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Sample records for katrin jgar aare

  1. The KATRIN Neutrino Mass Experiment

    NASA Astrophysics Data System (ADS)

    Parno, Diana; Katrin Collaboration

    2017-01-01

    While neutrino oscillation experiments have demonstrated that the particles have non-zero mass, the absolute neutrino mass scale is still unknown. The Karlsruhe Tritium Neutrino experiment (KATRIN) is designed to improve on previous laboratory limits by an order of magnitude, probing the effective neutrino mass with a sensitivity approaching 0.2 eV at 90% confidence via the kinematics of tritium beta decay. At the same time, KATRIN has the potential to scan for sterile neutrinos at eV and keV scales. After years of preparation, all major components are now on site and commissioning is underway. I will report on the current status of the experiment, including recent results and preparations for the introduction of tritium later this year. 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.

  2. 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.

  3. The KATRIN neutrino mass experiment

    NASA Astrophysics Data System (ADS)

    Wolf, Joachim; Katrin Collaboration

    2010-11-01

    The Karlsruhe Tritium Neutrino experiment (KATRIN) aims to determine the electron neutrino mass from tritium decay in a model-independent way, by a kinematic measurement of the energy of β-electrons. The unprecedented sensitivity of 0.2 eV/c2 will improve present limits by one order of magnitude. The decay electrons will originate from a 10 m long windowless gaseous tritium source. Super-conducting magnets will guide the electrons through a differential and cryogenic pumping section to the electro-static tandem spectrometer (MAG-E-filter), where the kinetic energy will be measured. The experiment is presently being built at the Forschungszentrum Karlsruhe by an international collaboration of more than 120 scientists. The largest component, the 1240 m3 main spectrometer, was delivered end of 2006 and first commissioning tests have been performed. This paper gives an overview of the goals and technological challenges of the experiment and reports on the progress in commissioning first major components. The start of first measurements is expected in 2012.

  4. Status of the KATRIN neutrino mass experiment

    NASA Astrophysics Data System (ADS)

    Martin, Eric; Katrin Collaboration

    2016-09-01

    The upcoming Karlsruhe Tritium Neutrino (KATRIN) experiment aims to explore neutrino mass down to 0.2 eV/c2 (90% CL) by measuring the shape of the tritium beta decay spectrum. Using magnetic adiabatic collimation with an electrostatic filter (MAC-E filter) KATRIN will measure the electron kinetic energy spectrum with a resolution better than one part in 104. All major components are on site and commissioning is underway, with first tritium data currently scheduled for 2017. The measurement technique will be explained along with an update on commissioning progress. This material is based upon work supported by the U.S. Department of Energy Office of Science, Office of Nuclear Physics under Award Number DE-FG02-97ER41020.

  5. Background processes in the KATRIN main spectrometer

    NASA Astrophysics Data System (ADS)

    Fraenkle, F. M.; KATRIN collaboration

    2017-09-01

    The KArlsruhe TRItium Neutrino (KATRIN) experiment is a large-scale experiment which aims for the model-independent determination of the effective mass of electron anti-neutrinos with a sensitivity of 200 meV/c2. It investigates the kinematics of electrons from tritium β-decay close to the endpoint of the energy spectrum. Low statistics at the endpoint requires an equally low background rate below 0.01 counts per second. 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. The background characteristics of the KATRIN main spectrometer were investigated in detail during two commissioning measurement phases. Of particular interest were backgrounds due to the decay of radon in the volume of the spectrometer, cosmic-muon-induced backgrounds, backgrounds due to natural radioactivity and Penning-discharge-related backgrounds. This proceeding will present results of the commissioning measurements and focuses on different background processes and their contribution to the overall background of the KATRIN experiment.

  6. Mutations in aarE, the ubiA homolog of Providencia stuartii, result in high-level aminoglycoside resistance and reduced expression of the chromosomal aminoglycoside 2'-N-acetyltransferase.

    PubMed

    Paradise, M R; Cook, G; Poole, R K; Rather, P N

    1998-04-01

    The aarE1 allele was identified on the basis of the resulting phenotype of increased aminoglycoside resistance. The aarE1 mutation also resulted in a small-colony phenotype and decreased levels of aac(2')-Ia mRNA. The deduced AarE gene product displayed 61% amino acid identity to the Escherichia coli UbiA protein, an octaprenyltransferase required for the second step of ubiquinone biosynthesis. Complementation experiments in both Providencia stuartii and E. coli demonstrated that aarE and ubiA are functionally equivalent.

  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. Automated Support for After Action Review (AAR) Presentation

    DTIC Science & Technology

    2009-09-01

    GDIS military training application. GDIS is based on the Valve Half-Life 2 commercial game engine. The use of commercial gaming technologies ...ASAP), a suite of intelligent technologies designed to enhance virtual AAR systems such as the Dismounted Infantry Virtual After Action Review System...CONTINUED) Page List of Figures Figure 1 GDIS

  9. High salt diet modulates vascular response in A2AAR (+/+) and A 2AAR (-/-) mice: role of sEH, PPARγ, and K ATP channels.

    PubMed

    Pradhan, Isha; Ledent, Catherine; Mustafa, S Jamal; Morisseau, Christophe; Nayeem, Mohammed A

    2015-06-01

    This study aims to investigate the signaling mechanism involved in HS-induced modulation of adenosine-mediated vascular tone in the presence or absence of adenosine A2A receptor (A2AAR). We hypothesized that HS-induced enhanced vascular relaxation through A2AAR and epoxyeicosatrienoic acid (EETs) is dependent on peroxisome proliferator-activated receptor gamma (PPARγ) and ATP-sensitive potassium channels (KATP channels) in A2AAR(+/+) mice, while HS-induced vascular contraction to adenosine is dependent on soluble epoxide hydrolase (sEH) that degrades EETs in A2AAR(-/-) mice. Organ bath and Western blot techniques were conducted in HS (4 % NaCl) and normal salt (NS, 0.45 % NaCl)-fed A2AAR(+/+) and A2AAR(-/-) mouse aorta. We found that enhanced vasodilation to A2AAR agonist, CGS 21680, in HS-fed A2AAR(+/+) mice was blocked by PPARγ antagonist (T0070907) and KATP channel blocker (Glibenclamide). Also, sEH inhibitor (AUDA)-dependent vascular relaxation was mitigated by PPARγ antagonist. PPARγ agonist (Rosiglitazone)-induced relaxation in HS-A2AAR(+/+) mice was attenuated by KATP channel blocker. Conversely, HS-induced contraction in A2AAR(-/-) mice was attenuated by sEH inhibitor. Overall, findings from this study that implicates the contribution of EETs, PPARγ and KATP channels downstream of A2AAR to mediate enhanced vascular relaxation in response to HS diet while, role of sEH in mediating vascular contraction in HS-fed A2AAR(-/-) mice.

  10. A mobile magnetic sensor unit for the KATRIN main spectrometer

    NASA Astrophysics Data System (ADS)

    Osipowicz, A.; Seller, W.; Letnev, J.; Marte, P.; Müller, A.; Spengler, A.; Unru, A.

    2012-06-01

    The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to measure the electron neutrino mass with an unprecedented sensitivity of 0.2 eV/c2, using β decay electrons from tritium decay. For the control of magnetic field in the main spectrometer area of the KATRIN experiment a mobile magnetic sensor unit is constructed and tested at the KATRIN main spectrometer site. The unit moves on inner rails of the support structures of the low field shaping coils which are arranged along the the main spectrometer. The unit propagates on a caterpillar drive and contains an electro motor, battery pack, board electronics, 2 triaxial flux gate sensors and 2 inclination senors. During operation all relevant data are stored on board and transmitted to the master station after the docking station is reached.

  11. Focal-plane detector system for the KATRIN experiment

    SciTech Connect

    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.; Frankle, F. M.; Furse, D.; Gemmeke, H.; Gluck, 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, II, D. G.; Renschler, P.; Robertson, R. G. H.; Schwarz, J.; Steidl, M.; Tcherniakhovski, D.; Thummler, T.; Van Wechel, T. D.; VanDevender, B. A.; Vocking, S.; Wall, B. L.; Wierman, K. L.; Wilkerson, J. F.; Wustling, S.

    2015-01-09

    Here, the local plane detector system for the KArlsiuhe 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.

  12. Focal-plane detector system for the KATRIN experiment

    DOE PAGES

    Amsbaugh, J. F.; Barrett, J.; Beglarian, A.; ...

    2015-01-09

    Here, the local plane detector system for the KArlsiuhe 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.

  13. A novel AARS mutation in a family with dominant myeloneuropathy

    PubMed Central

    Motley, William W.; Griffin, Laurie B.; Mademan, Inès; Baets, Jonathan; De Vriendt, Els; De Jonghe, Peter; Antonellis, Anthony; Jordanova, Albena

    2015-01-01

    Objective: To determine the genetic cause of neurodegeneration in a family with myeloneuropathy. Methods: We studied 5 siblings in a family with a mild, dominantly inherited neuropathy by clinical examination and electrophysiology. One patient had a sural nerve biopsy. After ruling out common genetic causes of axonal Charcot-Marie-Tooth disease, we sequenced 3 tRNA synthetase genes associated with neuropathy. Results: All affected family members had a mild axonal neuropathy, and 3 of 4 had lower extremity hyperreflexia, evidence of a superimposed myelopathy. A nerve biopsy showed evidence of chronic axonal loss. All affected family members had a heterozygous missense mutation c.304G>C (p.Gly102Arg) in the alanyl-tRNA synthetase (AARS) gene; this allele was not identified in unaffected individuals or control samples. The equivalent change in the yeast ortholog failed to complement a strain of yeast lacking AARS function, suggesting that the mutation is damaging. Conclusion: A novel mutation in AARS causes a mild myeloneuropathy, a novel phenotype for patients with mutations in one of the tRNA synthetase genes. PMID:25904691

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

    PubMed

    Bateman, Chris

    2010-11-09

    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%).

  15. Structural basis for dual roles of Aar2p in U5 snRNP assembly

    PubMed Central

    Weber, Gert; Cristão, Vanessa F.; Santos, Karine F.; Jovin, Sina Mozaffari; Heroven, Anna C.; Holton, Nicole; Lührmann, Reinhard; Beggs, Jean D.; Wahl, Markus C.

    2013-01-01

    Yeast U5 small nuclear ribonucleoprotein particle (snRNP) is assembled via a cytoplasmic precursor that contains the U5-specific Prp8 protein but lacks the U5-specific Brr2 helicase. Instead, pre-U5 snRNP includes the Aar2 protein not found in mature U5 snRNP or spliceosomes. Aar2p and Brr2p bind competitively to a C-terminal region of Prp8p that comprises consecutive RNase H-like and Jab1/MPN-like domains. To elucidate the molecular basis for this competition, we determined the crystal structure of Aar2p in complex with the Prp8p RNase H and Jab1/MPN domains. Aar2p binds on one side of the RNase H domain and extends its C terminus to the other side, where the Jab1/MPN domain is docked onto a composite Aar2p–RNase H platform. Known Brr2p interaction sites of the Jab1/MPN domain remain available, suggesting that Aar2p-mediated compaction of the Prp8p domains sterically interferes with Brr2p binding. Moreover, Aar2p occupies known RNA-binding sites of the RNase H domain, and Aar2p interferes with binding of U4/U6 di-snRNA to the Prp8p C-terminal region. Structural and functional analyses of phospho-mimetic mutations reveal how phosphorylation reduces affinity of Aar2p for Prp8p and allows Brr2p and U4/U6 binding. Our results show how Aar2p regulates both protein and RNA binding to Prp8p during U5 snRNP assembly. PMID:23442228

  16. Redefining the phenotype of ALSP and AARS2 mutation–related leukodystrophy

    PubMed Central

    Lakshmanan, Rahul; Adams, Matthew E.; Lynch, David S.; Kinsella, Justin A.; Phadke, Rahul; Schott, Jonathan M.; Murphy, Elaine; Rohrer, Jonathan D.; Chataway, Jeremy; Houlden, Henry; Fox, Nick C.

    2017-01-01

    Objective: To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation–related leukodystrophy (AARS2-L), and highlight key differentiating features. Methods: ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. Results: A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed “deep white matter diffusion dots.” Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. Conclusions: ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted. PMID:28243630

  17. A2A Adenosine Receptor (A2AAR) as a Therapeutic Target in Diabetic Retinopathy

    PubMed Central

    Ibrahim, Ahmed S.; El-shishtawy, Mamdouh M.; Zhang, Wenbo; Caldwell, Ruth B.; Liou, Gregory I.

    2011-01-01

    In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. A2A adenosine receptor (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in DR. Here, we evaluate the role of A2AAR and its underlying signaling in retinal complications associated with diabetes. Initial studies in wild-type mice revealed that the treatment with the A2AAR agonist resulted in marked decreases in hyperglycemia-induced retinal cell death and tumor necrosis factor (TNF)-α release. To further assess the role of A2AAR in DR, we studied the effects of A2AAR ablation on diabetes-induced retinal abnormalities. Diabetic A2AAR−/− mice had significantly more terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, TNF-α release, and intercellular adhesion molecule-1 expression compared with diabetic wild-type mice. To explore a potential mechanism by which A2AAR signaling regulates inflammation in DR, we performed additional studies using microglial cells treated with Amadori-glycated albumin, a risk factor in diabetic disorders. The results showed that activation of A2AAR attenuated Amadori-glycated albumin-induced TNF-α release in a cAMP/exchange protein directly activated by cAMP-dependent mechanism and significantly repressed the inflammatory cascade, C-Raf/extracellular signal-regulated kinase (ERK), in activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in DR and suggests that the retinal protective effect of A2AAR is mediated by abrogating the inflammatory response that occurs in microglia via interaction with C-Raf/ERK pathway. PMID:21514428

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

    SciTech Connect

    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.; Viveiros, L. De; 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.; Ureña, A. Gonzalez; 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.; Cascio, L. La; 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.

    2016-04-07

    The KATRIN experiment will probe the neutrino mass by measuring the β-electron energy spectrum near the endpoint of tritium β-decay. We performed an integral energy analysis 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. Furthermore, 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. We 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.

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

    DOE PAGES

    Arenz, M.; Babutzka, M.; Bahr, M.; ...

    2016-04-07

    The KATRIN experiment will probe the neutrino mass by measuring the β-electron energy spectrum near the endpoint of tritium β-decay. We performed an integral energy analysis 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. Furthermore, a system consisting of 6 turbo-molecular pumps and 3more » 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. We 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.« less

  20. 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.

  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. Sterile neutrinos and right-handed currents in KATRIN

    NASA Astrophysics Data System (ADS)

    Barry, James; Heeck, Julian; Rodejohann, Werner

    2014-07-01

    Kurie-plot experiments allow for neutrino-mass measurements based on kinematics in an almost model-independent manner. A future tritium-based KATRIN-like experiment can be sensitive to light sterile neutrinos with masses below 18 keV, which are among the prime candidates for warm dark matter. Here we consider such keV neutrinos in left-right symmetric extensions, i.e. coupled to right-handed currents, which allow for an enhanced contribution to beta decay even for small active-sterile mixing, without violating astrophysical X-ray constraints. The modified spectral shape is in principle distinguishable from the standard contribution — especially for sterile neutrino masses below 9 keV, which can lead to a distinct peak. We compare the sensitivity to constraints from the LHC and neutrinoless double beta decay.

  3. The Windowless Gaseous Tritium Source (WGTS) of the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Heizmann, Florian; Seitz-Moskaliuk, Hendrik; KATRIN collaboration

    2017-09-01

    The Karlsruhe Tritium Neutrino Experiment (KATRIN) will perform a direct, kinematics-based measurement of the neutrino mass with a sensitivity of 200 meV (90 % C. L.), which will be reached after 3 years of measurement time. The neutrino mass is obtained by investigating the shape of the energy spectrum of tritium β-decay electrons close to the endpoint at 18.6 keV with a spectrometer of MAC-E filter type. This contribution reviews the current status of the tritium source cryostat and magnet system which is currently in its first cool-down phase. Furthermore, the next steps of the comprehensive pre-tritium measurement programme to characterise the apparatus and investigate important systematics are outlined. This work is supported by BMBF (05A14VK2) and the Helmholtz Association.

  4. 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.

  5. Methodology and application of high performance electrostatic field simulation in the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Corona, Thomas

    The Karlsruhe Tritium Neutrino (KATRIN) experiment is a tritium beta decay experiment designed to make a direct, model independent measurement of the electron neutrino mass. The experimental apparatus employs strong ( O[T]) magnetostatic and (O[10 5 V/m]) electrostatic fields in regions of ultra high (O[10-11 mbar]) vacuum in order to obtain precise measurements of the electron energy spectrum near the endpoint of tritium beta-decay. The electrostatic fields in KATRIN are formed by multiscale electrode geometries, necessitating the development of high performance field simulation software. To this end, we present a Boundary Element Method (BEM) with analytic boundary integral terms in conjunction with the Robin Hood linear algebraic solver, a nonstationary successive subspace correction (SSC) method. We describe an implementation of these techniques for high performance computing environments in the software KEMField, along with the geometry modeling and discretization software KGeoBag. We detail the application of KEMField and KGeoBag to KATRIN's spectrometer and detector sections, and demonstrate its use in furthering several of KATRIN's scientific goals. Finally, we present the results of a measurement designed to probe the electrostatic profile of KATRIN's main spectrometer in comparison to simulated results.

  6. Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii.

    PubMed

    Macinga, D R; Parojcic, M M; Rather, P N

    1995-06-01

    The aarP gene has been identified in a search for activators of the 2-N-acetyltransferase [encoded by aac(2')-Ia] in Providencia stuartii. Introduction of aarP into P. stuartii on a multicopy plasmid resulted in a 9.9-fold increase in the accumulation of beta-galactosidase from an aac(2')-lacZ fusion. Northern (RNA) blot analysis demonstrated that this increased aac(2')-Ia expression occurred at the level of mRNA accumulation. The deduced AarP protein was 15,898 Da in size and exhibited significant homology to a number of transcriptional activators in the AraC/XyIS family, including TetD,Rob, MarA, and SoxS. The similarity of AarP to the MarA and SoxS proteins prompted an investigation to determine whether AarP is involved in activation of genes in either the multiple antibiotic resistance (Mar) phenotype or redox stress (SoxRS) system. Introduction of aarP on a multicopy plasmid into either P. stuartii or Escherichia coli conferred a Mar phenotype with higher levels of resistance to tetracycline, chloramphenicol, and ciprofloxacin. Multiple copies of aarP in E. coli also resulted in activation of the endonuclease IV gene (nfo), a gene in the SoxRS regulon of E. coli. The function of aarP in its single-copy state was addressed by using allelic replacement to construct an aarP::Cm disruption, which resulted in a fivefold reduction in the accumulation of aac(2')-Ia mRNA. Analysis of aarP regulation showed that aarP mRNA accumulation was slightly increased by exposure to tetracycline and dramatically increased in cells containing the aarB3 (aar3) mutation, which was previously shown to increase transcription of the aac(2')-Ia gene. (P.N. Rather, E. Oroz, K.J. Shaw, R. Hare, and G. Miller, J. Bacteriol. 175:6492-6498).

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

    PubMed Central

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

    2017-01-01

    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-1hyperphosphorylation, 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 phosphorylation (Ser101/Ser119/Ser169) 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 leucine deprivation. PMID:25957086

  8. Multi-Facet Multicultural School Assessment: Adapting and Norming the AARS/POSIT.

    ERIC Educational Resources Information Center

    French, Laurence; Picthall-French, Nancy

    The National Institute on Mental Health attempted to address the issue of providing a reliable baseline on alcohol-related problems among adolescents with the Adolescent Assessment Referral System (AARS). Part of this tool is the Problem Oriented Screening Instrument (POSIT), a 139-item questionnaire printed in English and Spanish. This…

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

    PubMed

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

    2015-09-05

    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.

  10. Deconvolution of the energy loss function of the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Hannen, V.; Heese, I.; Weinheimer, C.; Sejersen Riis, A.; Valerius, K.

    2017-03-01

    The KATRIN experiment aims at a direct and model independent determination of the neutrino mass with 0.2 eV/c2 sensitivity (at 90% C.L.) via a measurement of the endpoint region of the tritium beta-decay spectrum. The main components of the experiment are a windowless gaseous tritium source (WGTS), differential and cryogenic pumping sections and a tandem of a pre- and a main-spectrometer, applying the concept of magnetic adiabatic collimation with an electrostatic retardation potential to analyze the energy of beta decay electrons and to guide electrons passing the filter onto a segmented silicon PIN detector. One of the important systematic uncertainties of such an experiment are due to energy losses of β-decay electrons by elastic and inelastic scattering off tritium molecules within the source volume which alter the shape of the measured spectrum. To correct for these effects an independent measurement of the corresponding energy loss function is required. In this work we describe a deconvolution method to extract the energy loss function from measurements of the response function of the experiment at different column densities of the WGTS using a monoenergetic electron source.

  11. 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.

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

    PubMed

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

    1997-04-01

    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.

  13. Reduction in cryptosporidiosis associated with introduction of enhanced filtration of drinking water at Loch Katrine, Scotland.

    PubMed

    Pollock, K G J; Young, D; Robertson, C; Ahmed, S; Ramsay, C N

    2014-01-01

    Previous evidence has suggested an association between cryptosporidiosis and consumption of unfiltered drinking water from Loch Katrine in Scotland. Before September 2007, the water was only micro-strained and chlorinated; however, since that time, coagulation and rapid gravity filtration have been installed. In order to determine risk factors associated with cryptosporidiosis, including drinking water, we analysed data on microbiologically confirmed cases of cryptosporidiosis from 2004 to 2010. We identified an association between the incidence of cryptosporidiosis and unfiltered Loch Katrine drinking water supplied to the home (odds ratio 1.86, 95% confidence interval 1.11-3.11, P = 0.019). However, while filtration appears to be associated with initially reduced rates of cryptosporidiosis, evidence suggests it may paradoxically make those consumers more susceptible to other transmission routes in the long-term. These findings support implementation of similar treatment for other unfiltered drinking-water supplies, as a means of reducing cryptosporidiosis associated with drinking water.

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

    SciTech Connect

    Farzan, Yasaman; Hannestad, Steen E-mail: sth@phys.au.dk

    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.

  15. 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.

  16. 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.

  17. 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.

  18. Role of SspA in the density-dependent expression of the transcriptional activator AarP in Providencia stuartii.

    PubMed

    Ding, X; Baca-DeLancey, R R; Rather, P N

    2001-03-01

    The AarP protein in Providencia stuartii encodes a small transcriptional activator which activates the chromosomal aminoglycoside acetyltransferase aac(2')-Ia gene. In addition, AarP activates genes involved in a multiple antibiotic resistance (Mar) phenotype. Expression of an aarP-lacZ fusion increased in a density-dependent manner and reached peak levels at stationary phase. The expression of an aarP-lacZ fusion could be prematurely activated in cells at early to mid-exponential phase by the addition of spent culture supernatants from stationary phase cultures or by ethyl acetate extracts of these supernatants. Nutrient starvation had a negligible effect on aarP expression. In a search for mutations that block aarP activation at stationary phase, a mini-Tn5Cm insertion has been identified within a gene whose product was 77% identical to SspA, a regulatory protein involved in stationary phase gene expression and virulence. An unmarked sspA null allele (sspA2) was created by allelic replacement to further examine the role of sspA in P. stuartii. The sspA2 allele resulted in substantial decrease in aarP mRNA accumulation at various phases of growth. Furthermore, in an sspA mutant background, the aarP-lacZ fusion was no longer activated by an extracellular signal.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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…

  4. 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

    2015-05-19

    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.

  5. 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.

  6. 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

  7. 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

  8. A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N).

    PubMed

    McLaughlin, Heather M; Sakaguchi, Reiko; Giblin, William; Wilson, Thomas E; Biesecker, Leslie; Lupski, James R; Talbot, Kevin; Vance, Jeffery M; Züchner, Stephan; Lee, Yi-Chung; Kennerson, Marina; Hou, Ya-Ming; Nicholson, Garth; Antonellis, Anthony

    2012-01-01

    Charcot-Marie-Tooth (CMT) disease comprises a heterogeneous group of peripheral neuropathies characterized by muscle weakness and wasting, and impaired sensation in the extremities. Four genes encoding an aminoacyl-tRNA synthetase (ARS) have been implicated in CMT disease. ARSs are ubiquitously expressed, essential enzymes that ligate amino acids to cognate tRNA molecules. Recently, a p.Arg329His variant in the alanyl-tRNA synthetase (AARS) gene was found to segregate with dominant axonal CMT type 2N (CMT2N) in two French families; however, the functional consequence of this mutation has not been determined. To investigate the role of AARS in CMT, we performed a mutation screen of the AARS gene in patients with peripheral neuropathy. Our results showed that p.Arg329His AARS also segregated with CMT disease in a large Australian family. Aminoacylation and yeast viability assays showed that p.Arg329His AARS severely reduces enzyme activity. Genotyping analysis indicated that this mutation arose on three distinct haplotypes, and the results of bisulfite sequencing suggested that methylation-mediated deamination of a CpG dinucleotide gives rise to the recurrent p.Arg329His AARS mutation. Together, our data suggest that impaired tRNA charging plays a role in the molecular pathology of CMT2N, and that patients with CMT should be directly tested for the p.Arg329His AARS mutation.

  9. Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase.

    PubMed

    Stevenson, Lindsay G; Strisovsky, Kvido; Clemmer, Katy M; Bhatt, Shantanu; Freeman, Matthew; Rather, Philip N

    2007-01-16

    The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and is required for the production of an unknown quorum-sensing molecule. In a screen to identify rhomboid-encoding genes from Proteus mirabilis, tatA was identified as a multicopy suppressor and restored extracellular signal production as well as complementing all other phenotypes of a Prov. stuartii aarA mutant. TatA is a component of the twin-arginine translocase (Tat) protein secretion pathway and likely forms a secretion pore. By contrast, the native tatA gene of Prov. stuartii in multicopy did not suppress an aarA mutation. We find that TatA in Prov. stuartii has a short N-terminal extension that was atypical of TatA proteins from most other bacteria. This extension was proteolytically removed by AarA both in vivo and in vitro. A Prov. stuartii TatA protein missing the first 7 aa restored the ability to rescue the aarA-dependent phenotypes. To verify that loss of the Tat system was responsible for the various phenotypes exhibited by an aarA mutant, a tatC-null allele was constructed. The tatC mutant exhibited the same phenotypes as an aarA mutant and was epistatic to aarA. These data provide a molecular explanation for the requirement of AarA in quorum-sensing and uncover a function for the Tat protein export system in the production of secreted signaling molecules. Finally, TatA represents a validated natural substrate for a prokaryotic rhomboid protease.

  10. A pulsed, mono-energetic and angular-selective UV photo-electron source for the commissioning of the KATRIN experiment

    NASA Astrophysics Data System (ADS)

    Behrens, J.; Ranitzsch, P. C.-O.; Beck, M.; Beglarian, A.; Erhard, M.; Groh, S.; Hannen, V.; Kraus, M.; Ortjohann, H.-W.; Rest, O.; Schlösser, K.; Thümmler, T.; Valerius, K.; Wierman, K.; Wilkerson, J. F.; Winzen, D.; Zacher, M.; Weinheimer, C.

    2017-06-01

    The KATRIN experiment aims to determine the neutrino mass scale with a sensitivity of 200 {meV/c^2} (90% C. L.) by a precision measurement of the shape of the tritium β -spectrum in the endpoint region. The energy analysis of the decay electrons is achieved by a MAC-E filter spectrometer. To determine the transmission properties of the KATRIN main spectrometer, a mono-energetic and angular-selective electron source has been developed. In preparation for the second commissioning phase of the main spectrometer, a measurement phase was carried out at the KATRIN monitor spectrometer where the device was operated in a MAC-E filter setup for testing. The results of these measurements are compared with simulations using the particle-tracking software "Kassiopeia", which was developed in the KATRIN collaboration over recent years.

  11. Activation of the 2'-N-acetyltransferase gene [aac(2')-Ia] in Providencia stuartii by an interaction of AarP with the promoter region.

    PubMed

    Macinga, D R; Paradise, M R; Parojcic, M M; Rather, P N

    1999-07-01

    The aac(2')-Ia gene in Providencia stuartii encodes a 2'-N-acetyltransferase capable of acetylating both peptidoglycan and certain aminoglycoside antibiotics. Regulation of the aac(2')-Ia gene is influenced in a positive manner by the product of the aarP gene, which encodes a small transcriptional activator of the AraC (XylS) family. In this study, we demonstrate the sequence requirements at the aac(2')-Ia promoter for AarP binding and activation.

  12. The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations.

    PubMed

    Hamatani, Mio; Jingami, Naoto; Tsurusaki, Yoshinori; Shimada, Shino; Shimojima, Keiko; Asada-Utsugi, Megumi; Yoshinaga, Kenji; Uemura, Norihito; Yamashita, Hirofumi; Uemura, Kengo; Takahashi, Ryosuke; Matsumoto, Naomichi; Yamamoto, Toshiyuki

    2016-10-01

    Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.3 (AARS2_v001):c.1145C>A and NM_020745.3 (AARS2_v001):c.2255+1G>A was identified. Neither of the mutations has been previously reported, and this is the first report of alanyl-transfer RNA synthetase 2 mutation in Asia. We anticipate that further studies of the molecular basis of leukodystrophy will provide insight into its pathogenesis and hopefully lead to sophisticated diagnostic and treatment strategies.

  13. Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii.

    PubMed

    Clemmer, Katy M; Sturgill, Gwen M; Veenstra, Alexander; Rather, Philip N

    2006-05-01

    The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and required for the production of an extracellular signaling molecule that regulates cellular functions including peptidoglycan acetylation, methionine transport, and cysteine biosynthesis. Additional aarA-dependent phenotypes include (i) loss of an extracellular yellow pigment, (ii) inability to grow on MacConkey agar, and (iii) abnormal cell division. Since these phenotypes are easily assayed, the P. stuartii aarA mutant serves as a useful host system to investigate rhomboid function. The Escherichia coli GlpG protein was shown to be functionally similar to AarA and rescued the above aarA-dependent phenotypes in P. stuartii. GlpG proteins containing single alanine substitutions at the highly conserved catalytic triad of asparagine (N154A), serine (S201A), or histidine (H254A) residues were nonfunctional. The P. stuartii aarA mutant was also used as a biosensor to demonstrate that proteins from a variety of diverse sources exhibited rhomboid activity. In an effort to further investigate the role of a rhomboid protein in cell physiology, a glpG mutant of E. coli was constructed. In phenotype microarray experiments, the glpG mutant exhibited a slight increase in resistance to the beta-lactam antibiotic cefotaxime.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. Rhomboids of Mycobacteria: Characterization Using an aarA Mutant of Providencia stuartii and Gene Deletion in Mycobacterium smegmatis

    PubMed Central

    Kateete, David Patrick; Katabazi, Fred Ashaba; Okeng, Alfred; Okee, Moses; Musinguzi, Conrad; Asiimwe, Benon Byamugisha; Kyobe, Samuel; Asiimwe, Jeniffer; Boom, W. Henry; Joloba, Moses Lutaakome

    2012-01-01

    Background Rhomboids are ubiquitous proteins with unknown roles in mycobacteria. However, bioinformatics suggested putative roles in DNA replication pathways and metabolite transport. Here, mycobacterial rhomboid-encoding genes were characterized; first, using the Providencia stuartii null-rhomboid mutant and then deleted from Mycobacterium smegmatis for additional insight in mycobacteria. Methodology/Principal Findings Using in silico analysis we identified in M. tuberculosis genome the genes encoding two putative rhomboid proteins; Rv0110 (referred to as “rhomboid protease 1”) and Rv1337 (“rhomboid protease 2”). Genes encoding orthologs of these proteins are widely represented in all mycobacterial species. When transformed into P. stuartii null-rhomboid mutant (ΔaarA), genes encoding mycobacterial orthologs of “rhomboid protease 2” fully restored AarA activity (AarA is the rhomboid protein of P. stuartii). However, most genes encoding mycobacterial “rhomboid protease 1” orthologs did not. Furthermore, upon gene deletion in M. smegmatis, the ΔMSMEG_4904 single mutant (which lost the gene encoding MSMEG_4904, orthologous to Rv1337, “rhomboid protease 2”) formed the least biofilms and was also more susceptible to ciprofloxacin and novobiocin, antimicrobials that inhibit DNA gyrase. However, the ΔMSMEG_5036 single mutant (which lost the gene encoding MSMEG_5036, orthologous to Rv0110, “rhomboid protease 1”) was not as susceptible. Surprisingly, the double rhomboid mutant ΔMSMEG_4904–ΔMSMEG_5036 (which lost genes encoding both homologs) was also not as susceptible suggesting compensatory effects following deletion of both rhomboid-encoding genes. Indeed, transforming the double mutant with a plasmid encoding MSMEG_5036 produced phenotypes of the ΔMSMEG_4904 single mutant (i.e. susceptibility to ciprofloxacin and novobiocin). Conclusions/Significance Mycobacterial rhomboid-encoding genes exhibit differences in complementing aarA whereby

  19. Statistical sensitivity on right-handed currents in presence of eV scale sterile neutrinos with KATRIN

    NASA Astrophysics Data System (ADS)

    Steinbrink, Nicholas M. N.; Glück, Ferenc; Heizmann, Florian; Kleesiek, Marco; Valerius, Kathrin; Weinheimer, Christian; Hannestad, Steen

    2017-06-01

    The KATRIN experiment aims to determine the absolute neutrino mass by measuring the endpoint region of the tritium β-spectrum. As a large-scale experiment with a sharp energy resolution, high source luminosity and low background it may also be capable of testing certain theories of neutrino interactions beyond the standard model (SM). An example of a non-SM interaction are right-handed currents mediated by right-handed W bosons in the left-right symmetric model (LRSM). In this extension of the SM, an additional SU(2)R symmetry in the high-energy limit is introduced, which naturally includes sterile neutrinos and predicts the seesaw mechanism. In tritium β decay, this leads to an additional term from interference between left- and right-handed interactions, which enhances or suppresses certain regions near the endpoint of the beta spectrum. In this work, the sensitivity of KATRIN to right-handed currents is estimated for the scenario of a light sterile neutrino with a mass of some eV. This analysis has been performed with a Bayesian analysis using Markov Chain Monte Carlo (MCMC). The simulations show that, in principle, KATRIN will be able to set sterile neutrino mass-dependent limits on the interference strength. The sensitivity is significantly increased if the Q value of the β decay can be sufficiently constrained. However, the sensitivity is not high enough to improve current upper limits from right-handed W boson searches at the LHC.

  20. 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.

  1. Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway.

    PubMed

    Zhang, Jianwei; Li, Qi; Zhang, Shaojin; Xu, Quanquan; Wang, Tianen

    2016-11-15

    Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression. Firstly, Lgr4 was overexpressed by transfecting pcDNA3.1(+)/Lgr4 plasmids into PCa (LNCaP and PC-3) cell lines. Next, we found that Lgr4 overexpression promoted Jmjd2a mRNA expression, reduced cell apoptosis and arrested cell cycle in the S phase, these effects were reversed by Jmjd2a silencing. Moreover, Lgr4 overexpression markedly elevated AR levels and its interaction with Jmjd2a, which was tested by co-immunoprecipitation and luciferase reporter assays. Furthermore, interaction AR with PSA promoter (containing an AR response element) was obviously improved by Lgr4 overexpression, and PSA silencing reduced Lgr4-induced cell apoptosis and cell cycle arrest in PCa cells. Taken together, Lgr4 may be a novel tumor marker providing new mechanistic insights into PCa progression. Lgr4 activates Jmjd2a/AR signaling pathway to promote interaction AR with PSA promoter, causing reduction of PCa apoptosis and cell cycle arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 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

  3. Altitude of the upper boundary of AAR based on observations of ion beams in inverted-V structures: A case study

    NASA Astrophysics Data System (ADS)

    Cui, YanBo; Fu, SuiYan; Zong, QuiGang; Xie, Lun; Sun, WeiJie; Zhao, Duo; Wu, Tong; Parks, George

    2016-07-01

    Outflowing ion beams forming four successive inverted-V structures in the energy-time spectrograms of H+, He+, and O+ were observed at an altitude of 3.4 RE by Cluster satellites travelling above the auroral acceleration region (AAR) in the southern hemisphere on February 14, 2001. Energization by negative U-shaped potential structures in the AAR is believed to be responsible for the formation of these outflowing ion inverted-V structures. Thus, utilizing the different motion properties of the three ion species, the altitude of the upper boundary of the AAR is estimated to be 11100 km. Moreover, based on multi-satellite observations, each ofthese U-shaped potential structures involved in this event crosses the latitud in aldirection at 0.4°-1° invariant latitude (ILAT), moving poleward at an average speed of 0.2° ILAT per minute, before disappearing at 71.5° ILAT.

  4. 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

  5. Transient thrust events recorded in the Aare Massif, Bernese Alps (Grimsel Test Site, Switzerland)

    NASA Astrophysics Data System (ADS)

    Hartvich, F.; Stemberk, J.

    2016-12-01

    The Grimsel Test Site (GTS) is located at an altitude of 1730 m a.s.l. in the granitic formations of the Aare Massif 300 - 500 m under the surface. In November 2012, documented faults within the GTS were instrumented for 3-D monitoring of fault slips in the scope of the LArge Scale MOnitoring project (LASMO). In total 7 devices were installed across faults crossing a 350 m long section of the GTS. The instrumented faults have various strike: W-E, SW-NE, WNW-ESE and WSW-ENE. The faults are instrumented with optical-mechanical extensometers TM71 which allow to measure 3D micro-displacements as well as rotations on the basis of the moiré effect of optical interference. The devices installed in GTS reach the accuracy better than 0.007 mm and the angular deviation between two blocks separated by a discontinuity - i.e. their relative rotation - can be measured with a resolution better than 0.00016 rad. Regular monitoring has started on Dec. 5,2012 and the reading is performed regularly once per day. The first results of 3-D fault displacement monitoring show transient slips recorded during 2 short periods along all monitored faults, alternating with long periods of tectonic quiescence without any fault activity. The measured directions of fault slips enable us to estimate two approximately N - S oriented compression events, causing northwards thrust movements. First period lasted from Dec. 27, 2012 to Feb. 13, 2013. However, major phase of the displacement occurred between Jan. 26 and 29, 2013. Recorded fault slips represent northwards oriented thrusts and strike-slips. A value of individual slips ranges from 0.004 to 0.04 mm. Moreover, the strike-slip movements were recorded during days when two local micro-earthquakes were observed close to GTS: on Jan. 29, 2013 (M = 1.29) and on Feb. 13, 2013 (M = 1.15). The second period of activity lasted from Sept. 7, 2013 to Oct. 28, 2013, and occurred after more than 7 months of no recorded fault slips. The main phase of the

  6. 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.

  7. 3 Neutrino mass experiments fit a strange 3 + 3 model, but will KATRIN reveal the model's unique 3-part signature?

    NASA Astrophysics Data System (ADS)

    Ehrlich, R.

    2016-12-01

    Evidence is presented in support of an unconventional 3 + 3 model of the neutrino mass eigenstates with specific m2 > 0 and m2 < 0 masses. The two large m2 > 0 masses of the model were originally suggested based on a SN 1987A analysis, and they were further supported by several dark matter fits. The new evidence for one of the m2 > 0 mass values comes from an analysis of published data from the three most precise tritium β - decay experiments. The KATRIN experiment by virtue of a unique 3-part signature should either confirm or reject the model in its entirety.

  8. aarD, a Providencia stuartii homologue of cydD: role in 2'-N-acetyltransferase expression, cell morphology and growth in the presence of an extracellular factor.

    PubMed

    Macinga, D R; Rather, P N

    1996-02-01

    In a search for genes involved in regulation of the 2'-N-acetyltransferase in Providencia stuartii, a mini-Tn5Cm insertion has been isolated in a locus designated aarD. The aarD1::mini-Tn5Cm mutation resulted in a 4.7-fold increase in the levels of beta-galactosidase accumulation from an aac(2')-lacZ transcriptional fusion and a 32-fold increase in the levels of gentamicin resistance in P. stuartii. The wild-type aarD locus was cloned on a 5.0 kb Cla I fragment and complemented the aarD1 mutation. Nucleotide sequence analysis of this fragment identified two large open reading frames whose deduced products displayed significant amino acid identity, 64% and 64%, respectively, to the CydD and CydC proteins of Escherichia coli, which are involved in formation of the cytochrome d oxidase complex. Physical mapping indicated the aarD1::mini-Tn5Cm insertion was within the open reading homologous to CydD. The strain containing the aarD1 mutation was unable to grow in the presence of toluidine blue or on glycerol minimal media in the presence of zinc, suggesting that aarD is functionally equivalent to cydD. Additional phenotypes resulting from the aarD1 mutation included: altered cell morphology, a reduced growth rate and the inability of cells to grow beyond early log phase. Further examination of this phenomenon revealed that the aarD1 mutant was unable to grow in the presence of a self-produced extracellular factor(s). This novel phenotype was limited to P. stuartii as E. coli cydD and delta cydAB::kan mutants were also sensitive to a self-produced extracellular factor.

  9. Adaptive on-line classification for EEG-based brain computer interfaces with AAR parameters and band power estimates.

    PubMed

    Vidaurre, C; Schlögl, A; Cabeza, R; Scherer, R; Pfurtscheller, G

    2005-11-01

    We present the result of on-line feedback Brain Computer Interface experiments using adaptive and non-adaptive feature extraction methods with an on-line adaptive classifier based on Quadratic Discriminant Analysis. Experiments were performed with 12 naïve subjects, feedback was provided from the first moment and no training sessions were needed. Experiments run in three different days with each subject. Six of them received feedback with Adaptive Autoregressive parameters and the rest with logarithmic Band Power estimates. The study was done using single trial analysis of each of the sessions and the value of the Error Rate and the Mutual Information of the classification were used to discuss the results. Finally, it was shown that even subjects starting with a low performance were able to control the system in a few hours: and contrary to previous results no differences between AAR and BP estimates were found.

  10. Magnetic fabric (AMS, AAR) of the Santa Marta batholith (northern Colombia) and the shear deformation along the Caribbean Plate margin

    NASA Astrophysics Data System (ADS)

    Salazar, Carlos A.; Bustamante, Camilo; Archanjo, Carlos J.

    2016-10-01

    Anisotropy of low-field magnetic susceptibility (AMS) and anhysteretic remanence (AAR) were measured in the Santa Marta Batholith formed by subduction of the Caribbean Plate beneath the northern South America. The batholith, elongated in the N-S direction, records multiple pulses of quartzdiorite to tonalite and granodiorite magmas between 58 and 49 Ma. The high mean magnetic susceptibility (4 × 10-3 SI) combined with thermomagnetic and partial magnetic remanence measurements indicate that the magnetic susceptibility depends on Ti-poor magnetite. AMS is defined by ellipsoids that are dominantly oblate. The foliation was used to distinguish a narrow band of E-trending magnetic structures that separate the batholith in two lobes. The southern lobe is characterized by foliations that are broadly parallel to the contact with the wall rocks, while the northern lobe by foliations oblique to the batholith elongation. Late tonalitic magmas dated at c. 50 Ma record, in turn, a fabric apparently controlled by E-trending tectonic events. Partial AAR indicates that the subfabrics of magnetite with different grain sizes are nearly parallel to AMS, therefore discarding the possibility of superposed fabrics with different orientations. The magnetic fabric pattern is consistent with a magma emplaced in an arc setting deformed by a dextral shear. Synthetic extensional shear bands localize the magmatic deformation along East-trending corridors that probably were exploited to emplace the late magmatic pulses. Accretion of the Eocene batholith and the Late Cretaceous metasedimentary host-rocks to the South American continent defines a major strike-slip shear suture that resulted from the oblique convergence of the Caribbean Plate.

  11. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation.

