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Sample records for r2 r8 r5

  1. Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol hydrobromide

    Directory of Open Access Journals (Sweden)

    Amber L. Thompson

    2009-11-01

    Full Text Available X-ray crystallographic analysis of the title hydrobromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxylated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae leaves. In the crystal structure, molecules are linked by intermolecular O—H...Br and N—H...Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intramolecular O—H...O interactions occur.

  2. Synthesis of carbasugars from aldonolactones, part III - A study on the allylic substitution of (1R,5R,8R)- and (1R,5R,8S)-8-hydroxy-2-oxabicyclo[3.3.0]oct-6-en-3-one derivatives - Preparation of (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H-adenine

    DEFF Research Database (Denmark)

    Johansen, Steen Karsk; Lundt, Inge

    2001-01-01

    The palladium-catalyzed substitution of acylated (1R,5R,8R)- and (1R,SR,8S)-8-hydroxy-2-oxabicyclo[3.3.0] ones has been studied using a number of C- and N-nucleophiles, In all cases, the exo derivatives (8R) were found to be more reactive than the corresponding endo derivatives (8S). The reaction...... with these nucleophiles. Additionally, Mitsunobu substitution of (1R,5R,8R)-8-hydroxy-2-oxabicyclo[3.3.0]oct-B-en-3-one (3) with 6-chloropurine, followed by reduction of the lactone moiety and treatment with Liquid ammonia, gave the carbocyclic nucleoside (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H...

  3. Crystal structure of (1S,3R,8R,9R-2,2-dichloro-3,7,7-trimethyl-10-methylenetricyclo[6.4.0.01,3]dodecan-9-ol

    Directory of Open Access Journals (Sweden)

    Ahmed Benzalim

    2016-08-01

    Full Text Available The title compound, C16H24Cl2O, was synthesized by treating (1S,3R,8S,9R,10S-2,2-dichloro-3,7,7,10-tetramethyl-9,10-epoxytricyclo[6.4.0.01,3]dodecane with a concentrated solution of hydrobromic acid. It is built up from three fused rings: a cycloheptane ring, a cyclohexyl ring bearing alkene and hydroxy substituents, and a cyclopropane ring bearing two chlorine atoms. The asymmetric unit contains two molecules linked by an O—H...O hydrogen bond. In the crystal, further O—H...O hydrogen bonds build up an R44(8 cyclic tetramer. One of the molecules presents disorder that affects the seven-membered ring. In both molecules, the six-membered rings display a chair conformation, whereas the seven-membered rings display conformations intermediate between boat and twist-boat for the non-disordered molecule and either a chair or boat and twist-boat for the disordered molecule owing to the disorder. The absolute configuration for both molecules is 1S,3R,8R,9R and was deduced from the chemical pathway and further confirmed by the X-ray structural analysis.

  4. (1R,2R,3R,4R,5S-2,3-Bis[(2S′-2-acetoxy-2-phenylacetoxy]-4-azido-1-[(2,4-dinitrophenylhydrazonomethyl]bicyclo[3.1.0]hexane

    Directory of Open Access Journals (Sweden)

    Robert McDonald

    2008-02-01

    Full Text Available In the title compound, C38H29N7O12, the five-membered ring adopts an envelope conformation in which the `flap' is cis to the cyclopropane group. This conformation is similar to those of other bicyclo[3.1.0]hexane analogues for which crystal structures have been reported. The absolute configuration of the stereogenic centers on the cyclopentane ring, as determined by comparison with the known configurations of the stereogenic centers in the (2S-2-acetoxy-2-phenylacetoxy groups, is 1(R, 2(R, 3(R, 4(R and 5(S. An intramolecular N—H...O hydrogen bond is present.

  5. mGluR5

    DEFF Research Database (Denmark)

    Mølck, Christina; Harpsøe, Kasper; Gloriam, David E

    2014-01-01

    Since its discovery in 1992, mGluR5 has attracted significant attention and been linked to several neurological and psychiatric diseases. Ligand development was initially focused on the orthosteric binding pocket, but lack of subtype selective ligands changed the focus to the transmembrane...... allosteric binding pocket. This strategy has resulted in several drug candidates in clinical testing. In the present article we explore the orthosteric and allosteric binding pockets in terms of structure and ligand recognition across the mGluR subtypes and groups, and discuss the clinical potential...... of ligands targeting these pockets. We have performed binding mode analyses of non- and group-selective orthosteric ligands based on molecular docking in mGluR crystal structures and models. For the analysis of the allosteric binding pocket we have combined data from all mGluR5-mutagenesis studies...

  6. R2 Cognitive Computing

    Data.gov (United States)

    National Aeronautics and Space Administration — Robonaut 2, a crew assistant robotic prototype, will be integrated with IBM’s Watson. R2 will embody the artificial intelligence to enable new levels of robotic...

  7. Diaqua[(1R,2S,4R,8R,9S,11R-2,9-dimethyl-1,4,8,11-tetraazacyclotetradecane]nickel(II dichloride dihydrate

    Directory of Open Access Journals (Sweden)

    James Alan Townsend

    2012-08-01

    Full Text Available The crystal structure of the title complex, [Ni(C12H28N4(H2O2]Cl2·2H2O, displays O—H...Cl and O—H...O hydrogen bonding. The tetraazacyclotetradecane ligand interacts with the NiII atom in the cis V configuration and the final two ligand binding sites are occupied by water.

  8. 26 CFR 1.414(r)-8 - Separate application of section 410(b).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Separate application of section 410(b). 1.414(r)-8 Section 1.414(r)-8 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-8...

  9. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Mao

    Full Text Available Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5, but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95 and synapse-associated protein-97 (SAP97. Accordingly, delivery of Tat-GluR2(3Y, a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  10. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Science.gov (United States)

    Mao, Sheng-Chun; Chang, Chih-Hua; Wu, Chia-Chen; Orejarena, M Juliana; Orejanera, Maria Juliana; Manzoni, Olivier J; Gean, Po-Wu

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5), but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95) and synapse-associated protein-97 (SAP97). Accordingly, delivery of Tat-GluR2(3Y), a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  11. Instrumentation of air conditioning and ventilation system - R-5 project

    International Nuclear Information System (INIS)

    Kulkarni, P.B.; Naik, C.D.; Narasingha Rao, S.N.

    1977-01-01

    A detailed account of instrumentation proposed for airconditioning and ventilation system in the R-5, 100 MW thermal research reactor, under construction is presented. Controls and instrumentation provided in this system are electronic, pneumatic and hydraulic in nature depending on the application. They cater to the accurate operation of the system and maintain the conditions strictly within desired tolerances. (S.K.K.)

  12. Mastering Microsoft Windows Server 2008 R2

    CERN Document Server

    Minasi, Mark; Finn, Aidan

    2010-01-01

    The one book you absolutely need to get up and running with Windows Server 2008 R2. One of the world's leading Windows authorities and top-selling author Mark Minasi explores every nook and cranny of the latest version of Microsoft's flagship network operating system, Windows Server 2008 R2, giving you the most in-depth coverage in any book on the market.: Focuses on Windows Windows Server 2008 R2, the newest version of Microsoft's Windows' server line of operating system, and the ideal server for new Windows 7 clients; Author Mark Minasi is one of the world's leading Windows authorities and h

  13. The electric powertrain of the R8 e-tron. A sportive experience of electromobility; Der elektrische Antrieb im R8 e-tron. Elektromobilitaet sportlich erfahren

    Energy Technology Data Exchange (ETDEWEB)

    Eiser, A.; Enzinger, M.; Werner, M.; Wierl, U.; Kruse, A.; Westermaier, C.; Felkel, T. [Audi AG, Ingolstadt (Germany)

    2012-11-01

    This article presents the electric powertrain for the new Audi R8 e-tron. The special feature of this sports car is its high-performance electric powertrain, providing a fully usable stand-alone vehicle propulsion system. At the heart of the system are two permanent-magnet synchronous motors which drive the left and right rear wheels separately. The motors were developed specially for use in the R8 e-tron to feature maximum power density, sporty performance and optimum power utilisation. Based on the latest Audi networking technologies, Flex-Ray communication has been extended to the drive components. The application and balancing of vehicle characteristics, functional reliability and drive-ability was tested in parallel on the real vehicle from the very beginning, which meant that the development was completed in an outstandingly short time. (orig.)

  14. The Monoceros R2 Molecular Cloud

    Science.gov (United States)

    Carpenter, J. M.; Hodapp, K. W.

    2008-12-01

    The Monoceros R2 region was first recognized as a chain of reflection nebulae illuminated by A- and B-type stars. These nebulae are associated with a giant molecular cloud that is one of the closest massive star forming regions to the Sun. This chapter reviews the properties of the Mon R2 region, including the namesake reflection nebulae, the large scale molecula= r cloud, global star formation activity, and properties of prominent star forming regions in the cloud.

  15. Statistical analysis of LHC main interconnection splices room temperature resistance (R-8) results

    CERN Document Server

    Heck, S

    2012-01-01

    During the 2008/2009 shutdown the so-called R-8/R-16 room temperature resistance test has been introduced for the quality control of the LHC main interconnection splices. It has been found that at present two groups of LHC main interconnection splices can be distinguished, so-called “old” splices produced during LHC installation, and so-called “new” splices produced during 2009. 2009 production splices are considered as the state-of-the art, which is reflected by a much smaller R-8 distribution as compared to that of splices produced during first LHC installation.

  16. Windows Server 2012 R2 administrator cookbook

    CERN Document Server

    Krause, Jordan

    2015-01-01

    This book is intended for system administrators and IT professionals with experience in Windows Server 2008 or Windows Server 2012 environments who are looking to acquire the skills and knowledge necessary to manage and maintain the core infrastructure required for a Windows Server 2012 and Windows Server 2012 R2 environment.

  17. Studsvik's R2 reactor - Review of activities

    Energy Technology Data Exchange (ETDEWEB)

    Grounes, Mikael; Tomani, Hans; Graeslund, Christian; Rundquist, Hans; Skoeld, Kurt [Studsvik Nuclear AB, Nykoeping (Sweden)

    1993-07-01

    A general description of the R2 reactor, its associated facilities and its history is given. The facilities and range of work are described for the following types of activities: fuel testing, materials testing, neutron transmutation doping of silicon, activation analysis, radioisotope production and basic research including thermal neutron scattering, nuclear chemistry and neutron capture radiography. (author)

  18. Data of evolutionary structure change: 1JJ4B-1R8HE [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available in>B 1JJ4B RLRKH-SDHYR >HGGGG-GGG ...n> RLNDKHRHLFD ture>HHHHH GGG .../pdbID> B 1JJ4B WHWTE-----KTGIL ...> ----- EEE> ATOM 1523 CA TRP B 320 11.497 15.32...1R8HE WHWASPKAPHKHAIV > EEE>

  19. Mastering Windows Server 2012 R2

    CERN Document Server

    Minasi, Mark; Booth, Christian; Butler, Robert; McCabe, John; Panek, Robert; Rice, Michael; Roth, Stefan

    2013-01-01

    Check out the new Hyper-V, find new and easier ways to remotely connect back into the office, or learn all about Storage Spaces-these are just a few of the features in Windows Server 2012 R2 that are explained in this updated edition from Windows authority Mark Minasi and a team of Windows Server experts led by Kevin Greene. This book gets you up to speed on all of the new features and functions of Windows Server, and includes real-world scenarios to put them in perspective. If you're a system administrator upgrading to, migrating to, or managing Windows Server 2012 R2, find what you need to

  20. R2 inflation in anisotropic universes

    International Nuclear Information System (INIS)

    Berkin, A.L.

    1990-01-01

    The evolution of Bianchi type-I and type-IX universes for a theory of gravity with an εR 2 term added to the usual Lagrangian is considered. As in the spatially flat Robertson-Walker case considered previously by others, inflation is found to occur. For any amount of initial anisotropy, the anisotropy decays quickly relative to the length of the inflationary epoch, and the amount of expansion is enhanced by the anisotropy. The exceptions are Bianchi type-IX universes near or at isotropy. In these cases a wide range of initial parameters causes the universe to recollapse, thus reducing the phase space in which inflation can occur. The diagonal metric is shown to be the most general form in the R 2 theory for both Bianchi type-I universes with a perfect fluid and vacuum Bianchi type-IX models

  1. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  2. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  3. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    International Nuclear Information System (INIS)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results

  4. (E-2-((4R,5R-5-((Benzyloxymethyl-2,2-dimethyl-1,3-dioxolan-4-ylbut-2-ene-1,4-diol

    Directory of Open Access Journals (Sweden)

    Carlos R. Carreras

    2010-04-01

    Full Text Available The synthesis of (E-2-((4R,5R-5-((benzyloxymethyl-2,2-dimethyl-1,3-dioxolan-4-ylbut-2-ene-1,4-diol by a one-step reduction of the appropriate 2-substituted butenolide is reported. Product characterization was carried out by IR, 1H NMR, 13C NMR, MS, elemental analysis and optical rotation.

  5. R2 dark energy in the laboratory

    Science.gov (United States)

    Brax, Philippe; Valageas, Patrick; Vanhove, Pierre

    2018-05-01

    We analyze the role, on large cosmological scales and laboratory experiments, of the leading curvature squared contributions to the low-energy effective action of gravity. We argue for a natural relationship c0λ2≃1 at low energy between the R2 coefficients c0 of the Ricci scalar squared term in this expansion and the dark energy scale Λ =(λ MPl)4 in four-dimensional Planck mass units. We show how the compatibility between the acceleration of the expansion rate of the Universe, local tests of gravity and the quantum stability of the model all converge to select such a relationship up to a coefficient which should be determined experimentally. When embedding this low-energy theory of gravity into candidates for its ultraviolet completion, we find that the proposed relationship is guaranteed in string-inspired supergravity models with modulus stabilization and supersymmetry breaking leading to de Sitter compactifications. In this case, the scalar degree of freedom of R2 gravity is associated to a volume modulus. Once written in terms of a scalar-tensor theory, the effective theory corresponds to a massive scalar field coupled with the universal strength β =1 /√{6 } to the matter stress-energy tensor. When the relationship c0λ2≃1 is realized, we find that on astrophysical scales and in cosmology the scalar field is ultralocal and therefore no effect arises on such large scales. On the other hand, the scalar field mass is tightly constrained by the nonobservation of fifth forces in torsion pendulum experiments such as Eöt-Wash. It turns out that the observation of the dark energy scale in cosmology implies that the scalar field could be detectable by fifth-force experiments in the near future.

  6. Potentiating mGluR5 Function with a Positive Allosteric Modulator Enhances Adaptive Learning

    Science.gov (United States)

    Xu, Jian; Zhu, Yongling; Kraniotis, Stephen; He, Qionger; Marshall, John J.; Nomura, Toshihiro; Stauffer, Shaun R.; Lindsley, Craig W.; Conn, P. Jeffrey; Contractor, Anis

    2013-01-01

    Metabotropic glutamate receptor 5 (mGluR5) plays important roles in modulating neural activity and plasticity and has been associated with several neuropathological disorders. Previous work has shown that genetic ablation or pharmacological inhibition of mGluR5 disrupts fear extinction and spatial reversal learning, suggesting that mGluR5

  7. Genetics Home Reference: PPP2R5D-related intellectual disability

    Science.gov (United States)

    ... Health Conditions PPP2R5D-related intellectual disability PPP2R5D-related intellectual disability Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description PPP2R5D -related intellectual disability is a neurological disorder characterized by moderate to ...

  8. Conserved microRNA miR-8 in fat body regulates innate immune homeostasis in Drosophila.

    Science.gov (United States)

    Choi, In Kyou; Hyun, Seogang

    2012-05-01

    Antimicrobial peptides (AMPs) constitute a major arm of the innate immune system across diverse organisms. In Drosophila, septic injury by microbial pathogens rapidly induces the production of the AMPs in fat body via well elucidated pathways such as Toll and IMD. However, several epithelial tissues were reported to locally express AMPs without septic injury via poorly characterized ways. Here, we report that microRNA miR-8 regulates the levels of AMPs basally expressed in Drosophila. The levels of AMPs such as Drosomycin and Diptericin are significantly increased in miR-8 null animals in non-pathogen stimulated conditions. Analysis of various larval tissues revealed that the increase of Drosomycin is fat body specific. Supporting this observation, re-introduction of miR-8 only in the fat body restored the altered AMP expression in miR-8 null flies. Although loss of miR-8 impedes PI3K in the fat body, inhibition of PI3K does not phenocopy the AMP expression of miR-8 null flies, indicating that miR-8 regulates AMP independently of PI3K. Together, our findings suggest a role of miR-8 in systemic immune homeostasis in generally non-pathogenic conditions in flies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Center type performance of differentiable vector fields in R2

    International Nuclear Information System (INIS)

    Rabanal, Roland

    2007-08-01

    Let X : R 2 / D → R 2 be a differentiable vector field, where D is compact. If the eigenvalues of the jacobian matrix DX z are (nonzero) purely imaginary, for all z element of R 2 / D . Then, X + v has a center type performance at infinity, for some v element of R 2 . More precisely, X + v has a periodic trajectory Γ subset of R2/ D which is surrounding D such that in the unbounded component of (R 2 / D )/ Γ all the trajectories of X + v are nontrivial cycles. In the case of global vector fields Y : R 2R 2 with Y (0) = 0, we prove that such eigenvalue condition implies the topological equivalency of Y with the linear vector field (x, y) → (-y, x). (author)

  10. Multicenter R2* mapping in the healthy brain

    DEFF Research Database (Denmark)

    Ropele, Stefan; Wattjes, Mike P; Langkammer, Christian

    2014-01-01

    structures. METHODS: R2* mapping was performed in 81 healthy subjects in seven centers using different 3 T systems. R2* was calculated from a dual-echo gradient echo sequence and was assessed in several deep gray matter structures. The inter-scanner and inter-subject variability of R2* was calculated...

  11. Safe dismantling of the SVAFO research reactors R2 and R2-0 in Sweden

    International Nuclear Information System (INIS)

    ARNOLD, Hans-Uwe; BROY, Yvonne; Dirk Schneider

    2017-01-01

    The R2 and R2-0 reactors were part of the Swedish government's research program on nuclear power from the early 1960's. Both reactors were shut down in 2005 following a decision by former operator Studsvik Nuclear AB. The decommissioning of the R2 and R2-0 reactors is divided into three phases. The first phase - awarded to AREVA - involved dismantling of the reactors and associated systems in the reactor pool, treatment of the disassembled components as well as draining, cleaning and emptying the pool. In the second phase, the pool structure itself will be dismantled, while removal of remaining reactor systems, treatment and disposal of materials and clean-up will be carried out in the third stage. The entire work is planned to be completed before the end of this decade. The paper describes the several steps of phase 1 - starting with the team building, followed by the dismantling operations and covers challenges encountered and lessons learned as well. The reactors consist of 5.400 kg aluminum, 6.000 kg stainless steel restraint structures as well as, connection elements of the mostly flanged components (1.000 kg). The most demanding - from a radiological point of view - was the R2-0 reactor that was limited to ∼ 1 m"3 construction volumes but with an extremely heterogeneous activation profile. Based on the calculated radiological entrance data and later sampling, nuclide vectors for both reactors depending on the real placement of the single component and on the material (aluminum and stainless steel) were created. Finally, for the highest activated component from R2 reactor, 85 Sv/h were measured. The dismantling principles - adopted on a safety point of view - were the following: The always protected base area of the ponds served as a flexible buffer area for waste components and packaging. Specific protections were also installed on the walls to protect them from mechanical stress which may occur during dismantling work. A specific work platform was

  12. Three-body fragmentation of methane dications produced by slow A r8 + -ion impact

    Science.gov (United States)

    Zhang, Y.; Jiang, T.; Wei, L.; Luo, D.; Wang, X.; Yu, W.; Hutton, R.; Zou, Y.; Wei, B.

    2018-02-01

    The three-body fragmentation dynamics of CH4 2 + dications induced by single-electron capture of slow (3-keV/u) A r8 + ions is investigated. The experiment is performed on a newly built, highly charged ion collision platform which consists of an electron cyclotron resonance ion source and a cold target recoil ion momentum spectroscopy (COLTRIMS) setup. Using the COLTRIMS methodology, the complete kinematical information is determined for two three-body breakup channels, CH4 2 +→H++CH2 ++H and CH4 2 +→H2 ++C H++H . Then analyzing the complete kinematics with the Dalitz plot, very different fragmentation mechanisms (e.g., sequential and/or concerted pathway) are clearly identified for the two channels. To confirm the existence of some possible fragmentation pathways, we also simulate corresponding Dalitz plots employing a simple classical mechanical model. For the H++CH2 ++H channel, the dependence of the fragmentation pathway on its kinetic energy release is studied, which reflects the different nature of the corresponding states of CH4 2 + dications. Furthermore, the kinetic energy ratio of two ionic fragments is analyzed to infer the three-body fragmentation mechanism of CH4 2 + dications.

  13. Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD.

    Science.gov (United States)

    Zantomio, Daniela; Chana, Gursharan; Laskaris, Liliana; Testa, Renee; Everall, Ian; Pantelis, Christos; Skafidas, Efstratios

    2015-05-01

    The pathogenesis of Autism Spectrum Disorder (ASD), a serious neurodevelopmental disorder, is poorly understood. We review evidence for alterations in glutamatergic signalling in the aetiology of ASD, with a focus on the metabotropic glutamate receptor-5 (mGluR5). mGluR5 signalling is important for synapse formation, neuroplasticity and long term potentiation as well as neuroprotection and has been shown to have a regulatory role in neuroinflammation. Evidence for neuroinflammation in ASD is supported by increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid (CSF) and increased number and activation of microglia in postmortem dorsolateral prefrontal cortex (DLPFC). mGlur5 signalling has also been shown to downregulate microglial activation. Therefore, we focus on mGluR5 as a potential unifying explanation for synapse alteration and neuroinflammation seen in ASD. Data from mGluR5 knockout mouse models, and syndromic and non syndromic forms of ASD are discussed in relation to how alterations in mGluR5 are associated with ASD symptoms. This review supports altered mGluR5 functioning as a convergent point in ASD pathogenesis and indicates more research is warranted into mGluR5 as a potential therapeutic target. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.

    Directory of Open Access Journals (Sweden)

    Chris P Jew

    Full Text Available The group I metabotropic glutamate receptor 5 (mGluR5 has been implicated in the pathology of various neurological disorders including schizophrenia, ADHD, and autism. mGluR5-dependent synaptic plasticity has been described at a variety of neural connections and its signaling has been implicated in several behaviors. These behaviors include locomotor reactivity to novel environment, sensorimotor gating, anxiety, and cognition. mGluR5 is expressed in glutamatergic neurons, inhibitory neurons, and glia in various brain regions. In this study, we show that deleting mGluR5 expression only in principal cortical neurons leads to defective cannabinoid receptor 1 (CB1R dependent synaptic plasticity in the prefrontal cortex. These cortical glutamatergic mGluR5 knockout mice exhibit increased novelty-induced locomotion, and their locomotion can be further enhanced by treatment with the psychostimulant methylphenidate. Despite a modest reduction in repetitive behaviors, cortical glutamatergic mGluR5 knockout mice are normal in sensorimotor gating, anxiety, motor balance/learning and fear conditioning behaviors. These results show that mGluR5 signaling in cortical glutamatergic neurons is required for precisely modulating locomotor reactivity to a novel environment but not for sensorimotor gating, anxiety, motor coordination, several forms of learning or social interactions.

  15. Crystal structure of (1R,2S,4R,7R,8S,9R-3,3-dichloro-8,9-epoxy-4,8,12,12-tetramethyltricyclo[5.5.0.02,4]dodecane

    Directory of Open Access Journals (Sweden)

    Ahmed Benzalim

    2015-08-01

    Full Text Available The title compound, C16H24Cl2O, is built up from two fused six- and seven-membered rings which bear a dichlorocyclopropane group and an epoxy group, respectively. In the molecule, the six-membered ring adopts an envelope configuration with the C atom linking the epoxy ring at the flap, while the seven-membered ring adopts a boat–sofa conformation.

  16. Expression and distribution of PPP2R5C gene in leukemia

    Directory of Open Access Journals (Sweden)

    Li Bo

    2011-05-01

    Full Text Available Abstract Background Recently, we clarified at the molecular level novel chromosomal translocation t(14;14(q11;q32 in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the PPP2R5C gene. PPP2R5C is one of the regulatory B subunits of protein phosphatase 2A (PP2A. It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the PPP2R5C gene in leukemia, we analyzed the expression level of PPP2R5C in peripheral blood mononuclear cells from 77 patients with de novo leukemia, 26 patients with leukemia in complete remission (CR, and 20 healthy individuals by real-time PCR and identified the different variants of PPP2R5C by RT-PCR. Findings Significantly higher expression of PPP2R5C was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of PPP2R5C was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of PPP2R5C in the CML-CR group decreased significantly compared with that in the de novo CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of PPP2R5C could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of PPP2R5C were indicated. Conclusions Overexpression of PPP2R5C in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.

  17. Quantum Codes From Cyclic Codes Over The Ring R 2

    International Nuclear Information System (INIS)

    Altinel, Alev; Güzeltepe, Murat

    2016-01-01

    Let R 2 denotes the ring F 2 + μF 2 + υ 2 + μυ F 2 + wF 2 + μwF 2 + υwF 2 + μυwF 2 . In this study, we construct quantum codes from cyclic codes over the ring R 2 , for arbitrary length n, with the restrictions μ 2 = 0, υ 2 = 0, w 2 = 0, μυ = υμ, μw = wμ, υw = wυ and μ (υw) = (μυ) w. Also, we give a necessary and sufficient condition for cyclic codes over R 2 that contains its dual. As a final point, we obtain the parameters of quantum error-correcting codes from cyclic codes over R 2 and we give an example of quantum error-correcting codes form cyclic codes over R 2 . (paper)

  18. Creep-fatigue assessment of a thermina test specimen using the R5 procedure

    International Nuclear Information System (INIS)

    Booth, P.; Budden, P.J.; Bate, S.K.

    1997-01-01

    A creep-fatigue life assessment of an axisymmetric 316 stainless steel test specimen under constant mechanical and cyclic thermal shock loading using the R5 Procedure is described in this paper. This test was carried out at CEA, France, and formed part of the 'Thermina' series. Stress analysis has been carried out using both full inelastic finite element analysis and also the simplified shakedown methods, based on elastic calculation, within R5. The estimates of strain range and the stress at the start of the creep dwell have then been used with R5 to estimate creep and fatigue damage per cycle and hence to make predictions of component life. The predicted lives are compared with the lives observed in the tests. The simplified R5 estimate of life, based on development of a crack of depth 200 microns, is 260 cycles using best-estimate material properties. Experimentally, cracks of depth at least 150 microns were observed in between 526 and 650 cycles, for two similar tests. The simplified R5 route therefore leads to an estimate of life which is conservative but not unduly so on this component. Detailed cyclic inelastic analysis using the ORNL constitutive model and the ABAQUS finite element code to estimate the strain range and dwell stress led to a best estimate of 618 cycles to crack initiation using R5. (author). 16 refs, 11 figs, 4 tabs

  19. MGluR5 mediates the interaction between late-LTP, network activity, and learning.

    Directory of Open Access Journals (Sweden)

    Arthur Bikbaev

    2008-05-01

    Full Text Available Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1 a reduction of mGluR1a-expression in the dentate gyrus; 2 impaired dentate gyrus LTP; 3 enhanced CA1-LTP and 4 suppressed theta (5-10 Hz and gamma (30-100 Hz oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning.

  20. Some remarks on the space R2(E

    Directory of Open Access Journals (Sweden)

    Claes Fernström

    1983-01-01

    Full Text Available Let E be a compact subset of the complex plane. We denote by R(E the algebra consisting of the rational functions with poles off E. The closure of R(E in Lp(E, 1≤p1, as a necessary and sufficient condition for R2(E≠L2(E. We also construct a compact set E such that R2(E has an isolated bounded point evaluation. In section 3 we examine the smoothness properties of functions in R2(E at those points which admit bounded point evaluations.

  1. Microsoft System Center 2012 R2 Operations Manager cookbook

    CERN Document Server

    Beaumont (MVP), Steve; Odika, Chiyo; Ryan, Robert

    2015-01-01

    If you are tasked with monitoring the IT infrastructure within your organization, this book demonstrates how System Center 2012 R2 Operations Manager offers a radical and exciting solution to modern administration.

  2. Spectral sum rule for time delay in R2

    International Nuclear Information System (INIS)

    Osborn, T.A.; Sinha, K.B.; Bolle, D.; Danneels, C.

    1985-01-01

    A local spectral sum rule for nonrelativistic scattering in two dimensions is derived for the potential class velement ofL 4 /sup // 3 (R 2 ). The sum rule relates the integral over all scattering energies of the trace of the time-delay operator for a finite region Σis contained inR 2 to the contributions in Σ of the pure point and singularly continuous spectra

  3. Fear extinction induces mGluR5-mediated synaptic and intrinsic plasticity in infralimbic neurons.

    Science.gov (United States)

    Sepulveda-Orengo, Marian T; Lopez, Ana V; Soler-Cedeño, Omar; Porter, James T

    2013-04-24

    Studies suggest that plasticity in the infralimbic prefrontal cortex (IL) in rodents and its homolog in humans is necessary for inhibition of fear during the recall of fear extinction. The recall of extinction is impaired by locally blocking metabotropic glutamate receptor type 5 (mGluR5) activation in IL during extinction training. This finding suggests that mGluR5 stimulation may lead to IL plasticity needed for fear extinction. To test this hypothesis, we recorded AMPA and NMDA currents, AMPA receptor (AMPAR) rectification, and intrinsic excitability in IL pyramidal neurons in slices from trained rats using whole-cell patch-clamp recording. We observed that fear extinction increases the AMPA/NMDA ratio, consistent with insertion of AMPARs into IL synapses. In addition, extinction training increased inward rectification, suggesting that extinction induces the insertion of calcium-permeable (GluA2-lacking) AMPARs into IL synapses. Consistent with this, selectively blocking calcium-permeable AMPARs with Naspm reduced the AMPA EPSCs in IL neurons to a larger degree after extinction. Extinction-induced changes in AMPA/NMDA ratio, rectification, and intrinsic excitability were blocked with an mGluR5 antagonist. These findings suggest that mGluR5 activation leads to consolidation of fear extinction by regulating the intrinsic excitability of IL neurons and modifying the composition of AMPARs in IL synapses. Therefore, impaired mGluR5 activity in IL synapses could be one factor that causes inappropriate modulation of fear expression leading to anxiety disorders.

  4. Oracle JDeveloper 11gR2 Cookbook

    CERN Document Server

    Haralabidis, Nick

    2012-01-01

    "Oracle JDeveloper 11gR2 Cookbook" is a practical cookbook which goes beyond the basics with immediately applicable recipes for building ADF applications at an intermediate-to-advanced level. If you are a JavaEE developer who wants to go beyond the basics of building ADF applications with Oracle JDeveloper 11gR2 and get hands on with practical recipes, this book is for you. You should be comfortable with general Java development principles, the JDeveloper IDE, and ADF basics

  5. GluR2 ligand-binding core complexes

    DEFF Research Database (Denmark)

    Kasper, C; Lunn, M-L; Liljefors, T

    2002-01-01

    X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic...

  6. Equipment for thermal neutron flux measurements in reactor R2

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, E; Nilsson, T; Claeson, S

    1960-04-15

    For most of the thermal neutron flux measurements in reactor R2 cobalt wires will be used. The loading and removal of these wires from the reactor core will be performed by means of a long aluminium tube and electromagnets. After irradiation the wires will be scanned in a semi-automatic device.

  7. Microsoft System Center Data Protection Manager 2012 R2 cookbook

    CERN Document Server

    Hedblom, Robert

    2015-01-01

    If you are a DPM administrator, this book will help you verify your knowledge and provide you with everything you need to know about the 2012 R2 release. No prior knowledge about System Center DPM is required, however some experience of running backups will come in handy.

  8. R2E – identifying problems, mitigating risks

    CERN Document Server

    Anaïs Schaeffer

    2013-01-01

    During LS1, the R2E project team will be working on a task as painstaking as it is crucial: to achieve a sixfold reduction in the number of electronic malfunctions caused by radiation. On their success depends the ability of the accelerator to function correctly at nominal energy. No mean challenge, considering it comes on top of the tenfold reduction already achieved since 2009.   The graph plots the rate of LHC beam dumps due to single-event effects against beam luminosity. An indication of the challenge that faces the R2E project teams during LS1! The origins of the project known as R2E (Radiation to Electronics) go back to 2007, when the CNGS (CERN Neutrinos to Gran Sasso) experiment was being commissioned. "Right from the outset, some CNGS control systems were causing problems. They would regularly break down in operations with beam," recalls Markus Brugger, head of the R2E project. "Even though the beam intensity was very low, we began to suspect that radiati...

  9. Therapeutic potential of mGluR5 targeting in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Anil eKumar

    2015-06-01

    Full Text Available Decades of research dedicated towards Alzheimer's disease (AD has culminated in much of the current understanding of the neurodegeneration associated with disease. However, delineating the pathophysiology and finding a possible cure for the disease is still wanting. This is in part due to the lack of knowledge pertaining to the connecting link between neurodegenerative and neuroinflammatory pathways. Consequently, the inefficacy and ill-effects of the drugs currently available for AD encourage the need for alternative and safe therapeutic intervention. In this review we highlight the potential of mGluR5, a metabotropic glutamatergic receptor, in understanding the mechanism underlying the neuronal death and neuroinflammation in AD. We also discuss the role of mGlu5 receptor in mediating the neuron-glia interaction in the disease. Finally, we discuss the potential of mGluR5 as target for treating AD.

  10. mGluR5 Positive Allosteric Modulation Enhances Extinction Learning Following Cocaine Self-Administration

    OpenAIRE

    Cleva, Richard M.; Hicks, Megan P.; Gass, Justin T.; Wischerath, Kelly C.; Plasters, Elizabeth T.; Widholm, John J.; Olive, M. Foster

    2011-01-01

    Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study we investigated the effects of the type 5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in ...

  11. R 2 inflation to probe non-perturbative quantum gravity

    Science.gov (United States)

    Koshelev, Alexey S.; Sravan Kumar, K.; Starobinsky, Alexei A.

    2018-03-01

    It is natural to expect a consistent inflationary model of the very early Universe to be an effective theory of quantum gravity, at least at energies much less than the Planck one. For the moment, R + R 2, or shortly R 2, inflation is the most successful in accounting for the latest CMB data from the PLANCK satellite and other experiments. Moreover, recently it was shown to be ultra-violet (UV) complete via an embedding into an analytic infinite derivative (AID) non-local gravity. In this paper, we derive a most general theory of gravity that contributes to perturbed linear equations of motion around maximally symmetric space-times. We show that such a theory is quadratic in the Ricci scalar and the Weyl tensor with AID operators along with the Einstein-Hilbert term and possibly a cosmological constant. We explicitly demonstrate that introduction of the Ricci tensor squared term is redundant. Working in this quadratic AID gravity framework without a cosmological term we prove that for a specified class of space homogeneous space-times, a space of solutions to the equations of motion is identical to the space of backgrounds in a local R 2 model. We further compute the full second order perturbed action around any background belonging to that class. We proceed by extracting the key inflationary parameters of our model such as a spectral index ( n s ), a tensor-to-scalar ratio ( r) and a tensor tilt ( n t ). It appears that n s remains the same as in the local R 2 inflation in the leading slow-roll approximation, while r and n t get modified due to modification of the tensor power spectrum. This class of models allows for any value of r complete R 2 gravity a natural target for future CMB probes.

  12. Shadow corrosion evaluation in the Studsvik R2 reactor

    International Nuclear Information System (INIS)

    Sanders, Ch.; Lysell, G.

    2000-01-01

    Post-irradiation examination has shown that increased corrosion occurs when zirconium alloys are in contact with or in proximity to other metallic objects. The observations indicate an influence of irradiation from the adjacent component as the enhanced corrosion occurs as a 'shadow' of the metallic object on the zirconium surface. This phenomenon could ultimately limit the lifetime of certain zirconium alloy components in the reactor. The Studsvik R2 materials test reactor has an In-Core Autoclave (INCA) test facility especially designed for water chemistry and materials research. The INCA facility has been evaluated and found suitable for shadow corrosion studies. The R2 reactor core containing the INCA facility was modeled with the Monte Carlo N-Particle (MCNP) code in order to evaluate the electron deposition in various materials and to develop a hypothesis of the shadow corrosion mechanism. (authors)

  13. System Center 2012 R2 Virtual Machine Manager cookbook

    CERN Document Server

    Cardoso, Edvaldo Alessandro

    2014-01-01

    This book is a step-by-step guide packed with recipes that cover architecture design and planning. The book is also full of deployment tips, techniques, and solutions. If you are a solutions architect, technical consultant, administrator, or any other virtualization enthusiast who needs to use Microsoft System Center Virtual Machine Manager in a real-world environment, then this is the book for you. We assume that you have previous experience with Windows 2012 R2 and Hyper-V.

  14. A supersymmetric R2-action in six dimensions and torsion

    International Nuclear Information System (INIS)

    Bergshoeff, E.; Salam, A.; Sezgin, E.

    1986-01-01

    We give the superconformal extension of (Rsub(μνab)) 2 in six dimensions. We show that in a superconformal gauge the 3-form field Hsub(μνrho) has a natural torsion interpretation. We also give partial results on the superconformal extension of the Gauss-Bonnet combination: Rsub(μνab) 2 -4Rsub(μa) 2 +R 2 . (author)

  15. C2R2: Training Students To Build Coastal Resilience

    Science.gov (United States)

    Ferraro, C.; Kopp, R. E.; Jordan, R.; Gong, J.; Andrews, C.; Auermuller, L. M.; Herb, J.; McDonnell, J. D.; Bond, S.

    2017-12-01

    In the United States, about 23 million people live within 6 meters of sea level. In many parts of the country, sea-level rise between 1960 and 2010 has already led to a 2-5-fold increase in the rate of `nuisance' flooding. On top of rising seas, intensifying hurricanes and more frequent extremes of heat, humidity and precipitation pose additional risks to coastal societies, economies and ecosystems. Addressing risks posed by changing climate conditions in coastal areas demands innovative strategies that intersect multiple disciplines including engineering, ecology, communication, climate science, and community planning. To be usable, it also requires engaging coastal stakeholders in the development of research questions, the assessment of implications of research for planning and policy, and the communication of research results. Yet traditional, disciplinary programs are poorly configured to train the workforce needed to assess coastal climate risk and to develop and deploy integrated strategies for increasing coastal climate resilience. Coastal Climate Risk & Resilience (C2R2) is an NSF Research Traineeship (NRT) working to prepare the workforce that will build coastal resilience in the face of climate risks. Through its trainee and certificate programs, C2R2 works with graduate students at Rutgers University from multiple disciplines to better integrate all the elements of coastal systems and to communicate effectively with coastal stakeholders. C2R2 students will acquire the knowledge and practical skills needed to become leading researchers and practitioners tackling the critical challenges of coastal resilience.

  16. R5FORCE: a program to compute fluid induced forces using hydrodynamic output from the RELAP5 code

    International Nuclear Information System (INIS)

    Watkins, J.C.

    1983-01-01

    This paper describes the computer code R5FORCE, a postprocessor to the RELAP5/MOD1 thermal-hydraulics code. R5FORCE computes piping hydraulic force/time histories that can be input into various structural analysis computer codes. R5FORCE solves the momentum conservation equation using the pressure and wall shear force terms rather than the pressure and fluid acceleration terms; eliminating potential instabilities associated with computing the time derivative in the fluid acceleration term. The updates to REALP5 required to generate the input data to R5FORCE are also discussed

  17. (+-{1,2-Bis[(2R,5R-2,5-diethylphospholan-1-yl]ethane-κ2P,P′}(η4-cycloocta-1,5-dienerhodium(I tetrafluoridoborate

    Directory of Open Access Journals (Sweden)

    Stefan Schulz

    2010-11-01

    Full Text Available The title compound, [Rh(C8H12(C18H36P2]BF4, exhibits a rhodium(I complex cation with a bidentate bisphosphine ligand and a bidentate η2,η2-coordinated cycloocta-1,5-diene ligand. The ligands form a slightly distorted square-planar coordination environment for the Rh(I atom. An intramolecular P–Rh–P bite angle of 83.91 (2° is observed. The dihedral angle between the P—Rh—P and the X—Rh—X planes (X is the centroid of a double bond is 14.0 (1°. The BF4 anion is disordered over two positions in a 0.515 (7:0.485 (7 ratio.

  18. Linear microstructural features in R5(Si,Ge)4-type alloys: Difficulties in identification

    International Nuclear Information System (INIS)

    Chumbley, L.S.; Ugurlu, O.; McCallum, R.W.; Dennis, K.W.; Mudryk, Y.; Gschneidner, K.A.; Pecharsky, V.K.

    2008-01-01

    A brief review of the current literature concerning compounds based upon the R 5 (Si x Ge 1-x ) 4 structure reveals that essentially all examined alloys contain 'linear features' similar to those first observed by Szade et al. on the surface of Gd 5 Si 4 , Gd 5 Si 2 Ge 2 and Gd 5 Ge 4 samples. Attempts to characterize these features, using a variety of techniques, have proven to be a difficult task. Rather than becoming clearer and better understood, discrepancies in the reported data have resulted in much confusion. A series of comprehensive experiments involving optical, scanning and transmission electron microscopy, X-ray diffractometry, magnetization, and heat capacity measurements have been performed in an attempt to clarify the situation. These experiments, coupled with a critical examination of published data, allow certain misconceptions and apparent contradictions to be understood and explained. Of major importance is the discovery that the volume fraction of the linear feature present is far lower than what one may estimate on the basis of etched samples. The results of this study support previous data that show the linear features are a second phase of composition R 5 (Si x Ge 1-x ) 3 , and reveal the various difficulties associated with proper identification of this phase due to its small size scale and low volume percentage

  19. SU(2) Yang-Mills solitons in R2 gravity

    Science.gov (United States)

    Perapechka, I.; Shnir, Ya.

    2018-05-01

    We construct new family of spherically symmetric regular solutions of SU (2) Yang-Mills theory coupled to pure R2 gravity. The particle-like field configurations possess non-integer non-Abelian magnetic charge. A discussion of the main properties of the solutions and their differences from the usual Bartnik-McKinnon solitons in the asymptotically flat case is presented. It is shown that there is continuous family of linearly stable non-trivial solutions in which the gauge field has no nodes.

