Veronica; Colotti, Gianni; d'Amati, Giulia

    2016-01-01

    Mutations in mitochondrial (mt) genes coding for mt-tRNAs are responsible for a range of syndromes, for which no effective treatment is available. We recently showed that the carboxy-terminal domain (Cterm) of human mt-leucyl tRNA synthetase rescues the pathologic phenotype associated either with the m.3243A>G mutation in mt-tRNALeu(UUR) or with mutations in the mt-tRNAIle, both of which are aminoacylated by Class I mt-aminoacyl-tRNA synthetases (mt-aaRSs). Here we show, by using the human transmitochondrial cybrid model, that the Cterm is also able to improve the phenotype caused by the m.8344A>G mutation in mt-tRNALys, aminoacylated by a Class II aaRS. Importantly, we demonstrate that the same rescuing ability is retained by two Cterm-derived short peptides, β30_31 and β32_33, which are effective towards both the m.8344A>G and the m.3243A>G mutations. Furthermore, we provide in vitro evidence that these peptides bind with high affinity wild-type and mutant human mt-tRNALeu(UUR) and mt-tRNALys, and stabilize mutant mt-tRNALeu(UUR). In conclusion, we demonstrate that small Cterm-derived peptides can be effective tools to rescue cellular defects caused by mutations in a wide range of mt-tRNAs. PMID:26721932

  13. Autonomous Aerial Refueling Ground Test Demonstration—A Sensor-in-the-Loop, Non-Tracking Method

    PubMed Central

    Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

    2015-01-01

    An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously. PMID:25970254

  14. A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

    PubMed

    Santiago, Araceli E; Ruiz-Perez, Fernando; Jo, Noah Y; Vijayakumar, Vidhya; Gong, Mei Q; Nataro, James P

    2014-05-01

    We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

  15. A Characterization for the Hot Flow Behaviors of As-extruded 7050 Aluminum Alloy

    NASA Astrophysics Data System (ADS)

    Quan, Guo-zheng; Liu, Jin; Mao, An; Liu, Bo; Zhang, Jin-sheng

    2015-11-01

    The deep understanding of flow behaviors of as-extruded 7050 aluminum alloy significantly contributes to the accuracy simulation for its various plastic forming processes. In order to obtain the improved Arrhenius-type equation with variable parameters for this alloy, a series of compression tests were performed at temperatures of 573 K, 623 K, 673 K, 723 K and strain rates of 0.01 s-1, 0.1 s-1, 1 s-1, 10 s-1 with a height reduction of 60% on Gleeble-1500 thermo-mechanical simulator. It is obvious that strain rate, strain and temperature all have a significant effect on the hot flow behaviors, and the true stress-true strain curves indicate three types after the peak value: decreasing gradually to a steady state with sustaining DRX softening till a balance with work hardening, decreasing continuously with sustaining increasing DRX softening beyond work hardening and maintaining higher stress level after the peak value with a balance between work hardening and DRV softening. Based on the experimental data, the improved Arrhenius-type constitutive model was established to predict the high temperature flow stress of as-extruded 7050 aluminum alloy. The accuracy and reliability of the improved Arrhenius-type model were further evaluated in terms of the correlation coefficient (R), here 0.98428, the average absolute relative error (AARE), here 3.5%. The results indicate that the improved Arrhenius-type constitutive model presents a good predictable ability.

  16. Structure of Pyrrolysyl-tRNA Synthetase, an Archaeal Enzyme for Genetic Code Innovation

    SciTech Connect

    Kavran,J.; Gundllapalli, S.; O'Donoghue, P.; Englert, M.; Soll, D.; Steitz, T.

    2007-01-01

    Pyrrolysine (Pyl), the 22nd natural amino acid and genetically encoded by UAG, becomes attached to its cognate tRNA by pyrrolysyl-tRNA synthetase (PylRS). We have determined three crystal structures of the Methanosarcina mazei PylRS complexed with either AMP-PNP, Pyl-AMP plus pyrophosphate, or the Pyl analogue N-e-[(cylopentyloxy)carbonyl]-l-lysine plus ATP. The structures reveal that PylRS utilizes a deep hydrophobic pocket for recognition of the Pyl side chain. A comparison of these structures with previously determined class II tRNA synthetase complexes illustrates that different substrate specificities derive from changes in a small number of residues that form the substrate side-chain-binding pocket. The knowledge of these structures allowed the placement of PylRS in the aminoacyl-tRNA synthetase (aaRS) tree as the last known synthetase that evolved for genetic code expansion, as well as the finding that Pyl arose before the last universal common ancestral state. The PylRS structure provides an excellent framework for designing new aaRSs with altered amino acid specificity.

  17. Optical Remote Sensing of Glacier Characteristics: A Review with Focus on the Himalaya

    PubMed Central

    Racoviteanu, Adina E.; Williams, Mark W.; Barry, Roger G.