    PubMed

    Euro, Liliya; Konovalova, Svetlana; Asin-Cayuela, Jorge; Tulinius, Már; Griffin, Helen; Horvath, Rita; Taylor, Robert W; Chinnery, Patrick F; Schara, Ulrike; Thorburn, David R; Suomalainen, Anu; Chihade, Joseph; Tyynismaa, Henna

    2015-01-01

    The accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs) and the mitochondrial DNA-encoded tRNAs. The recent advances in whole-exome sequencing have revealed the importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is now recognized as a disease gene for mitochondrial disease. Typically, defects in each mtARS have been identified in one tissue-specific disease, most commonly affecting the brain, or in one syndrome. However, mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) have been reported both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. We present here an investigation of the effects of the described mutations on the structure of the synthetase, in an effort to understand the tissue-specific outcomes of the different mutations. The mtAlaRS differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged with incorrect amino acids. We show that the cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. Nevertheless, our structural analysis predicts that all mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. According to our model, the cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. These predictions provide a hypothesis for the molecular basis of the distinct tissue-specific phenotypic outcomes.

  12. 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.

  13. 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.

  14. Thermal properties of Central Aare granite for temperatures up to 500°C: Irreversible changes due to thermal crack formation

    NASA Astrophysics Data System (ADS)

    Kant, Michael A.; Ammann, Jens; Rossi, Edoardo; Madonna, Claudio; Höser, Dragana; Rudolf von Rohr, Philipp

    2017-01-01

    Thermal diffusivity, heat capacity, and thermal conductivity of Central Aare granite are reported in the temperature range from 25°C to 500°C. Each rock sample underwent three consecutive heating and cooling cycles. Significant irreversible changes in the properties due to thermal crack formation could be observed. After the first thermal cycle, both thermal diffusivity and conductivity dropped to about 75% of the initial value at room temperature, whereas the heat capacity did not show an irreversible decay. For subsequent thermal cycles, no further permanent changes of the investigated properties could be observed. From the conducted measurements, accurate correlations are derived, offering a platform for precise high-temperature experiments and other research on Central Aare granite and similar granitic rocks. The report shows that the assumption of constant thermal properties leads to significant inaccuracies at elevated temperatures, especially if thermal cycles are present.

  15. Lake Biel sediment record during the last 7500 years and impact of the Aare river deviation in 1878 AD.

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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 (Switzerland) with a maximum depth of 74 m and lies at 429 m asl. Our study focuses on the south-west basin, where the lake sedimentation was naturally mainly controlled by autochthonous sedimentation, and is now, since the artificial Aare river deviation through the Hagneck canal in 1878 AD, under the strong influence of water and sediment input from its catchment. A 10.05-m-long composite sediment sequence, cored in 2011 at 52 m water depth, was built from two cores retrieved with an Uwitec system. The cored sedimentary sequence begins in 1975 and spans the last 7500 years, as dated by seven 14C analyses and 210Pb/137Cs activity profiles. Magnetic susceptibility and density were measured with a Geotek MSCL at 0.5 cm resolution, granulometry with a CILAS grain sizer every 10 cm and X-ray fluorescence measurements were carried out using an Avaatech core scanner at 1-cm resolution. Lake Biel sediment record is subdivided in four main units. The lowest Unit A (651-1005 cm; 7355 to 5075 BP), with dark greyish clayey silty laminated layers and sedimentation rates between 0.10 to 0.29 cm/yr, shows stable low values for almost all proxies, excepted for allochtonous elements which increase between 7000-6000 BP. By analogy with Unit C facies (see below), Unit A is interpreted as influenced by the Aare river which probably flew into the south-west basin at that time. Unit B1 (651-343 cm, 5075 to 2036 BP) has lower sedimentation rate (0.10 cm/yr), high Ca/Ti ratio, light sediment color, constant clayey silty grain size and varying elemental profiles which point to the dominant influence of autochtonous lake processes influenced by climate. From the beginning of Unit B2 (343-147 cm, 2036 to 1878 AD) sediment grain size increases which possibly reflects a human influence over the lake system. The greatest

  16. Estimating the gas transfer velocity: a prerequisite for more accurate and higher resolution GHG fluxes (lower Aare River, Switzerland)

    NASA Astrophysics Data System (ADS)

    Sollberger, S.; Perez, K.; Schubert, C. J.; Eugster, W.; Wehrli, B.; Del Sontro, T.

    2013-12-01

    Currently, carbon dioxide (CO2) and methane (CH4) emissions from lakes, reservoirs and rivers are readily investigated due to the global warming potential of those gases and the role these inland waters play in the carbon cycle. However, there is a lack of high spatiotemporally-resolved emission estimates, and how to accurately assess the gas transfer velocity (K) remains controversial. In anthropogenically-impacted systems where run-of-river reservoirs disrupt the flow of sediments by increasing the erosion and load accumulation patterns, the resulting production of carbonic greenhouse gases (GH-C) is likely to be enhanced. The GH-C flux is thus counteracting the terrestrial carbon sink in these environments that act as net carbon emitters. The aim of this project was to determine the GH-C emissions from a medium-sized river heavily impacted by several impoundments and channelization through a densely-populated region of Switzerland. Estimating gas emission from rivers is not trivial and recently several models have been put forth to do so; therefore a second goal of this project was to compare the river emission models available with direct measurements. Finally, we further validated the modeled fluxes by using a combined approach with water sampling, chamber measurements, and highly temporal GH-C monitoring using an equilibrator. We conducted monthly surveys along the 120 km of the lower Aare River where we sampled for dissolved CH4 (';manual' sampling) at a 5-km sampling resolution, and measured gas emissions directly with chambers over a 35 km section. We calculated fluxes (F) via the boundary layer equation (F=K×(Cw-Ceq)) that uses the water-air GH-C concentration (C) gradient (Cw-Ceq) and K, which is the most sensitive parameter. K was estimated using 11 different models found in the literature with varying dependencies on: river hydrology (n=7), wind (2), heat exchange (1), and river width (1). We found that chamber fluxes were always higher than boundary

  17. 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.

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

    DOE PAGES

    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

  19. 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.

  20. Identification and characterization of aarF, a locus required for production of ubiquinone in Providencia stuartii and Escherichia coli and for expression of 2'-N-acetyltransferase in P. stuartii.

    PubMed

    Macinga, D R; Cook, G M; Poole, R K; Rather, P N

    1998-01-01

    Providencia stuartii contains a chromosomal 2'-N-acetyltransferase [AAC(2')-Ia] involved in the O acetylation of peptidoglycan. The AAC(2')-Ia enzyme is also capable of acetylating and inactivating certain aminoglycosides and confers high-level resistance to these antibiotics when overexpressed. We report the identification of a locus in P. stuartii, designated aarF, that is required for the expression of AAC(2')-Ia. Northern (RNA) analysis demonstrated that aac(2')-Ia mRNA levels were dramatically decreased in a P. stuartii strain carrying an aarF::Cm disruption. The aarF::Cm disruption also resulted in a deficiency in the respiratory cofactor ubiquinone. The aarF locus encoded a protein that had a predicted molecular mass of 62,559 Da and that exhibited extensive amino acid similarity to the products of two adjacent open reading frames of unknown function (YigQ and YigR), located at 86 min on the Escherichia coli chromosome. An E. coli yigR::Kan mutant was also deficient in ubiquinone content. Complementation studies demonstrated that the aarF and the E. coli yigQR loci were functionally equivalent. The aarF or yigQR genes were unable to complement ubiD and ubiE mutations that are also present at 86 min on the E. coli chromosome. This result indicates that aarF (yigQR) represents a novel locus for ubiquinone production and reveals a previously unreported connection between ubiquinone biosynthesis and the regulation of gene expression.

  1. How is strain localized in a meta-granitoid, mid-crustal basement section? Spatial distribution of deformation in the central Aar massif (Switzerland)

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

    This study investigates strain distribution in granitoid rocks formerly in the middle crust in the Central Aar massif, Switzerland and places the deformation behavior in the tectonic framework of the Alpine orogeny. Strain is heterogeneously distributed in terms of strain partitioning forming several hundreds of closely spaced shear zones (SZ) (>80 SZ/km with SZ thicknesses <10 cm; about 10 SZ/km with SZ thicknesses of 0.5-10 m) separating 3D bodies of low to moderate background strain. Both the degree of background-strain intensity as well as the number of shear zones increases from granitic to granodioritic host rocks and is controlled by primary variations in the mica content between 10 and 15 vol% (granodiorite) and <8 vol% (granite). Shear zones evolved from ductile shearing in granodiorites, whereas they often nucleated from fractures in the stronger granites. The majority of the steep shear zones preferentially accommodated upward motion by the southern block leading to an increase in peak metamorphic conditions from 250 °C in the North to 450 °C in the South of the Aar massif. The shear zones initiated at about 18-20 km depths during a stage of crustal thickening (Handegg phase). Subsequent deformation reactivated some shear zones with a gradual transition from reverse dip-slip over oblique-slip to strike-slip shear zones under local transpressional conditions (Oberaar phase).

  2. Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia.

    PubMed

    Lynch, David S; Zhang, Wei Jia; Lakshmanan, Rahul; Kinsella, Justin A; Uzun, Günes Altiokka; Karbay, Merih; Tüfekçioglu, Zeynep; Hanagasi, Hasmet; Burke, Georgina; Foulds, Nicola; Hammans, Simon R; Bhattacharjee, Anupam; Wilson, Heather; Adams, Matthew; Walker, Mark; Nicoll, James A R; Chataway, Jeremy; Fox, Nick; Davagnanam, Indran; Phadke, Rahul; Houlden, Henry

    2016-12-01

    Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations. These patients include those in whom the pathognomonic features of axonal spheroids and pigmented microglia have been found. Achieving a genetic diagnosis in these patients is important to our understanding of this disorder. To genetically characterize a group of patients with typical features of ALSP who do not carry CSF1R mutations. In this case series study, 5 patients from 4 families were identified with clinical, radiologic, or pathologic features of ALSP in whom CSF1R mutations had been excluded previously by sequencing. Data were collected between May 2014 and September 2015 and analyzed between September 2015 and February 2016. Focused exome sequencing was used to identify candidate variants. Family studies, long-range polymerase chain reaction with cloning, and complementary DNA sequencing were used to confirm pathogenicity. Of these 5 patients, 4 were men (80%); mean age at onset of ALSP was 29 years (range, 15-44 years). Biallelic mutations in the alanyl-transfer (t)RNA synthetase 2 (AARS2) gene were found in all 5 patients. Frameshifting and splice site mutations were common, found in 4 of 5 patients, and sequencing of complementary DNA from affected patients confirmed that the variants were loss of function. All patients presented in adulthood with prominent cognitive, neuropsychiatric, and upper motor neuron signs. Magnetic resonance imaging in

  3. A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti.

    PubMed

    Mullins, Elwood A; Francois, Julie A; Kappock, T Joseph

    2008-07-01

    Microbes tailor macromolecules and metabolism to overcome specific environmental challenges. Acetic acid bacteria perform the aerobic oxidation of ethanol to acetic acid and are generally resistant to high levels of these two membrane-permeable poisons. The citric acid cycle (CAC) is linked to acetic acid resistance in Acetobacter aceti by several observations, among them the oxidation of acetate to CO2 by highly resistant acetic acid bacteria and the previously unexplained role of A. aceti citrate synthase (AarA) in acetic acid resistance at a low pH. Here we assign specific biochemical roles to the other components of the A. aceti strain 1023 aarABC region. AarC is succinyl-coenzyme A (CoA):acetate CoA-transferase, which replaces succinyl-CoA synthetase in a variant CAC. This new bypass appears to reduce metabolic demand for free CoA, reliance upon nucleotide pools, and the likely effect of variable cytoplasmic pH upon CAC flux. The putative aarB gene is reassigned to SixA, a known activator of CAC flux. Carbon overflow pathways are triggered in many bacteria during metabolic limitation, which typically leads to the production and diffusive loss of acetate. Since acetate overflow is not feasible for A. aceti, a CO(2) loss strategy that allows acetic acid removal without substrate-level (de)phosphorylation may instead be employed. All three aar genes, therefore, support flux through a complete but unorthodox CAC that is needed to lower cytoplasmic acetate levels.

  4. 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.

  5. 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

    2015-12-20

    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.

  6. SU-E-T-644: QuAArC: A 3D VMAT QA System Based On Radiochromic Film and Monte Carlo Simulation of Log Files

    SciTech Connect

    Barbeiro, A.R.; Ureba, A.; Baeza, J.A.; Jimenez-Ortega, E.; Plaza, A. Leal; Linares, R.; Mateos, J.C.; Velazquez, S.

    2015-06-15

    Purpose: VMAT involves two main sources of uncertainty: one related to the dose calculation accuracy, and the other linked to the continuous delivery of a discrete calculation. The purpose of this work is to present QuAArC, an alternative VMAT QA system to control and potentially reduce these uncertainties. Methods: An automated MC simulation of log files, recorded during VMAT treatment plans delivery, was implemented in order to simulate the actual treatment parameters. The linac head models and the phase-space data of each Control Point (CP) were simulated using the EGSnrc/BEAMnrc MC code, and the corresponding dose calculation was carried out by means of BEAMDOSE, a DOSXYZnrc code modification. A cylindrical phantom was specifically designed to host films rolled up at different radial distances from the isocenter, for a 3D and continuous dosimetric verification. It also allows axial and/or coronal films and point measurements with several types of ion chambers at different locations. Specific software was developed in MATLAB in order to process and evaluate the dosimetric measurements, which incorporates the analysis of dose distributions, profiles, dose difference maps, and 2D/3D gamma index. It is also possible to obtain the experimental DVH reconstructed on the patient CT, by an optimization method to find the individual contribution corresponding to each CP on the film, taking into account the total measured dose, and the corresponding CP dose calculated by MC. Results: The QuAArC system showed high reproducibility of measurements, and consistency with the results obtained with the commercial system implemented in the verification of the evaluated treatment plans. Conclusion: A VMAT QA system based on MC simulation and high resolution dosimetry with film has been developed for treatment verification. It shows to be useful for the study of the real VMAT capabilities, and also for linac commissioning and evaluation of other verification devices.

  7. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

    PubMed

    Deng, Han; Qi, Xingshun; Guo, Xiaozhong

    2015-10-01

    Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis.

  8. Impact of ADC non-linearities on the sensitivity to sterile keV neutrinos with a KATRIN-like experiment

    NASA Astrophysics Data System (ADS)

    Dolde, Kai; Mertens, Susanne; Radford, David; Bode, Tobias; Huber, Anton; Korzeczek, Marc; Lasserre, Thierry; Slezak, Martin

    2017-03-01

    ADC non-linearities are a major systematic effect in the search for keV-scale sterile neutrinos with tritium β-decay experiments like KATRIN. They can significantly distort the spectral shape and thereby obscure the tiny kink-like signature of a sterile neutrino. In this work we demonstrate various mitigation techniques to reduce the impact of ADC non-linearities on the tritium β-decay spectrum to a level of < ppm . The best results are achieved with a multi-pixel (≥104 pixels) detector using full waveform digitization. In this case, active-to-sterile mixing angles of the order of sin2 θ =10-7 would be accessible from the viewpoint of ADC non-linearities. With purely peak-sensing ADCs a comparable sensitivity could be reached with highly linear ADCs, sufficient non-linearity corrections or by increasing the number of pixels to ≥105 .

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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).

  14. 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).

  15. 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.

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

    NASA Image and Video Library

    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...

  17. 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…

  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

    ... potential doses to the public from the residual radioactivity at the site, it was determined that..., ``Radiological Criteria for License Termination,'' are not being met and residual radioactivity at the site...

  19. 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.

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

    PubMed Central

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

    2012-01-01

    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

  2. Current Issues in the Use of Virtual Simulations for Dismounted Soldier Training

    DTIC Science & Technology

    2006-06-01

    Team A Fire Team B SAF AAR Battle Master Bravo Fire Team Leader Squad Leader 40 ft 10 ft10 ft10 ft10 ft AAR Facility Internet Connection Figure 1...Squad Leader 40 ft 10 ft10 ft10 ft10 ft AAR Facility Internet Connection 2004 V-IMTS Network Configuration AAR Leader AAR Operator DIVAARS SL

  3. 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

  4. Large scale 3D geometry of deformation structures in the Aar massif and overlying Helvetic nappes (Central Alps, Switzerland) - A combined remote sensing and field work approach

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

    Allowing deep insight into the formation history of a rock complex, shear zones, faults and joint systems represent important sources of geological information. The granitic rocks of the Haslital valley (Switzerland) show very good outcrop conditions to study these mechanical anisotropies. Furthermore, they permit a quantitative characterisation of the above-mentioned deformation structures on the large-scale, in terms of their 3D orientation, 3D spatial distribution, kinematics and evolution in 3D. A key problem while developing valid geological 3D models is the three-dimensional spatial distribution of geological structures, particularly with increasing distance from the surface. That is especially true in regions, where only little or even no "hard" underground data (e.g. bore holes, tunnel mappings and seismics) is available. In the study area, many subsurface data are available (e.g. cross sections, tunnel and pipeline mappings, bore holes etc.). Therefore, two methods dealing with the problems mentioned are developed: (1) A data acquisition, processing and visualisation method, (2) A methodology to improve the reliability of 3D models regarding the spatial trend of geological structures with increasing depth: 1) Using aerial photographs and a high-resolution digital elevation model, a GIS-based remote-sensing structural map of large-scale structural elements (shear zones, faults) of the study area was elaborated. Based on that lineament map, (i) a shear zone map was derived and (ii) a geostatistical analysis was applied to identify sub regions applicable for serving as field areas to test the methodology presented above. During fieldwork, the shear zone map was evaluated by verifying the occurrence and spatial distribution of the structures designated by remote sensing. Additionally, the geometry of the structures (e.g. 3D orientation, width, kinematics) was characterised and parameterised accordingly. These tasks were partially done using a GPS based Slate PC and the FieldMoveTM software, in order to ease the subsequent data processing. 2) Findings from the field work were visualised in 3D using the MoveTM software suite. Applying its specific tools and incorporating own field data, the structure's near-surface 3D settings was modelled. In a second step, the combined use of surface and subsurface data helped to predict their trend with increasing distance from the surface, bypassing a height difference of partially more than 2000m. Field work shows that the remote-sensing structural map fits very well with the field observations. Nevertheless, the shear zone map underwent an iterative refinement process, based on own observations in the field as well as on already existing maps. It now clearly describes the lithological subdivision of the study area. The incorporation of the data into the 3D modelling software points towards the fact, that own large-scale data fits very well with small-scale structures provided by recent studies in the same area. Yet, their exact interplay in terms of orientation, kinematics and evolution is not clear. Additional analysis is needed in order to gain more detailed insight into the deformation history of the rocks in the study area.

  5. Identification and biochemical characterization of plant acylamino acid-releasing enzyme.

    PubMed

    Yamauchi, Yasuo; Ejiri, Yukinori; Toyoda, Yasuyuki; Tanaka, Kiyoshi

    2003-08-01

    Plant acylamino acid-releasing enzyme (AARE) catalyzing the N-terminal hydrolysis of N(alpha)-acylpeptides to release N(alpha)-acylated amino acids, was biochemically characterized using recombinant and native AAREs. A cDNA encoding a deduced Arabidopsis thaliana AARE (AtAARE) was cloned and sequenced. The deduced amino acid sequence encoded a 764 amino acid protein of 83.9 kDa, which was 31.8% identical with that of rat AARE. In particular, the proposed catalytic residues (Ser, Asp, and His) of AARE, called the "catalytic triad residues, " were completely conserved. Recombinant AtAARE was expressed in Escherichia coli and confirmed to be a functional AARE. Native AAREs were prepared from A. thaliana and cucumber (Cucumis sativus, L.) plants. Both native AAREs were tetrameric proteins of 350 kDa comprising four subunits of 82 kDa, and showed typical enzymological properties of other AAREs, i.e. sensitivity to diisopropyl fluorophosphate, an optimum pH of around 7.0, and an optimum temperature of 37 degrees C. Both the native and recombinant AAREs were immunochemically homologous. Intracelluar fractionation analysis showed that the AARE was mainly present in the stroma of chloroplasts. Native AARE degraded the glycated ribulose-1,5-bisphoshate carboxylase/oxygenase protein but not the native protein. Thus, plant AARE might be involved in not only catalysis of the N-terminal hydrolysis of N(alpha)-acylpeptides but also the elimination of glycated proteins.

  6. 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.

  7. After Action Reviews With the Ground Soldier System

    DTIC Science & Technology

    2005-09-01

    The After Action Review (AAR) is critical to the Army’s training process . Much work conducted by the U.S. Army Research Institute (ARI) has been...them to apply their expertise and wisdom to the AAR process . Consequently, the aids suggested here should be viewed as providing a large collection...25 OC use of the LW System in the AAR Process

  8. The Adolescent Assessment/Referral System Manual.

    ERIC Educational Resources Information Center

    Rahdert, Elizabeth R., Ed.

    The goal of the Adolescent Assessment/Referral System (AARS) project was to identify, collect, and organize all the appropriate materials associated with assessment and treatment referral for troubled youth 12 through 19 years of age. This document discusses the components of the AARS. After an introduction to the AARS, the structure and function…

  9. The comparative effect of subjective and objective after-action reviews on team performance on a complex task.

    PubMed

    Villado, Anton J; Arthur, Winfred

    2013-05-01

    The after-action review (AAR; also known as the after-event review or debriefing) is an approach to training based on a review of trainees' performance on recently completed tasks or performance events. Used by the military for decades, nonmilitary organizations' use of AARs has increased dramatically in recent years. Despite the prevalence of AARs, empirical research investigating their effectiveness has been limited. This study sought to investigate the comparative effectiveness of objective AARs (reviews based on an objective recording and playback of trainees' recent performance) and subjective AARs (reviews based on a subjective, memory-based recall of trainees' recent performance). One hundred eighty-eight individuals, participating in 47 4-person teams, were assigned to 1 of 3 AAR conditions and practiced and tested on a cognitively complex performance task. Although there were no significant differences between objective and subjective AAR teams across the 5 training outcomes, AAR teams had higher levels of team performance, team efficacy, openness of communication, and cohesion than did non-AAR teams but no differences in their levels of team declarative knowledge. Our results suggest that AARs are effective at enhancing training outcomes. Furthermore, AARs may not be dependent on objective reviews and therefore may be a viable training intervention when objective reviews are not feasible or possible. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  10. High salt diet exacerbates vascular contraction in the absence of adenosine A2A receptor

    PubMed Central

    Pradhan, Isha; Zeldin, Darryl C.; Ledent, Catherine; Mustafa, S. Jamal; Falck, John R.; Nayeem, Mohammed A

    2014-01-01

    High salt (4%NaCl, HS) diet modulates adenosine-induced vascular response through adenosine A2A-receptor (A2AAR). Evidence suggests A2AAR stimulates cyp450-epoxygenases, leading to epoxyeicosatrienoic acids (EETs) generation. The aim of this study was to understand the vascular reactivity to HS and underlying signaling mechanism in the presence or absence of A2AAR. Therefore, we hypothesized that HS enhances adenosine-induced relaxation through EETs in A2AAR+/+, but exaggerates contraction in A2AAR−/−. Organ-bath and Western-blot experiments were conducted in HS and normal salt (NS, 0.18% NaCl)-fed A2AAR+/+ and A2AAR−/− mice aortae. HS produced concentration-dependent relaxation to non-selective adenosine analog, NECA in A2AAR+/+, whereas contraction was observed in A2AAR−/− mice and this was attenuated by A1AR antagonist (DPCPX). CGS-21680 (selective A2AAR-agonist) enhanced relaxation in HS-A2AAR+/+ vs. NS-A2AAR+/+, that was blocked by EETs antagonist (14,15-EEZE). Compared to NS, HS significantly upregulated expression of vasodilators A2AAR and cyp2c29, while vasoconstrictors A1AR and cyp4a in A2AAR+/+ were downregulated. In A2AAR−/− mice, however, HS significantly downregulated the expression of cyp2c29, while A1AR and cyp4a were upregulated compared to A2AAR+/+ mice. Hence, our data suggest that in A2AAR+/+, HS enhances A2AAR-induced relaxation through increased cyp-expoxygenases-derived EETs and decreased A1AR levels, whereas in A2AAR−/−, HS exaggerates contraction through decreased cyp-epoxygenases and increased A1AR levels. PMID:24390173

  11. An after-action review tool for EDs: learning from mass casualty incidents.

    PubMed

    Tami, Greenberg; Bruria, Adini; Fabiana, Eden; Tami, Chen; Tali, Ankri; Limor, Aharonson-Daniel

    2013-05-01

    Conducting a thorough after-action review (AAR) process is an important component in improving preparedness for mass casualty incidents (MCIs). The study aimed to develop a structured AAR tool for use by medical teams in emergency departments after an MCI and to identify the best possible procedure for its conduct. On the basis of knowledge acquired from an extensive literature review, a structured tool for conducting an AAR in the emergency department was developed. A modified Delphi process was conducted to achieve content validity of the tool, involving 48 medical professionals from all 6 level I trauma centers in Israel. The AAR tool was tested during a simulated MCI drill. All experts support the conduct of an AAR in the ED after an MCI to build and maintain capacity for an adequate emergency response. More than 80% agreement was achieved regarding 14 components that were implemented in the proposed AAR tool. Ninety-four percent perceived that AARs should be conducted within 24 hours from the event using both written reports and face-to-face discussions. Both physicians and nurses should participate. The incident manager should lead the AAR, limiting the time allocated for each speaker and for the AAR in whole. Conducting a structured AAR in all emergency departments after an MCI facilitates both learning lessons regarding the function of the medical staff and ventilation of feelings, thus mitigating anxieties and expediting a speedy return to normalcy. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. 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

  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. Angiographic validation of magnetic resonance assessment of myocardium at risk in non-ST-elevation myocardial infarction.

    PubMed

    Buckert, Dominik; Mariyadas, Manuela; Walcher, Thomas; Rasche, Volker; Wöhrle, Jochen; Rottbauer, Wolfgang; Bernhardt, Peter

    2013-08-01

    In the setting of acute myocardial ischemia, the hypoperfused portion of the myocardium is in danger of becoming irreversibly injured. This portion is called the area at risk (AAR). It is of clinical interest to be able to estimate the AAR for further evaluation and improvement of different revascularization strategies. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) has been shown to be a jeopardy score with a good performance for angiographic assessment of the myocardium supplied by a coronary vessel, representing the AAR. Recently, cardiac magnetic resonance imaging (CMR) has been demonstrated to also provide good results in determining the AAR, especially in the setting of acute ST-elevation infarction patients. Therefore, the aim of our trial was to compare T2-weighted CMR imaging for assessment of AAR in patients with non-ST-elevation myocardial infarction (NSTEMI) and to validate this approach against the angiographic APPROACH-score. We enrolled sixty-four patients presenting with acute NSTEMI that underwent coronary X-ray angiography within 72 h of symptom onset. Two blinded readers performed offline angiographic AAR assessment using the modified APPROACH-score, as being described elsewhere. Furthermore, with the use of a semi-automatic T2w-CMR approach, the AAR was quantified by two fully blinded readers. The resulting mean AAR determined by the modified APPROACH-score was 28.6 ± 10.0 %. The mean CMR derived AAR was 27.6 ± 12.7 %. CMR assessment tended to slightly underestimate the AAR in comparison to angiographic scoring (difference -0.09 ± 7.6 %). There is a good correlation between the AAR assessed by CMR and by angiography (r = 0.65, p < 0.001). T2-weigthed CMR is able to quantify the AAR with very good correlation to the angiographic APPROACH-score in NSTEMI patients.

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

    PubMed Central

    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

  16. Cross-talk from β-adrenergic receptors modulates α2A-adrenergic receptor endocytosis in sympathetic neurons via protein kinase A and spinophilin.

    PubMed

    Cottingham, Christopher; Lu, Roujian; Jiao, Kai; Wang, Qin

    2013-10-04

    Inter-regulation of adrenergic receptors (ARs) via cross-talk is a long appreciated but mechanistically unclear physiological phenomenon. Evidence from the AR literature and our own extensive studies on regulation of α2AARs by the scaffolding protein spinophilin have illuminated a potential novel mechanism for cross-talk from β to α2ARs. In the present study, we have characterized a mode of endogenous AR cross-talk in native adrenergic neurons whereby canonical βAR-mediated signaling modulates spinophilin-regulated α2AAR endocytosis through PKA. Our findings demonstrate that co-activation of β and α2AARs, either by application of endogenous agonist or by simultaneous stimulation with distinct selective agonists, results in acceleration of endogenous α2AAR endocytosis in native neurons. We show that receptor-independent PKA activation by forskolin is sufficient to accelerate α2AAR endocytosis and that α2AAR stimulation alone drives accelerated endocytosis in spinophilin-null neurons. Endocytic response acceleration by β/α2AAR co-activation is blocked by PKA inhibition and lost in spinophilin-null neurons, consistent with our previous finding that spinophilin is a substrate for phosphorylation by PKA that disrupts its interaction with α2AARs. Importantly, we show that α2AR agonist-mediated α2AAR/spinophilin interaction is blocked by βAR co-activation in a PKA-dependent fashion. We therefore propose a novel mechanism for cross-talk from β to α2ARs, whereby canonical βAR-mediated signaling coupled to PKA activation results in phosphorylation of spinophilin, disrupting its interaction with α2AARs and accelerating α2AAR endocytic responses. This mechanism of cross-talk has significant implications for endogenous adrenergic physiology and for therapeutic targeting of β and α2AARs.

  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. TRITIUM-β-DECAY Experiments - the Direct way to the Absolute Neutrino Mass

    NASA Astrophysics Data System (ADS)

    Bornschein, Lutz

    2013-11-01

    Tritium-β-decay experiments provide the most sensitive approach to measure the absolute neutrino mass in a model independent way. The Karlsruhe Tritium Neutrino experiment KATRIN will measure the neutrino mass scale with an expected sensitivity of 0.2 eV/c2 (90% C.L.) and so will help to clarify the roles of neutrinos in the early universe. KATRIN investigates spectroscopically the electron spectrum from tritium β-decay 3 H -> 3 {He} + {e}^ - + bar ν e close to the kinematic endpoint of 18.6 keV. It will use a windowless gaseous tritium source in combination with an electrostatic filter for energy analysis. KATRIN is currently under construction at the Karlsruhe Institute of Technology (KIT) Campus North. This proceeding will give an overview of the status of the main components of the KATRIN experiment.

  19. After-Action Reviews - who conducts them?

    Treesearch

    Anne E. Black; Kathleen Sutcliffe; Michelle Barton

    2009-01-01

    Reflecting on the links between intentions and outcomes is a key practice of a learning organization (Garvin 2000). The After-Action Review (AAR) is a formal reflection process intended to assist groups in capturing lessons learned from a task. AARs typically ask four questions regarding fire-response operations: (1) what did we set out to do, (2) what actually...

  20. After Action Reviews: Current Observations and Recommendations

    DTIC Science & Technology

    2007-01-01

    starting point for a training aid or self-assessment tool to facilitate this process . Based on the September briefing, the Operations Group immediately...1 Purpose of the Current Research ............................................................................ 1 The Arm y’s AAR Process ...Current Research The purpose of this research was to examine the AAR process as practiced at the Joint Readiness Training Center (JRTC). The Global War

  1. Free-flying dynamics and control of an astronaut assistant robot based on fuzzy sliding mode algorithm

    NASA Astrophysics Data System (ADS)

    Gao, Qing; Liu, Jinguo; Tian, Tongtong; Li, Yangmin

    2017-09-01

    Space robots can perform some tasks in harsh environment as assistants of astronauts or substitutions of astronauts. Taking the limited working time and the arduous task of the astronauts in the space station into account, an astronaut assistant robot (AAR-2) applied in the space station is proposed and designed in this paper. The AAR-2 is achieved with some improvements on the basis of AAR-1 which was designed before. It can exploit its position and attitude sensors and control system to free flight or hover in the space cabin. And it also has a definite environmental awareness and artificial intelligence to complete some specified tasks under the control of astronauts or autonomously. In this paper, it mainly analyzes and controls the 6-DOF motion of the AAR-2. Firstly, the system configuration of AAR-2 is specifically described, and the movement principles are analyzed. Secondly, according to the physical model of the AAR-2, the Newton - Euler equation is applied in the preparation of space dynamics model of 6-DOF motion. Then, according to the mathematical model's characteristics which are nonlinear and strong coupling, a dual closed loop position and attitude controller based on fuzzy sliding mode control is proposed and designed. Finally, simulation experiments are appropriate to provide for AAR-2 control system by using Matlab/Simulink. From the simulation results it can be observed that the designed fuzzy sliding mode controller can control the 6-DOF motion of AAR-2 quickly and precisely.

  2. 77 FR 42704 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... (LONGBOW component), 12 AN/APR-48A Radar Frequency Interferometers, 28 AN/AAR-57(V)7 Common Missile Warning... Global Positioning Systems with Inertial Navigation, 30 30mm Automatic Chain Guns, 8 Aircraft Ground...-48A Radar Frequency Interferometers, 28 AN/AAR-57(V)7 Common Missile Warning Systems, 30 AN/AVR-2B...

  3. 77 FR 69437 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-19

    ..., installed systems, and related software. 4. Inertial Navigation/Global Positioning System (INS/GPS): This... software is CONFIDENTIAL. Hardware is UNCLASSIFIED. 8. Radar Warning Receiver (AN/ALR-56M): The AN/ALR-56M.... 9. Missile Approach Warning System (AN/AAR-47): The AN/AAR-47 is an aircraft passive MWS designed...

  4. 78 FR 31523 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ... Processors/ Repeaters, 14 AN/AAR-54 Missile Warning Sensors, User Data Module Cards and Control Interface...), 11 Small Laser Transmitter Assemblies, 3 System Processors/Repeaters, 14 AN/AAR-54 Missile Warning... leadership, promoting the global engagement of a friendly country. The proposed sale of this equipment and...

  5. 76 FR 81482 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... Royce engines; 12 Electronic Warfare Self Protection Suites; 12 AAR-47A(V)2 Missile Warning Systems; 12 ALE-47(V) Threat Adaptive Countermeasures Dispensing Systems; 12 APR-39 Radar Warning Receivers; 13 AN... Protection Suites; 12 AAR-47A(V)2 Missile Warning Systems; 12 ALE-47(V) Threat Adaptive Countermeasures...

  6. 2014 Australian Association for Research in Education Presidential Address: Educational Research and the Tree of Knowledge in a Post Human Digital Age

    ERIC Educational Resources Information Center

    Moss, Julianne

    2016-01-01

    The 2014, 41st Australian Association for Research in Education (AARE) presidential address is both inspired and guided by the discursive genres of presidential addresses and the role of the president in a member association such as AARE. In the address, typically the president speaks to the members on an issue or issues that are to shape or…

  7. 49 CFR 179.400-8 - Thickness of plates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... tensile strength of the plate material, as prescribed in AAR Specifications for Tank Cars, appendix M... inches; S = minimum tensile strength of the plate material, as prescribed in AAR Specifications for Tank..., in inches; r = inside knuckle radius, in inches; S = minimum tensile strength of plate material, as...

  8. 49 CFR 179.400-8 - Thickness of plates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... = minimum required bursting pressure in psig; d = inside diameter, in inches; S = minimum tensile strength...; S = minimum tensile strength of the plate material, as prescribed in AAR Specifications for Tank... = inside knuckle radius, in inches; S = minimum tensile strength of plate material, as prescribed in AAR...

  9. 49 CFR 179.400-8 - Thickness of plates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... = minimum required bursting pressure in psig; d = inside diameter, in inches; S = minimum tensile strength...; S = minimum tensile strength of the plate material, as prescribed in AAR Specifications for Tank... = inside knuckle radius, in inches; S = minimum tensile strength of plate material, as prescribed in AAR...

  10. 49 CFR 179.400-8 - Thickness of plates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... = minimum required bursting pressure in psig; d = inside diameter, in inches; S = minimum tensile strength...; S = minimum tensile strength of the plate material, as prescribed in AAR Specifications for Tank... = inside knuckle radius, in inches; S = minimum tensile strength of plate material, as prescribed in AAR...

  11. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS...: (1) AAR means Association of American Railroads. (2) Approved means approval by the AAR Tank Car... 173 of this chapter also apply. (6) F means degrees Fahrenheit. (7) NGT means National Gas...

  12. 49 CFR Appendix A to Part 215 - Railroad Freight Car Components

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... 2. Farlow draft attachment. E.Plain journal bearings: Cartridge type. F.Roller bearings: 1. Nippon Sieko Kabushiki Kaish (NSK) size 61/2″ by 12″ (marked “AAR 11”). 2. Hyatt cylindrical bearing, all sizes... with letters “RJ” stamped on the end of the journal. C.Couplers: 1. AAR type “D”, top or...

  13. 76 FR 34802 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... locomotives equipped with New York Air Brake (NYAB) CCB-26 model brake systems in the same group as locomotives equipped with CCB-II brake systems. Also, AAR has requested that the distinction between...-26 brake system to the CCB-II brake system already covered under the waiver. In addition, AAR states...

  14. 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…

  15. Virtual Observer Controller (VOC) for Small Unit Infantry Laser Simulation Training

    DTIC Science & Technology

    2007-04-01

    KIA, WIA) Weapons/Ordnance Expects the Soldier to report the discovery to higher. Discovery VOC AAR Capabilities The VOC AAR user interface represents...organization can be depicted as in the figure below. Mehd ehd Mto XMethod [ to The tree structure results from the explicit intention of the CTA to

  16. Utilization of Participatory Electronic Technology in Group Communication and Decision-Making Processes. AIR 1983 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Roberts, Adrian R.; Garg, Devendra P.

    The use of an electronic feedback system, the Anonymous Audience Response System (AARS), in educational decision making is described, and the results of use studies in North Carolina are discussed. The AARS insures anonymity of an individual participant's responses, and at the same time, provides immediate feedback of the group's collective…

  17. 2014 Australian Association for Research in Education Presidential Address: Educational Research and the Tree of Knowledge in a Post Human Digital Age

    ERIC Educational Resources Information Center

    Moss, Julianne

    2016-01-01

    The 2014, 41st Australian Association for Research in Education (AARE) presidential address is both inspired and guided by the discursive genres of presidential addresses and the role of the president in a member association such as AARE. In the address, typically the president speaks to the members on an issue or issues that are to shape or…

  18. 75 FR 13775 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ...; Comment Request, 1660-NEW; Homeland Security Exercise and Evaluation Program (HSEEP) After Action Report... 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)....

  19. 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. © 2015 S. Karger AG, Basel.

  20. Trends in organised sport membership: impact on sustainability.

    PubMed

    Eime, Rochelle; Payne, Warren; Harvey, Jack

    2009-01-01

    Sporting clubs play a key role in community-level physical activity. This study investigated participation trends in sport club membership. A survey of 50 State sports governing bodies in Victoria, Australia collected information on factors affecting membership trends. The records for four of these sports were analysed for the 6 years, 1998-2003. Three sports reported increases in total membership (average annual rates (AARs): 0.3, 1.9 and 12.4%), and one reported a decrease (AAR: -1.0%). There was a decrease in both the absolute number (AARs: -1.1%, -2.3%, and -3.5%) and the proportion (AARs: -0.5%, -0.7%, -1.7% and -2.3%) of adult members. The number of junior club members increased slightly over the 6-year period in two sports (AARs: 0.5% and 0.7%), increased substantially in one (AAR: 12.2%) and decreased in one (AAR: -6.7%). The number of members playing modified sports increased in two sports (AARs: 2.8% and 3.3%), increased substantially in one (AARs: 53.1%) and decreased in one (AAR: -16.3%). The introduction of modified sport for younger participants is relatively new, resulting in sports accessing a new market to maintain or increase their total membership. However, the influx of younger members was not matched by associated increases in adult members. This places increased pressure upon adult members to maintain the infrastructure to support younger members. The issues of decreased adult membership and increased junior membership need to be addressed in order to ensure that community sporting clubs can be sustained and fulfil their potential to act as a vehicle for public health initiatives.

  1. Assessment of nasal obstruction with rhinomanometry and subjective scales and outcomes of surgical and medical treatment.

    PubMed

    Lara-Sánchez, Hugo; Álvarez Nuño, Candelas; Gil-Carcedo Sañudo, Elisa; Mayo Iscar, Agustín; Vallejo Valdezate, Luis Ángel

    Prospective study of patients with nasal obstruction (NO) in order to measure therapeutic success by anterior active rhinomanometry (AAR), Nasal Obstruction Symptom Evaluation (NOSE) scale and Visual Analogue Scale (VAS) and to establish the correlation between these tests. Patients with NO, on whom we performed an AAR, NOSE and VAS scales at baseline and after medical treatment (topical nasal steroid) or surgery (septoplasty, turbinoplasty or septoplasty and turbinoplasty). The nasal flow obtained by the AAR and the score of both subjective scales (NOSE and VAS) were compared and analyzed. A total of 102 patients were included in the study. Surgical treatment resulted in statistically significant differences with the AAR and the subjective scales. While in patients with medical treatment there was an increase in the AAR nasal flow but without statistical significance (P=.1363). The correlation between the AAR, the NOSE and VAS scales was measured finding a strong correlation between the NOSE and VAS scales only (r=.83327). The patients with NO treated surgically have better results when these are evaluated by AAR or with subjective scales. There is no significant correlation between AAR, NOSE and VAS scales, this is considered to be because the AAR and subjective scales are complementary and measure different aspects of NO. The AAR and subjective scales are useful tools to be used together for the follow up of patients with NO. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  2. Myocardium at risk in ST-segment elevation myocardial infarction comparison of T2-weighted edema imaging with the MR-assessed endocardial surface area and validation against angiographic scoring.

    PubMed

    Fuernau, Georg; Eitel, Ingo; Franke, Vinzenz; Hildebrandt, Lysann; Meissner, Josefine; de Waha, Suzanne; Lurz, Philipp; Gutberlet, Matthias; Desch, Steffen; Schuler, Gerhard; Thiele, Holger

    2011-09-01

    The objective of this study was to assess the area at risk (AAR) in ST-segment elevation myocardial infarction with 2 different cardiac magnetic resonance (CMR) imaging methods and to compare them with the validated angiographic Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) in a large consecutive patient cohort. Edema imaging with T(2)-weighted CMR and the endocardial surface area (ESA) assessed by late gadolinium enhancement have been introduced as relatively new methods for AAR assessment in ST-segment elevation myocardial infarction. However, data on the utility and validation of these techniques are limited. A total of 197 patients undergoing primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction were included. AAR (assessed with T(2)-weighted edema imaging and the ESA method), infarct size, and myocardial salvage (AAR minus infarct size) were determined by CMR 2 to 4 days after primary angioplasty. Angiographic AAR scoring was performed by use of the APPROACH-score. All measurements were done offline by blinded observers. The AAR assessed by T(2)-weighted imaging showed good correlation with the angiographic AAR (r = 0.87; p < 0.001), whereas the ESA showed only a moderate correlation either to T(2)-weighted imaging (r = 0.56; p < 0.001) or the APPROACH-score (r = 0.44; p < 0.001). Mean AAR by ESA (20.0 ± 11.7% of left ventricular mass) was significantly (p < 0.001) smaller than the AAR assessed by T(2)-weighted imaging (35.6 ± 10.9% of left ventricular mass) or the APPROACH-score (27.9 ± 10.5% of left ventricular mass) and showed a significant negative dependence on myocardial salvage index. In contrast, no dependence of T(2)-weighted edema imaging or the APPROACH-score on myocardial salvage index was seen. The AAR can be reliably assessed by T(2)-weighted CMR, whereas assessment of the AAR by ESA seems to be dependent on the degree of myocardial salvage, thereby

  3. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity

    PubMed Central

    Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity. PMID:27694818

  4. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity.

    PubMed

    Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-10-03

    Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity.