  20. R2 effect-size measures for mediation analysis

    Science.gov (United States)

    Fairchild, Amanda J.; MacKinnon, David P.; Taborga, Marcia P.; Taylor, Aaron B.

    2010-01-01

    R2 effect-size measures are presented to assess variance accounted for in mediation models. The measures offer a means to evaluate both component paths and the overall mediated effect in mediation models. Statistical simulation results indicate acceptable bias across varying parameter and sample-size combinations. The measures are applied to a real-world example using data from a team-based health promotion program to improve the nutrition and exercise habits of firefighters. SAS and SPSS computer code are also provided for researchers to compute the measures in their own data. PMID:19363189

  1. R2 effect-size measures for mediation analysis.

    Science.gov (United States)

    Fairchild, Amanda J; Mackinnon, David P; Taborga, Marcia P; Taylor, Aaron B

    2009-05-01

    R(2) effect-size measures are presented to assess variance accounted for in mediation models. The measures offer a means to evaluate both component paths and the overall mediated effect in mediation models. Statistical simulation results indicate acceptable bias across varying parameter and sample-size combinations. The measures are applied to a real-world example using data from a team-based health promotion program to improve the nutrition and exercise habits of firefighters. SAS and SPSS computer code are also provided for researchers to compute the measures in their own data.

  2. Robotic Range Clearance Competition (R2C2)

    Science.gov (United States)

    2011-10-01

    MON TUE MAP MAP VEG automated vegetation clearance, automated Aug 10 Aug 11 WED THU Med VEG ia and Visitor D MAP ay Aug 12 FRI SURF...competitors will not be penalized if they enter this area. For the competition we will add an additional Pan , Tilt, Zoom (PTZ) Camera that will be...Johnston’s Corner –Gas Station Restaurant: Pizza, Fired Chicken , Subs 550 W Whalen St., Guernsey, WY 82214 (307) 836-3155 R2C2 Competitor Information

  3. R2 cosmology: Inflation without a phase transition

    International Nuclear Information System (INIS)

    Mijic, M.B.; Morris, M.S.; Suen, W.

    1986-01-01

    A pure gravity inflationary model for the Universe is examined which is based on adding an εR 2 term to the usual gravitational Lagrangian. The classical evolution is worked out, including eventual particle production and the subsequent join to radiation-dominated Friedmann behavior. We show that this model gives significant inflation essentially independent of initial conditions. The model has only one free parameter which is bounded from above by observational constraints on scalar and tensorial perturbations and from below by both the need for standard baryogenesis and the need for galaxy formation. This requires 10/sup 11/<ε/sup -1/2/<10/sup 13/ GeV

  4. Foundations of SQL Server 2008 R2 Business Intelligence

    CERN Document Server

    Fouche, Guy

    2011-01-01

    Foundations of SQL Server 2008 R2 Business Intelligence introduces the entire exciting gamut of business intelligence tools included with SQL Server 2008. Microsoft has designed SQL Server 2008 to be more than just a database. It's a complete business intelligence (BI) platform. The database is at its core, and surrounding the core are tools for data mining, modeling, reporting, analyzing, charting, and integration with other enterprise-level software packages. SQL Server 2008 puts an incredible amount of BI functionality at your disposal. But how do you take advantage of it? That's what this

  5. Mass distribution and spatial organization of the linear bacterial motor of Spiroplasma citri R8A2.

    Science.gov (United States)

    Trachtenberg, Shlomo; Andrews, S Brian; Leapman, Richard D

    2003-03-01

    In the simple, helical, wall-less bacterial genus Spiroplasma, chemotaxis and motility are effected by a linear, contractile motor arranged as a flat cytoskeletal ribbon attached to the inner side of the membrane along the shortest helical line. With scanning transmission electron microscopy and diffraction analysis, we determined the hierarchical and spatial organization of the cytoskeleton of Spiroplasma citri R8A2. The structural unit appears to be a fibril, approximately 5 nm wide, composed of dimers of a 59-kDa protein; each ribbon is assembled from seven fibril pairs. The functional unit of the intact ribbon is a pair of aligned fibrils, along which pairs of dimers form tetrameric ring-like repeats. On average, isolated and purified ribbons contain 14 fibrils or seven well-aligned fibril pairs, which are the same structures observed in the intact cell. Scanning transmission electron microscopy mass analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified cytoskeletons indicate that the 59-kDa protein is the only constituent of the ribbons.

  6. Absorption and transport of deuterium-substituted 2R,4'R,8'R-alpha-tocopherol in human lipoproteins

    International Nuclear Information System (INIS)

    Traber, M.G.; Ingold, K.U.; Burton, G.W.; Kayden, H.J.

    1988-01-01

    Oral administration of a single dose of tri- or hexadeuterium substituted 2R,4'R,8'R-alpha-tocopheryl acetate (d3- or d6-alpha-T-Ac) to humans was used to follow the absorption and transport of vitamin E in plasma lipoproteins. Three hr after oral administration of d3-alpha-T-Ac (15 mg) to 2 subjects, plasma levels of d3-alpha-T were detectable; these increased up to 10 hr, reached a plateau at 24 hr, then decreased. Following administration of d6-alpha-T-Ac (15-16 mg) to 2 subjects, the percentage of deuterated tocopherol relative to the total tocopherol in chylomicrons increased more rapidly than the corresponding percentage in whole plasma. Chylomicrons and plasma lipoproteins were isolated from 2 additional subjects following administration of d3-alpha-T-Ac (140 or 60 mg). The percentage of deuterated tocopherol relative to the total tocopherol increased most rapidly in chylomicrons, then in very low density lipoproteins (VLDL), followed by essentially identical increases in low and high density lipoproteins (LDL and HDL, respectively) and lastly, in the red blood cells. This pattern of appearance of deuterated tocopherol is consistent with the concept that newly absorbed vitamin E is secreted by the intestine into chylomicrons; subsequently, chylomicron remnants are taken up by the liver from which the vitamin E is secreted in VLDL. The metabolism of VLDL in the circulation results in the simultaneous delivery of vitamin E into LDL and HDL

  7. Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(-)-myrtenol nitrate.

    Science.gov (United States)

    Bew, Sean P; Hiatt-Gipson, Glyn D; Mills, Graham P; Reeves, Claire E

    2016-01-01

    Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a 'halide for nitrate' substitution. Employing readily available starting materials, reagents and Horner-Wadsworth-Emmons chemistry the synthesis of easily separable, synthetically versatile 'key building blocks' (E)- and (Z)-3-methyl-4-chlorobut-2-en-1-ol as well as (E)- and (Z)-1-((2-methyl-4-bromobut-2-enyloxy)methyl)-4-methoxybenzene has been achieved using cheap, 'off the shelf' materials. Exploiting their reactivity we have studied their ability to undergo an 'allylic halide for allylic nitrate' substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates ('isoprene nitrates') in 66-80% overall yields. Using NOESY experiments the elucidation of the carbon-carbon double bond configuration within the purified isoprene nitrates has been established. Further exemplifying our 'halide for nitrate' substitution chemistry we outline the straightforward transformation of (1R,2S)-(-)-myrtenol bromide into the previously unknown monoterpene nitrate (1R,2S)-(-)-myrtenol nitrate.

  8. Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Denis Hélène

    2008-12-01

    Full Text Available Abstract Background In order to determine whether human prostate can be productively infected by HIV-1 strains with different tropism, and thus represent a potential source of HIV in semen, an organotypic culture of prostate from men undergoing prostatic adenomectomy for benign prostate hypertrophy (BPH was developed. The presence of potential HIV target cells in prostate tissues was investigated using immunohistochemistry. The infection of prostate explants following exposures with HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in culture supernatants, the quantification of HIV DNA in the explants and the detection of HIV RNA+ cells in situ. Results The overall prostate characteristics were retained for 21/2 weeks in culture. Numerous potential HIV-1 target cells were detected in the prostate stroma. Whilst HIV-1 R5SF162 strain consistently productively infected prostatic T lymphocytes and macrophages, the prototypic X4IIIB strain and a primary R5X4 strain showed less efficient replication in this organ. Conclusion The BPH prostate is a site of HIV-1 R5 replication that could contribute virus to semen. A limited spreading of HIV-1 X4 and R5X4 in this organ could participate to the preferential sexual transmission of HIV-1 R5 strains.

  9. R2E strategy and activities during LS1

    International Nuclear Information System (INIS)

    Perrot, A.L.

    2012-01-01

    The level of the flux of hadrons with energy in the multi MeV range expected from the collimation system at Point 7 and from the collisions at the interaction Points 1, 5 and 8 will induce Single Event Errors (SEEs) of the standard electronics present in the equipment located around these Points. Such events would perturb LHC operation. As a consequence, within the framework of the R2E (Radiation to Electronics) Mitigation Project, the sensitive equipment will be shielded or relocated to safer areas. These mitigation activities will be performed mainly during Long Shutdown 1 (LS1). About 15 groups (including equipment owners) will be involved in these activities with work periods from a few days to several months. Some of them will have to work in parallel in several LHC points. This document presents these mitigation activities with their associated planning, organization process, and main concerns as identified today. (author)

  10. Renormalization group procedure for potential −g/r2

    Directory of Open Access Journals (Sweden)

    S.M. Dawid

    2018-02-01

    Full Text Available Schrödinger equation with potential −g/r2 exhibits a limit cycle, described in the literature in a broad range of contexts using various regularizations of the singularity at r=0. Instead, we use the renormalization group transformation based on Gaussian elimination, from the Hamiltonian eigenvalue problem, of high momentum modes above a finite, floating cutoff scale. The procedure identifies a richer structure than the one we found in the literature. Namely, it directly yields an equation that determines the renormalized Hamiltonians as functions of the floating cutoff: solutions to this equation exhibit, in addition to the limit-cycle, also the asymptotic-freedom, triviality, and fixed-point behaviors, the latter in vicinity of infinitely many separate pairs of fixed points in different partial waves for different values of g.

  11. 6. Investigation of R2M17 compounds

    International Nuclear Information System (INIS)

    Elemans, J.B.A.A.; Buschow, K.H.J.

    1975-01-01

    A discussion is presented of the different crystallographic forms that arise in the parent RM 5 (R rare earth including yttrium or thorium; M = Fe, Co or Ni) with CaCu 5 structure in which every third R is replaced by a pair of M. This results in the stoichiometric composition R 2 M 17 . Metallographic studies of well annealed and quenched specimens of CeFesub(x), HoFesub(x) and TmFesub(x) with x varying from 8 to 9.5 showed that only those with x = 8.5 consisted of one phase. Similar experiments with ThNisub(x) and YNisub(x), x varying from 6.5 to 8.5 revealed that in these cases, single phases were obtained with x = 7.5

  12. Microstructure in Zircaloy Creep Tested in the R2 Reactor

    International Nuclear Information System (INIS)

    Pettersson, Kjell

    2004-12-01

    Tubular specimens of Zircaloy-4 have been creep tested in bending in the R2 reactor in Studsvik. The creep deformation in the reactor core is accelerated in comparison with creep deformation outside the reactor core. The possible mechanisms behind this behaviour are described briefly. In order to determine which the actual mechanism is, the microstructure of the material creep tested in the R2 reactor has been examined by transmission electron microscopy. Due to the bending, material subjected to both tensile and compressive stress during creep was available. Since some of the proposed mechanisms might give microstructures which are different when the material is subjected to compressive or tensile stress it was assumed that examination of both types of material would give valuable information with regard to the operating mechanism. The result of the examination was that in the as-irradiated condition there were no obvious differences detected between materials which had been deformed in tension or compression. After a heat treatment to coarsen the irradiation induced microstructure there were still no significant differences between the two types of material. However it was now observed that in addition to dislocation loops the microstructure also contained network dislocations which presumably had been invisible in the electron microscope before heat treatment due to the high density of small dislocation loops in this state. It is therefore concluded that the most probable mechanism for irradiation creep in this case is climb and glide of the network dislocations. The role of irradiation is two-fold: It accelerates climb due to the production of point defects of which more interstitials than vacancies arrive to the network dislocations stopped at an obstacles. This leads to a net climb after which a dislocation is released from the obstacle and an amount of glide takes place. The second effect is the production of loops which serve as an increasing density of

  13. The R + var-epsilon R2 cosmology

    International Nuclear Information System (INIS)

    Morris, M.S.

    1988-01-01

    This thesis presents the study of a model cosmology based on the R + var-epsilon R 2 gravitational Lagrangian. It may be roughly divided into two distinct parts. First, the classical inflationary scenario is developed. Then, the formalism of quantum cosmology is employed to determined initial conditions for the classical model. In the work on the classical model, the evolution equations for an isotropic and homogeneous universe are solved to exhibit both early-time inflation and a smooth transition to subsequent radiation-dominated behavior. Then perturbations on this isotropic background are evolved through the model to provide constraints on the model parameters from the observational limits on anisotropy today. In the work on the wave function, the two boundary conditions of Vilenkin and Hartle and Hawking are compared. The wave functions obtained are restricted to the initial edge of classical Lorentzian inflationary trajectories as distributions over initial conditions for the classical inflationary model. It is found that Vilenkin's wave function prefers the universe to undergo a great deal of inflation, whereas Hartle and Hawking's wave function prefers the universe to undergo little inflation. Finally, both boundary conditions are shown to require the inhomogeneous perturbative modes start out in their ground states

  14. Scalaron from R2-gravity as a heavy field

    Science.gov (United States)

    Pi, Shi; Zhang, Ying-li; Huang, Qing-Guo; Sasaki, Misao

    2018-05-01

    We study a model of inflation in which a scalar field χ is non-minimally coupled to Starobinsky's R2 gravity. After transforming it to the Einstein frame, a new scalar field, the scalaron phi, will appear and couple to χ with a nontrivial field metric, while χ acquires a positive mass via the non-minimal coupling. Initially inflation occurs along the phi direction with χ trapped near its origin by this induced mass. After phi crosses a critical value, it starts rolling down rapidly and proceeds to damped oscillations around an effective local minimum determined by the value of χ, while inflation still continues, driven by the χ field at this second stage where the effect of the non-minimal coupling becomes negligible. The presence of the damped oscillations during the transition from the first to second stage of inflation causes enhancement and oscillation features in the power spectrum of the curvature perturbation. Assuming that the oscillations may be treated perturbatively, we calculate these features by using the δ N formalism, and discuss its observational implications to large scale CMB anomalies or primordial black hole formation, depending on the scale of the features.

  15. (3R,5S,7R,8R,9S,10S,12S,13R,14S-10,13-Dimethyl-17-[5-oxo-5-(prop-2-yn-1-yloxypentan-2-yl]hexadecahydro-1H-cyclopenta[a]phenanthrene-3,7,12-triyl triacetate

    Directory of Open Access Journals (Sweden)

    T. Kavitha

    2017-03-01

    Full Text Available In the title compound, C33H48O8, four terminal H atoms of cholic acid are replaced by three acetyl and one terminal alkyne group. All the acetyl residues are twisted with respect to the rings (A, B and C to which they are attached. The cyclopentane ring D adopts an envelope conformation with the methyl-substituted C atom as the flap. Rings A, B and C have chair conformations. The dihedral angle between the mean planes of rings C and D is 4.70 (11°. In the crystal, molecules are linked by C—H...O hydrogen bonds, forming a three-dimensional structure.

  16. Evolution of R5 and X4 human immunodeficiency virus type 1 gag sequences in vivo: evidence for recombination

    International Nuclear Information System (INIS)

    Rij, Ronald P. van; Worobey, Michael; Visser, Janny A.; Schuitemaker, Hanneke

    2003-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection is in general established by CCR5-utilizing (R5) virus variants, which persist throughout the course of infection. R5 HIV-1 variants evolve into CXCR4-utilizing (X4) HIV-1 variants in approximately half of the infected individuals. We have previously observed an ongoing genetic evolution with a continuous divergence of envelope gp120 sequences of coexisting R5 and X4 virus variants over time. Here, we studied evolution of gag p17 sequences in two patients who developed X4 variants in the course of infection. In contrast to the envelope gp120 sequences, gag p17 sequences of R5 and X4 virus populations intermingled in phylogenetic trees and did not diverge from each other over time. Statistical evaluation using the Shimodaira-Hasegawa test indicated that the different genomic regions evolved along different topologies, supporting the hypothesis of recombination. Therefore, our data imply that recombination between R5 and X4 HIV-1 variants occurs in vivo

  17. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

    Science.gov (United States)

    Holst, Sebastian C; Sousek, Alexandra; Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich; Tafti, Mehdi; Landolt, Hans-Peter

    2017-10-05

    Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.

  18. Optimization and validation of a neutralizing antibody assay for HIV-1 in A3R5 cells.

    Science.gov (United States)

    Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju; Todd, Christopher A; Bilska, Miroslawa; Martelli, Amanda; LaBranche, Celia; Perez, Lautaro G; Ochsenbauer, Christina; Kappes, John C; Rountree, Wes; Denny, Thomas N; Montefiori, David C

    2014-07-01

    A3R5 is a human CD4(+) lymphoblastoid cell line that was engineered to express CCR5 and is useful for the detection of weak neutralizing antibody responses against tier 2 strains of HIV-1. Here we describe the optimization and validation of the HIV-1 neutralizing antibody assay that utilizes A3R5 cells, performed in compliance with Good Clinical Laboratory Practice (GCLP) guidelines. The assay utilizes Renilla luciferase-expressing replication competent infectious molecular clones (IMC) encoding heterologous env genes from different HIV-1 clades. Key assay validation parameters tested included specificity, accuracy, precision, limit of detection and quantitation, specificity, linearity and range, and robustness. Plasma samples demonstrated higher non-specific activity than serum samples in the A3R5 assay. This assay can tolerate a wide range of virus input but is more sensitive to cell concentration. The higher sensitivity of the A3R5 assay in neutralization responses to tier 2 strains of HIV-1 makes it complementary to, but not a substitute for the TZM-bl assay. The validated A3R5 assay is employed as an endpoint immunogenicity test for vaccine-elicited neutralizing antibodies against tier 2 strains of HIV-1, and to identify correlates of protection in HIV-1 vaccine trials conducted globally. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation

    Science.gov (United States)

    Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich

    2017-01-01

    Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep. PMID:28980941

  20. An approach to estimate the reactivity worth of R-5 poison tube system and experimental verification in ZERLINA reactor

    International Nuclear Information System (INIS)

    Khosla, S.K.; Paul, O.P.K.; Sengupta, S.N.

    1976-01-01

    It is proposed to employ a liquid poison injection system as an emergency shut down device for R-5 reactor. The liquid poison consists of gadolinium nitrate solution, which is injected into twenty poison tubes made of zircaloy that are located in between the regular lattice positions in R-5 reactor. The calculational model adopted to estimate the reactivity worth of the poison tubes so as to hold the reactor subcritical by 50 mk at full tank, is described. Similar reactivity estimates have also been carried out for R-5 poison tubes installed in Zerlina reactor in order to assess the adequacy of the calculational mode. The results of the calculations are compared with experimental values for single poison tubes. (author)

  1. Evaluation of role 2 (R2) medical resources in the Afghanistan combat theater: Initial review of the joint trauma system R2 registry.

    Science.gov (United States)

    Mann-Salinas, Elizabeth A; Le, Tuan D; Shackelford, Stacy A; Bailey, Jeffrey A; Stockinger, Zsolt T; Spott, Mary Ann; Wirt, Michael D; Rickard, Rory; Lane, Ian B; Hodgetts, Timothy; Cardin, Sylvain; Remick, Kyle N; Gross, Kirby R

    2016-11-01

    A Role 2 registry (R2R) was developed in 2008 by the US Joint Trauma System (JTS). The purpose of this project was to undertake a preliminary review of the R2R to understand combat trauma epidemiology and related interventions at these facilities to guide training and optimal use of forward surgical capability in the future. A retrospective review of available JTS R2R records; the registry is a convenience sample entered voluntarily by members of the R2 units. Patients were classified according to basic demographics, affiliation, region where treatment was provided, mechanism of injury, type of injury, time and method of transport from point of injury (POI) to R2 facility, interventions at R2, and survival. Analysis included trauma patients aged ≥18 years or older wounded in year 2008 to 2014, and treated in Afghanistan. A total of 15,404 patients wounded and treated in R2 were included in the R2R from February 2008 to September 2014; 12,849 patients met inclusion criteria. The predominant patient affiliations included US Forces, 4,676 (36.4%); Afghan Forces, 4,549 (35.4%); and Afghan civilians, 2,178 (17.0%). Overall, battle injuries predominated (9,792 [76.2%]). Type of injury included penetrating, 7,665 (59.7%); blunt, 4,026 (31.3%); and other, 633 (4.9%). Primary mechanism of injury included explosion, 5,320 (41.4%); gunshot wounds, 3,082 (24.0%); and crash, 1,209 (9.4%). Of 12,849 patients who arrived at R2, 167 (1.3%) were dead; of 12,682 patients who were alive upon arrival, 342 (2.7%) died at R2. This evaluation of the R2R describes the patient profiles of and common injuries treated in a sample of R2 facilities in Afghanistan. Ongoing and detailed analysis of R2R information may provide evidence-based guidance to military planners and medical leaders to best prepare teams and allocate R2 resources in future operations. Given the limitations of the data set, conclusions must be interpreted in context of other available data and analyses, not in isolation

  2. R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus

    NARCIS (Netherlands)

    Berkowitz, R. D.; van't Wout, A. B.; Kootstra, N. A.; Moreno, M. E.; Linquist-Stepps, V. D.; Bare, C.; Stoddart, C. A.; Schuitemaker, H.; McCune, J. M.

    1999-01-01

    Some individuals infected with only R5 strains of human immunodeficiency virus type 1 progress to AIDS as quickly as individuals harboring X4 strains. We determined that three R5 viruses were much less pathogenic than an X4 virus in SCID-hu Thy/Liv mice, suggesting that R5 virus-mediated rapid

  3. A Multifunctional and Possible Skin UV Protectant, (3R-5-Hydroxymellein, Produced by an Endolichenic Fungus Isolated from Parmotrema austrosinense

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    2016-12-01

    Full Text Available Lichens are considered a great bio-resource because they produce large numbers of secondary metabolites with many biological activities; however, they have not been cultivated under artificial conditions to date. As a result, lichen substances from natural sources are limited and have not been widely utilized in commercial applications. Accordingly, interest in lichen-associated fungi, especially endogenic fungi, has increased. Ultraviolet (UV radiation in sunlight is harmful to human health, resulting in demand for effective UV filtering agents for use in sunscreen. In this study, we purified (3R-5-hydroxymellein, which has UVA absorption activity, from the secondary metabolites of an endolichenic fungus (ELF000039. The antioxidant properties were then assessed by in vitro tests. The antioxidant activity of (3R-5-hydroxymellein was high when compared to the recognized antioxidants ascorbic acid (ASA and butyl hydroxyl anisole (BHA. Moreover, the compound exhibited no cytotoxicity toward mouse melanoma cell lines, B16F1 and B16F10, or the normal cell line, HaCaT. Furthermore, (3R-5-hydroxymellein recovered the damage caused by UVB irradiation and inhibited melanin synthesis. Taken together, these results suggest that (3R-5-hydroxymellein could have an interesting and vital profile to go further development as a multifunctional skin UV protectant.

  4. Hippocampal mGluR5 predicts an occurrence of helplessness behavior after repetitive exposure to uncontrollable stress.

    Science.gov (United States)

    Yim, Yeong Shin; Lee, Jinu; Kim, Gun-Tae; Song, Teresa; Kim, Chul Hoon; Kim, Dong Goo

    2012-06-21

    An individual's behavior is generally based on genetic blueprint and previous experiences. A coping strategy, affected by personal interpretation of past events, can be determined by behavioral controllability of stress. In this study, we examined the relationship between the hippocampal mGluR5 expression and coping strategies to stress. Rats were exposed to stress via inescapable and unpredictable footshocks on PNDs 14 and 90. Coping strategies to stress were also measured. Hippocampal mGluR5 was found to be linked to the behavioral coping strategy, as it increased in rats that showed helplessness behavior (HL (+) group) and decreased in those that did not (HL (-) group). Also, the HL (+) group showed a lack of adaptation in a novel environment but the HL (-) group did not. The results suggest that mGluR5 has a pivotal role in the controllability-based coping strategy. Hippocampal mGluR5 could be a target molecule in the manipulation of neuropsychiatric conditions for which maladaptation is a part of behavioral consequences. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Stereochemistry and molecular pharmacology of (S)-thio-ATPA, a new potent and selective GluR5 agonist

    DEFF Research Database (Denmark)

    Stensbøl, T B; Jensen, H S; Nielsen, B

    2001-01-01

    )-Glu) receptors (EC(50)=14 microM), comparable in potency with ATPA (EC(50)=34 microM). Recent findings, that (S)-ATPA is a potent (EC(50)=0.48 microM) and selective agonist at homomerically expressed ionotropic GluR5, prompted us to resolve thio-ATPA using chiral chromatography and pharmacologically characterize...

  6. User Guide for the R5EXEC Coupling Interface in the RELAP5-3D Code

    Energy Technology Data Exchange (ETDEWEB)

    Forsmann, J. Hope [Idaho National Lab. (INL), Idaho Falls, ID (United States); Weaver, Walter L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-04-01

    This report describes the R5EXEC coupling interface in the RELAP5-3D computer code from the users perspective. The information in the report is intended for users who want to couple RELAP5-3D to other thermal-hydraulic, neutron kinetics, or control system simulation codes.

  7. R2*-relaxometry of the pancreas in patients with human hemochromatosis protein associated hereditary hemochromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, B., E-mail: benjamin.henninger@i-med.ac.at [Department of Radiology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck (Austria); Rauch, S. [Department of Radiology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck (Austria); Zoller, H. [Department of Internal Medicine, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck (Austria); Plaikner, M.; Jaschke, W.; Kremser, C. [Department of Radiology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck (Austria)

    2017-04-15

    Highlights: • MRI with R2* relaxometry is suitable to detect iron overload of the pancreas. • Pancreatic iron overload can be present in HFE associated hereditary hemochromatosis. • R2* relaxometry of the pancreas should then be performed when liver iron is present. • It can be omitted in cases with no sign of hepatic iron. - Abstract: Purpose: To evaluate pancreatic iron in patients with human hemochromatosis protein associated hereditary hemochromatosis (HHC) using R2* relaxometry. Materials and methods: 81 patients (58 male, 23 female; median age 49.5, range 10–81 years) with HHC were retrospectively studied. All underwent 1.5 T magnetic resonance imaging (MRI) of the abdomen. A fat-saturated multi-gradient echo sequence with 12 echoes (TR = 200 ms; TE-initial 0.99 ms; Delta-TE 1.41 ms; 12 echoes; flip-angle: 20°) was used for the R2* quantification of the liver and the pancreas. Parameter maps were analyzed using regions of interest (3 in the liver and 2 in the pancreas) and R2* values were correlated. Results: 59/81 patients had a liver R2* ≥ 70 1/s of which 10/59 patients had a pancreas R2* ≥ 50 1/s. No patient presented with a liver R2* < 70 1/s and pancreas R2* ≥ 50 1/s. All patients with pancreas R2* values ≥ 50 1/s had liver R2* values ≥ 70 1/s. ROC analysis resulted in a threshold of 209.4 1/s for liver R2* values to identify HFE positive patients with pancreas R2* values ≥ 50 1/s with a median specificity of 78.87% and a median sensitivity of 90%. Conclusion: In patients with HHC R2* relaxometry of the pancreas should be performed when liver iron overload is present and can be omitted in cases with no sign of hepatic iron.

  8. R2*-relaxometry of the pancreas in patients with human hemochromatosis protein associated hereditary hemochromatosis

    International Nuclear Information System (INIS)

    Henninger, B.; Rauch, S.; Zoller, H.; Plaikner, M.; Jaschke, W.; Kremser, C.

    2017-01-01

    Highlights: • MRI with R2* relaxometry is suitable to detect iron overload of the pancreas. • Pancreatic iron overload can be present in HFE associated hereditary hemochromatosis. • R2* relaxometry of the pancreas should then be performed when liver iron is present. • It can be omitted in cases with no sign of hepatic iron. - Abstract: Purpose: To evaluate pancreatic iron in patients with human hemochromatosis protein associated hereditary hemochromatosis (HHC) using R2* relaxometry. Materials and methods: 81 patients (58 male, 23 female; median age 49.5, range 10–81 years) with HHC were retrospectively studied. All underwent 1.5 T magnetic resonance imaging (MRI) of the abdomen. A fat-saturated multi-gradient echo sequence with 12 echoes (TR = 200 ms; TE-initial 0.99 ms; Delta-TE 1.41 ms; 12 echoes; flip-angle: 20°) was used for the R2* quantification of the liver and the pancreas. Parameter maps were analyzed using regions of interest (3 in the liver and 2 in the pancreas) and R2* values were correlated. Results: 59/81 patients had a liver R2* ≥ 70 1/s of which 10/59 patients had a pancreas R2* ≥ 50 1/s. No patient presented with a liver R2* < 70 1/s and pancreas R2* ≥ 50 1/s. All patients with pancreas R2* values ≥ 50 1/s had liver R2* values ≥ 70 1/s. ROC analysis resulted in a threshold of 209.4 1/s for liver R2* values to identify HFE positive patients with pancreas R2* values ≥ 50 1/s with a median specificity of 78.87% and a median sensitivity of 90%. Conclusion: In patients with HHC R2* relaxometry of the pancreas should be performed when liver iron overload is present and can be omitted in cases with no sign of hepatic iron.

  9. Using R2* values to evaluate brain tumours on magnetic resonance imaging: Preliminary results

    International Nuclear Information System (INIS)

    Liu, Zhenghua; Liao, Haibo; Yin, Jianhua; Li, Yanfang

    2014-01-01

    To determine the usefulness of the R2* value in assessing the histopathological grade of glioma at magnetic resonance imaging and differentiating various brain tumours. Sixty-four patients with brain tumours underwent R2* mapping and diffusion-weighted imaging examinations. ANOVA was performed to analyse R2* values among four groups of glioma and among high-grade gliomas (grades III and IV), low-grade gliomas (grades I and II), meningiomas, and brain metastasis. Spearman's correlation coefficients were used to determine the relationships between the R2* values or apparent diffusion coefficient (ADC) and the histopathological grade of gliomas. R2* values of low- and high-grade gliomas were analysed with the receiver-operator characteristic curve. R2* values were significantly different among high-grade gliomas, low-grade gliomas, meningiomas, and brain metastasis, but not between grade I and grade II or between grade III and grade IV. The R2* value (18.73) of high-grade gliomas provided a very high sensitivity and specificity for differentiating low-grade gliomas. A strong correlation existed between the R2* value and the pathological grade of gliomas. R2* mapping is a useful sequence for determining grade of gliomas and in distinguishing benign from malignant tumours. R2* values are better than ADC for characterising gliomas. (orig.)

  10. Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-06-14

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  11. Structure and Mechanism of Receptor Sharing by the IL-10R2 Common Chain

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

    2010-07-19

    IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

  12. Preferential occupancy of R2 retroelements on the B chromosomes of the grasshopper Eyprepocnemis plorans.

    Directory of Open Access Journals (Sweden)

    Eugenia E Montiel

    Full Text Available R2 non-LTR retrotransposons exclusively insert into the 28S rRNA genes of their host, and are expressed by co-transcription with the rDNA unit. The grasshopper Eyprepocnemis plorans contains transcribed rDNA clusters on most of its A chromosomes, as well as non-transcribed rDNA clusters on the parasitic B chromosomes found in many populations. Here the structure of the E. plorans R2 element, its abundance relative to the number of rDNA units and its retrotransposition activity were determined. Animals screened from five populations contained on average over 12,000 rDNA units on their A chromosomes, but surprisingly only about 100 R2 elements. Monitoring the patterns of R2 insertions in individuals from these populations revealed only low levels of retrotransposition. The low rates of R2 insertion observed in E. plorans differ from the high levels of R2 insertion previously observed in insect species that have many fewer rDNA units. It is proposed that high levels of R2 are strongly selected against in E. plorans, because the rDNA transcription machinery in this species is unable to differentiate between R2-inserted and uninserted units. The B chromosomes of E. plorans contain an additional 7,000 to 15,000 rDNA units, but in contrast to the A chromosomes, from 150 to over 1,500 R2 elements. The higher concentration of R2 in the inactive B chromosomes rDNA clusters suggests these chromosomes can act as a sink for R2 insertions thus further reducing the level of insertions on the A chromosomes. These studies suggest an interesting evolutionary relationship between the parasitic B chromosomes and R2 elements.

  13. The Implementation of C-ID, R2D2 Model on Learning Reading Comprehension

    Science.gov (United States)

    Rayanto, Yudi Hari; Rusmawan, Putu Ngurah

    2016-01-01

    The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…

  14. R2*-relaxometry of the pancreas in patients with human hemochromatosis protein associated hereditary hemochromatosis.

    Science.gov (United States)

    Henninger, B; Rauch, S; Zoller, H; Plaikner, M; Jaschke, W; Kremser, C

    2017-04-01

    To evaluate pancreatic iron in patients with human hemochromatosis protein associated hereditary hemochromatosis (HHC) using R2* relaxometry. 81 patients (58 male, 23 female; median age 49.5, range 10-81 years) with HHC were retrospectively studied. All underwent 1.5T magnetic resonance imaging (MRI) of the abdomen. A fat-saturated multi-gradient echo sequence with 12 echoes (TR=200ms; TE-initial 0.99ms; Delta-TE 1.41ms; 12 echoes; flip-angle: 20°) was used for the R2* quantification of the liver and the pancreas. Parameter maps were analyzed using regions of interest (3 in the liver and 2 in the pancreas) and R2* values were correlated. 59/81 patients had a liver R2*≥70 1/s of which 10/59 patients had a pancreas R2*≥50 1/s. No patient presented with a liver R2*pancreas R2*≥50 1/s. All patients with pancreas R2* values≥50 1/s had liver R2* values≥70 1/s. ROC analysis resulted in a threshold of 209.4 1/s for liver R2* values to identify HFE positive patients with pancreas R2* values≥50 1/s with a median specificity of 78.87% and a median sensitivity of 90%. In patients with HHC R2* relaxometry of the pancreas should be performed when liver iron overload is present and can be omitted in cases with no sign of hepatic iron. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. MCSA Windows Server 2012 R2 installation and configuration study guide exam 70-410

    CERN Document Server

    Panek, William

    2015-01-01

    Master Windows Server installation and configuration withhands-on practice and interactive study aids for the MCSA: WindowsServer 2012 R2 exam 70-410 MCSA: Windows Server 2012 R2 Installation and ConfigurationStudy Guide: Exam 70-410 provides complete preparationfor exam 70-410: Installing and Configuring Windows Server 2012 R2.With comprehensive coverage of all exam topics and plenty ofhands-on practice, this self-paced guide is the ideal resource forthose preparing for the MCSA on Windows Server 2012 R2. Real-worldscenarios demonstrate how the lessons are applied in everydaysettings. Reader

  16. R2P in the UN Security Council: Darfur, Libya and beyond

    OpenAIRE

    Gifkins, J

    2016-01-01

    It has been argued that consensus on the responsibility to protect (R2P) was lost in the UN Security Council as a result of the NATO-led intervention in Libya in 2011. This argument assumes that there was more agreement on R2P before the Libyan intervention than there was afterwards. Yet a close examination of the Security Council’s use of language on R2P shows the opposite: R2P was highly contentious within the Security Council prior to the Libyan intervention, and less so afterwards. Not on...

  17. mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism.

    Directory of Open Access Journals (Sweden)

    Mili V Mehta

    Full Text Available Autism spectrum disorders (ASD are highly disabling developmental disorders with a population prevalence of 1-3%. Despite a strong genetic etiology, there are no current therapeutic options that target the core symptoms of ASD. Emerging evidence suggests that dysfunction of glutamatergic signaling, in particular through metabotropic glutamate receptor 5 (mGluR5 receptors, may contribute to phenotypic deficits and may be appropriate targets for pharmacologic intervention. This study assessed the therapeutic potential of 2-methyl-6-phenylethyl-pyrididine (MPEP, an mGluR5-receptor antagonist, on repetitive and anxiety-like behaviors in the valproic acid (VPA mouse model of autism. Mice were exposed prenatally on day E13 to VPA and assessed for repetitive self-grooming and marble burying behaviors as adults. Anxiety-like behavior and locomotor activity were measured in an open-field. VPA-exposed mice displayed increased repetitive and anxiety-like behaviors, consistent with previously published results. Across both marble burying and self-grooming assays, MPEP significantly reduced repetitive behaviors in VPA-treated mice, but had no effect on locomotor activity. These results are consistent with emerging preclinical literature that mGluR5-antagonists may have therapeutic efficacy for core symptoms of autism.

  18. γ-Aminobutyric Acid Type B (GABAB) Receptor Internalization Is Regulated by the R2 Subunit*

    Science.gov (United States)

    Hannan, Saad; Wilkins, Megan E.; Dehghani-Tafti, Ebrahim; Thomas, Philip; Baddeley, Stuart M.; Smart, Trevor G.

    2011-01-01

    γ-Aminobutyric acid type B (GABAB) receptors are important for slow synaptic inhibition in the CNS. The efficacy of inhibition is directly related to the stability of cell surface receptors. For GABAB receptors, heterodimerization between R1 and R2 subunits is critical for cell surface expression and signaling, but how this determines the rate and extent of receptor internalization is unknown. Here, we insert a high affinity α-bungarotoxin binding site into the N terminus of the R2 subunit and reveal its dominant role in regulating the internalization of GABAB receptors in live cells. To simultaneously study R1a and R2 trafficking, a new α-bungarotoxin binding site-labeling technique was used, allowing α-bungarotoxin conjugated to different fluorophores to selectively label R1a and R2 subunits. This approach demonstrated that R1a and R2 are internalized as dimers. In heterologous expression systems and neurons, the rates and extents of internalization for R1aR2 heteromers and R2 homomers are similar, suggesting a regulatory role for R2 in determining cell surface receptor stability. The fast internalization rate of R1a, which has been engineered to exit the endoplasmic reticulum, was slowed to that of R2 by truncating the R1a C-terminal tail or by removing a dileucine motif in its coiled-coil domain. Slowing the rate of internalization by co-assembly with R2 represents a novel role for GPCR heterodimerization whereby R2 subunits, via their C terminus coiled-coil domain, mask a dileucine motif on R1a subunits to determine the surface stability of the GABAB receptor. PMID:21724853

  19. Building a SuAVE browse interface to R2R's Linked Data

    Science.gov (United States)

    Clark, D.; Stocks, K. I.; Arko, R. A.; Zaslavsky, I.; Whitenack, T.

    2017-12-01

    The Rolling Deck to Repository program (R2R) is creating and evaluating a new browse portal based on the SuAVE platform and the R2R linked data graph. R2R manages the underway sensor data collected by the fleet of US academic research vessels, and provides a discovery and access point to those data at its website, www.rvdata.us. R2R has a database-driven search interface, but seeks a more capable and extensible browse interface that could be built off of the substantial R2R linked data resources. R2R's Linked Data graph organizes its data holdings around key concepts (e.g. cruise, vessel, device type, operator, award, organization, publication), anchored by persistent identifiers where feasible. The "Survey Analysis via Visual Exploration" or SuAVE platform (suave.sdsc.edu) is a system for online publication, sharing, and analysis of images and metadata. It has been implemented as an interface to diverse data collections, but has not been driven off of linked data in the past. SuAVE supports several features of interest to R2R, including faceted searching, collaborative annotations, efficient subsetting, Google maps-like navigation over an image gallery, and several types of data analysis. Our initial SuAVE-based implementation was through a CSV export from the R2R PostGIS-enabled PostgreSQL database. This served to demonstrate the utility of SuAVE but was static and required reloading as R2R data holdings grew. We are now working to implement a SPARQL-based ("RDF Query Language") service that directly leverages the R2R Linked Data graph and offers the ability to subset and/or customize output.We will show examples of SuAVE faceted searches on R2R linked data concepts, and discuss our experience to date with this work in progress.

  20. The influence of molecular order and microstructure on the R2* and the magnetic susceptibility tensor.

    Science.gov (United States)

    Wisnieff, Cynthia; Liu, Tian; Wang, Yi; Spincemaille, Pascal

    2016-06-01

    In this work, we demonstrate that in the presence of ordered sub-voxel structure such as tubular organization, biomaterials with molecular isotropy exhibits only apparent R2* anisotropy, while biomaterials with molecular anisotropy exhibit both apparent R2* and susceptibility anisotropy by means of susceptibility tensor imaging (STI). To this end, R2* and STI from gradient echo magnitude and phase data were examined in phantoms made from carbon fiber and Gadolinium (Gd) solutions with and without intrinsic molecular order and sub-voxel structure as well as in the in vivo brain. Confidence in the tensor reconstructions was evaluated with a wild bootstrap analysis. Carbon fiber showed both apparent anisotropy in R2* and anisotropy in STI, while the Gd filled capillary tubes only showed apparent anisotropy on R2*. Similarly, white matter showed anisotropic R2* and magnetic susceptibility with higher confidence, while the cerebral veins displayed only strong apparent R2* tensor anisotropy. Ordered sub-voxel tissue microstructure leads to apparent R2* anisotropy, which can be found in both white matter tracts and cerebral veins. However, additional molecular anisotropy is required for magnetic susceptibility anisotropy, which can be found in white matter tracts but not in cerebral veins. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry

    DEFF Research Database (Denmark)

    Pyatigorskaya, Nadya; Sharman, Michael; Corvol, Jean-Christophe

    2015-01-01

    symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia...

  2. R2U2: Monitoring and Diagnosis of Security Threats for Unmanned Aerial Systems

    Science.gov (United States)

    Schumann, Johann; Moosbruger, Patrick; Rozier, Kristin Y.