    2008-01-01

    The increased availability of remote sensing platforms with appropriate spatial and temporal resolution, global coverage and low financial costs allows for fast, semi-automated, and cost-effective estimates of changes in glacier parameters over large areas. Remote sensing approaches allow for regular monitoring of the properties of alpine glaciers such as ice extent, terminus position, volume and surface elevation, from which glacier mass balance can be inferred. Such methods are particularly useful in remote areas with limited field-based glaciological measurements. This paper reviews advances in the use of visible and infrared remote sensing combined with field methods for estimating glacier parameters, with emphasis on volume/area changes and glacier mass balance. The focus is on the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor and its applicability for monitoring Himalayan glaciers. The methods reviewed are: volumetric changes inferred from digital elevation models (DEMs), glacier delineation algorithms from multi-spectral analysis, changes in glacier area at decadal time scales, and AAR/ELA methods used to calculate yearly mass balances. The current limitations and on-going challenges in using remote sensing for mapping characteristics of mountain glaciers also discussed, specifically in the context of the Himalaya.

  18. Enhancing Alkane Production in Cyanobacterial Lipid Droplets: A ModeFl Platform for Industrially Relevant Compound Production

    PubMed Central

    Peramuna, Anantha; Morton, Ray; Summers, Michael L.

    2015-01-01

    Cyanobacterial lipid droplets (LDs) are packed with hydrophobic energy-dense compounds and have great potential for biotechnological expression and the compartmentalization of high value compounds. Nostoc punctiforme normally accumulates LDs containing neutral lipids, and small amounts of heptadecane, during the stationary phase of growth. In this study, we further enhanced heptadecane production in N. punctiforme by introducing extrachromosomal copies of aar/adc genes, and report the discovery of a putative novel lipase encoded by Npun_F5141, which further enhanced alkane production. Extra copies of all three genes in high light conditions resulted in a 16-fold higher accumulation of heptadecane compared to the wild type strain in the exponential phase. LD accumulation during exponential phase also increased massively to accommodate the heptadecane production. A large number of small, less fluorescent LDs were observed at the cell periphery in exponential growth phase, whereas fewer number of highly fluorescent, much larger LDs were localized towards the center of the cell in the stationary phase. These advances demonstrate that cyanobacterial LDs are an ideal model platform to make industrially relevant compounds, such as alkanes, during exponential growth, and provide insight into LD formation in cyanobacteria. PMID:25821934

  19. A Simple Technique for the Prediction of Interacting Proteins Reveals a Direct Brn-3a-Androgen Receptor Interaction*

    PubMed Central

    Berwick, Daniel C.; Diss, James K. J.; Budhram-Mahadeo, Vishwanie S.; Latchman, David S.

    2010-01-01

    The formation of multiprotein complexes constitutes a key step in determining the function of any translated gene product. Thus, the elucidation of interacting partners for a protein of interest is of fundamental importance to cell biology. Here we describe a simple methodology for the prediction of novel interactors. We have applied this to the developmental transcription factor Brn-3a to predict and verify a novel interaction between Brn-3a and the androgen receptor (AR). We demonstrate that these transcription factors form complexes within the nucleus of ND7 neuroblastoma cells, while in vitro pull-down assays show direct association. As a functional consequence of the Brn-3a-AR interaction, the factors bind cooperatively to multiple elements within the promoter of the voltage-gated sodium channel, Nav1.7, leading to a synergistic increase in its expression. Thus, these data define AR as a direct Brn-3a interactor and verify a simple interacting protein prediction methodology that is likely to be useful for many other proteins. PMID:20228055

  20. Nonradioactive GTP binding assay to monitor activation of g protein-coupled receptors.

    PubMed

    Frang, Heini; Mukkala, Veli-Matti; Syystö, Rita; Ollikka, Pia; Hurskainen, Pertti; Scheinin, Mika; Hemmilä, Ilkka

    2003-04-01

    GPCRs represent important targets for drug discovery because GPCRs participate in a wide range of cellular signaling pathways that play a role in a variety of pathological conditions. A large number of screening assays have been developed in HTS laboratories for the identification of hits or lead compounds acting on GPCRs. One type of assay that has found relatively widespread application, due to its at least in part generic nature, relies on the use of a radioactive GTP analogue, [(35)S]GTPgammaS. The G-protein alpha subunit is an essential part of the interaction between receptor and G proteins in transmembrane signaling, where the activated receptor catalyzes the release of GDP from Galpha, thereby enabling the subsequent binding of GTP or a GTP analogue. [(35)S]GTPgammaS allows the extent of this interaction to be followed quantitatively by determining the amount of radioactivity associated with cell membranes. However, with the increased desire to move assays to nonradioactive formats, there is a considerable need to develop a nonradioactive GTP binding assay to monitor ligand-induced changes in GPCR activity. The Eu-GTP binding assay described here is based on TRF that exploits the unique fluorescence properties of lanthanide chelates, and provides a powerful alternative to assays using radioisotopes. In this article, we have used the human alpha(2A)-AR as a model GPCR system to evaluate the usefulness of this Eu-GTP binding assay. PMID:15090192