  5. A2A adenosine receptors are up-regulated in lymphocytes from amyotrophic lateral sclerosis patients.

    PubMed

    Vincenzi, Fabrizio; Corciulo, Carmen; Targa, Martina; Casetta, Ilaria; Gentile, Mauro; Granieri, Enrico; Borea, Pier Andrea; Popoli, Patrizia; Varani, Katia

    2013-09-01

    Adenosine, a purine nucleoside interacting with A1, A2A, A2B and A3 adenosine receptors (ARs), is a potent endogenous modulator of inflammatory and neuronal processes involved in the pathophysiology of several neurodegenerative diseases. In the present study, ARs were investigated in lymphocytes from patients with amyotrophic lateral sclerosis (ALS) and compared with age-matched healthy subjects. In ALS patients A2AARs were analysed by using RT-PCR, Western blotting and saturation binding experiments. The effect of A2AAR stimulation on cyclic AMP levels was evaluated in lymphocytes from ALS patients and healthy subjects. An up-regulation of A2AARs was observed in ALS patients with respect to healthy subjects while A1, A2B and A3AR affinity and density did not change. In ALS patients, the A2AAR density values correlated with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, the stimulation of A2AARs mediated a significant increase in cyclic AMP levels in lymphocytes from ALS patients, with a higher potency than in lymphocytes from healthy subjects. In conclusion, the positive correlation between A2AAR density and ALSFRS-R scores could indicate a possible protective effect of this receptor subtype, representing an interesting starting point for the study of alternative therapeutic approaches for ALS based on A2AAR modulation.

  6. 25-Hydroxyvitamin D, IL-31, and IL-33 in children with allergic disease of the airways.

    PubMed

    Bonanno, Anna; Gangemi, Sebastiano; La Grutta, Stefania; Malizia, Velia; Riccobono, Loredana; Colombo, Paolo; Cibella, Fabio; Profita, Mirella

    2014-01-01

    Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH) Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC), 11 allergic rhinitis (AR) patients, and 35 allergic asthma with rhinitis (AAR) patients. We found significant lower levels of 25(OH) Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH) Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH) Vit D. In AAR 25(OH) Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH) Vit D in AR and AAR. In conclusion, low levels of 25(OH) Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity.

  7. 25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

    PubMed Central

    Bonanno, Anna; Gangemi, Sebastiano; La Grutta, Stefania; Malizia, Velia; Profita, Mirella

    2014-01-01

    Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH) Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC), 11 allergic rhinitis (AR) patients, and 35 allergic asthma with rhinitis (AAR) patients. We found significant lower levels of 25(OH) Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH) Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH) Vit D. In AAR 25(OH) Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH) Vit D in AR and AAR. In conclusion, low levels of 25(OH) Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity. PMID:25061262

  8. 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.

  9. Dual allosteric modulation of opioid antinociceptive potency by a2A-adrenoceptors

    PubMed Central

    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.

    2015-01-01

    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 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 α2AKO 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. Genetic evidence for involvement of multiple effector systems in alpha 2A-adrenergic receptor inhibition of stimulus-secretion coupling.

    PubMed

    Lakhlani, P P; Lovinger, D M; Limbird, L E

    1996-07-01

    The alpha 2A-adrenergic receptor (alpha 2AAR), via its interaction with the pertussis toxin-sensitive Gi/G(o) class of G proteins, modulates multiple effector systems, including inhibition of adenylyl cyclase and Ca2+ channels and activation of K+ channels. Mutation of a membrane-embedded aspartate residue, highly conserved among G protein-coupled receptors, in the alpha 2AAR to asparagine (D79N alpha 2AAR) results in selective uncoupling of the receptor to K+ currents but retention of inhibition of cAMP production and of voltage-sensitive Ca2+ currents when expressed in AtT20 anterior pituitary cells in culture. It is known that attenuation of cAMP synthesis alone cannot account for alpha 2AAR suppression of stimulus-secretion coupling; thus, the D79N alpha 2AAR provides a unique tool with which to assess the relative contribution of K+ current activation and Ca2+ current suppression in mediating the cellular responses of alpha 2AAR. The wild-type alpha 2AAR suppresses basal and secretagogue-evoked adrenocorticotropic hormone (ACTH) release in a manner indistinguishable from response to the endogenous somatostatin receptor. In contrast, the D79N alpha 2AAR does not attenuate basal ACTH release and is only partially effective in suppressing ACTH secretion evoked by the secretagogue isoproterenol. Regulation of ACTH release evoked by 8-bromo-cAMP, which bypasses receptor regulation of cAMP synthesis, suggests that attenuation of cAMP production, although not sufficient for inhibition of ACTH secretion, nevertheless participates in a functionally relevant manner. Taken together, the present findings indicate that alpha 2AAR-mediated suppression of neuropeptide secretion requires concomitant regulation of K+ and Ca2+ currents in parallel with attenuation of cAMP production.

  11. Can one measure the Cosmic Neutrino Background?

    NASA Astrophysics Data System (ADS)

    Faessler, Amand; Hodák, Rastislav; Kovalenko, Sergey; Šimkovic, Fedor

    The Cosmic Microwave Background (CMB) yields information about our Universe at around 380,000 years after the Big Bang (BB). Due to the weak interaction of the neutrinos with matter, the Cosmic Neutrino Background (CNB) should give information about a much earlier time of our Universe, around one second after the BB. Probably, the most promising method to "see" the CNB is the capture of the electron neutrinos from the Background by Tritium, which then decays into 3He and an electron with the energy of the the Q-value = 18.562 keV plus the electron neutrino rest mass. The "KArlsruhe TRItium Neutrino" (KATRIN) experiment, which is in preparation, seems presently the most sensitive proposed method for measuring the electron antineutrino mass. At the same time, KATRIN can also look by the reaction νe(˜1.95K) + 3H → 3He + e-(Q = 18.6keV + mνec2). The capture of the Cosmic Background Neutrinos (CNB) should show in the electron spectrum as a peak by the electron neutrino rest mass above Q. Here, the possibility to see the CNB with KATRIN is studied. A detection of the CNB by KATRIN seems not to be possible at the moment. But KATRIN should be able to determine an upper limit for the local electron neutrino density of the CNB.

  12. Can one measure the Cosmic Neutrino Background?

    NASA Astrophysics Data System (ADS)

    Faessler, Amand; Hodák, Rastislav; Kovalenko, Sergey; Šimkovic, Fedor

    The Cosmic Microwave Background (CMB) yields information about our Universe at around 380,000 years after the Big Bang (BB). Due to the weak interaction of the neutrinos with matter, the Cosmic Neutrino Background (CNB) should give information about a much earlier time of our Universe, around one second after the BB. Probably, the most promising method to “see” the CNB is the capture of the electron neutrinos from the Background by Tritium, which then decays into 3He and an electron with the energy of the the Q-value = 18.562keV plus the electron neutrino rest mass. The “KArlsruhe TRItium Neutrino” (KATRIN) experiment, which is in preparation, seems presently the most sensitive proposed method for measuring the electron antineutrino mass. At the same time, KATRIN can also look by the reaction νe(˜ 1.95K) +3H →3He + e‑(Q = 18.6keV + m νec2). The capture of the Cosmic Background Neutrinos (CNB) should show in the electron spectrum as a peak by the electron neutrino rest mass above Q. Here, the possibility to see the CNB with KATRIN is studied. A detection of the CNB by KATRIN seems not to be possible at the moment. But KATRIN should be able to determine an upper limit for the local electron neutrino density of the CNB.

  13. Temporal and spatial characteristics of the area at risk investigated using computed tomography and T1-weighted magnetic resonance imaging

    PubMed Central

    van der Pals, Jesper; Hammer-Hansen, Sophia; Nielles-Vallespin, Sonia; Kellman, Peter; Taylor, Joni; Kozlov, Shawn; Hsu, Li-Yueh; Chen, Marcus Y.; Arai, Andrew E.

    2015-01-01

    Aims Cardiovascular magnetic resonance (CMR) imaging can measure the myocardial area at risk (AAR), but the technique has received criticism for inadequate validation. CMR commonly depicts an AAR that is wider than the infarct, which in turn would require a lateral perfusion gradient within the AAR. We investigated the presence of a lateral perfusion gradient within the AAR and validated CMR measures of AAR against three independent reference standards of high quality. Methods and results Computed tomography (CT) perfusion imaging, microsphere blood flow analysis, T1-weighted 3T CMR and fluorescent microparticle pathology were used to investigate the AAR in a canine model (n = 10) of ischaemia and reperfusion. AAR size by CMR correlated well with CT (R2 = 0.80), microsphere blood flow (R2 = 0.80), and pathology (R2 = 0.74) with good limits of agreement [−0.79 ± 4.02% of the left ventricular mass (LVM) vs. CT; −1.49 ± 4.04% LVM vs. blood flow and −1.01 ± 4.18% LVM vs. pathology]. The lateral portion of the AAR had higher perfusion than the core of the AAR by CT perfusion imaging (40.7 ± 11.8 vs. 25.2 ± 17.7 Hounsfield units, P = 0.0008) and microsphere blood flow (0.11 ± 0.04 vs. 0.05 ± 0.02 mL/g/min, lateral vs. core, P = 0.001). The transmural extent of MI was lower in the lateral portion of the AAR than the core (28.2 ± 10.2 vs. 17.4 ± 8.4% of the wall, P = 0.001). Conclusion T1-weighted CMR accurately quantifies size of the AAR with excellent agreement compared with three independent reference standards. A lateral perfusion gradient results in lower transmural extent of infarction at the edges of the AAR compared with the core. PMID:25881901

  14. 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

  15. A(2A) adenosine receptors are differentially modulated by pharmacological treatments in rheumatoid arthritis patients and their stimulation ameliorates adjuvant-induced arthritis in rats.

    PubMed

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

    2013-01-01

    A(2A) 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 A(2A)ARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A(2A)AR stimulation in a rat model of arthritis. We investigated A(2A)AR 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. A(2A)ARs 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 A(2A)AR 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 A(2A)AR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A(2A)AR 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 A(2A)AR 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 A(2A)AR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A(2A)ARs in lymphocytes from RA patients. The effectiveness of A(2A)AR stimulation in a rat model of arthritis supported the role of A(2A)AR agonists as potential pharmacological treatment for RA.

  16. 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 as...

  17. 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 as...

  18. 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 as...

  19. 77 FR 31588 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-29

    ... electronic support measures system (ESM), and AN/APS- 153 Multi-Mode Radar (MMR). The electronic warfare systems include the AN/AAR-47 missile warning system, AN/ALQ-144 infrared jammer, Identify Friend or...

  20. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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)...

  1. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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)...

  2. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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)...

  3. 49 CFR 179.220-26 - Stenciling.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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 indicate...

  4. 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 inches...

  5. 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 indicate...

  6. 49 CFR 179.220-26 - Stenciling.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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 indicate...

  7. 49 CFR 179.220-26 - Stenciling.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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 indicate...

  8. 78 FR 61871 - Grenada Railway, LLC-Rail Line in Grenada, Montgomery, Carroll, Holmes, Yazoo and Madison...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-04

    ... appear and speak on the effects of the embargo.\\2\\ \\1\\ The Association of American Railroads (AAR... continue until all interested persons or parties have had an opportunity to speak. Persons wishing to speak...

  9. 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)...

  10. Concrete modelling for expertise of structures affected by alkali aggregate reaction

    SciTech Connect

    Grimal, E.; Sellier, A.; Multon, S.; Le Pape, Y.; Bourdarot, E.

    2010-04-15

    Alkali aggregate reaction (AAR) affects numerous civil engineering structures and causes irreversible expansion and cracking. In order to control the safety level and the maintenance cost of its hydraulic dams, Electricite de France (EDF) must reach better comprehension and better prediction of the expansion phenomena. For this purpose, EDF has developed a numerical model based on the finite element method in order to assess the mechanical behaviour of damaged structures. The model takes the following phenomena into account: concrete creep, the stress induced by the formation of AAR gel and the mechanical damage. A rheological model was developed to assess the coupling between the different phenomena (creep, AAR and anisotropic damage). Experimental results were used to test the model. The results show the capability of the model to predict the experimental behaviour of beams subjected to AAR. In order to obtain such prediction, it is necessary to take all the phenomena occurring in the concrete into consideration.

  11. 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 Specifications...

  12. 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 Specifications...

  13. 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 Specifications...

  14. 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...

  15. 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...

  16. Cloning of genes responsible for acetic acid resistance in Acetobacter aceti.

    PubMed Central

    Fukaya, M; Takemura, H; Okumura, H; Kawamura, Y; Horinouchi, S; Beppu, T

    1990-01-01

    Five acetic acid-sensitive mutants of Acetobacter aceti subsp. aceti no. 1023 were isolated by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Three recombinant plasmids that complemented the mutations were isolated from a gene bank of the chromosome DNA of the parental strain constructed in Escherichia coli by using cosmid vector pMVC1. One of these plasmids (pAR1611), carrying about a 30-kilobase-pair (kb) fragment that conferred acetic acid resistance to all five mutants, was further analyzed. Subcloning experiments indicated that a 8.3-kb fragment was sufficient to complement all five mutations. To identify the mutation loci and genes involved in acetic acid resistance, insertional inactivation was performed by insertion of the kanamycin resistance gene derived from E. coli plasmid pACYC177 into the cloned 8.3-kb fragment and successive integration into the chromosome of the parental strain. The results suggested that three genes, designated aarA, aarB, and aarC, were responsible for expression of acetic acid resistance. Gene products of these genes were detected by means of overproduction in E. coli by use of the lac promoter. The amino acid sequence of the aarA gene product deduced from the nucleotide sequence was significantly similar to those of the citrate synthases (CSs) of E. coli and other bacteria. The A. aceti mutants defective in the aarA gene were found to lack CS activity, which was restored by introduction of a plasmid containing the aarA gene. A mutation in the CS gene of E. coli was also complemented by the aarA gene. These results indicate that aarA is the CS gene. Images FIG. 2 PMID:2156811

  17. Revising the National Exercise Program

    DTIC Science & Technology

    2008-03-01

    After-Action Report, (Washington D.C.: 2001), 1, http://biotech.law.lsu.edu/ blaw /dhs/TOPOFF-2000-AAR.PDF (accessed October 6, 2007). 19 not...After-Action Report. Washington DC: 2001, http://biotech.law.lsu.edu/ blaw /dhs/TOPOFF- 2000-AAR.PDF(accessed October 6, 2007). North American...Information Center Ft. Belvoir, VA 2. Dudley Knox Library Naval Postgraduate School Monterey, VA 3. Director of Logistics and Engineering

  18. ATF4-dependent regulation of the JMJD3 gene during amino acid deprivation can be rescued in Atf4-deficient cells by inhibition of deacetylation.

    PubMed

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

    2012-10-19

    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.

  19. UGV Control Interoperability Profile (IOP), Version 0

    DTIC Science & Technology

    2011-12-21

    save mission information Msn Plan - AAR C SW2 CTRL-Msn Plan-28 retrieve of mission information Msn Plan - AAR C SW2 3.9 Mobility...for public release. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to...and completing and reviewing the collection of information . Send comments regarding this burden estimate or any other aspect of this collection of

  20. Novel arylpiperazines as selective alpha1-adrenergic receptor antagonists.

    PubMed

    Li, X; Murray, W V; Jolliffe, L; Pulito, V

    2000-05-15

    A novel series of arylpiperazines has been synthesized and identified as antagonists of alpha1a adrenergic receptor (alpha1a-AR) implicated in benign prostatic hyperplasia. These compounds selectively bind to membrane bound alpha1a-AR with K(i)s as low as 0.66 nM. As such, these potentially represent a viable treatment for BPH without the side effects associated with known alpha1-adrenergic antagonists.

  1. Reorganization of Defense Coordinating Officer and Element

    DTIC Science & Technology

    2012-12-06

    increased effectiveness and efficiency enabled by the increased level of coordination is the federal response operations after Hurricane Irene made landfall...36 Ibid, 12. 37 U.S. Army North, “ Hurricane Irene AAR: Consolidated Observation,” (San Antonio...scene.do?shortName=Nation (accessed May 21, 2012). U.S. Army North. " Hurricane Irene AAR: Consolidated Observation." unpublished. San Antonio: US Army

  2. 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

  3. The Role of the After Action Review Leader in REALTRAIN: Research and Training Needs

    DTIC Science & Technology

    1979-01-01

    upon. This peer feedback , when integrated with a learner’s own recollections of what led up to the moment he became a casualty, allows him to see...troops (who know what casualties they inflicted/suffered) are inclined either to argue with the leader or to "clam up." Thus, the learning benefit...27 Table C-I. Percentages of Participant Responses to AAR-Related Questions .. .. ... . ...... 28 Figure C-I. Amount Learned from AAR Not

  4. The aspartate aminotransferase-to-alanine aminotransferase ratio predicts all-cause and cardiovascular mortality in patients with type 2 diabetes

    PubMed Central

    Zoppini, Giacomo; Cacciatori, Vittorio; Negri, Carlo; Stoico, Vincenzo; Lippi, Giuseppe; Targher, Giovanni; Bonora, Enzo

    2016-01-01

    Abstract An increased aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been widely used as a marker of advanced hepatic fibrosis. Increased AAR was also shown to be significantly associated with the risk of developing cardiovascular (CV) disease. The aim of this study was to assess the relationship between the AAR and mortality risk in a well-characterized cohort of patients with type 2 diabetes. A cohort of 2529 type 2 diabetic outpatients was followed-up for 6 years to collect cause-specific mortality. Cox regression analyses were modeled to estimate the independent association between AAR and the risk of all-cause and CV mortality. Over the 6-year follow-up period, 12.1% of patients died, 47.5% of whom from CV causes. An increased AAR, but not its individual components, was significantly associated with an increased risk of all-cause (adjusted-hazard risk 1.83, confidence interval [CI] 95% 1.14–2.93, P = 0.012) and CV (adjusted-hazard risk 2.60, CI 95% 1.38–4.90, P < 0.003) mortality after adjustment for multiple clinical risk factors and potential confounding variables. The AAR was independently associated with an increased risk of both all-cause and CV mortality in patients with type 2 diabetes. These findings suggest that an increased AAR may reflect more systemic derangements that are not simply limited to liver damage. Further studies are needed to elucidate the pathophysiological implications of an increased AAR. PMID:27787357

  5. Exploring Data Sharing Between Geographically Distributed Mobile and Fixed Nodes Supporting Extended Maritime Interdiction Operations (EMIO)

    DTIC Science & Technology

    2008-06-01

    Figure 16. VPN Cloud Connecting MIO with Global Collaborators................................50 Figure 17. SAOFDM Ship-to-Shore Link Operational on...VPN Cloud Connecting MIO with Global Collaborators................................62 Figure 26. YBI NOC Showing Austria and Germany Video Feed...in SF Bay Area (From TNT 07-1 AAR) 50 Figure 16. VPN Cloud Connecting MIO with Global Collaborators (From TNT 07-1 AAR) 51 Figure

  6. Enhanced production of n-alkanes in Escherichia coli by spatial organization of biosynthetic pathway enzymes.

    PubMed

    Rahmana, Ziaur; Sung, Bong Hyun; Yi, Ji-Yeun; Bui, Le Minh; Lee, Jun Hyoung; Kim, Sun Chang

    2014-12-20

    Alkanes chemically mimic hydrocarbons found in petroleum, and their demand as biofuels is steadily increasing. Biologically, n-alkanes are produced from fatty acyl-ACPs by acyl-ACP reductases (AARs) and aldehyde deformylating oxygenases (ADOs). One of the major impediments in n-alkane biosynthesis is the low catalytic turnover rates of ADOs. Here, we studied n-alkane biosynthesis in Escherichia coli using a chimeric ADO-AAR fusion protein or zinc finger protein-guided ADO/AAR assembly on DNA scaffolds to control their stoichiometric ratios and spatial arrangements. Bacterial production of n-alkanes with the ADO-AAR fusion protein was increased 4.8-fold (24 mg/L) over a control strain expressing ADO and AAR separately. Optimal n-alkane biosynthesis was achieved when the ADO:AAR binding site ratio on a DNA scaffold was 3:1, yielding an 8.8-fold increase (44 mg/L) over the control strain. Our findings indicate that the spatial organization of alkane-producing enzymes is critical for efficient n-alkane biosynthesis in E. coli.

  7. Effects of hippocampal stimulation on retention and extinction of one way active avoidance response in cats.

    PubMed

    Gralewicz, K; Gralewicz, S

    1984-01-01

    We found previously that hippocampal stimulation (HiSt) at 20 cps, 100 mikroA, applied jointly with a tone (500 Hz) CS in the course of retention test, improved the performance and retarded the extinction of one way active avoidance response (AAR) in cats. During this test failures to perform the AAR were not punished in all but two trials it the beginning of each session. The first experiment of the present studies demonstrated that - (i) the AAR facilitating the effect of HiSt might be prevented by m all electrolytic lesions made around the tips of the stimulating electrodes, (ii) large lesions of the hippocampus exerted little effect on the AAR acquisition, but the response was extinguished faster during the retention test. In the second experiment two response prevention trials (non-reinforced presentations of the CS with no possibility to make the AAR) were run at the beginning of each session after the end of training. In these conditions the HiSt resulted in a faster extinction of the AAR as compared with implanted unstimulated animals. Large lesions of the hippocampus had no effect on the extinction rate. We conclude that the facilitation of retrieval from memory may be responsible for the effects of HiSt on conditioned behavior.

  8. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response.

    PubMed

    Fu, Lingchen; Kilberg, Michael S

    2013-02-15

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR.

  9. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

    PubMed Central

    Fu, Lingchen

    2013-01-01

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR. PMID:23269699

  10. 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

  11. Protein kinase Cε is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs.

    PubMed

    Schuster, Daniel J; Kitto, Kelley F; Overland, Aaron C; Messing, Robert O; Stone, Laura S; Fairbanks, Carolyn A; Wilcox, George L

    2013-08-14

    We recently showed that spinal synergistic interactions between δ opioid receptors (δORs) and α2A adrenergic receptors (α2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between δORs and α2AARs using the tail flick assay of thermal nociception in mice. Only a PKCε inhibitor abolished synergy between a δOR agonist and an α2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCε knock-out mice and found that all four combinations of a δOR agonist and an α2AAR agonist required PKCε for antinociceptive synergy. None of the combinations of a μOR agonist with an α2AR agonist required PKCε. Immunohistochemistry confirmed that PKCε could be found in the population of peptidergic primary afferent nociceptors where δORs and α2AARs have been found to extensively colocalize. Immunoreactivity for PKCε was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCε is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between δORs and α2AARs.

  12. Diverse arrestin-recruiting and endocytic profiles of tricyclic antipsychotics acting as direct α2A adrenergic receptor ligands.

    PubMed

    Cottingham, Christopher; Che, Pulin; Zhang, Wei; Wang, Hongxia; Wang, Raymond X; Percival, Stefanie; Birky, Tana; Zhou, Lufang; Jiao, Kai; Wang, Qin

    2017-04-01

    The therapeutic mechanism of action underlying many psychopharmacological agents remains poorly understood, due largely to the extreme molecular promiscuity exhibited by these agents with respect to potential central nervous system targets. Agents of the tricyclic chemical class, including both antidepressants and antipsychotics, exhibit a particularly high degree of molecular promiscuity; therefore, any clarification of how these agents interact with specific central nervous system targets is of great potential significance to the field. Here, we present evidence demonstrating that tricyclic antipsychotics appear to segregate into three distinct groups based upon their molecular interactions with the centrally-important α2A adrenergic receptor (AR). Specifically, while the α2AAR binds all antipsychotics tested with similar affinities, and none of the agents are able to induce classical heterotrimeric G protein-mediated α2AAR signaling, significant differences are observed with respect to arrestin3 recruitment and receptor endocytosis. All antipsychotics tested induce arrestin3 recruitment to the α2AAR, but with differing strengths. Both chlorpromazine and clozapine drive significant α2AAR endocytosis, but via differing clathrin-dependent and lipid raft-dependent pathways, while fluphenazine does not drive a robust response. Intriguingly, in silico molecular modeling suggests that each of the three exhibits unique characteristics in interacting with the α2AAR ligand-binding pocket. In addition to establishing these three antipsychotics as novel arrestin-biased ligands at the α2AAR, our findings provide key insights into the molecular actions of these clinically-important agents.

  13. Immunohistochemical localization of alpha(1a)-adrenoreceptors in muscle spindles of rabbit masseter muscle.

    PubMed

    Bombardi, C; Grandis, A; Chiocchetti, R; Bortolami, R; Johansson, H; Lucchi, M L

    2006-04-01

    The expression of alpha(1a)-adrenoreceptors (alpha(1a)-ARs) within the muscle spindles of rabbit masseter muscle was investigated. The alpha(1a)-ARs were detected by immunohistochemical fluorescent method and examined along the entire length of 109 cross serially sectioned spindles. The sympathetic fibers were visualized by the immunofluorescent labeling of the noradrenaline synthesizing enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In order to recognize the intrafusal muscle fiber types, antibodies for different myosin heavy chain isoforms (MyHCI) were used. TH and DBH immunolabeled nerve fibers have been observed within the capsule lamellar layers, in the periaxial fluid space and close to intrafusal muscle fibers. The alpha(1a)-ARs were detected on the smooth muscle cells of the blood vessels coursing in the muscle and in the capsule lamellar layers or within the periaxial fluid space of the spindles. Moreover, at the polar regions of a high percentage (88.1%) of muscle spindles a strong alpha(1a)-ARs immunoreactivity was present on the intrafusal muscle fibers. In double immunostained sections for alpha(1a)-ARs and MyHCI it was evidenced that both bag, and nuclear chain fibers express alpha(1a)-ARs. The receptors that we have detected by immunofluorescence may support a direct control by adrenergic fibers on muscle spindle.

  14. Evolutionary history of Arabidopsis thaliana aminoacyl-tRNA synthetase dual-targeted proteins.

    PubMed

    Brandão, Marcelo M; Silva-Filho, Marcio C

    2011-01-01

    Aminoacyl-transfer RNA (tRNA) synthetases (aaRS) are key players in translation and act early in protein synthesis by mediating the attachment of amino acids to their cognate tRNA molecules. In plants, protein synthesis may occur in three subcellular compartments (cytosol, mitochondria, and chloroplasts), which requires multiple versions of the protein to be correctly delivered to its proper destination. The organellar aaRS are nuclear encoded and equipped with targeting information at the N-terminal sequence, which enables them to be specifically translocated to their final location. Most of the aaRS families present organellar proteins that are dual targeted to mitochondria and chloroplasts. Here, we examine the dual targeting behavior of aaRS from an evolutionary perspective. Our results show that Arabidopsis thaliana aaRS sequences are a result of a horizontal gene transfer event from bacteria. However, there is no evident bias indicating one single ancestor (Cyanobacteria or Proteobacteria). The dual-targeted aaRS phylogenetic relationship was characterized into two different categories (paralogs and homologs) depending on the state recovered for both dual-targeted and cytosolic proteins. Taken together, our results suggest that the dual-targeted condition is a gain-of-function derived from gene duplication. Selection may have maintained the original function in at least one of the copies as the additional copies diverged.

  15. Feasibility of tobacco interventions in anesthesiology practices: a pilot study.

    PubMed

    Warner, David O

    2009-06-01

    Abstinence from smoking can improve postoperative outcomes, and surgery is also an excellent opportunity for smokers to permanently quit. One strategy for perioperative tobacco interventions is that anesthesiologists Ask, Advise, and Refer (AAR) -- Ask their patients about tobacco use, Advise them to abstain, and Refer them to resources such as telephone quit-lines. This pilot project determined the feasibility and acceptability of the AAR strategy in anesthesiology practices. An educational program, including presentations, written materials, and Web-based resources, was developed and disseminated to 14 U.S. anesthesiology practices, representing both academic and private practices, who agreed to implement the AAR strategy as a part of their routine clinical practice. Three months after implementation, a survey was administered to those members of these practices who were instructed in the AAR strategy. There were 97 respondents (75% response rate). Since the pilot project began, 91%, 79%, and 58% of respondents reported that they frequently or almost always asked, advised, and referred their patients who smoke, respectively. The majority of respondents (56%) agreed that they were responsible for helping patients get the help they need to quit smoking. Most (74%) also agreed that they planned to incorporate the AAR strategy into their routine practice. These results suggest that the AAR strategy is potentially feasible and well-accepted in anesthesiology clinical practice. Further work will be needed to define whether these practices and attitudes can be sustained and whether they are ultimately effective in modifying perioperative smoking behavior in surgical patients.

  16. 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.

  17. Protein Kinase Cϵ Is Required for Spinal Analgesic Synergy between Delta Opioid and Alpha-2A Adrenergic Receptor Agonist Pairs

    PubMed Central

    Schuster, Daniel J.; Kitto, Kelley F.; Overland, Aaron C.; Messing, Robert O.; Stone, Laura S.; Fairbanks, Carolyn A.

    2013-01-01

    We recently showed that spinal synergistic interactions between δ opioid receptors (δORs) and α2A adrenergic receptors (α2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between δORs and α2AARs using the tail flick assay of thermal nociception in mice. Only a PKCϵ inhibitor abolished synergy between a δOR agonist and an α2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCϵ knock-out mice and found that all four combinations of a δOR agonist and an α2AAR agonist required PKCϵ for antinociceptive synergy. None of the combinations of a μOR agonist with an α2AR agonist required PKCϵ. Immunohistochemistry confirmed that PKCϵ could be found in the population of peptidergic primary afferent nociceptors where δORs and α2AARs have been found to extensively colocalize. Immunoreactivity for PKCϵ was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCϵ is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between δORs and α2AARs. PMID:23946412

  18. Kamstrupp's Wow-Effect: Re-Examined and Expanded

    ERIC Educational Resources Information Center

    King, Elizabeth M.; Dickmann, Ellyn M.; Johnson, Barbara Z.

    2016-01-01

    This review examines Anne Katrine Kamstrupp'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 Kamstrupp's article through the lens of technology as a pedagogical choice and philosophy. This is…

  19. Kamstrupp's Wow-Effect: Re-Examined and Expanded

    ERIC Educational Resources Information Center

    King, Elizabeth M.; Dickmann, Ellyn M.; Johnson, Barbara Z.

    2016-01-01

    This review examines Anne Katrine Kamstrupp'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 Kamstrupp's article through the lens of technology as a pedagogical choice and philosophy. This is…

  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. Environmental contaminants in oil field produced waters discharged into wetlands

    SciTech Connect

    Ramirez, P. Jr.

    1994-12-31

    The 866-acre Loch Katrine wetland complex in Park County, Wyoming provides habitat for many species of aquatic birds. The complex is sustained primarily by oil field produced waters. This study was designed to determine if constituents in oil field produced waters discharged into Custer Lake and to Loch Katrine pose a risk to aquatic birds inhabiting the wetlands. Trace elements, hydrocarbons and radium-226 concentrations were analyzed in water, sediment and biota collected from the complex during 1992. Arsenic, boron, radium-226 and zinc were elevated in some matrices. The presence of radium-226 in aquatic vegetation suggests that this radionuclide is available to aquatic birds. Oil and grease concentrations in water from the produced water discharge exceeded the maximum 10 mg/l permitted by the WDEQ (1990). Total aliphatic and aromatic hydrocarbon concentrations in sediments were highest at the produced water discharge, 6.376 {mu}g/g, followed by Custer Lake, 1.104 {mu}g/g. The higher levels of hydrocarbons found at Custer Lake, compared to Loch Katrine, may be explained by Custer Lake`s closer proximity to the discharge. Benzo(a)pyrene was not detected in bile from gadwalls collected at Loch Katrine but was detected in bile from northern shovelers collected at Custer Lake. Benzo(a)pyrene concentrations in northern shoveler bile ranged from 500 to 960 ng/g (ppb) wet weight. The presence of benzo(a)pyrene in the shovelers indicates exposure to petroleum hydrocarbons.

  2. 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

    2014-12-02

    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.

  3. Psychophysiological Assessment in Pilots Performing Challenging Simulated and Real Flight Maneuvers.

    PubMed

    Johannes, Bernd; Rothe, Stefanie; Gens, André; Westphal, Soeren; Birkenfeld, Katja; Mulder, Edwin; Rittweger, Jörn; Ledderhos, Carla

    2017-09-01

    The objective assessment of psychophysiological arousal during challenging flight maneuvers is of great interest to aerospace medicine, but remains a challenging task. In the study presented here, a vector-methodological approach was used which integrates different psychophysiological variables, yielding an integral arousal index called the Psychophysiological Arousal Value (PAV). The arousal levels of 15 male pilots were assessed during predetermined, well-defined flight maneuvers performed under simulated and real flight conditions. The physiological data, as expected, revealed inter- and intra-individual differences for the various measurement conditions. As indicated by the PAV, air-to-air refueling (AAR) turned out to be the most challenging task. In general, arousal levels were comparable between simulator and real flight conditions. However, a distinct difference was observed when the pilots were divided by instructors into two groups based on their proficiency in AAR with AWACS (AAR-Novices vs. AAR-Professionals). AAR-Novices had on average more than 2000 flight hours on other aircrafts. They showed higher arousal reactions to AAR in real flight (contact: PAV score 8.4 ± 0.37) than under simulator conditions (7.1 ± 0.30), whereas AAR-Professionals did not (8.5 ± 0.46 vs. 8.8 ± 0.80). The psychophysiological arousal value assessment was tested in field measurements, yielding quantifiable arousal differences between proficiency groups of pilots during simulated and real flight conditions. The method used in this study allows an evaluation of the psychophysiological cost during a certain flying performance and thus is possibly a valuable tool for objectively evaluating the actual skill status of pilots.Johannes B, Rothe S, Gens A, Westphal S, Birkenfeld K, Mulder E, Rittweger J, Ledderhos C. Psychophysiological assessment in pilots performing challenging simulated and real flight maneuvers. Aerosp Med Hum Perform. 2017; 88(9):834-840.

  4. 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

  5. α1A- and α1B-Adrenergic Receptors Differentially Modulate Antidepressant-Like Behavior in the Mouse

    PubMed Central

    Doze, Van A.; Handel, Evelyn M.; Jensen, Kelly A.; Darsie, Belle; Luger, Elizabeth J.; Haselton, James R.; Talbot, Jeffery N.; Rorabaugh, Boyd R.

    2009-01-01

    Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of α1-adrenergic receptors (α1-ARs). Yet, it is unclear whether increased α1-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant α1A-ARs (CAM α1A-AR) or CAM α1B-ARs were used to examine the effects of α1A- and α1B-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM α1A-AR mice, but not CAM α1B-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective α1-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an α1A-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM α1A-AR mice but not in CAM α1B-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM α1A-AR, and CAM α1B-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that α1A- and α1B-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that α1A-ARs may be a useful therapeutic target for the treatment of depression. PMID:19540213

  6. alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.

    PubMed

    Doze, Van A; Handel, Evelyn M; Jensen, Kelly A; Darsie, Belle; Luger, Elizabeth J; Haselton, James R; Talbot, Jeffery N; Rorabaugh, Boyd R

    2009-08-18

    Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive-compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of alpha(1)-adrenergic receptors (alpha(1)-ARs). Yet, it is unclear whether increased alpha(1)-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit. In this study, mice expressing constitutively active mutant alpha(1A)-ARs (CAM alpha(1A)-AR) or CAM alpha(1B)-ARs were used to examine the effects of alpha(1A)- and alpha(1B)-AR signaling on rodent behavioral models of depression, OCD, and anxiety. CAM alpha(1A)-AR mice, but not CAM alpha(1B)-AR mice, exhibited antidepressant-like behavior in the tail suspension test and forced swim test. This behavior was reversed by prazosin, a selective alpha(1)-AR inverse agonist, and mimicked by chronically treating wild type mice with cirazoline, an alpha(1A)-AR agonist. Marble burying behavior, commonly used to model OCD in rodents, was significantly decreased in CAM alpha(1A)-AR mice but not in CAM alpha(1B)-AR mice. In contrast, no significant differences in anxiety-related behavior were observed between wild type, CAM alpha(1A)-AR, and CAM alpha(1B)-AR animals in the elevated plus maze and light/dark box. This is the first study to demonstrate that alpha(1A)- and alpha(1B)-ARs differentially modulate antidepressant-like behavior in the mouse. These data suggest that alpha(1A)-ARs may be a useful therapeutic target for the treatment of depression.

  7. [Values of the sperm deformity index, acrosome abnormity rate, and sperm DNA fragmentation index of optimized sperm in predicting IVF fertilization failure].

    PubMed

    Jiang, Wei-jie; Jin, Fan; Zhou, Li-ming

    2016-02-01

    To investigate the values of the sperm deformity index (SDI), acrosome abnormity rate (AAR), and DNA fragmentation index (DFI) of optimized sperm in the prediction of fertilization failure (fertilization rate < 25%) in conventional in vitro fertilization (IVF). We selected 695 cycles of conventional IVF for pure oviductal infertility in this study, including 603 cycles of normal fertilization and 92 cycles of fertilization failure. On the day of oocyte retrieval, we examined sperm morphology, acrosome morphology, and DNA fragmentation using the Diff-Quik, PSA-FITC and SCD methods. We established the joint predictor (JP) by logistic equation and analyzed the values of different parameters in predicting fertilization failure with the receiver operating characteristic (ROC) curve. The fertilization rate was negatively correlated with SDI (r = - 0.07; P = 0.03), AAR (r = -0.49; P < 0.01), and DFI (r = -0. 21; P < 0.01). The SDI, AAR, and DFI in the normal fertilization group were 1.24 ± 0.20, (7.75 ± 2.28)%, and (7.87 ± 3.15)%, and those in the fertilization failure group were 1.42 ± 0.15, (12.02 ± 3.06)%, and (13.32 ± 4.13)%, respectively, all with statistically significant differences between the two groups (P < 0.05). SDI, AAR, and DFI were all risk factors of fertilization failure ( OR = 2.68, 14.11, and 3.85; P = 0.01, < 0.01, and < 0.01). The areas under the ROC curves for SDI, AAR, DFI, and JP were 0.651 ± 0.033, 0.895 ± 0.019, 0.789 ± 0.022, and 0.915 ± 0.017, respectively. According to the Youden index, the optimal cut-off values of SDI, AAR, and DFI obtained for the prediction of fertilization failure were approximately 1.45, 10%, and 12%. The SDI, AAR and DFI of optimized sperm are closely associated with the fertilization rate, and all have the value for predicting fertilization failure in IVF. The AAR is more valuable than the other single predictors, but JP is more effective than the AAR.

  8. IL-33/ST2 axis controls Th2/IL-31 and Th17 immune response in allergic airway diseases.

    PubMed

    Vocca, Lavinia; Di Sano, Caterina; Uasuf, Carina G; Sala, Angelo; Riccobono, Loredana; Gangemi, Sebastiano; Albano, Giusy Daniela; Bonanno, Anna; Gagliardo, Rosalia; Profita, Mirella

    2015-08-01

    IL-33 targeting ST2 receptor (T1/ST2), expressed on Th2 cell surface, regulates the production of cytokines like IL-17A and IL-31. We studied the role of IL-33/ST2 axis in IL-31 and IL-17A production in patients with allergic rhinitis (AR) and with concomitant allergic asthma and rhinitis (AAR). 20 healthy control subjects (HC), 14 AR and 17 AAR subjects were recruited and blood samples collected. IL-33, soluble ST2 (sST2), IL-17A and IL-31 plasma concentrations were measured by ELISA method. T1/ST2, IL-31 and IL-17A cellular expression were studied in peripheral blood mononuclear cells (PBMC) from HC, AR and AAR (n=6 for each group) by flow-cytometry. In vitro, we also evaluated the effect of beclomethasone dipropionate (BDP) on T1/ST2, IL-31 and IL-17A expression in CD3(+)T-cells from PBMC of AAR (n=6). Plasma levels of IL-33, IL-31 and IL-17A were significantly higher and sST2 was lower in patients with AR and AAR than in HC. IL-31 and IL-17A intracellular levels significantly increased, whereas T1/ST2 expression was significantly lower, in CD3(+)T-cells from AR and AAR compared to HC. Positive correlations were observed between plasmatic components of IL-33/ST2 axis and IL-31 in both AR and AAR and IL-17A in AAR. In vitro IL-31 and IL-17A intracellular levels decreased after BDP treatment, whereas T1/ST2 expression increased in cultured CD3(+)T-cells obtained from AAR. IL-33/ST2 axis is involved in Th2/IL-31 and Th17 immune response during the progression of allergic airway disease. In vitro BDP is able to control Th2/IL-31 and Th17 immune response in PBMC from allergic patients. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A₂A and A₃ adenosine receptor ligands.

    PubMed

    Hou, Xiyan; Majik, Mahesh S; Kim, Kyunglim; Pyee, Yuna; Lee, Yoonji; Alexander, Varughese; Chung, Hwa-Jin; Lee, Hyuk Woo; Chandra, Girish; Lee, Jin Hee; Park, Seul-Gi; Choi, Won Jun; Kim, Hea Ok; Phan, Khai; Gao, Zhan-Guo; Jacobson, Kenneth A; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin

    2012-01-12

    Truncated N(6)-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)AR docking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

  10. G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody.

    PubMed

    Hino, Tomoya; Arakawa, Takatoshi; Iwanari, Hiroko; Yurugi-Kobayashi, Takami; Ikeda-Suno, Chiyo; Nakada-Nakura, Yoshiko; Kusano-Arai, Osamu; Weyand, Simone; Shimamura, Tatsuro; Nomura, Norimichi; Cameron, Alexander D; Kobayashi, Takuya; Hamakubo, Takao; Iwata, So; Murata, Takeshi

    2012-01-29

    G-protein-coupled receptors are the largest class of cell-surface receptors, and these membrane proteins exist in equilibrium between inactive and active states. Conformational changes induced by extracellular ligands binding to G-protein-coupled receptors result in a cellular response through the activation of G proteins. The A(2A) adenosine receptor (A(2A)AR) is responsible for regulating blood flow to the cardiac muscle and is important in the regulation of glutamate and dopamine release in the brain. Here we report the raising of a mouse monoclonal antibody against human A(2A)AR that prevents agonist but not antagonist binding to the extracellular ligand-binding pocket, and describe the structure of A(2A)AR in complex with the antibody Fab fragment (Fab2838). This structure reveals that Fab2838 recognizes the intracellular surface of A(2A)AR and that its complementarity-determining region, CDR-H3, penetrates into the receptor. CDR-H3 is located in a similar position to the G-protein carboxy-terminal fragment in the active opsin structure and to CDR-3 of the nanobody in the active β(2)-adrenergic receptor structure, but locks A(2A)AR in an inactive conformation. These results suggest a new strategy to modulate the activity of G-protein-coupled receptors.

  11. Effect of continuing repeated passive and active exercises on knee's position senses in patients with hemiplegia.

    PubMed

    Kwon, Oh Sung; Lee, Seung Won

    2013-01-01

    To determine the repeated passive movement (RPM) and repeated active movement (RAM) exercise on position sense of the knee joint in patients with hemiplegia. 45 hemiplegia patients were randomly allocated to either the control group(no exercise), RPM group, or RAM group, with 15 subjects in each group. The exercise was repeated 60 times on the angle 10 to 100 degrees of the knee joint with an angle speed of 120°/s, with three sets for 15 minutes. Evaluation was performed using Passive Angle Repositioning (PAR) and Active Angle Repositioning (AAR). Error of positioning sense showed a decrease in PAR and AAR in the RPM group (p < 0.01) and an increase in AAR was observed in the RAM group (p < 0.05). In comparison of knee joint position sense error value and rate of change among the three groups, the RPM group is decreased mostly in PAR and AAR (p < 0.01), and Error value (p < 0.05) and rate of change (p < 0.01) of the RAM group showed a greater increase in AAR than the control group. RAM exercise can support an increase in proprioception on the knee joint of hemiplegia; however, RAM exercise that causes fatigue can decrease proprioception.

  12. Accelerated acute allograft rejection accompanied by enhanced T-cell proliferation and attenuated Treg function in RBP-J deficient mice.