    2015-01-01

    We present R2U2, a novel framework for runtime monitoring of security properties and diagnosing of security threats on-board Unmanned Aerial Systems (UAS). R2U2, implemented in FPGA hardware, is a real-time, REALIZABLE, RESPONSIVE, UNOBTRUSIVE Unit for security threat detection. R2U2 is designed to continuously monitor inputs from the GPS and the ground control station, sensor readings, actuator outputs, and flight software status. By simultaneously monitoring and performing statistical reasoning, attack patterns and post-attack discrepancies in the UAS behavior can be detected. R2U2 uses runtime observer pairs for linear and metric temporal logics for property monitoring and Bayesian networks for diagnosis of security threats. We discuss the design and implementation that now enables R2U2 to handle security threats and present simulation results of several attack scenarios on the NASA DragonEye UAS.

  3. Positive allosteric modulation of mGluR5 accelerates extinction learning but not relearning following methamphetamine self-administration

    Directory of Open Access Journals (Sweden)

    Peter R Kufahl

    2012-11-01

    Full Text Available Recent studies have implicated glutamate neurotransmission as an important substrate for the extinction of conditioned behaviors, including responding for drug reinforcement. Positive allosteric modulation of the type-5 metabotropic glutamate receptor (mGluR5 in particular has emerged as a treatment strategy for the enhancement of extinction of drug-motivated behaviors. Here, we investigated the effects of the mGluR5 positive allosteric modulator CDPPB, a compound known for its cognitive enhancing effects in rodents, on extinction learning in rats with different histories of methamphetamine (METH training. Rats were trained to self-administer METH under two conditions: 16 daily sessions of short access (90 min/day, ShA, or 8 daily sessions of short access followed by 8 sessions of long access (6 hr/day, LgA. Control rats self-administered sucrose pellets in daily 30 min sessions. Next, rats were administered vehicle or 30 mg/kg CDPPB prior to 7 consecutive daily extinction sessions, subjected to additional extinction sessions to re-establish a post-treatment baseline, and then tested for reinstatement of behavior in the presence of METH- or sucrose-paired cues. Rats were then subjected to a second series of extinction sessions, preceded by vehicle or 30 mg/kg CDPPB, and an additional test for cue-triggered reinstatement. CDPPB treatment resulted in a more rapid extinction of responding on the active lever, especially in the early sessions of the first extinction sequence. However, treatment effects were minimal during subsequent cue reinstatement tests and nonexistent during the second series of extinction sessions. Rats with histories of ShA, LgA and sucrose training expressed similar behavioral sensitivities to CDPPB, with LgA rats demonstrating a modestly higher treatment effect. Positive allosteric modulation of mGluR5 may therefore have some beneficial effects on efforts to facilitate extinction learning and reduce methamphetamine seeking.

  4. Retrospective comparison of gradient recalled echo R2* and spin-echo R2 magnetic resonance analysis methods for estimating liver iron content in children and adolescents

    Energy Technology Data Exchange (ETDEWEB)

    Serai, Suraj D.; Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, MLC 5031, Cincinnati, OH (United States); Quinn, Charles T. [Cincinnati Children' s Hospital Medical Center, Division of Hematology, Cincinnati, OH (United States); Zhang, Bin [Cincinnati Children' s Hospital Medical Center, Division of Biostatistics and Epidemiology, Cincinnati, OH (United States); Podberesky, Daniel J. [Nemours Children' s Health System Nemours Children' s Hospital, Department of Radiology, Orlando, FL (United States)

    2015-10-15

    Serial surveillance of liver iron concentration (LIC) provides guidance for chelation therapy in patients with iron overload. The diagnosis of iron overload traditionally relies on core liver biopsy, which is limited by invasiveness, sampling error, cost and general poor acceptance by pediatric patients and parents. Thus noninvasive diagnostic methods such as MRI are highly attractive for quantification of liver iron concentration. To compare two MRI-based methods for liver iron quantification in children. 64 studies on 48 children and young adults (age range 4-21 years) were examined by gradient recalled echo (GRE) R2* and spin-echo R2 MRI at 1.5T to evaluate liver iron concentration. Scatter plots and Bland-Altman difference plots were generated to display and assess the relationship between the methods. With the protocols used in this investigation, Bland-Altman agreement between the methods is best when LIC is <20 mg/g dry tissue. Scatter plots show that all values with LIC <20 mg/g dry tissue fall within the 95% prediction limits. Liver iron concentration as determined by the R2* and R2 MR methods is statistically comparable, with no statistical difference between these methods for LIC <20 mg/g. (orig.)

  5. LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus?

    Directory of Open Access Journals (Sweden)

    Otto Christoph

    2011-02-01

    Full Text Available Abstract Background Investigation of the expression of an intestinal stem cell marker in esophageal adenocarcinomas (EAC with and without Barrett's Esophagus (BE, with respect to a cancer stem cell (CSC hypothesis. Materials and methods Expression of a putative intestinal stem cell marker LgR5 was analyzed in esophageal cancer specimen (n = 70: 41 EAC with BE, 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC and in the adenocarcinoma cell line OE-33. Ki-67 and Cdx-2 were co-labelled with LgR5 in double staining experiments. Immunhistochemical expression results were confirmed by RT-PCR and correlated with tumor stage and five-year survival rates. Results LgR5was found expressed in 35 of 41 (85% EAC with BE and in 16 of 19 (81% EAC without BE. By contrast, LgR5 was not found to be expressed in ESCC. Quantification of immunolabeling showed 15% LgR5+ cells in EAC with BE, 32% LgR5+ cells in adjacent BE and 13% in EAC without BE. Immunofluorescence double staining experiments with LgR5 and Ki-67 revealed a subpopulation (~5% of proliferating LgR+/Ki-67+ cells. On mRNA-level, expression of LgR5 was higher in BE in comparison to EAC (p = 0.0159. High levels of LgR5 expression in BE associated EAC were associated with poorer survival in univariate analysis. Conclusion The stem cell marker LgR5 is expressed in EAC, irrespective of association with BE, and appears to have negative impact on survival. The subset of proliferating LgR5+ cells (

  6. ChR2 transgenic animals in peripheral sensory system: Sensing light as various sensations.

    Science.gov (United States)

    Ji, Zhi-Gang; Wang, Hongxia

    2016-04-01

    Since the introduction of Channelrhodopsin-2 (ChR2) to neuroscience, optogenetics technology was developed, making it possible to activate specific neurons or circuits with spatial and temporal precision. Various ChR2 transgenic animal models have been generated and are playing important roles in revealing the mechanisms of neural activities, mapping neural circuits, controlling the behaviors of animals as well as exploring new strategy for treating the neurological diseases in both central and peripheral nervous system. An animal including humans senses environments through Aristotle's five senses (sight, hearing, smell, taste and touch). Usually, each sense is associated with a kind of sensory organ (eyes, ears, nose, tongue and skin). Is it possible that one could hear light, smell light, taste light and touch light? When ChR2 is targeted to different peripheral sensory neurons by viral vectors or generating ChR2 transgenic animals, the animals can sense the light as various sensations such as hearing, touch, pain, smell and taste. In this review, we focus on ChR2 transgenic animals in the peripheral nervous system. Firstly the working principle of ChR2 as an optogenetic actuator is simply described. Then the current transgenic animal lines where ChR2 was expressed in peripheral sensory neurons are presented and the findings obtained by these animal models are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. NEAR-INFRARED CIRCULAR AND LINEAR POLARIMETRY OF MONOCEROS R2

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jungmi; Tamura, Motohide [Department of Astronomy, Graduate School of Science, The University of Tokyo, 113-0033 (Japan); Hough, James H. [University of Hertfordshire, Hatfield, Herts AL10 9AB (United Kingdom); Nagata, Tetsuya [Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan); Kusakabe, Nobuhiko [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan)

    2016-09-01

    We have conducted simultaneous JHK{sub s}-band imaging circular and linear polarimetry of the Monoceros R2 (Mon R2) cluster. We present results from deep and wide near-infrared linear polarimetry of the Mon R2 region. Prominent and extended polarized nebulosities over the Mon R2 field are revisited, and an infrared reflection nebula associated with the Mon R2 cluster and two local reflection nebulae, vdB 67 and vdB 69, is detected. We also present results from deep imaging circular polarimetry in the same region. For the first time, the observations show relatively high degrees of circular polarization (CP) in Mon R2, with as much as approximately 10% in the K{sub s} band. The maximum CP extent of a ring-like nebula around the Mon R2 cluster is approximately 0.60 pc, while that of a western nebula, around vdB 67, is approximately 0.24 pc. The extended size of the CP is larger than those seen in the Orion region around IRc2, while the maximum degree of CP of ∼10% is smaller than those of ∼17% seen in the Orion region. Nonetheless, both the CP size and degree of this region are among the largest in our infrared CP survey of star-forming regions. We have also investigated the time variability of the degree of the polarization of several infrared sources and found possible variations in three sources.

  8. An R2 statistic for fixed effects in the linear mixed model.

    Science.gov (United States)

    Edwards, Lloyd J; Muller, Keith E; Wolfinger, Russell D; Qaqish, Bahjat F; Schabenberger, Oliver

    2008-12-20

    Statisticians most often use the linear mixed model to analyze Gaussian longitudinal data. The value and familiarity of the R(2) statistic in the linear univariate model naturally creates great interest in extending it to the linear mixed model. We define and describe how to compute a model R(2) statistic for the linear mixed model by using only a single model. The proposed R(2) statistic measures multivariate association between the repeated outcomes and the fixed effects in the linear mixed model. The R(2) statistic arises as a 1-1 function of an appropriate F statistic for testing all fixed effects (except typically the intercept) in a full model. The statistic compares the full model with a null model with all fixed effects deleted (except typically the intercept) while retaining exactly the same covariance structure. Furthermore, the R(2) statistic leads immediately to a natural definition of a partial R(2) statistic. A mixed model in which ethnicity gives a very small p-value as a longitudinal predictor of blood pressure (BP) compellingly illustrates the value of the statistic. In sharp contrast to the extreme p-value, a very small R(2) , a measure of statistical and scientific importance, indicates that ethnicity has an almost negligible association with the repeated BP outcomes for the study.

  9. 26 CFR 31.3306(r)(2)-1 - Treatment of amounts deferred under certain nonqualified deferred compensation plans.

    Science.gov (United States)

    2010-04-01

    ... nonqualified deferred compensation plans. 31.3306(r)(2)-1 Section 31.3306(r)(2)-1 Internal Revenue INTERNAL..., Internal Revenue Code of 1954) § 31.3306(r)(2)-1 Treatment of amounts deferred under certain nonqualified deferred compensation plans. (a) In general. Section 3306(r)(2) provides a special timing rule for the tax...

  10. MCSA Windows Server 2012 R2 administration study guide exam 70-411

    CERN Document Server

    Panek, William

    2015-01-01

    Complete exam coverage, hands-on practice, and interactive studytools for the MCSA: Administering Windows Server 2012 R2 exam70-411 MCSA: Windows Server 2012 R2 Administration Study Guide: Exam70-411 provides comprehensive preparation for exam 70-411:Administering Windows Server 2012 R2. With full coverage of allexam domains, this guide contains everything you need to know to befully prepared on test day. Real-world scenarios illustrate thepractical applications of the lessons, and hands-on exercises allowyou to test yourself against everyday tasks. You get access to aninteractive practice te

  11. An ODIP effort to map R2R ocean data terms to international vocabularies

    Science.gov (United States)

    Ferreira, Renata; Stocks, Karen; Arko, Robert

    2014-05-01

    The heterogeneity of terminology used in describing data creates a barrier to the efficient discovery and re-use of data, particularly across institutional, programmatic, and disciplinary boundaries. Here we explore the outcomes of a student project to crosswalk terms between the Rolling Deck to Repository (R2R) program and other international systems, as part of the Ocean Data Interoperability Platform (ODIP). R2R is a US program developing and implementing an information management system to preserve and provide access to routine underway data collected by U.S academic research vessels. R2R participates in ODIP, an international forum for improving the interoperability and effective sharing of marine data resources through technical workshops and joint prototypes. The vocabulary mapping effort lays a foundation for future ocean data portals through which users search and access international ocean data using familiar terms. R2R describes its data with a suite of controlled vocabularies (http://www.rvdata.us/voc) some of which were developed locally or are specific to the US. The goal of this student project is to crosswalk local/national vocabularies to authoritative international vocabularies, where they exist, or to vocabularies widely used by ODIP partners. Specifically, R2R developed the following crosswalks: R2R science party names to ORCID person identifiers, UNOLS ports to SeaDataNet Ports Gazetteer, R2R Device Models to NVS SeaVoX Device Catalog, and R2R Organizations to the European Directory of Marine Organizations (EDMO). Mappings were done in simple spreadsheets using synonymy relationships only, and will be published as part of the R2R Linked Data resources. The level of success in crosswalking was variable. The majority of ports were successfully mapped. Differences in the character sets (i.e. whether diacritic marks were used) caused automated matching to fail occasionally, but the number of ports was small enough that these could be manually

  12. Crystal structure of the compounds R8Ga3Co (R=Ce, Pr, Nd, Sm, Tb, Dy, Ho, Er, Tm)

    International Nuclear Information System (INIS)

    Grin', Yu.N.; Sichevich, O.M.; Gladyshevskij, R.E.; Yarmolyuk, Ya.P.

    1984-01-01

    The crystal structure of Pr 8 Ga 3 Co compounds is studied by the method of monocrystal (autodiffractometer, MoKsub(α)): space group P6 3 mc, a=10.489, c=6.910 A, Z=2. Coordination numbers of atoms are 11-14 for Pr, 11 for Ga, 7 for Co. The shortest interatomic distances are 3.365 for Pr-Pr, 3.047 for Pr-Ga, 2.75 A for Pr-Co. Pr 3 Ga 3 Co structure is akin to structures of R 2 In compounds (Ni 2 In type) and R 2 Ga (Cl 2 Pb type). Isostructural compounds form in systems of other rare earth metals with gallium and cobalt

  13. Unobtrusive Software and System Health Management with R2U2 on a Parallel MIMD Coprocessor

    Science.gov (United States)

    Schumann, Johann; Moosbrugger, Patrick

    2017-01-01

    Dynamic monitoring of software and system health of a complex cyber-physical system requires observers that continuously monitor variables of the embedded software in order to detect anomalies and reason about root causes. There exists a variety of techniques for code instrumentation, but instrumentation might change runtime behavior and could require costly software re-certification. In this paper, we present R2U2E, a novel realization of our real-time, Realizable, Responsive, and Unobtrusive Unit (R2U2). The R2U2E observers are executed in parallel on a dedicated 16-core EPIPHANY co-processor, thereby avoiding additional computational overhead to the system under observation. A DMA-based shared memory access architecture allows R2U2E to operate without any code instrumentation or program interference.

  14. [The construction of cell-penetrating peptide R8 and pH sensitive cleavable polyethylene glycols co-modified liposomes].

    Science.gov (United States)

    Zhang, Li; Wang, Yang; Gao, Hui-le; He, Qin

    2015-06-01

    The purpose of the study is to construct R8 peptide (RRRRRRRR) and pH sensitive polyethylene glycols (PEG) co-modified liposomes (Cl-Lip) and utilize them in breast cancer treatment. The co-modified liposomes were prepared with soybean phospholipid, cholesterol, DSPE-PEG2K-R8 and PEG5K-Hz-PE (pH sensitive PEG). The size and zeta potential of Cl-Lip were also characterized. The in vitro experiment demonstrated that the Cl-Lip had high serum stability in 50% fetal bovine serum. The cellular uptake of Cl-Lip under different pre-incubated conditions was evaluated on 4T1 cells. And the endocytosis pathway, lysosome escape ability and tumor spheroid penetration ability were also evaluated. The results showed the particle size of the Cl-Lip was (110.4 ± 5.2) nm, PDI of the Cl-Lip was 0.207 ± 0.039 and zeta potential of the Cl-Lip was (-3.46 ± 0.05) mV. The cellular uptake of Cl-Lip on 4T1 cells was pH sensitive, as the cellular uptake of Cl-Lip pre-incubated in pH 6.0 was higher than that of pH 7.4 under each time point. The main endocytosis pathways of Cl-Lip under pH 6.0 were micropinocytosis and energy-dependent pathway. At the same time, the Cl-Lip with pre-incubation in pH 6.0 had high lysosome escape ability and high tumor spheroid penetration ability. All the above results demonstrated that the Cl-Lip we constructed had high pH sensitivity and is a promising drug delivery system.

  15. Instrumentation and monitoring of the nextgen road infrastructure: Some results and perspectives from the R5G project

    Science.gov (United States)

    Hautière, Nicolas; Bourquin, Frédéric

    2017-04-01

    Through the centuries, the roads - which today constitute in France a huge transport network of 1 millions kilometers length - have always been able to cope with society needs and challenges. As a consequence, the next generation road infrastructure will have to take into account at least three societal transitions: ecological, energetic and digital. The goal of the 5th generation road project (R5G©) [1], led by Ifsttar in France, aligned with the Forever Open program [2], is to design and build demonstrators of such future road infrastructures. The goal of this presentation is to present different results related to the greening of road materials [3], the design of energy-positive roads [4, 5], the test of roads that self-diagnose [6], the design of roads adapted for connected [7], autonomous [8] and electrified vehicles [9], etc. In terms of perspectives, we will demonstrate that the road infrastructures will soon become a complex system: On one side road users will benefit from new services, on the other side such massively connected and instrumented infrastructures will potentially become an opportune sensor for knowledge development in geoscience, such as air quality, visibility and fog monitoring. References: [1] R5G project. r5g.ifsttar.fr [2] Forever Open Road project. www.foreveropenroad.eu [3] Biorepavation project. www.infravation.net/projects/BIOREPAVATION [4] N. Le Touz, J. Dumoulin. Numerical study of the thermal behavior of a new deicing road structure design with energy harvesting capabilities. EGU General Assembly 2015, Apr 2015, Vienne, Austria. [5] S. Asfour, F. Bernardin, E. Toussaint, J.-M. Piau. Hydrothermal modeling of porous pavement for its surface de-freezing. Applied Thermal Engineering. Volume 107, 25 August 2016, Pages 493-500 [6] LGV BPL Instrumentation. http://railenium.eu/wp-content/uploads/2016/08/INSTRUMENTATION-BPL-FR.pdf [7] SCOOP@F project. https://ec.europa.eu/inea/en/connecting

  16. R2R - software to speed the depiction of aesthetic consensus RNA secondary structures

    Science.gov (United States)

    2011-01-01

    Background With continuing identification of novel structured noncoding RNAs, there is an increasing need to create schematic diagrams showing the consensus features of these molecules. RNA structural diagrams are typically made either with general-purpose drawing programs like Adobe Illustrator, or with automated or interactive programs specific to RNA. Unfortunately, the use of applications like Illustrator is extremely time consuming, while existing RNA-specific programs produce figures that are useful, but usually not of the same aesthetic quality as those produced at great cost in Illustrator. Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams. Results We created R2R, a computer program that facilitates the generation of aesthetic and readable drawings of RNA consensus diagrams in a fraction of the time required with general-purpose drawing programs. Since the inference of a consensus RNA structure typically requires a multiple-sequence alignment, the R2R user annotates the alignment with commands directing the layout and annotation of the RNA. R2R creates SVG or PDF output that can be imported into Adobe Illustrator, Inkscape or CorelDRAW. R2R can be used to create consensus sequence and secondary structure models for novel RNA structures or to revise models when new representatives for known RNA classes become available. Although R2R does not currently have a graphical user interface, it has proven useful in our efforts to create 100 schematic models of distinct noncoding RNA classes. Conclusions R2R makes it possible to obtain high-quality drawings of the consensus sequence and structural models of many diverse RNA structures with a more practical amount of effort. R2R software is available at http://breaker.research.yale.edu/R2R and as an Additional file. PMID:21205310

  17. R2R--software to speed the depiction of aesthetic consensus RNA secondary structures.

    Science.gov (United States)

    Weinberg, Zasha; Breaker, Ronald R

    2011-01-04

    With continuing identification of novel structured noncoding RNAs, there is an increasing need to create schematic diagrams showing the consensus features of these molecules. RNA structural diagrams are typically made either with general-purpose drawing programs like Adobe Illustrator, or with automated or interactive programs specific to RNA. Unfortunately, the use of applications like Illustrator is extremely time consuming, while existing RNA-specific programs produce figures that are useful, but usually not of the same aesthetic quality as those produced at great cost in Illustrator. Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams. We created R2R, a computer program that facilitates the generation of aesthetic and readable drawings of RNA consensus diagrams in a fraction of the time required with general-purpose drawing programs. Since the inference of a consensus RNA structure typically requires a multiple-sequence alignment, the R2R user annotates the alignment with commands directing the layout and annotation of the RNA. R2R creates SVG or PDF output that can be imported into Adobe Illustrator, Inkscape or CorelDRAW. R2R can be used to create consensus sequence and secondary structure models for novel RNA structures or to revise models when new representatives for known RNA classes become available. Although R2R does not currently have a graphical user interface, it has proven useful in our efforts to create 100 schematic models of distinct noncoding RNA classes. R2R makes it possible to obtain high-quality drawings of the consensus sequence and structural models of many diverse RNA structures with a more practical amount of effort. R2R software is available at http://breaker.research.yale.edu/R2R and as an Additional file.

  18. Improved liver R2* mapping by pixel-wise curve fitting with adaptive neighborhood regularization.

    Science.gov (United States)

    Wang, Changqing; Zhang, Xinyuan; Liu, Xiaoyun; He, Taigang; Chen, Wufan; Feng, Qianjin; Feng, Yanqiu

    2018-08-01

    To improve liver R2* mapping by incorporating adaptive neighborhood regularization into pixel-wise curve fitting. Magnetic resonance imaging R2* mapping remains challenging because of the serial images with low signal-to-noise ratio. In this study, we proposed to exploit the neighboring pixels as regularization terms and adaptively determine the regularization parameters according to the interpixel signal similarity. The proposed algorithm, called the pixel-wise curve fitting with adaptive neighborhood regularization (PCANR), was compared with the conventional nonlinear least squares (NLS) and nonlocal means filter-based NLS algorithms on simulated, phantom, and in vivo data. Visually, the PCANR algorithm generates R2* maps with significantly reduced noise and well-preserved tiny structures. Quantitatively, the PCANR algorithm produces R2* maps with lower root mean square errors at varying R2* values and signal-to-noise-ratio levels compared with the NLS and nonlocal means filter-based NLS algorithms. For the high R2* values under low signal-to-noise-ratio levels, the PCANR algorithm outperforms the NLS and nonlocal means filter-based NLS algorithms in the accuracy and precision, in terms of mean and standard deviation of R2* measurements in selected region of interests, respectively. The PCANR algorithm can reduce the effect of noise on liver R2* mapping, and the improved measurement precision will benefit the assessment of hepatic iron in clinical practice. Magn Reson Med 80:792-801, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  19. R2R - software to speed the depiction of aesthetic consensus RNA secondary structures

    Directory of Open Access Journals (Sweden)

    Weinberg Zasha

    2011-01-01

    Full Text Available Abstract Background With continuing identification of novel structured noncoding RNAs, there is an increasing need to create schematic diagrams showing the consensus features of these molecules. RNA structural diagrams are typically made either with general-purpose drawing programs like Adobe Illustrator, or with automated or interactive programs specific to RNA. Unfortunately, the use of applications like Illustrator is extremely time consuming, while existing RNA-specific programs produce figures that are useful, but usually not of the same aesthetic quality as those produced at great cost in Illustrator. Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams. Results We created R2R, a computer program that facilitates the generation of aesthetic and readable drawings of RNA consensus diagrams in a fraction of the time required with general-purpose drawing programs. Since the inference of a consensus RNA structure typically requires a multiple-sequence alignment, the R2R user annotates the alignment with commands directing the layout and annotation of the RNA. R2R creates SVG or PDF output that can be imported into Adobe Illustrator, Inkscape or CorelDRAW. R2R can be used to create consensus sequence and secondary structure models for novel RNA structures or to revise models when new representatives for known RNA classes become available. Although R2R does not currently have a graphical user interface, it has proven useful in our efforts to create 100 schematic models of distinct noncoding RNA classes. Conclusions R2R makes it possible to obtain high-quality drawings of the consensus sequence and structural models of many diverse RNA structures with a more practical amount of effort. R2R software is available at http://breaker.research.yale.edu/R2R and as an Additional file.

  20. Engineering Assessment and Certification of Integrity of the 177-R2 tank system

    International Nuclear Information System (INIS)

    Graser, D.A.; Schwartz, W.W.

    1993-10-01

    This Engineering Assessment and Certification of Integrity of retention tanks 177-R2U1, 177-R2Al, and 177-R2A2 has been prepared in response to 40 CFR 265.192(a) and 22 CCR 66265.192(a) for new tank systems that store hazardous waste and have secondary containment. The regulations require that this assessment be completed and certified by an independent, qualified, California-registered professional engineer before the tank system is placed in use as a hazardous waste storage tank system. The technical assessments for the 177-R2Ul, 177-R2A1, and 177-R2A2 tank systems have been reviewed by an independent, qualified, California-registered professional engineer, who has certified that the tank systems have sufficient structural integrity, are acceptable for transferring and storing hazardous waste, are compatible with the stored waste, and the tanks and containment system are suitably designed to achieve the requirements of the applicable regulations so they will not collapse, rupture, or fail. This document will be kept on file by the Lawrence Livermore National Laboratory (LLNL) Environment Protection Department

  1. R2R-printed inverted OPV modules - towards arbitrary patterned designs

    Science.gov (United States)

    Välimäki, M.; Apilo, P.; Po, R.; Jansson, E.; Bernardi, A.; Ylikunnari, M.; Vilkman, M.; Corso, G.; Puustinen, J.; Tuominen, J.; Hast, J.

    2015-05-01

    We describe the fabrication of roll-to-roll (R2R) printed organic photovoltaic (OPV) modules using gravure printing and rotary screen-printing processes. These two-dimensional printing techniques are differentiating factors from coated OPVs enabling the direct patterning of arbitrarily shaped and sized features into visual shapes and, increasing the freedom to connect the cells in modules. The inverted OPV structures comprise five layers that are either printed or patterned in an R2R printing process. We examined the rheological properties of the inks used and their relationship with the printability, the compatibility between the processed inks, and the morphology of the R2R-printed layers. We also evaluate the dimensional accuracy of the printed pattern, which is an important consideration in designing arbitrarily-shaped OPV structures. The photoactive layer and top electrode exhibited excellent cross-dimensional accuracy corresponding to the designed width. The transparent electron transport layer extended 300 µm beyond the designed values, whereas the hole transport layer shrank 100 µm. We also examined the repeatability of the R2R fabrication process when the active area of the module varied from 32.2 cm2 to 96.5 cm2. A thorough layer-by-layer optimization of the R2R printing processes resulted in realization of R2R-printed 96.5 cm2 sized modules with a maximum power conversion efficiency of 2.1% (mean 1.8%) processed with high functionality.

  2. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition.

    Science.gov (United States)

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-08-11

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 ( GluR2 ) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2 . This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT.

  3. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

    Science.gov (United States)

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability to glutamate. However, the mechanism of this TBT-induced GluR2 decrease remains unknown. Therefore, we examined the effects of TBT on the activity of transcription factors that control GluR2 expression. Exposure of primary cortical neurons to 20 nM TBT for 3 h to 9 days resulted in a decrease in GluR2 mRNA expression. Moreover, TBT inhibited the DNA binding activity of nuclear respiratory factor-1 (NRF-1), a transcription factor that positively regulates the GluR2. This result indicates that TBT inhibits the activity of NRF-1 and subsequently decreases GluR2 expression. In addition, 20 nM TBT decreased the expression of genes such as cytochrome c, cytochrome c oxidase (COX) 4, and COX 6c, which are downstream of NRF-1. Our results suggest that NRF-1 inhibition is an important molecular action of the neurotoxicity induced by low-concentration TBT. PMID:28800112

  4. (5S,6R-5-Methyl-6-phenyl-4-propyl-1,3,4-oxadiazinane-2-thione

    Directory of Open Access Journals (Sweden)

    Joshua L. Kocher

    2009-06-01

    Full Text Available The title molecule, C13H18N2OS, is an oxadiazinanthione derived from (1R,2S-norephedrine. There are two molecules in the asymmetric. Both adopt roughly half-chair conformations; however, the 5-position carbon orients out of opposite faces of the oxadiazinanthiones plane in the two molecules. In the crystal structure, they are oriented as a dimer linked by a pair of N—H...S hydrogen bonds. The absolute configuration has been established from anomalous dispersion and confirms the known stereochemistry based on the synthetic procedure.

  5. Stability Indicating HPLC Method for the Determination of Chiral Purity of R-(-)-5-[2-aminopropyl]-2-methoxybenzene Sulfonamide.

    Science.gov (United States)

    Kasawar, G B; Farooqui, M N

    2009-09-01

    A chiral reverse phase liquid chromatographic method was developed for the enantiomeric resolution of racemic mixture of (-)-5-[2-aminopropyl]-2-methoxybenzene sulfonamide in bulk drug. The enantiomeric separation of sulfonamide was resolved on a Crownpak CR (+) column using perchloric acid buffer of pH 1.0 as mobile phase and with UV detection at 226 nm. The method is validated and proved to be robust. The limit of detection and quantification of S (-)-(5)-[2-aminopropyl]-2-methoxybenzene sulfonamide] was found to be 0.084 and 0.159 mug/ml, respectively for 20 mul injection volume. The percentage recovery of S (-)-(5)-[2-aminopropyl]-2-methoxybenzene sulfonamide] ranged from 99.57 to 101.88 in bulk drug samples of R (-)-(5)-[2- aminopropyl]-2-methoxybenzene sulfonamide].

  6. Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load.

    Science.gov (United States)

    Karlsson, Ulf; Antonsson, Liselotte; Ljungberg, Bengt; Medstrand, Patrik; Esbjörnsson, Joakim; Jansson, Marianne; Gisslen, Magnus

    2012-09-10

    To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4 T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4 T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4 T-cell counts. The use of other alternative coreceptors was less pronounced. Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4 T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS.

  7. Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

    Science.gov (United States)

    Kumar, Jaya; Hapidin, Hermizi; Bee, Yvonne-Tee Get; Ismail, Zalina

    2013-11-26

    Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

  8. Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

    Science.gov (United States)

    Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

    2014-03-21

    It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.

  9. Antigen-presenting cells represent targets for R5 HIV-1 infection in the first trimester pregnancy uterine mucosa.

    Directory of Open Access Journals (Sweden)

    Romain Marlin

    Full Text Available BACKGROUND: During the first trimester of pregnancy, HIV-1 mother-to-child transmission is relatively rare despite the permissivity of placental cells to cell-to-cell HIV-1 infection. The placenta interacts directly with maternal uterine cells (decidual cells but the physiological role of the decidua in the control of HIV-1 transmission and whether decidua could be a source of infected cells is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To answer to this question, decidual mononuclear cells were exposed to HIV-1 in vitro. Decidual cells were shown to be more susceptible to infection by an R5 HIV-1, as compared to an X4 HIV-1. Infected cells were identified by flow cytometry analysis. The results showed that CD14(+ cells were the main targets of HIV-1 infection in the decidua. These infected CD14(+ cells expressed DC-SIGN, CD11b, CD11c, the Fc gamma receptor CD16, CD32 and CD64, classical MHC class-I and class-II and maturation and activation molecules CD83, CD80 and CD86. The permissivity of decidual tissue was also evaluated by histoculture. Decidual tissue was not infected by X4 HIV-1 but was permissive to R5 HIV-1. Different profiles of infection were observed depending on tissue localization. CONCLUSIONS/SIGNIFICANCE: The presence of HIV-1 target cells in the decidua in vitro and the low rate of in utero mother-to-child transmission during the first trimester of pregnancy suggest that a natural control occurs in vivo limiting cell-to-cell infection of the placenta and consequently infection of the fetus.

  10. R2SM: a package for the analytic computation of the R2 Rational terms in the Standard Model of the Electroweak interactions

    International Nuclear Information System (INIS)

    Garzelli, M.V.

    2011-01-01

    The analytical package written in FORM presented in this paper allows the computation of the complete set of Feynman Rules producing the Rational terms of kind R 2 contributing to the virtual part of NLO corrections in the Standard Model of the Electroweak interactions. Building block topologies filled by means of generic scalars, vectors and fermions, allowing to build these Feynman Rules in terms of specific elementary particles, are explicitly given in the R ξ gauge class, together with the automatic dressing procedure to obtain the Feynman Rules from them. The results in more specific gauges, like the 't Hooft Feynman one, follow as particular cases, in both the HV and the FDH dimensional regularization schemes. As a check on our formulas, the gauge independence of the total Rational contribution (R 1 +R 2 ) to renormalized S-matrix elements is verified by considering the specific example of the H →γγ decay process at 1-loop. This package can be of interest for people aiming at a better understanding of the nature of the Rational terms. It is organized in a modular way, allowing a further use of some its files even in different contexts. Furthermore, it can be considered as a first seed in the effort towards a complete automation of the process of the analytical calculation of the R 2 effective vertices, given the Lagrangian of a generic gauge theory of particle interactions. (orig.)

  11. [Value of R2(*) in evaluating the biological behavior of primary hepatocellular carcinoma].

    Science.gov (United States)

    Tian, S F; Liu, A L; Liu, J H; Li, Y; Liu, X D; Huang, K; Song, Q W; Xu, M Z; Guo, W Y

    2016-04-19

    To investigate the correlation between R2(*) value of enhanced T2 star-weighted angiography (ESWAN) sequence and primary hepatocellular carcinoma infiltration and tumor thrombus, and investigate the biological behavior of HCC. A total of 221 cases of patients' imaging data with MRI examination(including ESWAN sequence) diagnosed as primary HCC were retrospectively analyzed.All the patients were collected from January 2014 to September 2015 in the First Affiliated Hospital of Dalian Medical University.The differences of R2(*) values in different MR types of HCC were analyzed.All patients were divided into infiltration group and non-infiltration group, tumor thrombus group and non-tumor thrombus group, the R2(*) values of the paired groups were compared.The diagnostic efficiency of R2(*) in HCC infiltration and tumor thrombus were evaluated by ROC curve, and to find out the threshold values. The MR types of 221 patients included 90 cases of nodular type, 62 cases of massive type, 69 cases of diffuse type.70 patients had tumor thrombus.The R2(*) values of different MR types were (21.82±8.52), (24.17±8.84)and (34.45±11.73) Hz, respectively.There was no statistically significant difference between the nodular and the massive types (P=0.144), while the difference between the nodular and diffuse type, the massive and diffuse types were statistically significant(P=0.000). The R2(*) values of infiltration group and non-infiltration group were (34.45±11.73) and (22.78±8.70) Hz , the R2(*) values of tumor thrombus group and non-tumor thrombus group were (31.20±12.17) and (24.21±9.90) Hz, the difference also had statistically significant(t=7.397 and 4.534, P=0.000 and 0.000). The AUC of R2(*) values for infiltration and tumor thrombus were 0.804, 0.681. R2(*) ≥24.68 Hz was the threshold value to diagnose the infiltration and tumor thrombus. R2(*) value can be used as a MR non-enhancement quantitative index to evaluate the biological behavior of HCC.

  12. In Vivo Quantification of Cerebral R2FNx01-Response to Graded Hyperoxia at 3 Tesla

    Directory of Open Access Journals (Sweden)

    Grigorios Gotzamanis

    2015-01-01

    Full Text Available Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen. Materials and Methods: The transverse relaxation rate (R2FNx01 of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO 2 , and heart pulse rate were monitored during the challenge. R2FNx01 maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI data, acquired at 3.0T. The average values in the segmented white matter (WM and gray matter (GM were tested by the analysis of variance (ANOVA, with Bonferroni post-hoc correction. The GM R2FNx01-reactivity to hyperoxia was modeled using the Hill′s equation. Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05 decrease of the R2FNx01 in GM. Under normoxia the GM-R2FNx01 was 17.2 ± 1.1 s -1 . At 75% O 2 supply, the R2FNx01 had reached a saturation level, with 16.4 ± 0.7 s -1 (P = 0.02, without a significant further decrease for 100% O 2 . The R2FNx01-response of GM correlated positively with CO 2 partial pressure (R = 0.69 ± 0.19 and negatively with SaO 2 (R = -0.74 ± 0.17. The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055. The Hill′s model predicted a maximum R2FNx01 response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration. Conclusions: The GM-R2FNx01 responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2FNx01-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.

  13. NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin

    Science.gov (United States)

    Alagarsamy, Sudar; Saugstad, Julie; Warren, Lee; Mansuy, Isabelle M.; Gereau, Robert W.; Conn, P. Jeffrey

    2010-01-01

    Previous reports have shown that activation of N-methyl-D-aspartate (NMDA) receptors potentiates responses to activation of the group I metabotropic glutamate receptor mGluR5 by reversing PKC-mediated desensitization of this receptor. NMDA-induced reversal of mGluR5 desensitization is dependent on activation of protein phosphatases. However, the specific protein phosphatase involved and the precise mechanism by which NMDA receptor activation reduces mGluR desensitization are not known. We have performed a series of molecular, biochemical, and genetic studies to show that NMDA-induced regulation of mGluR5 is dependent on activation of calcium-dependent protein phosphatase 2B/calcineurin (PP2B/CaN). Furthermore, we report that purified calcineurin directly dephosphorylates the C-terminal tail of mGluR5 at sites that are phosphorylated by PKC. Finally, immunoprecipitation and GST fusion protein pull-down experiments reveal that calcineurin interacts with mGluR5, suggesting that these proteins could be colocalized in a signaling complex. Taken together with previous studies, these data suggest that activation of NMDA receptors leads to activation of calcineurin and that calcineurin modulates mGluR5 function by directly dephosphorylating mGluR5 at PKC sites that are involved in desensitization of this receptor. 2005 Elsevier Ltd. All rights reserved. PMID:16005030

  14. mGluR5 stimulating Homer–PIKE formation initiates icariin induced cardiomyogenesis of mouse embryonic stem cells by activating reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Limin; Huang, Yujie; Zhang, Yingying [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China); Zhao, Qingwei [The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qing Chun Road, Hangzhou 310003 (China); Zheng, Bei; Lou, Yijia [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China); Zhu, Danyan, E-mail: zdyzxb@zju.edu.cn [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China)

    2013-06-10

    Icariin (ICA) has been reported to facilitate cardiac differentiation of mouse embryonic stem (ES) cells; however, the mechanism by which ICA induced cardiomyogenesis has not been fully elucidated yet. Here, an underlying signaling network including metabotropic glutamate receptor 5 (mGluR5), Homer, phosphatidylinositol 3-Kinase Enhancer (PIKE), phosphatidylinositol 3-Kinase (PI3K), reactive oxygen species (ROS) and nuclear factor-kappaB (NF-κB) was investigated in ICA induced cardiomyogenesis. Our results showed that the co-expression of mGluR5 together with α-actinin or Troponin T in embryoid bodies (EBs) treated with ICA was elevated to 10.86% and 9.62%, compared with the case in the control (4.04% and 3.45%, respectively). Exposure of EBs to ICA for 2 h remarkably increased the dimeric form of mGluR5, which was inhibited by small interfering RNA targeting mGluR5 (si-mGluR5). Moreover, the extracellular glutamate concentration in ICA treatment medium was elevated to 28.9±3.5 μM. Furthermore, the activation of mGluR5 by ICA triggered the formation of Homer–PIKE complex and activated PI3K, stimulating ROS generation and NF-κB nuclear translocation. Knockdown of mGluR5 or inhibition of PI3K by LY294002 blocked ICA induced cardiomyogenesis via repressing mGluR5 pathway, reducing ROS and NF-κB activation. These results revealed that the inducible mechanisms of ICA were related to activate mGluR5 pathway. -- Highlights: • ICA increased mGluR5 expression in cardiac differentiation of ES cells. • ICA enhanced the glutamate level and the receptor mGluR5 dimerization, stimulating the formation of Homer–PIKE complex. • Knockdown of mGluR5 or inhibition of PI3K by LY294002 inhibited ICA induced ROS generation and NF-κB nuclear translocation.

  15. Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Diana L Price

    2010-11-01

    Full Text Available Dementia with Lewy bodies (DLB and Parkinson's Disease (PD are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn. Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR, particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipitated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the

  16. Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Yoona Seo

    Full Text Available Neuroblastoma (NB originates from immature neuronal cells and currently has a poor clinical outcome. NB cells possess cancer stem cells (CSCs characteristics that facilitate the initiation of a tumor, as well as its metastasis. Human bitter taste receptors, referred to as TAS2Rs, are one of five types of basic taste receptors and they belong to a family of G-protein coupled receptors. The recent finding that taste receptors are expressed in non-gustatory tissues suggest that they mediate additional functions distinct from taste perception. While it is generally admitted that the recognition of bitter tastes may be associated with a self-defense system to prevent the ingestion of poisonous food compounds, this recognition may also serve as a disease-related function in the human body. In particular, the anti-cancer stemness and invasion effects of TAS2Rs on NB cells remain poorly understood. In the present study, endogenous expression of TAS2R8 and TAS2R10 in SK-N-BE(2C and SH-SY5Y cells was examined. In addition, higher levels of TAS2R8 and TAS2R10 expression were investigated in more differentiated SY5Y cells. Both TAS2Rs were up-regulated following the induction of neuronal cell differentiation by retinoic acid. In addition, ectopic transfection of the two TAS2Rs induced neurite elongation in the BE(2C cells, and down-regulated CSCs markers (including DLK1, CD133, Notch1, and Sox2, and suppressed self-renewal characteristics. In particular, TAS2RS inhibited tumorigenicity. Furthermore, when TAS2Rs was over-expressed, cell migration, cell invasion, and matrix metalloproteinases activity were inhibited. Expression levels of hypoxia-inducible factor-1α, a well-known regulator of tumor metastasis, as well as its downstream targets, vascular endothelial growth factor and glucose transporter-1, were also suppressed by TAS2Rs. Taken together, these novel findings suggest that TAS2Rs targets CSCs by suppressing cancer stemness characteristics and NB

  17. The correlation between R2' and bone mineral measurements in human vertebrae: an in vitro study

    International Nuclear Information System (INIS)

    Brismar, T.B.; Karlsson, M.; Li, T.Q.; Ringertz, H.

    1999-01-01

    The aim of this study was to investigate whether MR imaging of trabecular bone structure using magnetic inhomogeneity measurements is related to the amount of bone mineral in human vertebrae. Weight, bone mineral content (BMC DXA ), bone mineral per area (BMA DXA ) and bone mineral density (BMD CT ) were determined in 12 defatted human lumbar vertebrae (L2-L4) by weighing, dual X-ray absorptiometry (DXA) and CT. Inhomogeneity caused by susceptibility differences between trabecular bone and surrounding water was studied with MR imaging at 1.5 T using the GESFIDE sequence. The pulse sequence determines the transverse relaxation rate R2 * and its two components, the non-reversible transverse relaxation rate (R2) and the reversible transverse relaxation rate (R2'; i. e. relaxation rate due to magnetic susceptibility) in a single scan. Voxel size was 0.9 x 1.9 x 5.0 mm. Positive significant correlations between R2' and weight, BMC DXA , BMA DXA and BMD CT were observed (r > 0.61 and p DXA and BMD CT (r > 0.66 and p DXA . Thus, R2' measurements are related to the amount of bone mineral, but they also provide information which is not obtainable from bone mineral measurements. (orig.) (orig.)

  18. Prenatal Exposure to Tributyltin Decreases GluR2 Expression in the Mouse Brain.

    Science.gov (United States)

    Ishida, Keishi; Saiki, Takashi; Umeda, Kanae; Miyara, Masatsugu; Sanoh, Seigo; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), a common environmental contaminant, is widely used as an antifouling agent in paint. We previously reported that exposure of primary cortical neurons to TBT in vitro decreased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate receptor 2 (GluR2) expression and subsequently increased neuronal vulnerability to glutamate. Therefore, to identify whether GluR2 expression also decreases after TBT exposure in vivo, we evaluated the changes in GluR2 expression in the mouse brain after prenatal or postnatal exposure to 10 and 25 ppm TBT through pellet diets. Although the mean feed intake and body weight did not decrease in TBT-exposed mice compared with that in control mice, GluR2 expression in the cerebral cortex and hippocampus decreased after TBT exposure during the prenatal period. These results indicate that a decrease in neuronal GluR2 may be involved in TBT-induced neurotoxicity, especially during the fetal period.

  19. Effects of microwave exposure on motor learning and GluR2 phosphorylation in rabbit cerebellum

    International Nuclear Information System (INIS)

    Liu Yong; Wang Denggao; Zhang Guangbin; Zhou Wen; Yang Xuesen

    2007-01-01

    Objective: To investigate the effects of microwave exposure on motor learning and Glutamate receptor 2(GluR2) phosphorylation in rat cerebellum. Methods: The rabbits were trained for seven days to form eye-blink conditioning, and then divided randomly into control and microwave exposure group (at hours 0,3,24 and 72 subgroups after exposure, respectively). The rabbits were accepted 90 mW/cm 2 microwave exposure for 30 minutes, and the rectal temperature were detected immediately after exposure and specific absorption rate (SAR) value were calculated. Eye-blink conditioning were detected immediately after exposure, and cerebellar GluR2 protein and GluR2 phosphorylation were detected with Western blotting. Results: Rectal temperature of rabbits were increased by 3.02 degree C after exposure, and SAR value was 8.74 W/kg. The eye-blink conditioning decreased significantly after exposure, and cerebellar GluR2 protein expression had no significant alteration but phosphorylation reduced significantly after exposure. Conclusions: 90 mW/cm 2 microwave exposure has injurious effects on cerebellar GluR2 phosphorylation and motor learning. (authors)

  20. Statistical mechanics of the $N$-point vortex system with random intensities on $R^2$

    Directory of Open Access Journals (Sweden)

    Cassio Neri

    2005-01-01

    Full Text Available The system of N -point vortices on $mathbb{R}^2$ is considered under the hypothesis that vortex intensities are independent and identically distributed random variables with respect to a law $P$ supported on $(0,1]$. It is shown that, in the limit as $N$ approaches $infty$, the 1-vortex distribution is a minimizer of the free energy functional and is associated to (some solutions of the following non-linear Poisson Equation:$$ -Delta u(x = C^{-1}int_{(0,1]} rhbox{e}^{-eta ru(x- gamma r|x|^2}P(hbox{d}r, quadforall xin mathbb{R}^2, $$where $displaystyle C = int_{(0,1]}int_{mathbb{R}^2}hbox{e}^{-eta ru(y - gamma r|y|^2}hbox{d} yP(hbox{d}r$

  1. Some thermoelectric properties of the light rare earth sesquiselenides (R2Se/sub 3-x/)

    International Nuclear Information System (INIS)

    Takeshita, T.; Beaudry, B.J.; Gschneidner, K.A. Jr.

    1981-01-01

    Rare earth sesquiselenides of the Th 3 P 4 structure show variable electric properties over their homogeneity range, i.e., ranging from metallic (R 3 Se 4 ) to semimetallic (R 2 Se/sub 3-x/, where 0.14 > x > 0) to semiconducting (R 2 Se 3 ). The composition change is due to the formation of metal vacancies in the Th 3 P 4 structure with no vacancies at R 3 Se 4 and 4.75 at. % vacancies at R 2 Se 3 . The rare earth sesquiselenides are also refractory materials and therefore are of interest for high temperature thermoelectric applications. Preliminary results of thermoelectric power and electrical resistivity measurements on the light lanthanide sesquiselenides (La through Sm) are presented

  2. Data Retrieved by ARCADE-R2 Experiment On Board the BEXUS-17 Balloon

    Science.gov (United States)

    Barbetta, M.; Branz, F.; Carron, A.; Olivieri, L.; Prendin, J.; Sansone, F.; Savioli, L.; Spinello, F.; Francesconi, A.

    2015-09-01

    The Autonomous Rendezvous, Control And Docking Experiment — Reflight 2 (ARCADE-R2) is a technology demonstrator aiming to prove automatic attitude determination and control, rendezvous and docking capabilities for small scale spacecraft and aircraft. The development of such capabilities could be fundamental to create, in the near future, fleets of cooperative, autonomous unmanned aerial vehicles for mapping, surveillance, inspection and remote observation of hazardous environments; small-class satellites could also benefit from the employment of docking systems to extend and reconfigure their mission profiles. ARCADE-R2 is designed to test these technologies on a stratospheric flight on board the BEXUS-17 balloon, allowing to demonstrate them in a harsh environment subjected to gusty winds and high pressure and temperature variations. In this paper, ARCADE-R2 architecture is introduced and the main results obtained from a stratospheric balloon flight are presented.

  3. Activation of mGluR5 induces spike afterdepolarization and enhanced excitability in medium spiny neurons of the nucleus accumbens by modulating persistent Na+ currents

    Science.gov (United States)

    D’Ascenzo, Marcello; Podda, Maria Vittoria; Fellin, Tommaso; Azzena, Gian Battista; Haydon, Philip; Grassi, Claudio

    2009-01-01

    The involvement of metabotropic glutamate receptors type 5 (mGluR5) in drug-induced behaviours is well-established but limited information is available on their functional roles in addiction-relevant brain areas like the nucleus accumbens (NAc). This study demonstrates that pharmacological and synaptic activation of mGluR5 increases the spike discharge of medium spiny neurons (MSNs) in the NAc. This effect was associated with the appearance of a slow afterdepolarization (ADP) which, in voltage-clamp experiments, was recorded as a slowly inactivating inward current. Pharmacological studies showed that ADP was elicited by mGluR5 stimulation via G-protein-dependent activation of phospholipase C and elevation of intracellular Ca2+ levels. Both ADP and spike aftercurrents were significantly inhibited by the Na+ channel-blocker, tetrodotoxin (TTX). Moreover, the selective blockade of persistent Na+ currents (INaP), achieved by NAc slice pre-incubation with 20 nm TTX or 10 μm riluzole, significantly reduced the ADP amplitude, indicating that this type of Na+ current is responsible for the mGluR5-dependent ADP. mGluR5 activation also produced significant increases in INaP, and the pharmacological blockade of this current prevented the mGluR5-induced enhancement of spike discharge. Collectively, these data suggest that mGluR5 activation upregulates INaP in MSNs of the NAc, thereby inducing an ADP that results in enhanced MSN excitability. Activation of mGluR5 will significantly alter spike firing in MSNs in vivo, and this effect could be an important mechanism by which these receptors mediate certain aspects of drug-induced behaviours. PMID:19433572

  4. Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors

    Directory of Open Access Journals (Sweden)

    Simmonds Peter

    2008-01-01

    Full Text Available Abstract Background HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node. Results R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542, but with increased resistance to the anti-CD4 monoclonal antibody (mab, Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120. Conclusion Variation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.

  5. R2d2 Drives Selfish Sweeps in the House Mouse.

    Science.gov (United States)

    Didion, John P; Morgan, Andrew P; Yadgary, Liran; Bell, Timothy A; McMullan, Rachel C; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J; Campbell, Karl J; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J; Crowley, James J; Chesler, Elissa J; Förster, Daniel W; French, John E; Gabriel, Sofia I; Gatti, Daniel M; Garland, Theodore; Giagia-Athanasopoulou, Eva B; Giménez, Mabel D; Grize, Sofia A; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C; Herman, Jeremy S; Holt, James M; Hua, Kunjie; Jolley, Wesley J; Lindholm, Anna K; López-Fuster, María J; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P; Searle, Jeremy B; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L; Thomas-Laemont, Patricia; Threadgill, David W; Ventura, Jacint; Weinstock, George M; Pomp, Daniel; Churchill, Gary A; Pardo-Manuel de Villena, Fernando

    2016-06-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Simplified prediction of postoperative cardiac surgery outcomes with a novel score: R2CHADS2.

    Science.gov (United States)

    Peguero, Julio G; Lo Presti, Saberio; Issa, Omar; Podesta, Carlos; Parise, Helen; Layka, Ayman; Brenes, Juan C; Lamelas, Joseph; Lamas, Gervasio A

    2016-07-01

    To compare the accuracy of R2CHADS2, CHADS2, and CHA2DS2-VASc scores vs the Society of Thoracic Surgeons (STS) score as predictors of morbidity and mortality after cardiovascular surgery. All patients who underwent cardiothoracic surgery at our institution from January 2008 to July 2013 were analyzed. Only those patients who fulfilled the criteria for STS score calculation were included. The R2CHADS2 score was computed as follows: 2 points for GFR < 60 mL/min/1.73 m(2) (R2), prior stroke or TIA (S2); 1 point for history of congestive heart failure (C), hypertension (H), age ≥75 years (A), or diabetes (D). Area under the curve (AUC) analysis was used to estimate the accuracy of the different scores. The end point variables included operative mortality, permanent stroke, and renal failure as defined by the STS database system. Of the 3,492 patients screened, 2,263 met the inclusion criteria. These included 1,160 (51%) isolated valve surgery, 859 (38%) coronary artery bypass graft surgery, and 245 (11%) combined procedures. There were 147 postoperative events: 75 (3%) patients had postoperative renal failure, 48 (2%) had operative mortality, and 24 (1%) had permanent stroke. AUC analysis revealed that STS, R2CHADS2, CHADS2, and CHA2DS2-VASc reliably estimated all postoperative outcomes. STS and R2CHADS2 scores had the best accuracy overall, with no significant difference in AUC values between them. The R2CHADS2 score estimates postoperative events with acceptable accuracy and if further validated may be used as a simple preoperative risk tool calculator. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. MiR-2 family regulates insect metamorphosis by controlling the juvenile hormone signaling pathway.

    Science.gov (United States)

    Lozano, Jesus; Montañez, Raúl; Belles, Xavier

    2015-03-24

    In 2009 we reported that depletion of Dicer-1, the enzyme that catalyzes the final step of miRNA biosynthesis, prevents metamorphosis in Blattella germanica. However, the precise regulatory roles of miRNAs in the process have remained elusive. In the present work, we have observed that Dicer-1 depletion results in an increase of mRNA levels of Krüppel homolog 1 (Kr-h1), a juvenile hormone-dependent transcription factor that represses metamorphosis, and that depletion of Kr-h1 expression in Dicer-1 knockdown individuals rescues metamorphosis. We have also found that the 3'UTR of Kr-h1 mRNA contains a functional binding site for miR-2 family miRNAs (for miR-2, miR-13a, and miR-13b). These data suggest that metamorphosis impairment caused by Dicer-1 and miRNA depletion is due to a deregulation of Kr-h1 expression and that this deregulation is derived from a deficiency of miR-2 miRNAs. We corroborated this by treating the last nymphal instar of B. germanica with an miR-2 inhibitor, which impaired metamorphosis, and by treating Dicer-1-depleted individuals with an miR-2 mimic to allow nymphal-to-adult metamorphosis to proceed. Taken together, the data indicate that miR-2 miRNAs scavenge Kr-h1 transcripts when the transition from nymph to adult should be taking place, thus crucially contributing to the correct culmination of metamorphosis.

  8. Analysis of OECD/CSNI ISP-42 phase A PANDA experiment using coupled code R5G (RELAP5-GOTHIC)

    International Nuclear Information System (INIS)

    Bencik, V.; Debrecin, N.; Grgic, D.; Bajs, T.

    2010-01-01

    In the paper, the results of the analysis of OECD/CSNI ISP-42 Phase A experiment at PANDA facility using stand-alone codes RELAP5/mod3.3 and GOTHIC 7.2b as well as coupled code R5G (RELAP5/mod3.3-GOTHIC 7.2b) are presented. PANDA is a large-scale thermal-hydraulic test facility installed at PSI (Paul Scherrer Institute) in Switzerland. The OECD/CSNI ISP-42 test consists of six sequential phases (Phase A through F). The present work deals with the post-test calculation of the Phase A, including the break of the main steam line and the Passive Containment Cooling (PCC) System Start-Up. The objective of the test is to investigate the start-up phenomenology of passive cooling system when steam is injected into cold vessel filled with air. The calculation was performed using stand-alone RELAP5/mod3.3 and GOTHIC 7.2b models, and then the same calculation was performed using coupled code with RELAP5 being responsible for reactor part of the model and GOTHIC being responsible for containment part of the model. The prediction capability, running time and modeling aspects were discussed for all three cases. (authors)

  9. Regulation of capacitative and non-capacitative Ca2+ entry in A7r5 vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    COLIN W TAYLOR

    2004-01-01

    Full Text Available A capacitative Ca2+ entry (CCE pathway, activated by depletion of intracellular Ca2+ stores, is thought to mediate much of the Ca2+ entry evoked by receptors that stimulate phospholipase C (PLC. However, in A7r5 vascular smooth muscle cells, vasopressin, which stimulates PLC, empties intracellular Ca2+ stores but simultaneously inhibits their ability to activate CCE. The diacylglycerol produced with the IP3 that empties the stores is metabolized to arachidonic and this leads to activation of nitric oxide (NO synthase, production of NO and cyclic GMP, and consequent activation of protein kinase G. The latter inhibits CCE. In parallel, NO directly activates a non-capacitative Ca2+ entry (NCCE pathway, which is entirely responsible for the Ca2+ entry that occurs in the presence of vasopressin. This reciprocal regulation of two Ca2+ entry pathways ensures that there is sequential activation of first NCCE in the presence of vasopressin, and then a transient activation of CCE when vasopressin is removed. We suggest that the two routes for Ca2+ entry may selectively direct Ca2+ to processes that mediate activation and then recovery of the cell.

  10. Rolling Deck to Repository (R2R): Standards and Semantics for Open Access to Research Data

    Science.gov (United States)

    Arko, Robert; Carbotte, Suzanne; Chandler, Cynthia; Smith, Shawn; Stocks, Karen

    2015-04-01

    In recent years, a growing number of funding agencies and professional societies have issued policies calling for open access to research data. The Rolling Deck to Repository (R2R) program is working to ensure open access to the environmental sensor data routinely acquired by the U.S. academic research fleet. Currently 25 vessels deliver 7 terabytes of data to R2R each year, acquired from a suite of geophysical, oceanographic, meteorological, and navigational sensors on over 400 cruises worldwide. R2R is working to ensure these data are preserved in trusted repositories, discoverable via standard protocols, and adequately documented for reuse. R2R maintains a master catalog of cruises for the U.S. academic research fleet, currently holding essential documentation for over 3,800 expeditions including vessel and cruise identifiers, start/end dates and ports, project titles and funding awards, science parties, dataset inventories with instrument types and file formats, data quality assessments, and links to related content at other repositories. A Digital Object Identifier (DOI) is published for 1) each cruise, 2) each original field sensor dataset, 3) each post-field data product such as quality-controlled shiptrack navigation produced by the R2R program, and 4) each document such as a cruise report submitted by the science party. Scientists are linked to personal identifiers, such as the Open Researcher and Contributor ID (ORCID), where known. Using standard global identifiers such as DOIs and ORCIDs facilitates linking with journal publications and generation of citation metrics. Since its inception, the R2R program has worked in close collaboration with other data repositories in the development of shared semantics for oceanographic research. The R2R cruise catalog uses community-standard terms and definitions hosted by the NERC Vocabulary Server, and publishes ISO metadata records for each cruise that use community-standard profiles developed with the NOAA Data

  11. Pro EDI in BizTalk Server 2006 R2 electronic document interchange solutions

    CERN Document Server

    Beckner, Mark

    2008-01-01

    As business becomes more dependent on working with partners, suppliers, and other organizations in a streamlined way, Electronic Data Interchange (EDI) is one of the next big waves in connected systems. Microsoft BizTalk Server 2006 R2 offers an efficient, integrated way to deploy EDI solutions, and with the help of this book, readers will see how EDI can be used in their business and how best to get it set up with BizTalk. This book offers insights into the brand-new Biztalk 2006 R2--based EDI functionality, including the far greater flexibility in handling interchange. It gives advice coveri

  12. MCSA Windows Server 2012 R2 configuring advanced services study guide exam 70-412

    CERN Document Server

    Panek, William

    2015-01-01

    The bestselling MCSA study guide, with expert instruction andhands-on practice MCSA Windows Server 2012 R2 Configuring Advanced ServicesStudy Guide provides focused preparation for exam 70-412 and isfully updated to align with the latest Windows Server 2012 R2objectives. This comprehensive guide covers 100 percent of all examobjective domains, and includes hundreds of practice questions andanswers. You get access to video demonstrations, electronicflashcards, and practice exams, and hands-on exercises based onreal-world scenarios allow you to apply your skills to everydaytasks. Organized by o

  13. Curved fronts in the Belousov-Zhabotinskii reaction-diffusion systems in R2

    Science.gov (United States)

    Niu, Hong-Tao; Wang, Zhi-Cheng; Bu, Zhen-Hui

    2018-05-01

    In this paper we consider a diffusion system with the Belousov-Zhabotinskii (BZ for short) chemical reaction. Following Brazhnik and Tyson [4] and Pérez-Muñuzuri et al. [45], who predicted V-shaped fronts theoretically and discovered V-shaped fronts by experiments respectively, we give a rigorous mathematical proof of their results. We establish the existence of V-shaped traveling fronts in R2 by constructing a proper supersolution and a subsolution. Furthermore, we establish the stability of the V-shaped front in R2.

  14. Microsoft® Office Communications Server 2007 R2 Resource Kit

    CERN Document Server

    Maximo, Rui; Ramanathan, Rajesh; Kamdar, Nirav

    2009-01-01

    In-depth, comprehensive, and fully revised for R2-this RESOURCE KIT delivers the information you need to deploy, manage, and troubleshoot Microsoft Office Communications Server 2007 R2. Get technical insights, scenarios, and best practices from those who know the technology best-the engineers who designed and developed it-along with 90+ Windows PowerShell™ scripts, bonus references, and other essential resources on CD. Get expert advice on how to: Plan server roles, infrastructure, topology, and securityDesign and manage enterprise instant messaging (IM), presence, and conferencing solutio

  15. Oracle Data Guard 11gR2 administration beginner's guide

    CERN Document Server

    Baransel, Emre

    2013-01-01

    Using real-world examples and hands-on tasks, Oracle Data Guard 11gR2 Administration Beginner's Guide will give you a solid foundation in Oracle Data Guard. It has been designed to teach you everything you need to know to successfully create and operate Data Guard environments with maximum flexibility, compatibility, and effectiveness.If you are an Oracle database administrator who wants to configure and administer Data Guard configurations, then ""Oracle Data Guard 11gR2 Administration Beginner's Guide"" is for you. With a basic understanding of Oracle database administration, you'll be able

  16. Thermal expansion and spontaneous magnetostriction of R2Co7 intermetallic compounds

    International Nuclear Information System (INIS)

    Andreev, A.V.; Bartashevich, M.I.; Deryagin, A.V.; Zadvorkin, S.M.; Tarasov, E.N.

    1988-01-01

    Thermal expansion of R 2 Co 7 (R=Y, Nd, Gd, Tb) single crystals was invesigated by the method of X-ray dilatometry. Anomalous of thermal expansion, taking place during magnetic ordering and spin reorientation were used to determine linear and volumetric magnetistriction deformations. Constants of anisotropic magnetostriction of all R 2 Co 7 compounds with nonzero orbital moment of rare earth ion were calculated on the basis of single-ion model according to deformation values and with account of temperature dependences of the magnitude and direction of magnetic moment

  17. Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy

    NARCIS (Netherlands)

    Sarma, Satyam; Li, Na; van Oort, Ralph J.; Reynolds, Corey; Skapura, Darlene G.; Wehrens, Xander H. T.

    2010-01-01

    Aberrant intracellular Ca(2+) regulation is believed to contribute to the development of cardiomyopathy in Duchenne muscular dystrophy. Here, we tested whether inhibition of protein kinase A (PKA) phosphorylation of ryanodine receptor type 2 (RyR2) prevents dystrophic cardiomyopathy by reducing SR

  18. Genome-wide identification and characterization of R2R3MYB family in Rosaceae.

    Science.gov (United States)

    González, Máximo; Carrasco, Basilio; Salazar, Erika

    2016-09-01

    Transcription factors R2R3MYB family have been associated with the control of secondary metabolites, development of structures, cold tolerance and response to biotic and abiotic stress, among others. In recent years, genomes of Rosaceae botanical family are available. Although this information has been used to study the karyotype evolution of these species from an ancestral genome, there are no studies that treat the evolution and diversity of gene families present in these species or in the botanical family. Here we present the first comparative study of the R2R3MYB subfamily of transcription factors in three species of Rosaceae family (Malus domestica, Prunus persica and Fragaria vesca). We described 186, 98 and 86 non-redundant gene models for apple, peach and strawberry, respectively. In this research, we analyzed the intron-exon structure and genomic distribution of R2R3MYB families mentioned above. The phylogenetic comparisons revealed putative functions of some R2R3MYB transcription factors. This analysis found 44 functional subgroups, seven of which were unique for Rosaceae. In addition, our results showed a highly collinearity among some genes revealing the existence of conserved gene models between the three species studied. Although some gene models in these species have been validated under several approaches, more research in the Rosaceae family is necessary to determine gene expression patterns in specific tissues and development stages to facilitate understanding of the regulatory and biochemical mechanism in this botanical family.

  19. Convex Bodies With Minimal Volume Product in R^2 --- A New Proof

    OpenAIRE

    Lin, Youjiang

    2010-01-01

    In this paper, a new proof of the following result is given: The product of the volumes of an origin symmetric convex bodies $K$ in R^2 and of its polar body is minimal if and only if $K$ is a parallelogram.

  20. R2/R0-WTR decommissioning cost. Comparison and benchmarking analysis

    International Nuclear Information System (INIS)

    Varley, Geoff; Rusch, Chris

    2001-10-01

    SKI charged NAC International with the task of determining whether or not the decommissioning cost estimates of R2/R0 (hereafter simply referred to as R2) and Aagesta research reactors are reasonable. The associated work was performed in two phases. The objective in Phase I was to make global comparisons of the R2 and Aagesta decommissioning estimates with the estimates/actual costs for the decommissioning of similar research reactors in other countries. This report presents the results of the Phase II investigations. Phase II focused on selected discrete work packages within the decommissioning program of the WTR reactor. To the extent possible a comparison of those tasks with estimates for the R2 reactor has been made, as a basis for providing an opinion on the reasonableness of the R2 estimate. The specific WTR packages include: reactor vessel and internals dismantling; biological shield dismantling; primary coolant piping dismantling; electrical equipment removal; waste packaging; transportation and disposal of radioactive concrete and reactor components; project management, licensing and engineering; and removal of ancillary facilities. The specific tasks were characterised and analysed in terms of fundamental parameters including: task definition; labour hours expended; labour cost; labour productivity; length of work week; working efficiency; working environment and impact on job execution; external costs (contract labour, materials and equipment); total cost; waste volumes; and waste packaging and transport costs. Based on such detailed raw data, normalised unit resources have been derived for selected parts of the decommissioning program, as a first step towards developing benchmarking data for D and D activities at research reactors. Several general conclusions emerged from the WTR decommissioning project. Site characterisation can confirm or negate major assumptions, quantify waste volumes, delineate obstacles to completing work, provide an understanding

  1. Substrate recognition and function of the R2TP complex in response to cellular stress

    Czech Academy of Sciences Publication Activity Database

    von Morgen, Patrick; Hořejší, Zuzana; Macůrek, Libor

    2015-01-01

    Roč. 6, February 2015 (2015) ISSN 1664-8021 R&D Projects: GA ČR(CZ) GA14-34264S; GA MŠk LO1220 Institutional support: RVO:68378050 Keywords : R2TPcomplex * proteinfolding * DNAdamageresponse Subject RIV: EB - Genetics ; Molecular Biology

  2. Chiral recognition in electron scattering by S- and R-2-butanol

    DEFF Research Database (Denmark)

    Jones, Nykola C.; Hoffmann, Søren Vrønning; Field, David

    2015-01-01

    Experiments are described involving the low energy scattering of electrons from the two optical enantiomers S- and R- 2-butanol. Using a synchrotron radiation photoionization source on the ASTRID storage ring, scattering spectra are reported between a few meV and 140 meV at an electron energy...

  3. (2S,4R-2-[(1R-1-(4-Bromophenyl-2-nitroethyl]-4-ethylcyclohexanone

    Directory of Open Access Journals (Sweden)

    Chi-Xiao Zhang

    2013-02-01

    Full Text Available The crystal structure of the title compound, C16H20BrNO3, contains three chiral centers in the configuration 1R,2S,6R. The cyclohexane ring is in a chair conformation. In the crystal, molecules are linked by weak C—H...O interactions, forming chains along the a-axis direction.

  4. Mapping HL7 CDA R2 Formatted Mass Screening Data to OpenEHR Archetypes.

    Science.gov (United States)

    Kobayashi, Shinji; Kume, Naoto; Yoshihara, Hiroyuki

    2017-01-01

    Mass screening of adults was performed to manage employee healthcare. The screening service defined the data collection format as HL7 Clinical Document Architecture (CDA) R2. To capture mass screening data for nationwide electronic health records (her), we programmed a model within the CDA format and mapped the data items to the ISO13606/openEHR archetype for semantic interoperabiilty.

  5. Herschel/HIFI observations of CO, H2O and NH3 in Monoceros R2

    NARCIS (Netherlands)

    Pilleri, P.; Fuente, A.; Cernicharo, J.; Ossenkopf, V.; Berne, O.; Gerin, M.; Pety, J.; Goicoechea, J. R.; Rizzo, J. R.; Montillaud, J.; Gonzalez-Garcia, M.; Joblin, C.; Le Bourlot, J.; Le Petit, F.; Kramer, C.

    Context. Mon R2, at a distance of 830 pc, is the only ultracompact H II region (UCH II) where the associated photon-dominated region (PDR) can be resolved with Herschel. Owing to its brightness and proximity, it is one of the best-suited sources for investigating the chemistry and physics of highly

  6. Abrasion Testing of Products Containing Nanomaterials, SOP-R-2: Scientific Operating Procedure Series: Release (R)

    Science.gov (United States)

    2016-04-01

    Nanotechnologies -- Terminology and definitions for nano-objects -- Nanoparticle, nanofibre and nanoplate Definitions Abrasion - wearing away...ER D C SR -1 6- 2 Environmental Consequences of Nanotechnologies Abrasion Testing of Products Containing Nanomaterials, SOP-R-2...ERDC online library at http://acwc.sdp.sirsi.net/client/default. Environmental Consequences of Nanotechnologies ERDC SR-16-2 April 2016

  7. Synthesis and steriostructure of 5-(5-R-2- furfur lidene)- barbituric acid

    International Nuclear Information System (INIS)

    Abdel-Wahab, A.

    2012-01-01

    Heterocyclic compounds 5-(5-R-2-furfur lidene)- barbituric acid were obtained and their physical and chemical properties were studied. Their structures were identified by spectroscopic methods. This study proved by 1 H-NMR Spectroscopy data that these compounds exist in S-cis form. (author)

  8. The nature of hydrogen bonding in R-2(2)(8) crystal motifs - a computational exploration

    Czech Academy of Sciences Publication Activity Database

    Deepa, Palanisamy; Solomon, R. V.; Vedha, S. A.; Kolandaivel, P.; Venuvanalingam, P.

    2014-01-01

    Roč. 112, č. 24 (2014), s. 3195-3205 ISSN 0026-8976 Institutional support: RVO:61388963 Keywords : NCI plot * hydrogen bonds * R-2(2)(8) motif * organic crystals * NBO * QTAIM analysis Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.720, year: 2014

  9. Instant migration from Windows Server 2008 and 2008 R2 to 2012 how-to

    CERN Document Server

    Sivarajan, Santhosh

    2013-01-01

    Presented in a hands-on reference manual style, with real-world scenarios to lead you through each process. This book is intended for Windows server administrators who are performing migrations from their existing Windows Server 2008 / 2008 R2 environment to Windows Server 2012. The reader must be familiar with Windows Server 2008.

  10. R2R Eventlogger: Community-wide Recording of Oceanographic Cruise Science Events

    Science.gov (United States)

    Maffei, A. R.; Chandler, C. L.; Stolp, L.; Lerner, S.; Avery, J.; Thiel, T.

    2012-12-01

    Methods used by researchers to track science events during a science research cruise - and to note when and where these occur - varies widely. Handwritten notebooks, printed forms, watch-keeper logbooks, data-logging software, and customized software have all been employed. The quality of scientific results is affected by the consistency and care with which such events are recorded and integration of multi-cruise results is hampered because recording methods vary widely from cruise to cruise. The Rolling Deck to Repository (R2R) program has developed an Eventlogger system that will eventually be deployed on most vessels in the academic research fleet. It is based on the open software package called ELOG (http://midas.psi.ch/elog/) originally authored by Stefan Ritt and enhanced by our team. Lessons have been learned in its development and use on several research cruises. We have worked hard to find approaches that encourage cruise participants to use tools like the eventlogger. We examine these lessons and several eventlogger datasets from past cruises. We further describe how the R2R Science Eventlogger works in concert with the other R2R program elements to help coordinate research vessels into a coordinated mobile observing fleet. Making use of data collected on different research cruises is enabled by adopting common ways of describing science events, the science instruments employed, the data collected, etc. The use of controlled vocabularies and the practice of mapping these local vocabularies to accepted oceanographic community vocabularies helps to bind shipboard research events from different cruises into a more cohesive set of fleet-wide events that can be queried and examined in a cross-cruise manner. Examples of the use of the eventlogger during multi-cruise oceanographic research programs along with examples of resultant eventlogger data will be presented. Additionally we will highlight the importance of vocabulary use strategies to the success of the

  11. Decreased placental and maternal serum TRAIL-R2 levels are associated with placenta accreta.

    Science.gov (United States)

    Oztas, Efser; Ozler, Sibel; Ersoy, Ali Ozgur; Ersoy, Ebru; Caglar, Ali Turhan; Uygur, Dilek; Yucel, Aykan; Ergin, Merve; Danisman, Nuri

    2016-03-01

    TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) is produced both by decidual and trophoblast cells during pregnancy and known to participate in apoptosis. In this study, we aimed to determine and to compare maternal serum and placental TRAIL-R2 levels in patients with placenta accreta, non-adherent placenta previa and in healthy pregnancies. We also aimed to analyze the association of placenta accreta with the occurrence of previous C-sections. A total of 82 pregnant women were enrolled in this case-control study (27 placenta accreta patients, 26 non-adherent placenta previa patients and 29 age-, and BMI-matched healthy, uncomplicated pregnant controls). TRAIL-R2 levels were studied in both maternal serum and placental tissue homogenates. Determining the best predictor(s) which discriminate placenta accreta was analyzed by multiple logistic regression analyses. Adjusted odds ratios and 95% confidence intervals were also calculated. Both placental and serum TRAIL-R2 levels were significantly lower in placenta accreta group (median 34.82 pg/mg and 19.85 pg/mL, respectively) when compared with both non-adherent placenta previa (median 39.24 pg/mg and 25.99 pg/mL, respectively) and the control groups (median 41.62 pg/mg and 25.87 pg/mL, respectively) (p Placental TRAIL-R2 levels and previous cesarean section were found to be significantly associated with placenta accreta (OR: 0.934 95% CI 0.883-0.987, p = 0.016 and OR:7.725 95% CI: 2.717-21.965, p Placental and serum TRAIL-R2 levels were positively correlated. Decreased levels of placental TRAIL-R2 and previous history of cesarean section were found to be significantly associated with placenta accreta, suggesting a possible role of apoptosis in abnormal trophoblast invasion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation.

    Science.gov (United States)

    Lee, Hyunyeol; Englund, Erin K; Wehrli, Felix W

    2018-03-23

    Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO 2 ) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO 2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R 2 ' and intravascular R 2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBV v ) as well as venous blood R 2 (to yield HbO 2 ). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO 2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ± 3.3% for HbO 2 and 3.1 ± 0.5 and 2.0 ± 0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBV v and HbO 2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters. Copyright © 2018. Published by Elsevier Inc.

  13. GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin, E-mail: hjjang@khu.ac.kr

    2015-12-04

    Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

  14. GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell

    International Nuclear Information System (INIS)

    Park, Jiyoung; Kim, Ki-Suk; Kim, Kang-Hoon; Lee, In-Seung; Jeong, Hyeon-soo; Kim, Yumi; Jang, Hyeung-Jin

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) hormone is known to regulate blood glucose by an insulinotropic effect and increases proliferation as and also prevents apoptosis of pancreatic β cells. We know that GLP-1 is secreted by nutrients such as fatty acids and sweet compounds but also bitter compounds via stimulation of G-protein coupled receptors (GPCRs) in the gut. Among these, bitter compounds are multiply-contained in phytochemicals or artificial materials and perceived as ligands of various bitter taste receptors. We hypothesized that GLP-1 hormone is secreted through stimulation of a single bitter taste receptor by 1,10-phenanthroline which is known agonist of taste receptor type 2 member 5 (T2R5). To prove this hypothesis, we used the representatively well-known 1,10-phenanthroline as ligand of single receptor and evaluated the existence of T2R5 by double-labeling immunofluorescence and then 1,10-phenanthroline is able to secrete GLP-1 hormone through stimulation of T2R5 in human enteroendocrine cells. Consequently, we verify that GLP-1 hormone is colocalized with T2R5 in the human duodenum and ileum tissue and is secreted by 1,10-phenanthroline via T2R5 signal transduction in differentiated human enteroendocrine L cells. - Highlights: • Taste receptor type 2 member 5 (T2R5) is colocalized with GLP-1 hormone in human enteroendocrine cells. • GLP-1 secretion is stimulated by 1,10-phenanthroline via stimulation of T2R5. • Inhibition of the bitter taste pathway reduce GLP-1 secretion.

  15. Voltage-dependent modulation of cardiac ryanodine receptors (RyR2 by protamine.

    Directory of Open Access Journals (Sweden)

    Paula L Diaz-Sylvester

    Full Text Available It has been reported that protamine (>10 microg/ml blocks single skeletal RyR1 channels and inhibits RyR1-mediated Ca2+ release from sarcoplasmic reticulum microsomes. We extended these studies to cardiac RyR2 reconstituted into planar lipid bilayers. We found that protamine (0.02-20 microg/ml added to the cytosolic surface of fully activated RyR2 affected channel activity in a voltage-dependent manner. At membrane voltage (V(m; SR lumen-cytosol = 0 mV, protamine induced conductance transitions to several intermediate states (substates as well as full block of RyR2. At V(m>10 mV, the substate with the highest level of conductance was predominant. Increasing V(m from 0 to +80 mV, decreased the number of transitions and residence of the channel in this substate. The drop in current amplitude (full opening to substate had the same magnitude at 0 and +80 mV despite the approximately 3-fold increase in amplitude of the full opening. This is more similar to rectification of channel conductance induced by other polycations than to the action of selective conductance modifiers (ryanoids, imperatoxin. A distinctive effect of protamine (which might be shared with polylysines and histones but not with non-peptidic polycations is the activation of RyR2 in the presence of nanomolar cytosolic Ca2+ and millimolar Mg2+ levels. Our results suggest that RyRs would be subject to dual modulation (activation and block by polycationic domains of neighboring proteins via electrostatic interactions. Understanding these interactions could be important as such anomalies may be associated with the increased RyR2-mediated Ca2+ leak observed in cardiac diseases.

  16. A NEW RADIO RECOMBINATION LINE MASER OBJECT TOWARD THE MonR2 H II REGION

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez-Serra, I.; Zhang, Q.; Dierickx, M.; Patel, N. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Baez-Rubio, A.; Rivilla, V. M.; Martin-Pintado, J., E-mail: ijimenez-serra@cfa.harvard.edu, E-mail: qzhang@cfa.harvard.edu, E-mail: mdierickx@cfa.harvard.edu, E-mail: npatel@cfa.harvard.edu, E-mail: ryvendel@gmail.com, E-mail: jmartin@cab.inta-csic.es, E-mail: baezra@cab.inta-csic.es [Centro de Astrobiologia (CSIC/INTA), Ctra. de Torrejon a Ajalvir km 4, E-28850 Torrejon de Ardoz, Madrid (Spain)

    2013-02-10

    We report the detection of a new radio recombination line (RRL) maser object toward the IRS2 source in the MonR2 ultracompact H II region. The continuum emission at 1.3 mm and 0.85 mm and the H30{alpha} and H26{alpha} lines were observed with the Submillimeter Array (SMA) at angular resolutions of {approx}0.''5-3''. The SMA observations show that the MonR2-IRS2 source is very compact and remains unresolved at spatial scales {<=}400 AU. Its continuum power spectrum at millimeter wavelengths is almost flat ({alpha} = -0.16, with S{sub {nu}}{proportional_to}{nu}{sup {alpha}}), indicating that this source is dominated by optically thin free-free emission. The H30{alpha} and H26{alpha} RRL emission is also compact and peaks toward the position of the MonR2-IRS2 source. The measured RRL profiles are double peaked with the H26{alpha} line showing a clear asymmetry in its spectrum. Since the derived line-to-continuum flux ratios ({approx}80 and 180 km s{sup -1} for H30{alpha} and H26{alpha}, respectively) exceed the LTE predictions, the RRLs toward MonR2-IRS2 are affected by maser amplification. The amplification factors are, however, smaller than those found toward the emission-line star MWC349A, indicating that MonR2-IRS2 is a weakly amplified maser. Radiative transfer modeling of the RRL emission toward this source shows that the RRL masers arise from a dense and collimated jet embedded in a cylindrical ionized wind, oriented nearly along the direction of the line of sight. High-angular resolution observations at submillimeter wavelengths are needed to unveil weakly amplified RRL masers in very young massive stars.

  17. Decommissioning of the Nuclear Reactors R2 and R2-0 at Studsvik, Sweden. General Data as called for under Article 37 of the Euratom Treaty

    International Nuclear Information System (INIS)

    2009-01-01

    This document describes the plans for decommissioning of the nuclear research and material test reactors R2 and R2-0, situated at the Studsvik site close to the city of Nykoeping, Sweden. The purpose of the document is to serve as information for the European Commission, and to fulfil the requirements of Article 37 of the Euratom Treaty. Studsvik is situated on the Baltic coast, about 20 km east of Nykoeping and 80 km southwest of Stockholm. The site comprises the reactors R2 and R2-0 and several facilities for material investigation and radioactive waste treatment and storage. The reactors were used for a number of different purposes from 1960 until June 2005, when they were shut down following a decision by the operator. Decommissioning of the reactor facility is planned to be completed in 2016 after dismantling and conditioning of radioactive parts and demolition of the facility. Solid and liquid radioactive wastes from the dismantling activities will be treated and stored on-site awaiting final disposal. The waste treatment facilities, which are situated in other buildings at the Studsvik site, are planned to continue operation during and after the decommissioning of the reactor facility. All nuclear fuel has been transferred to a separate storage facility and is being shipped to the US according to existing agreements. The objective of the planned dismantling activities is to achieve clearance of the facility to make it possible to either demolish the buildings or use them for other purposes. The operator has divided the planning for dismantling and demolition of the facility into three phases [1]: Dismantling 1, including primary system decontamination, dismantling of the reactors with systems in the reactor pool, draining, cleaning and temporary covering of the reactor pool. This phase has begun and is due to last till approximately December 2009. Dismantling 2, including dismantling of systems in the reactor facility, removal of equipment, radiological

  18. Genome-wide identification, functional prediction, and evolutionary analysis of the R2R3-MYB superfamily in Brassica napus.

    Science.gov (United States)

    Hajiebrahimi, Ali; Owji, Hajar; Hemmati, Shiva

    2017-10-01

    R2R3-MYB transcription factors (TFs) have been shown to play important roles in plants, including in development and in various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus, called BnaR2R3-MYB TFs, clustered into 38 clades. BnaR2R3-MYB TFs were distributed on 19 chromosomes of B. napus. Sixteen gene clusters were identified. BnaR2R3-MYB TFs were characterized by motif prediction, gene structure analysis, and gene ontology. Evolutionary analysis revealed that BnaR2R3-MYB TFs are mainly formed as a result of whole-genome duplication. Orthologs and paralogs of BnaR2R3-MYB TFs were identified in B. napus, B. rapa, B. oleracea, and Arabidopsis thaliana using synteny-based methods. Purifying selection was pervasive within R2R3-MYB TFs. K n /K s values lower than 0.3 indicated that BnaR2R3-MYB TFs are being functionally converged. The role of gene conversion in the formation of BnaR2R3-MYB TFs was significant. Cis-regulatory elements in the upstream regions of BnaR2R3-MYB genes, miRNA targeting BnaR2R3MYB TFs, and post translational modifications were identified. Digital expression data revealed that BnaR2R3-MYB genes were highly expressed in the roots and under high salinity treatment after 24 h. BnaMYB21, BnaMYB141, and BnaMYB148 have been suggested for improving salt-tolerant B. napus. BnaR2R3-MYB genes were mostly up regulated on the 14th day post inoculation with Leptosphaeria biglobosa and L. maculan. BnaMYB150 is a candidate for increased tolerance to Leptospheria in B. napus.