    PubMed

    Fu, Tao; Zhang, Ping; Feng, Lei; Ji, Gang; Wang, Xiao-Hong; Zheng, Min-Hua; Qin, Hong-Yan; Chen, Dong-Li; Wang, Wei-Zhong; Han, Hua

    2011-02-01

    Acute allograft rejection (AAR) involves both the innate and the adaptive immune systems. As a critical pathway in peripheral T-cell differentiation and function, Notch signaling is potentially involved in the modulation of AAR, but its role in alloimmune responses has not been fully addressed. By using fully MHC-mismatched allograft transplantation model and T-cell specific RBP-J deficient mice, we examined the role of Notch/RBP-J pathway in alloimmune responses in vivo. AAR was significantly accelerated in RBP-J deficient mice compared with the wild-type controls, as demonstrated by the marked reduction in graft survival. The reduction in graft survival was associated with augmented alloantigen specific T-cell proliferation and increased number of Th1, Th2, and Th17 cells in the RBP-J deficient recipient mice. Furthermore, although the frequency of CD4(+)CD25(+)Foxp3(+) Tregs was intact in RBP-J knockout recipients, their ability to suppress Teff responses in vitro was significantly dampened. These findings suggest that Notch/RBP-J pathway may attenuate AAR by suppressing in vivo expansion of alloreactive T-cell proliferation and facilitating CD4(+)CD25(+) Treg suppression ability, indicating that Notch pathway could be exploited to limit T-cell-mediated AAR. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Structure of an agonist-bound human A2A adenosine receptor.

    PubMed

    Xu, Fei; Wu, Huixian; Katritch, Vsevolod; Han, Gye Won; Jacobson, Kenneth A; Gao, Zhan-Guo; Cherezov, Vadim; Stevens, Raymond C

    2011-04-15

    Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.

  15. α2 Adrenergic Receptor Trafficking as a Therapeutic Target in Antidepressant Drug Action.

    PubMed

    Cottingham, Christopher; Ferryman, Craig J; Wang, Qin

    2015-01-01

    Antidepressant drugs remain poorly understood, especially with respect to pharmacological mechanisms of action. This lack of knowledge results from the extreme complexity inherent to psychopharmacology, as well as to a corresponding lack of knowledge regarding depressive disorder pathophysiology. While the final analysis is likely to be multifactorial and heterogeneous, compelling evidence exists for upregulation of brain α2 adrenergic receptors (ARs) in depressed patients. This evidence has sparked a line of research into actions of a particular antidepressant drug class, the tricyclic antidepressants (TCAs), as direct ligands at α(2A)ARs. Our findings, as outlined herein, demonstrate that TCAs function as arrestin-biased ligands at α(2A)ARs. Importantly, TCA-induced α(2A)AR/arrestin recruitment leads to receptor endocytosis and downregulation of α(2A)AR expression with prolonged exposure. These findings represent a novel mechanism linking α(2)AR trafficking with antidepressant pharmacology.

  16. 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.

  17. The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment

    PubMed Central

    Saint-Léger, Adélaïde; Sinadinos, Christopher; Ribas de Pouplana, Lluís

    2016-01-01

    ABSTRACT Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes. PMID:26963157

  18. The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment.

    PubMed

    Saint-Léger, Adélaïde; Sinadinos, Christopher; Ribas de Pouplana, Lluís

    2016-04-02

    Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes.

  19. 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.

  20. 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.

  1. 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.

  2. An ex vivo comparison of working length determination by three electronic root canal length measurement devices integrated into endodontic rotary motors.

    PubMed

    Ali, Manal Maree; Wigler, Ronald; Lin, Shaul; Kaufman, Arieh Y

    2016-11-01

    The objective of this study was to compare the accuracy of working length (WL) determination by X-Smart Dual, ENDOAce, and Gold Reciproc motor, in manual mode and mechanical preparation set to auto apical reverse (AAR) mode. Forty-five anterior teeth were included in the study. The canal length was determined by introducing #10 file into the canal until it emerged at the apical foramen. The incisal edges were adjusted to obtain 18 mm standard length. The teeth were embedded in Plexiglas tubes, filled with alginate, and measured in manual and AAR modes. Within and between the groups, there was no significant difference in WL measurements, both in manual and AAR modes. In the X-Smart Dual group, all manual measurements were within root canal limits, while 13 % of AAR mode measurements were recorded when the file tip passed the apical foramen. In the ENDOAce group, 13 and 7 % of the measurements, in manual and AAR modes respectively, were recorded when the file tip passed the foramen. In the Gold Reciproc motor group, 27 and 33 % of the measurements, in manual and AAR modes respectively, were recorded when the file tip passed the foramen. With the limitation of this ex vivo study, the tested devices presented no significant differences in length measurements and were within the clinical accepted margin of error. Mechanical preparation must be confined to the root canal system. The adverse results of overinstrumentation emphasize the need to reconsider the ±0.50 mm margin of error that is clinically acceptable for WL measurements.

  3. Learning in the thick of it.

    PubMed

    Darling, Marilyn; Parry, Charles; Moore, Joseph

    2005-01-01

    The U.S. Army's Opposing Force (OPFOR) is a 2,500-member brigade whose job is to help prepare soldiers for combat. Created to be the meanest, toughest foe that soldiers will ever face, OPFOR engages units-in-training in a variety of mock campaigns under a wide range of conditions. Every month, a fresh brigade of more than 4,000 soldiers takes on this standing enemy. OPFOR, which is stationed in the California desert, always has the home-court advantage. But the force being trained--called BLU FOR--is numerically and technologically superior. It possesses more resources and better, more available data. It is made up of experienced soldiers. And it knows just what to expect, because OPFOR shares its methods from previous campaigns with BLUFOR's commanders. In short, each BLUFOR brigade is given practically every edge. Yet OPFOR almost always wins. Underlying OPFOR's consistent success is the way it uses the after-action review (AAR), a method for extracting lessons from one event or project and applying them to others. AAR meetings became a popular business tool after Shell Oil began experimenting with them in 1998. Most corporate AARs, however, are faint echoes of the rigorous reviews performed by OPFOR. Companies tend to treat the process as a pro-forma wrap-up, drawing lessons from an action but rarely learning them. OPFOR's AARs, by contrast, generate raw material that is fed back into the execution cycle. And while OPFOR's reviews extract numerous lessons, the brigade does not consider a lesson to be learned until it is successfully applied and validated. It might not make sense for companies to adopt OPFOR's AAR processes in their entirety, but four fundamentals are mandatory: Lessons must benefit the team that extracts them. The AAR process must start atthe beginning of the activity. Lessons must link explicitly to future actions. And leaders must hold everyone, especially themselves, accountable for learning.

  4. Adverse reactions in horses that underwent general anesthesia and cervical myelography.

    PubMed

    Mullen, K R; Furness, M C; Johnson, A L; Norman, T E; Hart, K A; Burton, A J; Bicahlo, R C; Ainsworth, D M; Thompson, M S; Scrivani, P V

    2015-01-01

    The study was prompted by a perceived high prevalence of myelographic complications varying in severity and type, and attributed to the contrast material or the procedure. 1. Any adverse reaction (AAR) is associated with a change in CSF volume induced either by removal of CSF or addition of contrast material. 2. AAR occurs more frequently in horses with higher premyelography neurologic grade. 3. Nonspecific hyperthermia is attenuated by anti-inflammatory and osmotic agents. Horses (n = 278) that underwent myelography between 2000 and 2012 at 5 institutions: A (87), B (68), C (65), D (46), and E (12). Multi-institutional, retrospective, observational cross-sectional study. AAR were observed in 95/278 (34%) horses, were associated with longer general anesthesia time (P = .04) and higher contrast-medium volume (P = .04); euthanasia because of AAR was performed in 5/278 (2%) horses. Adverse neurologic reactions were the most common type of complication observed occurring in 15/278 (5%) and 42/235 (18%) of horses in the intra- and postmyelography periods. A relationship between AAR and premyelography neurologic grade was not identified (P = .31). Nonspecific hyperthermia was observed in 25/235 (11%) horses; no relationship was observed with administration of anti-inflammatory drugs and osmotic agents (P = .30). The category of AAR occurred in one-third of the horses generally was mild and self-limiting. These reactions were associated with increased contrast-medium volume and longer anesthesia time; but, no specific procedural recommendations could be made because of small odds ratios (OR) of <2 for each 1 mL increase in contrast material and for each 1 minute of additional anesthesia time. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 5: a guide on the management of rosacea.

    PubMed

    Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Tanghetti, Emil; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

    2014-03-01

    The last article in this 5-part series provides a final overview of consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. Optimal management of rosacea requires careful assessment of the patient's clinical features with integration of therapies that adequately treat the presenting signs and symptoms. The treatment consensus recommendations from the AARS are based on 2 major common clinical presentations of rosacea: (1) centrofacial erythema with papulopustular lesions, and (2) centrofacial erythema without papulopustular lesions. The recommendations provided here serve to guide clinicians in their clinical practice.

  6. Acute Infarct Extracellular Volume Mapping to Quantify Myocardial Area at Risk and Chronic Infarct Size on Cardiovascular Magnetic Resonance Imaging.

    PubMed

    Garg, Pankaj; Broadbent, David A; Swoboda, Peter P; Foley, James R J; Fent, Graham J; Musa, Tarique A; Ripley, David P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Haaf, Philip; Kidambi, Ananth; van der Geest, Rob J; Greenwood, John P; Plein, Sven

    2017-07-01

    Late gadolinium enhancement (LGE) imaging overestimates acute infarct size. The main aim of this study was to investigate whether acute extracellular volume (ECV) maps can reliably quantify myocardial area at risk (AAR) and final infarct size (IS). Fifty patients underwent cardiovascular magnetic resonance imaging acutely (24-72 hours) and at convalescence (3 months). The cardiovascular magnetic resonance protocol included cines, T2-weighted imaging, native T1 maps, 15-minute post-contrast T1 maps, and LGE. Optimal AAR and IS ECV thresholds were derived in a validation group of 10 cases (160 segments). Eight hundred segments (16 per patient) were analyzed to quantify AAR/IS by ECV maps (ECV thresholds for AAR is 33% and IS is 46%), T2-weighted imaging, T1 maps, and acute LGE. Follow-up LGE imaging was used as the reference standard for final IS and viability assessment. The AAR derived from ECV maps (threshold of >33) demonstrated good agreement with T2-weighted imaging-derived AAR (bias, 0.18; 95% confidence interval [CI], -1.6 to 1.3) and AAR derived from native T1 maps (bias=1; 95% CI, -0.37 to 2.4). ECV demonstrated the best linear correlation to final IS at a threshold of >46% (R=0.96; 95% CI, 0.92-0.98; P<0.0001). ECV maps demonstrated better agreement with final IS than acute IS on LGE (ECV maps: bias, 1.9; 95% CI, 0.4-3.4 versus LGE imaging: bias, 10; 95% CI, 7.7-12.4). On multiple variable regression analysis, the number of nonviable segments was independently associated with IS by ECV maps (β=0.86; P<0.0001). ECV maps can reliably quantify AAR and final IS in reperfused acute myocardial infarction. Acute ECV maps were superior to acute LGE in terms of agreement with final IS. IS quantified by ECV maps are independently associated with viability at follow-up. © 2017 American Heart Association, Inc.

  7. Atmospheric Photochemical Modeling of Turbine Engine Fuels and Exhausts. Phase 2. Computer Model Development. Volume 1

    DTIC Science & Technology

    1988-05-01

    parameters of m-xylene. ALK3BENZ AAR5 Tni- and poly-alkylbenzeneu. Uses parameters of 135-TMB. TETRALIN AAR.3 Tetralin. Also used for indans. NAPHTHAL ...Tri- and poly-alkyl benzenes. Represented by 1,3,5-trimethylbenzene. NAPHTHAL (LM2 only) Naphthalene ME-NAPH (LM2 only) Monoalkyl naphthalenes...216 .0 12 24 0 0 0 E C12-OLE2 217 Naphthalene 217 1. 10 8 0 0 0 0 SN NAPHTHAL 218 3-Methylundecane or isomer 218 1. 12 26 0 0 0 0 BA BR-C12 219 1,2

  8. Message Network Simulation

    DTIC Science & Technology

    1990-03-01

    i.96*SR10 Si UR10 = AR10+1. 96*SR10 LBF = ABF-1.96*SBF UBF = ABF+1.96*SBF LPMR = APMR-1. 96*SPMR UPHR = APMR+1. 96*SPMR LAR = AAR-1. 96*SAR...WRITEC13,141) LN,AR1,AR2,AR3,AR6A,AR4,AR5,AR7,AR10 WRITE(13,141) LN,UR1,UR2,UR3,UR6A,UR4,UR5,UR7, UR10 WRITEC15,137) LN,LRS,LPMR,LBF,LAR,LAC,LR9

  9. Magnetic susceptibility and partial anhysteretic remanence anisotropies in the magnetite-bearing granite pluton of Tourão, NE Brazil

    NASA Astrophysics Data System (ADS)

    Trindade, Ricardo I. F.; Raposo, M. Irene B.; Ernesto, Marcia; Siqueira, Roberto

    1999-12-01

    Rock magnetism and magnetic fabric studies were performed in the Tourão granite (western part of Seridó belt, NE Brazil). This pluton (350 km 2) is composed of K-rich calc-alkalic monzogranites and was emplaced between a set of NE- and E-trending dextral strike-slip shear zones. Electronic and optical microscopy, thermomagnetic curves, hysteresis data and coercivity spectra revealed that magnetite (fine- and coarse-grained) is the unique ferromagnetic mineral in these rocks. Anisotropy of low-field magnetic susceptibility (AMS) was measured in 83 sites, and for many sites from central and southern parts of the intrusive body a large scatter was noticed. Anisotropy of partial anhysteretic remanence (pAAR) was determined for 29 sites in the 0-50 mT (pAAR 0-50) and 19 sites in the 50-90 mT (pAAR 50-90) windows to isolate the fabric contribution of the remanence bearing grains (magnetite). In most sites AMS is dominantly carried by magnetite, whereas in some sites the paramagnetic contribution exceeds 60% of the bulk susceptibility. The pAAR 0-50 is assumed to be related to coarse-grained early crystallized magnetites, while the pAAR 50-90 is interpreted as due to fine needle-shaped magnetites hosted in biotites. The combined analysis of these magnetic techniques permits interpretation in terms of fabric formation in the Tourão granite and the inference that at least two successive kinematic events were recorded in this intrusive body devoid of any solid-state deformation overprint. The AMS and pAAR 0-50 fabrics for most of the sites correlate with the early NNE-trending magmatic fabric, whereas pAAR 50-90 reveals a different fabric, probably related to late partitioning of magmatic straining along the E-trending shear zones. In the southern part of the body, a completely different pAAR 0-50 fabric is correlated with the late intrusion of charnockite stocks.

  10. 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

  11. Analytical Support Across the Range of Military Operations

    DTIC Science & Technology

    2011-04-06

    Michael Mayne , USMC, interview by MCCLL Mr. Robert Clark. Company Commander, B Co 1/3 (April15, 2009). 13 Mayne , AAR 2009. 14 2Bn 24th Mar "AAR OIF...Michael Mayne , USMC, interview by MCCLL Mr."Robert Clark. Company Commander, B Co 1/3 (April15, 2009). 17 Major General Michael T. Flynn, Captain...USMC, interview by MCCLL LNO Mr. Chris Wilk.Battalion S2 Intelligence Officer 112 (April 15, 2009). Captain Michael Mayne , USMC, interview by M’CCLL

  12. Determination of depths to centroids of three-dimensional sources of potential-field anomalies with examples from environmental and geologic applications

    NASA Astrophysics Data System (ADS)

    Ravat, D.; Taylor, Patrick T.

    1998-09-01

    A method is developed for determining the depth to the centroid (the geometric center) of `semi-compact' sources. The method, called the anomaly attenuation rate (AAR) method, involves computing radial averages of AARs with increasing distances from a range of assumed source centers. For well-isolated magnetic anomalies from `semi-compact' sources, the theoretical AARs range from ˜2 (close to the sources) to ˜3 (in the far-field region); the corresponding theoretical range of AARs for gravity anomalies is ˜1 to ˜2. When the estimated source centroid is incorrect, the AARs either exceed or fall short of the theoretical values. The levelling-off of the far-field AARs near their theoretical maximum values indicates the upper (deeper) bound of the centroid location. Similarly, near-field AARs lower than the theoretical minimum indicate the lower (shallower) bound of the centroid location. It is not always possible to determine usable upper and lower bounds of the centroids because the method depends on characteristics of sources/anomalies and the noise level of the data. For the environmental magnetic examples considered in this study, the determined deeper bounds were within 4% of the true centroid-to-observation distance. For the case of the gravity anomaly from the Bloomfield Pluton, Missouri, USA, determination of only the shallower bound of the centroid location (˜7 km) was possible. This estimate agrees closely with the centroid of a previously determined three-dimensional model of the Bloomfield Pluton. For satellite magnetic anomalies, the method is appropriate only for high-amplitude, near-circular anomalies due to the inherent low signal-to-noise ratio of satellite magnetic anomalies. Model studies indicate that the AAR method is able to place depths within ±20-30 km of actual center locations from a 400-km observation altitude. Thus, the method may be able to discriminate between upper crustal, lower crustal, and mantle magnetic sources. The results

  13. Dynamic Raman spectroscopy of hydrogen isotopomer mixtures in-line at TILO

    NASA Astrophysics Data System (ADS)

    Lewis, R. J.; Telle, H. H.; Bornschein, B.; Kazachenko, O.; Kernert, N.; Sturm, M.

    2008-07-01

    The pure rotational and vibration-rotational Stokes Raman spectra of flowing gaseous mixtures of the hydrogen isotopomers H2, HD, and D2 were measured in order to test the performance of the proposed tritium purity monitoring system designed for the Karlsruhe Tritium Neutrino (KATRIN) mass experiment, which utilises 532 nm CW laser excitation and fibre-coupled scattered light collection, exploiting 90° excitation observation geometry. Short (100-300 s) exposure times were used to simulate the real-time in-line measurement of hydrogen isotopomer composition at the low (~ 100-150 mbar) pressure required for KATRIN. At 100 s exposure time, an in-line sensitivity of better than 1% was achieved for dynamic changes in the sample gas composition.

  14. 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

  15. Learning for Semantic Parsing and Natural Language Generation Using Statistical Machine Translation Techniques

    DTIC Science & Technology

    2007-08-01

    well (Lapata and Brew , 1999). In this case, the fact that a chair is a physical GOAL makes it more likely that tied means “to physically attach”. These...Ben Gurion University, Beer Sheva, Israel. Katrin Erk (2005). Frame assignment as word sense disambiguation. In Proceed- ings of the Sixth...Generation (INLG-2002), pp. 17–24. Harriman, NY. Maria Lapata and Chris Brew (1999). Using subcategorization to resolve verb class ambiguity. In

  16. Actigraphy of Wrist and Ankle for Measuring Sleep Duration in Altitude Travelers.

    PubMed

    Latshang, Tsogyal Daniela; Mueller, Daniela Juliana; Lo Cascio, Christian Maurizio; Stöwhas, Anne-Christin; Stadelmann, Katrin; Tesler, Noemi; Achermann, Peter; Huber, Reto; Kohler, Malcolm; Bloch, Konrad Ernst

    2016-09-01

    Latshang, Tsogyal Daniela, Daniela Juliana Mueller, Christian Maurizio Lo Cascio, Anne-Christin Stöwhas, Katrin Stadelmann, Noemi Tesler, Peter Achermann, Reto Huber, Malcolm Kohler, and Konrad Ernst Bloch. Actigraphy of wrist and ankle for measuring sleep duration in altitude travelers. High Alt Med Biol. 17:194-202, 2016-Aims: Actigraphy might be convenient to assess sleep disturbances in altitude field studies. Therefore, we evaluated whether actigraphy accurately measures sleep duration in healthy subjects traveling to altitude.

  17. Polymers from plants to develop biodegradable plastics.

    PubMed

    Conrad, Udo

    2005-11-01

    Katrin Neumann et al. have recently shown that transgenic tobacco and potato plants can accumulate high levels of cyanophycin, a possible source for poly-aspartate. This work opens the way to the future production of biodegradable plastics using a plant-based production system. Several problems need to be overcome first, such as growth retardation as a result of cyanophycin accumulating in the cytosol, and a co-production system needs to be developed for economical reasons.

  18. Swine Influenza A Outbreak, Fort Dix, New Jersey, 1976

    DTIC Science & Technology

    2006-01-01

    Incorporated, Gaithersburg, Maryland, USA; ‡Northeast Center for Special Care, Lake Katrine, New York, USA; and §Albert B. Sabin Vaccine Institute , New...assessment, and enhanced surveillance resulted from excellent collaboration between Fort Dix, New Jersey Department of Health, Walter Reed Army Institute ...even less contact with other companies. On arrival, recruits received the 1975–1976 influenza vaccine (A/Port Chalmers/1/73 [H3N2], A/Scotland/840

  19. Towards a Precision Measurement of the Tritium Helium-3 Mass Difference

    NASA Astrophysics Data System (ADS)

    Myers, Edmund; Rana, Raman; Wesson, Bridget; Erickson, Austin

    2012-03-01

    Fitting a low-energy beta-decay spectrum near its endpoint is a direct method for determining the absolute mass scale of electron neutrinos. This is the subject of the large-scale tritium beta-decay experiment KATRIN. Besides a value (or a limit) for a sum of squares of neutrino mass eigenvalues, the fit to KATRIN data, with absolute energy calibration, will also produce a value for ``the electron endpoint for zero neutrino mass'' which is closely related to the Q-value for the beta-decay. Hence, an independent value for the tritium beta-decay Q-value, derived from the 3T - 3He mass difference, can provide a strong test of the systematics of KATRIN. The Florida State University precision Penning trap mass spectrometer has previously produced the most precise values of more than 26 atomic masses, many of which have application to neutrinoless double-beta-decay and to determining fundamental constants. The system is currently being modified for measurements of ions with small m/q ratio, and that are radioactive, to enable a precise measurement of the tritium helium-3 mass difference.

  20. Final scientific and technical report: New experiments to measure the neutrino mass scale

    SciTech Connect

    Monreal, Benjamin

    2016-11-19

    In this work, we made material progress towards future measurements of the mass of the neutrino. The neutrino is a fundamental particle, first observed in the 1950s and subjected to particularly intense study over the past 20 years. It is now known to have some, non-zero mass, but we are in an unusual situation of knowing the mass exists but not knowing what value it takes. The mass may be determined by precise measurements of certain radioactive decay distributions, particularly the beta decay of tritium. The KATRIN experiment is an international project which is nearing the beginning of a tritium measurement campaign using a large electrostatic spectrumeter. This research included participation in KATRIN, including construction and delivery of a key calibration subsystem, the ``Rear Section''. To obtain sensitivity beyond KATRIN's, new techniques are required; this work included R\\&D on a new technique we call CRES (Cyclotron Resonance Electron Spectroscopy) which has promise to enable even-more-sensitive tritium decay measurements. We successfully carried out CRES spectroscopy in a model system in 2014, making an important step towards the design of a next-generation tritium experiment with new neutrino mass measurement abilities.

  1. Reisen im freien Fall - Teil 2: Das Zwillingsparadoxon aus dem Blickwinkel der ART

    NASA Astrophysics Data System (ADS)

    Sonne, Bernd; Weiß, Reinhard

    2013-07-01

    Nachdem wir uns mit den Prinzipien der ART und einigen Beispielen vertraut gemacht haben, kommen wir nun zur Berechnung des Zwillingsparadoxons aus Sicht des reisenden Zwillings. Dabei spielt das Äquivalenzprinzip eine große Rolle. Deshalb wird die Bewegungssituation noch einmal erläutert, diesmal aus Sicht von Katrin. Sie befindet sich in ihrem System S'in Ruhe. In ihrem System läuft die Zeit t'ab. Nach dem Start fühlt Katrin jedoch eine Kraft, die sie als Gravitationskraft interpretieren kann. Sie merkt es daran, dass sie in den Sitz gedrückt wird. Nach einiger Zeit werden die Triebwerke abgeschaltet, und das Raumschiff fliegt mit konstanter Geschwindigkeit weiter, Phase 2. Anschließend wird der Schub der Triebwerke solange umgekehrt, bis das Raumschiff irgendwo mit der Geschwindigkeit null am Umkehrpunkt U landet, Phase 3 (Abb. 15.1). Die Erde, auf der sich Michael befindet, bewegt sich mit x'(t') aus Sicht von Katrin im freien Fall von ihr weg, s. das Experiment mit dem steigenden Fahrstuhl in Abschn. 13.2.1.

  2. 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) and...

  3. 75 FR 75448 - Revised Proposal for Revisions to the Schedules of Civil Penalties for a Violation of a Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ... time to review all the penalties listed in the proposal to determine if they match the severity-scale... period in order to allow AAR more time to review the penalties in the severity scale and to identify and comment more fully on which individual penalties do not in its opinion satisfy the severity-scale criteria...

  4. JPRS Report, Soviet Union, Military Affairs.

    DTIC Science & Technology

    2007-11-02

    General I. Pavlov . Ivan Andreyevich later explained that the call was from the party gorkom, that they had asked for a deferment from the draft for a...Are Prepared for Military Service in Leningrad, and by Whom"] [Text] I went to see Major General I. Pavlov , military commissar for Leningrad

  5. Imperial Parallels: Analyzing the U.S. Army Regionally Aligned Force Strategy in the Context of Historical Imperialism

    DTIC Science & Technology

    2014-06-13

    MILITARY ART AND SCIENCE Strategic Studies by KEVIN WARD, MAJ, U.S. ARMY B.S., United States Military Academy, West Point, New York...10 History of United States Imperialism and Foreign Policy ........................................ 12 United ...ACRONYMS AAR After Action Review ABCT Armored Brigade Combat Team AFRICOM United States African Command AOR Area of Responsibility ASCC Army

  6. 77 FR 25024 - Certification of Compliance With Meal Requirements for the National School Lunch Program Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... foods, and high in sodium, fat and added sugars. The 2005 Dietary Guidelines recommend that Americans... selected local educational agencies that have a demonstrated level of, or are at high risk for...)). Because AARs target local educational agencies that have a demonstrated level of, or are at high risk for...

  7. Automatic anatomy recognition on CT images with pathology

    NASA Astrophysics Data System (ADS)

    Huang, Lidong; Udupa, Jayaram K.; Tong, Yubing; Odhner, Dewey; Torigian, Drew A.

    2016-03-01

    Body-wide anatomy recognition on CT images with pathology becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem because various diseases result in various abnormalities of objects such as shape and intensity patterns. We previously developed an automatic anatomy recognition (AAR) system [1] whose applicability was demonstrated on near normal diagnostic CT images in different body regions on 35 organs. The aim of this paper is to investigate strategies for adapting the previous AAR system to diagnostic CT images of patients with various pathologies as a first step toward automated body-wide disease quantification. The AAR approach consists of three main steps - model building, object recognition, and object delineation. In this paper, within the broader AAR framework, we describe a new strategy for object recognition to handle abnormal images. In the model building stage an optimal threshold interval is learned from near-normal training images for each object. This threshold is optimally tuned to the pathological manifestation of the object in the test image. Recognition is performed following a hierarchical representation of the objects. Experimental results for the abdominal body region based on 50 near-normal images used for model building and 20 abnormal images used for object recognition show that object localization accuracy within 2 voxels for liver and spleen and 3 voxels for kidney can be achieved with the new strategy.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 49 CFR 1180.4 - Procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Waybill Sample. (7) Federal Reserve Board Production Statistics. (8) AAR compilations of bad order ratios... order. At any time, the Board may require the submission of additional copies of any document previously...) Prefiling notification. When filing the notice of intent required by paragraph (b)(1) of this...

  10. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 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...

  11. The Emergence of Organizational Fit: Applying Configuration Theory to the Snohomish County (WA) Emergency Operations Center

    DTIC Science & Technology

    2016-03-01

    BLANK xiii LIST OF ACRONYMS AND ABBREVIATIONS AAR After Action Report CEMP Comprehensive Emergency Management Plan DHS Department of Homeland...Security EOC Emergency Operations Center ESF Emergency Support Function FEMA Federal Emergency Management Agency ICP Incident Command Post ICS...configuration), especially as they moved from decision-making to problem solving . Each also interacted with a large number of external factors and

  12. 78 FR 30896 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ... Warning Sensors, User Data Module Cards and Control Interface Units, Multi-role Electro-Optic End-to-End... Small Laser Transmitter Assemblies, 3 System Processors/Repeaters, 14 AN/AAR-54 Missile Warning Sensors... leadership, promoting stability and global engagement of a friendly country. The proposed sale of this...

  13. 76 FR 4727 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-26

    ... date following the company name and location of each determination references the impact date for all...-Kreuzer Candle Syracuse, NY May 12, 2009. Company. 74,983 AAR Manufacturing, Cadillac, MI December 7, 2009. Inc., Mobility Systems Division. 75,030 Weyerhaeuser Company, Hot Springs, AR December 21, 2009...

  14. Wide Area Recovery and Resiliency Program (WARRP) Knowledge Enhancement Working Group: Multi-Agency Coordination After Action Report

    DTIC Science & Technology

    2012-02-23

    OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 25 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c ...14 Annex C – Participant Feedback...summary of workshop findings are found in Annex C – Participant Feedback. For information on the planning team, or to get more information on this AAR

  15. 78 FR 44189 - Petition for Modification of Single Car Air Brake Test Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... Federal Railroad Administration Petition for Modification of Single Car Air Brake Test Procedures In... the Federal Railroad Administration (FRA) per 49 CFR 232.307 to modify the single car air brake test procedures located in AAR Standard S-486, Code of Air Brake System Tests for Freight Equipment-- Single Car...

  16. 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…

  17. Sublytic complement attack reduces infarct size in rabbit isolated hearts: evidence for C5a-mediated cardioprotection.

    PubMed

    Tanhehco, E J; Lee, H; Lucchesi, B R

    2000-09-01

    Sublytic complement attack can elicit protective cellular responses without precipitating cell death. Our investigation examined the effects of non-lethal complement activation in isolated hearts. New Zealand white rabbit hearts were subjected to 30 min of ischemia followed by 1 h of reperfusion. Prior to ischemia, hearts were perfused for 20 min with 0.5% normal human plasma (NHP). Hearts treated with NHP developed significantly (p<0.05) smaller infarcts compared with controls, expressed as percent of area at risk (AAR) (25.3+/-4.0% vs. 40.9+/-4.3%, respectively). Heat-inactivation, soluble complement receptor 1 (sCR1; 20 nM), and anti-C5a antibody reversed the protective effect of NHP (39.0+/-3.1%, 41.7+/-5.1% and 38.4+/-2.3% AAR, respectively). Hearts treated with 3 nM C5a exhibited infarct sizes similar to those exposed to NHP (27.6+/-5.0% AAR). sCR1 alone did not affect infarct size (37.9+/-4.5% AAR). The results suggest that non-lethal complement activation attenuates reperfusion injury through formation of C5a.

  18. 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 over...

  19. Marine Corps Center for Lessons Learned. Volume 8, Issue 11, November 2012

    DTIC Science & Technology

    2012-11-01

    district, they also provided overwatch for the AUP when necessary. The AAR points out that language and culture training should be narrowly focused on...Uniformed Police ( AUP ). Following its deployment, 2/6 prepared a OEF 11.2/12.1 Post-Deployment Briefi ng that is available on the MCCLL SIPR website

  20. The role of α1-adrenergic receptors in regulating metabolism: increased glucose tolerance, leptin secretion and lipid oxidation.

    PubMed

    Shi, Ting; Papay, Robert S; Perez, Dianne M

    2017-04-01

    The role of α1-adrenergic receptors (α1-ARs) and their subtypes in metabolism is not well known. Most previous studies were performed before the advent of transgenic mouse models and utilized transformed cell lines and poorly selective antagonists. We have now studied the metabolic regulation of the α1A- and α1B-AR subtypes in vivo using knock-out (KO) and transgenic mice that express a constitutively active mutant (CAM) form of the receptor, assessing subtype-selective functions. CAM mice increased glucose tolerance while KO mice display impaired glucose tolerance. CAM mice increased while KO decreased glucose uptake into white fat tissue and skeletal muscle with the CAM α1A-AR showing selective glucose uptake into the heart. Using indirect calorimetry, both CAM mice demonstrated increased whole body fatty acid oxidation, while KO mice preferentially oxidized carbohydrate. CAM α1A-AR mice displayed significantly decreased fasting plasma triglycerides and glucose levels while α1A-AR KO displayed increased levels of triglycerides and glucose. Both CAM mice displayed increased plasma levels of leptin while KO mice decreased leptin levels. Most metabolic effects were more efficacious with the α1A-AR subtype. Our results suggest that stimulation of α1-ARs results in a favorable metabolic profile of increased glucose tolerance, cardiac glucose uptake, leptin secretion and increased whole body lipid metabolism that may contribute to its previously recognized cardioprotective and neuroprotective benefits.

  1. 49 CFR 179.103-5 - Bottom outlets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... approved modification thereof. (See appendix E. Fig. E17 of the AAR Specifications for Tank Cars for... 1-inch NPT pipe plug (see Fig. E17.1) or including an auxiliary valve with a threaded closure. (ii) A threaded cap closure arrangement including a minimum 1-inch NPT pipe plug (see Fig. E17.2) or...

  2. 76 FR 40701 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... installed and 2 spares), 6 AN/ APR-39A(V)4 Radar Signal Detecting Sets, 80 AN/AVS-9 Night Vision Devices, 6 Star Safire III Forward Looking Infrared Radar Systems, 6 AAR-57(V)3 Common Missile Warning Systems, 6... Systems and Weather Radars, Aviation Mission Planning Station, government furnished equipment, ferry...

  3. Investigation of Diesel Fuel Fire Vulnerability Parameters in Armored Personnel Carriers due to Ballistic Penetration

    DTIC Science & Technology

    1985-03-22

    BRADELY FIGHTING CDR VEHICLE SYS US ARMY FOREIGN SCIENCE & TECH ATTN: AMCPM-FVS-M I CENTER WARREN MI 48090 ATTN: AMXST-MT-1 AMXST-BA PROG MGR, M113...ATZL-CAT-A 6 ATTN: CODE 05M4 (MR R LAYNE) FORT. LEAVENWORTH KA 66027 WASHINGTON DC 20362 CDR CDR US ARMY LOGISTICS CIRCDATTN: ARYLOGS (R AARS ) I DAVID

  4. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  5. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  6. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  7. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  8. Tobacco users' perceptions of a brief tobacco cessation intervention in community pharmacies.

    PubMed

    Patwardhan, Pallavi D; Chewning, Betty A

    2010-01-01

    To explore factors affecting tobacco users' perceived appropriateness of a brief and proactive tobacco cessation counseling program, ask, advise, and refer (AAR), at community pharmacies. Inductive thematic analysis. Southern Wisconsin during fall 2008. 24 tobacco users who had recently received brief and proactive tobacco cessation counseling at a community pharmacy. Semistructured telephone interviews conducted by primary author. Perceptions of a brief and proactive tobacco cessation counseling program conducted at community pharmacies. In conducting the thematic analysis, eight distinct themes were identified. Display of information and resources at pharmacies for use by tobacco users as needed was identified as the most predominant theme and was found to be most helpful by many respondents. Other themes identified in decreasing order of prevalence were: tobacco users' perceptions of the role of pharmacists in health care, tobacco users' belief that smoking could interact with a current medication or health condition, tobacco users' sensitivity toward their tobacco use behavior or being told what to do, nonconfrontational and friendly approach of pharmacists, tobacco users' readiness to quit at the time of AAR counseling, tobacco user initiation of tobacco use discussion, and tobacco users' belief that tobacco use is bad. Overall, this qualitative investigation suggests that several factors might influence tobacco users' perceived appropriateness of AAR counseling at community pharmacies. AAR might be well received by tobacco users and pharmacy patrons as long as it is done in a professional and respectful manner.

  9. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRAKE SYSTEM SAFETY STANDARDS FOR FREIGHT... 49 Transportation 4 2012-10-01 2012-10-01 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...

  10. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRAKE SYSTEM SAFETY STANDARDS FOR FREIGHT... 49 Transportation 4 2011-10-01 2011-10-01 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...

  11. 75 FR 4703 - Track Safety Standards; Continuous Welded Rail (CWR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... received one petition questioning the definitions of ``adjusting/de-stressing'' and ``buckling-prone... the petitioner. ``Buckling-Prone Condition'' Definition In the petition, AAR stated that the definition of ``buckling prone condition'' included in the final rule at Sec. 213.119(l) was not proposed...

  12. 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...

  13. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... weld metal and heat affected zone prepared and tested in accordance with AAR Specifications for Tank...) Insulation must be of approved material. (c) Excess flow valves must be installed under all liquid and vapor... OPERATING TEMPERATURE _ °F. (i) The tank car and insulation must be designed to prevent the vapor pressure...

  14. 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

  15. 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...

  16. Impulse-response testing to evaluate the degree of alkali-aggregate reaction in concrete drilled-shaft foundations for electricity transmission towers

    NASA Astrophysics Data System (ADS)

    Davis, Allen; Kennedy, James

    1998-03-01

    Alkali-aggregate reaction (AAR) has affected the concrete in drilled shafts (cast in place piles) beneath electricity transmission towers along a 42-mile (67 km) section of transmission line in Southern California. In order to prioritize the maintenance program for these shafts, a nondestructive test methodology was sought to quantify the severity of the AAR with depth in each shaft. Shaft diameters of 19, 30, 36, 42, and 54 inches (475, 760, 910, 1067 and 1660 mm) were present, with shaft lengths between 10 and 30 feet (3 and 6 m). Over the last thirty years, impulse-response (I-R) testing has been successfully used to evaluate the integrity of drilled shafts, and computer simulation programs have also been developed for matching I-R test responses with theoretical shaft shapes and concrete quality. A program to test as many shafts as could be accessed in the difficult, mountainous terrain along this transmission line included mobilization of equipment and testing personnel by helicopter. Two hundred ten shafts were tested along the line in five days. Matching of test response mobility-frequency plots in computer simulation was achieved by varying the simulated concrete modulus and density, as well as the shaft cross section area. Up to three grades of concrete quality were identified in each shaft, representing the decreasing degree of AAR with depth. The tested shafts were then rated for increasing AAR severity, in order to select shafts for repair or replacement.

  17. 49 CFR 232.603 - Design, interoperability, and configuration management requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Pneumatic (ECP) Braking Systems § 232.603 Design, interoperability, and configuration management... reference, include the following: (1) AAR S-4200, “Electronically Controlled Pneumatic (ECP) Cable-Based... both, where testing or demonstration, or both, will be conducted pursuant to an FRA-recognized industry...

  18. T2-weighted cardiac MR assessment of the myocardial area-at-risk and salvage area in acute reperfused myocardial infarction: comparison of state-of-the-art dark blood and bright blood T2-weighted sequences.

    PubMed

    Viallon, Magalie; Mewton, Nathan; Thuny, Franck; Guehring, Jens; O'Donnell, Thomas; Stemmer, Alto; Bi, Xiaoming; Rapacchi, Stanislas; Zuehlsdorff, Sven; Revel, Didier; Croisille, Pierre

    2012-02-01

    To compare different state-of-the-art T2-weighted (T2w) imaging sequences combined with late gadolinium enhancement (LGE) for myocardial salvage area (MSA) assessment by cardiac magnetic resonance (CMR). T2w imaging has been used to assess the myocardial area at risk (AAR) in acute myocardial infarction (AMI) patients, but its clinical application is challenging due to technical and physical limitations. Thirty patients with reperfused AMI underwent complete CMR imaging 2-5 days after hospital admission. Myocardial AAR and MSA were quantified on four different T2w sequences: (a) free-breathing T2-prepared single-shot balanced steady-state free precession (T2p_ssbSSFP); (b) breathhold T2-weighted acquisition for cardiac unified T2 edema (ACUTE); (c) breathhold T2w dark-blood inversion recovery turbo-spin echo (IR-TSE) (short-term inversion recovery: STIR); and (d) free-breathing high-resolution T2 dark-blood navigated BLADE. The diagnostic performance of each technique was also assessed. Quantitative analysis showed significant differences in myocardial AAR extent as quantified by the four T2w sequences (P < 0.05). There were also significant differences in sensitivity, specificity and overall diagnostic performance. Detection and quantification of AAR, and thus of MSA, by T2wCMR in reperfused AMI patients varied significantly between different T2w sequences in the same clinical setting. Copyright © 2011 Wiley Periodicals, Inc.

  19. Video-rhino-hygrometer: a new method for evaluation of nasal breathing after nasal surgery.

    PubMed

    Casale, Manuele; Pappacena, Marco; Setola, Roberto; Soda, Paolo; Cusimano, Valerio; Vitali, Massimiliano; Mladina, Ranko; Salvinelli, Fabrizio

    2010-01-01

    Nasal obstruction is one of the most frequent symptoms in the ear, nose, and throat (ENT) setting. It can be evaluated either subjectively or objectively. In a subjective way, a visual analog scale (VAS) and the Sino-Nasal Outcome Test 20 (SNOT 20) can rapidly quantify the degree of obstruction, whereas the most commonly used objective methods are nasal endoscopy and active anterior rhinomanometry (AAR). It is still a matter of controversy to what extent the sense of nasal obstruction is associated with objective measures for nasal space and airflow. The aim of the study was to evaluate nasal breathing before and after functional nasal surgery by video-rhino-hygrometer (VRH) comparing the results with widely accepted methods. Twenty patient candidates for septoplasty and inferior turbinate reduction were included in the study. SNOT-20, VAS, nasal endoscopy, and AAR were analyzed and compared with VRH values. Before surgery VRH showed variability of nasal respiratory flow between individuals and between nostrils. After surgery we had an increase (p < 0.05) of airflow in both nostrils. VRH data were found to be correlated with VAS and SNOT-20 values (p < 0.05) both pre- and postoperatively. Despite the statistically significant correlation of AAR with SNOT-20 and VAS, no statistically significant correlation between AAR and VRH was found. VRH provides an immediate, easy, and noninvasive assessment of nasal respiration. For these reasons it can be used, in association with rhinoscopic data and other instrumental tests, to evaluate nasal breathing in daily ENT practice.

  20. 49 CFR 179.220-14 - Openings in the tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.220-14... with AAR Specifications for Tank Cars, appendix E (IBR, see § 171.7 of this subchapter). In determining the required reinforcement area for openings in the outer shell, t shall be one-fourth inch. [68 FR...

  1. Obstacle Avoidance Control for the REMUS Autonomous Underwater Vehicle

    DTIC Science & Technology

    2002-12-01

    the advent of improved mines, submarine quieting, and other littoral threats. It has often been said that the best way to combat threats in a...are often linearized using Tayor series expansion terms in individual motion components. These expansion terms are termed ‘hydrodynamic

  2. Carcass and meat quality of Assaf milk fed lambs: Effect of rearing system and sex.

    PubMed

    Rodríguez, A B; Landa, R; Bodas, R; Prieto, N; Mantecón, A R; Giráldez, F J

    2008-10-01

    The effect of sex and rearing system on growth and carcass and meat characteristics of milk fed Assaf lambs was studied. Thirty-six lambs, 18 males and 18 females were used. Twelve lambs remained with their mothers throughout the experiment (NR). Within 24-36h of birth, the rest were housed individually and fed twice a day ad libitum (AAR) or at 70% of ad libitum consumption (RAR) with reconstituted cow's milk. Sex did not affect animal performance, yet females showed higher carcass and non-carcass fat deposits. NR lambs showed greater BWG than AAR fed lambs, and AAR, higher than the RAR. Differences between naturally and artificially reared lambs in CCW and killing out percentage were not significant. Empty digestive tract and mesenteric fat weights were greater for RAR than NR lambs, with the AAR lambs demonstrating intermediate values; conversely, omental fat was greater in NR lambs. Carcass ether extract content was greater for NR lambs, possibly due to the greater growth. Use of ad libitum cow's milk substitute in suckling lambs twice a day resulted in less body weight gain but similar killing out percentages compared to naturally raised lambs. A 70% restricted supply increased the days in suckling and reduced carcass fatness and compactness. Except for water loss, which was less in NR than artificially fed lambs, no differences were found in meat characteristics.

  3. Properties of Jupiter's auroral acceleration region inferred with HST-STIS spectral images

    NASA Astrophysics Data System (ADS)

    Arridge, C. S.; Ray, L. C.; Gustin, J.; Grodent, D. C.

    2016-12-01

    Jupiter's dynamic auroral region is the signature of magnetosphere-ionosphere coupling. Precipitating auroral electrons are part of a current system which transports angular momentum from the planetary atmosphere to sub-corotating magnetospheric plasma. The magnitude of the currents and hence precipitating energy flux, are sensitive to the characteristics of the high-latitude magnetosphere, in particular the location of the auroral acceleration region (AAR) and the density and temperature of the high-latitude electron population. We use HST STIS observations of Jupiter's aurora (Gustin et al. [2016]) to infer the location of the AAR and the properties of the precipitating auroral electrons. To do this, we determine the energy of the precipitating electrons and incident energy flux for the two distinct regions within the main aurora and within flare regions. The resulting relationships between energy flux and electron precipitation energy for the main auroral emission are then compared to the theoretical relationship derived by Lundin & Sandahl [1978], in order to derive the location of the AAR and the temperatures and densities of the electrons at the top of the AAR prior to acceleration. We find that that each emission region is best reproduced using a multiple auroral acceleration regions with different properties, rather than a single auroral acceleration region with a varying potential drop strength.

  4. 78 FR 47824 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION... continue in service a car if an end of car cushioning unit is leaking clearly formed droplets. In its... droplets. AAR requests a 3-year test period during which it may be shown that end of car cushioning...

  5. 76 FR 76217 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION...)(3), which requires that end platforms on boxcars be ``centered on each end of car between inner ends... inches. AAR and ASLRRA stated that more than 18,000 cars and 20 different car owners are affected....

  6. 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 of...

  7. 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 of...

  8. 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 of...

  9. 49 CFR 179.400-12 - Postweld heat treatment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 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 of...

  10. Developing Learning Organizations at the Small Unit Level

    DTIC Science & Technology

    2010-01-01

    the After Action Review (AAR) is another highlighted success in its holistic attempts to become a learning organization. In his Harvard Business Review article...reexamined/index.html. Garvin, David A., Edmondson, Amy C. & Gino Francesca (2008). Is Yours a Learning Organization? Harvard Business Review . www.hbr.org

  11. 49 CFR 180.517 - Reporting and record retention requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., see § 171.7 of this subchapter) apply. The builder of the car or a facility performing work on the car... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.517 Reporting and... car must retain the certificate of construction (AAR Form 4-2) and related papers certifying that...

  12. 49 CFR 180.517 - Reporting and record retention requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., see § 171.7 of this subchapter) apply. The builder of the car or a facility performing work on the car... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.517 Reporting and... car must retain the certificate of construction (AAR Form 4-2) and related papers certifying that...

  13. 49 CFR 179.4 - Changes in specifications for tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Changes in specifications for tank cars. 179.4... TANK CARS Introduction, Approvals and Reports § 179.4 Changes in specifications for tank cars. (a...—Tank Car Safety, AAR, for consideration by its Tank Car Committee. An application for construction...

  14. 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...

  15. 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...

  16. 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.

  17. Ridge Tectonics, Magma Supply, and Ridge-Hotpot Interaction at the Eastern End of the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    During 2011-2013 the Korea Polar Research Institute (KOPRI) conducted three successive expeditions to the eastern end of the Australian-Antarctic Ridge (AAR) to investigate the tectonics, geochemistry, and hydrothermal activity of this intermediate fast spreading system. On board the Korean icebreaker R/V Araon, the science party collected multiple types of data including multibeam bathymetry, gravity, magnetics, as well as rock and water column samples. In addition, Miniature Autonomous Plume Recorders (MAPRs) were deployed at each of the wax-core rock sampling sites to detect the presence of active hydrothermal vents. In this study, we present a detailed analysis of a 360-km-long super-segment at the eastern end of the AAR to quantify the spatial variations in ridge morphology and investigate its respond to changes in melt supply. The study region contains several intriguing bathymetric features including (1) abrupt changes in the axial topography, alternating between rift valleys and axial highs within relatively short ridge segments; (2) overshooting ridge tips at the ridge-transform intersections; (3) systematic migration patterns of hooked ridges; (4) a 350-km-long mega-transform fault; and (5) robust axial and off-axis volcanisms. To obtain a proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with a shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle than the conjugate northern flank. Furthermore, this N-S asymmetry becomes more prominent toward the super-segment of the AAR. Such regional variations in seafloor topography and RMBA are consistent with the hypothesis that ridge segments in the study area have interacted with the Balleny hotspot, currently lies southwest of the AAR. However, the influence of

  18. 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

  19. The infarct-sparing effect of IB-MECA against myocardial ischemia/reperfusion injury in mice is mediated by sequential activation of adenosine A3 and A 2A receptors.

    PubMed

    Tian, Yikui; Marshall, Melissa; French, Brent A; Linden, Joel; Yang, Zequan

    2015-03-01

    Conflicting results exist regarding the role of A3 adenosine receptors (A3ARs) in mediating cardioprotection during reperfusion following myocardial infarction. We hypothesized that the effects of the A3AR agonist IB-MECA to produce cardioprotection might involve activation of other adenosine receptor subtypes. C57Bl/6 (B6), A3AR KO, A2AAR KO, and A2AAR KO/WT bone marrow chimeric mice were assigned to 12 groups undergoing either hemodynamic studies or 45 min of LAD occlusion and 60 min of reperfusion. IB-MECA (100 μg/kg) or vehicle was administered by iv bolus 5 min before reperfusion. Radioligand binding assays showed that IB-MECA has high affinity for the mouse A3AR (K i = 0.17 ± 0.05 nM), but also can bind with lower affinity to the A1AR (9.0 ± 2.4 nM) or the A2AAR (56.5 ± 10.2 nM). IB-MECA caused bi-phasic hemodynamic changes, which were completely absent in A3AR KO mice and were modified by A2AAR blockade or deletion. IB-MECA stimulated histamine release, increased heart rate, and significantly reduced IF size in B6 mice from 61.5 ± 1.4 to 48.6 ± 2.4% of risk region (RR; 21% reduction, p < 0.05) but not in A3AR KO mice. Compared to B6, A3AR KO mice had significantly reduced IF size (p < 0.05). In B6/B6 bone marrow chimeras, IB-MECA caused a 47% reduction of IF size (from 47.3 ± 3.9 to 24.7 ± 4.5, p < 0.05). However, no significant cardioprotective effect of IB-MECA was observed in A2AARKO/B6 mice, which lacked A2AARs only on their bone marrow-derived cells. Activation of A3ARs induces a bi-phasic hemodynamic response, which is partially mediated by activation of A2AARs. The cardioprotective effect of IB-MECA is due to the initial activation of A3AR followed by activation of A2AARs in bone marrow-derived cells.

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

    DOE PAGES

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

    2016-05-23

    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. Here 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 andmore » 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. Finally, 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.« less

  1. Geophysical Characteristics of the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    Between 2011 and 2013, the Korea Polar Research Institute (KOPRI) conducted three consecutive geologic surveys at the little explored eastern ends of the Australian-Antarctic Ridge (AAR) to characterize the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. Using the Korean icebreaker R/V Araon, the multi-disciplinary research team collected bathymetry, gravity, magnetics, and rock and water column samples. In addition, Miniature Autonomous Plume Recorders (MAPRs) were deployed at wax-core rock sampling sites to detect the presence of active hydrothermal vents. Here we present a detailed analysis of a 300-km-long supersegment of the AAR to quantify the spatial variations in ridge morphology and robust axial and off-axis volcanisms. 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 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 than 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 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

  2. Accuracy of Area at Risk Quantification by Cardiac Magnetic Resonance According to the Myocardial Infarction Territory.

    PubMed

    Fernández-Friera, Leticia; García-Ruiz, José Manuel; García-Álvarez, Ana; Fernández-Jiménez, Rodrigo; Sánchez-González, Javier; Rossello, Xavier; Gómez-Talavera, Sandra; López-Martín, Gonzalo J; Pizarro, Gonzalo; Fuster, Valentín; Ibáñez, Borja

    2017-05-01

    Area at risk (AAR) quantification is important to evaluate the efficacy of cardioprotective therapies. However, postinfarction AAR assessment could be influenced by the infarcted coronary territory. Our aim was to determine the accuracy of T2-weighted short tau triple-inversion recovery (T2W-STIR) cardiac magnetic resonance (CMR) imaging for accurate AAR quantification in anterior, lateral, and inferior myocardial infarctions. Acute reperfused myocardial infarction was experimentally induced in 12 pigs, with 40-minute occlusion of the left anterior descending (n = 4), left circumflex (n = 4), and right coronary arteries (n = 4). Perfusion CMR was performed during selective intracoronary gadolinium injection at the coronary occlusion site (in vivo criterion standard) and, additionally, a 7-day CMR, including T2W-STIR sequences, was performed. Finally, all animals were sacrificed and underwent postmortem Evans blue staining (classic criterion standard). The concordance between the CMR-based criterion standard and T2W-STIR to quantify AAR was high for anterior and inferior infarctions (r = 0.73; P = .001; mean error = 0.50%; limits = -12.68%-13.68% and r = 0.87; P = .001; mean error = -1.5%; limits = -8.0%-5.8%, respectively). Conversely, the correlation for the circumflex territories was poor (r = 0.21, P = .37), showing a higher mean error and wider limits of agreement. A strong correlation between pathology and the CMR-based criterion standard was observed (r = 0.84, P < .001; mean error = 0.91%; limits = -7.55%-9.37%). T2W-STIR CMR sequences are accurate to determine the AAR for anterior and inferior infarctions; however, their accuracy for lateral infarctions is poor. These findings may have important implications for the design and interpretation of clinical trials evaluating the effectiveness of cardioprotective therapies. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  3. Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts.

    PubMed

    Zhou, Zhichao; Rajamani, Uthra; Labazi, Hicham; Tilley, Stephen L; Ledent, Catherine; Teng, Bunyen; Mustafa, S Jamal

    2015-06-01

    Adenosine increases coronary flow mainly through the activation of A2A and A2B adenosine receptors (ARs). However, the mechanisms for the regulation of coronary flow are not fully understood. We previously demonstrated that adenosine-induced increase in coronary flow is in part through NADPH oxidase (Nox) activation, which is independent of activation of either A1 or A3ARs. In this study, we hypothesize that adenosine-mediated increase in coronary flow through Nox activation depends on A2A but not A2BARs. Functional studies were conducted using isolated Langendorff-perfused mouse hearts. Hydrogen peroxide (H2O2) production was measured in isolated coronary arteries from WT, A2AAR knockout (KO), and A2BAR KO mice using dichlorofluorescein immunofluorescence. Adenosine-induced concentration-dependent increase in coronary flow was attenuated by the specific Nox2 inhibitor gp91 ds-tat or reactive oxygen species (ROS) scavenger EUK134 in both WT and A2B but not A2AAR KO isolated hearts. Similarly, the A2AAR selective agonist CGS-21680-induced increase in coronary flow was significantly blunted by Nox2 inhibition in both WT and A2BAR KO, while the A2BAR selective agonist BAY 60-6583-induced increase in coronary flow was not affected by Nox2 inhibition in WT. In intact isolated coronary arteries, adenosine-induced (10 μM) increase in H2O2 formation in both WT and A2BAR KO mice was attenuated by Nox2 inhibition, whereas adenosine failed to increase H2O2 production in A2AAR KO mice. In conclusion, adenosine-induced increase in coronary flow is partially mediated by Nox2-derived H2O2, which critically depends upon the presence of A2AAR.

  4. 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.

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

    SciTech Connect

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

    2016-05-23

    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. Here 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. Finally, 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.

  6. Different APC genotypes in proximal and distal sporadic colorectal cancers suggest distinct WNT/β-catenin signalling thresholds for tumourigenesis.

    PubMed

    Christie, M; Jorissen, R N; Mouradov, D; Sakthianandeswaren, A; Li, S; Day, F; Tsui, C; Lipton, L; Desai, J; Jones, I T; McLaughlin, S; Ward, R L; Hawkins, N J; Ruszkiewicz, A R; Moore, J; Burgess, A W; Busam, D; Zhao, Q; Strausberg, R L; Simpson, A J; Tomlinson, I P M; Gibbs, P; Sieber, O M

    2013-09-26

    Biallelic protein-truncating mutations in the adenomatous polyposis coli (APC) gene are prevalent in sporadic colorectal cancer (CRC). Mutations may not be fully inactivating, instead producing WNT/β-catenin signalling levels 'just-right' for tumourigenesis. However, the spectrum of optimal APC genotypes accounting for both hits, and the influence of clinicopathological features on genotype selection remain undefined. We analysed 630 sporadic CRCs for APC mutations and loss of heterozygosity (LOH) using sequencing and single-nucleotide polymorphism microarrays, respectively. Truncating APC mutations and/or LOH were detected in 75% of CRCs. Most truncating mutations occurred within a mutation cluster region (MCR; codons 1282-1581) leaving 1-3 intact 20 amino-acid repeats (20AARs) and abolishing all Ser-Ala-Met-Pro (SAMP) repeats. Cancers commonly had one MCR mutation plus either LOH or another mutation 5' to the MCR. LOH was associated with mutations leaving 1 intact 20AAR. MCR mutations leaving 1 vs 2-3 intact 20AARs were associated with 5' mutations disrupting or leaving intact the armadillo-repeat domain, respectively. Cancers with three hits had an over-representation of mutations upstream of codon 184, in the alternatively spliced region of exon 9, and 3' to the MCR. Microsatellite unstable cancers showed hyper-mutation at MCR mono- and di-nucleotide repeats, leaving 2-3 intact 20AARs. Proximal and distal cancers exhibited different preferred APC genotypes, leaving a total of 2 or 3 and 0 to 2 intact 20AARs, respectively. In conclusion, APC genotypes in sporadic CRCs demonstrate 'fine-tuned' interdependence of hits by type and location, consistent with selection for particular residual levels of WNT/β-catenin signalling, with different 'optimal' thresholds for proximal and distal cancers.

  7. 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

  8. Distribution of adrenergic receptors in the enteric nervous system of the guinea pig, mouse, and rat.

    PubMed

    Nasser, Yasmin; Ho, Winnie; Sharkey, Keith A

    2006-04-10

    Adrenergic receptors in the enteric nervous system (ENS) are important in control of the gastrointestinal tract. Here we describe the distribution of adrenergic receptors in the ENS of the ileum and colon of the guinea pig, rat, and mouse by using single- and double-labelling immunohistochemistry. In the myenteric plexus (MP) of the rat and mouse, alpha2a-adrenergic receptors (alpha2a-AR) were widely distributed on neurons and enteric glial cells. alpha2a-AR mainly colocalized with calretinin in the MP, whereas submucosal alpha2a-AR neurons colocalized with vasoactive intestinal polypeptide (VIP), neuropeptide Y, and calretinin in both species. In the guinea pig ileum, we observed widespread alpha2a-AR immunoreactivity on nerve fibers in the MP and on VIP neurons in the submucosal plexus (SMP). We observed extensive beta1-adrenergic receptor (beta1-AR) expression on neurons and nerve fibers in both the MP and the SMP of all species. Similarly, the beta2-adrenergic receptor (beta2-AR) was expressed on neurons and nerve fibers in the SMP of all species, as well as in the MP of the mouse. In the MP, beta1- and beta2-AR immunoreactivity was localized to several neuronal populations, including calretinin and nitrergic neurons. In the SMP of the guinea pig, beta1- and beta2-AR mainly colocalized with VIP, whereas, in the rat and mouse, beta1- and beta2-AR were distributed among the VIP and calretinin populations. Adrenergic receptors were widely localized on specific neuronal populations in all species studied. The role of glial alpha2a-AR is unknown. These results suggest that sympathetic innervation of the ENS is directed toward both enteric neurons and enteric glia.

  9. Automated Quantification of Myocardial Salvage in a Rat Model of Ischemia–Reperfusion Injury Using 3D High‐Resolution Magnetic Resonance Imaging (MRI)

    PubMed Central

    Grieve, Stuart M.; Mazhar, Jawad; Callaghan, Fraser; Kok, Cindy Y.; Tandy, Sarah; Bhindi, Ravinay; Figtree, Gemma A.

    2014-01-01

    Background Quantification of myocardial “area at risk” (AAR) and myocardial infarction (MI) zone is critical for assessing novel therapies targeting myocardial ischemia–reperfusion (IR) injury. Current “gold‐standard” methods perfuse the heart with Evan's Blue and stain with triphenyl tetrazolium chloride (TTC), requiring manual slicing and analysis. We aimed to develop and validate a high‐resolution 3‐dimensional (3D) magnetic resonance imaging (MRI) method for quantifying MI and AAR. Methods and Results Forty‐eight hours after IR was induced, rats were anesthetized and gadopentetate dimeglumine was administered intravenously. After 10 minutes, the coronary artery was re‐ligated and a solution containing iron oxide microparticles and Evan's Blue was infused (for comparison). Hearts were harvested and transversally sectioned for TTC staining. Ex vivo MR images of slices were acquired on a 9.4‐T magnet. T2* data allowed visualization of AAR, with microparticle‐associated signal loss in perfused regions. T1 data demonstrated gadolinium retention in infarcted zones. Close correlation (r=0.92 to 0.94; P<0.05) of MRI and Evan's Blue/TTC measures for both AAR and MI was observed when the combined techniques were applied to the same heart slice. However, 3D MRI acquisition and analysis of whole heart reduced intra‐observer variability compared to assessment of isolated slices, and allowed automated segmentation and analysis, thus reducing interobserver variation. Anatomical resolution of 81 μm3 was achieved (versus ≈2 mm with manual slicing). Conclusions This novel, yet simple, MRI technique allows precise assessment of infarct and AAR zones. It removes the need for tissue slicing and provides opportunity for 3D digital analysis at high anatomical resolution in a streamlined manner accessible for all laboratories already performing IR experiments. PMID:25146703

  10. 5-HT1A receptor pharmacophores to screen for off-target activity of α1-adrenoceptor antagonists

    NASA Astrophysics Data System (ADS)

    Ngo, Tony; Nicholas, Timothy J.; Chen, Junli; Finch, Angela M.; Griffith, Renate

    2013-04-01

    The α1-adrenoceptors (α1-ARs), in particular the α1A-AR subtype, are current therapeutic targets of choice for the treatment of urogenital conditions, such as benign prostatic hyperplasia (BPH). Due to the similarity between the transmembrane domains of the α1-AR subtypes, and the serotonin receptor subtype 1A (5-HT1A-R), currently used α1-AR subtype-selective drugs to treat BPH display considerable off-target affinity for the 5-HT1A-R, leading to side effects. We describe the construction and validation of pharmacophores for 5-HT1A-R agonists and antagonists. Through the structural diversity of the training sets used in their development, these pharmacophores define the properties of a compound needed to bind to 5-HT1A receptors. Using these and previously published pharmacophores in virtual screening and profiling, we have identified unique chemical compounds (hits) that fit the requirements to bind to our target, the α1A-AR, selectively over the off-target, the 5-HT1A-R. Selected hits have been obtained and their affinities for α1A-AR, α1B-AR and 5-HT1A-R determined in radioligand binding assays, using membrane preparations which contain human receptors expressed individually. Three of the tested hits demonstrate statistically significant selectivity for α1A-AR over 5-HT1A-R. All seven tested hits bind to α1A-AR, with two compounds displaying K i values below 1 μM, and a further two K i values of around 10 μM. The insights and knowledge gained through the development of the new 5-HT1A-R pharmacophores will greatly aid in the design and synthesis of derivatives of our lead compound, and allow the generation of more efficacious and selective ligands.

  11. Incidence, treatment, and outcome of acute aortic valve regurgitation complicating percutaneous balloon aortic valvuloplasty.

    PubMed

    Dall'Ara, Gianni; Saia, Francesco; Moretti, Carolina; Marrozzini, Cinzia; Taglieri, Nevio; Bordoni, Barbara; Chiarabelli, Matteo; Ciuca, Cristina; Rapezzi, Claudio; Marzocchi, Antonio

    2017-03-01

    To evaluate the incidence, treatment, and outcomes of acute aortic regurgitation (ARR) complicating BAV. In the transcatheter aortic valve implantation (TAVI) era, there is an increase of percutaneous balloon aortic valvuloplasty (BAV) procedures with different indications. From the prospective BAV registry of the University of Bologna, which has enrolled patients between the year 2000 and the present, we selected those who suffered intraprocedural AAR with overt hemodynamic instability. Worsening of baseline aortic insufficiency without hemodynamic collapse, treatment of degenerated biological valve prosthesis, and BAV performed within a planned TAVI procedure were excluded. The main endpoints were in-hospital and 30-day mortality. Out of 1517 BAVs, we identified 26 cases of AAR (1.7%). This complication occurred in 80.8% of cases after one or two balloon inflations. Mean transaortic gradient decreased from 50.6 ± 19.3 to 26.0 ± 14.4 mm Hg (p < 0.01). In 8(30.8%) patients, AAR spontaneously resolved within few minutes; in 18 cases, the operators had to perform a rescue maneuver to reposition a valve leaflet got stuck in the opening position (this maneuver was successful in 13/18 of the cases, 72.2%). Out of 5 persistent AAR, 3 were managed with emergency TAVI or surgery, while 2 were unresolved. In-hospital mortality was 15.4% (n = 4), whereas no more deaths occurred up to 30 days. AAR is a fearsome complication of BAV and portends a grim prognosis. In some cases, it can be resolved with appropriate technical maneuvers; in others, a rescue TAVI or surgical valve replacement may be necessary. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  12. Cell membrane chromatography competitive binding analysis for characterization of α1A adrenoreceptor binding interactions.

    PubMed

    Du, Hui; Ren, Jing; Wang, Sicen; He, Langchong

    2011-07-01

    A new high α(1A) adrenoreceptor (α(1A)AR) expression cell membrane chromatography (CMC) method was developed for characterization of α(1A)AR binding interactions. HEK293 α(1A) cell line, which expresses stably high levels of α(1A)AR, was used to prepare the stationary phase in the CMC model. The HEK293 α(1A)/CMC-offline-HPLC system was applied to specifically recognize the ligands which interact with the α(1A)AR, and the dissociation equilibrium constants (K (D)) obtained from the model were (1.87 ± 0.13) × 10(-6) M for tamsulosin, (2.86 ± 0.20) × 10(-6) M for 5-methylurapidil, (3.01 ± 0.19) × 10(-6) M for doxazosin, (3.44 ± 0.19) × 10(-6) M for terazosin, (3.50 ± 0.21) × 10(-6) M for alfuzosin, and (7.57 ± 0.31) × 10(-6) M for phentolamine, respectively. The competitive binding study between tamsulosin and terazosin indicated that the two drugs interacted at the common binding site of α(1A)AR. However, that was not the case between tamsulosin and oxymetazoline. The results had a positive correlation with those from radioligand binding assay and indicated that the CMC method combined modified competitive binding could be a quick and efficient way for characterizing the drug-receptor interactions.

  13. Tricyclic antidepressants exhibit variable pharmacological profiles at the α2A adrenergic receptor

    PubMed Central

    Cottingham, Christopher; Percival, Stefanie; Birky, Tana; Wang, Qin

    2014-01-01

    Antidepressant mechanisms of action remain shrouded in mystery, greatly hindering our ability to develop therapeutics which can fully treat patients suffering from depressive disorders. In an attempt to shed new light on this topic, we have undertaken a series of studies investigating actions of tricyclic antidepressant drugs (TCAs) at the α2A adrenergic receptor (AR), a centrally important receptor, dysregulation of which has been linked to depression. Our previous work established a particular TCA, desipramine, as an arrestin-biased α2AAR ligand driving receptor endocytosis and downregulation but not canonical heterotrimeric G protein-mediated signaling. The present work is aimed at broadening our understanding of how members of the TCA drug class act at the α2AAR, as we have selected the closely related but subtly different TCAs imipramine and amitriptyline for evaluation. Our data demonstrate that these drugs do also function as direct arrestin-biased α2AAR ligands. However, these data reveal differences in receptor affinity and in the extent/nature of arrestin recruitment to and endocytosis of α2AARs. Specifically, amitriptyline exhibits an approximately 14-fold stronger interaction with the receptor, is a weaker driver of arrestin recruitment, and preferentially recruits a different arrestin subtype. Extent of endocytosis is similar for all TCAs studied so far, and occurs in an arrestin-dependent manner, although imipramine uniquely retains a slight ability to drive α2AAR endocytosis in arrestin-null cells. These findings signify an important expansion of our mechanistic understanding of antidepressant pharmacology, and provide useful insights for future medicinal chemistry efforts. PMID:25128275

  14. Tricyclic antidepressants exhibit variable pharmacological profiles at the α(2A) adrenergic receptor.

    PubMed

    Cottingham, Christopher; Percival, Stefanie; Birky, Tana; Wang, Qin

    2014-08-29

    Antidepressant mechanisms of action remain shrouded in mystery, greatly hindering our ability to develop therapeutics which can fully treat patients suffering from depressive disorders. In an attempt to shed new light on this topic, we have undertaken a series of studies investigating actions of tricyclic antidepressant drugs (TCAs) at the α2A adrenergic receptor (AR), a centrally important receptor, dysregulation of which has been linked to depression. Our previous work established a particular TCA, desipramine, as an arrestin-biased α2AAR ligand driving receptor endocytosis and downregulation but not canonical heterotrimeric G protein-mediated signaling. The present work is aimed at broadening our understanding of how members of the TCA drug class act at the α2AAR, as we have selected the closely related but subtly different TCAs imipramine and amitriptyline for evaluation. Our data demonstrate that these drugs do also function as direct arrestin-biased α2AAR ligands. However, these data reveal differences in receptor affinity and in the extent/nature of arrestin recruitment to and endocytosis of α2AARs. Specifically, amitriptyline exhibits an approximately 14-fold stronger interaction with the receptor, is a weaker driver of arrestin recruitment, and preferentially recruits a different arrestin subtype. Extent of endocytosis is similar for all TCAs studied so far, and occurs in an arrestin-dependent manner, although imipramine uniquely retains a slight ability to drive α2AAR endocytosis in arrestin-null cells. These findings signify an important expansion of our mechanistic understanding of antidepressant pharmacology, and provide useful insights for future medicinal chemistry efforts. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex

    PubMed Central

    Cathel, Alessandra M.; Reyes, Beverly A. S.; Wang, Qin; Palma, Jonathan; Mackie, Kenneth; Bockstaele, Elisabeth J. Van; Kirby, Lynn G.

    2014-01-01

    Endocannabinoids acting at the cannabinoid type 1 receptor (CB1R) are known to regulate attention, cognition and mood. Previous studies have shown that, in the rat medial prefrontal cortex (mPFC), CB1R agonists increase norepinephrine release, an effect that may be attributed, in part, to CB1Rs localized to noradrenergic axon terminals. The present study was aimed at further characterizing functional interactions between CB1R and adrenergic receptor (AR) systems in the mPFC using in-vitro intracellular electrophysiology and high-resolution neuroanatomical techniques. Whole-cell patch-clamp recordings of layer V/VI cortical pyramidal neurons in rats revealed that both acute and chronic treatment with the synthetic CB1R agonist WIN 55,212-2 blocked elevations in cortical pyramidal cell excitability and increases in input resistance evoked by the α2-adrenergic receptor (α2-AR) agonist clonidine, suggesting a desensitization of α2-ARs. These CB1R–α2-AR interactions were further shown to be both action potential- and gamma-aminobutyric acid-independent. To better define sites of cannabinoid–AR interactions, we localized α2A-ARs in a genetically modified mouse that expressed a hemoagglutinin (HA) tag downstream of the α2A-AR promoter. Light and electron microscopy indicated that HA-α2A-AR was distributed in axon terminals and somatodendritic processes especially in layer V of the mPFC. Triple-labeling immunocytochemistry revealed that α2A-AR and CB1R were localized to processes that contained dopamine-β-hydroxylase, a marker of norepinephrine. Furthermore, HA-α2A-AR was localized to processes that were directly apposed to CB1R. These findings suggest multiple sites of interaction between cortical cannabinoid–adrenergic systems that may contribute to understanding the effect of cannabinoids on executive functions and mood. PMID:25131562

  16. 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

  17. 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.

  18. 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.

  19. Expression of striatal adenosine and dopamine receptors in mice deficient in the p50 subunit of NF-κB

    PubMed Central

    Xie, Xiaobin; Jhaveri, Krishna A.; Ding, Ming; Hughes, Larry F.; Toth, Linda A.; Ramkumar, Vickram

    2007-01-01

    The striatal dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AAR) exhibit mutually antagonistic effects through physical interactions and by differential modulation of post-receptor signaling pathways. The expression of the A2AAR and the D2R are differentially regulated by nuclear factor-κB (NFkB). In this report, we determined the role of NFkB in regulation of these receptors by comparing mice deficient in the NFκB p50 subunit (p50 KO) with genetically intact B6129PF2/J (F2) mice. Quantification of adenosine receptor (AR) subtypes in mouse striatum by real time PCR, immunocytochemistry and radioligand binding assays showed more A2AAR but less A1AR in p50 KO mice as compared with F2 mice. Striata from p50 KO mice also had less D2R mRNA and [3H]-methylspiperone binding than did striata from F2 mice. Gαolf and Gαs proteins, which are transducers of A2AAR signals, were also present at a higher level in striata from the p50 KO versus F2 mice. In contrast, the Gαi1 protein, which transduces signals from the A1AR and D2R, was significantly reduced in striata from p50-/ mice. Behaviorally, p50 KO mice exhibited increased locomotor activity relative to that of F2 mice after caffeine ingestion. These data are consistent with a role for the NFkB in the regulation of A1AR, A2AAR, D2R and possibly their coupling G proteins in the striatum. Dysregulation of these receptors in the striata of p50 KO mice might sensitize these animals to locomotor stimulatory action of caffeine. PMID:17869311

  20. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

    PubMed Central

    Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

    2017-01-01

    We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO

  1. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group.

    PubMed

    Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F; Schuh, Andre C; Beach, C L; Swern, Arlene S; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R; Hojas, Sabine; Rogulj, Inga M; Andel, Johannes; Greil, Richard

    2017-02-15

    We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine ("AML-001" cohort; n = 214) with AAR patients meeting the same inclusion criteria ("AAR (001-like)" cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for "AML-001" versus "AAR (001-like)" cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML ("AAR (WHO-AML)" cohort; n

  2. The presence of β2-adrenoceptors sensitizes α2A-adrenoceptors to desensitization after chronic epinephrine treatment

    PubMed Central

    Bawa-Khalfe, Tasneem; Altememi, Ghazi F; Mandyam, Chitra D; Schwarz, Lindsay A; Eikenburg, Douglas C; Standifer, Kelly M

    2007-01-01

    Background In addition to the regulation of blood pressure, α2- and β-adrenoceptor (AR) subtypes play an important role in the modulation of noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest that the α2-AR responsiveness in cells and tissues after chronic epinephrine (EPI) or norepinephrine (NE) exposure may vary, depending on the β-AR activity present there. Recently, we reported that in BE(2)-C human neuroblastoma cells (endogenously expressing α2A- and β2-AR), chronic EPI treatment (300 nM) produced a dramatic β-adrenoceptor-dependent desensitization of the α2A-AR response. The aim of this study is to determine if stable addition of a β2-AR to a second neuroblastoma cell line (SH-SY5Y), that normally expresses only α2A-ARs that are not sensitive to 300 nM EPI exposure, would suddenly render α2A-ARs in that cell line sensitive to treatment with the same EPI concentration. Methods These studies employed RT-PCR, receptor binding and inhibition of cAMP accumulation to confirm α2-AR subtype expression. Stable clones of SH-SY5Y cells transfected to stably express functional β2-ARs (SHβ2AR4) were selected to compare sensitivity of α2-AR to EPI in the presence or absence of β2-ARs. Results A series of molecular, biochemical and pharmacological studies indicated that the difference between the cell lines could not be attributed to α2-AR heterogeneity. We now report that after transfection of functional β2-AR into SH-SY5Y cells (SHβ2AR4), chronic treatment with modest levels of EPI desensitizes the α2A-AR. This effect results from a β2-AR dependent down-regulation of native α2A-ARs by EPI accompanied by enhanced translocation of GRK2 and GRK3 to the membrane (required for GRK-mediated phosphorylation of agonist-occupied receptors). Conclusion This study further supports the hypothesis that the presence of the β-AR renders the α2A-AR more susceptible to desensitization with physiological levels of EPI. PMID:18096057

  3. 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.

  4. The estimation of average areal rainfall by percentage weighting polygon method in Southeastern Anatolia Region, Turkey

    NASA Astrophysics Data System (ADS)

    Bayraktar, Hanefi; Turalioglu, F. Sezer; Şen, Zekai

    2005-01-01

    The percentage weighting polygon (PWP) method is proposed as an alternative to the Thiessen method for calculating the average areal rainfall (AAR) over a given catchment area. The basis of the method is to divide the study area into subareas by considering the rainfall percentages obtained at three adjacent station locations. This method is more reliable and flexible than the Thiessen polygon procedure where the subareas remain the same, independent of the measured rainfall amounts. In this paper, the PWP method is applied to the Southeastern Anatolia Region of Turkey for the first time by considering 10 meteorological stations. In PWP method, higher rainfall values are represented with the smaller subareas than in the case of the Thiessen and the other conventional methods. It is observed that the PWP method yields 13.5% smaller AAR value among the other conventional methods.

  5. Improvements of a Brain-Computer Interface Applied to a Robotic Wheelchair

    NASA Astrophysics Data System (ADS)

    Ferreira, André; Bastos-Filho, Teodiano Freire; Sarcinelli-Filho, Mário; Sánchez, José Luis Martín; García, Juan Carlos García; Quintas, Manuel Mazo

    Two distinct signal features suitable to be used as input to a Support-Vector Machine (SVM) classifier in an application involving hands motor imagery and the correspondent EEG signal are evaluated in this paper. Such features are the Power Spectral Density (PSD) components and the Adaptive Autoregressive (AAR) parameters. The best result (an accuracy of 97.1%) is obtained when using PSD components, while the AAR parameters generated an accuracy of 91.4%. The results also demonstrate that it is possible to use only two EEG channels (bipolar configuration around C 3 and C 4), discarding the bipolar configuration around C z . The algorithms were tested with a proprietary EEG data set involving 4 individuals and with a data set provided by the University of Graz (Austria) as well. The resulting classification system is now being implemented in a Brain-Computer Interface (BCI) used to guide a robotic wheelchair.

  6. 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. (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

  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. Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images.

    PubMed

    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

    2014-07-01

    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

  9. 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

  10. 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.

  11. 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.

  12. After Action Review in Simulation-Based Training

    DTIC Science & Technology

    2007-07-01

    feedback to organizations on their performance of collective tasks. It is an active process that requires unit members to participate in order to... processes . A second more recent form of constructive simulation is more entity and rule-based. These simulations provide semi-automated forces to...feedback. Extrinsic feedback can be used to correct misperceptions and clarify events and effects. The AAR process may provide unit members with a view

  13. Energy Efficient Wireless Sensor Networks Using Fuzzy Logic

    DTIC Science & Technology

    2005-06-01

    Sensor Network, Energy Efficiency, Fuzzy Logic. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER 19a. NAME OF RESPONSIBLE PERSON a...are well defined, including detection of false alarms or misses, classification errors, and track quality. 3 Spectrum Efficient Coding Scheme for...tracking, and classification . Therefore, compared to ad-hoc networks, WSN should be event-centric. In this paper, we propose an event forecasting scheme for

  14. Ultrafast Spectroscopic Noninvasive Probe of Vertical Carrier Transport in Heterostructure Devices

    DTIC Science & Technology

    2016-03-01

    Connelly, Grace D Metcalfe, and Stefan Svensson Sensors and Electron Devices Directorate, ARL Approved for public release...13 Fig. 12 Normalized electroabsorption pump-probe data at several injection levels on n-GaN/i-In1-xGaxN/p-GaN heterostructures with (a...are generally indirect and convoluted. For instance, one method applied to InGaAs/InP superlattice p-n junctions used a combination of capacitance

  15. Strategy Differences in Map Information Use for Route Following in Unfamiliar Cities; Implications for In-Car Navigation Systems (Strategieverschillen in Kaart-Informatiegebruik bij het Volgen van Routes in Onbekends Steden; Implicaties voor Navigatie-Systemen in Auto’s)

    DTIC Science & Technology

    1990-04-03

    Technology, INRETS-LEN, Philips Research Laboratories, Saab/Scania, TNO Institute for Perception, YARD Ltd., NRC-Applied Psychology Unit, Tregie...Renault Regie, Swedish Road and Traffic Researh Institute VTI, Universitat der Bundeswehr HMnchen, and University College Dublin are represented as...Siegel, A.W., and Rosin’ki, R.R. (1978). The role of perceptual context in structuring spatial knowledge. Journal of Experimental Psychology : H-Aar

  16. Galvanic Corrosion Study on Stainless Steel Cartridge Design

    DTIC Science & Technology

    2008-11-01

    Department of Defense, Washington Headquarters Services Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway...NJ 07806- 5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S. Army ARDEC, ESIC Technical...Research Center (AMSRD-AAR-EIK) Picatinny Arsenal, NJ 07806- 5000 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) Technical

  17. 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.

  18. Value of Bulk Heat Flux Parameterizations for Ocean SST Prediction

    DTIC Science & Technology

    2008-01-01

    HYCOM uses a penetrating solar radiation scheme (Kara ct al., 2005a) that accounts for spatial and temporal water turbidity (Kara et al.. 2005b,c...high temporal variability in the forcing, while maintaining a climatology. The original atmospheric forcing data set from ERA-15 spans the period I...Radiation (A>AR in m ’). The shortwave radiation at depth is calculated using a spatially and temporally varying monthly ApAK climatology as

  19. Force XXI Battle Command - Brigade and Below (FBCB2) - EXFOR; White Paper for future Improvements for the force XXI Battle Command - Brigade and Below fort hood SIMNET/JANUS Warfighting Facility

    DTIC Science & Technology

    1997-02-07

    0 Transmitting SINCGARS Transmitting EPLRS = EPLRS FDX Needline © SINCGARS Net No. Bam!« Active comms link (transmitting) Operational, link...Observer / Controllers (O/Cs) to observe, record, annotate, and replay Applique activities . This capability is resident in the AAR system that is...the screen state of selected Applique terminals at all times; it allows an O/C to observe and record Applique activities , to flag them for future

  20. Defense AT and L. Volume 45, Issue 1

    DTIC Science & Technology

    2016-02-01

    often enough to be writing this piece, that the recommended course of action is consistent with “BBP principles.” (Presumably, the idea is that this...competition’s strategy and tactics. Conducting an AAR, writing a report and developing a man- agement briefing are major undertakings. A lack of time al- ways...or program? Willing to share your expertise with the acquisition community? Want to help change the way DoD does business? Write an article

  1. Correcting Blindness In the Nerve Center: How To Improve Situational Awareness

    DTIC Science & Technology

    2015-12-01

    situational awareness, common operating picture, emergency management, emergency operations center, intelligence process, fusion center, information sharing...LIST OF ACRONYMS AND ABBREVIATIONS AAR After Action Report COP Common Operating Picture CPG Comprehensive Preparedness Guide DHS Department of...to the consequences of such complex events.SA and a shared common operating picture (COP)1 enable first responders on scene to be in sync with

  2. Getting Ready for a Nuclear-Ready Iran

    DTIC Science & Technology

    2005-10-01

    long as most nations buy Tehran’s argument that the NPT’s guarantee to “peaceful” nuclear energy gives it and all other members the right to...example, Syria asked the Soviet Union if it could buy up to four VVER-1000 power reactors and the associated fuel.148 Russia and Syria signed a...are in the advanced stages of negotiations in Russia to buy deuterium gas” as a booster for thermonuclear warheads.4 Iran has insisted on

  3. Health Survey of U.S. Navy Divers from 1960 to 1990: A First Look

    DTIC Science & Technology

    2011-09-01

    Military Divers Using Magnetic Resonance Imaging.” European Journal of Radiology 15 (2005): 368–375. Bove, A. A., ed. Diving Medicine. 4th ed...and both this report and an article had been subsequently published in a peer- reviewed journal . Disclosure of Information from This Study...Kambestad, and J. A. Aarli, “Influence of Occupational Diving upon the Nervous System: An Epidemiological Study,” British Journal of Industrial

  4. Increasing the Resolution of Simulated Combat Trauma Injuries in a High Level Architecture (HLA) Environment.

    DTIC Science & Technology

    1999-01-01

    EXPANDED TEST INJURY PROFILE DATABASE 100-102 APPENDIX F: PATIENT INJURY DATA FROM CTPS TEST RUNS 103-118 APPENDIX G: CTPS PHASE III VERSION 0 FOM 119...CONFIGURATION 49 FIGURE 6: RTI C++ INTERFACE 50 FIGURE 7: EXAMPLE PATIENT INJURY PROFILE FROM CTPS TEST RUN 54 XI LIST OF ACRONYMS AAR AIS ARL After...Object Model Development Tool Operational Requirements-based Casualty Assessment PATSIM Patient Simulator RTI RTI SO SOM STRICOM Run Time

  5. 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.

  6. Comparisons of noninvasive indices based on daily practice parameters for predicting liver cirrhosis in chronic hepatitis B and hepatitis C patients in hospital and community populations.

    PubMed

    Tseng, Po-Lin; Wang, Jing-Houng; Hung, Chao-Hung; Tung, Hung-Da; Chen, Tsung-Ming; Huang, Wu-Shiung; Liu, Shiann-Long; Hu, Tsung-Hui; Lee, Chuan-Mo; Lu, Sheng-Nan

    2013-07-01

    Several noninvasive indices have been proposed for predicting liver cirrhosis (LC), particularly in chronic hepatitis C (CHC). In this study, noninvasive indices for predicting LC and hepatocellular carcinoma (HCC) were compared. A total of 119 chronic hepatitis B (CHB) patients and 240 CHC patients were evaluated in a hospital-based setting using various predictors for pathologic LC such as aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (AAR), AAR-to-platelet ratio index (AARPRI), AST-to-platelet ratio index (APRI), age-platelet (AP) index, and platelet counts. In addition, these indices were used to predict LC [based on ultrasound (US)] in a community-based population of 201 patients with endemic hepatitis C virus (HCV). These indices were evaluated for their ability to predict HCC in CHB and CHC patients (n = 200). In CHB patients, the diagnostic performance of all indices was inadequate for predicting LC (areas under receiver operating characteristic curves < 0.7). Thrombocytopenia consistently demonstrated comparable accuracy to AARPRI ≥ 0.7 in CHB and AP index ≥ 7.0 in CHC patients. The best cut-off values for APRI, AARPRI, and AP index in predicting LC in CHC were 1.3, 0.8, and 7.0, respectively. The best cut-off values for APRI, AARPRI, and AP index in predicting LC (based on US) were 1.0, 1.2, and 8.0, respectively, in a HCV endemic community. An AAR > 1.4 might be a useful tool to identify candidates at high risk for HCC. In conclusion, platelet count was both consistent and accurate in predicting LC. An AAR > 1.4 is proposed as a possible surrogate marker for identifying patients at high risk for developing HCC.