  19. Biosynthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate by carbonyl reductase from Rhodosporidium toruloides in mono and biphasic media.

    Science.gov (United States)

    Liu, Zhi-Qiang; Wu, Lin; Zheng, Ling; Wang, Wen-Zhong; Zhang, Xiao-Jian; Jin, Li-Qun; Zheng, Yu-Guo

    2018-02-01

    tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is the key intermediate for synthesis of atorvastatin and rosuvastatin. Carbonyl reductase exhibits excellent activity toward tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH) to synthesize (3R,5S)-CDHH. In this study, a whole cell biosynthesis reaction system to produce (3R,5S)-CDHH was constructed in organic solvents. A solution of 10% (v/v) Tween-80 was introduced to the reaction system as a co-solvent, which greatly enhanced biotransformation process, giving 98.9% yield, >99% ee and 1.8-fold higher space time yield in 5 h bioconversion of 1 M (S)-CHOH, compared with 98.7% yield and >99% ee in 9 h bioconversion of a purely aqueous reaction system. Moreover, a water-octanol biphasic reaction system was built and 20% of octanol was added as reservoir of substrate resulting in 98% yield, >99% ee and 4.08 mmol L -1  h -1  g -1 (wet cell weight) space time yield. This study paved a way for the whole cell biosynthesis of (3R,5S)-CDHH in mono and biphasic media. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Antihypoxic activity of benzylidenhydrazides of 4-R-5- (thiophene-2-ylmethyl-1,2,4-triazol-3-ilthioacetic acid

    Directory of Open Access Journals (Sweden)

    O. A. Suhak

    2017-08-01

    of 4-R-5-(thiophene-2-ylmethyl-1,2,4-triazol-3-il thioacetic acid shows expressive antihypoxic action.

  1. TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species

    International Nuclear Information System (INIS)

    Yan, Jidong; Xu, Jing; Fei, Yao; Jiang, Congshan; Zhu, Wenhua; Han, Yan; Lu, Shemin

    2016-01-01

    Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

  2. TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jidong [Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Xu, Jing [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Fei, Yao [College of Life Sciences, Northwest University, Xi’an, Shaanxi Province 710069 (China); Jiang, Congshan; Zhu, Wenhua; Han, Yan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Lu, Shemin, E-mail: lushemin@xjtu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China (China)

    2016-05-15

    Thioredoxin reductase 2 (TrxR2) is a selenium (Se) containing protein. Se deficiency is associated with an endemic osteoarthropathy characterized by impaired cartilage formation. It is unclear whether TrxR2 have roles in cartilage function. We examined the effects of TrxR2 on chondrogenic ATDC5 cells through shRNA-mediated gene silencing of TrxR2. We demonstrated TrxR2 deficiencies could enhance chondrogenic differentiation and apoptosis of ATDC5 cells. TrxR2 deficiencies increased accumulation of cartilage glycosaminoglycans (GAGs) and mineralization. TrxR2 deficiencies also stimulated expression of extracellular (ECM) gene including Collagen II and Aggrecan. The enhanced chondrogenic properties were further confirmed by activation of Akt signaling which are required for chondrogenesis. In addition, TrxR2 deficiencies promoted chondrocyte proliferation through acceleration of cell cycle progression by increase in both S and G2/M phase cell distribution accompanied with induction of parathyroid hormone-related protein (PTHrP). Moreover, TrxR2 deficiencies induced chondrocyte death via apoptosis and increased cell sensitivity to exogenous oxidative stress. Furthermore, TrxR2 deficiencies induced emission of mitochondrial reactive oxygen species (ROS) without alteration of mitochondrial membrane potential and intracellular ATP content. Finally, treatment of TrxR2 deficiency cells with N-acetylcysteine (NAC) inhibited mitochondrial ROS production and chondrocyte apoptosis. NAC also prevented chondrogenic differentiation of TrxR2 deficiency cells by suppression of ECM gene expression, GAGs accumulation and mineralization, as well as attenuation of Akt signaling. Thus, TrxR2-mediated mitochondrial integrity is indispensable for chondrogenic differentiation of ATDC5 cells. TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Se deficiency. Notably, this study also uncover the roles of

  3. 4-bit digital to analog converter using R-2R ladder and binary weighted resistors

    Science.gov (United States)

    Diosanto, J.; Batac, M. L.; Pereda, K. J.; Caldo, R.

    2017-06-01

    The use of a 4-bit digital-to-analog converter using two methods; Binary Weighted Resistors and R-2R Ladder is designed and presented in this paper. The main components that were used in constructing both circuits were different resistor values, operational amplifier (LM741) and single pole double throw switches. Both circuits were designed using MULTISIM software to be able to test the circuit for its ideal application and FRITZING software for the layout designing and fabrication to the printed circuit board. The implementation of both systems in an actual circuit benefits in determining and comparing the advantages and disadvantages of each. It was realized that the binary weighted circuit is more efficient DAC, having lower percentage error of 0.267% compared to R-2R ladder circuit which has a minimum of percentage error of 4.16%.

  4. Radiolabeling and in vitro and in vivo characterization of [18F]FB-[R(8,15,21), L17]-VIP as a PET imaging agent for tumor overexpressed VIP receptors.

    Science.gov (United States)

    Cheng, Dengfeng; Yin, Duanzhi; Li, Gucai; Wang, Mingwei; Li, Shiqiang; Zheng, Mingqiang; Cai, Hancheng; Wang, Yongxian

    2006-12-01

    In an effort to develop a peptide-based radiopharmaceutical for the detection of tumors overexpressed vasoactive intestinal peptide receptors with positron emission tomography, we have prepared a novel [R(8,15,21), L17]-VIP peptide for 18F-labeling. This peptide inhibited 125I-VIP binding to rats lung membranes with high affinity [half-maximal inhibitory concentrations (IC50) of 0.12 nm]. Additionally, [R(8,15,21), L17]-VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N-succinimidyl 4-[18F] fluorobenzoate as labeling prosthetic group, [18F]FB-[R(8,15,21), L17]-VIP was obtained in >99% radiochemical purity within 100 min in decay-for-corrected radiochemical yield of 33.6 +/- 3% (n = 5) and a specific radioactivity 255 GBq/micromol at the end of synthesis. Stability of [18F]FB-[R(8,15,21), L17]-VIP in vitro and in vivo were investigated. Biodistribution of this trace was carried out in mice with induced C26 colorectal tumor. Fast clearance of [18F]FB-[R(8,15,21), L17]-VIP from non-target tissues and specific uptakes by tumors realized higher tumor-to-muscle ratio (3.55) and tumor-to-blood ratio (2.37) 60 min postinjection. Clear difference was observed between the blocking and unblocking experiments in biodistribution and whole body radioautography. [18F]FB-[R(8,15,21), L17]-VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.

  5. High-grade histologic features of DCIS are associated with R5 rather than R3 calcifications in breast screening mammography.

    LENUS (Irish Health Repository)

    Hayes, Brian D

    2013-01-01

    Mammographic calcification is an important radiologic feature of early breast carcinoma whose index of suspicion for malignancy may be reported by a five-tier R-category system. This study aims to describe the histologic diagnoses underlying screen-detected mammographic calcifications using both digital and screen-film mammography, and to correlate these findings with radiologic R-categories. Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2011 were identified, who underwent needle-core biopsy for assessment of mammographic calcifications without associated mass or architectural distortion. Radiologic R-category was correlated with biopsy and excision histology reports. A total of 776 cases of calcification were identified, involving 769 individual patients. The radiologic R-categories were as follows: R3 513 (66.1%), R4 192 (24.7%), R5 71 (9.1%). The positive predictive values for malignancy were R3 32.6%, R4 69.8%, R5 95.8%. Several histologic features of DCIS were associated with R5 rather than R3 radiology: high nuclear grade, solid or cribriform architecture, necrosis, periductal inflammation or fibrosis, and associated microinvasive or invasive carcinoma. Mammographic lesions and histologic whole and invasive tumors increased in size from R3 to R5. Radiologic size of calcifications correlated with whole (but not invasive) tumor size, although it tended to underestimate it by several millimeters. Digital-detected calcifications were more likely than screen-film detected to be categorized as R3 and less likely R4 or R5, and there was no significant difference in positive predictive value between the two imaging techniques in any R-category. In conclusion, histologic features of DCIS, in particular those associated with high grade, are associated with R5 radiology. There is no significant difference in positive predictive value for malignancy in any R-category between digital and screen-film mammography.

  6. JESS-D-16-00284 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  7. JESS-D-16-00189 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  8. JESS-D-16-00274 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  9. JESS-D-16-00392 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  10. JESS-D-16-00575 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  11. JESS-D-16-00024 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  12. JESS-D-16-00523 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  13. JESS-D-16-00354R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  14. JESS-D-16-00043 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  15. JESS-D-16-00107 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  16. JESS-D-16-00032 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  17. JESS-D-16-00351 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  18. JESS-D-16-00222 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  19. JESS-D-16-00044 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  20. JESS-D-16-00263 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  1. JESS-D-16-00005R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00005R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  2. Low-Concentration Tributyltin Decreases GluR2 Expression via Nuclear Respiratory Factor-1 Inhibition

    OpenAIRE

    Ishida, Keishi; Aoki, Kaori; Takishita, Tomoko; Miyara, Masatsugu; Sakamoto, Shuichiro; Sanoh, Seigo; Kimura, Tomoki; Kanda, Yasunari; Ohta, Shigeru; Kotake, Yaichiro

    2017-01-01

    Tributyltin (TBT), which has been widely used as an antifouling agent in paints, is a common environmental pollutant. Although the toxicity of high-dose TBT has been extensively reported, the effects of low concentrations of TBT are relatively less well studied. We have previously reported that low-concentration TBT decreases ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor subunit 2 (GluR2) expression in cortical neurons and enhances neuronal vulnerability ...

  3. JESS-D-16-00578 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00578 R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  4. JESS-D-16-00482 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00482 R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  5. JESS-D-16-00067 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00067 R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  6. JESS-D-16-00542 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00542 R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  7. JESS-D-16-00450 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  8. JESS-D-16-00589 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  9. JESS-D-16-00197 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  10. JESS-D-16-00418 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  11. JESS-D-16-00127R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  12. JESS-D-16-00307 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  13. JESS-D-16-00302 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00302 R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  14. JESS-D-16-00429 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  15. JESS-D-16-00330 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  16. JESS-D-16-00409 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  17. JESS-D-16-00287 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00287 R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  18. JESS-D-15-00464R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

    Home; public; Volumes; jess; forthcoming; JESS-D-15-00464R2.pdf. 404! error. The page your are looking for can not be found! Please check the link or use the navigation bar at the top. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. 29th Mid-year meeting. Posted on 19 January 2018. The 29th Mid-year ...

  19. JESS-D-16-00567 R2.pdf | forthcoming | jess | Volumes | public ...

    Indian Academy of Sciences (India)

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  20. Rolling Deck to Repository (R2R): Collaborative Development of Linked Data for Oceanographic Research

    Science.gov (United States)

    Arko, Robert; Chandler, Cynthia; Stocks, Karen; Smith, Shawn; Clark, Paul; Shepherd, Adam; Moore, Carla; Beaulieu, Stace

    2013-04-01

    The Rolling Deck to Repository (R2R) program is developing infrastructure to ensure the underway sensor data from U.S. academic oceanographic research vessels are routinely and consistently documented, preserved in long-term archives, and disseminated to the science community. The entire R2R Catalog is published online as a Linked Data collection, making it easily accessible to encourage discovery and integration with data at other repositories. We are developing the R2R Linked Data collection with specific goals in mind: 1.) We facilitate data access and reuse by publishing the richest possible collection of resources to describe vessels, cruises, instruments, and datasets from the U.S. academic fleet, including data quality assessment results and clean trackline navigation; 2.) We facilitate data citation through the entire lifecycle from field acquisition to shoreside archiving to journal articles and global syntheses, by publishing Digital Object Identifiers (DOIs) for datasets and encoding them directly into our Linked Data resources; and 3.) We facilitate federation with other repositories such as the Biological and Chemical Oceanography Data Management Office (BCO-DMO), InterRidge Vents Database, and Index to Marine and Lacustrine Geological Samples (IMLGS), by reciprocal linking between RDF resources and supporting the RDF Query Language. R2R participates in the Ocean Data Interoperability Platform (ODIP), a joint European-U.S.-Australian partnership to facilitate the sharing of data and documentation across international borders. We publish our controlled vocabularies as a Simple Knowledge Organization System (SKOS) concept collection, and are working toward alignment with SeaDataNet and other community-standard terms using the NERC Vocabulary Server (NVS). http://rvdata.us/

  1. FED-R2: concept and magnet design of a low-cost FED

    International Nuclear Information System (INIS)

    Williams, J.E.C.; Becker, H.; Blackfield, D.; Bobrov, E.; Bromberg, L.; Cohn, D.R.; Diatchenko, N.; LeClaire, R.

    1982-12-01

    High performance resistive magnet technology was used to develop a design for a compact, low cost version of the fusion engineering device FED. We refer to this design as FED-R2, for FED-resistive magnet design 2 to distinguish it from the larger resistive magnet design for FED which uses demountable coils (FED-R1). The main objectives of FED-R2 are: (1) to demonstrate reliable, quasi-steady state (long pulse, high duty factor) operation with Q/sub p/ approx. 5; (2) to demonstrate Q/sub p/ > 5 operation for a limited number of pulses; (3) to provide high neutron flux for irradiation of nuclear test modules with a total area greater tha 20m 2 ; (4) to utilize steady-state RF current drive if this option appears promising. Based upon the costing codes at the Fusion Engineering Design Center and upon TFTR costs, the estimated direct costs of FED-R2 would be on the range 380 to 460M, a factor of about 2 below that of the baseline FED design

  2. High-pressure synthesis and characterizations of the R2Pt2O7 pyrochlores.

    Science.gov (United States)

    Cai, Yunqi; Cui, Qi; Cheng, Jinguang; Dun, Zhiling; Zhou, Haidong; Ma, Jie; Cruz, C. Dela; Yan, Jiaqiang; Li, Xiang; Zhou, Jianshi

    Pyrochlore R2B2O7 where R3 + stands for rear-earth ion and B4 + for a nonmagnetic cation such as Sn4 +or Ti4 +consist of an important family of geometrically frustrated magnets, which have been the focus of extensive investigations over last decades. To further enlarge the R2B2O7, we have chosen to stabilize the Pt-based cubic pyrochlores under HPHT conditions for two reasons: (1) Pt4 + is in a low-spin state which ionic radius is located in between Ti4 + (0.605\\x85) and Sn4 + (0.69\\x85), and (2) Pt4 + has a spatially much more extended 5d orbitals and thus enhanced Pt 5d-O 2p hybridizations that might modify the local anisotropic exchange interactions. Such an effect has never been taken into account in the previous studies. In this work, we will present the detailed characterizations on the pyrochlores R2Pt2O7 obtained under HPHT conditions. This work is supported by the National Science Foundation of China (Grant Nos.11304371, 11574377), part of the work was supported by the CEM, and NSF MRSEC, under Grant DMR-1420451, and Grant No. NSF-DMR-1350002.

  3. Antifungal potential of Bacillus vallismortis R2 against different phytopathogenic fungi

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, P.K.; Kaur, J.; Saini, H.S.

    2015-07-01

    The cash crops grown in an agro-climatic region are prone to infection by various fungal pathogens. The use of chemical fungicides over the years has resulted in emergence of resistant fungal strains, thereby necessitating the development of effective and environmental friendly alternatives. The natural antagonistic interactions among different microbial populations have been exploited as an eco-friendly approach for controlling fungal pathogens resistant to synthetic chemicals. Morphologically distinct bacterial cultures (150), isolated from rhizospheric soils of wheat, rice, onion and tomato plants were screened for their antifungal potential against seven phytopathogenic fungi prevalent in the State of Punjab (India). The bacterial isolate R2, identified as Bacillus vallismortis, supported more than 50% inhibition of different phytopathogenic fungi (Alternaria alternata, Rhizoctonia oryzae, Fusarium oxysporum, Fusarium moniliforme, Colletotrichum sp, Helminthosporium sp and Magnaporthe grisea) in dual culture plate assay. The thin layer chromatography based bio-autography of acid-precipitated biomolecules (APB) indicated the presence of more than one type of antifungal molecule, as evidenced from zones of inhibition against the respective fungal pathogen. The initial analytical studies indicated the presence of surfactin, iturin A and fengycin-like compounds in APB. The antifungal activity of whole cells and APB of isolate R2 was evaluated by light and scanning electron microscopy. The wheat grains treated with APB and exposed to spores of A. alternata showed resistance to the development of black point disease, thereby indicating the potential application of R2 and its biomolecules at field scale level. (Author)

  4. R2* mapping for brain iron: associations with cognition in normal aging.

    Science.gov (United States)

    Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2015-02-01

    Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Magnetic phase transitions in R2Fe17 compounds under pressure

    International Nuclear Information System (INIS)

    Arnold, Z.; Kamarad, J.

    1994-01-01

    The effect of the pressure up to 1.4 GPa on the Curie temperature T c in the R 2 Fe 17 intermetallics with R = Nd, Er and Y was measured using a low field susceptibility technique. The identical character of the temperature dependence of susceptibility χ(T) of the R 2 Fe 17 intermetallics observed at ambient pressure (sharp step-like drop at T c ) is preserved at high pressures only in the case of Nd 2 Fe 17 . Pronounced broadening and splitting of the sharp drop of χ(T) was observed in Er 2 Fe 17 and Y 2 Fe 17 respectively. The initial pressure slopes of dTc/dp are large and negative for all studied compounds, having nearly the same values (dTc/dp = -36K/GPa for Nd 2 Fe 17 compound). The results are discussed from the point of view of the sensitivity of T c on the crystal structure, the number of nearest neighbors of Fe atoms and the possible effect of disordered structures in the R 2 Fe 17 intermetallics

  6. Apoptosis Induction by Targeting Interferon Gamma Receptor 2 (IFNgammaR2) in Prostate Cancer: Ligand (IFNgamma) Independent Novel Function of IFNgammaR2 as a Bax Inhibitor

    Science.gov (United States)

    2016-10-01

    Cisplatin (2uM, 30 hrs) PN (5uM, 55hrs) + Cisplatin (2uM, 30 hrs) •  Thorough studies are needed to examine the unknown mechanism of IFNgR2 and Bax as well as...mouse xenograft model. Task3: To determine the mechanism of increased IFNγR2 expression in PCa. We found that NFkB inhibitor suppressed IFNγR2 expression...suggesting that hyper-activation of NFkB may be one of the mechanisms of IFNγR2 overexpression in PCa. These results support our hypothesis that

  7. A R2R3-MYB transcription factor from Epimedium sagittatum regulates the flavonoid biosynthetic pathway.

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    Full Text Available Herba epimedii (Epimedium, a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1 from Epimedium sagittatum (Sieb. Et Zucc. Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR and anthocyanidin synthase (ANS. In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants.

  8. A R2R3-MYB transcription factor from Epimedium sagittatum regulates the flavonoid biosynthetic pathway.

    Science.gov (United States)

    Huang, Wenjun; Sun, Wei; Lv, Haiyan; Luo, Ming; Zeng, Shaohua; Pattanaik, Sitakanta; Yuan, Ling; Wang, Ying

    2013-01-01

    Herba epimedii (Epimedium), a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs) have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1) from Epimedium sagittatum (Sieb. Et Zucc.) Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade) of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS). In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants.

  9. Rolling Deck to Repository (R2R): Technical Design - Experiences and Lessons (Invited)

    Science.gov (United States)

    Arko, R. A.; Carbotte, S. M.; Miller, S. P.; Chandler, C. L.; Ferrini, V.; Stocks, K.; Maffei, A. R.; Smith, S. R.; Bourassa, M. A.; McLean, S. J.; Alberts, J. C.

    2009-12-01

    The NSF-funded Rolling Deck to Repository (R2R) project envisions the academic research fleet as an integrated global observing system, with routine “underway” sensor data flowing directly from research vessels to a central shore-side repository. It is a complex endeavor involving many stakeholders - technicians at sea, data managers on shore, ship schedulers, clearance officers, funding agencies, National Data Centers, data synthesis projects, the science community, and the public - working toward a common goal of acquiring, documenting, archiving, evaluating, and disseminating high-quality scientific data. The technical design for R2R is guided by several key principles: 1) The data pipeline is modular, so that initial stages (e.g. inventory and review of data shipments, posting of catalog records and track maps) may proceed routinely for every cruise, while later stages (e.g. quality assessment and production of file-level metadata) may proceed at different rates for different data types; 2) Cruise documentation (e.g. sailing orders, review/release of data inventories, vessel profiles) is gathered primarily via an authenticated Web portal, linked with the UNOLS scheduling database to synchronize vocabularies and eliminate redundancies; and 3) Every data set will be documented and delivered to the appropriate National Data Center for long-term archiving and dissemination after proprietary holds are cleared, while R2R maintains a master cruise catalog that links all the data sets together. This design accommodates the diversity of instrument types, data volumes, and shipment schedules among fleet operators. During its pilot development period, R2R has solicited feedback at community workshops, UNOLS meetings, and conference presentations, including fleet-wide surveys of current practices and instrument inventories. Several vessel operators began submitting cruise data and documentation during the pilot, providing a test bed for database development and Web

  10. Decommissioning of the Nuclear Reactors R2 and R2-0 at Studsvik, Sweden. General Data as called for under Article 37 of the Euratom Treaty

    Energy Technology Data Exchange (ETDEWEB)

    2009-01-15

    This document describes the plans for decommissioning of the nuclear research and material test reactors R2 and R2-0, situated at the Studsvik site close to the city of Nykoeping, Sweden. The purpose of the document is to serve as information for the European Commission, and to fulfil the requirements of Article 37 of the Euratom Treaty. Studsvik is situated on the Baltic coast, about 20 km east of Nykoeping and 80 km southwest of Stockholm. The site comprises the reactors R2 and R2-0 and several facilities for material investigation and radioactive waste treatment and storage. The reactors were used for a number of different purposes from 1960 until June 2005, when they were shut down following a decision by the operator. Decommissioning of the reactor facility is planned to be completed in 2016 after dismantling and conditioning of radioactive parts and demolition of the facility. Solid and liquid radioactive wastes from the dismantling activities will be treated and stored on-site awaiting final disposal. The waste treatment facilities, which are situated in other buildings at the Studsvik site, are planned to continue operation during and after the decommissioning of the reactor facility. All nuclear fuel has been transferred to a separate storage facility and is being shipped to the US according to existing agreements. The objective of the planned dismantling activities is to achieve clearance of the facility to make it possible to either demolish the buildings or use them for other purposes. The operator has divided the planning for dismantling and demolition of the facility into three phases [1]: Dismantling 1, including primary system decontamination, dismantling of the reactors with systems in the reactor pool, draining, cleaning and temporary covering of the reactor pool. This phase has begun and is due to last till approximately December 2009. Dismantling 2, including dismantling of systems in the reactor facility, removal of equipment, radiological

  11. Development of a simple measurement method for GluR2 protein expression as an index of neuronal vulnerability

    Directory of Open Access Journals (Sweden)

    Chihiro Sugiyama

    2015-01-01

    Full Text Available In vitro estimating strategies for potential neurotoxicity are required to screen multiple substances. In a previous study, we showed that exposure to low-concentrations of some chemicals, such as organotin, decreased the expression of GluR2 protein, which is a subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA-type glutamate receptors, and led to neuronal vulnerability. This result suggested that GluR2 decreases as an index of neuronal cell sensitivity and vulnerability to various toxic insults. Accordingly, we developed a versatile method that is a large scale determination of GluR2 protein expression in the presence of environmental chemicals by means of AlphaLISA technology. Various analytical conditions were optimized, and then GluR2 protein amount was measured by the method using AlphaLISA. The GluR2 amounts were strongly correlated with that of measured by western blotting, which is currently used to determine GluR2 expression. An ideal standard curve could be written with the authentic GluR2 protein from 0 ng to 100 ng. Subsequently, twenty environmental chemicals were screened and nitenpyram was identified as a chemical which lead to decrease in GluR2 protein expression. This assay may provide a tool for detecting neurotoxic chemicals according to decreases in GluR2 protein expression.

  12. R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling.

    Science.gov (United States)

    Su, Rui; Dong, Lei; Li, Chenying; Nachtergaele, Sigrid; Wunderlich, Mark; Qing, Ying; Deng, Xiaolan; Wang, Yungui; Weng, Xiaocheng; Hu, Chao; Yu, Mengxia; Skibbe, Jennifer; Dai, Qing; Zou, Dongling; Wu, Tong; Yu, Kangkang; Weng, Hengyou; Huang, Huilin; Ferchen, Kyle; Qin, Xi; Zhang, Bin; Qi, Jun; Sasaki, Atsuo T; Plas, David R; Bradner, James E; Wei, Minjie; Marcucci, Guido; Jiang, Xi; Mulloy, James C; Jin, Jie; He, Chuan; Chen, Jianjun

    2018-01-11

    R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N 6 -methyladenosine (m 6 A) RNA modification in R-2HG-sensitive leukemia cells, which in turn decreases the stability of MYC/CEBPA transcripts, leading to the suppression of relevant pathways. Ectopically expressed mutant IDH1 and S-2HG recapitulate the effects of R-2HG. High levels of FTO sensitize leukemic cells to R-2HG, whereas hyperactivation of MYC signaling confers resistance that can be reversed by the inhibition of MYC signaling. R-2HG also displays anti-tumor activity in glioma. Collectively, while R-2HG accumulated in IDH1/2 mutant cancers contributes to cancer initiation, our work demonstrates anti-tumor effects of 2HG in inhibiting proliferation/survival of FTO-high cancer cells via targeting FTO/m 6 A/MYC/CEBPA signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.

    Directory of Open Access Journals (Sweden)

    Wyatt B Potter

    Full Text Available Tuberous sclerosis complex (TSC is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/- CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/- hippocampal slices. We also report that adult TSC2(+/- mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.

  14. Directed Evolution of Carbonyl Reductase from Rhodosporidium toruloides and Its Application in Stereoselective Synthesis of tert-Butyl (3R,5S)-6-Chloro-3,5-dihydroxyhexanoate.

    Science.gov (United States)

    Liu, Zhi-Qiang; Wu, Lin; Zhang, Xiao-Jian; Xue, Ya-Ping; Zheng, Yu-Guo

    2017-05-10

    tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is a key intermediate of atorvastatin and rosuvastatin synthesis. Carbonyl reductase RtSCR9 from Rhodosporidium toruloides exhibited excellent activity toward tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH). For the activity of RtSCR9 to be improved, random mutagenesis and site-saturation mutagenesis were performed. Three positive mutants were obtained (mut-Gln95Asp, mut-Ile144Lys, and mut-Phe156Gln). These mutants exhibited 1.94-, 3.03-, and 1.61-fold and 1.93-, 3.15-, and 1.97-fold improvement in the specific activity and k cat /K m , respectively. Asymmetric reduction of (S)-CHOH by mut-Ile144Lys coupled with glucose dehydrogenase was conducted. The yield and enantiomeric excess of (3R,5S)-CDHH reached 98 and 99%, respectively, after 8 h bioconversion in a single batch reaction with 1 M (S)-CHOH, and the space-time yield reached 542.83 mmol L -1 h -1 g -1 wet cell weight. This study presents a new carbonyl reductase for efficient synthesis of (3R,5S)-CDHH.

  15. Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

    Directory of Open Access Journals (Sweden)

    Rekosh David

    2008-05-01

    Full Text Available Abstract AIDS-associated, CCR5-tropic (R5 HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

  16. Molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 8 or r(8(::p12→q13.1:: associated with phenotypic abnormalities

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2016-12-01

    Conclusion: Mosaic sSMC(8 derived from r(8(::p12→q13.1:: can present phenotypic abnormalities. Chromosome 8q12 duplication syndrome should be included in differential diagnosis when an sSMC(8 contains 8q12.2 and CHD7.

  17. The onion (Allium cepa L. R2R3-MYB gene MYB1 regulates anthocyanin biosynthesis

    Directory of Open Access Journals (Sweden)

    Kathy Schwinn

    2016-12-01

    Full Text Available Bulb colour is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales. The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red, flavonols (pale yellow and chalcones (bright yellow. Flavonoid regulation is poorly characterised in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs that commonly activate anthocyanin (SG6, MYB1 or flavonol (SG7, MYB29 production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5. MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressd and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (A. sativum L. plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

  18. The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis

    Science.gov (United States)

    Schwinn, Kathy E.; Ngo, Hanh; Kenel, Fernand; Brummell, David A.; Albert, Nick W.; McCallum, John A.; Pither-Joyce, Meeghan; Crowhurst, Ross N.; Eady, Colin; Davies, Kevin M.

    2016-01-01

    Bulb color is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species. PMID:28018399

  19. Kinematic Study of Ionized and Molecular Gases in Ultracompact HII Region in Monoceros R2

    Science.gov (United States)

    Kim, Hwihyun; Lacy, John H.; Jaffe, Daniel Thomas

    2017-06-01

    Monoceros R2 (Mon R2) is an UltraCompact HII region (UCHII) surrounded by several PhotoDissociation Regions (PDRs). It is an excellent example to investigate the chemistry and physics of early stage of massive star formation due to its proximity (830pc) and brightness. Previous studies suggest that the wind from the star holds the ionized gas up against the dense molecular core and the higher pressure at the head drives the ionized gas along the shell. In order for the model to work, there should be evidence for dense molecular gas along the shell walls, irradiated by the UCHII region and perhaps entrained into the flow along the walls.We obtained the Immersion Grating INfrared Spectrograph (IGRINS) spectra of Mon R2 to study the kinematic patterns in the areas where ionized and molecular gases interact. The position-velocity maps from the high resolution (R~45,000) H- and K-band (1.4-2.5μm) IGRINS spectra demonstrate that the ionized gases (Brackett and Pfund series, He and Fe emission lines; Δv ≈ 40km/s) flow along the walls of the surrounding clouds. This is consistent with the model by Zhu et al. (2008). In the PV maps of the H2 emission lines there is no obvious motion (Δv ≈ 10km/s) of the molecular hydrogen right at the ionization boundary. This implies that the molecular gas is not taking part in the flow as the ionized gas is moving along the cavity walls.This work used the Immersion Grating Infrared Spectrograph (IGRINS) that was developed under a collaboration between the University of Texas at Austin and the Korea Astronomy and Space Science Institute (KASI) with the financial support of the US National Science Foundation (NSF; grant AST-1229522), of the University of Texas at Austin, and of the Korean GMTProject of KASI.

  20. The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis.

    Science.gov (United States)

    Schwinn, Kathy E; Ngo, Hanh; Kenel, Fernand; Brummell, David A; Albert, Nick W; McCallum, John A; Pither-Joyce, Meeghan; Crowhurst, Ross N; Eady, Colin; Davies, Kevin M

    2016-01-01

    Bulb color is an important consumer trait for onion ( Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic ( Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum maju s of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

  1. Neutron scattering study on R2PdSi3 (R=Ho,Er,Tm) compounds

    International Nuclear Information System (INIS)

    Tang, Fei

    2010-01-01

    Previous studies on the family of inter-metallic rare-earth compounds R 2 PdSi 3 revealed multifaceted magnetic properties, for instance, spin-glass like behavior. Experimental observations include: Signs of a crystallographic superstructure, complicated magnetic structures both in zero field and in applied magnetic fields as well as a generic phase in applied fields for compounds in the series with the heavy rare-earths R=Gd, Tb, Dy, Ho, Er and Tm. This thesis expands the studies on the magnetic properties of R 2 PdSi 3 employing mainly neutron scattering on single crystals with the focus on the compounds with R=Ho, Er and Tm. A detailed analysis of the crystallographic superstructure using modulation wave approach and group theory is presented. The resulting structure implies the existence of two different rare-earth sites with reduced symmetry and an arrangement of the different sites according to sequences as determined by the superstructure. It is shown that the reduced symmetry of the rare-earth sites is explicitly observed in the energy spectra of inelastic neutron scattering. The results on the magnetic structures and excitations are shown and discussed in the framework of the superstructure model. Specifically the generic phase in applied fields is interpreted as a direct consequence of the crystallographic superstructure. It is rather unusual that a crystallographic superstructure is playing such a decisive, and through the field dependence also tunable role in determining the magnetic properties as observed in R 2 PdSi 3 . The mediating interactions between the crystallographic part and the magnetic part of the system are discussed. (orig.)

  2. Predictive power of Brazilian equity fund performance using R2 as a measure of selectivity

    Directory of Open Access Journals (Sweden)

    Marcelo dos Santos Guzella

    2017-03-01

    Full Text Available ABSTRACT This paper aimed to investigate the impact of levels of selectivity on the performance of equity funds using a methodology applied for the first time ever (as far as we know in the Brazilian market. As an indicator of the activity level of a fund, we proposed the coefficient of determination (R2 of the regression of its returns over market returns. In total, 867 funds were analyzed in the period between November 2004 and October 2014. The hypothesis tested is that more selective funds perform better to compensate for their higher operating costs. This hypothesis was confirmed in the Brazilian market. Dynamic equally-weighted portfolios of funds were simulated, according to their past R2 and alphas, with monthly rebalancing and 12-month moving windows. The portfolio of the most selective funds had a Sharpe ratio of 0.0494, on a monthly basis, while the portfolio of the least selective funds had a Sharpe ratio of -0.0314. Performance was also higher in evaluations involving excess returns, Jensen’s alpha, and accumulated returns, as well as when compared to randomly selected portfolios. Moreover, past performance (as measured by Jensen’s alpha was also a predictor of future performance. Particularly, the portfolio composed by funds with a higher past alpha and lower past R2 presented a Sharpe ratio of 0.1483 and a Jensen’s alpha of 0.87% (significant at 1%, while the one composed of funds with a lower past alpha and lower activity level presented a Sharpe ratio of -0.0673 and an alpha of -0.32% (also significant at 1%.

  3. R2WinBUGS: A Package for Running WinBUGS from R

    Directory of Open Access Journals (Sweden)

    Sibylle Sturtz

    2005-01-01

    Full Text Available The R2WinBUGS package provides convenient functions to call WinBUGS from R. It automatically writes the data and scripts in a format readable by WinBUGS for processing in batch mode, which is possible since version 1.4. After the WinBUGS process has finished, it is possible either to read the resulting data into R by the package itself--which gives a compact graphical summary of inference and convergence diagnostics--or to use the facilities of the coda package for further analyses of the output. Examples are given to demonstrate the usage of this package.

  4. Power measurement in the boiling capsules in R2 using delayed neutron detector

    International Nuclear Information System (INIS)

    Roennberg, G.

    1979-03-01

    LWR fuel testing is performed in the R2 reactor by irradiation in both loops and so-called boiling capsules. The loops have forced cooling, and the power can be measured calorimetrically by conventional instrumentation. The boiling capsules have convection cooling, and it has therefore been necessary to develop a special technique for power measurement, the delayed neutron detector (DND). The DND is a pneumatic rabbit system, which activates small uranium samples in the boiling capsules and counts the delayed neutrons for determination of the fission rate. This report describes the equipment used, the procedure of measurement, and the method of evaluation. (atuhor)

  5. Recursion Formulae for Obtaining Surfaces with Constant Mean Curvature in R2,1

    International Nuclear Information System (INIS)

    Tian Yongbo; Nan Zhijie; Tian Chou

    2007-01-01

    Though the Baecklund transformation on time-like surfaces with constant mean curvature surfaces in R 2,1 has been obtained, it is not easy to obtain corresponding surfaces because the procedure of solving the related integrable system cannot be avoided when the Baecklund transformation is used. For sake of this, in this article, some special work is done to reform the Baecklund transformation to a recursion formula, by which we can construct time-like surfaces with constant mean curvature form known ones just by quadrature procedure.

  6. Site-specific magnetic anisotropies in R2Fe14B systems

    Science.gov (United States)

    Yoshioka, T.; Tsuchiura, H.

    2018-04-01

    The local magnetic anisotropy of R ions in R2Fe14B (R = Dy, Ho) systems is studied based on a microscopic effective spin model constructed from the information obtained by using first-principles calculations. By taking into account up to 6-th order crystal electric field parameters, the model satisfactory describes the observed magnetization curves and the temperature dependence of anisotropy constants. We found that at low temperatures, the noncollinear structure appears in the Ho2Fe14B system reflecting the local magnetic anisotropy.

  7. Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations

    DEFF Research Database (Denmark)

    Broendberg, Anders Krogh; Nielsen, Jens Cosedis; Bjerre, Jesper

    2017-01-01

    probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope).As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years...... (IQR, 10-33) vs 43 years (IQR, 25-54), pnear-fatal events (ASCD, SCD) (16vs5, p... events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives....

  8. Degradation and stability of R2R manufactured polymer solar cells

    DEFF Research Database (Denmark)

    Norrman, Kion; Krebs, Frederik C

    2009-01-01

    Polymer solar cells have many advantages such as light weight, flexibility, environmental friendliness, low thermal budget, low cost and most notably very fast modes of production by printing techniques. Production experiments have shown that it is highly feasible with existing technology to mass...... produce polymer solar cells at a very low cost. We have employed state-of-the-art analytical techniques to address the challenging issues of degradation and stability of R2R manufactured devices. We have specifically studied the relative effect of oxygen and water on the operational devices in regard...

  9. Rolling Deck to Repository (R2R): Linking and Integrating Data for Oceanographic Research

    Science.gov (United States)

    Arko, R. A.; Chandler, C. L.; Clark, P. D.; Shepherd, A.; Moore, C.

    2012-12-01

    The Rolling Deck to Repository (R2R) program is developing infrastructure to ensure the underway sensor data from NSF-supported oceanographic research vessels are routinely and consistently documented, preserved in long-term archives, and disseminated to the science community. We have published the entire R2R Catalog as a Linked Data collection, making it easily accessible to encourage linking and integration with data at other repositories. We are developing the R2R Linked Data collection with specific goals in mind: 1.) We facilitate data access and reuse by providing the richest possible collection of resources to describe vessels, cruises, instruments, and datasets from the U.S. academic fleet, including data quality assessment results and clean trackline navigation. We are leveraging or adopting existing community-standard concepts and vocabularies, particularly concepts from the Biological and Chemical Oceanography Data Management Office (BCO-DMO) ontology and terms from the pan-European SeaDataNet vocabularies, and continually re-publish resources as new concepts and terms are mapped. 2.) We facilitate data citation through the entire data lifecycle from field acquisition to shoreside archiving to (ultimately) global syntheses and journal articles. We are implementing globally unique and persistent identifiers at the collection, dataset, and granule levels, and encoding these citable identifiers directly into the Linked Data resources. 3.) We facilitate linking and integration with other repositories that publish Linked Data collections for the U.S. academic fleet, such as BCO-DMO and the Index to Marine and Lacustrine Geological Samples (IMLGS). We are initially mapping datasets at the resource level, and plan to eventually implement rule-based mapping at the concept level. We work collaboratively with partner repositories to develop best practices for URI patterns and consensus on shared vocabularies. The R2R Linked Data collection is implemented as a

  10. Rolling Deck to Repository (R2R): Big Data and Standard Services for the Fleet Community

    Science.gov (United States)

    Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Smith, S. R.; Stocks, K. I.

    2014-12-01

    The Rolling Deck to Repository (R2R; http://rvdata.us/) program curates underway environmental sensor data from the U.S. academic oceanographic research fleet, ensuring data sets are routinely and consistently documented, preserved in long-term archives, and disseminated to the science community. Currently 25 in-service vessels contribute 7 terabytes of data to R2R each year, acquired from a full suite of geophysical, oceanographic, meteorological, and navigational sensors on over 400 cruises worldwide. To accommodate this large volume and variety of data, R2R has developed highly efficient stewardship procedures. These include scripted "break out" of cruise data packages from each vessel based on standard filename and directory patterns; automated harvest of cruise metadata from the UNOLS Office via Web Services and from OpenXML-based forms submitted by vessel operators; scripted quality assessment routines that calculate statistical summaries and standard ratings for selected data types; adoption of community-standard controlled vocabularies for vessel codes, instrument types, etc, provided by the NERC Vocabulary Server, in lieu of maintaining custom local term lists; and a standard package structure based on the IETF BagIt format for delivering data to long-term archives. Documentation and standard post-field products, including quality-controlled shiptrack navigation data for every cruise, are published in multiple services and formats to satisfy a diverse range of clients. These include Catalog Service for Web (CSW), GeoRSS, and OAI-PMH discovery services via a GeoNetwork portal; OGC Web Map and Feature Services for GIS clients; a citable Digital Object Identifier (DOI) for each dataset; ISO 19115-2 standard geospatial metadata records suitable for submission to long-term archives as well as the POGO global catalog; and Linked Open Data resources with a SPARQL query endpoint for Semantic Web clients. R2R participates in initiatives such as the Ocean Data

  11. 75 FR 3471 - International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the...

    Science.gov (United States)

    2010-01-21

    ...] International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of... the availability of a guidance entitled ``M3(R2) Nonclinical Safety Studies for the Conduct of Human... auspices of the International Conference on Harmonisation of Technical Requirements for Registration of...

  12. Design Concepts of Emergency Response Robot Platform K-R2D2

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Sun Young; Jeong, Kyungmin [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    From the analysis for various mobile robots competed in DARPA Robotics Challenge, there are some drawbacks in using two or four legs because bipedal locomotion is not yet suitable for maintaining stability and quadrupedal locomotion is difficult to go through narrow aisles. Motivated by the above observations, we propose a K-R2D2 robot platform with three legs arranged in the form of a triangle like as R2-D2 robot which is a fictional robot character in the Star Wars movies. This robot has 3 legs with tracks in each sole of the leg. It is statically stable since there are three contact points to ground. In addition, three legs are also possible to design a structure walking stairs that can expand and contract in the vertical direction. This paper has presented the conceptual design, it is developed on the purpose of quick response instead of emergent workers to the extreme conditions disasters. This robot is emergency response robot platform KR2D2 with three legs, which is statically stable to walk or wheel depending on the terrains and move quickly as possible as on uneven terrain or stairs.

  13. Shadow corrosion testing in the INCA facility in the Studsvik R2 reactor

    International Nuclear Information System (INIS)

    Nystrand, A.C.; Lassing, A.