  7. Challenges in Logistic Support for Polish Armed Forces

    DTIC Science & Technology

    2010-03-01

    additional assets . The EDA has already investigated possible acquisition models for other purposes (Air to Air Refueling (AAR) capability)). These... models could be applicable to a pooled acquisition of A400M. Of particular interest is whether a pooled 18 acquisition of assets and a form of...certain assets and resources. This may also require contracting particular sources and perhaps outsourcing other capabilities. This SRP describes

  8. Global Climate Change - U.S. Economic and National Security Opportunity

    DTIC Science & Technology

    2009-03-20

    The most recent findings of the Intergovernmental Panel on Climate Change (IPCC) state that the current trajectory of greenhouse gas (GHG) emissions...challenges and opportunities for the United States as they balance national security and economic interests. The effects of climate change could act as a...are various opportunities associated with climate change including opening arctic navigational channels and the vast oil and natural gas resources

  9. An approach to identify dairy cows being responsive to recombinant bovine somatotropin.

    PubMed

    Rodrigues, P H M; Santos, M V; Fonseca, L F L; Meyer, P M; Lucci, C S

    2006-12-01

    Forty-eight primiparous and pregnant Holstein cows at 202 (+/-59) days in milk and average daily milk production (DMP) of 22 (+/-5.3) kg at the beginning of the trial were used to study the possibility of identifying animals that are more responsive to recombinant bovine somatotropin (rbST). Animals were housed in free-stall barns, milked three times a day and fed a total mixed ration. Animals were injected with one dose (500 mg each) of rbST every 21 days during a 105-day total period (five doses in all). Daily milk production was recorded to measure average apparent response (AAR) and peak of apparent response (PAR). Average apparent response was defined as the average increase in milk production, expressed as kilogram per cow per day, for days 0-18 after dosing, as compared to the average production calculated for days -1, -2, -3, 19, 20 and 21 after dosing. Peak of apparent response was calculated as the increase in milk production for each day from 0 to 18 days after dosing as compared to the average production for days -1, -2 and -3. There was a positive linear correlation (r = 0.608; p = 0.0001) between AAR for the first 21 days and AAR for the total 105-day period (AATR). A correlation coefficient was calculated between each individual PAR value and AATR. The highest correlation coefficient (r = 0.511; p = 0.0002) was observed for days 8, 9 and 10, and therefore these days were considered the best estimates for calculating AAR when DMP records are not available. Also, high somatic cells count had a negative impact on milk yield response to treatment (p = 0.0162).

  10. The Implications of ISO 9000 and the European Community on the U.S. Construction Industry.

    DTIC Science & Technology

    1992-08-01

    Design and Construction." The Structural Engineer, V69(3), February 5 , 1991, 52. Saunders, Mary (1991A...are: 1. General Principles. 2. Concrete Structures . 3. Steel Structures . 4. Composite Steel and Concrete Structures . 5 . Timber Structures . 6. Masonry...Construction Producers Directive: Its Influence on Design and Construction." The Structural Engineer, V69(3), February 5 , 1991, 52. Saunders, Mary

  11. Data Supporting Mobile Application Development for Use within the Marine Air-Ground Task Force

    DTIC Science & Technology

    2015-09-01

    ACRONYMS AND ABBREVIATIONS 3G third generation 4G fourth generation AAR after action report AFRICOM United States Africa command ACE air combat...is in the process of returning to its amphibious roots by positioning itself as what the 35th Commandant, General James Amos (2012), calls “a...crises quickly. General Amos refers to this mindset in Expeditionary Force 21 as being “expeditionary” in nature—to be able to deploy and arrive

  12. Impact of white blood cell count on myocardial salvage, infarct size, and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a magnetic resonance imaging study.

    PubMed

    Chung, Seungmin; Song, Young Bin; Hahn, Joo-Yong; Chang, Sung-A; Lee, Sang-Chol; Choe, Yeon Hyeon; Choi, Seung-Hyuk; Choi, Jin-Ho; Lee, Sang Hoon; Oh, Jae K; Gwon, Hyeon-Cheol

    2014-01-01

    We sought to determine the relationship between white blood cell count (WBCc) and infarct size assessed by cardiovascular magnetic resonance imaging (CMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). In 198 patients undergoing primary PCI for STEMI, WBCc was measured upon arrival and CMR was performed a median of 7 days after the index event. Infarct size was measured on delayed enhancement imaging and the area at risk (AAR) was quantified on T2-weighted images. Baseline characteristics were not significantly different between the high WBCc group (>11,000/mm(3), n = 91) and low WBCc group (≤11,000/mm(3), n = 107). The median infarct size was larger in the high WBCc group than in the low WBCc group [22.0% (16.7-33.9) vs. 14.7% (8.5-24.7), p < 0.01]. Compared with the low WBCc group, the high WBCc group had a greater extent of AAR and a smaller myocardial salvage index [MSI = (AAR-infarct size)/AAR × 100]. The major adverse cardiovascular events (MACE) including cardiac death, nonfatal reinfarction, and rehospitalization for congestive heart failure at 12-month occurred more frequently in the high WBCc group (12.1 vs. 0.9%, p < 0.01). In multivariate analysis, high WBCc significantly increased the risk of a large infarct (OR 3.04 95% CI 1.65-5.61, p < 0.01), a low MSI (OR 2.08, 95% CI 1.13-3.86, p = 0.02), and 1-year MACE (OR 16.0, 95% CI 1.89-134.5, p = 0.01). In patients undergoing primary PCI for STEMI, an elevated baseline WBCc is associated with less salvaged myocardium, larger infarct size and poorer clinical outcomes.

  13. Geotechnical Factors in the Dredgeability of Sediments. Report 2. Geotechnical Site Investigation Strategy for Dredging Projects

    DTIC Science & Technology

    1993-10-01

    site investigations must be commu- tifed and discussed. Guidance on sequencing nicated to and understood by all persons in- an investigation includes a...are mechanically compacted in the containment area. 34. DiGeorge and Herbich (1978) reported a laboratory study of bulking factors in fine-grained...occupied by the same amount of soil in-situ. Laboratory tests used for this purpose were described in DiGeorge and Herbich (1978), based on work by Lacasse

  14. 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.

  15. Leveraging Lesson Learning in Tactical Units

    DTIC Science & Technology

    1997-01-01

    WALLP Wartime Army Lessons Learned Program VI CHAPTER 1 INTRODUCTION Vignette One: Learning in Bosnia-Herzegovina (1995-96) In December of 1995...and cannot rest completely on the shoulders of CALL. Army Regulation (AR) 11-33, Army Lessons Learned Program : System Development and Application...focal point for the Army Lessons Learned Program .4 AR 11-33 clearly establishes the requirement for major Army commands (MACOM) to provide AARs to

  16. Publications of the Division of Mechanical Engineering and the National Aeronautical Establishment. Series Number 2, Supplement Number 7.

    DTIC Science & Technology

    1982-01-01

    Joukowski condition for a trailing edge with crossflow - are derived from the theory of the Cauchy type integral . The method utilizes flat panels... integral of the sectional force, which is a function of the spanwise location and time. The non-stationary load is represented as the product of a...are combined in an optimal fashion to form an integrated navigation system based on the concepts of Kalman filtering. A ten-state Doppler/VLF Kalman

  17. Large Space Structure Figure Estimation and Control

    DTIC Science & Technology

    1989-01-01

    adjusted via manipulation of the LQG design parameters so that the control system acts primarily upon the first two bands of the boom-dish modes, for a...are applied. Each focuses on adjusting parameters in the estimator to achieve a more robust design. One approach which will be demonstrated is to... adjust parameters in the Kalman filter design in a way that asymptotically recovers the loop gain of the full state feedback. This method is called loop

  18. α1A-Adrenergic Receptor Induces Activation of Extracellular Signal-Regulated Kinase 1/2 through Endocytic Pathway

    PubMed Central

    Liu, Fei; He, Kangmin; Yang, Xinxing; Xu, Ning; Liang, Zhangyi; Xu, Ming; Zhao, Xinsheng; Han, Qide; Zhang, Youyi

    2011-01-01

    G protein-coupled receptors (GPCRs) activate mitogen-activated protein kinases through a number of distinct pathways in cells. Increasing evidence has suggested that endosomal signaling has an important role in receptor signal transduction. Here we investigated the involvement of endocytosis in α1A-adrenergic receptor (α1A-AR)-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Agonist-mediated endocytic traffic of α1A-AR was assessed by real-time imaging of living, stably transfected human embryonic kidney 293A cells (HEK-293A). α1A-AR was internalized dynamically in cells with agonist stimulation, and actin filaments regulated the initial trafficking of α1A-AR. α1A-AR-induced activation of ERK1/2 but not p38 MAPK was sensitive to disruption of endocytosis, as demonstrated by 4°C chilling, dynamin mutation and treatment with cytochalasin D (actin depolymerizing agent). Activation of protein kinase C (PKC) and C-Raf by α1A-AR was not affected by 4°C chilling or cytochalasin D treatment. U73122 (a phospholipase C [PLC] inhibitor) and Ro 31–8220 (a PKC inhibitor) inhibited α1B-AR- but not α1A-AR-induced ERK1/2 activation. These data suggest that the endocytic pathway is involved in α1A-AR-induced ERK1/2 activation, which is independent of Gq/PLC/PKC signaling. PMID:21738688

  19. Strategic Partners: South Korea and the United States

    DTIC Science & Technology

    1989-01-01

    South Korea’s economic growth, has fallen off, forcing South Korea into new mar- kets. In 1984, the construction industry received a...are in - cluded in the calculation. Since the 1970s, South Korea and the United States have begun a new stage of extensive economic contact, although...The Japanese Outlook 78 The Korean Peninsula’s Future 80 6. US INTERESTS AND OPTIONS IN SOUTH KOREA 83 Carter Administration Korean Policy 83

  20. The structure of the Alpine distal margin: insights from the proximal margin shortening kinematics during collision, Western Alps

    NASA Astrophysics Data System (ADS)

    Bellahsen, N.; Mouthereau, F.; Lacombe, O.; Jolivet, L.

    2011-12-01

    In mountain belts, along strike variations of inherited passive margin structure can affect the collision dynamics. Particularly, the structure the distal part can potentially drive the collision evolution and thus the proximal part inversion. In most orogens however (as in the Alps for example), the initial structure of the subducted distal margin is largely hidden by subduction- and exhumation-related deformations and metamorphism. In this contribution, the structure of the European distal margin in Western Alps is discussed in the light of the collision kinematics. More precisely, we aim at constraining the structure of the "distal" Dauphinois/Helvetic that might be the western lateral termination of the Valais ocean in Switzerland separating Europe and the Brianconnais block. The Dauphinois/Helvetic zone deformation is characterized and described using several balanced cross-sections. The timing, amount of shortening and exhumation of various External Crystalline Massifs from France to Switzerland (Oisans, Mont Blanc, Aar) are compared. In the Aar and Mont Blanc massifs, the averaged amount of shortening and exhumation during Oligo-Miocene times is around three times higher than in the Oisans massif. The P,T conditions are of higher grade in the Aar and Mont Blanc and the foreland basin (the Oligo-miocene molasse) is more developed. Finally, deformation mechanisms and geometries are significantly different, from brittle-ductile to ductile, from south to north, respectively. We tentatively propose that these differences can be due to an evolution from hyper-extended crust with mantle exhumation in the Northeast (Aar) to an "aborted rift" configuration in the Southwest (Oisans). The presence of a (light) continental crust in the Southwest may have prevented a strong tectonic burying of the proximal margin and promoted its early shortening.

  1. Intelligent Information Retrieval for a Multimedia Database Using Captions

    DTIC Science & Technology

    1992-07-23

    can be moved to optical storage (presently a 10-platter magneto optical jukebox) when needed. The reason to move it to optical storage is that the...aircraft’ program, noun-1, , noun-1, ’A-7’, noun-1, noun-1, ’A-7’, noun-1, [ noun-1, ’A-7’, noun-1, [ ’AAR-47’, noun-1, ’ electro- optica ’AC-130

  2. Leader Development in Army Units: Views From the Field

    DTIC Science & Technology

    2008-01-01

    Classroom lectures or seminars on leadership topics Developing and following a self-development plan Professional reading AARs for a deployment or field...PlatoonLeader.army.mil Staff rides to sites off base Classroom lectures or seminars on leadership topics Developing and following a self-development...Staff rides to sites off base Classroom lectures or seminars on leadership topics Developing and following a self-development plan Professional reading

  3. Orientation-dependent potential of mean force for protein folding.

    PubMed

    Mukherjee, Arnab; Bhimalapuram, Prabhakar; Bagchi, Biman

    2005-07-01

    We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other sites through an orientation-dependent interaction potential which we construct in the following fashion. First, the site-site potential of mean force (PMF) between heavy atoms is calculated [following F. Melo and E. Feytsman, J. Mol. Biol. 267, 207 (1997)] from statistics of their distance separation obtained from crystal structures. These site-site potentials are then used to calculate the distance and the orientation-dependent potential between side chains of all the amino acid residues (AAR). The distance and orientation dependencies show several interesting results. For example, we find that the PMF between two hydrophobic AARs, such as phenylalanine, is strongly attractive at short distances (after the obvious repulsive region at very short separation) and is characterized by a deep minimum, for specific orientations. For the interaction between two hydrophilic AARs, such a deep minimum is absent and in addition, the potential interestingly reveals the combined effect of polar (charge) and hydrophobic interactions among some of these AARs. The effectiveness of our potential has been tested by calculating the Z-scores for a large set of proteins. The calculated Z-scores show high negative values for most of them, signifying the success of the potential to identify the native structure from among a large number of its decoy states.

  4. Assessment of circumferential endocardial extent of myocardial edema and infarction in patients with reperfused acute myocardial infarction: a cardiovascular magnetic resonance study.

    PubMed

    Ota, Shingo; Tanimoto, Takashi; Hirata, Kumiko; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Ishibashi, Kohei; Yamano, Takashi; Ino, Yasushi; Kitabata, Hironori; Yamaguchi, Tomoyuki; Kubo, Takashi; Imanishi, Toshio; Akasaka, Takashi

    2014-01-01

    T2 weighted (T2W) images on cardiovascular magnetic resonance (CMR) visualizes myocardial edema, which reflects the myocardial area at risk (AAR) in reperfused acute myocardial infarction (AMI). Late gadolinium enhancement (LGE) demonstrates myocardial infarction. LGE images cover the whole left ventricle, but T2W images are obtained from a few slices of the left ventricle due to the long sequence time, so the quantification of AAR of the entire left ventricle is difficult. We hypothesize that we can quantify AAR with only LGE images if there is a strong correlation between the circumferential endocardial extent of myocardial edema and infarction. Thirty patients with first AMI were enrolled. All patients underwent successfully reperfusion therapy and CMR was performed within the first week after the event. We measured the circumferential extent of edema and infarction on short-axis views (T2 angle and LGE angle), respectively. A total of 82 short-axis slices showed transmural edema on T2W images. Corresponding LGE images were analyzed for the circumferential extent of infarction. The median [interquartile range] of T2 angle and DE angle were 147° [116°-219°] and 134° [104°-200°] in patients with LAD culprit lesion, 91° [87°-101°] and 85° [80°-90°] in LCX, and 110° [94°-123°] and 104° [89°-118°] in RCA, respectively. T2 angle was well correlated with LGE angle (r = 0.99, P < 0.01). There is a strong correlation between the circumferential extent of edema and infarction in reperfused AMI. Thus, T2 weighted imaging can be skipped to quantify the amount of AAR.

  5. Aerial Refueling Clearance Initiation Request

    DTIC Science & Technology

    2016-07-14

    Signed] _________ __________ [Signed] _________ Thomas Swiderek, Omega Air Working Group Lead Group Number 5 Thomas Swiderek, Omega Air Document...Definitions ARSAG Aerial Refueling Systems Advisory Group, International AR Aerial Refueling AAR Air -to- Air Refueling AR Boom Tanker fuel delivery system via...1995 NATO ATP 3.3.4.2, Air to Air Refuelling Ed C Ver 1 Edition D accepting edits through April 2016. Expected Promulgation Sep 2016. Nov 2013 AR

  6. On the Design and Optimization of Distributed Signal Detection and Parameter Estimation Systems.

    DTIC Science & Technology

    1987-09-01

    Assume that the costs C,, i, - Ol ,... ,M-l and the a priori probabilities are known. For the Bayesian DDF system of Figure 3.1, the optimum fusion rule...nLnormation Theory, IT-I4, pp. 349-353, March 1968. £362 J. F. Walker, "Performance Data for a Double-Threshold Detection Radar," EEE TranmaAar- espa " and

  7. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid

    PubMed Central

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128

  8. International Infantry and Joint Services Small Arms Systems Annual Symposium Exhibition and Firing Demonstration

    DTIC Science & Technology

    2005-05-19

    Sensor Fusion Technology Assessment Image Intensification Thermal Imaging EO/IR Fusion Example Project Approach to Sensor Fusion Assessment The...5 0 2 5 0 0 R A N G E M E T E R S THERMAL DETECTION THERMAL RECOGNITION OPTICAL IDENTIFICATION FUSED SENSOR OPTICAL RECOGNITION OPTICAL DETECTION L A...are reservedSingapore Technologies Kinetics Features 40mm HV HE 40mm ABM HE 12.7mm Celotex Firing Direction 12.7mm Celotex Firing Direction Simulate

  9. Adenosine receptors and the central nervous system.

    PubMed

    Sebastião, Ana M; Ribeiro, Joaquim A

    2009-01-01

    The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as part of the adenosine's attempt to control synaptic transmission. A(2A)ARs are more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain areas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripartite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and arousal, cognition, memory and learning, whereas under pathological conditions (e.g., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as early neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs are now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases.

  10. EC02-0282-1

    NASA Image and Video Library

    2002-12-11

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft participated 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 acted as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  11. EC02-0282-3

    NASA Image and Video Library

    2002-12-11

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft participated 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 acted as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  12. EC02-0282-5

    NASA Image and Video Library

    2002-12-11

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft participated 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 acted as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  13. Prediction of the Impact Sensitivity of Energetic Molecules Using Symmetry Adapted Perturbation Theory

    DTIC Science & Technology

    2011-05-01

    Bukowski , R.; Szalewicz, K. J. Chem. Theory Comput. 2006, 2, 400. 20. Bukowski , R.; Cencek, W.; Jankowski, P.; Jeziorski, B.; Jeziorska, M.; Kucharski, S...udel.edu/~szalewic/SAPT/license.html (accessed 10 January 2009). 21. Podeszwa, R.; Bukowski , R.; Rice, B. M.; Szalewicz, K. Phys. Chem. Chem. Phys...106B GOLDEN CO 80401 7 DIRECTOR US ARMY ARDEC AMSRD AAR AEE W W DAVIS L COSTAS A DAWSON W BUKOWSKI R SURAPANENI R

  14. Novel Alexa Fluor-488 labeled antagonist of the A(2A) adenosine receptor: Application to a fluorescence polarization-based receptor binding assay.

    PubMed

    Kecskés, Miklós; Kumar, T Santhosh; Yoo, Lena; Gao, Zhan-Guo; Jacobson, Kenneth A

    2010-08-15

    Fluorescence polarization (FP) assay has many advantages over the traditional radioreceptor binding studies. We developed an A(2A) adenosine receptor (AR) FP assay using a newly synthesized fluorescent antagonist of the A(2A)AR (MRS5346), a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivative conjugated to the fluorescent dye Alexa Fluor-488. MRS5346 displayed a K(i) value of 111+/-16nM in radioligand binding using [(3)H]CGS21680 and membranes prepared from HEK293 cells stably expressing the human A(2A)AR. In a cyclic AMP functional assay, MRS5346 was shown to be an A(2A)AR antagonist. MRS5346 did not show any effect on A(1) and A(3) ARs in binding or the A(2B)AR in a cyclic AMP assay at 10microM. Its suitability as a fluorescent tracer was indicated in an initial observation of an FP signal following A(2A)AR binding. The FP signal was optimal with 20nM MRS5346 and 150microg protein/mL HEK293 membranes. The association and dissociation kinetic parameters were readily determined using this FP assay. The K(d) value of MRS5346 calculated from kinetic parameters was 16.5+/-4.7nM. In FP competition binding experiments using MRS5346 as a tracer, K(i) values of known AR agonists and antagonists consistently agreed with K(i) values from radioligand binding. Thus, this FP assay, which eliminates using radioisotopes, appears to be appropriate for both routine receptor binding and high-throughput screening with respect to speed of analysis, displaceable signal and precision. The approach used in the present study could be generally applicable to other GPCRs.

  15. Sustainment of Army Forces in Operation Iraqi Freedom. Battlefield Logistics and Effects on Operations

    DTIC Science & Technology

    2005-01-01

    prepare and format the document. Rick Eden and John Dumond provided excellent comments to help with the organization of the report. LTG (retired...the problems or symptoms should be determined. Thus, this ____________ 8 Eric Peltz, Marc L. Robbins, Kenneth J. Girardini, Rick Eden , John M...Memorandum for Record, Subject: Operation Iraqi Freedom AAR, 19 May 2003. Interviews at 3rd ID Division Support Com- mand with LTC Bobby Towery (3rd FSB

  16. 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.

  17. Projectile Roll Dynamics and Control With a Low-Cost Skid-to-Turn Maneuver System

    DTIC Science & Technology

    2013-03-01

    11 viii INTENTIONALLY LEFT BLANK. 1 1. Introduction The overarching motivation for this...attack at 10-Hz initial roll rate – deflections. 8. Conclusions The motivation for this effort is a new capability of affordable interception of...TACOM ARDEC RDAR MEM M C MOEHRINGER J TRAVAILLE BLDG 94 PICATINNY ARSENAL NJ 07806-5000 1 US ARMY TACOM ARDEC AMSRD AAR AEPS J

  18. 49 CFR Appendix A to Part 215 - Railroad Freight Car Components

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... with letters “RJ” stamped on the end of the journal. C.Couplers: 1. AAR type “D”, top or bottom.... Arch bar type. 2. Truck with cast steel pedestal side frame, short wheel base, and no bolster. H.Truck... the symbol “70T” cast on the back of the wheel plate; they are not marked “U-1.” B.Wheels dated...

  19. Failure Mechanisms and Interphase Chemistry of Gold Films on Ti6Al4V. Part II. Etching of Ti6Al4V and its Effect on Evaporated Gold and Commercial Adhesive Adhesion.

    DTIC Science & Technology

    1980-01-01

    varying periods of time in aqueous solution of hydrofluoric acid and ammonium phosphate . Following etching, one-half of the specimens were covered with...Observed in Gold Peel Tests Using 19 Commercial Transparent Tape 4 Single Overlap Shear Test Results for Etched Specimens 20 Held in Condensing Steam A...are results from specimens held for 16 hours in condens - ing steam. It can be seen that the trend here is the same as in the gold coated specimens; that

  20. Effects of Electromagnetic Pulses on a Multilayered System

    DTIC Science & Technology

    2014-07-01

    University at Buffalo, 230 Davis Hall, Buffalo, NY 14260 H. L. Moore, P. Haney US Army ARDEC, AMSRD-AAR-MEM, Building 65 S, Picatinny Arsenal, NJ...types of EMPs that are of concern regarding electronics and system infrastructures; they are high-altitude EMP ( HEMP ) generated from nuclear...is for 3-D full-wave electromagnetic field simulation and high frequency and high speed components [2]. The model used was designed and imported

  1. 49 CFR 179.102-17 - Hydrogen chloride, refrigerated liquid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... fabricated of material listed in paragraph (b)(1) or (b)(2) of this section. (1) Stainless steel, ASTM A 240... tests are not required; or (2) Steel conforming to ASTM A 516/A 516M (IBR, see § 171.7 of this subchapter), Grade 70; ASTM A 537/A 537M, (IBR, see § 171.7 of this subchapter) Class 1; or AAR Specification...

  2. Method for Designing an Acoustic Array

    DTIC Science & Technology

    2014-05-01

    and their surfaces are coated with copper or silver that act as the electrode. Piezo-rubber materials have particles of piezoceramics suspended in a...are available in continuous sheet forms, are semi-flexible, and their surfaces are coated with copper or silver that act as the electrode. The 1-3...polyurethanes). Their surfaces are coated with copper or silver that act as the electrode. These are also available in sheet form, are semi-flexible

  3. Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease

    PubMed Central

    Kessoku, Takaomi; Ogawa, Yuji; Yoneda, Masato; Imajo, Kento; Sumida, Yoshio; Eguchi, Yuichiro; Fujii, Hideki; Hyogo, Hideyuki; Ono, Masafumi; Suzuki, Yasuaki; Kawaguchi, Takumi; Chayama, Kazuaki; Tanaka, Saiyu; Fujimoto, Kazuma; Anzai, Keizo; Saibara, Toshiji; Sata, Michio; Itoh, Yoshito; Nakajima, Atsushi; (JSG-NAFLD), Takeshi Okanoue; Japan Study Group of NAFLD

    2014-01-01

    AIM: To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, 190; stage 4, 38). The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy clothing. Venous blood samples were obtained in the morning after the patients had fasted overnight for 12 h. Laboratory evaluation was performed in all patients. Statistical analysis was conducted using SPSS version 12.0. Continuous variables were expressed as mean ± SD. RESULTS: The optimal cutoff value of platelet count, serum albumin, and aminotransferase/alanine aminotransferase ratio (AAR) was set at < 15.3 104/μL, < 4.0 g/dL, and > 0.9, respectively, by the receiver operating characteristic curve. These three variables were combined in an unweighted sum (platelet count = 1 point, serum albumin = 1 point, AAR = 1 point) to form an easily calculated composite score for predicting cirrhosis in NAFLD patients, called the PLALA (platelet, albumin, AAR) score. The diagnosis of PLALA ≥ 2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients. CONCLUSION: The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use. PMID:25110437

  4. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

    PubMed

    Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2015-10-01

    Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

  5. All-cancers mortality rates approaching diseases of the heart mortality rates as leading cause of death in Texas.

    PubMed

    Wyatt, Stephen W; Maynard, William Ryan; Risser, David R; Hakenewerth, Anne M; Williams, Melanie A; Garcia, Rebecca

    2014-01-01

    Diseases of the heart and malignant neoplasms (all-cancers) are the leading causes of death in the United States. The gap between the two has been closing in recent years. To assess the gap status in Texas and to establish a baseline to support evaluation efforts for the Cancer Prevention Research Institute of Texas, mortality data from 2006 to 2009 were analyzed. Immediate cause of death data in Texas for the years 2006-2009 were analyzed and rates developed by sex, race/ethnicity, and four metropolitan counties. Overall, for the years 2006-2009, the age-adjusted mortality rates (AARs) among Texas residents for both diseases of the heart and all-cancers decreased; however, during this time frame, there was greater improvement in diseases of the heart AARs as compared with all-cancers AARs. For the four large metropolitan counties of Bexar, Dallas, Harris, and Travis, data were analyzed by sex and race/ethnicity, and 11 of the 12 largest percent mortality rate decreases were for diseases of the heart. Age-adjusted mortality rates among Texas residents from diseases of the heart are showing improvement as compared with the rates for all-cancers.

  6. Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

    PubMed Central

    Carraro, Valérie; Maurin, Anne-Catherine; Lambert-Langlais, Sarah; Averous, Julien; Chaveroux, Cédric; Parry, Laurent; Jousse, Céline; Örd, Daima; Örd, Tõnis; Fafournoux, Pierre; Bruhat, Alain

    2010-01-01

    In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver. PMID:21203563

  7. Improvement of regional myocardial blood flow and function and reduction of infarct size with ivabradine: protection beyond heart rate reduction.

    PubMed

    Heusch, Gerd; Skyschally, Andreas; Gres, Petra; van Caster, Patrick; Schilawa, Dustin; Schulz, Rainer

    2008-09-01

    Effects of the bradycardic agent ivabradine on regional blood flow, contractile function, and infarct size were studied in a pig model of myocardial ischaemia/reperfusion. Heart rate reduction by beta-blockade is associated with negative inotropism and unmasked alpha-adrenergic coronary vasoconstriction. Ivabradine is the only available bradycardic agent for clinical use. Anaesthetized pigs were subjected to 90 min controlled left anterior descending coronary artery hypoperfusion and 120 min reperfusion. Regional blood flow was measured with microspheres, regional function with sonomicrometry, and infarct size with triphenyl tetrazolium chloride staining. Pigs received placebo or ivabradine (0.6 mg/kg i.v.) before or during ischaemia or before reperfusion, respectively. Pre-treatment with ivabradine reduced infarct size from 35 +/- 4 (SEM) to 19 +/- 4% of area at risk (AAR). Ivabradine 15-20 min after the onset of ischaemia increased regional myocardial blood flow from 2.12 +/- 0.31 to 3.55 +/- 0.56 microL/beat/g and systolic wall thickening from 6.7 +/- 1.0 to 16.3 +/- 3.0%; infarct size was reduced from 12 +/- 4 to 2 +/- 1% of AAR. Ivabradine 5 min before reperfusion still reduced infarct size from 36 +/- 4 to 21 +/- 5% of AAR. The benefit of ivabradine on flow and function was eliminated by atrial pacing, but part of the reduction of infarct size by ivabradine was not. Ivabradine's protection goes beyond heart rate reduction.

  8. Galvanising the NHS to Adopt Innovation

    PubMed Central

    Parris, Stuart; Cochrane, Gavin; Marjanovic, Sonja; Ling, Tom; Chataway, Joanna

    2016-01-01

    Abstract The Department of Health and the Wellcome Trust, in co-operation with NHS England, asked RAND Europe to conduct a limited consultation with key stakeholders about the practicality of measures and incentives proposed as part of the NHS Accelerated Access Review (AAR), which aims to assess the pathways for the development, assessment, and adoption of innovative medicines and medical technology. Through a focused engagement exercise with key healthcare stakeholders this project explored the implications of selected interim AAR propositions and feasibility of implementation for key actors, in primary and secondary care as well as commissioners and academia. Specifically, the project investigated the feasibility of implementation of three specific propositions including: a new earmarked fund to encourage AHSNs and other key innovation actors to re-design systems to embrace innovation; mobilising the influence of clinical system leaders to champion change; and encouraging secondary care organisations to take on “innovation champion” roles linked to financial incentives and a new emphasis on accountable care organisations. Data was collected on the feasibility of the three AAR propositions from a workshop with AHSN CEOs and Commercial Directors and interviews with senior NHS staff in three AHSN regions (South West, University College London Partners, and North East, North Cumbria). The study concludes with reflections on the feasibility of each recommendation and identifies factors expected to facilitate or challenge their implementation, as well as considering the wider cross cutting issues that may influence the adoption and diffusion of innovation in the NHS. PMID:28083436

  9. Galvanising the NHS to Adopt Innovation: The Feasibility and Practicality of Recommendations from the Interim Report of the Accelerated Access Review.

    PubMed

    Parris, Stuart; Cochrane, Gavin; Marjanovic, Sonja; Ling, Tom; Chataway, Joanna

    2016-06-20

    The Department of Health and the Wellcome Trust, in co-operation with NHS England, asked RAND Europe to conduct a limited consultation with key stakeholders about the practicality of measures and incentives proposed as part of the NHS Accelerated Access Review (AAR), which aims to assess the pathways for the development, assessment, and adoption of innovative medicines and medical technology. Through a focused engagement exercise with key healthcare stakeholders this project explored the implications of selected interim AAR propositions and feasibility of implementation for key actors, in primary and secondary care as well as commissioners and academia. Specifically, the project investigated the feasibility of implementation of three specific propositions including: a new earmarked fund to encourage AHSNs and other key innovation actors to re-design systems to embrace innovation; mobilising the influence of clinical system leaders to champion change; and encouraging secondary care organisations to take on "innovation champion" roles linked to financial incentives and a new emphasis on accountable care organisations. Data was collected on the feasibility of the three AAR propositions from a workshop with AHSN CEOs and Commercial Directors and interviews with senior NHS staff in three AHSN regions (South West, University College London Partners, and North East, North Cumbria). The study concludes with reflections on the feasibility of each recommendation and identifies factors expected to facilitate or challenge their implementation, as well as considering the wider cross cutting issues that may influence the adoption and diffusion of innovation in the NHS.

  10. 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.

  11. Structural diversity and protein engineering of the aminoacyl-tRNA synthetases.

    PubMed

    Perona, John J; Hadd, Andrew

    2012-11-06

    Aminoacyl-tRNA synthetases (aaRS) are the enzymes that ensure faithful transmission of genetic information in all living cells, and are central to the developing technologies for expanding the capacity of the translation apparatus to incorporate nonstandard amino acids into proteins in vivo. The 24 known aaRS families are divided into two classes that exhibit functional evolutionary convergence. Each class features an active site domain with a common fold that binds ATP, the amino acid, and the 3'-terminus of tRNA, embellished by idiosyncratic further domains that bind distal portions of the tRNA and enhance specificity. Fidelity in the expression of the genetic code requires that the aaRS be selective for both amino acids and tRNAs, a substantial challenge given the presence of structurally very similar noncognate substrates of both types. Here we comprehensively review central themes concerning the architectures of the protein structures and the remarkable dual-substrate selectivities, with a view toward discerning the most important issues that still substantially limit our capacity for rational protein engineering. A suggested general approach to rational design is presented, which should yield insight into the identities of the protein-RNA motifs at the heart of the genetic code, while also offering a basis for improving the catalytic properties of engineered tRNA synthetases emerging from genetic selections.

  12. Age estimation based on aspartic acid racemization in human sclera.

    PubMed

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  13. 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.

  14. The DarkSide physics program and its recent results

    DOE PAGES

    D'Angelo, D.

    2017-01-12

    Here, DarkSide (DS) at Gran Sasso underground laboratory is a direct Dark Matter search program based on Time Projection Chambers (TPC) with liquid Argon from underground sources. The DarkSide-50 (DS-50) TPC, with 150 kg of Argon is installed inside active neutron and muon detectors. DS-50 has been taking data since November 2013 with Atmospheric Argon (AAr) and since April 2015 with Underground Argon (UAr), depleted in radioactive 39Ar by a factor ~1400. The exposure of 1422 kg d of AAr has demonstrated that the operation of DS-50 for three years in a background free condition is a solid reality, thanksmore » to the superb performance of the Pulse Shape Analysis. The first release of results from an exposure of 2616 kg d of UAr has shown no candidate Dark Matter events. We have set the best limit for Spin-Independent elastic nuclear scattering of WIMPs obtained by Argon-based detectors, corresponding to a cross-section of 2 10–44 cm2 at a WIMP mass of 100 GeV. We present the detector design and performance, the results from the AAr run and the first results from the UAr run and we briefly introduce the future of the DarkSide program.« less

  15. Alkane production by the marine cyanobacterium Synechococcus sp. NKBG15041c possessing the α-olefin biosynthesis pathway.

    PubMed

    Yoshino, Tomoko; Liang, Yue; Arai, Daichi; Maeda, Yoshiaki; Honda, Toru; Muto, Masaki; Kakunaka, Natsumi; Tanaka, Tsuyoshi

    2015-02-01

    The production of alkanes in a marine cyanobacterium possessing the α-olefin biosynthesis pathway was achieved by introducing an exogenous alkane biosynthesis pathway. Cyanobacterial hydrocarbons are synthesized via two separate pathways: the acyl-acyl carrier protein (ACP) reductase/aldehyde-deformylating oxygenase (AAR/ADO) pathway for the alkane biosynthesis and the α-olefin synthase (OLS) pathway for the α-olefin biosynthesis. Coexistence of these pathways has not yet been reported. In this study, the marine cyanobacterium Synechococcus sp. NKBG15041c was shown to produce α-olefins similar to those of Synechococcus sp. PCC7002 via the α-olefin biosynthesis pathway. The production of heptadecane in Synechococcus sp. NKBG15041c was achieved by expressing the AAR/ADO pathway genes from Synechococcus elongatus PCC 7942. The production yields of heptadecane in Synechococcus sp. NKBG15041c varied with the expression level of the aar and ado genes. The maximal yield of heptadecane was 4.2 ± 1.2 μg/g of dried cell weight in the transformant carrying a homologous promoter. Our results also suggested that the effective activation of ADO may be more important for the enhancement of alkane production by cyanobacteria.

  16. 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.

  17. One-step fixation of atlantoaxial rotatory subluxation: technical note and report of three cases.

    PubMed

    Dahdaleh, Nader S; Dlouhy, Brian J; Menezes, Arnold H

    2013-12-01

    To describe a successful one-step intraoperative reduction of atlantoaxial rotatory subluxation (AARS) using neuromuscular blockade and intraoperative traction. While the patient was undergoing continuous somatosensory evoked potential monitoring, crown halo traction was applied under general anesthesia. A muscle relaxant was administered, and an intraoperative computed tomography scan was performed using the O-arm Surgical Imaging System in the supine position verifying adequate reduction. The patient was placed in the prone position, and a repeat image was obtained verifying persistent reduction in the position that the patient would undergo dorsal fixation. Occipitocervical fixation was then performed. This technique was performed successfully in three pediatric patients with chronic AARS. There were no complications related to the procedure. Intraoperative traction and neuromuscular blockade achieved a one-step reduction before fixation for subacute and chronic irreducible AARS. This one-step reduction obviates preoperative traction, which is often inconvenient and not tolerated by pediatric patients. Successful reduction is also demonstrated in detail intraoperatively with three-dimensional imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 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

  19. 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

  20. Genetic enhancement of ventricular contractility protects against pressure-overload-induced cardiac dysfunction.

    PubMed

    Du, Xiao-Jun; Fang, Lin; Gao, Xiao-Ming; Kiriazis, Helen; Feng, Xinheng; Hotchkin, Elodie; Finch, Angela M; Chaulet, Hervé; Graham, Robert M

    2004-11-01

    In response to pressure-overload, cardiac function deteriorates and may even progress to fulminant heart failure and death. Here we questioned if genetic enhancement of left ventricular (LV) contractility protects against pressure-overload. Transgenic (TG) mice with cardiac-restricted overexpression (66-fold) of the alpha(1A)-adrenergic receptor (alpha(1A)-AR) and their non-TG (NTG) littermates, were subjected to transverse aorta constriction (TAC)-induced pressure-overload for 12 weeks. TAC-induced hypertrophy was similar in the NTG and TG mice but the TG mice were less likely to die of heart failure compared to the non-TG animals (P <0.05). The hypercontractile phenotype of the TG mice was maintained over the 12-week period following TAC with LV fractional shortening being significantly greater than in the NTG mice (42+/-2 vs 29+/-1%, P <0.01). In the TG animals, 11-week beta-AR-blockade with atenolol neither induced hypertrophy nor suppressed the hypercontractile phenotype. The hypertrophic response to pressure-overload was not altered by cardiac alpha(1A)-AR overexpression. Moreover, the inotropic phenotype of alpha(1A)-AR overexpression was well maintained under conditions of pressure overload. Although the functional decline in contractility with pressure overload was similar in the TG and NTG animals, given that contractility was higher before TAC in the TG mice, their LV function was better preserved and heart failure deaths were fewer after induction of pressure overload.

  1. Molecular evolution of aminoacyl tRNA synthetase proteins in the early history of life.

    PubMed

    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.

  2. 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.

  3. 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.

  4. 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.

  5. MCAR is not necessary for the complete cases to constitute a simple random subsample of the target sample.

    PubMed

    Galati, John C; Seaton, Katherine A

    2016-08-01

    Missing data is the norm rather than the exception in complex epidemiological studies. Complete-case analyses, which discard all subjects with some data values missing, are known to be valid under the very restrictive assumption that the response mechanism is missing completely at random (MCAR). While conditions weaker than MCAR are known under which estimators of regression coefficients are unbiased, one often comes across the view in the literature that MCAR is necessary for the complete cases to form a simple random subsample of the target sample. In this paper, we explain why this is not the case, and we distill an assumption weaker than MCAR under which the simple random subsample condition holds, which we call available at random (AAR). Moreover, we show that, unlike MCAR, AAR response mechanisms can be missing not at random (MNAR). We also suggest how approximate AAR mechanisms might arise in practice through cancellation of selection and drop-out effects, and we conclude that before pooling partially complete and complete cases into an analysis, the investigator should consider how selection might impact on the representativeness of the cases included in the pooled analysis (compared to those comprising the complete cases only). © The Author(s) 2013.

  6. Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria.

    PubMed

    Haen, Karri M; Pett, Walker; Lavrov, Dennis V

    2010-10-01

    Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa.

  7. 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.

  8. The DarkSide physics program and its recent results

    NASA Astrophysics Data System (ADS)

    D'Angelo, D.; Agnes, P.; Agostino, L.; F. M. Albuquerque, I.; Alexander, T.; K. Alton, A.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Bottino, B.; Brigatti, A.; Brodsky, J.; Budano, F.; Bussino, S.; Cadeddu, M.; Cadonati, L.; Cadoni, M.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Carlini, M.; Catalanotti, S.; Cavalcante, P.; Chepurnov, A.; Cocco, A. G.; Covone, G.; Crippa, L.; D'Incecco, M.; Davini, S.; De Cecco, S.; De Deo, M.; De Vincenzi, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Giganti, C.; M. Goretti, A.; Granato, F.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; R. Hackett, B.; Herner, K.; V. Hungerford, E.; Ianni, Al.; Ianni, An.; James, I.; Jollet, C.; Keeter, K.; L. Kendziora, C.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Lissia, M.; Li, X.; Lombardi, P.; Luitz, S.; N. Machulin, I.; Mandarano, A.; Maricic, J.; Marini, L.; M. Mari, S.; J. Martoff, C.; Ma, Y.; Meregaglia, A.; D. Meyers, P.; Miletic, T.; Milincic, R.; Montanari, D.; Monte, A.; Montuschi, M.; Monzani, M.; Mosteiro, P.; J. Mount, B.; N. Muratova, V.; Musico, P.; Napolitano, J.; Nelson, A.; Odrowski, S.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; A. Pugachev, D.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; L. Renshaw, A.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Savarese, C.; Segreto, E.; A. Semenov, D.; Shields, E.; N. Singh, P.; D. Skorokhvatov, M.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Trinchese, P.; V. Unzhakov, E.; Vishneva, A.; Vogelaar, B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; W. Watson, A.; Westerdale, S.; Wilhelmi, J.; M. Wojcik, M.; Xiang, X.; Xu, J.; Yang, C.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhong, W.; Zhu, C.; Zuzel, G.

    2017-07-01

    DarkSide (DS) at Gran Sasso underground laboratory is a direct Dark Matter search program based on Time Projection Chambers (TPC) with liquid Argon from underground sources. The DarkSide-50 (DS-50) TPC, with 150kg of Argon is installed inside active neutron and muon detectors. DS-50 has been taking data since November 2013 with Atmospheric Argon (AAr) and since April 2015 with Underground Argon (UAr), depleted in radioactive ^{39} Ar by a factor {˜}1400 . The exposure of 1422kg d of AAr has demonstrated that the operation of DS-50 for three years in a background free condition is a solid reality, thanks to the superb performance of the Pulse Shape Analysis. The first release of results from an exposure of 2616kg d of UAr has shown no candidate Dark Matter events. We have set the best limit for Spin-Independent elastic nuclear scattering of WIMPs obtained by Argon-based detectors, corresponding to a cross-section of 2 10^{-44}{ cm2} at a WIMP mass of 100GeV. We present the detector design and performance, the results from the AAr run and the first results from the UAr run and we briefly introduce the future of the DarkSide program.