    1999-01-01

    Shadow corrosion is a phenomenon which occurs when zirconium alloys are in contact with or in proximity to other metallic objects in a boiling water reactor environment (BWR, RBMK, SGHWR etc.). An enhanced corrosion occurs on the zirconium alloy with the appearance of a 'shadow' of the metallic object. The magnitude of the shadow corrosion can be significant, and is potentially limiting for the lifetime of certain zirconium alloy components in BWRs and other reactors with a similar water chemistry. In order to evaluate the suitability of the In-Core Autoclave (INCA) in the Studsvik R2 materials testing reactor as an experimental facility for studying shadow corrosion, a demonstration test has been performed. A number of test specimens consisting of Zircaloy-2 tubing in contact with Inconel were exposed in an oxidising water chemistry. Some of the specimens were placed within the reactor core and some above the core. The conclusion of this experiment after post irradiation examination is that it is possible to use the INCA facility in the Studsvik R2 reactor to develop a significant level of shadow corrosion after only 800 hours of irradiation. (author)

  14. Design Concepts of Emergency Response Robot Platform K-R2D2

    International Nuclear Information System (INIS)

    Noh, Sun Young; Jeong, Kyungmin

    2016-01-01

    From the analysis for various mobile robots competed in DARPA Robotics Challenge, there are some drawbacks in using two or four legs because bipedal locomotion is not yet suitable for maintaining stability and quadrupedal locomotion is difficult to go through narrow aisles. Motivated by the above observations, we propose a K-R2D2 robot platform with three legs arranged in the form of a triangle like as R2-D2 robot which is a fictional robot character in the Star Wars movies. This robot has 3 legs with tracks in each sole of the leg. It is statically stable since there are three contact points to ground. In addition, three legs are also possible to design a structure walking stairs that can expand and contract in the vertical direction. This paper has presented the conceptual design, it is developed on the purpose of quick response instead of emergent workers to the extreme conditions disasters. This robot is emergency response robot platform KR2D2 with three legs, which is statically stable to walk or wheel depending on the terrains and move quickly as possible as on uneven terrain or stairs

  15. Minimal $R+R^2$ Supergravity Models of Inflation Coupled to Matter

    CERN Document Server

    Ferrara, S

    2014-01-01

    The supersymmetric extension of "Starobinsky" $R+\\alpha R^2$ models of inflation is particularly simple in the "new minimal" formalism of supergravity, where the inflaton has no scalar superpartners. This paper is devoted to matter couplings in such supergravity models. We show how in the new minimal formalism matter coupling presents certain features absent in other formalisms. In particular, for the large class of matter couplings considered in this paper, matter must possess an R-symmetry, which is gauged by the vector field which becomes dynamical in the "new minimal" completion of the $R+\\alpha R^2$ theory. Thus, in the dual formulation of the theory, where the gauge vector is part of a massive vector multiplet, the inflaton is the superpartner of the massive vector of a nonlinearly realized R-symmetry. The F-term potential of this theory is of no-scale type, while the inflaton potential is given by the D-term of the gauged R-symmetry. The absolute minimum of the potential is always exactly supersymmetri...

  16. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    Science.gov (United States)

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  17. Facilitating Semantic Interoperability Among Ocean Data Systems: ODIP-R2R Student Outcomes

    Science.gov (United States)

    Stocks, K. I.; Chen, Y.; Shepherd, A.; Chandler, C. L.; Dockery, N.; Elya, J. L.; Smith, S. R.; Ferreira, R.; Fu, L.; Arko, R. A.

    2014-12-01

    With informatics providing an increasingly important set of tools for geoscientists, it is critical to train the next generation of scientists in information and data techniques. The NSF-supported Rolling Deck to Repository (R2R) Program works with the academic fleet community to routinely document, assess, and preserve the underway sensor data from U.S. research vessels. The Ocean Data Interoperability Platform (ODIP) is an EU-US-Australian collaboration fostering interoperability among regional e-infrastructures through workshops and joint prototype development. The need to align terminology between systems is a common challenge across all of the ODIP prototypes. Five R2R students were supported to address aspects of semantic interoperability within ODIP. Developing a vocabulary matching service that links terms from different vocabularies with similar concept. The service implements Google Refine reconciliation service interface such that users can leverage Google Refine application as a friendly user interface while linking different vocabulary terms. Developing Resource Description Framework (RDF) resources that map Shipboard Automated Meteorological Oceanographic System (SAMOS) vocabularies to internationally served vocabularies. Each SAMOS vocabulary term (data parameter and quality control flag) will be described as an RDF resource page. These RDF resources allow for enhanced discoverability and retrieval of SAMOS data by enabling data searches based on parameter. Improving data retrieval and interoperability by exposing data and mapped vocabularies using Semantic Web technologies. We have collaborated with ODIP participating organizations in order to build a generalized data model that will be used to populate a SPARQL endpoint in order to provide expressive querying over our data files. Mapping local and regional vocabularies used by R2R to those used by ODIP partners. This work is described more fully in a companion poster. Making published Linked Data

  18. Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers.

    Science.gov (United States)

    Hamill, Terence G; Krause, Stephen; Ryan, Christine; Bonnefous, Celine; Govek, Steve; Seiders, T Jon; Cosford, Nicholas D P; Roppe, Jeffrey; Kamenecka, Ted; Patel, Shil; Gibson, Raymond E; Sanabria, Sandra; Riffel, Kerry; Eng, Waisi; King, Christopher; Yang, Xiaoqing; Green, Mitchell D; O'Malley, Stacey S; Hargreaves, Richard; Burns, H Donald

    2005-06-15

    Three metabotropic glutamate receptor subtype 5 (mGluR5) PET tracers have been labeled with either carbon-11 or fluorine-18 and their in vitro and in vivo behavior in rhesus monkey has been characterized. Each of these tracers share the common features of high affinity for mGluR5 (0.08-0.23 nM vs. rat mGluR5) and moderate lipophilicity (log P 2.8-3.4). Compound 1b was synthesized using a Suzuki or Stille coupling reaction with [11C]MeI. Compounds 2b and 3b were synthesized by a SNAr reaction using a 3-chlorobenzonitrile precursor. Autoradiographic studies in rhesus monkey brain slices using 2b and 3b showed specific binding in cortex, caudate, putamen, amygdala, hippocampus, most thalamic nuclei, and lower binding in the cerebellum. PET imaging studies in monkey showed that all three tracers readily enter the brain and provide an mGluR5-specific signal in all gray matter regions, including the cerebellum. The specific signal observed in the cerebellum was confirmed by the autoradiographic studies and saturation binding experiments that showed tracer binding in the cerebellum of rhesus monkeys. In vitro metabolism studies using the unlabeled compounds showed that 1a, 2a, and 3a are metabolized slower by human liver microsomes than by monkey liver microsomes. In vivo metabolism studies showed 3b to be long-lived in rhesus plasma with only one other more polar metabolite observed. (c) 2005 Wiley-Liss, Inc.

  19. GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism.

    Science.gov (United States)

    Fatemi, S Hossein; Folsom, Timothy D

    2015-09-01

    Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia, mood disorders, and autism. Abnormal expression of mRNA and protein for multiple GABA receptors has also been observed in multiple brain regions leading to alterations in the balance between excitatory/inhibitory signaling in the brain with potential profound consequences for normal cognition and maintenance of mood and perception. Altered expression of GABAA receptor subunits has been documented in fragile X mental retardation 1 (FMR1) knockout mice, suggesting that loss of its protein product, fragile X mental retardation protein (FMRP), impacts GABAA subunit expression. Recent postmortem studies from our laboratory have shown reduced expression of FMRP in the brains of subjects with schizophrenia, bipolar disorder, major depression, and autism. FMRP acts as a translational repressor and, under normal conditions, inhibits metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. In fragile X syndrome (FXS), the absence of FMRP is hypothesized to lead to unregulated mGluR5 signaling, ultimately resulting in the behavioral and intellectual impairments associated with this disorder. Our laboratory has identified changes in mGluR5 expression in autism, schizophrenia, and mood disorders. In the current review article, we discuss our postmortem data on GABA receptors, FMRP, and mGluR5 levels and compare our results with other laboratories. Finally, we discuss the interactions between these molecules and the potential for new therapeutic interventions that target these interconnected signaling systems. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. A predominance of R5-like HIV genotypes in vaginal secretions is associated with elevated plasma HIV-1 RNA levels and the absence of anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Lacour Nedra

    2008-07-01

    Full Text Available Abstract HIV expressed in genital secretions provides the inoculum from which transmitting variants are selected, both in sexual transmission and mother-to-infant transmission during partuition. Characterization of HIV levels and genotypes found in vaginal secretions and the impact of anti-retroviral therapy (ART on this virus can provide valuable insight for the prevention of HIV transmission. Vaginal HIV was evaluated in a cohort of 43 women attending a New Orleans HIV outpatient clinic. Predominant vaginal genotypes were characterized as R5- or X4-like by heteroduplex tracking analyses of the envelope V3 region. Most women (67.4% shed R5-like genotypes in vaginal secretions which was associated with elevated plasma HIV levels (≥ 10,000 copies HIV-RNA/mL and absence of ART. Because R5-like genotypes are more frequently associated with transmission, these observations suggest that the majority of women shedding HIV in genital secretions present a transmission risk. The levels of vaginal virus were similar between both groups, but shedding of X4-like genotypes was associated with lower plasma viral loads and the use of ART, suggesting that ART use may impact the genotypes of virus found in the female genital compartment.

  1. Crystal-fields at rare-earth sites in R2Fe14B compounds

    International Nuclear Information System (INIS)

    Adam, S.; Adam, G.; Burzo, E.

    1985-12-01

    Crystal-field effects are expected to be important in R 2 Fe 14 B compounds. Within a model-independent approach, it is proved that four distinct rare-earth sites exist with respect to the crystalline electric fields, namely, R(4f; z=0), R(4f; z=0.5 c), R(4g; z=0), and R(4g; z=0.5 c), and relationships are established between the corresponding crystal-fields coefficients. Further, generalized Stevens parametrizations of the crystal field coefficients are derived at three levels of approximation for the interatomic forces inside the crystal. A crystal lattice dressing effect upon the radial electronic integrals is found to occur, the magnitude of which depends on the deviation of the interatomic forces from Coulombian. Finally, computation of crystal-field coefficients in Nd 2 Fe 14 B leads to results which raise questions about the validity of the simple Coulomb point-charge model. (author)

  2. Problems with change in R2 as applied to theory of reasoned action research.

    Science.gov (United States)

    Trafimow, David

    2004-12-01

    The paradigm of choice for theory of reasoned action research seems to depend largely on the notion of change in variance accounted for (DeltaR2) as new independent variables are added to a multiple regression equation. If adding a particular independent variable of interest increases the variance in the dependent variable that can be accounted for by the list of independent variables, then the research is deemed to be 'successful', and the researcher is considered to have made a convincing argument about the importance of the new variable. In contrast to this trend, I present arguments that suggest serious problems with the paradigm, and conclude that studies on attitude-behaviour relations would advance the field of psychology to a far greater extent if researchers abandoned it.

  3. Experience with the RE fuel transition at the Studsvik R2 reactor

    International Nuclear Information System (INIS)

    Pazsit, I.; Saltvedt, K.

    1991-01-01

    Irradiation of 7 LEU fuel elements is underway in the Studsvik R2 reactor. Four of these have 490 g U-235, and three 320 g U-235 loading, and the enrichment is 19.7% for all of them. The irradiation of LEU fuel started in 1987. The heavier elements have burnup figures 67% (CERCA), 50% (B and W), 47% (NUKEM) and 19% (B and W). One of the lighter elements has reached a burnup of 65%. To support the whole-core conversion process, reactor physical calculations were performed to see if a one-step conversion is possible with a suitable fuel management strategy such that all HEU fuel is burned up. The calculations show that it is possible to perform such a conversion with fuel elements containing 400 g U-235. (orig.)

  4. Power cycling and ramp test in R-2 and Mihama Unit 2 for MHI PWR fuels

    International Nuclear Information System (INIS)

    Baba, T.; Takahashi, T.; Kubo, H.; Fujiwara, Y.; Kondo, Y.

    1983-01-01

    Up to the present time, Mitsubishi has manufactured approximately 3000 fuel assemblies for Japanese PWRs, of which performance in reactors is satisfactory under base load operation. For the forthcoming load following age in Japan, expected in mid eighties, Mitsubishi is performing various R and D programs, so that load following operation can be smoothly introduced with current good performance maintained. R and D programs consist of two phases. One is the verification and demonstration of power ramping and cycling capability of the current design fuels, and the other is the development of remedy fuels with more operational margin. This paper describes the recent results obtained for the former phase, especially for the following two programs: (1) Power cycling and ramp test in R-2; (2) Power ramp demonstration (PRD) in Mihama Unit 2 (PRD-1). PIE works for power cycling and ramp test rods have been almost completed. The second PRD will be performed early in 1983

  5. Micro-heterogeneities in R2O-RO-B2O3

    International Nuclear Information System (INIS)

    Kawazoe, H.; Kokumai, H.; Hosono, H.; Kanazawa, T.

    1980-01-01

    ESR of incorporated Cu 2+ was used in the detection of micro-inhomogeneity in xR 2 O x yMgO x (100-x-y)B 2 O 3 glasses. The inhomogeneous region determined by ESR was found to be far wider than that obtained by opalescence. It was concluded that in the glasses of x + y approx. 2+ tends to accelerate the simultaneous formation of boroxol and diborate groups and in the glasses of x + y approx. < 15, boroxol group and pyroborate ion. The conclusion was confirmed by laser Raman scattering. Molecular volume was measured over the whole glass-forming region to explore the correlation between the micro-structure and a macroscopic property of the glasses. It showed no marked change at the specified composition where micro-structure changed. (orig.)

  6. pyres: a Python wrapper for electrical resistivity modeling with R2

    Science.gov (United States)

    Befus, Kevin M.

    2018-04-01

    A Python package, pyres, was written to handle common as well as specialized input and output tasks for the R2 electrical resistivity (ER) modeling program. Input steps including handling field data, creating quadrilateral or triangular meshes, and data filtering allow repeatable and flexible ER modeling within a programming environment. pyres includes non-trivial routines and functions for locating and constraining specific known or separately-parameterized regions in both quadrilateral and triangular meshes. Three basic examples of how to run forward and inverse models with pyres are provided. The importance of testing mesh convergence and model sensitivity are also addressed with higher-level examples that show how pyres can facilitate future research-grade ER analyses.

  7. The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain

    Directory of Open Access Journals (Sweden)

    Amanda Lorraine Wright

    2012-04-01

    Full Text Available AMPA receptors are comprised of different combinations of GluR1-GluR4 (also known as GluA1-GluA4 and GluR-A to GluR-D subunits. The GluR2 subunit is subject to Q/R site RNA editing by the ADAR2 enzyme, which converts a codon for glutamine (Q, present in the GluR2 gene, to a codon for arginine (R found in the mRNA. AMPA receptors are calcium (Ca2+-permeable if they contain the unedited GluR2(Q subunit or if they lack the GluR2 subunit. While most AMPA receptors in the brain contain the edited GluR2(R subunit and are therefore Ca2+-impermeable, recent evidence suggests that Ca2+-permeable GluR2-lacking AMPA receptors are important in synaptic plasticity and learning. However, the presence of Ca2+-permeable AMPA receptors containing unedited GluR2 leads to excitotoxic cell loss. Recent studies have indicated that RNA editing of GluR2 is deregulated in diseases, such as amyotrophic lateral sclerosis (ALS, as well in acute neurodegenerative conditions, such as ischemia. More recently, studies have investigated the regulation of RNA editing and possible causes for its deregulation during disease. In this review, we will explore the role of GluR2 RNA editing in the healthy and diseased brain and outline new insights into the mechanisms that control this process.

  8. EXPOSE-R2: The Astrobiological ESA Mission on Board of the International Space Station

    Directory of Open Access Journals (Sweden)

    Elke Rabbow

    2017-08-01

    Full Text Available On July 23, 2014, the Progress cargo spacecraft 56P was launched from Baikonur to the International Space Station (ISS, carrying EXPOSE-R2, the third ESA (European Space Agency EXPOSE facility, the second EXPOSE on the outside platform of the Russian Zvezda module, with four international astrobiological experiments into space. More than 600 biological samples of archaea, bacteria (as biofilms and in planktonic form, lichens, fungi, plant seeds, triops eggs, mosses and 150 samples of organic compounds were exposed to the harsh space environment and to parameters similar to those on the Mars surface. Radiation dosimeters distributed over the whole facility complemented the scientific payload. Three extravehicular activities later the chemical samples were returned to Earth on March 2, 2016, with Soyuz 44S, having spent 588 days in space. The biological samples arrived back later, on June 18, 2016, with 45S, after a total duration in space of 531 days. The exposure of the samples to Low Earth Orbit vacuum lasted for 531 days and was divided in two parts: protected against solar irradiation during the first 62 days, followed by exposure to solar radiation during the subsequent 469 days. In parallel to the space mission, a Mission Ground Reference (MGR experiment with a flight identical Hardware and a complete flight identical set of samples was performed at the premises of DLR (German Aerospace Center in Cologne by MUSC (Microgravity User Support Center, according to the mission data either downloaded from the ISS (temperature data, facility status, inner pressure status or provided by RedShift Design and Engineering BVBA, Belgium (calculated ultra violet radiation fluence data. In this paper, the EXPOSE-R2 facility, the experimental samples, mission parameters, environmental parameters, and the overall mission and MGR sequences are described, building the background for the research papers of the individual experiments, their analysis and results.

  9. Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.

    Science.gov (United States)

    Ohishi, Akihiro; Nishida, Kentaro; Yamanaka, Yuri; Miyata, Ai; Ikukawa, Akiko; Yabu, Miharu; Miyamoto, Karin; Bansho, Saho; Nagasawa, Kazuki

    2016-01-01

    As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible.

  10. Radial Ultrashort TE Imaging Removes the Need for Breath-Holding in Hepatic Iron Overload Quantification by R2* MRI.

    Science.gov (United States)

    Tipirneni-Sajja, Aaryani; Krafft, Axel J; McCarville, M Beth; Loeffler, Ralf B; Song, Ruitian; Hankins, Jane S; Hillenbrand, Claudia M

    2017-07-01

    The objective of this study is to evaluate radial free-breathing (FB) multiecho ultrashort TE (UTE) imaging as an alternative to Cartesian FB multiecho gradient-recalled echo (GRE) imaging for quantitative assessment of hepatic iron content (HIC) in sedated patients and subjects unable to perform breath-hold (BH) maneuvers. FB multiecho GRE imaging and FB multiecho UTE imaging were conducted for 46 test group patients with iron overload who could not complete BH maneuvers (38 patients were sedated, and eight were not sedated) and 16 control patients who could complete BH maneuvers. Control patients also underwent standard BH multiecho GRE imaging. Quantitative R2* maps were calculated, and mean liver R2* values and coefficients of variation (CVs) for different acquisitions and patient groups were compared using statistical analysis. FB multiecho GRE images displayed motion artifacts and significantly lower R2* values, compared with standard BH multiecho GRE images and FB multiecho UTE images in the control cohort and FB multiecho UTE images in the test cohort. In contrast, FB multiecho UTE images produced artifact-free R2* maps, and mean R2* values were not significantly different from those measured by BH multiecho GRE imaging. Motion artifacts on FB multiecho GRE images resulted in an R2* CV that was approximately twofold higher than the R2* CV from BH multiecho GRE imaging and FB multiecho UTE imaging. The R2* CV was relatively constant over the range of R2* values for FB multiecho UTE, but it increased with increases in R2* for FB multiecho GRE imaging, reflecting that motion artifacts had a stronger impact on R2* estimation with increasing iron burden. FB multiecho UTE imaging was less motion sensitive because of radial sampling, produced excellent image quality, and yielded accurate R2* estimates within the same acquisition time used for multiaveraged FB multiecho GRE imaging. Thus, FB multiecho UTE imaging is a viable alternative for accurate HIC assessment

  11. Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [{sup 18}F]F-PEB

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shil [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: shailendra_patel@merck.com; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E. [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

    2007-11-15

    Binding of [{sup 18}F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([{sup 18}F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K{sub D}=0.1-0.15 nM, n{>=}3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [{sup 18}F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B{sub max}) measured using [{sup 18}F]F-PEB followed the rank order cortex{approx}caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B{sub max} being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [{sup 18}F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex{approx}caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum

  12. Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [18F]F-PEB

    International Nuclear Information System (INIS)

    Patel, Shil; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E.

    2007-01-01

    Binding of [ 18 F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([ 18 F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K D =0.1-0.15 nM, n≥3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [ 18 F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B max ) measured using [ 18 F]F-PEB followed the rank order cortex∼caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B max being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [ 18 F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex∼caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum) from all three species confirmed previous in vivo

  13. [Quantitative magnetic resonance imaging of brain iron deposition: comparison between quantitative susceptibility mapping and transverse relaxation rate (R2*) mapping].

    Science.gov (United States)

    Guan, Ji-Jing; Feng, Yan-Qiu

    2018-03-20

    To evaluate the accuracy and sensitivity of quantitative susceptibility mapping (QSM) and transverse relaxation rate (R2*) mapping in the measurement of brain iron deposition. Super paramagnetic iron oxide (SPIO) phantoms and mouse models of Parkinson's disease (PD) related to iron deposition in the substantia nigra (SN) underwent 7.0 T magnetic resonance (MR) scans (Bruker, 70/16) with a multi-echo 3D gradient echo sequence, and the acquired data were processed to obtain QSM and R2*. Linear regression analysis was performed for susceptibility and R2* in the SPIO phantoms containing 5 SPIO concentrations (30, 15, 7.5, 3.75 and 1.875 µg/mL) to evaluate the accuracy of QSM and R2* in quantitative iron analysis. The sensitivities of QSM and R2* mapping in quantitative detection of brain iron deposition were assessed using mouse models of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine (MPTP) in comparison with the control mice. In SPIO phantoms, QSM provided a higher accuracy than R2* mapping and their goodness-of-fit coefficients (R 2 ) were 0.98 and 0.89, respectively. In the mouse models of PD and control mice, the susceptibility of the SN was significantly higher in the PD models (5.19∓1.58 vs 2.98∓0.88, n=5; Pbrain iron deposition than R2*, and the susceptibility derived by QSM can be a potentially useful biomarker for studying PD.

  14. Evaluation of SAMe-TT2R2 Score on Predicting Success With Extended-Interval Warfarin Monitoring.

    Science.gov (United States)

    Hwang, Andrew Y; Carris, Nicholas W; Dietrich, Eric A; Gums, John G; Smith, Steven M

    2018-06-01

    In patients with stable international normalized ratios, 12-week extended-interval warfarin monitoring can be considered; however, predictors of success with this strategy are unknown. The previously validated SAMe-TT 2 R 2 score (considering sex, age, medical history, treatment, tobacco, and race) predicts anticoagulation control during standard follow-up (every 4 weeks), with lower scores associated with greater time in therapeutic range. To evaluate the ability of the SAMe-TT 2 R 2 score in predicting success with extended-interval warfarin follow-up in patients with previously stable warfarin doses. In this post hoc analysis of a single-arm feasibility study, baseline SAMe-TT 2 R 2 scores were calculated for patients with ≥1 extended-interval follow-up visit. The primary analysis assessed achieved weeks of extended-interval follow-up according to baseline SAMe-TT 2 R 2 scores. A total of 47 patients receiving chronic anticoagulation completed a median of 36 weeks of extended-interval follow-up. The median baseline SAMe-TT 2 R 2 score was 1 (range 0-5). Lower SAMe-TT 2 R 2 scores appeared to be associated with greater duration of extended-interval follow-up achieved, though the differences between scores were not statistically significant. No individual variable of the SAMe-TT 2 R 2 score was associated with achieved weeks of extended-interval follow-up. Analysis of additional patient factors found that longer duration (≥24 weeks) of prior stable treatment was significantly associated with greater weeks of extended-interval follow-up completed ( P = 0.04). Conclusion and Relevance: This pilot study provides limited evidence that the SAMe-TT 2 R 2 score predicts success with extended-interval warfarin follow-up but requires confirmation in a larger study. Further research is also necessary to establish additional predictors of successful extended-interval warfarin follow-up.

  15. (2R,5S)-Theaspirane Identified as the Kairomone for the Banana Weevil, Cosmopolites sordidus, from Attractive Senesced Leaves of the Host Banana, Musa spp.

    Science.gov (United States)

    Abagale, Samson A; Woodcock, Christine M; Hooper, Antony M; Caulfield, John C; Withall, David; Chamberlain, Keith; Acquaah, Samuel O; Van Emden, Helmut; Braimah, Haruna; Pickett, John A; Birkett, Michael A

    2018-04-12

    The principal active component produced by highly attractive senesced host banana leaves, Musa spp., for the banana weevil, Cosmopolites sordidus, is shown by coupled gas chromatography-electroantennography (GC-EAG), coupled GC-mass spectrometry (GC-MS), chemical synthesis and coupled enantioselective (chiral) GC-EAG to be (2R,5S)-theaspirane. In laboratory behaviour tests, the synthetic compound is as attractive as natural host leaf material and presents a new opportunity for pest control. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Synthesis, physical-chemical properties of 2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioacetohydrazides

    Directory of Open Access Journals (Sweden)

    O. A. Suhak

    2017-04-01

    Full Text Available Aim. Analysis of the scientific literature over the past decade has shown that large synthetic possibilities towards creating new and effective drug substances have heterocyclic compounds, in particular the derivatives of 1,2,4-triazole. 1,2,4-Triazole is a structural fragment of many synthetic drugs. The special interest cause ylidene hydrazides of 2-(5-R-1,2,4-triazole-3-ylthioacetic acids as potential biologically active compounds, among which highly effective medicines can be found. With the aim of finding new biologically active compounds the derivatives of 2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazides have been synthesized, their physical-chemical properties have been studied with the use of modern methods, namely elemental analysis, IR,1H-NMR spectroscopy, and their individuality by HPLC-MS. Materials and methods. N'-R1-еden-2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazides were received by adding aromatic (2-BrC6H4, 2,3-(OCH32C6H3, 3,5-(OCH32C6H3, 4-N(CH32C6H4, 3,4-F2C6H3, 2-NO2C6H4,4-NO2C6H4, 4-OHC6H4, 2-OHC6H4, 4-FC6H4, 2-CI-6-FC6H3 or heterocyclic (2-SC4H3, 5-NO2-2-C4H2O aldehyde to an equivalent amount of the appropriate 2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazide in the acetic acid medium. The study of physical-chemical properties of obtained compounds was carried out according to the methods outlined in SPU. Chromato-mass-spectral studies were performed on hazarding chromatograph Agilent 1260 Infinity HPLC equipped with mass spectrometer Agilent 6120 with ionization in electro-spray (ESI. Conclusion. This suggests the possibility for further study of biological action of the synthesized compounds. As a result of studies the N'-R1-eden-2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazides have been synthesized and their physical-chemical properties have been studied.

  17. An R2R3-MYB transcription factor regulates carotenoid pigmentation in Mimulus lewisii flowers.

    Science.gov (United States)

    Sagawa, Janelle M; Stanley, Lauren E; LaFountain, Amy M; Frank, Harry A; Liu, Chang; Yuan, Yao-Wu

    2016-02-01

    Carotenoids are yellow, orange, and red pigments that contribute to the beautiful colors and nutritive value of many flowers and fruits. The structural genes in the highly conserved carotenoid biosynthetic pathway have been well characterized in multiple plant systems, but little is known about the transcription factors that control the expression of these structural genes. By analyzing a chemically induced mutant of Mimulus lewisii through bulk segregant analysis and transgenic experiments, we have identified an R2R3-MYB, Reduced Carotenoid Pigmentation 1 (RCP1), as the first transcription factor that positively regulates carotenoid biosynthesis during flower development. Loss-of-function mutations in RCP1 lead to down-regulation of all carotenoid biosynthetic genes and reduced carotenoid content in M. lewisii flowers, a phenotype recapitulated by RNA interference in the wild-type background. Overexpression of this gene in the rcp1 mutant background restores carotenoid production and, unexpectedly, results in simultaneous decrease of anthocyanin production in some transgenic lines by down-regulating the expression of an activator of anthocyanin biosynthesis. Identification of transcriptional regulators of carotenoid biosynthesis provides the 'toolbox' genes for understanding the molecular basis of flower color diversification in nature and for potential enhancement of carotenoid production in crop plants via genetic engineering. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  18. Irradiation of Superheater Test Fuel Elements in the Steam Loop of the R2 Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Ravndal, F

    1967-12-15

    The design, fabrication, irradiation results, and post-irradiation examination for three superheater test fuel elements are described. During the spring of 1966 these clusters, each consisting of six fuel rods, were successfully exposed in the superheater loop No. 5 in the R2 reactor for a maximum of 24 days at a maximum outer cladding surface temperature of {approx} 650 deg C. During irradiation the linear heat rating of the rods was in the range 400-535 W/cm. The diameter of the UO{sub 2} pellets was 11.5 and 13.0 mm; the wall thickness of the 20/25 Nb and 20/35 cladding was in every case 0.4 mm. The diametrical gap between fuel and cladding was one of the main parameters and was chosen to be 0.05, 0.07 and 0.10 mm. These experiments, to be followed by one high cladding temperature irradiation ({approx} 750 deg C) and one long time irradiation ({approx} 6000 MWd/tU), were carried out to demonstrate the operational capability of short superheater test fuel rods at steady and transient operational environments for the Marviken superheater fuel elements and also to provide confirmation of design criteria for the same fuel elements.

  19. Evaluation of results from an in-pile creep test in the Studsvik R2 reactor

    Energy Technology Data Exchange (ETDEWEB)

    Pettersson, Kjell [Entropy Materials, Stockholm (Sweden)

    2002-01-01

    An in-pile creep test with bowing of cladding tubes has been performed in a hot water loop in the Studsvik R2 reactor . One test was performed in the core and one outside the core. The out-of-pile sample showed some minor primary creep strain while the in-pile specimen deformed at a steady rate of 5x10{sup -7}/h . However, when the results were compared to a broader data base of Zircaloy in-pile creep it became clear that the creep deformation observed is a primary creep which occurs before the irradiation creep in Zircaloy reaches a constant steady state creep rate. This primary stage is interpreted as a consequence of the development of an irradiation induced microstructure in Zircaloy which does not reach a steady state until a dose of about 10{sup 21} n/cm{sup 2} . At this stage the steady state irradiation creep starts. From this interpretation it is concluded that it is quite feasible to use the test method on pre-irradiated material in which it can be expected that the steady state will be reached already after short irradiation times.

  20. Excitation of chiral molecules and their hydrated by clusters by R2PI studies

    International Nuclear Information System (INIS)

    Satta, M.; Piccirillo, S.; Scuderia, D.; Paladini, A.; Della Vedova, L.; Filippi, A.; Speranza, M.; Giardini, A.

    2002-01-01

    Molecular clusters play a key role in the molecular scale explanation of macroscopic phenomena, being in between the isolated gas phase and the condensed phase. Thus, allowing to obtain information on intermolecular forces simply by studying the physicochemical properties of isolated clusters and to extend them macroscopic systems. A comprehensive study of the short-range forces operating in the molecular complexes between several chiral aromatic alcohols (M) and water (solv), through the application of mass resolved REMPI technique is reported. The experimental setup was composed by a supersonic molecular beam, two Nd-YAG pumped dye lasers and a time of flight mass spectrometer. The photoionization efficiency curves were obtained as follows: a) the first exciting laser (hv 1 ) was tuned on the S 1 0 transition of the species of interest; b) the laser intensity is lowered to about 1 % of the initial fluence to minimize the hv 1 absorption; c)a second laser (hv 2 ) is scanned through the cluster ionization and fragmentation threshold regions. The binding energy of the M-solv adduct was computed from the differences between its dissociative ionization threshold and the ionization threshold of bare M. The mass-resolved one colour R2PI excitation spectra of l-tetralol (THN R ), THN R -H 2 O, l i ndanol (I R ) and I R -H 2 O are given. (nevyjel)

  1. Anomalous magnetoresistance in antiferromagnetic polycrystalline materials R2Ni3Si5 (R=rare earth)

    International Nuclear Information System (INIS)

    Mazumdar, C.; Nigam, A.K.; Nagarajan, R.; Gupta, L.C.; Chandra, G.; Padalia, B.D.; Godart, C.; Vijayaraghaven, R.

    1997-01-01

    Magnetoresistance (MR) studies on polycrystalline R 2 Ni 3 Si 5 , (R=Y, rare earth) which order antiferromagnetically at low temperatures, are reported here. MR of the Nd, Sm, and Tb members of the series exhibit positive giant magnetoresistance, largest among polycrystalline materials (85%, 75%, and 58% for Tb 2 Ni 3 Si 5 , Sm 2 Ni 3 Si 5 , and Nd 2 Ni 3 Si 5 , respectively, at 4.4 K in a field of 45 kG). These materials have, to the best of our knowledge, the largest positive GMR reported ever for any bulk polycrystalline compounds. The magnitude of MR does not correlate with the rare earth magnetic moments. We believe that the structure of these materials, which can be considered as a naturally occurring multilayer of wavy planes of rare earth atoms separated by Ni endash Si network, plays a role. The isothermal MR of other members of this series (R=Pr,Dy,Ho) exhibits a maximum and a minimum, below their respective T N close-quote s. We interpret these in terms of a metamagnetic transition and short-range ferromagnetic correlations. The short-range ferromagnetic correlations seem to be dominant in the temperature region just above T N . copyright 1997 American Institute of Physics

  2. Assessing and Adapting Scientific Results for Space Weather Research to Operations (R2O)

    Science.gov (United States)

    Thompson, B. J.; Friedl, L.; Halford, A. J.; Mays, M. L.; Pulkkinen, A. A.; Singer, H. J.; Stehr, J. W.

    2017-12-01

    Why doesn't a solid scientific paper necessarily result in a tangible improvement in space weather capability? A well-known challenge in space weather forecasting is investing effort to turn the results of basic scientific research into operational knowledge. This process is commonly known as "Research to Operations," abbreviated R2O. There are several aspects of this process: 1) How relevant is the scientific result to a particular space weather process? 2) If fully utilized, how much will that result improve the reliability of the forecast for the associated process? 3) How much effort will this transition require? Is it already in a relatively usable form, or will it require a great deal of adaptation? 4) How much burden will be placed on forecasters? Is it "plug-and-play" or will it require effort to operate? 5) How can robust space weather forecasting identify challenges for new research? This presentation will cover several approaches that have potential utility in assessing scientific results for use in space weather research. The demonstration of utility is the first step, relating to the establishment of metrics to ensure that there will be a clear benefit to the end user. The presentation will then move to means of determining cost vs. benefit, (where cost involves the full effort required to transition the science to forecasting, and benefit concerns the improvement of forecast reliability), and conclude with a discussion of the role of end users and forecasters in driving further innovation via "O2R."

  3. Tumor VEGF-R2 imaging with Tc-99m DTPA-dextran-DC101

    International Nuclear Information System (INIS)

    Kim, E. M.; Jeong, H. J.; Kim, S. L.; Jeong, S. J.; Lee, C. M.; Kim, D. W.; Lim, S. T.; Sohn, M. H.

    2007-01-01

    Vascular endothelial growth factor (VEGF) and its receptor (fetal liver kinase 1/kinase insert domain-containing receptor) play an important role in vascular permeability and tumor angiogenesis. Here, we investigated the Tc-99m DC101-dextran for VEGF-R2 imaging in tumor xenografted mice. DTPA conjugated amino-dextran was synthesized and then this was reacted with sulfo-LC-SPDP. Synthesis was identified by 1H-NMR. DTPA-dextran-SPDP was reacted with DC101. Binding affinity was checked by ELISA assay. Female athymic nude mice bearing B16F10 tumors were each injected via the tail vein with about 18.5 MBq of the Tc-99m DTPA-dextran-DC101, Tc-99m DTPA-DC101 and I-131 DC101. Biodistribution was performed at 1, 6, and 24h. DTPA-dextran-DC101 bind to FLK-1 in a dose-dependent manner. And this was blocked by significantly by free DC101. Labeling efficiency was approximately above 99% at 24 hr. Tc-99m DTPA-DC101 and I-131 DC101 showed rapid liver uptake, whereas Tc-99m DTPA-dextran-DC101 weak liver uptake and kidney elimination. In biodistribution results, Tc-99m DTPA-dextran-DC101 showed rapid renal clearance, and increased tumor uptake according to the time. Conjugation of antibody with dextran polymer is responsible for the decreased liver uptake and increased tumor uptake

  4. Does Fat Suppression via Chemically Selective Saturation (CHESS) Affect R2*-MRI for Transfusional Iron Overload Assessment? A Clinical Evaluation at 1.5 and 3 Tesla

    Science.gov (United States)

    Krafft, Axel J.; Loeffler, Ralf B.; Song, Ruitian; Bian, Xiao; McCarville, M. Beth; Hankins, Jane S.; Hillenbrand, Claudia M.

    2015-01-01

    Purpose Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat-water oscillations in multi-echo gradient echo (mGRE) R2*-MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. Here, we investigate the effect of CHESS on R2* and describe a heuristic correction for the observed CHESS-induced R2* changes. Methods Eighty patients (49/31 female/male, mean age: 18.3±11.7 years) with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at 1.5T and 3T. Mean liver R2* values were evaluated using 3 published fitting approaches. Measured and model-corrected R2* values were compared and statistically analyzed. Results At 1.5T, CHESS led to a systematic R2* reduction (PCHESS-induced R2* bias after correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2* reductions were found at 3T. Conclusion The CHESS-induced R2* bias at 1.5T needs to be considered when applying R2*-LIC biopsy calibrations for clinical LIC assessment which were established without FS at 1.5T. The proposed model corrects the R2* bias and could therefore improve clinical iron overload assessment based on linear R2*-LIC calibrations. PMID:26308155

  5. Non-LTR R2 element evolutionary patterns: phylogenetic incongruences, rapid radiation and the maintenance of multiple lineages.

    Directory of Open Access Journals (Sweden)

    Andrea Luchetti

    Full Text Available Retrotransposons of the R2 superclade specifically insert within the 28S ribosomal gene. They have been isolated from a variety of metazoan genomes and were found vertically inherited even if their phylogeny does not always agree with that of the host species. This was explained with the diversification/extinction of paralogous lineages, being proved the absence of horizontal transfer. We here analyze the widest available collection of R2 sequences, either newly isolated from recently sequenced genomes or drawn from public databases, in a phylogenetic framework. Results are congruent with previous analyses, but new important issues emerge. First, the N-terminal end of the R2-B clade protein, so far unknown, presents a new zinc fingers configuration. Second, the phylogenetic pattern is consistent with an ancient, rapid radiation of R2 lineages: being the estimated time of R2 origin (850-600 Million years ago placed just before the metazoan Cambrian explosion, the wide element diversity and the incongruence with the host phylogeny could be attributable to the sudden expansion of available niches represented by host's 28S ribosomal genes. Finally, we detect instances of coexisting multiple R2 lineages showing a non-random phylogenetic pattern, strongly similar to that of the "library" model known for tandem repeats: a collection of R2s were present in the ancestral genome and then differentially activated/repressed in the derived species. Models for activation/repression as well as mechanisms for sequence maintenance are also discussed within this framework.

  6. R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5.

    Science.gov (United States)

    Cavarelli, Mariangela; Foglieni, Chiara; Rescigno, Maria; Scarlatti, Gabriella

    2013-05-01

    The gastrointestinal tract is a principal route of entry and site of persistence of human immunodeficiency virus type 1 (HIV-1). The intestinal mucosa, being rich of cells that are the main target of the virus, represents a primary site of viral replication and CD4(+) T-cell depletion. Here, we show both in vitro and ex vivo that HIV-1 of R5 but not X4 phenotype is capable of selectively triggering dendritic cells (DCs) to migrate within 30 min between intestinal epithelial cells to sample virions and transfer infection to target cells. The engagement of the chemokine receptor 5 on DCs and the viral envelope, regardless of the genetic subtype, drive DC migration. Viruses penetrating through transient opening of the tight junctions likely create a paracellular gradient to attract DCs. The formation of junctions with epithelial cells may initiate a haptotactic process of DCs and at the same time favour cell-to-cell viral transmission. Our findings indicate that HIV-1 translocation across the intestinal mucosa occurs through the selective engagement of DCs by R5 viruses, and may guide the design of new prevention strategies. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  7. The on-line synthesis of enzyme functionalized silica nanoparticles in a microfluidic reactor using polyethylenimine polymer and R5 peptide

    International Nuclear Information System (INIS)

    He Ping; Greenway, Gillian; Haswell, Stephen J

    2008-01-01

    A simple microfluidic reactor system is described for the effective synthesis of enzyme functionalized nanoparticles which offers many advantages over batch reactions, including excellent enzyme efficiencies. Better control of the process parameters in the microfluidic reactor system over batch based methodology enables the production of silica nanoparticles with the optimum size for efficient enzyme immobilization with long-term stability. The synthetic approach is demonstrated with glucose oxidase (GOD) and two different nucleation catalysts of similar molecular mass: the natural R5 peptide, and polyethylenimine (PEI) polymer. Near-quantitative immobilization of GOD in the nanoparticles is obtained using PEI; the immobilization is attributed to electrostatic interaction between PEI and GOD. This interaction, however, limits the mobility of the immobilized enzyme, producing orientation hindrance of the enzyme's active sites as compared to free GOD in solution. In contrast, when the GOD is immobilized inside the silica nanoparticles using R5, lower enzyme immobilization efficiencies are obtained compared to using PEI polymers; however, similar Michaelis-Menten kinetic parameters (i.e. Michaelis constant and turnover number) to those of free GOD are observed. Reactions were monitored in situ using simple, rapid, separation-free amperometric detection

  8. Peptide-derivatized SB105-A10 dendrimer inhibits the infectivity of R5 and X4 HIV-1 strains in primary PBMCs and cervicovaginal histocultures.

    Directory of Open Access Journals (Sweden)

    Isabella Bon

    Full Text Available Peptide dendrimers are a class of molecules that exhibit a large array of biological effects including antiviral activity. In this report, we analyzed the antiviral activity of the peptide-derivatized SB105-A10 dendrimer, which is a tetra-branched dendrimer synthetized on a lysine core, in activated peripheral blood mononuclear cells (PBMCs that were challenged with reference and wild-type human immunodeficiency virus type 1 (HIV-1 strains. SB105-A10 inhibited infections by HIV-1 X4 and R5 strains, interfering with the early phases of the viral replication cycle. SB105-A10 targets heparan sulfate proteoglycans (HSPGs and, importantly, the surface plasmon resonance (SPR assay revealed that SB105-A10 strongly binds gp41 and gp120, most likely preventing HIV-1 attachment/entry through multiple mechanisms. Interestingly, the antiviral activity of SB105-A10 was also detectable in an organ-like structure of human cervicovaginal tissue, in which SB105-A10 inhibited the HIV-1ada R5 strain infection without altering the tissue viability. These results demonstrated the strong antiviral activity of SB105-A10 and suggest a potential microbicide use of this dendrimer to prevent the heterosexual transmission of HIV-1.

  9. The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro

    Directory of Open Access Journals (Sweden)

    Tabolacci Elisabetta

    2012-03-01

    Full Text Available Abstract Background Fragile X syndrome (FXS, the leading cause of inherited mental retardation, is due to expansion and methylation of a CGG sequence in the FMR1 gene, which result in its silencing and consequent absence of FMRP protein. This absence causes loss of repression of metabotropic glutamate receptor 5 (mGluR5-mediated pathways resulting in the behavioral and cognitive impairments associated with FXS. In a randomized, double-blind trial it was recently demonstrated a beneficial effect of AFQ056, a selective inhibitor of metabotrobic glutamate receptor type 5 (mGluR5, on fully methylated FXS patients respect to partially methylated FXS ones. Methods To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, here we treated three FXS lymphoblastoid cell lines and one normal control male line. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. To assess the methylation status of the FMR1 gene promoter it was carried out a bisulphite sequencing analysis. Results Both FMR1-mRNA levels and DNA methylation were unmodified with respect to untreated controls. Conclusions These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1.

  10. Production, extraction and characterization of exopolysaccharides produced by the native Leuconostoc pseudomesenteroides R2 strain

    Directory of Open Access Journals (Sweden)

    Elinalva M. Paulo

    2012-06-01

    Full Text Available The genus Leuconostoc belongs to a group of lactic acid bacteria usually isolated from fermented vegetables, which includes species involved in the production of exopolysaccharides (EPS. These biopolymers possess considerable commercial potential. Because of the wide variety of industrial applications of EPS, this study aimed to produce and characterize the native exopolysaccharide strain Leuconostoc pseudomesenteroides R2, which was isolated from cabbage collected in a semi-arid region of Bahia. We employed the following conditions for the production of EPS: 10.7% sucrose, pH 8.2, without agitation and incubation at 28ºC for 30 hours. The fermentation broth was treated with ethanol and generated two types of polysaccharide substances (EPS I and EPS II. The identification of EPS I and EPS II was conducted using FT-IR, ¹H, 13C and DEPT-135 NMR spectra. The two substances were identified as linear dextran α polysaccharides (1 → 6 which indicated different characteristics with respect to thermal analysis and density of free packaging, viscosity and time of solubilization. Both dextrans are of low density, possess high thermal stability and exhibited the behavior characteristic of pseudoplastic polymers.O gênero Leuconostoc pertence a um grupo de bactérias lácticas normalmente isoladas de vegetais fermentados, que inclui espécies envolvidas na produção de exopolissacarídeos (EPS. Esses biopolímeros possuem potencial comercial considerável. Devido à grande variedade de aplicações industriais, de EPS, o presente estudo teve como objetivo produzir e caracterizar o nativo exopolissacarídeo cepa Leuconostoc pseudomesenteroides R2, que foi isolado de repolho coletado em uma região semi-árida da Bahia. Utilizamos as seguintes condições para a produção de EPS: 10,7% de sacarose, pH 8,2, sem agitação e incubação a 28º C por 30 horas. O caldo fermentado foi tratado com etanol, gerando dois tipos de substâncias de polissacar

  11. Rolling Deck to Repository (R2R): Products and Services for the U.S. Research Fleet Community

    Science.gov (United States)

    Arko, R. A.; Carbotte, S. M.; Chandler, C. L.; Smith, S. R.; Stocks, K. I.

    2016-02-01

    The Rolling Deck to Repository (R2R) program is working to ensure open access to environmental sensor data routinely acquired by the U.S. academic research fleet. Currently 25 vessels deliver 7 TB/year of data to R2R from a suite of geophysical, oceanographic, meteorological, and navigational sensors on over 400 cruises worldwide. R2R ensures these data are preserved in trusted repositories, discoverable via standard protocols, and adequately documented for reuse. R2R has recently expanded to include the vessels Sikuliaq, operated by the University of Alaska; Falkor, operated by the Schmidt Ocean Institute; and Ronald H. Brown and Okeanos Explorer, operated by NOAA. R2R maintains a master catalog of U.S. research cruises, currently holding over 4,670 expeditions including vessel and cruise identifiers, start/end dates and ports, project titles and funding awards, science parties, dataset inventories with instrument types and file formats, data quality assessments, and links to related content at other repositories. Standard post-field cruise products are published including shiptrack navigation, near-real-time MET/TSG data, underway geophysical profiles, and CTD profiles. Software tools available to users include the R2R Event Logger and the R2R Nav Manager. A Digital Object Identifier (DOI) is published for each cruise, original field sensor dataset, standard post-field product, and document (e.g. cruise report) submitted by the science party. Scientists are linked to personal identifiers such as ORCIDs where available. Using standard identifiers such as DOIs and ORCIDs facilitates linking with journal publications and generation of citation metrics. R2R collaborates in the Ocean Data Interoperability Platform (ODIP) to strengthen links among regional and national data systems, populates U.S. cruises in the POGO global catalog, and is working toward membership in the DataONE alliance. It is a lead partner in the EarthCube GeoLink project, developing Semantic Web

  12. Use of the p-SINE1-r2 in inferring evolutionary relationships of Thai rice varieties with AA genome

    Directory of Open Access Journals (Sweden)

    Preecha Prathepha

    2006-01-01

    Full Text Available In a previous study we described the prevalence and distribution in Thailand of the retroposon p- SINE1-r2, in the intron 10 of the waxy gene in cultivated and wild rice with the AA genome. In this study, additional varieties of rice were collected and sequencing was used to further characterize p-SINE1-r2. It was found that the length of the p-SINE1-r2 nucleotide sequences was about 125 bp, flanked by identical direct repeats of a 14 bp sequence. These sequences were compared and found to be similar to the sequences of p- SINE1-r2 found in Nipponbare, a rice strain discussed in a separate study. However, when compared the 48 DNA sequences identified in this study, much dissimilarity was found within the nucleotide sequences of p- SINE1-r2, in the form of base substitution mutations. Phylogenetic relationships inferred from the nucleotide sequences of these elements in cultivated rice (O. sativa and wild rice (O. nivara. It was found that rice accessions collected from the same geographical distribution have been placed in the same clade. The phylogenetic tree supports the origin and distribution of these rice strains.

  13. Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in Gossypium raimondii

    Science.gov (United States)

    He, Qiuling; Jones, Don C.; Li, Wei; Xie, Fuliang; Ma, Jun; Sun, Runrun; Wang, Qinglian; Zhu, Shuijin; Zhang, Baohong

    2016-01-01

    The R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement. PMID:27009386

  14. Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

    International Nuclear Information System (INIS)

    Golubovskaya, Vita M.; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G.

    2014-01-01

    Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53 +/+ and p53 −/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53 +/+ cells but not in p53 −/− cells. Among up-regulated genes in HCT p53 +/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53 +/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach

  15. The development and optimisation of 3D black-blood R2* mapping of the carotid artery wall.

    Science.gov (United States)

    Yuan, Jianmin; Graves, Martin J; Patterson, Andrew J; Priest, Andrew N; Ruetten, Pascal P R; Usman, Ammara; Gillard, Jonathan H

    2017-12-01

    To develop and optimise a 3D black-blood R 2 * mapping sequence for imaging the carotid artery wall, using optimal blood suppression and k-space view ordering. Two different blood suppression preparation methods were used; Delay Alternating with Nutation for Tailored Excitation (DANTE) and improved Motion Sensitive Driven Equilibrium (iMSDE) were each combined with a three-dimensional (3D) multi-echo Fast Spoiled GRadient echo (ME-FSPGR) readout. Three different k-space view-order designs: Radial Fan-beam Encoding Ordering (RFEO), Distance-Determined Encoding Ordering (DDEO) and Centric Phase Encoding Order (CPEO) were investigated. The sequences were evaluated through Bloch simulation and in a cohort of twenty volunteers. The vessel wall Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and R 2 *, and the sternocleidomastoid muscle R 2 * were measured and compared. Different numbers of acquisitions-per-shot (APS) were evaluated to further optimise the effectiveness of blood suppression. All sequences resulted in comparable R 2 * measurements to a conventional, i.e. non-blood suppressed sequence in the sternocleidomastoid muscle of the volunteers. Both Bloch simulations and volunteer data showed that DANTE has a higher signal intensity and results in a higher image SNR than iMSDE. Blood suppression efficiency was not significantly different when using different k-space view orders. Smaller APS achieved better blood suppression. The use of blood-suppression preparation methods does not affect the measurement of R 2 *. DANTE prepared ME-FSPGR sequence with a small number of acquisitions-per-shot can provide high quality black-blood R 2 * measurements of the carotid vessel wall. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Factor structure and reliability of the Arabic adaptation of the Hypomania Check List-32, second revision (HCL-32-R2).

    Science.gov (United States)

    Fornaro, Michele; Elassy, Mai; Mounir, Mina; Abd-Elmoneim, Noran; Ashour, Hala; Hamed, Rania; Al-Shehri, Abdullah; Bedir, Samir; Rashed, Ibrahem; Amer, Noha; Mohammed, Talal A; De Berardis, Domenico; Mazza, Monica; Pino, Mariachiara; Koshy, Ann Sarah; De Pasquale, Concetta; Okasha, Tarek; Angst, Jules

    2015-05-01

    To assess the psychometric properties of the Arabic adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) inpatients suffering a current major depressive episode (MDE). The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" Arabic module of the HCL-32-R2 was administered to mother-tongue Arabic MDE inpatients between March 2013 and October 2014. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses were made adopting the mini-international neuropsychiatric interview, using bipolar disorder (BD) patients as controls. In our sample (n=500, of whom, BD-I=329; BD-II=70; MDD=101), using a cut-off of 17 allowed the HCL-32-R2 to discriminate DSM-IV-defined MDD patients between "true unipolar" (HCL-32-R2(-)) and "sub-threshold bipolar depression" (HCL-32-R2(+)) with sensitivity=82% and specificity=77%. Area under the curve was .883; positive and negative predictive values were 93.44% and 73.23% respectively. Owing to clinical interpretability considerations and consistency with previous adaptations of the HCL-32, a two-factor solution (F1="hyperactive/elated" vs. F2="irritable/distractible/impulsive") was preferred using exploratory and confirmatory factors analyses. Item n.33 ("I gamble more") and n.34 ("I eat more") introduced in the R2 version of the HCL-32 loaded onto F1, though very slightly. Cronbach's alphas were F1=.86 and F2=.60. No cross-validation with any additional validated screening tool. Inpatients only sample; recall bias; no systematic evaluation of eventual medical/psychiatric comorbidities, current/lifetime pharmacological history, or record of severity of current MDE. In our sample, the HCL-32 fairly discriminated between MDD and BD-I but not BD-II, therefore soliciting for replication studies for use in Arabic-speaking depressed inpatients. Copyright © 2015. Published by Elsevier Inc.

  17. Improved R2* liver iron concentration assessment using a novel fuzzy c-mean clustering scheme

    International Nuclear Information System (INIS)

    Saiviroonporn, Pairash; Viprakasit, Vip; Krittayaphong, Rungroj

    2015-01-01

    In thalassemia patients, R2* liver iron concentration (LIC) measurement is a common clinical tool for assessing iron overload and for determining necessary chelator dose and evaluating its efficacy. Despite the importance of accurate LIC measurement, existing methods suffer from LIC variability, especially at the severe iron overload range due to inclusion of vessel parts in LIC calculation. In this study, we build upon previous Fuzzy C-Mean (FCM) clustering work to formulate a scheme with superior performance in segmenting vessel pixels from the parenchyma. Our method (MIX-FCM) combines our novel 2D-FCM with the existing 1D-FCM algorithm. This study further assessed possible optimal clustering parameters (OP scheme) and proposed a semi-automatic (SA) scheme for routine clinical application. Segmentation of liver parenchyma and vessels was performed on T2* images and their LIC maps in 196 studies from 147 thalassemia major patients. We used manual segmentation as the reference. 1D-FCM clustering was performed on the acquired image alone and 2D-FCM used both the acquired image and its LIC data. To execute the MIX-FCM method, the best outcome (OP-MIX-FCM) was selected from the aforementioned methods and was compared to the SA-MIX-FCM scheme. We used the percent value of the normalized interquartile range (nIQR) to its median to evaluate the variability of all methods. 2D-FCM clustering is more effective than 1D-FCM clustering at the severe overload range only, but inferior for other ranges (where 1D-FCM provides suitable results). This complementary performance between the two methods allows MIX-FCM to improve results for all ranges. OP-MIX-FCM clustering error was 2.1 ± 2.3 %, compared with 10.3 ± 9.9 % and 7.0 ± 11.9 % from 1D- and 2D-FCM clustering, respectively. SA-MIX-FCM result was comparable to OP-MIX-FCM result, with both schemes showing ability to decrease overall nIQR by approximately 30 %. Our proposed 2D-FCM algorithm is not as superior to 1D-FCM as

  18. OBSERVATIONAL AND DYNAMICAL CHARACTERIZATION OF MAIN-BELT COMET P/2010 R2 (La Sagra)

    International Nuclear Information System (INIS)

    Hsieh, Henry H.; Yang Bin; Haghighipour, Nader; Jedicke, Robert; Wainscoat, Richard J.; Denneau, Larry; Kaluna, Heather M.; Kleyna, Jan; Novaković, Bojan; Abe, Shinsuke; Chen Wenping; Ip, Wing; Kinoshita, Daisuke; Fitzsimmons, Alan; Lacerda, Pedro; Granvik, Mikael; Grav, Tommy; Knight, Matthew M.; Lisse, Carey M.; Maclennan, Eric

    2012-01-01

    We present observations of the recently discovered comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope (operated by the MiNDSTEp consortium) at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed to be present from 2010 August through 2011 February, while a dust trail aligned with the object's orbit plane is also observed from 2010 December through 2011 August. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between 2010 August and December, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of H R = 17.9 ± 0.2 mag, corresponding to a nucleus radius of ∼0.7 km, assuming an albedo of p = 0.05. Comparing the observed scattering surface areas of the dust coma to that of the nucleus when P/La Sagra was active, we find dust-to-nucleus area ratios of A d /A N = 30-60, comparable to those computed for fellow main-belt comets 238P/Read and P/2008 R1 (Garradd), and one to two orders of magnitude larger than for two other main-belt comets (133P/Elst-Pizarro and 176P/LINEAR). Using optical spectroscopy to search for CN emission, we do not detect any conclusive evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q CN 23 mol s –1 , from which we infer an H 2 O production rate of Q H 2 O 26 mol s –1 . Numerical simulations indicate that P/La Sagra is dynamically stable for >100 Myr, suggesting that it is likely native to its current location and that its composition is

  19. Thermal instability observations during ramp tests in the Studsvik R2 reactor

    International Nuclear Information System (INIS)

    Roennberg, G.; Kjaer-Pedersen, N.

    1984-01-01

    A series of ramp tests on ENC-built BWR fuel from the Big Rock Point reactor was performed in September 1982 in the Studsvik R2 Reactor. The tests involved segmented rods with a burnup of 18 MWd/KgU, and constituted part of the Fuel Performance Improvement Program sponsored by the United States Department of Energy. Rods of different designs were tested. The reference design had solid, dished pellets and was unpressurized. The alternative designs were annular pellets and sphere-pac. Some of the rods with annular pellets were prepressurized, and some were not. During the ramp tests the rod power is controlled by a helium depressurization loop which causes a strictly linear power ramp versus time. The thermal output of the test rig is measured calorimetrically, the data immediately being recorded on a strip chart and later processed by a computer. Furthermore, elongation detectors permit the immediate recording of the rod length variation versus time. For some of the rods the thermal output went constant for a fraction of a minute after reaching a certain value, then continued to rise, while the helium depressurization continued to proceed linearly with time. For the duration of this plateau of the thermal output curve the slope of the elongation detector signal was significantly higher than before, but fell back to its original value after the plateau. This observation was made only for the reference rods. None of the annular rods, with or without prepressurization, nor the sphere-pac rods, showed the effect. When observed, the effect occurred at about 40 kw/m. The effect is attributed to fission gas release rapidly being enhanced by thermal feedback. The increase in stored energy associated with the temperature rise in the fuel causes the delay in thermal output. The larger available internal volume and/or the prepressurization of the annular rods, and the lack of a distinct fuel-clad gap for the sphere-pac rods prevented the effect from occurring in those other

  20. The Microsoft Data Warehouse Toolkit With SQL Server 2008 R2 and the Microsoft Business Intelligence Toolset

    CERN Document Server

    Mundy, Joy; Kimball, Ralph

    2011-01-01

    Best practices and invaluable advice from world-renowned data warehouse expertsIn this book, leading data warehouse experts from the Kimball Group share best practices for using the upcoming "Business Intelligence release" of SQL Server, referred to as SQL Server 2008 R2. In this new edition, the authors explain how SQL Server 2008 R2 provides a collection of powerful new tools that extend the power of its BI toolset to Excel and SharePoint users and they show how to use SQL Server to build a successful data warehouse that supports the business intelligence requirements that are common to most

  1. Spectroscopic studies of the iron and manganese reconstituted tyrosyl radical in Bacillus cereus ribonucleotide reductase R2 protein.

    Directory of Open Access Journals (Sweden)

    Ane B Tomter

    Full Text Available Ribonucleotide reductase (RNR catalyzes the rate limiting step in DNA synthesis where ribonucleotides are reduced to the corresponding deoxyribonucleotides. Class Ib RNRs consist of two homodimeric subunits: R1E, which houses the active site; and R2F, which contains a metallo cofactor and a tyrosyl radical that initiates the ribonucleotide reduction reaction. We studied the R2F subunit of B. cereus reconstituted with iron or alternatively with manganese ions, then subsequently reacted with molecular oxygen to generate two tyrosyl-radicals. The two similar X-band EPR spectra did not change significantly over 4 to 50 K. From the 285 GHz EPR spectrum of the iron form, a g(1-value of 2.0090 for the tyrosyl radical was extracted. This g(1-value is similar to that observed in class Ia E. coli R2 and class Ib R2Fs with iron-oxygen cluster, suggesting the absence of hydrogen bond to the phenoxyl group. This was confirmed by resonance Raman spectroscopy, where the stretching vibration associated to the radical (C-O, ν(7a = 1500 cm(-1 was found to be insensitive to deuterium-oxide exchange. Additionally, the (18O-sensitive Fe-O-Fe symmetric stretching (483 cm(-1 of the metallo-cofactor was also insensitive to deuterium-oxide exchange indicating no hydrogen bonding to the di-iron-oxygen cluster, and thus, different from mouse R2 with a hydrogen bonded cluster. The HF-EPR spectrum of the manganese reconstituted RNR R2F gave a g(1-value of ∼2.0094. The tyrosyl radical microwave power saturation behavior of the iron-oxygen cluster form was as observed in class Ia R2, with diamagnetic di-ferric cluster ground state, while the properties of the manganese reconstituted form indicated a magnetic ground state of the manganese-cluster. The recent activity measurements (Crona et al., (2011 J Biol Chem 286: 33053-33060 indicates that both the manganese and iron reconstituted RNR R2F could be functional. The manganese form might be very important, as it has 8

  2. On the anisotropy energies for YCo5, RCo5, Y2Co17, and R2Co17

    International Nuclear Information System (INIS)

    Takahashi, H.; Hikosaka, K.; Ohtsuka, S.; Seo, A.; Ukai, T.; Mori, N.

    1988-01-01

    The approximate d bands for YCo 5 , RCo 5 , Y 2 Co 17 , and R 2 Co 17 (Th 2 Zn 17 and Th 2 Ni 17 type) are formulated by Deegan's prescription and the formulas of Slater and Koster. The experimental results of YCo 5 and Y 2 Co 17 are discussed by using these approximate d bands. For RCo 5 and R 2 Co 17 the discussions are made by adopting the localized model and the band model for 4f electrons

  3. Practical evaluation of organic polymer thermoelectrics by large-area R2R processing on flexible substrates

    OpenAIRE

    Søndergaard, Roar R.; Hösel, Markus; Espinosa Martinez, Nieves; Jørgensen, Mikkel; Krebs, Frederik C

    2013-01-01

    Here, we present a process based on roll-to-roll (R2R) technology which allows for very fast processing of polymer thermoelectric (TE) devices and we furthermore demonstrate a simplified but more efficient way of serially connecting these devices by means of R2R thin-film processing. The new device architecture makes it possible to use only one TE material (opposed to two materials which are employed in well-known Peltier elements), and a total of 18,000 serially connected junctions were prep...

  4. The pKR+ values of coordinated propargyl cations [Cp2Mo2(CO)4(μ-η2, η3-HC≡CCR1R2)]+

    International Nuclear Information System (INIS)

    Barinov, I.V.

    1998-01-01

    The pK R + values metal-stabilised carbocations [Cp 2 Mo 2 (CO) 4 (μ-η 2 , η 3 -HC≡CCR 1 R 2 )] + (R 1 = R 2 H, R 1 = H, R 2 = Me and R 1 = R 2 = Me) are measured in 50 % aqueous MeCN. Stability of the cations is increased on going from tertiary to primary carbocations [ru

  5. Investigation of chemical bond characteristics, thermal expansion coefficients and bulk moduli of alpha-R2MoO6 and R2Mo2O7 (R = rare earths) by using a dielectric chemical bond method.

    Science.gov (United States)

    Li, Huaiyong; Zhang, Siyuan; Zhou, Shihong; Cao, Xueqiang

    2009-09-01

    Theoretical researches are performed on the alpha-R2MoO6 (R = Y, Gd, Tb Dy, Ho, Er, Tm and Yb) and pyrochlore-type R2Mo2O7 (R = Y, Nd, Sm, Gd, Tb and Dy) rare earth molybdates by using chemical bond theory of dielectric description. The chemical bonding characteristics and their relationship with thermal expansion property and compressibility are explored. The calculated values of linear thermal expansion coefficient (LTEC) and bulk modulus agree well with the available experimental values. The calculations reveal that the LTECs and the bulk moduli do have linear relationship with the ionic radii of the lanthanides: the LTEC decreases from 6.80 to 6.62 10(-6)/K and the bulk modulus increases from 141 to 154 GPa when R goes in the order Gd, Tb Dy, Ho, Er, Tm, and Yb in the alpha-R2MoO6 series; while in the R2Mo2O7 series, the LTEC ranges from 6.80 to 6.61 10(-6)/K and the bulk modulus ranges from 147 to 163 GPa when R varies in the order Nd, Sm, Gd, Tb and Dy. Copyright 2008 Wiley Periodicals, Inc.

  6. Référentiel APSAD R5 robinets d'incendie armés et postes d'incendie additivés

    CERN Document Server

    2013-01-01

    Le référentiel APSAD R5 a pour objectif d’accompagner les utilisateurs, prescripteurs et installateurs dans la conduite d’un projet de conception et d’installation de robinets d’incendie armés (RIA) dans tous types de bâtiments. Il s’applique également aux postes d’incendie additivés (PIA) utilisés en complément pour la protection de certains risques particuliers. Les caractéristiques techniques des matériels, leur implantation, les sources d’eau et le réseau de canalisations ainsi que les opérations de surveillance, de vérification et de maintenance font l’objet d’exigences particulières à respecter pour une installation fiable. Une étude de cas aidera à appréhender la démarche.

  7. Evaluation of a bolus/infusion protocol for 11C-ABP688, a PET tracer for mGluR5

    International Nuclear Information System (INIS)

    Burger, Cyrill; Deschwanden, Alexandra; Ametamey, Simon; Johayem, Anass; Mancosu, Bruno; Wyss, Matthias; Hasler, Gregor; Buck, Alfred

    2010-01-01

    11 C-ABP-688 is a selective tracer for the mGluR5 receptor. Its kinetics is fast and thus favourable for an equilibrium approach to determine receptor-related parameters. The purpose of this study was to test the hypothesis that the pattern of the 11 C-ABP688 uptake using a bolus-plus-infusion (B/I) protocol at early time points corresponds to the perfusion and at a later time point to the total distribution volume. Methods: A bolus and a B/I study (1 h each) was performed in five healthy male volunteers. With the B/I protocol, early and late scans were normalized to gray matter, cerebellum and white matter. The same normalization was done on the maps of the total distribution volume (Vt) and K 1 which were calculated in the study with bolus only injection and the Logan method (Vt) and a two-tissue compartment model (K 1 ). Results: There was an excellent correlation close to the identity line between the pattern of the late uptake in the B/I study and Vt of the bolus-only study for all three normalizations. The pattern of the early uptake in the B/I study correlated well with the K 1 maps, but only when normalized to gray matter and cerebellum, not to white matter. Conclusion: It is demonstrated that with a B/I protocol the 11 C-ABP688 distribution in late scans reflects the pattern of the total distribution volume and is therefore a measure for the density pattern of mGluR5. The early scans following injection are related to blood flow, although not in a fully quantitative manner. The advantage of the B/I protocol is that no arterial blood sampling is required, which is advantageous in clinical studies.

  8. Transport and biotransformation of the new cytostatic complex cis-diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) by the rat liver.

    Science.gov (United States)

    Macias, R I; Monte, M J; El-Mir, M Y; Villanueva, G R; Marin, J J

    1998-09-01

    Rat liver uptake and bile output of the cytostatic complex cis-diammineplatinum(II)-chlorocholylglycinate (Bamet-R2) were studied. Up to 100 microM, Bamet-R2 uptake by rat hepatocytes in primary culture followed saturation kinetics (Vmax = 0.65 +/- 0.12 nmol/5 min per mg protein; K(M) = 45.2 +/- 10.7 microM). Bamet-R2 uptake was lower than that of cholylglycinate (CG) but higher than that of cisplatin. Replacement of 116 mM NaCl by 116 mM choline chloride did not significantly reduce Bamet-R2 uptake. Addition of 500 microM CG, cholic acid, estrone sulfate, or ouabain to 50 microM Bamet-R2-containing incubation media inhibited Bamet-R2 uptake. No liver biotransformation of Bamet-R2 occurred, as indicated by HPLC analysis of bile collected from anesthetized rats after intravenous administration of the drug. Bamet-R2 uptake and secretion into bile by isolated rat livers exceeded those of cisplatin but were lower than those of CG. Differences between Bamet-R2 and CG were more marked for bile output than for liver uptake. Thus, higher Bamet-R2 than CG or cisplatin liver content was found. Co-administration of Bamet-R2 and CG revealed that CG induced a slight reduction in Bamet-R2 uptake and a marked inhibition in Bamet-R2 bile output. By contrast, Bamet-R2 had no effect on CG on either liver uptake or bile output. In sum, the present data indicate that Bamet-R2 is efficiently taken up and secreted into bile by the rat liver by mechanisms shared in part by natural bile acids.

  9. OBSERVATIONAL AND DYNAMICAL CHARACTERIZATION OF MAIN-BELT COMET P/2010 R2 (La Sagra)

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Henry H.; Yang Bin; Haghighipour, Nader; Jedicke, Robert; Wainscoat, Richard J.; Denneau, Larry; Kaluna, Heather M.; Kleyna, Jan [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu HI 96822 (United States); Novakovic, Bojan [Department of Astronomy, Faculty of Mathematics, University of Belgrade, Studentski trg 16, 11000 Belgrade (Serbia); Abe, Shinsuke; Chen Wenping; Ip, Wing; Kinoshita, Daisuke [Institute of Astronomy, National Central University, 300 Jhongda Rd, Jhongli 32001, Taiwan (China); Fitzsimmons, Alan; Lacerda, Pedro [Astronomy Research Centre, Queens University Belfast, Belfast BT7 1NN (United Kingdom); Granvik, Mikael [Department of Physics, P.O. Box 64, 00014 University of Helsinki (Finland); Grav, Tommy [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); Knight, Matthew M. [Lowell Observatory, 1400 West Mars Hill Road, Flagstaff, AZ 86001 (United States); Lisse, Carey M. [Planetary Exploration Group, Space Department, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723 (United States); Maclennan, Eric, E-mail: hsieh@ifa.hawaii.edu [Department of Physics and Astronomy, Northern Arizona University, 602 South Humphreys Street, Flagstaff, AZ 86011 (United States); and others

    2012-05-15

    We present observations of the recently discovered comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope (operated by the MiNDSTEp consortium) at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed to be present from 2010 August through 2011 February, while a dust trail aligned with the object's orbit plane is also observed from 2010 December through 2011 August. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between 2010 August and December, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of H{sub R} = 17.9 {+-} 0.2 mag, corresponding to a nucleus radius of {approx}0.7 km, assuming an albedo of p = 0.05. Comparing the observed scattering surface areas of the dust coma to that of the nucleus when P/La Sagra was active, we find dust-to-nucleus area ratios of A{sub d} /A{sub N} = 30-60, comparable to those computed for fellow main-belt comets 238P/Read and P/2008 R1 (Garradd), and one to two orders of magnitude larger than for two other main-belt comets (133P/Elst-Pizarro and 176P/LINEAR). Using optical spectroscopy to search for CN emission, we do not detect any conclusive evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q{sub CN} < 6 Multiplication-Sign 10{sup 23} mol s{sup -1}, from which we infer an H{sub 2}O production rate of Q{sub H{sub 2O}} < 10{sup 26} mol s{sup -1}. Numerical simulations indicate that P/La Sagra is dynamically stable for >100 Myr

  10. Dielectric properties of thin C r2O3 films grown on elemental and oxide metallic substrates

    Science.gov (United States)

    Mahmood, Ather; Street, Michael; Echtenkamp, Will; Kwan, Chun Pui; Bird, Jonathan P.; Binek, Christian

    2018-04-01

    In an attempt to optimize leakage characteristics of α-C r2O3 thin films, its dielectric properties were investigated at local and macroscopic scale. The films were grown on Pd(111), Pt(111), and V2O3 (0001), supported on A l2O3 substrate. The local conductivity was measured by conductive atomic force microscopy mapping of C r2O3 surfaces, which revealed the nature of defects that formed conducting paths with the bottom Pd or Pt layer. A strong correlation was found between these electrical defects and the grain boundaries revealed in the corresponding topographic scans. In comparison, the C r2O3 film on V2O3 exhibited no leakage paths at similar tip bias value. Electrical resistance measurements through e-beam patterned top electrodes confirmed the resistivity mismatch between the films grown on different electrodes. The x-ray analysis attributes this difference to the twin free C r2O3 growth on V2O3 seeding.

  11. Hybridogenesis and a potential case of R2 non-LTR retrotransposon horizontal transmission in Bacillus stick insects (Insecta Phasmida).

    Science.gov (United States)

    Scavariello, Claudia; Luchetti, Andrea; Martoni, Francesco; Bonandin, Livia; Mantovani, Barbara

    2017-02-06

    Horizontal transfer (HT) is an event in which the genetic material is transferred from one species to another, even if distantly related, and it has been demonstrated as a possible essential part of the lifecycle of transposable elements (TEs). However, previous studies on the non-LTR R2 retrotransposon, a metazoan-wide distributed element, indicated its vertical transmission since the Radiata-Bilateria split. Here we present the first possible instances of R2 HT in stick insects of the genus Bacillus (Phasmida). Six R2 elements were characterized in the strictly bisexual subspecies B. grandii grandii, B. grandii benazzii and B. grandii maretimi and in the obligatory parthenogenetic taxon B. atticus. These elements were compared with those previously retrieved in the facultative parthenogenetic species B. rossius. Phylogenetic inconsistencies between element and host taxa, and age versus divergence analyses agree and support at least two HT events. These HT events can be explained by taking into consideration the complex Bacillus reproductive biology, which includes also hybridogenesis, gynogenesis and androgenesis. Through these non-canonical reproductive modes, R2 elements may have been transferred between Bacillus genomes. Our data suggest, therefore, a possible role of hybridization for TEs survival and the consequent reshaping of involved genomes.

  12. R2P’s “Ulterior Motive Exemption” and the Failure to Protect in Libya

    Directory of Open Access Journals (Sweden)

    Jeffrey Bachman

    2015-11-01

    Full Text Available Mass atrocity prevention has been controversial, both when members of the international community have taken action as well as when they have failed to do so. In 1999, then UN Secretary-General Kofi Annan challenged the international community to reconcile the need to respect state sovereignty with the need to protect populations from egregious human rights violations. R2P’s emergence offered an opportunity to move past the discourse and practice associated with its predecessor—“humanitarian intervention.” However, while R2P has succeeded in changing the discourse, it has failed to make a change in practice. A source of this failure is R2P’s “ulterior motive exemption.” Using the R2P intervention in Libya as a case study, this article concludes that because ulterior motives existed: (1 NATO’s primary intent of civilian protection quickly evolved into the intent to overthrow Muammar Qaddafi; (2 in exceeding its mandate, NATO committed an act of aggression; (3 NATO continued to militarily support the rebels while they were committing war crimes and severe human rights violations; (4 NATO’s actions resulted in civilian casualties, which NATO has refused to investigate; and (5 NATO abdicated its responsibility to protect Libyans from the human suffering that continued subsequent to Qaddafi’s execution.

  13. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

    NARCIS (Netherlands)

    Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

    2010-01-01

    Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the

  14. R-1 (C-620-A) and R-2 (C-620-B) air compressor control logic, computer software description. Revision 1

    International Nuclear Information System (INIS)

    Walter, K.E.

    1995-01-01

    This document provides an updated computer software description for the software used on the FFTF R-1 (C-620-A) and R-2 (C-620-B) air compressor programmable controllers. Logic software design changes were required to allow automatic starting of a compressor that had not been previously started

  15. Herschel observations in the ultracompact HII region Mon R2 : Water in dense photon-dominated regions (PDRs)

    NARCIS (Netherlands)

    Fuente, A.; Berne, O.; Cernicharo, J.; Rizzo, J. R.; Gonzalez-Garcia, M.; Goicoechea, J. R.; Pilleri, P.; Ossenkopf, V.; Gerin, M.; Guesten, R.; Akyilmaz, M.; Benz, A. O.; Boulanger, F.; Bruderer, S.; Dedes, C.; France, K.; Garcia-Burillo, S.; Harris, A.; Joblin, C.; Klein, T.; Kramer, C.; Le Petit, F.; Lord, S. D.; Martin, P. G.; Martin-Pintado, J.; Mookerjea, B.; Neufeld, D. A.; Okada, Y.; Pety, J.; Phillips, T. G.; Roellig, M.; Simon, R.; Stutzki, J.; van der Tak, F.; Teyssier, D.; Usero, A.; Yorke, H.; Schuster, K.; Melchior, M.; Lorenzani, A.; Szczerba, R.; Fich, M.; McCoey, C.; Pearson, J.; Dieleman, P.

    2010-01-01

    Context. Monoceros R2, at a distance of 830 pc, is the only ultracompact Hii region (UC Hii) where the photon-dominated region (PDR) between the ionized gas and the molecular cloud can be resolved with Herschel. Therefore, it is an excellent laboratory to study the chemistry in extreme PDRs (G0 >

  16. Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury

    NARCIS (Netherlands)

    Poppelaars, Felix; van Werkhoven, Maaike B; Kotimaa, Juha; Veldhuis, Zwanida J; Ausema, Albertina; Broeren, Stefan G M; Damman, Jeffrey; Hempel, Julia C.; Leuvenink, Henri G D; Daha, Mohamed R; van Son, Willem J; van Kooten, Cees; van Os, Ronald P; Hillebrands, Jan-Luuk; Seelen, Marc A

    The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR

  17. The Eucalyptus grandis R2R3-MYB transcription factor family: evidence for woody growth-related evolution and function.

    Science.gov (United States)

    Soler, Marçal; Camargo, Eduardo Leal Oliveira; Carocha, Victor; Cassan-Wang, Hua; San Clemente, Hélène; Savelli, Bruno; Hefer, Charles A; Paiva, Jorge A Pinto; Myburg, Alexander A; Grima-Pettenati, Jacqueline

    2015-06-01

    The R2R3-MYB family, one of the largest transcription factor families in higher plants, controls a wide variety of plant-specific processes including, notably, phenylpropanoid metabolism and secondary cell wall formation. We performed a genome-wide analysis of this superfamily in Eucalyptus, one of the most planted hardwood trees world-wide. A total of 141 predicted R2R3-MYB sequences identified in the Eucalyptus grandis genome sequence were subjected to comparative phylogenetic analyses with Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera. We analysed features such as gene structure, conserved motifs and genome location. Transcript abundance patterns were assessed by RNAseq and validated by high-throughput quantitative PCR. We found some R2R3-MYB subgroups with expanded membership in E. grandis, V. vinifera and P. trichocarpa, and others preferentially found in woody species, suggesting diversification of specific functions in woody plants. By contrast, subgroups containing key genes regulating lignin biosynthesis and secondary cell wall formation are more conserved across all of the species analysed. In Eucalyptus, R2R3-MYB tandem gene duplications seem to disproportionately affect woody-preferential and woody-expanded subgroups. Interestingly, some of the genes belonging to woody-preferential subgroups show higher expression in the cambial region, suggesting a putative role in the regulation of secondary growth. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  18. High-yield conversion of (R)-2-octanol from the corresponding racemate by stereoinversion using Candida rugosa.

    Science.gov (United States)

    Nie, Yao; Xu, Yan; Qing Mu, Xiao; Tang, Yan; Jiang, Juan; Hao Sun, Zhi

    2005-01-01

    Whole cells of Candida rugosa catalyzed the conversion of (R)-2-octanol from the corresponding racemate with the optical purity of 97% e.e. and yield of 92% in 10 h. The product was formed through a stereoinversion involving enantioselective oxidation and asymmetric reduction with 2-octanone as the intermediate.

  19. Assessment of response to anti-angiogenic targeted therapy in pulmonary metastatic renal cell carcinoma: R2* value as a predictive biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guangyu; Liu, Guiqin; Suo, Shiteng; Liu, Xiaosheng; Xu, Jianrong [Shanghai Jiao Tong University, Department of Radiology, Renji Hospital, School of Medicine, Shanghai (China); Kong, Wen; Zhang, Jin [Shanghai Jiao Tong University, Department of Urinary Surgery, Renji Hospital, School of Medicine, Shanghai (China); Qu, Jianxun [GE Healthcare, Shanghai (China)

    2017-09-15

    To evaluate the utility of MR R2*-mapping and the optimal time-point for assessing the response of pulmonary metastatic renal cell carcinoma (mRCC) to anti-angiogenic targeted therapy (aATT). The exploration-sample group and the validation-sample group consisted of 22 and 16 patients. The parameters of MR R2*-mapping, including the R2* value at each time-point (R2*{sub base}, R2*{sub 1cyc} and R2*{sub 2cyc}) and change between different time-points (R2*{sub (1cyc-base)/base}, R2*{sub (2cyc-base)/base} and R2*{sub (2cyc-1cyc)/1cyc}), were evaluated with a receiver-operating-characteristic analysis, and a cut-off value derived from the clinical outcome was applied to the Kaplan-Meier method to assess the value of R2* mapping and Response-Evaluation-Criteria in Solid Tumours (RECIST) during treatment evaluation. The inter-, intra-observer agreements and inter-scan consistency were excellent (p > 0.80). For the exploration-sample group, the areas under the curve for the parameters of MR R2* mapping were 0.55, 0.60, 0.83, 0.64, 0.88 and 0.83 for R2*{sub base}, R2*{sub 1cyc}, R2*{sub 2cyc}, R2*{sub (1cyc-base)/base}, R2*{sub (2cyc-base)/base} and R2*{sub (2cyc-1cyc)/1cyc.} For the validation-sample, R2*{sub (2cyc-base)/base} better predicted progression-free survival (p = 0.03) than RECIST and other R2* mapping parameters with a lower p value. Assessing aATT outcome based on changes in the R2* value between baseline and second treatment is more accurate than assessment at other time-points and assessment based on the RECIST. (orig.)

  20. Protection but maintained dysfunction of nigral dopaminergic nerve cell bodies and striatal dopaminergic terminals in MPTP-lesioned mice after acute treatment with the mGluR5 antagonist MPEP.

    Science.gov (United States)

    Aguirre, Jose A; Kehr, Jan; Yoshitake, Takashi; Liu, Fang-Ling; Rivera, Alicia; Fernandez-Espinola, Sergio; Andbjer, Beth; Leo, Giuseppina; Medhurst, Andrew D; Agnati, Luigi F; Fuxe, Kjell

    2005-02-08

    The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.

  1. Experiments towards establishing of design rules for R2R-UV-NIL with polymer working shims

    Science.gov (United States)

    Nees, Dieter; Ruttloff, Stephan; Palfinger, Ursula; Stadlober, Barbara

    2016-03-01

    Roll-to-Roll-UV-nanoimprint lithography (R2R-UV-NIL) enables high resolution large area patterning of flexible substrates and is therefore of increasing industrial interest. We have set up a custom-made R2R-UV-NIL pilot machine which is able to convert 10 inch wide web with velocities of up to 30 m/min. In addition, we have developed self-replicable UV-curable resins with tunable surface energy and Young's modulus for UV-imprint material as well as for polymer working stamp/shim manufacturing. Now we have designed test patterns for the evaluation of the impact of structure shape, critical dimension, pitch, depth, side wall angle and orientation relative to the web movement onto the imprint fidelity and working shim life time. We have used female (recessed structures) silicon masters of that design with critical dimensions between CD = 200 nm and 1600 nm, and structure depths of d = 500 nm and 1000 nm - all with vertical as well as inclined side walls. These entire master patterns have been transferred onto single male (protruding structures) R2R polymer working shims. The polymer working shims have been used for R2R-UV-NIL runs of several hundred meters and the imprint fidelity and process stability of the various test patterns have been compared. This study is intended as a first step towards establishing of design rules and developing of nanoimprint proximity correction strategies for industrial R2R-UV-NIL processes using polymer working shims.