  9. Sfp-type 4'-phosphopantetheinyl transferase is indispensable for fungal pathogenicity.

    PubMed

    Horbach, Ralf; Graf, Alexander; Weihmann, Fabian; Antelo, Luis; Mathea, Sebastian; Liermann, Johannes C; Opatz, Till; Thines, Eckhard; Aguirre, Jesús; Deising, Holger B

    2009-10-01

    In filamentous fungi, Sfp-type 4'-phosphopantetheinyl transferases (PPTases) activate enzymes involved in primary (alpha-aminoadipate reductase [AAR]) and secondary (polyketide synthases and nonribosomal peptide synthetases) metabolism. We cloned the PPTase gene PPT1 of the maize anthracnose fungus Colletotrichum graminicola and generated PPTase-deficient mutants (Deltappt1). Deltappt1 strains were auxotrophic for Lys, unable to synthesize siderophores, hypersensitive to reactive oxygen species, and unable to synthesize polyketides (PKs). A differential analysis of secondary metabolites produced by wild-type and Deltappt1 strains led to the identification of six novel PKs. Infection-related morphogenesis was affected in Deltappt1 strains. Rarely formed appressoria of Deltappt1 strains were nonmelanized and ruptured on intact plant. The hyphae of Deltappt1 strains colonized wounded maize (Zea mays) leaves but failed to generate necrotic anthracnose disease symptoms and were defective in asexual sporulation. To analyze the pleiotropic pathogenicity phenotype, we generated AAR-deficient mutants (Deltaaar1) and employed a melanin-deficient mutant (M1.502). Results indicated that PPT1 activates enzymes required at defined stages of infection. Melanization is required for cell wall rigidity and appressorium function, and Lys supplied by the AAR1 pathway is essential for necrotrophic development. As PPTase-deficient mutants of Magnaporthe oryzea were also nonpathogenic, we conclude that PPTases represent a novel fungal pathogenicity factor.

  10. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment

    PubMed Central

    Zhao, Xin; Chen, Minsheng; Huang, Biyun; Ji, Hong; Yuan, Mu

    2011-01-01

    The α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-oneout cross-validation correlation coefficients were q2 CoMFA = 0.840 and q2 CoMSIA = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r2 pred/CoMFA = 0.694; r2 pred/CoMSIA = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α1A-AR antagonists. PMID:22072933

  11. Hematopoietic activity of Smilax aristolochiaefolia (zarzaparrilla) in mice with aplastic anemia.

    PubMed

    Velasco-Lezama, Rodolfo; Muñoz Torres, Antonio; Tapia Aguilar, Rafaela; Flores Saenz, José Luis; Fregoso Padilla, Martha; Vega Avila, Elisa; Barrera Escorcia, Eduardo

    2009-01-01

    Smilax aristolochiaefolia (Liliaceae) has been used in Mexican traditional medicine for the treatment of tumors, leprosy, anemia and as a tonic for skin infections and anemia. Aplastic anemia (AA) was induced in CD1 mice 8-12 weeks old distributed 10 animals each in Groups VSC, AA, AASa and AAr. Groups AA, AASa and AAr received benzene (2 ml/kg diluted v/v with corn oil) subcutaneously every three days until 20 dosages had been administered. The vehicular solution control group (VSC) received corn oil and the HC group (healthy control) received saline solution. Two days after the last benzene inoculation, groups AA and HC were bled and sacrificed to count blood and bone marrow cells. Group AASa received an aqueous S. aristolochiaefolia (0.4 g/kg) solution orally on days 3, 5 and 7 after the last dosage of benzene, meanwhile group AAr received no treatment after induction of AA (self recovery). On day 9 these groups were bled and sacrificed to count blood and bone marrow cells. Mice with aplastic anemia treated with S. aristolochiaefolia extract, recovered normal platelet levels and nucleated bone marrow cells as compared with the control, but the counts of erythrocytes and leukocyte were lower than controls (p<0.005). The aqueous extract of S. aristolochiaefolia (zarzaparrilla) restores hematopoeisis in the bone marrow of mice with aplastic anemia.

  12. In search of novel ligands using a structure-based approach: a case study on the adenosine A2A receptor

    NASA Astrophysics Data System (ADS)

    Lenselink, Eelke B.; Beuming, Thijs; van Veen, Corine; Massink, Arnault; Sherman, Woody; van Vlijmen, Herman W. T.; IJzerman, Adriaan P.

    2016-10-01

    In this work, we present a case study to explore the challenges associated with finding novel molecules for a receptor that has been studied in depth and has a wealth of chemical information available. Specifically, we apply a previously described protocol that incorporates explicit water molecules in the ligand binding site to prospectively screen over 2.5 million drug-like and lead-like compounds from the commercially available eMolecules database in search of novel binders to the adenosine A2A receptor (A2AAR). A total of seventy-one compounds were selected for purchase and biochemical assaying based on high ligand efficiency and high novelty (Tanimoto coefficient ≤0.25 to any A2AAR tested compound). These molecules were then tested for their affinity to the adenosine A2A receptor in a radioligand binding assay. We identified two hits that fulfilled the criterion of 50 % radioligand displacement at a concentration of 10 μM. Next we selected an additional eight novel molecules that were predicted to make a bidentate interaction with Asn2536.55, a key interacting residue in the binding pocket of the A2AAR. None of these eight molecules were found to be active. Based on these results we discuss the advantages of structure-based methods and the challenges associated with finding chemically novel molecules for well-explored targets.

  13. 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

  14. Segmentation of cytoplasm and nuclei of abnormal cells in cervical cytology using global and local graph cuts.

    PubMed

    Zhang, Ling; Kong, Hui; Chin, Chien Ting; Liu, Shaoxiong; Chen, Zhi; Wang, Tianfu; Chen, Siping

    2014-07-01

    Automation-assisted reading (AAR) techniques have the potential to reduce errors and increase productivity in cervical cancer screening. The sensitivity of AAR relies heavily on automated segmentation of abnormal cervical cells, which is handled poorly by current segmentation algorithms. In this paper, a global and local scheme based on graph cut approach is proposed to segment cervical cells in images with a mix of healthy and abnormal cells. For cytoplasm segmentation, the multi-way graph cut is performed globally on the a* channel enhanced image, which can be effective when the image histogram presents a non-bimodal distribution. For segmentation of nuclei, especially when they are abnormal, we propose to use graph cut adaptively and locally, which allows the combination of intensity, texture, boundary and region information. Two concave points-based approaches are integrated to split the touching-nuclei. As part of an ongoing clinical trial, preliminary validation results obtained from 21 cervical cell images with non-ideal imaging condition and pathology show that our segmentation method achieved 93% accuracy for cytoplasm, and 88.4% F-measure for abnormal nuclei, outperforming state of the art methods in terms of accuracy. Our method has the potential to improve the sensitivity of AAR in screening for cervical cancer.

  15. 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

  16. Lin28A and androgen receptor expression in ER-/Her2+ breast cancer.

    PubMed

    Shen, Honghong; Yang, Yong; Zhao, Lin; Yuan, Jinyang; Niu, Yun

    2016-02-01

    The aim of this study was to examine the expression of Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, and to research the association of Lin28A and AR co-expression status with patients' prognosis. The expression of Lin28A and AR in formalin-fixed and paraffin-embedded surgical sections from 305 patients with ER-/Her2+ breast cancer was analyzed by immunohistochemistry, and the co-expression patterns in breast cancer cells were investigated by immunofluorescent staining. The impact of the expression of Lin28A and AR in prognosis was also assessed by the Kaplan-Meier, univariate, and multivariate logistic regression models. This study included 305 cases ER-/Her2+ breast cancer patients. Lin28A and AR were expressed in 240 cases (78.7 %) and 220 cases (72.1 %), respectively. Lin28A tended to be higher in AR-positive patients (75.0 %). Lin28A and AR co-expression (Lin28+/AR+) was significantly associated with high tumor grade (G3) (p = 0.023) and high Ki67 index (p = 0.020). The mRNA and protein expression levels of Lin28A and AR were higher in MDA-MB-453 cells (ER-/Her2+) than in the MDA-MB-231 cells (ER-/Her2-). In univariate analysis, Lin28A+/AR+ was significant risk factors associated with unfavorable OS (p = 0.049) and RFS (p = 0.019). Kaplan-Meier analysis showed that Lin28A+/AR+ expression showed lower RFS rates compared with Lin28A-/AR+ (p = 0.043) and Lin28A-/AR- patients(p = 0.019). Multivariate cox model showed that Lin28A+/AR+ remained an independent negative prognostic factor for RFS. Our study showed that Lin28A and AR co-expressed in ER-/Her-2+ breast cancer and correlated with poor prognosis. The possibility that Lin28A may drive AR expression via a positive feedback mechanism remains to be tested.

  17. High salt diet exacerbates vascular contraction in the absence of adenosine A₂A receptor.

    PubMed

    Pradhan, Isha; Zeldin, Darryl C; Ledent, Catherine; Mustafa, Jamal S; Falck, John R; Nayeem, Mohammed A

    2014-05-01

    High salt (4% NaCl, HS) diet modulates adenosine-induced vascular response through adenosine A(2A) receptor (A(2A)AR). Evidence suggests that A(2A)AR stimulates cyp450-epoxygenases, leading to epoxyeicosatrienoic acids (EETs) generation. The aim of this study was to understand the vascular reactivity to HS and underlying signaling mechanism in the presence or absence of A(2A)AR. Therefore, we hypothesized that HS enhances adenosine-induced relaxation through EETs in A(2A)AR⁺/⁺, but exaggerates contraction in A(2A)AR⁻/⁻. Organ bath and Western blot experiments were conducted in HS and normal salt (NS, 0.18% NaCl)-fed A(2A)AR⁺/⁺ and A(2A)AR⁻/⁻ mice aorta. HS produced concentration-dependent relaxation to non-selective adenosine analog, NECA in A(2A)AR⁺/⁺, whereas contraction was observed in A(2A)AR⁻/⁻ mice and this was attenuated by A₁AR antagonist (DPCPX). CGS 21680 (selective A(2A)AR agonist) enhanced relaxation in HS-A(2A)AR⁺/⁺ versus NS-A(2A)AR⁺/⁺, which was blocked by EETs antagonist (14,15-EEZE). Compared with NS, HS significantly upregulated the expression of vasodilators A(2A)AR and cyp2c29, whereas vasoconstrictors A₁AR and cyp4a in A(2A)AR⁺/⁺ were downregulated. In A(2A)AR⁻/⁻ mice, however, HS significantly downregulated the expression of cyp2c29, whereas A₁AR and cyp4a were upregulated compared with A(2A)AR⁺/⁺ mice. Hence, our data suggest that in A(2A)AR⁺/⁺, HS enhances A(2A)AR-induced relaxation through increased cyp-expoxygenases-derived EETs and decreased A₁AR levels, whereas in A(2A)AR⁻/⁻, HS exaggerates contraction through decreased cyp-epoxygenases and increased A₁AR levels.

  18. Helium postconditioning regulates expression of caveolin-1 and -3 and induces RISK pathway activation after ischaemia/reperfusion in cardiac tissue of rats.

    PubMed

    Flick, Moritz; Albrecht, Martin; Oei, Gezina T M L; Steenstra, Renske; Kerindongo, Raphaela P; Zuurbier, Coert J; Patel, Hemal H; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2016-11-15

    Caveolae, lipid enriched invaginations of the plasma membrane, are epicentres of cellular signal transduction. The structural proteins of caveolae, caveolins, regulate effector pathways in anaesthetic-induced cardioprotection, including the RISK pathway. Helium (He) postconditioning (HePoc) is known to mimic anaesthetic conditioning and to prevent damage from myocardial infarction. We hypothesize that HePoc regulates caveolin-1 and caveolin-3 (Cav-1 and Cav-3) expression in the rat heart and activates the RISK pathway. Male Wistar rats (n=8, each group) were subjected to 25min of cardiac ischaemia followed by reperfusion (I/R) for 5, 15 or 30min (I/R 5/15/30). The HePoc groups underwent I/R with 70% helium ventilation during reperfusion (IR+He 5/15/30min). Sham animals received surgical treatment without I/R. After each protocol blood and hearts were retrieved. Tissue was obtained from the area-at-risk (AAR) and non-area-at-risk (NAAR) and processed for western blot analyses and reverse-transcription-real-time-polymerase-chain-reaction (RT-qPCR). Protein analyses revealed increased amounts of Cav-1 and Cav-3 in the membrane of I/R+He15 (AAR: Cav-1, P<0.05; Cav-3, P<0.05; both vs. I/R15). In serum, Cav-3 was found to be elevated in I/R+He15 (P<0.05 vs. I/R15). RT-qPCR showed increased expression of Cav-1 in IR+He15 in AAR tissue (P<0.05 vs. I/R15). Phosphorylation of RISK pathway proteins pERK1/2 (AAR: P<0.05 vs. I/R15) and pAKT (AAR: P<0.05; NAAR P<0.05; both vs. I/R15) was elevated in the cytosolic fraction of I/R+He15. These results suggest that 15min of HePoc regulates Cav-1 and Cav-3 and activates RISK pathway kinases ERK1/2 and AKT. These processes might be crucially involved in HePoc mediated cardioprotection. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. 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

  20. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium.

    PubMed

    Estrada, Juan A; Williams, Arthur G; Sun, Jie; Gonzalez, Leticia; Downey, H Fred; Caffrey, James L; Mallet, Robert T

    2016-03-01

    Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5-8 daily, 5-10 min cycles of moderate, normobaric hypoxia (FIO2 0.095-0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 μg/kg, sc) or antioxidant N-acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 ± 5 % (n = 12) to 1.8 ± 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 ± 0.3 to 0.7 ± 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 ± 5 % and arrhythmia score 3.7 ± 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 ± 3 % and arrhythmia score 4.7 ± 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 ± 8 %; arrhythmia score 4.5 ± 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia.

  1. α2A-Adrenergic receptor polymorphism potentiates platelet reactivity in patients with stable coronary artery disease carrying the cytochrome P450 2C19*2 genetic variant.

    PubMed

    Peace, Aaron J; Mangiacapra, Fabio; Bailleul, Els; Delrue, Leen; Dierickx, Karen; Conte, Micaela; Puymirat, Etienne; Fraeymans, Anne Lies; Meeus, Pieter; Bartunek, Jozef; Volpe, Massimo; Barbato, Emanuele

    2014-06-01

    Platelet α2A-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α2A-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α2A-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy). Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 μmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (P<0.05) apart from 10 μmol/L (P=0.077). Percentage inhibition was lower (P=0.048) in 6.3-kb α2A-AR carriers. Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037) and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3-kb α2A-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own. The 6.3-kb α2A-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy. © 2014 American Heart Association, Inc.

  2. Gaseous 83mKr generator of monoenergetic electrons based on 83Rb deposited in zeolite

    NASA Astrophysics Data System (ADS)

    Sentkerestiová, J.; Vénos, D.; Slezák, M.

    2017-09-01

    The gaseous 83mKr electron source is currently used in neutrino mass experiments KATRIN and Project 8, dark matter experiments XENON, LUX and DarkSide, and ALICE (CERN) experiment. The main attractive features of this radioactive noble gas are its monoenergetic conversion electrons with well known energies and a half-life of 1.8 h, which is short enough to avoid any long-lasting contamination of the system. The long half-life of the mother 83Rb isotope (T1/2 = 86.2 d) enables more time demanding measurement. Particularly, in the neutrino mass experiments with gaseous tritium in which the 83mKr is applied in the same manner as the tritium, the K-32 conversion electrons with energy conveniently close to the beta spectrum endpoint represent an important test and calibration tool. Here, the design and characteristics of the gaseous 83mKr generator, including the 83mKr source itself, for KATRIN (KArlsruhe TRItium Neutrino) experiment are presented.

  3. Featured Image: The Q Continuum Simulation

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-10-01

    Each frame in this image (click for the full view!) represents a different stage in the simulated evolution of our universe, ending at present day in the rightmost panel. In a recently-published paper, Katrin Heitmann (Argonne National Laboratory) and collaborators reveal the results from and challenges inherent in the largest cosmological simulation currently available: the Q Continuum simulation. Evolving a volume of (1300 Mpc)3, this massive N-body simulation tracks over half a trillion particles as they clump together as a result of their mutual gravity, imitating the evolution of our universe over the last 13.8 billion years. Cosmological simulations such as this one are important for understanding observations, testing analysis pipelines, investigating the capabilities of future observing missions, and much more. For more information and the original image (as well as several other awesome images!), see the paper below.Citation:Katrin Heitmann et al 2015 ApJS 219 34. doi:10.1088/0067-0049/219/2/34

  4. TRIMS: Validating T2 Molecular Effects for Neutrino Mass Experiments

    NASA Astrophysics Data System (ADS)

    Lin, Ying-Ting; Bodine, Laura; Enomoto, Sanshiro; Kallander, Matthew; Machado, Eric; Parno, Diana; Robertson, Hamish; Trims Collaboration

    2017-01-01

    The upcoming KATRIN and Project 8 experiments will measure the model-independent effective neutrino mass through the kinematics near the endpoint of tritium beta-decay. A critical systematic, however, is the understanding of the molecular final-state distribution populated by tritium decay. In fact, the current theory incorporated in the KATRIN analysis framework predicts an observable that disagrees with an experimental result from the 1950s. The Tritium Recoil-Ion Mass Spectrometer (TRIMS) experiment will reexamine branching ratio of the molecular tritium (T2) beta decay to the bound state (3HeT+). TRIMS consists of a magnet-guided time-of-flight mass spectrometer with a detector located on each end. By measuring the kinetic energy and time-of-flight difference of the ions and beta particles reaching the detectors, we will be able to distinguish molecular ions from atomic ones and hence derive the ratio in question.We will give an update on simulation software, analysis tools, and the apparatus, including early commissioning results. U.S. Department of Energy Office of Science, Office of Nuclear Physics, Award Number DE-FG02-97ER41020.

  5. Kassiopeia: a modern, extensible C++ particle tracking package

    NASA Astrophysics Data System (ADS)

    Furse, Daniel; Groh, Stefan; Trost, Nikolaus; Babutzka, Martin; Barrett, John P.; Behrens, Jan; Buzinsky, Nicholas; Corona, Thomas; Enomoto, Sanshiro; Erhard, Moritz; Formaggio, Joseph A.; Glück, Ferenc; Harms, Fabian; Heizmann, Florian; Hilk, Daniel; Käfer, Wolfgang; Kleesiek, Marco; Leiber, Benjamin; Mertens, Susanne; Oblath, Noah S.; Renschler, Pascal; Schwarz, Johannes; Slocum, Penny L.; Wandkowsky, Nancy; Wierman, Kevin; Zacher, Michael

    2017-05-01

    The Kassiopeia particle tracking framework is an object-oriented software package using modern C++ techniques, written originally to meet the needs of the KATRIN collaboration. Kassiopeia features a new algorithmic paradigm for particle tracking simulations which targets experiments containing complex geometries and electromagnetic fields, with high priority put on calculation efficiency, customizability, extensibility, and ease-of-use for novice programmers. To solve Kassiopeia's target physics problem the software is capable of simulating particle trajectories governed by arbitrarily complex differential equations of motion, continuous physics processes that may in part be modeled as terms perturbing that equation of motion, stochastic processes that occur in flight such as bulk scattering and decay, and stochastic surface processes occurring at interfaces, including transmission and reflection effects. This entire set of computations takes place against the backdrop of a rich geometry package which serves a variety of roles, including initialization of electromagnetic field simulations and the support of state-dependent algorithm-swapping and behavioral changes as a particle’s state evolves. Thanks to the very general approach taken by Kassiopeia it can be used by other experiments facing similar challenges when calculating particle trajectories in electromagnetic fields. It is publicly available at https://github.com/KATRIN-Experiment/Kassiopeia.

  6. Dark matter in the local group of galaxies

    NASA Astrophysics Data System (ADS)

    Morley, P. D.; Buettner, D. J.

    We describe the neutrino flavor (e = electron, μ = muon, τ = tau) masses as mi=e,μ,τ = m + Δmi with |Δmi| m < 1 and probably |Δmi| m ≪ 1. The quantity m is the degenerate neutrino mass. Because neutrino flavor is not a quantum number, this degenerate mass appears in the neutrino equation-of-state [P. D. Morley and D. J. Buettner, Int. J. Mod. Phys. D (2014), doi:10.1142/s0218271815500042.]. We apply a Monte Carlo computational physics technique to the Local Group (LG) of galaxies to determine an approximate location for a Dark Matter embedding Condensed Neutrino Object (CNO) [P. D. Morley and D. J. Buettner, Int. J. Mod. Phys. D (2016), doi:10.1142/s0218271816500899.]. The calculation is based on the rotational properties of the only spiral galaxies within the LG: M31, M33 and the Milky Way. CNOs could be the Dark Matter everyone is looking for and we estimate the CNO embedding the LG to have a mass 5.17 × 1015 M⊙ and a radius 1.316 Mpc, with the estimated value of m ≃ 0.8 eV/c2. The up-coming KATRIN experiment [https://www.katrin.kit.edu.] will either be the definitive result or eliminate condensed neutrinos as a Dark Matter candidate.

  7. 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.

  8. Kassiopeia: a modern, extensible C++ particle tracking package

    DOE PAGES

    Furse, Daniel; Groh, Stefan; Trost, Nikolaus; ...

    2017-05-16

    The Kassiopeia particle tracking framework is an object-oriented software package using modern C++ techniques, written originally to meet the needs of the KATRIN collaboration. Kassiopeia features a new algorithmic paradigm for particle tracking simulations which targets experiments containing complex geometries and electromagnetic fields, with high priority put on calculation efficiency, customizability, extensibility, and ease-of-use for novice programmers. To solve Kassiopeia's target physics problem the software is capable of simulating particle trajectories governed by arbitrarily complex differential equations of motion, continuous physics processes that may in part be modeled as terms perturbing that equation of motion, stochastic processes that occur inmore » flight such as bulk scattering and decay, and stochastic surface processes occurring at interfaces, including transmission and reflection effects. This entire set of computations takes place against the backdrop of a rich geometry package which serves a variety of roles, including initialization of electromagnetic field simulations and the support of state-dependent algorithm-swapping and behavioral changes as a particle's state evolves. Thanks to the very general approach taken by Kassiopeia it can be used by other experiments facing similar challenges when calculating particle trajectories in electromagnetic fields. It is publicly available at https://github.com/KATRIN-Experiment/Kassiopeia.« less

  9. The current deglaciation of the Ortles-Cevedale massif (Eastern Italian Alps): impacts, controls and degree of imbalance

    NASA Astrophysics Data System (ADS)

    Carturan, L.; Filippi, R.; Seppi, R.; Gabrielli, P.; Notarnicola, C.; Bertoldi, L.; Paul, F.; Rastner, P.; Cazorzi, F.; Dalla Fontana, G.

    2012-04-01

    glaciers by comparing the current Accumulation Area Ratios (AAR) with the balanced-budget AAR (AAR0), the latter also accounting for the debris cover of glaciers. We found that the total area loss of the Ortles-Cevedale glaciers from 1987 to 2009 amounts to 23.5 km2, i.e. 23.4% of the initial area. On the other hand, the AAR of the entire glacier system was 0.3 in both investigated years. The overall debris cover increased from 10.5% to 16.3%. The geodetic mass balance rate was -0.7 m w.e. y-1(as an average on 112 ice bodies), ranging from -0.1 to -1.7 m w.e. y-1. We also found that the main controls of the differing change of single glaciers are related to their hypsometry (elevation range and slope), AAR, feeding source and debris cover. Interestingly, a significant correlation was found between AAR, AAR0 and debris cover. This information was used to assess and visualize the needed additional reduction of individual glaciers to reach equilibrium with the current size of their accumulation areas. This amounts on average to a further reduction of ~40% of the current areal extent of glaciers.

  10. 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.

  11. 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

  12. 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

  13. [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.

  14. Differential modulation of α-1 adrenoceptor subtypes by antidepressants in the rat brain.

    PubMed

    Ramakrishna, D; Subhash, M N

    2010-12-01

    The aim of the present study was to examine the effect of chronic antidepressants treatment on the density of α₁-adrenoceptor (AR) subtypes in rat brain. Density of total α₁ and α(1A)- and α(1Β)-ARs was measured in cortex and cerebellum of rats treated with amitriptyline (AMI), desipramine (DMI) and fluoxetine (FLX), (10 mg/kg body wt), for 30 days, using [³H]prazosin in presence and absence of WB-4101. The density of cortical total α₁-ARs was significantly decreased with AMI (54%) and DMI (25%) treatment, without altering the affinity of the receptor. Fluoxetine did not alter the density of cortical α₁-ARs. The density of cortical α(1A)-ARs was also significantly decreased with AMI (85%) and DMI (50%) treatment, without affecting the affinity. The density of cerebellar total α₁-ARs was significantly decreased with AMI (37%), DMI (50%) and FLX (70%) treatment, without affecting the affinity for [³H]prazosin. The density of α(1A)-ARs was significantly decreased with AMI (67%), DMI (59%) and FLX (92%) treatment. α(1B)-AR density was decreased only with FLX (47%) and DMI (47%) treatment. Correspondingly the basal IP3 and NE (10 μM) stimulated IP3 levels were significantly decreased in AMI (47%), DMI (22%) and FLX (48%) treated rat cortex. The results suggest that chronic antidepressant (AD) treatment down-regulates the cortical and cerebellar total α₁-ARs in rat brain. However, α(1A) subtype is predominantly down-regulated by AMI and DMI, where as FLX affects cerebellar α(1A)-ARs. The region-specific and subtype specific down-regulation of α₁-ARs density, which occurs after prolonged AD treatment, may underline the therapeutic mechanism of action.

  15. 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

  16. Association between epicardial adipose tissue volume and myocardial salvage in patients with a first ST-segment elevation myocardial infarction: An epicardial adipose tissue paradox.

    PubMed

    Gohbara, Masaomi; Iwahashi, Noriaki; Akiyama, Eiichi; Maejima, Nobuhiko; Tsukahara, Kengo; Hibi, Kiyoshi; Kosuge, Masami; Ebina, Toshiaki; Umemura, Satoshi; Kimura, Kazuo

    2016-11-01

    Epicardial adipose tissue (EAT), defined as the adipose tissue between the visceral pericardium and the outer margin of the myocardium, is associated with coronary artery disease in the general population. However, the clinical implications of EAT in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. A total of 142 patients with a first STEMI, who received reperfusion therapy within 12h from symptom onset, were enrolled. All patients underwent cardiac magnetic resonance imaging to evaluate infarct core (Core), area at risk (AAR), and EAT volume. Myocardial salvage index (MSI) was defined as AAR minus Core divided by AAR. Patients in the lower tertile of EAT volume were classified as the low EAT group (group L) and the other two-thirds as the high EAT group (group H). The mean MSI was lower in group L than in group H (0.43±0.13 vs 0.49±0.13, p=0.01), and the mean extent of Core was higher in group L than in group H (25±10% vs 19±10%, p<0.01). Multivariate linear regression analysis including coronary risk factors and previously reported predictors of infarct size demonstrated that EAT volume was an independent predictor of MSI (β coefficient=0.002 per 1mL, p=0.002). A lower EAT volume is associated with less myocardial salvage and larger infarct size in patients with a first STEMI. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2016-01-01

    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

  18. Insulin restores L-arginine transport requiring adenosine receptors activation in umbilical vein endothelium from late-onset preeclampsia.

    PubMed

    Salsoso, R; Guzmán-Gutiérrez, E; Sáez, T; Bugueño, K; Ramírez, M A; Farías, M; Pardo, F; Leiva, A; Sanhueza, C; Mate, A; Vázquez, C; Sobrevia, L

    2015-03-01

    Preeclampsia is associated with impaired placental vasodilation and reduced endothelial nitric oxide synthase (eNOS) activity in the foetoplacental circulation. Adenosine and insulin stimulate vasodilation in endothelial cells, and this activity is mediated by adenosine receptor activation in uncomplicated pregnancies; however, this activity has yet to be examined in preeclampsia. Early onset preeclampsia is associated with severe placental vasculature alterations that lead to altered foetus growth and development, but whether late-onset preeclampsia (LOPE) alters foetoplacental vascular function is unknown. Vascular reactivity to insulin (0.1-1000 nmol/L, 5 min) and adenosine (1 mmol/L, 5 min) was measured in KCl-preconstricted human umbilical vein rings from normal and LOPE pregnancies using a wire myograph. The protein levels of human cationic amino acid transporter 1 (hCAT-1), adenosine receptor subtypes, total and Ser¹¹⁷⁷- or Thr⁴⁹⁵-phosphorylated eNOS were detected via Western blot, and L-arginine transport (0-1000 μmol/L L-arginine, 3 μCi/mL L-[³H]arginine, 20 s, 37 °C) was measured in the presence or absence of insulin and adenosine receptor agonists or antagonists in human umbilical vein endothelial cells (HUVECs) from normal and LOPE pregnancies. LOPE increased the maximal L-arginine transport capacity and hCAT-1 and eNOS expression and activity compared with normal conditions. The A(2A) adenosine receptor (A(2A)AR) antagonist ZM-241385 blocked these effects of LOPE. Insulin-mediated umbilical vein ring relaxation was lower in LOPE pregnancies than in normal pregnancies and was restored using the A(2A)AR antagonist. The reduced foetoplacental vascular response to insulin may result from A(2A)AR activation in LOPE pregnancies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. APC mutations as a potential biomarker for sensitivity to tankyrase inhibitors in colorectal cancer.

    PubMed

    Tanaka, Noritaka; Mashima, Tetsuo; Mizutani, Anna; Sato, Ayana; Aoyama, Aki; Gong, Bo; Yoshida, Haruka; Muramatsu, Yukiko; Nakata, Kento; Matsuura, Masaaki; Katayama, Ryohei; Nagayama, Satoshi; Fujita, Naoya; Sugimoto, Yoshikazu; Seimiya, Hiroyuki

    2017-02-08

    In most colorectal cancers (CRCs), Wnt/β-catenin signaling is activated by loss-of-function mutations in the adenomatous polyposis coli (APC) gene and plays a critical role in tumorigenesis. Tankyrases poly(ADP-ribosyl)ate and destabilize Axins, a negative regulator of β-catenin, and upregulate β-catenin signaling. Tankyrase inhibitors downregulate β-catenin and are expected to be promising therapeutics for CRC. However, CRC cells are not always sensitive to tankyrase inhibitors, and predictive biomarkers for the drug sensitivity remain elusive. Here we demonstrate that the short-form APC mutations predict the sensitivity of CRC cells to tankyrase inhibitors. By using well-established CRC cell lines, we found that tankyrase inhibitors downregulated β-catenin in the drug-sensitive but not resistant CRC cells. The drug-sensitive cells showed higher Tcf/LEF transcriptional activity than the resistant cells and possessed 'short' truncated APCs lacking all seven β-catenin-binding 20-amino-acid repeats (20-AARs). By contrast, the drug-resistant cells possessed 'long' APC retaining two or more 20-AARs. Knockdown of the long APCs with two 20-AARs increased β-catenin, Tcf/LEF transcriptional activity and its target gene AXIN2 expression. Under these conditions, tankyrase inhibitors were able to downregulate β-catenin in the resistant cells. These results indicate that the long APCs are hypomorphic mutants whereas they exert a dominant-negative effect on Axin-dependent β-catenin degradation caused by tankyrase inhibitors. Finally, we established 16 patient-derived CRC cells and confirmed that the tankyrase inhibitor-responsive cells harbor the short-form APC mutations. These observations exemplify the predictive importance of APC mutations, the most common genetic alteration in CRCs, for molecular targeted therapeutics.

  20. Adenosine A2B receptor blockade slows growth of bladder and breast tumors.

    PubMed

    Cekic, Caglar; Sag, Duygu; Li, Yuesheng; Theodorescu, Dan; Strieter, Robert M; Linden, Joel

    2012-01-01

    The accumulation of high levels of adenosine in tumors activates A(2A) and A(2B) receptors on immune cells and inhibits their ability to suppress tumor growth. Deletion of adenosine A(2A) receptors (A(2A)ARs) has been reported to activate antitumor T cells, stimulate dendritic cell (DC) function, and inhibit angiogenesis. In this study, we evaluated the effects of intermittent intratumor injection of a nonselective adenosine receptor antagonist, aminophylline (AMO; theophylline ethylenediamine) and, for the first time to our knowledge, a selective A(2B)AR antagonist, ATL801. AMO and ATL801 slowed the growth of MB49 bladder and 4T1 breast tumors in syngeneic mice and reduced by 85% metastasizes of breast cancer cells from mammary fat to lung. Based on experiments with A(2A)AR(-/-) or adenosine A(2B) receptor(-/-) mice, the effect of AMO injection was unexpectedly attributed to A(2B)AR and not to A(2A)AR blockade. AMO and ATL801 significantly increased tumor levels of IFN-γ and the IFN-inducible chemokine CXCL10, which is a ligand for CXCR3. This was associated with an increase in activated tumor-infiltrating CXCR3(+) T cells and a decrease in endothelial cell precursors within tumors. Tumor growth inhibition by AMO or ATL801 was eliminated in CXCR3(-/-) mice and RAG1(-/-) mice that lack mature T cells. In RAG1(-/-) mice, A(2B)AR deletion enhanced CD86 expression on CD11b(-) DCs. Bone marrow chimera experiments demonstrated that CXCR3 and A(2B)AR expression on bone marrow cells is required for the antitumor effects of AMO. The data suggest that blockade of A(2B)ARs enhances DC activation and CXCR3-dependent antitumor responses.

  1. Inpatient procedures in elderly women: an analysis over time.

    PubMed

    Oliphant, Sallie S; Ghetti, Chiara; McGough, Richard L; Wang, Li; Bunker, Clareann H; Lowder, Jerry L

    2013-08-01

    To describe inpatient surgical and diagnostic/therapeutic procedures in women ≥65 years old and assess procedure trends over time. Procedure data for all women ≥65 years was collected using the National Hospital Discharge Survey, a federal dataset drawn from a representative sampling of U.S. inpatient hospitals which includes patient and hospital demographics and ICD-9-CM diagnosis and procedure codes for admissions from 1979 to 2006. Age-adjusted rates (AAR) per 1000 women were created using 1990 U.S. Census data to compare trends over time. Over 96 million procedures were performed in women age≥65 years from 1979 to 2006. Women age≥65 years constituted 17% of women with ≥1 inpatient procedure in 1979, rising to 32% in 2006. The most common surgical procedures were lower extremity joint replacement, open reduction internal fixation, and cholecystectomy. The most common concurrent diagnosis was femoral neck fracture. Women with femoral neck fracture were more likely to undergo open reduction internal fixation compared to joint replacement. AARs for ORIF fell from 4.3 to 3.2 (p=.02) from 1979 to 2006, while AARs for joint replacement increased from 0.2 to 3.4 (p≤.001, 1979-1988; p=.14, 1990-2006). The rate of women age≥65 years undergoing inpatient procedures has increased dramatically in the last 30 years. Hip fracture was the most common diagnosis for elderly women, highlighting the impact of osteoporosis and falls and the importance of prevention strategies and optimization of peri-operative care in this population. Further comparative study of hip fracture treatment strategies in this population is needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Insulin/adenosine axis linked signalling.

    PubMed

    Silva, Luis; Subiabre, Mario; Araos, Joaquín; Sáez, Tamara; Salsoso, Rocío; Pardo, Fabián; Leiva, Andrea; San Martín, Rody; Toledo, Fernando; Sobrevia, Luis

    2017-06-01

    Regulation of blood flow depends on systemic and local release of vasoactive molecules such as insulin and adenosine. These molecules cause vasodilation by activation of plasma membrane receptors at the vascular endothelium. Adenosine activates at least four subtypes of adenosine receptors (A1AR, A2AAR, A2BAR, A3AR), of which A2AAR and A2BAR activation leads to increased cAMP level, generation of nitric oxide, and relaxation of the underlying smooth muscle cell layer. Vasodilation caused by adenosine also depends on plasma membrane hyperpolarization due to either activation of intermediate-conductance Ca(2+)-activated K(+) channels in vascular smooth muscle or activation of ATP-activated K(+) channels in the endothelium. Adenosine also causes vasoconstriction via a mechanism involving A1AR activation resulting in lower cAMP level and increased thromboxane release. Insulin has also a dual effect causing NO-dependent vasodilation, but also sympathetic activity- and increased endothelin 1 release-dependent vasoconstriction. Interestingly, insulin effects require or are increased by activation or inactivation of adenosine receptors. This is phenomenon described for d-glucose and l-arginine transport where A2AAR and A2BAR play a major role. Other studies show that A1AR activation could reduce insulin release from pancreatic β-cells. Whether adenosine modulation of insulin biological effect is a phenomenon that depends on co-localization of adenosine receptors and insulin receptors, and adenosine plasma membrane transporters is something still unclear. This review summarizes findings addressing potential involvement of adenosine receptors to modulate insulin effect via insulin receptors with emphasis in the human vasculature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Automatic anatomy recognition via fuzzy object models

    NASA Astrophysics Data System (ADS)

    Udupa, Jayaram K.; Odhner, Dewey; Falcão, Alexandre X.; Ciesielski, Krzysztof C.; Miranda, Paulo A. V.; Matsumoto, Monica; Grevera, George J.; Saboury, Babak; Torigian, Drew A.

    2012-02-01

    To make Quantitative Radiology a reality in routine radiological practice, computerized automatic anatomy recognition (AAR) during radiological image reading becomes essential. As part of this larger goal, last year at this conference we presented a fuzzy strategy for building body-wide group-wise anatomic models. In the present paper, we describe the further advances made in fuzzy modeling and the algorithms and results achieved for AAR by using the fuzzy models. The proposed AAR approach consists of three distinct steps: (a) Building fuzzy object models (FOMs) for each population group G. (b) By using the FOMs to recognize the individual objects in any given patient image I under group G. (c) To delineate the recognized objects in I. This paper will focus mostly on (b). FOMs are built hierarchically, the smaller sub-objects forming the offspring of larger parent objects. The hierarchical pose relationships from the parent to offspring are codified in the FOMs. Several approaches are being explored currently, grouped under two strategies, both being hierarchical: (ra1) those using search strategies; (ra2) those strategizing a one-shot approach by which the model pose is directly estimated without searching. Based on 32 patient CT data sets each from the thorax and abdomen and 25 objects modeled, our analysis indicates that objects do not all scale uniformly with patient size. Even the simplest among the (ra2) strategies of recognizing the root object and then placing all other descendants as per the learned parent-to-offspring pose relationship bring the models on an average within about 18 mm of the true locations.

  4. Functional Class I and II Amino Acid-activating Enzymes Can Be Coded by Opposite Strands of the Same Gene*

    PubMed Central

    Martinez-Rodriguez, Luis; Erdogan, Ozgün; Jimenez-Rodriguez, Mariel; Gonzalez-Rivera, Katiria; Williams, Tishan; Li, Li; Weinreb, Violetta; Collier, Martha; Chandrasekaran, Srinivas Niranj; Ambroggio, Xavier; Kuhlman, Brian; Carter, Charles W.

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRS) catalyze both chemical steps that translate the universal genetic code. Rodin and Ohno offered an explanation for the existence of two aaRS classes, observing that codons for the most highly conserved Class I active-site residues are anticodons for corresponding Class II active-site residues. They proposed that the two classes arose simultaneously, by translation of opposite strands from the same gene. We have characterized wild-type 46-residue peptides containing ATP-binding sites of Class I and II synthetases and those coded by a gene designed by Rosetta to encode the corresponding peptides on opposite strands. Catalysis by WT and designed peptides is saturable, and the designed peptides are sensitive to active-site residue mutation. All have comparable apparent second-order rate constants 2.9–7.0E-3 m−1 s−1 or ∼750,000–1,300,000 times the uncatalyzed rate. The activities of the two complementary peptides demonstrate that the unique information in a gene can have two functional interpretations, one from each complementary strand. The peptides contain phylogenetic signatures of longer, more sophisticated catalysts we call Urzymes and are short enough to bridge the gap between them and simpler uncoded peptides. Thus, they directly substantiate the sense/antisense coding ancestry of Class I and II aaRS. Furthermore, designed 46-mers achieve similar catalytic proficiency to wild-type 46-mers by significant increases in both kcat and Km values, supporting suggestions that the earliest peptide catalysts activated ATP for biosynthetic purposes. PMID:26088142

  5. Functional Class I and II Amino Acid-activating Enzymes Can Be Coded by Opposite Strands of the Same Gene.

    PubMed

    Martinez-Rodriguez, Luis; Erdogan, Ozgün; Jimenez-Rodriguez, Mariel; Gonzalez-Rivera, Katiria; Williams, Tishan; Li, Li; Weinreb, Violetta; Collier, Martha; Chandrasekaran, Srinivas Niranj; Ambroggio, Xavier; Kuhlman, Brian; Carter, Charles W

    2015-08-07

    Aminoacyl-tRNA synthetases (aaRS) catalyze both chemical steps that translate the universal genetic code. Rodin and Ohno offered an explanation for the existence of two aaRS classes, observing that codons for the most highly conserved Class I active-site residues are anticodons for corresponding Class II active-site residues. They proposed that the two classes arose simultaneously, by translation of opposite strands from the same gene. We have characterized wild-type 46-residue peptides containing ATP-binding sites of Class I and II synthetases and those coded by a gene designed by Rosetta to encode the corresponding peptides on opposite strands. Catalysis by WT and designed peptides is saturable, and the designed peptides are sensitive to active-site residue mutation. All have comparable apparent second-order rate constants 2.9-7.0E-3 M(-1) s(-1) or ∼750,000-1,300,000 times the uncatalyzed rate. The activities of the two complementary peptides demonstrate that the unique information in a gene can have two functional interpretations, one from each complementary strand. The peptides contain phylogenetic signatures of longer, more sophisticated catalysts we call Urzymes and are short enough to bridge the gap between them and simpler uncoded peptides. Thus, they directly substantiate the sense/antisense coding ancestry of Class I and II aaRS. Furthermore, designed 46-mers achieve similar catalytic proficiency to wild-type 46-mers by significant increases in both kcat and Km values, supporting suggestions that the earliest peptide catalysts activated ATP for biosynthetic purposes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Sleep disorders in Latin-American children with asthma and/or allergic rhinitis and normal controls.

    PubMed

    Urrutia-Pereira, M; Solé, D; Chong Neto, H J; Acosta, V; Cepeda, A M; Álvarez-Castelló, M; Almendarez, C F; Lozano-Saenz, J; Sisul-Alvariza, J C; Rosario, N A; Castillo, A J; Valentin-Rostan, M; Badellino, H; Castro-Almarales, R L; González-León, M; Sanchez-Silot, C; Avalos, M M; Fernandez, C; Berroa, F; De la Cruz, M M; Sarni, R O S

    Asthma and/or allergic rhinitis have been associated with sleep disorders. The aim of this study was to evaluate sleep disorders in Latin-American children (4-10 years) from nine countries, with persistent asthma (A) and/or allergic rhinitis (AR) and in normal controls (C). Parents from 454 C children and 700 A and/or AR children followed up in allergy reference clinics completed the Children's Sleep Habits Questionnaire (CSHQ) which is a retrospective one-week questionnaire composed of 33 questions composed of seven subscales (bedtime resistance, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing and daytime sleepiness). The total scale of CSHQ and the subscales were compared between groups C and A+AR, A (n=285) vs. AR (n=390), and between controlled A (CA, n=103) vs. partially controlled/uncontrolled A (UA, n=182). The comparison between C and A+AR showed no significant differences in age (6.7 years vs. 7.0 years, respectively), mean Body Mass Index and total scale of CSHQ (53.3 vs. 63.2, respectively) and the subscales were significantly higher in the A+AR group. Comparison between groups A and AR, except for sleep anxiety, showed significantly higher values for CSHQ total scale (66.9 vs. 61.0, respectively) and subscales for group A. The UA group showed significantly higher values for total CSHQ scale and subscales in comparison to CA (71.1 vs. 59.4, respectively). Latin-American children with asthma and/or allergic rhinitis showed sleep disorders identified by the CSHQ when compared to normal controls. Despite being treated, asthma causes sleep impairment, especially when uncontrolled. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  7. A large family of anti‐activators accompanying XylS/AraC family regulatory proteins

    PubMed Central

    Yan, Michael B.; Tran, Minh; Wright, Nathan; Luzader, Deborah H.; Kendall, Melissa M.; Ruiz‐Perez, Fernando; Nataro, James P.

    2016-01-01

    Summary 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

  8. Estimation of glacier mass balance: An approach based on satellite-derived transient snowlines and a temperature index driven by meteorological observations

    NASA Astrophysics Data System (ADS)

    Tawde, S. A.; Kulkarni, A. V.; Bala, G.

    2015-12-01

    In the Himalaya, large area is comprised of glaciers and seasonal snow, mainly due to its high elevated mountain ranges. Long term and continuous assessment of glaciers in this region is important for climatological and hydrological applications. However, rugged terrains and severe weather conditions in the Himalaya lead to paucity in field observations. Therefore, in recent decades, glacier dynamics are extensively monitored using remote sensing in inaccessible terrain like Himalaya. Estimation of glacier mass balance using empirical relationship between mass balance and area accumulation ratio (AAR) requires an accurate estimate of equilibrium-line altitude (ELA). ELA is defined as the snowline at the end of the hydrological year. However, identification of ELA, using remote sensing is difficult because of temporal gaps, cloud cover and intermediate snowfall on glaciers. This leads to large uncertainty in glacier mass-balance estimates by the conventional AAR method that uses satellite-derived highest snowline in ablation season as an ELA. The present study suggests a new approach to improve estimates of ELA location. First, positions of modelled snowlines are optimized using satellite-derived snowlines in the early melt season. Secondly, ELA at the end of the glaciological year is estimated by the melt and accumulation models driven using in situ temperature and precipitation records. From the modelled ELA, mass balance is estimated using the empirical relationship between AAR and mass balance. The modelled mass balance is validated using field measurements on Chhota Shigri and Hamtah glaciers, Himachal Pradesh, India. The new approach shows a substantial improvement in glacier mass-balance estimation, reducing bias by 46% and 108% for Chhota Shigiri and Hamtah glaciers respectively. The cumulative mass loss reconstructed from our approach is 0.85 Gt for nine glaciers in the Chandra basin from 2001 to 2009. The result of the present study is in agreement with

  9. 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

  10. Counselling increases physical activity behaviour nine weeks after rehabilitation.

    PubMed

    van der Ploeg, H P; Streppel, K R M; van der Beek, A J; van der Woude, L H V; Vollenbroek-Hutten, M M R; van Harten, W H; van Mechelen, W

    2006-03-01

    For people with disabilities, a physically active lifestyle can reduce the risk of secondary health problems and improve overall functioning. To determine the effects of the sport stimulation programme "rehabilitation and sports" (R&S) and R&S combined with the daily physical activity promotion programme "active after rehabilitation" (AaR) on sport participation and daily physical activity behaviour nine weeks after inpatient or outpatient rehabilitation. Subjects in four intervention rehabilitation centres were randomised to a group receiving R&S only (n = 315) or a group receiving R&S and AaR (n = 284). Subjects in six control rehabilitation centres (n = 603) received the usual care. Most common diagnoses were stroke, neurological disorders, and back disorders. Two sport and two daily physical activity outcomes were assessed with questionnaires seven weeks before and nine weeks after the end of rehabilitation. Data were analysed by intention to treat and on treatment multilevel analyses, comparing both intervention groups with the control group. The R&S group showed no significant change. Intention to treat analyses of the R&S+AaR group showed significant improvements in one sport (p = 0.02) and one physical activity outcome (p = 0.03). On treatment analyses in the R&S+AaR group showed significant improvements in both sport outcomes (p<0.01 and p = 0.02) and one physical activity outcome (p<0.01). Only the combination of R&S and AaR had increased sports participation and daily physical activity behaviour nine weeks after the end of inpatient or outpatient rehabilitation.

  11. 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

  12. 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

  13. Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation

    PubMed Central

    Sieber, O M; Segditsas, S; Knudsen, A L; Zhang, J; Luz, J; Rowan, A J; Spain, S L; Thirlwell, C; Howarth, K M; Jaeger, E E M; Robinson, J; Volikos, E; Silver, A; Kelly, G; Aretz, S; Frayling, I; Hutter, P; Dunlop, M; Guenther, T; Neale, K; Phillips, R; Heinimann, K; Tomlinson, I P M

    2006-01-01

    Background Attenuated familial adenomatous polyposis (AFAP) is associated with germline mutations in the 5′, 3′, and exon 9 of the adenomatous polyposis coli (APC) gene. These mutations probably encode a limited amount of functional APC protein. Methods and results We found that colonic polyp number varied greatly among AFAP patients but members of the same family tended to have more similar disease severity. 5′ Mutants generally had more polyps than other patients. We analysed somatic APC mutations/loss of heterozygosity (LOH) in 235 tumours from 35 patients (16 families) with a variety of AFAP associated germline mutations. In common with two previous studies of individual kindreds, we found biallelic changes (“third hits”) in some polyps. We found that the “third hit” probably initiated tumorigenesis. Somatic mutation spectra were similar in 5′ and 3′ mutant patients, often resembling classical FAP. In exon 9 mutants, in contrast, “third hits” were more common. Most “third hits” left three 20 amino acid repeats (20AARs) on the germline mutant APC allele, with LOH (or proximal somatic mutation) of the wild‐type allele; but some polyps had loss of the germline mutant with mutation leaving one 20AAR on the wild‐type allele. Conclusions We propose that mutations, such as nt4661insA, that leave three 20AARs are preferentially selected in cis with some AFAP mutations because the residual protein function is near optimal for tumorigenesis. Not all AFAP polyps appear to need “three hits” however. AFAP is phenotypically and genetically heterogeneous. In addition to effects of different germline mutations, modifier genes may be acting on the AFAP phenotype, perhaps influencing the quantity of functional protein produced by the germline mutant allele. PMID:16461775

  14. 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

  15. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process.

    PubMed

    Woese, C R; Olsen, G J; Ibba, M; Söll, D

    2000-03-01

    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.

  16. Understanding and identifying amino acid repeats

    PubMed Central

    Nijveen, Harm

    2014-01-01

    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

  17. Distinct Correlation Structure Supporting a Rate-Code for Sound Localization in the Owl’s Auditory Forebrain

    PubMed Central

    2017-01-01

    Abstract While a topographic map of auditory space exists in the vertebrate midbrain, it is absent in the forebrain. Yet, both brain regions are implicated in sound localization. The heterogeneous spatial tuning of adjacent sites in the forebrain compared to the midbrain reflects different underlying circuitries, which is expected to affect the correlation structure, i.e., signal (similarity of tuning) and noise (trial-by-trial variability) correlations. Recent studies have drawn attention to the impact of response correlations on the information readout from a neural population. We thus analyzed the correlation structure in midbrain and forebrain regions of the barn owl’s auditory system. Tetrodes were used to record in the midbrain and two forebrain regions, Field L and the downstream auditory arcopallium (AAr), in anesthetized owls. Nearby neurons in the midbrain showed high signal and noise correlations (RNCs), consistent with shared inputs. As previously reported, Field L was arranged in random clusters of similarly tuned neurons. Interestingly, AAr neurons displayed homogeneous monotonic azimuth tuning, while response variability of nearby neurons was significantly less correlated than the midbrain. Using a decoding approach, we demonstrate that low RNC in AAr restricts the potentially detrimental effect it can have on information, assuming a rate code proposed for mammalian sound localization. This study harnesses the power of correlation structure analysis to investigate the coding of auditory space. Our findings demonstrate distinct correlation structures in the auditory midbrain and forebrain, which would be beneficial for a rate-code framework for sound localization in the nontopographic forebrain representation of auditory space. PMID:28674698

  18. Manual thrombectomy efficiency in relationship to the area at risk in patients with myocardial infarction with TIMI 0-1 coronary flow: Insights from an all comers registry.

    PubMed

    Luz, André; Silveira, Inês; Brochado, Bruno; Rodrigues, Patrícia; João Sousa, Maria; Santos, Raquel; Trêpa, Maria; Santos, Mário; Silveira, João; Torres, Severo; Leite-Moreira, Adelino F; Carvalho, Henrique

    2017-02-13

    To review the effectiveness of manual thrombectomy (MT) in a series of patients with ST-elevation myocardial infarction (STEMI) exclusively presenting with TIMI 0-1 flow undergoing percutaneous coronary intervention (PCI), in accordance to the angiographically estimated area at risk (AAR). Second, to assess major in-hospital clinical events, emphasizing neurological outcomes. The routine utilization of MT in STEMI is not recommended. However, in recent trials, a significant proportion of patients had neither large thrombus burden nor a totally occluded coronary segment, neutralizing the expected benefits of MT. In addition, the efficiency of MT to remove thrombus has rarely been addressed. Finally, MT diminished distal embolization, which has been related to mortality. In 850 consecutive STEMI-patients, MT was utilized in 525 (62%) and it was considered efficient (TIMI 2-3 flow after MT) in 445 (85%). We found a significant interaction between the AAR and the effectiveness of MT to reduce infarct size (P-interaction = 0.014). In patients having AAR ≥ 28% (n = 184), efficient MT conferred lesser infarct size compared to inefficient MT (Ln-transformed peak CK): 7.87 ± 0.86 versus 8.36 ± 0.41 IU/L, P = 0.005, with no impact for AAR <28%. Clinical outcomes including stroke between MT and PCI-only groups were not different. In comparison with the group where MT was inefficient, efficient MT may modestly reduce final infarct size without a significant clinical benefit. In comparison with PCI-only, no difference was found regarding stroke. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Ash recycling - the coming of age!

    SciTech Connect

    Barnes, J.M.; Roffman, H.K.; Roethel, F.J.

    1997-12-01

    A major concern of the Waste-To-Energy (WTE) industry is ash disposal and the uncertainty of controlled long term ash management. Ash management costs have risen steadily over the last ten years making it the fastest rising cost segment of the WTE industry. The challenge of how to curb the rising cost while maintaining the protection of human health and the environment has been accomplished by responsibly recycling the ash on a commercial basis. American Ash Recycling Corp. (AAR), utilizing the Duos Engineering (USA), Inc. patent pending ash recycling technology, has promoted ash recycling on a commercial basis in the United States. An important product of the processing and recycling of non-hazardous municipal waste combustor (MWC) ash is Treated Ash Aggregate (TAA). Additionally, ferrous and non-ferrous metals are recovered and unburned materials removed and returned to the WTE facility for re-combustion. The TAA is sized and then treated by the WES-PHix{reg_sign} immobilization process in order to reduce the potential solubility and environmental availability of the metal constituents of the MWC ash. The TAA is available for commercial use in such applications as an aggregate substitute in roadway materials, asphalt and concrete applications, as structural fill, and as landfill cover. Commercial and technical considerations that must be addressed before ash can be beneficially recycled are: permitting requirements, physical and chemical characteristics, potential end uses, environmental concerns (product safety), product market development, and economic viability. True recycling only occurs if all of these considerations can be addressed. This paper presents the details of AAR`s most recent experience in the development of an ash recycling facility in the State of Maine and the associated beneficial use of the TAA product. Each of the considerations listed above are discussed with a special focus on the permitting process.

  20. Assessment of soil nitrogen and related enzymes as influenced by the incorporation time of field pea cultivated as a catch crop in Alfisol.

    PubMed

    Piotrowska-Długosz, Anna; Wilczewski, Edward

    2014-12-01

    The effect of the time of catch crop (field pea) incorporation [catch crop incorporated in the autumn (A) or in the spring (B) versus plots without a catch crop (C)] on the soil enzymes related to N transformation (urease - UR, protease - PRO, nitrate reductase - NR, arginine ammonification rate - AAR), the total N and mineral N as well as microbial biomass N (MBN) contents were investigated in a 3-year experiment. The catch crop was sown at the beginning of August and plowed in the autumn in 2008, 2009 and 2010 or left as mulch during the winter. Soil samples for microbial activity were taken from spring barley plots that were grown in 2009, 2010 and 2011 before sowing (March), during the tillering phase (May), shooting (June) and after the harvesting of spring barley (August). The use of catch crop significantly increased the soil mineral and MBN contents as well as the activities of PRO and NR as compared to the control soil. The spring incorporation of the field pea significantly increased the MBN content in contrast to the autumn application, while the activity of N-cycle enzymes were clearly unaffected (UR and AAR) regardless of the time of the incorporation of field pea or else the results were inconsistent (PRO and NR). When the catch crop was incorporated in the spring, a significantly higher content of mineral N as compared to autumn incorporation was noted on only two of the four sampling dates. The enzymatic activity (PRO and AAR) was about 1.3-2.8 times higher in May and June as compared with March and August. Both spring or autumn incorporation of catch crop can be a useful management practice to increase the soil mineral N content and enhance the soil biological activity.

  1. Proteomic-coupled-network analysis of T877A-androgen receptor interactomes can predict clinical prostate cancer outcomes between White (non-Hispanic) and African-American groups.

    PubMed

    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.

  2. Reversible Unfolding of Rhomboid Intramembrane Proteases

    PubMed Central

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

    2016-01-01

    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

  3. Under-representation of women and ethnic minorities in vascular surgery randomized controlled trials.

    PubMed

    Hoel, Andrew W; Kayssi, Ahmed; Brahmanandam, Soma; Belkin, Michael; Conte, Michael S; Nguyen, Louis L

    2009-08-01

    Gender and ethnicity are factors affecting the incidence and severity of vascular disease as well as subsequent treatment outcomes. Although well studied in other fields, balanced enrollment of patients with relevant demographic characteristics in vascular surgery randomized controlled trials (RCTs) is not well known. This study describes the reporting of gender and ethnicity data in vascular surgery RCTs and analyzes whether these studies adequately represent our diverse patient population. We conducted a retrospective review of United States-based RCTs from 1983 through 2007 for three broadly defined vascular procedures: aortic aneurysm repair (AAR), carotid revascularization (CR), and lower extremity revascularization (LER). Included studies were examined for gender and ethnicity data, study parameters, funding source, and geographic region. The Nationwide Inpatient Sample (NIS) database was analyzed to obtain group-specific procedure frequency as an estimate of procedure frequency in the general population. We reviewed 77 studies, and 52 met our inclusion criteria. Only 85% reported gender, and 21% reported ethnicity. Reporting of ethnicity was strongly associated with larger (>280 participants), multicenter, government-funded trials (P < .001 for all). Women are disproportionately under-represented in RCTs for all procedure categories (AAR, 9.0% vs 21.5%; CR, 30.0% vs 42.9%; LER, 22.4% vs 41.3%). Minorities are under-represented in AAR studies (6.0% vs 10.7%) and CR studies (6.9% vs 9.5%) but are over-represented in LER studies (26.0% vs 21.8%, P < .001 for all). Minority ethnicity and female gender are under-reported and under-represented in vascular surgery RCTs, particularly in small, non-government-funded and single-center trials. The generalizability of some trial results may not be applicable to these populations. Greater effort to enroll a balanced study population in RCTs may yield more broadly applicable results.

  4. Mantle domain and segmentation at the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    The Australian-Antarctic ridge (AAR) is the largest unexplored expanse of the global mid-ocean ridges. Using the Korean Icebreaker Araon, we carried out a multi-disciplinary study of two segments (KR1 and KR2) of intermediate spreading AAR in three expeditions from 2011 to 2013. KR1, a 300-km-long supersegment located in the center of AAR, has large transform faults at its two ends, only small 3rd and 4th order offsets between the transforms, and no overlapping spreading centers. Nonetheless there are large variations in axial morphology from axial high to rift valley, as well as large changes in chemical and Pb isotopic composition. The KR2 segment is located about 200 km northwest of KR1 and connected to it by the Balleny transform. KR2 is a 180 km-long 1st order segment bounded by two transforms and consists of a western segment with axial high and an eastern segment with rift valley. Along-axis geochemical variations indicate that the magma flux and ridge morphology of are influenced by changing mantle composition on a fine scale, and thus magma transport to the crust must occur at multiple locations along this single segment. Both the KR1 and KR2 segments are on the Pacific side of the Australian-Antarctic-Discordance, long considered as the boundary between Pacific and Indian mantle. However, isotopic and trace elements data of these segments differ from samples from the Pacific-Antarctic Ridge, so flow of Pacific mantle into Indian mantle bounded by the Australian-Antarctic-Discordance is no longer supported.

  5. Domain structure characterization of the multifunctional alpha-aminoadipate reductase from Penicillium chrysogenum by limited proteolysis. Activation of alpha-aminoadipate does not require the peptidyl carrier protein box or the reduction domain.

    PubMed

    Hijarrubia, Maria José; Aparicio, Jesús F; Martín, Juan F

    2003-03-07

    The alpha-aminoadipate reductase (alpha-AAR) of Penicillium chrysogenum, an enzyme that activates the alpha-aminoadipic acid by forming an alpha-aminoadipyl adenylate and reduces the activated intermediate to alpha-aminoadipic semialdehyde, was purified to homogeneity by immunoaffinity techniques, and the kinetics for alpha-aminoadipic acid, ATP, and NADPH were determined. Sequencing of the N-terminal end confirmed the 10 first amino acids deduced from the nucleotide sequence. Its domain structure has been investigated using limited proteolysis and active site labeling. Trypsin and elastase were used to cleave the multienzyme, and the location of fragments within the primary structure was established by N-terminal sequence analysis. Initial proteolysis generated two fragments: an N-terminal fragment housing the adenylation and the peptidyl carrier protein (PCP) domains (116 kDa) and a second fragment containing most of the reductive domain (28 kDa). Under harsher conditions the adenylation domain (about 64 kDa) and the PCP domain (30 kDa) become separated. Time-dependent acylation of alpha-AAR and of fragments containing the adenylation domain with tritiated alpha-aminoadipate occurred in vitro in the absence of NADPH. Addition of NADPH to the labeled alpha-AAR released most of the radioactive substrate. A fragment containing the adenylation domain was labeled even in absence of the PCP box. The labeling of this fragment (lacking PCP) was always weaker than that observed in the di-domain (adenylating and PCP) fragment suggesting that the PCP domain plays a role in the stability of the acyl intermediate. Low intensity direct acylation of the PCP box has also been observed. A domain structure of this multienzyme is proposed.

  6. Predictors of mortality in leptospirosis: an observational study from two hospitals in Kolkata, eastern India.

    PubMed

    Goswami, Rudra P; Goswami, Rama P; Basu, Ayan; Tripathi, Santanu Kumar; Chakrabarti, Sanghamitra; Chattopadhyay, Indrajit

    2014-12-01

    Leptospirosis has a mortality rate of 5-20%. Poor prognostic factors are older age; oliguria; elevated potassium, creatinine and/or bilirubin levels; and altered mental status. We conducted this retrospective study to analyse the predictors of mortality among Indian patients with leptospirosis. Clinical, biochemical, demographic and treatment related data (time between onset of symptoms and commencement of leptospira specific antibiotics) of 101 leptospirosis patients were reviewed. Predictors identified by univariate analysis were analysed by multivariable Cox regression for survival analysis. Prominent clinical features were: fever (101/101, 100%), jaundice (62, 62.4%), vomiting (42, 41.6%), oliguria (35, 34.7%), cough (18, 17.8%) and dyspnoea (10, 10.0%). Common complications were acute kidney injury (22, 21.8%), cardiovascular collapse (13, 12.9%), haemorrhages (10, 10.0%), meningitis (7, 6.9%), acute respiratory distress syndrome and pancreatitis (5, 5.0% each). Seventeen patients died (16.8%). Univariate predictors of mortality were older age, delayed antibiotic therapy, higher bilirubin, aspartate aminotransferase, alkaline phosphatase, leucocyte count and aspartate/alanine aminotransferase ratio (AAR). Only AAR (HR 1.208, 95% CI 1.051-1.388) and number of days the patient was symptomatic before access to specific antibiotic therapy (HR 1.304, 95% CI 1.081-1.574) remained significant predictors after Cox regression. Multivariate analysis showed high AAR and delayed antibiotic therapy might be associated with fatality. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. 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.

  8. Liposomal Tetrahydrobiopterin Preserves eNOS Coupling in the Post-ischemic Heart Conferring in vivo Cardioprotection

    PubMed Central

    Xie, Lin; Talukder, M A Hassan; Sun, Jian; Varadharaj, Saradhadevi; Zweier, Jay L.

    2015-01-01

    Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), and reduced BH4 availability leads to endothelial NOS (eNOS) uncoupling and increased reactive oxygen species (ROS) generation. Questions remain regarding the functional state of eNOS and role of BH4 availability in the process of in vivo myocardial ischemia-reperfusion (I/R) injury. Rats were subjected to 60-minutes of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic liposomal BH4 supplementation (1 mg/kg, iv). Myocardial infarction was correlated with cardiac BH4 content, eNOS protein level, NOS enzyme activity, and ROS generation. In the vehicle group, 60-min ischemia drastically reduced myocardial BH4 content in the area at risk (AAR) compared to non-ischemic (NI) area and the level remained lower during early reperfusion followed by recovery after 24-hr reperfusion. Activated eNOS protein level (eNOS Ser1177 phosphorylation) and NOS activity were also significantly reduced during ischemia and/or early reperfusion, but recovered after 24-hr reperfusion. With liposomal BH4 treatment, BH4 levels were identical in the AAR and NI area during ischemia and/or early reperfusion, and were significantly higher than with vehicle. BH4 pre-treatment preserved eNOS Ser1177 phosphorylation and NOS activity in the AAR, and significantly reduced myocardial ROS generation and infarction compared to vehicle. These findings provide direct evidence that in vivo I/R induces eNOS dysfunction secondary to BH4 depletion, and that pre-ischemic liposomal BH4 administration preserves eNOS function conferring cardioprotection with reduced oxidative stress. PMID:26116866

  9. Liposomal tetrahydrobiopterin preserves eNOS coupling in the post-ischemic heart conferring in vivo cardioprotection.

    PubMed

    Xie, Lin; Talukder, M A Hassan; Sun, Jian; Varadharaj, Saradhadevi; Zweier, Jay L

    2015-09-01

    Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), and reduced BH4 availability leads to endothelial NOS (eNOS) uncoupling and increased reactive oxygen species (ROS) generation. Questions remain regarding the functional state of eNOS and role of BH4 availability in the process of in vivo myocardial ischemia-reperfusion (I/R) injury. Rats were subjected to 60min of in vivo left coronary artery occlusion and varying periods of reperfusion with or without pre-ischemic liposomal BH4 supplementation (1mg/kg, iv). Myocardial infarction was correlated with cardiac BH4 content, eNOS protein level, NOS enzyme activity, and ROS generation. In the vehicle group, 60-min ischemia drastically reduced myocardial BH4 content in the area at risk (AAR) compared to non-ischemic (NI) area and the level remained lower during early reperfusion followed by recovery after 24-h reperfusion. Total eNOS, activated eNOS protein level (eNOS Ser1177 phosphorylation) and NOS activity were also significantly reduced during ischemia and/or early reperfusion, but recovered after 24-h reperfusion. With liposomal BH4 treatment, BH4 levels were identical in the AAR and NI area during ischemia and/or early reperfusion, and were significantly higher than with vehicle. BH4 pre-treatment preserved eNOS Ser1177 phosphorylation and NOS activity in the AAR, and significantly reduced myocardial ROS generation and infarction compared to vehicle. These findings provide direct evidence that in vivo I/R induces eNOS dysfunction secondary to BH4 depletion, and that pre-ischemic liposomal BH4 administration preserves eNOS function conferring cardioprotection with reduced oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Coral injuries observed at Mesophotic Reefs after the Deepwater Horizon oil discharge

    NASA Astrophysics Data System (ADS)

    Silva, Mauricio; Etnoyer, Peter J.; MacDonald, Ian R.

    2016-07-01

    Pathologies in over 400 octocoral and antipatharian colonies were quantified in the aftermath of the DWH oil discharge. Observations were made in September 2011 at water depths of 65-75 m in the Pinnacle Reef trend area offshore from Mississippi and Alabama, Gulf of Mexico, using a digital macro camera deployed from an ROV to examine the coral populations for injury at two principal sites: Alabama Alps Reef (AAR) and Roughtongue Reef (RTR). Taxa observed to exhibit injury included gorgonian octocorals Hypnogorgia pendula, Bebryce spp., Thesea nivea, and Swiftia exserta, the antipatharian Antipathes atlantica, and the sea whips Stichopathes sp., and Ellisella barbadensis. The most common type of injury was a biofilm with a clumped or flake-like appearance covering sea-fan branches. Extreme injuries were characterized by bare skeletons, broken and missing branches. Comparing the 2011 results to previous photo surveys of the same study sites between 1997 and 1999, we found significantly more occurrences of injury in 2011 among taxa with growth forms >0.5 m. We hypothesize that Tropical Storm Bonnie facilitated and accelerated the mixing process of dispersant-treated hydrocarbons into the water column, resulting in harmful contact with coral colonies at mesophotic depths. Analysis of total polycyclic aromatic hydrocarbon (tPAH) concentrations in sediments at AAR and RTR found levels elevated above pre-discharge values, but orders of magnitude below toxicity thresholds established for fauna in estuarine sediments. The tPAH concentrations measured in octocoral and echinoderm tissue samples from AAR and RTR were detectable (mean values ranged from 51 to 345 ppb); however, bioeffect thresholds do not currently exist with which to evaluate the potential harm these levels may cause. Our findings indicate that coral injuries observed in 2011 may have resulted from an acute, isolated event rather than ongoing natural processes.

  11. Physics-Based Constitutive Model to Predict Dynamic Recovery Behavior of BFe10-1-2 Cupronickel Alloy during Hot Working

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Zhang, Xiaolu; Wang, Kuaishe; Miao, Chengpeng

    2016-11-01

    The hot deformation behavior of BFe10-1-2 cupronickel alloy was investigated over wide ranges of deformation temperature and strain rate. The physics-based constitutive model was developed to predict the dynamic recovery (DRV) behavior of BFe10-1-2 cupronickel alloy at elevated temperatures. In order to verify the validity of the developed constitutive equation, the correlation coefficient (R) and average absolute relative error (AARE) were introduced to make statistics. The results indicated that the developed constitutive equation lead a good agreement between the calculated and experimental data and can accurately characterize the hot DRV behaviors for the BFe10-1-2 cupronickel alloy.

  12. Surface electric properties of emulsions of apolar reagents

    SciTech Connect

    Baichenko, A.A.; Baran, A.A.

    1986-09-01

    This article presents the results of studies of surface electric properties of kerosene and AAR-2 (apolar aromatized reagent) emulsons in water, which can be used in coal slime flotation, in presence of various salts and high-molecular flocculants. The data obtained were compared with the effect of electrolytes on the surface electric properties of a model emulsion of heptane in water stabilized by sodium hapthenate. The studies indicate that similarity of changes in the electrokinetic properties of various emulsions in presence of electrolytes and flocculants.

  13. Naval Medical Center Portsmouth as Federal Coordinating Center, National Disaster Medical System: An Analysis of Activation Preparedness

    DTIC Science & Technology

    2009-07-21

    an earthguake occurred in Memphis, TN measuring 8.0 on the Richter scale. These exercises allowed players to interact and share their knowledge and...Memphis, TN measuring 8.0 on the Richter scale with numerous significant aftershocks. Note: Taken from AAR/IP 2009. Exercise Goals Although this...San Francisco VAMC (CA) VA San Francisco 9 CA VA Long Beach HCS (CA) VA Long Beach, Orange County 9 CA VA Loma Linda HCS (CA) VA Loma Linda 9 CA VA

  14. Overview of overseas humanitarian, disaster, and civic aid programs.

    PubMed

    Drifmeyer, Jeff; Llewellyn, Craig

    2003-12-01

    The U.S. Department of Defense (DoD) conducts humanitarian assistance missions under the Overseas Humanitarian Disaster and Civic Aid program for the statutory purposes of training military personnel, serving the political interests of the host nation and United States, and providing humanitarian relief to foreign civilians. These purposes are undertaken via the humanitarian assistance (HA), humanitarian and civic assistance, and excess property donation programs. DoD conducts over 200 such projects annually at a direct cost of approximately 27 million dollars in fiscal year 2001. Although varying by year and command, as many as one-half of these projects involve aspects of health care. These range from short-term patient care to donation of medical supplies and equipment excess to the needs of the DoD. Despite the considerable resources invested and importance of international actions, there is presently no formal evaluation system for these HA projects. Current administrative staffing of these programs by military personnel is often by individuals with many other duties and responsibilities. As a result, humanitarian projects are often inadequately coordinated with nongovernmental organizations, private volunteer organizations, or host-nation officials. Nonmedical military personnel sometimes plan health-related projects with little or no coordination with medical experts, military or civilian. After action reports (AARs) on these humanitarian projects are often subjective, lack quantitative details, and are devoid of measures of effectiveness. AARs are sometimes inconsistently completed, and there is no central repository of information for analysis of lessons learned. (The approximate 100 AARs used in the conduct of these studies are available for official use in the Learning Resources Center, Uniformed Services University of Health Sciences.) Feedback from past humanitarian projects is rare and with few exceptions; DoD-centric projects of a similar design are

  15. Regional differences of myocardial infarct development and ischemic preconditioning.

    PubMed

    Schulz, Rainer; Gres, Petra; Konietzka, Ina; Heusch, Gerd

    2005-01-01

    The spatial and temporal development of myocardial infarction depends on the area at risk (AAR), the severity and duration of blood flow reduction (energy supply) as well as on heart rate and regional wall function (energy demand). Both supply and demand can vary within the AAR of a given heart, potentially resulting in differences in infarct development. We therefore retrospectively analyzed infarct size (IS, %AAR, TTC) in 24 anesthetized pigs in vivo following 90 min hypoperfusion and 120 min reperfusion of the LAD coronary artery, which supplies parts of the LV septum (LVS) and anterior free wall (LVAFW). The total LAD perfusion territory averaged 49.8 +/- 14.2 (SD) g (49.2 +/- 8.4% of LV); 61.4 +/- 8.1% of the AAR was LVAFW. IS within the LVS was 25.3 +/- 15.1%, while IS within the LVAFW was 16.6 +/-10.1% (p<0.05). While ischemic blood flow (radiolabeled microspheres) did not differ between LVS (0.05 +/- 0.02 ml/min/g) and LVAFW (0.05 +/- 0.03 ml/min/g), perivascular connective tissue (56 +/- 9 vs. 38+/-7 microm(2), p < 0.05) and the capillary-to-myocyte distance (1.65 +/- 0.23 vs. 1.18 +/- 0.23 mm, p < 0.05) were larger in LVS than in LVAFW. Interestingly, IS in LVS (9.3 +/- 9.6%, n = 24) and LVAFW (9.2 +/- 9.1%) were reduced to the same absolute extent by ischemic preconditioning with one cycle of 10 min ischemia and 15 min reperfusion, suggesting that a similar regional difference exists also in the protection afforded by ischemic preconditioning. The mechanism(s) for that remain(s) to be established. In pigs, regional differences in infarct development and protection from it exist in the LAD perfusion territory, which are independent of ischemic blood flow but apparently related to pre-existing structural differences.

  16. Comparison of magnetic resonance imaging findings in non-ST-segment elevation versus ST-segment elevation myocardial infarction patients undergoing early invasive intervention.

    PubMed

    Xu, Jianqiang; Song, Young Bin; Hahn, Joo-Yong; Chang, Sung-A; Lee, Sang-Chol; Choe, Yeon Hyeon; Choi, Seung-Hyuk; Choi, Jin-Ho; Lee, Sang Hoon; Oh, Jae K; Gwon, Hyeon-Cheol

    2012-08-01

    To define causes and pathological mechanisms underlying differences in clinical outcomes, we compared the findings of contrast-enhanced magnetic resonance imaging (CE-MRI) between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). In 168 patients undergoing early invasive intervention for STEMI (n = 113) and NSTEMI (n = 55), CE-MRI was performed a median of 6 days after the index event. Infarct size was measured on delayed-enhancement imaging, and area at risk (AAR) was quantified on T2-weighted images. The median infarct size was significantly smaller in the NSTEMI group than in the STEMI group (10.7% [5.6-18.1] vs. 19.2% [10.3-30.7], P < 0.001). Although there was a trend toward a greater myocardial salvage index ([AAR - infarct size] × 100/AAR) in the NSTEMI group compared to the STEMI group (48.2 [30.4-66.8] vs. 40.5 [24.8-53.5], P = 0.056), myocardial salvage index was similar between the groups in patients with anterior infarction (39.6 [20.0-54.9] vs. 35.5 [23.2-53.4], P = 0.96). The NSTEMI group also had a significantly lower extent of microvascular obstruction and a smaller number of segments with >75% of infarct transmurality relative to the STEMI group (0% [0-0.6] vs. 0.9% [0-2.3], P < 0.001 and 3.0 ± 2.3 vs. 4.6 ± 2.9, P = 0.001, respectively). Myocardial hemorrhage was detected less frequently in the NSTEMI group than the STEMI group (22.6% vs. 43.8%, P = 0.029). In the multivariate analysis, baseline Thrombolysis In Myocardial Infarction flow grade 3 and hemorrhagic infarction were closely associated with ST-segment elevation (OR 0.32, 95% CI 0.13-0.81, P = 0.017; OR 5.66, 95% CI 1.77-18.12, P = 0.003, respectively). In conclusion, in vivo pathophysiological differences revealed by CE-MRI assessment include more favorable infarct size, AAR, myocardial salvage and reperfusion injury in patients with NSTEMI compared to those with STEMI undergoing early invasive intervention.

  17. Crystal structures of the A2A adenosine receptor and their use in medicinal chemistry.

    PubMed

    Jacobson, Kenneth A

    2013-12-20

    New insights into drug design are derived from the X-ray crystallographic structures of G protein-coupled receptors (GPCRs), and the adenosine receptors (ARs) are at the forefront of this effort. The 3D knowledge of receptor binding and activation promises to enable drug discovery for GPCRs in general, and specifically for the ARs. The predictability of modeling based on the X-ray structures of the A2AAR has been well demonstrated in the identification, design and modification of both known and novel AR agonists and antagonists. It is expected that structure-based design of drugs acting through ARs will provide new avenues to clinically useful agents.

  18. Variability of Major Organic Components in Aircraft Fuels. Volume 2. Illustrations

    DTIC Science & Technology

    1984-06-27

    90 90 6• TABUE 14. FIRST PAGE OF OUTPUT FROM POST ANALYSIS PROGRM KOVPGl CORRELATION OF RETENTION TIMES (MIN) WITH KOVATS INDEX FOR SAMPLES...PARAM-P ILE 4. REPORTS RVIC ORPTS I T7, 1 2 /E P." fr 98 TABUS 17’. RIM FOR A DATA BASE CONTAINING 14 BKPxzz FILES CRZATED BY DFAms DATA ANALYSIS OF...1.5.DiaethylaaPbtbslene or l"aar + 1 25492 265 -n8.3 140?-1 41. e2U2 ( toteme . bicyclec or cyclic ellen.) 255.48 1411.11 *281 41.42,69 j W. (le ma

  19. The "Legal Vacuum" of Detainee Rights

    DTIC Science & Technology

    1997-04-01

    Parkerson]. 5See DEP’T OF ARMY, FIELD MANUAL 100-5, OPERATIONS 13-0 (June 1993) [hereinafter FM 100-5]; DEP’T OF ARMY, FIELD MANUAL 100-23, PEACE OPERATIONS...34 approaches. HAmI AAR, supra note 6, at 60 n. 188; DEP’T OF ARMY, FIELD MANUAL 34-52, INTELLIGENCE INTERROGATIONS, App. (1989). The interrogation...up arms and commit hostile acts,... may be tried and sentenced to execution or imprisonment." DEP’T OF ARMY, FIELD MANUAL 27-10, THE LAW OF LAND

  20. The Lucky Seventh in the Bulge: A Case Study for the Airland Battle

    DTIC Science & Technology

    1985-05-15

    Why then did VIII Corps not advise Jones of the truth? 9 7th AD Combat Interview3, Major Fred Sweat, S-3 CCR, 28 December 1944. * l0 lt is difficult...1SG Hoyle H. Ladd. Ladd brought out thirty-five soldiers of the original six 81 % officers and 136 enlisted men. See, AARs of 23rd AIB, 38th AIB, 87th...Vith) was probably in the worst shaoe. First Sergeant Hoyle Ladd, senior surviving man in the troop brought out only thirty-- .five soldiers when the

  1. Hi Observations of the Supermassive Binary Black Hole System in 0402+379

    DTIC Science & Technology

    2009-05-20

    2003a detail- ing observational evidence for supermassive black hole bina- ries). Some source properties like X -shaped radio galaxies and double–double...discovered by the Chandra X - ray observatory, was found to have a pair of active supermassive black holes at its center (Komossa et al. 2003b), separated by a...are found toward the southern jet of the source , one redshifted by 370 ± 10 km s−1 and the other blueshifted by 700 ± 10 km s−1 with respect to the

  2. An Irreversible Thermodynamics Model for Graphite Sublimation in Intense Radiation Environments.

    DTIC Science & Technology

    1980-09-15

    27 8. Relationship of T w to 4rad at Several Pressures, Irreversible Thermodynamics Model ... ............. .... 29 TABLES 1. Q ...rela- tionships [see Eqs. (lla,b)]. -11- -~~RGO -11 --- ___RGO I RESERVOIRR I1 Fig 1 Rprsetaio o Pas C ang Trb[em as a T Dicniu Syte REGONII REIO& where...AT AAR (17a) q qqI qv T ~AT Jv A - (17b) 17 1Schrage, R. W., A Theoretical Study of Interphase Mass Transfer, Columbia University Press, New York

  3. A luminol chemiluminescence method for sensing histidine and lysine using enzyme reactions.

    PubMed

    Kugimiya, Akimitsu; Fukada, Rie; Funamoto, Daiki

    2013-12-01

    The analysis of free amino acids in urine and plasma is useful for estimating disease status in clinical diagnoses. Changes in the concentration of free amino acids in foods are also useful markers of freshness, nutrition, and taste. In this study, the specific interaction between aminoacyl-tRNA synthetase (aaRS) and its corresponding amino acid was used to measure amino acid concentrations. Pyrophosphate released by the amino acid-aaRS binding reaction was detected by luminol chemiluminescence; the method provided selective quantitation of 1.0-30 μM histidine and 1.0-60 μM lysine. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Operation Strong Wind (Fort Lee’s Response to a Local Tornado Disaster, 6 August 1993)

    DTIC Science & Technology

    1993-11-01

    A. Maps of area and mall B. AAR of HQ 49th QM Group(Petroleum) by MAJ Victoria Spinelli C. 49th Gp, EOC Log D. Fort Lee’s Duty Officer’s Log E. Kenner...for cellular phone services. Reaction and Organization On Fort Lee, MAJ Victoria Spinelli , acting commander of the 49th Quartermaster Group (Petroleum...the tornado had touched down. After the phone conversation with COL Ferguson, MAJ Spinelli drove to his office in Mifflin Hall about 1355, and met with

  5. Manual for Calculating the Seepage Strength of Earthfill Dams,

    DTIC Science & Technology

    1976-07-01

    soIOyfoIa COOTneTcrBeHHO "oa ro- P1130HTOM Bo~bi aBRepxifem Hf HHWHeMf 6be~pax; L - ropH3oflTa~lbHoe PaCCTOgHte MeWAY ype33IM Babi Bepx~ero H Hmwiccro...rPSAmeiRTa iSmIoca (..~) AAR KazAoro SOASHEOrO paauepa Cy4ftO8HOHHMX ’IaCTRIu AHImeT- porn d <~ del’ 8 aMae se.igxqKRy npotteitTa DHHtoca STIX qa

  6. Doing Business with the Naval Air Systems Command

    DTIC Science & Technology

    2014-08-13

    PRECISION APPROACH & LANDING SYSTEM (JPALS) • E -2D ADVANCED HAWKEYE (AHE) • EA-6B ICAP-III • EA-18G AIRBORNE ELECTRONIC ATTACK • F/A-18E/F...ARRESTING GEAR • ALR-67(V)3 ADVANCED SPECIAL RECEIVER (ASR) • E -6B MERCURY BLOCK 1 MOD • F/A-18 IRST ACAT III • EA-6B ALQ-99 LOW BAND...CONTROL AND COMMUNICATIONS E -6B MERCURY PMA272 ADVANCED TACTICAL AIRCRAFT PROTECTION SYSTEMS ALR67(V)2 ADV SPECIAL RECEIVER AAR-47

  7. A Comparative of Nuclear Technology and Direct Energy Conversion Methods for Space Power Systems

    DTIC Science & Technology

    1997-06-01

    An SNPS is designed to be safe during all modes of operation. These modes include, transportation, storage, pre-launch, launch, and normal operation...The term safe is used here to mean that in the modes prior to normal operation, the SNPS reactor will remain in a subcritical state. In the event of a...are formed inside the generator in two ways. One of these occurs in each of the three modes of operation of a cesium vapor converter. In the low

  8. EC03-0293-06

    NASA Image and Video Library

    2003-09-18

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  9. EC03-0293-03

    NASA Image and Video Library

    2003-09-18

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  10. EC02-0294-2

    NASA Image and Video Library

    2002-12-19

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft (No. 843) flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  11. EC03-0293-15

    NASA Image and Video Library

    2003-09-18

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  12. EC02-0294-4

    NASA Image and Video Library

    2002-12-19

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft (No. 843) flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  13. EC02-0294-1

    NASA Image and Video Library

    2002-12-19

    NASA Dryden's Automated Aerial Refueling (AAR) project evaluated the capability of an F/A-18A aircraft as an in-flight refueling tanker with the objective of developing analytical models for an automated aerial refueling system for unmanned air vehicles. The F/A-18 "tanker" aircraft (No. 847) underwent flight test envelope expansion with an aerodynamic pod containing air-refueling equipment carried beneath the fuselage. The second aircraft (No. 843) flew as the receiver aircraft during the study to assess the free-stream hose and drogue dynamics on the F/A-18A.

  14. Forward Air Controller: Task Analysis and Development of Team Training Measures for Close Air Support

    DTIC Science & Technology

    2007-12-01

    d’AAR, ainsi que de déterminer les mesures adéquates pour évaluer le rendement de l’équipe. À cette fin, on a effectué une analyse hiérarchique des...certain nombre de recommandations visant à améliorer l’instrument avant son application aux exercices futurs de simulation répartie. Les...assessing the team’s performance as a whole. To that end, the contractor constructed hierarchical task analyses for the principal members of this team, the

  15. Magneto-Optic Materials for Biasing Ring Laser Gyros. Report Number 3. (Computer Model for Evaluating Scattering from Multi-Layer Dielectric Thin Film Structures Containing a Magnetic Layer.

    DTIC Science & Technology

    1980-09-30

    program used here. That error, in the transverse Kerr Fresnel coefficients 7, and t.., was pointed out to us by R.E. McClure and the correct derivation can...optical coefficient Q. Note that nu and Q are complex quantities while the other parame- ters are real. Let Ep*+A be the total electric vector of a...are 2 x 2 matrices of Fresnel coefficients . The Fresnel matrices are defined by kI ~k 1k -k where the Fresnel reflection coefficients at the k

  16. Exercise Black Skies 2008: Enhancing Live Training Through Virtual Preparation -- Part Two: An Evaluation of Tools and Techniques

    DTIC Science & Technology

    2009-06-01

    software testing, an improvised ‘air warfare game ’ was conducted in place of the AAR session on Day 2. This game required each ABM to pair with a SIMOP...and control two fighter pairs. The aim of the game was to be the first formation to fly through the centre of an arbitrary hexagonal airspace and...the latest simulation tools. The software proved to be stable throughout the game and the remaining vignettes. 2.1.5 Procedure DSTO human

  17. Installation Restoration Program. Phase 2. Confirmation McClellan AFB, California. Volume 1

    DTIC Science & Technology

    1983-06-01

    orductan one n r o eesaiyroeett of th_2a0wae-bern zoe Scais n M;4 0 2GEERL RGINA GRUNWAERCOTORS0 THUARMNOVLE SPIN 408 NOTE: UEL. U ( Tlffhe s i co tr raef ...Agricultural Sciences, November 1974 (Coauthors A.A.R. Hafez , J. Azevedo, and P. R. Stout). I3 I . . I. .. - . . . .. .. .. . .. . . . II "- - III II IllI...34 Journal of Environmental Quality, 1977 (Coauthors R. Siegel, A. Hafez , and P.R. Stout). California Soils: An Assessment (State of California

  18. 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.

  19. 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

  20. 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