  2. Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

    Science.gov (United States)

    Cowger, Taku A; Tang, Wei; Zhen, Zipeng; Hu, Kai; Rink, David E; Todd, Trever J; Wang, Geoffrey D; Zhang, Weizhong; Chen, Hongmin; Xie, Jin

    2015-01-01

    Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

  3. Astrocyte IP3R2-dependent Ca2+ signaling is not a major modulator of neuronal pathways governing behavior.

    Directory of Open Access Journals (Sweden)

    Jeremy ePetravicz

    2014-11-01

    Full Text Available Calcium-dependent release of gliotransmitters by astrocytes is reported to play a critical role in synaptic transmission and be necessary for long-term potentiation (LTP, long-term depression (LTD and other forms of synaptic modulation that are correlates of learning and memory . Further, physiological processes reported to be dependent on Ca2+ fluxes in astrocytes include functional hyperemia, sleep, and regulation of breathing. The preponderance of findings indicate that most, if not all, receptor dependent Ca2+ fluxes within astrocytes are due to release of Ca2+ through IP3 receptor/channels in the endoplasmic reticulum. Findings from several laboratories indicate that astrocytes only express IP3 receptor type 2 (IP3R2 and that a knockout of IP3R2 obliterates the GPCR-dependent astrocytic Ca2+ responses. Assuming that astrocytic Ca2+ fluxes play a critical role in synaptic physiology, it would be predicted that eliminating of astrocytic Ca2+ fluxes would lead to marked changes in behavioral tests. Here, we tested this hypothesis by conducting a broad series of behavioral tests that recruited multiple brain regions, on an IP3R2 conditional knockout mouse model. We present the novel finding that behavioral processes are unaffected by lack of astrocyte IP3R-mediated Ca2+ signals. IP3R2 cKO animals display no change in anxiety or depressive behaviors, and no alteration to motor and sensory function. Morris water maze testing, a behavioral correlate of learning and memory, was unaffected by lack of astrocyte IP3R2-mediated Ca2+-signaling. Therefore, in contrast to the prevailing literature, we find that neither receptor-driven astrocyte Ca2+ fluxes nor, by extension, gliotransmission is likely to be a major modulating force on the physiological processes underlying behavior.

  4. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors.

    Science.gov (United States)

    Zhang, D; Wang, X; Wang, B; Garza, J C; Fang, X; Wang, J; Scherer, P E; Brenner, R; Zhang, W; Lu, X-Y

    2017-07-01

    Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD.

  5. Crystal structure of (1S,3R,8R,10S-2,2-dichloro-10-hydroxy-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodecan-9-one

    Directory of Open Access Journals (Sweden)

    Ahmed Benzalim

    2016-05-01

    Full Text Available The asymmetric unit of the title compound, C16H24Cl2O2, contains two independent molecules (A and B which are built from three fused rings, viz. a seven-membered heptane ring, a six-membered cyclohexyl ring bearing a ketone and an alcohol group, and a cyclopropane ring bearing two Cl atoms. In the crystal, the two molecules are linked via two O—H...O hydrogen bonds, forming an A–B dimer with an R22(10 ring motif. The A molecules of these dimers are linked via a C—H...O hydrogen bond, forming chains propagating along the a-axis direction. Both molecules have the same absolute configuration, i.e. 1S,3R,8R,10S, which is based on the synthetic pathway and further confirmed by resonant scattering [Flack parameter = 0.03 (5].

  6. Rolling Deck to Repository (R2R): Supporting Global Data Access Through the Ocean Data Interoperability Platform (ODIP)

    Science.gov (United States)

    Arko, R. A.; Stocks, K.; Chandler, C. L.; Smith, S. R.; Miller, S. P.; Maffei, A. R.; Glaves, H. M.; Carbotte, S. M.

    2013-12-01

    The U.S. National Science Foundation supports a fleet of academic research vessels operating throughout the world's oceans. In addition to supporting the mission-specific goals of each expedition, these vessels routinely deploy a suite of underway environmental sensors, operating like mobile observatories. Recognizing that the data from these instruments have value beyond each cruise, NSF funded R2R in 2009 to ensure that these data are routinely captured, cataloged and described, and submitted to the appropriate national repository for long-term public access. In 2013, R2R joined the Ocean Data Interoperability Platform (ODIP; http://odip.org/). The goal of ODIP is to remove barriers to the effective sharing of data across scientific domains and international boundaries, by providing a forum to harmonize diverse regional systems. To advance this goal, ODIP organizes international workshops to foster the development of common standards and develop prototypes to evaluate and test potential standards and interoperability solutions. ODIP includes major organizations engaged in ocean data stewardship in the EU, US, and Australia, supported by the International Oceanographic Data and Information Exchange (IODE). Within the broad scope of ODIP, R2R focuses on contributions in 4 key areas: ● Implement a 'Linked Open Data' approach to disseminate data and documentation, using existing World Wide Web Consortium (W3C) specifications and machine-readable formats. Exposing content as Linked Open Data will provide a simple mechanism for ODIP collaborators to browse and compare data sets among repositories. ● Map key vocabularies used by R2R to their European and Australian counterparts. The existing heterogeneity among terms inhibits data discoverability, as a user searching on the term with which s/he is familiar may not find all data of interest. Mapping key terms across the different ODIP partners, relying on the backbone thesaurus provided by the NERC Vocabulary Server

  7. Comparison of R5 and G12 Antibody-Based ELISA Used for the Determination of the Gluten Content in Official Food Samples

    Directory of Open Access Journals (Sweden)

    Rupert Hochegger

    2015-11-01

    Full Text Available Celiac Disease (CD is one of the most common food intolerances. It comes along with serious damage of the mucosa in the small intestine and is caused by the storage proteins—termed “gluten”—of wheat, rye, barley and possibly oats. Sensitive individuals need to stick to a strict gluten-free diet. The gluten level in food products labeled as “gluten-free”, must not exceed 20 mg/kg. It is obvious that effective test methods are needed to accurately determine the gluten concentration in foods. The determination of the presence of gluten in foodstuffs is mainly done by means of an immunochemical method called ELISA (enzyme-linked immunosorbent assay. To check the suitability of a G12 antibody-based gluten detection kit for its use in official control systems a number of routine samples were tested in parallel with two different test kits, as would be done in a routine lab. The determination of the gluten content was performed on samples entering the official laboratory including samples from official control plans, commercially available and private samples to request gluten-free labels. The results obtained with the G12 antibody ELISA assay were comparable to the official R5 method. A validation of the two different methods was not part of this study.

  8. Curcumin Protects against Monosodium Glutamate Neurotoxicity and Decreasing NMDA2B and mGluR5 Expression in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Rania M. Khalil

    2016-08-01

    Full Text Available Background: Monosodium glutamate (MSG is a flavor enhancer used in food industries. MSG is well documented to induce neurotoxicity. Curcumin (CUR reportedly possesses beneficial effects against various neurotoxic insults. Hence, this present study has been designed to evaluate the neuroprotective effect of curcumin on MSG-induced neurotoxicity in rats. Methods: Thirty-two male Wister rats were divided into four groups (n=8: Control group, MSG group, CUR group and MSG + CUR group. CUR (Curcumin 150 mg/kg, orally was given day after day for four weeks along with MSG (4 mg/kg, orally. After 4 weeks, rats were sacrificed and brain hippocampus was isolated immediately on ice. Inflammatory marker TNFα and acetylcholinesterase (AChE activity (marker for cholinergic function were estimated. Gene expressions of metabotropic glutamate receptor 5 (mGluR5 and N-methyl-D-aspartate receptor 2B (NMDA2B along with glutamate concentration were assessed. Results: Treatment with CUR significantly attenuated AChE activity and TNFα in MSG-treated animals. The anti-inflammatory properties of CUR may be responsible for this observed neuroprotective action. A possible role of CUR to attenuate both glutamate level and gene expression of NMDA2B and mGLUR5 in brain hippocampus was established when compared to MSG group. Conclusion: We concluded that CUR as flavor enhancer protects against MSG-induced neurotoxicity in rats.

  9. Ab initio calculation of electronic structure and magnetic properties of R2Fe14BNx (R = Pr,Nd)

    Science.gov (United States)

    Tian, Guang; Zha, Liang; Yang, Wenyun; Qiao, Guanyi; Wang, Changsheng; Yang, Yingchang; Yang, Jinbo

    2018-05-01

    The site preference of N atom for R2Fe14BNx (R= Pr, Nd) and the interstitial nitrogen effect on the magnetic properties have been studied by the first-principles method. It was found that the nitrogen is more likely to occupy the 4e site for Pr2Fe14BNx compound, while 4f site for Nd2Fe14BNx. When N atoms entering some specific crystal sites (such as 2a and 4f), the total magnetic moments of these compounds are not reduced, but slightly increased. Although the doping of N may reduce the total magnetic moments of some R2Fe14B compounds in the cases of optimal occupancy, the volumetric effect caused by N doping can still change the electron density distributions of Fe near the Fermi level, improving the magnetic ordering temperature of such compounds.

  10. Electronic, elastic and optical properties of divalent (R+2X) and trivalent (R+3X) rare earth monochalcogenides

    Science.gov (United States)

    Kumar, V.; Chandra, S.; Singh, J. K.

    2017-08-01

    Based on plasma oscillations theory of solids, simple relations have been proposed for the calculation of bond length, specific gravity, homopolar energy gap, heteropolar energy gap, average energy gap, crystal ionicity, bulk modulus, electronic polarizability and dielectric constant of rare earth divalent R+2X and trivalent R+3X monochalcogenides. The specific gravity of nine R+2X, twenty R+3X, and bulk modulus of twenty R+3X monochalcogenides have been calculated for the first time. The calculated values of all parameters are compared with the available experimental and the reported values. A fairly good agreement has been obtained between them. The average percentage deviation of two parameters: bulk modulus and electronic polarizability for which experimental data are known, have also been calculated and found to be better than the earlier correlations.

  11. Evaluation of Role 2 (R2) Medical Resources in the Afghanistan Combat Theater: Past, Present and Future

    Science.gov (United States)

    2017-10-01

    those of the author(s) and should not be construed  as an official Department of the Army position, policy or  decision  unless so designated by other...sustainment and evaluation for medical staff (physicians, nurses , other licensed professionals, medics) deployed to the R2 environment. 15. SUBJECT TERMS...leaders will be unable to best allocate R2  resources in future operations. Furthermore, the  clinical  competencies required for each medical team member to

  12. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

    OpenAIRE

    Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

    2010-01-01

    Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all th...

  13. On the entropy of four-dimensional near-extremal N = 2 black holes with R2-terms

    International Nuclear Information System (INIS)

    Gruss, Eyal; Oz, Yaron

    2007-01-01

    We consider the entropy of four-dimensional near-extremal N = 2 black holes. The Bekenstein-Hawking entropy formula has the structure of the extremal black holes entropy with a shift of the charges depending on the non-extremality parameter and the moduli at infinity. We construct a class of near-extremal horizon solutions with R 2 -terms, and show that the generalized Wald entropy formula exhibits the same property

  14. Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity.

    Science.gov (United States)

    Jayakumar, Sundarraj; Patwardhan, Raghavendra S; Pal, Debojyoti; Singh, Babita; Sharma, Deepak; Kutala, Vijay Kumar; Sandur, Santosh Kumar

    2017-12-01

    Mitocurcumin is a derivative of curcumin, which has been shown to selectively enter mitochondria. Here we describe the anti-tumor efficacy of mitocurcumin in lung cancer cells and its mechanism of action. Mitocurcumin, showed 25-50 fold higher efficacy in killing lung cancer cells as compared to curcumin as demonstrated by clonogenic assay, flow cytometry and high throughput screening assay. Treatment of lung cancer cells with mitocurcumin significantly decreased the frequency of cancer stem cells. Mitocurcumin increased the mitochondrial reactive oxygen species (ROS), decreased the mitochondrial glutathione levels and induced strand breaks in the mitochondrial DNA. As a result, we observed increased BAX to BCL-2 ratio, cytochrome C release into the cytosol, loss of mitochondrial membrane potential and increased caspase-3 activity suggesting that mitocurcumin activates the intrinsic apoptotic pathway. Docking studies using mitocurcumin revealed that it binds to the active site of the mitochondrial thioredoxin reductase (TrxR2) with high affinity. In corroboration with the above finding, mitocurcumin decreased TrxR activity in cell free as well as the cellular system. The anti-cancer activity of mitocurcumin measured in terms of apoptotic cell death and the decrease in cancer stem cell frequency was accentuated by TrxR2 overexpression. This was due to modulation of TrxR2 activity to NADPH oxidase like activity by mitocurcumin, resulting in higher ROS accumulation and cell death. Thus, our findings reveal mitocurcumin as a potent anticancer agent with better efficacy than curcumin. This study also demonstrates the role of TrxR2 and mitochondrial DNA damage in mitocurcumin mediated killing of cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Generation of baryon excess in SUsub(L)(2) x SUsub(R)(2) x SUsub(c)(4)

    International Nuclear Information System (INIS)

    Deo, B.B.; Prasad, V.B.

    1980-08-01

    We have calculated the magnitude of the cosmological baryon asymmetry in a gauge theory based on the group SUsub(L)(2) x SUsub(R)(2) x SUsub(c)(4) and find that plausible parameters exist in the model to explain the baryon excess with a subunifying mass scale of 10 4 -10 5 GeV. The novel idea used is that the vacuum eats away antimatter through the VEV of the Higgs meson. (author)

  16. Comparing consistency of R2* and T2*-weighted BOLD analysis of resting state fetal fMRI

    Science.gov (United States)

    Seshamani, Sharmishtaa; Blazejewska, Anna I.; Gatenby, Christopher; Mckown, Susan; Caucutt, Jason; Dighe, Manjiri; Studholme, Colin

    2015-03-01

    Understanding when and how resting state brain functional activity begins in the human brain is an increasing area of interest in both basic neuroscience and in the clinical evaluation of the brain during pregnancy and after premature birth. Although fMRI studies have been carried out on pregnant women since the 1990's, reliable mapping of brain function in utero is an extremely challenging problem due to the unconstrained fetal head motion. Recent studies have employed scrubbing to exclude parts of the time series and whole subjects from studies in order to control the confounds of motion. Fundamentally, even after correction of the location of signals due to motion, signal intensity variations are a fundamental limitation, due to coil sensitivity and spin history effects. An alternative technique is to use a more parametric MRI signal derived from multiple echoes that provides a level of independence from basic MRI signal variation. Here we examine the use of R2* mapping combined with slice based multi echo geometric distortion correction for in-utero studies. The challenges for R2* mapping arise from the relatively low signal strength of in-utero data. In this paper we focus on comparing activation detection in-utero using T2W and R2* approaches. We make use a subset of studies with relatively limited motion to compare the activation patterns without the additional confound of significant motion. Results at different gestational ages indicate comparable agreement in many activation patterns when limited motion is present, and the detection of some additional networks in the R2* data, not seen in the T2W results.

  17. Rapid Response Command and Control (R2C2): a systems engineering analysis of scaleable communications for Regional Combatant Commanders

    OpenAIRE

    Sullivan, Lisa; Cannon, Lennard; Reyes, Ronel; Bae, Kitan; Colgary, James; Minerowicz, Nick; Leong, Chris; Lim, Harry; Lim, Hang Sheng; Ng, Chin Chin; Neo, Tiong Tien; Tan, Guan Chye; Ng, Yu Loon; Wong, Eric; Wong, Heng Yue

    2006-01-01

    Includes supplementary material. Disaster relief operations, such as the 2005 Tsunami and Hurricane Katrina, and wartime operations, such as Operation Enduring Freedom and Operation Iraqi Freedom, have identified the need for a standardized command and control system interoperable among Joint, Coalition, and Interagency entities. The Systems Engineering Analysis Cohort 9 (SEA-9) Rapid Response Command and Control (R2C2) integrated project team completed a systems engineering (SE) ...

  18. The Complete Calibration of the Color–Redshift Relation (C3R2) Survey: Survey Overview and Data Release 1

    Energy Technology Data Exchange (ETDEWEB)

    Masters, Daniel C. [Infrared Processing and Analysis Center, Pasadena, CA 91125 (United States); Stern, Daniel K.; Rhodes, Jason D. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Cohen, Judith G. [California Institute of Technology, Pasadena, CA 91125 (United States); Capak, Peter L. [Spitzer Science Center, Pasadena, CA 91125 (United States); Castander, Francisco J. [Institut de Ciències de lEspai (ICE, IEEC/CSIC), E-08193 Bellaterra (Barcelona) (Spain); Paltani, Stéphane [Department of Astronomy, University of Geneva, Ch. dEcogia 16, 1290 Versoix (Switzerland)

    2017-06-01

    A key goal of the Stage IV dark energy experiments Euclid , LSST, and WFIRST is to measure the growth of structure with cosmic time from weak lensing analysis over large regions of the sky. Weak lensing cosmology will be challenging: in addition to highly accurate galaxy shape measurements, statistically robust and accurate photometric redshift (photo- z ) estimates for billions of faint galaxies will be needed in order to reconstruct the three-dimensional matter distribution. Here we present an overview of and initial results from the Complete Calibration of the Color–Redshift Relation (C3R2) survey, which is designed specifically to calibrate the empirical galaxy color–redshift relation to the Euclid depth. These redshifts will also be important for the calibrations of LSST and WFIRST . The C3R2 survey is obtaining multiplexed observations with Keck (DEIMOS, LRIS, and MOSFIRE), the Gran Telescopio Canarias (GTC; OSIRIS), and the Very Large Telescope (VLT; FORS2 and KMOS) of a targeted sample of galaxies that are most important for the redshift calibration. We focus spectroscopic efforts on undersampled regions of galaxy color space identified in previous work in order to minimize the number of spectroscopic redshifts needed to map the color–redshift relation to the required accuracy. We present the C3R2 survey strategy and initial results, including the 1283 high-confidence redshifts obtained in the 2016A semester and released as Data Release 1.

  19. Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells.

    Science.gov (United States)

    Li, Mingwei; Sun, Jianxia; Zou, Feiyan; Bai, Shun; Jiang, Xinwei; Jiao, Rui; Ou, Shiyi; Zhang, Hui; Su, Zhijian; Huang, Yadong; Bai, Weibin

    2017-10-01

    The food contaminant acrylamide (AA) is usually recognized as a probable human carcinogen. In addition, AA has also been found able to induce male infertility in animals. Interestingly, resent research work revealed that the toxic effect of AA on the ability of male reproduction in vivo may due to glycidamide (GA) which is the metabolite of AA. In this study, R2C Leydig cells was used to investigate the toxic effects of GA on progesterone production. GA caused dose-dependent inhibition on the cell growth, with IC 25 , IC 50, and IC 75 values found at 0.635, 0.872, and 1.198 mM, respectively. The results of single cell gel/Comet assay showed that GA significantly induced early-phase cell apoptosis, reduced progesterone production, as well as decreasing the protein expression of steroidogenic acute regulatory (StAR) in R2C cells. Furthermore, GA induced overproduction of intracellular reactive oxygen species (ROS), upregulated Bax expression, decreased mitochondrial membrane potential, and triggered mitochondria-mediated cell apoptosis. Consequently, the downstream effector caspase-3 was activated, resulting in Leydig cells apoptosis. Overall, our results showed that GA could damage R2C Leydig cells by the lesion of the ability of progesterone genesis and inducing cells apoptosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The Complete Calibration of the Color–Redshift Relation (C3R2) Survey: Survey Overview and Data Release 1

    International Nuclear Information System (INIS)

    Masters, Daniel C.; Stern, Daniel K.; Rhodes, Jason D.; Cohen, Judith G.; Capak, Peter L.; Castander, Francisco J.; Paltani, Stéphane

    2017-01-01

    A key goal of the Stage IV dark energy experiments Euclid , LSST, and WFIRST is to measure the growth of structure with cosmic time from weak lensing analysis over large regions of the sky. Weak lensing cosmology will be challenging: in addition to highly accurate galaxy shape measurements, statistically robust and accurate photometric redshift (photo- z ) estimates for billions of faint galaxies will be needed in order to reconstruct the three-dimensional matter distribution. Here we present an overview of and initial results from the Complete Calibration of the Color–Redshift Relation (C3R2) survey, which is designed specifically to calibrate the empirical galaxy color–redshift relation to the Euclid depth. These redshifts will also be important for the calibrations of LSST and WFIRST . The C3R2 survey is obtaining multiplexed observations with Keck (DEIMOS, LRIS, and MOSFIRE), the Gran Telescopio Canarias (GTC; OSIRIS), and the Very Large Telescope (VLT; FORS2 and KMOS) of a targeted sample of galaxies that are most important for the redshift calibration. We focus spectroscopic efforts on undersampled regions of galaxy color space identified in previous work in order to minimize the number of spectroscopic redshifts needed to map the color–redshift relation to the required accuracy. We present the C3R2 survey strategy and initial results, including the 1283 high-confidence redshifts obtained in the 2016A semester and released as Data Release 1.

  1. Prediction of radiation necrosis in a rodent model using magnetic resonance imaging apparent transverse relaxation (R_{2}^{*} )

    Science.gov (United States)

    Belliveau, Jean-Guy; Jensen, Michael D.; Stewart, James M. P.; Solovey, Igor; Klassen, L. Martyn; Bauman, Glenn S.; Menon, Ravi S.

    2018-02-01

    Background and purpose. Radiation necrosis remains an irreversible long-term side-effect following radiotherapy to the brain. The ability to predict areas that could ultimately develop into necrosis could lead to prevention and management of radiation necrosis. Materials and Methods. Fischer 344 rats were irradiated using two platforms (micro-CT irradiator and x-Rad 225 IGRT) with radiation up to 30 Gy for the micro-CT and 40 Gy for the xRAD-224 to half the brain. Animals were subsequently imaged using a 9.4 T MRI scanner every 2-4 weeks for up to 28 weeks using a 7-echo gradient echo sequence. The apparent transverse relaxation constant (R2* ) was calculated and retrospectively analyzed. Results. Animals irradiated with the low-dose rate micro-CT did not exhibit any symptoms or imaging changes associated with RN. Animals irradiated with the xRAD-225 exhibited imaging changes consistent with RN at week 24. Analysis of the R2* coefficient within the lesion and hippocampus shows the potential for detection of RN up to 10 weeks prior to morphological changes. Conclusions. The ability to predict areas of RN and increases of R2* within the hippocampus provides a method for long-term monitoring and prediction of RN.

  2. Rolling Deck to Repository (R2R): A "Linked Data" Approach for the U.S. Academic Research Fleet

    Science.gov (United States)

    Arko, R. A.; Chandler, C. L.; Clark, P. D.; Milan, A.; Mize, J.

    2011-12-01

    The U.S. academic research fleet is an essential mobile observing platform for ocean science. The NSF-funded Rolling Deck to Repository (R2R) program is working with the fleet community to routinely document, assess, and preserve data from the underway sensor systems on each vessel. The R2R facility maintains a master catalog of vessels, instrument systems, operating institutions, cruises, personnel, and data sets. In less than two years, the catalog has grown to over 2,000 cruises including unique identifiers for vessel deployments, project titles, chief scientists, dates, ports, survey targets, and navigation tracks. This master catalog is of great value to peer data systems, ranging from large national data centers to small disciplinary data offices, as an aid in organizing, extending, and quality controlling their own collections and finding related data from authoritative sources. R2R breaks with the tradition of stovepipe portals built around complex search interfaces tightly bound to backend databases. Instead, we have adopted a Linked Data approach to publish our catalog content, based on the W3C Resource Description Framework (RDF) and Uniform Resource Identifiers (URIs). Our data model is published as a collection of W3C Simple Knowledge Organization System (SKOS) concepts, mapped to partner vocabularies such as those developed by the Global Change Master Directory (GCMD) and the pan-European SeaDataNet partnership, and our catalog content is published as collections of RDF resources with globally unique and persistent identifiers. The combination of exposing our data model, mapping local terms to community-wide vocabularies, and using reliable identifiers improves interoperability and reduces ambiguity. R2R's metric of success is the degree to which peer data systems routinely harvest and reuse our content. R2R is working collaboratively with the NOAA National Data Centers and the NSF-funded Biological and Chemical Oceanography Data Management Office

  3. Functional Characterization of a Novel R2R3-MYB Transcription Factor Modulating the Flavonoid Biosynthetic Pathway from Epimedium sagittatum

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    2017-07-01

    Full Text Available Epimedium species have been widely used both as traditional Chinese medicinal plants and ornamental perennials. Both flavonols, acting as the major bioactive components (BCs and anthocyanins, predominantly contributing to the color diversity of Epimedium flowers belong to different classes of flavonoids. It is well-acknowledged that flavonoid biosynthetic pathway is predominantly regulated by R2R3-MYB transcription factor (TF as well as bHLH TF and WD40 protein at the transcriptional level. MYB TFs specifically regulating anthocyanin or flavonol biosynthetic pathway have been already isolated and functionally characterized from Epimedium sagittatum, but a R2R3-MYB TF involved in regulating both these two pathways has not been functionally characterized to date in Epimedium plants. In this study, we report the functional characterization of EsMYB9, a R2R3-MYB TF previously isolated from E. sagittatum. The previous study indicated that EsMYB9 belongs to a small subfamily of R2R3-MYB TFs containing grape VvMYB5a and VvMYB5b TFs, which regulate flavonoid biosynthetic pathway. The present studies show that overexpression of EsMYB9 in tobacco leads to increased transcript levels of flavonoid pathway genes and increased contents of anthocyanins and flavonols. Yeast two-hybrid assay indicates that the C-terminal region of EsMYB9 contributes to the autoactivation activity, and EsMYB9 interacts with EsTT8 or AtTT8 bHLH regulator. Transient reporter assay shows that EsMYB9 slightly activates the expression of EsCHS (chalcone synthase promoter in transiently transformed leaves of Nicotiana benthamiana, but the addition of AtTT8 or EsTT8 bHLH regulator strongly enhances the transcriptional activation of EsMYB9 against five promoters of the flavonoid pathway genes except EsFLS (flavonol synthase. In addition, co-transformation of EsMYB9 and EsTT8 in transiently transfected tobacco leaves strongly induces the expressions of flavonoid biosynthetic genes. The

  4. Rolling Deck to Repository (R2R): A "Linked Data" Approach for the U.S. Academic Research Fleet

    Science.gov (United States)

    Arko, R.; Chandler, C.; Clark, P.; Milan, A.; Mize, J.

    2012-04-01

    The Rolling Deck to Repository (R2R; http://rvdata.us/) program is developing infrastructure to routinely document, assess, and preserve the underway sensor data from U.S. academic research vessels. The R2R master catalog of vessels, instrument systems, operating institutions, cruises, personnel, data sets, event logs, and field reports has grown to over 2,200 cruises in less than two years, and is now accessible via Web services. This catalog is of great value to peer data systems, ranging from large inter/national data centers to small disciplinary data offices, as an aid in quality controlling their own collections and finding related data from authoritative sources. R2R breaks with the tradition of stovepipe portals built around complex search interfaces tightly bound to backend databases. Instead, we have adopted a Linked Data approach to publish our catalog content, based on the W3C Resource Description Framework (RDF) and Uniform Resource Identifiers (URIs). Our data model is published as a collection of W3C Simple Knowledge Organization System (SKOS) concepts, mapped to partner vocabularies such as those developed by the Global Change Master Directory (GCMD) and the pan-European SeaDataNet partnership, and our catalog content is published as collections of RDF resources with globally unique and persistent identifiers. The combination of exposing our data model, mapping local terms to community-wide vocabularies, and using reliable identifiers improves interoperability and reduces ambiguity. R2R's metric of success is the degree to which peer data systems harvest and reuse our content. R2R is working collaboratively with the NOAA National Data Centers and the NSF-funded Biological and Chemical Oceanography Data Management Office (BCO-DMO) on a range of Linked Data pilot applications, including production of ISO-compliant metadata and deployment of a RDF Query Language (SPARQL) interface. Our objective is to support a distributed, loosely federated network of

  5. Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

    Science.gov (United States)

    Lakhashe, Samir K; Velu, Vijayakumar; Sciaranghella, Gaia; Siddappa, Nagadenahalli B; Dipasquale, Janet M; Hemashettar, Girish; Yoon, John K; Rasmussen, Robert A; Yang, Feng; Lee, Sandra J; Montefiori, David C; Novembre, Francis J; Villinger, François; Amara, Rama Rao; Kahn, Maria; Hu, Shiu-Lok; Li, Sufen; Li, Zhongxia; Frankel, Fred R; Robert-Guroff, Marjorie; Johnson, Welkin E; Lieberman, Judy; Ruprecht, Ruth M

    2011-08-05

    We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4β7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Neutralization of X4- and R5-tropic HIV-1 NL4-3 variants by HOCl-modified serum albumins

    Directory of Open Access Journals (Sweden)

    Schwalbe Birco

    2010-06-01

    Full Text Available Abstract Background Myeloperoxidase (MPO, an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl from H2O2 and chloride, which is released into body fluids. Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected in vivo. Findings This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus. The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques. Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage. Viral infection was monitored by a standard p24 or X-gal staining assay. Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV glycoprotein in contrast to non-modified albumin. Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding. In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner. Conclusions Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120. Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide.

  7. Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL to maraviroc.

    Directory of Open Access Journals (Sweden)

    Yuzhe Yuan

    Full Text Available Maraviroc, an (HIV-1 entry inhibitor, binds to CCR5 and efficiently prevents R5 human immunodeficiency virus type 1 (HIV-1 from using CCR5 as a coreceptor for entry into CD4(+ cells. However, HIV-1 can elude maraviroc by using the drug-bound form of CCR5 as a coreceptor. This property is known as noncompetitive resistance. HIV-1(V3-M5 derived from HIV-1(JR-FLan is a noncompetitive-resistant virus that contains five mutations (I304V/F312W/T314A/E317D/I318V in the gp120 V3 loop alone. To obtain genetic and structural insights into maraviroc resistance in HIV-1, we performed here mutagenesis and computer-assisted structural study. A series of site-directed mutagenesis experiments demonstrated that combinations of V3 mutations are required for HIV-1(JR-FLan to replicate in the presence of 1 µM maraviroc, and that a T199K mutation in the C2 region increases viral fitness in combination with V3 mutations. Molecular dynamic (MD simulations of the gp120 outer domain V3 loop with or without the five mutations showed that the V3 mutations induced (i changes in V3 configuration on the gp120 outer domain, (ii reduction of an anti-parallel β-sheet in the V3 stem region, (iii reduction in fluctuations of the V3 tip and stem regions, and (iv a shift of the fluctuation site at the V3 base region. These results suggest that the HIV-1 gp120 V3 mutations that confer maraviroc resistance alter structure and dynamics of the V3 loop on the gp120 outer domain, and enable interactions between gp120 and the drug-bound form of CCR5.

  8. Optimisation of the magnetic properties of mechanically milled R5.5Fe73.5-xCoxCr3B18 nanocomposites

    International Nuclear Information System (INIS)

    O'Sullivan, J.F.; Smith, P.A.I.; Coey, J.M.D.

    1998-01-01

    Mechanical milling and subsequent annealing of R 4.5 R'Fe 73.5-x Co x Cr 3 B 18 (R=Nd,Pr and R'=Tb,Dy) ingots has been found to produce hard magnetic nanocomposites of (R,R') 2 (Fe,Co) 14 B, (Fe,Cr) 2 B and α-(Fe,Co) phases. Here we report on the optimisation of the composition of such nanocomposites. Substituting different rare-earth metals has a significant effect on the magnetic properties. The replacement of Nd with Pr produces higher coercivity and remanence, and better loop squareness. However, the replacement of Tb with Dy produced inferior properties when the main rare-earth component was Nd. Improved properties were obtained with the combination of Pr and Dy or Tb. Substitution of Co for Fe was found to lower coercivity but increase the remanence. The best combination of properties measured was for Pr 4.5 Dy 1 Fe 68.5 Co 5 Cr 3 B 1x , where H c =0.41 MA/m, J r =1 T, and (BH) max for the powder was 100 kJ/m 3 . These results will be discussed in terms of the grain size and the intrinsic properties of the hard and soft magnetic phases identified using X-ray diffraction. (orig.)

  9. An R2R3-MYB transcription factor, OjMYB1, functions in anthocyanin biosynthesis in Oenanthe javanica.

    Science.gov (United States)

    Feng, Kai; Xu, Zhi-Sheng; Que, Feng; Liu, Jie-Xia; Wang, Feng; Xiong, Ai-Sheng

    2018-02-01

    This study showed that an R2R3-MYB transcription factor, OjMYB1, is involved in anthocyanin biosynthesis and accumulation in Oenanthe javanica. Anthocyanins can be used as safe natural food colorants, obtained from many plants. R2R3-MYB transcription factors (TFs) play important roles in anthocyanins biosynthesis during plant development. Oenanthe javanica is a popular vegetable with high nutritional values and numerous medical functions. O. javanica has purple petioles that are mainly due to anthocyanins accumulation. In the present study, the gene encoding an R2R3-MYB TF, OjMYB1, was isolated from purple O. javanica. Sequencing results showed that OjMYB1 contained a 912-bp open reading frame encoding 303 amino acids. Sequence alignments revealed that OjMYB1 contained bHLH-interaction motif ([DE]Lx2[RK]x3Lx6Lx3R) and ANDV motif ([A/G]NDV). Phylogenetic analysis indicated that the OjMYB1 classified into the anthocyanins biosynthesis clade. Subcellular localization assay showed that OjMYB1 was a nuclear protein in vivo. The heterologous expression of OjMYB1 in Arabidopsis could enhance the anthocyanins content and up-regulate the expression levels of the structural genes-related anthocyanins biosynthesis. Yeast two-hybrid assay indicated that OjMYB1 could interact with AtTT8 and AtEGL3 proteins. Enzymatic analysis revealed that overexpression of OjMYB1 gene up-regulated the enzyme activity of 3-O-glycosyltransferase encoded by AtUGT78D2 in transgenic Arabidopsis. Our results provided a comprehensive understanding of the structure and function of OjMYB1 TF in O. javanica.

  10. ß-Adrenergic Stimulation Increases RyR2 Activity via Intracellular Ca2+ and Mg2+ Regulation

    Science.gov (United States)

    Li, Jiao; Imtiaz, Mohammad S.; Beard, Nicole A.; Dulhunty, Angela F.; Thorne, Rick; vanHelden, Dirk F.; Laver, Derek R.

    2013-01-01

    Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs) by intracellular Ca2+ and Mg2+ and the role of these changes in SR Ca2+ release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control) and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca2+] adrenergic stimulation increased luminal Ca2+ activation of single RyR channels, decreased luminal Mg2+ inhibition and decreased inhibition of RyRs by mM cytoplasmic Mg2+. At cytoplasmic [Ca2+] >1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg2+ and Ca2+ inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca2+ activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1) increasing the activating potency of Ca2+ binding to the luminal Ca2+ site and decreasing its affinity for luminal Mg2+ and 2) decreasing affinity of the low-affinity Ca2+/Mg2+ cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter. PMID:23533585

  11. ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.

    Directory of Open Access Journals (Sweden)

    Jiao Li

    Full Text Available Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs by intracellular Ca(2+ and Mg(2+ and the role of these changes in SR Ca(2+ release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca(2+] 1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg(2+ and Ca(2+ inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca(2+ activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1 increasing the activating potency of Ca(2+ binding to the luminal Ca(2+ site and decreasing its affinity for luminal Mg(2+ and 2 decreasing affinity of the low-affinity Ca(2+/Mg(2+ cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter.

  12. Functional Characterization of Cotton GaMYB62L, a Novel R2R3 TF in Transgenic Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Hamama Islam Butt

    Full Text Available Drought stress can trigger the production of ABA in plants, in response to adverse conditions, which induces the transcript of stress-related marker genes. The R2R3 MYB TFs are implicated in regulation of various plants developmental, metabolic and multiple environmental stress responses. Here, a R2R3-MYB cloned gene, GaMYB62L, was transformed in Arabidopsis and was functionally characterized. The GaMYB62L protein contains two SANT domains with a conserved R2R3 imperfect repeats. The GaMYB62L cDNA is 1,017 bp with a CDS of 879, encodes a 292-residue polypeptide with MW of 38.78 kD and a pI value of 8.91. Overexpressed GaMYB62L transgenic Arabidopsis have increased proline and chlorophyll content, superior seed germination rate under salt and osmotic stress, less water loss rate with reduced stomatal apertures, high drought avoidance as compared to WT on water deprivation and also significant plant survival rates at low temperature. In addition, overexpressed GaMYB62L lines were more sensitive to ABA mediated germination and root elongation assay. Moreover, ABA induced GaMYB62L overexpression, enhanced the expression of ABA stress related marker genes like RD22, COR15A, ADH1, and RD29A. Together, overexpression of GaMYB62L suggested having developed better drought, salt and cold tolerance in transgenic Arabidopsis and thus presented it as a prospective candidate gene to achieve better abiotic stress tolerance in cotton crop.

  13. REDESIGN OF OUTER HOOD PANEL OF ESEMKA R2 CAR TO IMPROVE PEDESTRIAN PROTECTION USING FINITE ELEMENT MODELING

    Directory of Open Access Journals (Sweden)

    Binyamin Binyamin

    2016-12-01

    Full Text Available Traffic accidents are terrible scourge that occur in many countries, specially for developing countries where transportation affairs like tangled yarn. Besides functioning as an engine compartment cover, the hood of modern compact SUV can also help to manage the impact energy of a pedestrian’s head in a vehicle-pedestrian impact. This paper presents outer hood design of Esemka R2 that has a potential to improve hood’s ability and also to absorb the impact energy of a pedestrian’s head. The developed method for the design of an outer hood configuration aims to provide a robust design and homogeneous of Head Injury Criterion (HIC for impact position at WAD 1000 and three different thicknesses (1.25 mm, 1.35 mm & 1.50 mm of outer hood panel of Esemka R2 compact SUV, taking into consideration the limited space available for deformation. The non-linear Finite Element Analysis (FEA software (Explicit Dynamics was used in this research to simulate the testing procedurs of head impact for child pedestrian. The results show that the average of comparison dimensional of outer hood panel of Esemka R2 was 4.89 mm. The minimum of deformation space meet the requirement for HIC value which required obtaining robust and homogeneous head impact performance. Outer hood thickness and materials were identified as the factors to influence the stress and HIC value of the hood. By comparing all outer hood panels, aluminium alloy as the best selected material which has the lowest value is 32.78% for the pedestrian protection.

  14. Multiple R2R3-MYB transcription factors involved in the regulation of anthocyanin accumulation in peach flower

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    2016-10-01

    Full Text Available Anthocyanin accumulation is responsible for flower coloration in peach. Here, we report the identification and functional characterization of eight flavonoid-related R2R3-MYB transcription factors, designated PpMYB10.2, PpMYB9, PpMYBPA1, Peace, PpMYB17, PpMYB18, PpMYB19 and PpMYB20, respectively, in peach flower transcriptome. PpMYB10.2 and PpMYB9 are able to activate transcription of anthocyanin biosynthetic genes, whilst PpMYBPA1 and Peace have a strong activation on the promoters of proanthocyanin (PA biosynthetic genes. PpMYB17-20 show a strong repressive effect on transcription of flavonoid pathway genes such as DFR. These results indicate that anthocyanin accumulation in peach flower is coordinately regulated by a set of R2R3-MYB genes. In addition, PpMYB9 and PpMYB10.2 are closely related but separated into two groups, designated MYB9 and MYB10, respectively. PpMYB9 shows a strong activation on the PpUGT78A2 promoter, but with no effect on the promoter of PpUGT78B (commonly called PpUFGT in previous studies. In contrast, PpMYB10.2 is able to activate the PpUFGT promoter, but not for the PpUGT78A2 promoter. Unlike the MYB10 gene that is universally present in plants, the MYB9 gene is lost in most dicot species. Therefore, the PpMYB9 gene represents a novel group of anthocyanin-related MYB activators, which may have diverged in function from the MYB10 genes. Our study will aid in understanding the complex mechanism regulating floral pigmentation in peach and functional divergence of the R2R3-MYB gene family in plants.

  15. Transfer of deuterium from [1R-2H]- and [1S-2H] ethanol to reduced metabolites formed in vivo

    International Nuclear Information System (INIS)

    Cronholm, T.; Fors, C.

    1977-01-01

    Since alcohol dehydrogenase is stereospecific and only removes the 1-pro-R hydrogen of ethanol, it is possible to label selectively NADH formed at the alcohol dehydrogenase by using [1R- 2 H]-ethanol. In contrast, [1S- 2 H]ethanol may be used to label NADH formed in the aldehyde dehydrogenase reaction. The present investigation is an attempt to study the relationship between the NADH pools at these two dehydrogenases, with special reference to subcellular localization, by using chiral monodeuteroethanols

  16. Smooth manifolds for certain dynamical systems and periodic solitons for nonlinear Klein-Gordon equations on R2

    International Nuclear Information System (INIS)

    Vuillermot, P.A.

    1988-01-01

    We present and discuss three new theorems concerning the existence of smooth manifolds associated with certain infinite-dimensional dynamical systems defined from nonlinear Klein-Gordon equations of the form u tt (x, t) = u xx (x, t)-g(u(x, t)), where g: R → R is analytic and where (x, t) ε R 2 . In particular, we prove the nonexistence of small amplitude soliton bound state solutions in the classical Φ 4 -theory, a fact recently brought about by the perturbative analysis of Kruskal and Segur [fr

  17. Final report on the IAEA research contracts No. 1194/RB, 1194/R1/RB and 1194/R2/RB

    International Nuclear Information System (INIS)

    Zobor, E.; Janosy, J.S.; Szentgali, A.

    1980-09-01

    The final report summarizes the research activities made in the framework of the IAEA Research Contracts No. 1194/RB, 1194/R1/RB and 1194/R2/RB. A multilevel hierarchical control system is treated which uses weakly-coupled low dimensional subsystems under the supervision of a dynamic coordinator program. This self-organizing adaptive control system was checked by a 5 MW research reactor. As an example the paper describes the experimental computer control system of the 5 MW WWR-SM research reactor, where the reactor power and outlet temperature have been controlled on the basis of the treated control concept since 1978. (author)

  18. P(O)R2-Directed Enantioselective C-H Olefination toward Chiral Atropoisomeric Phosphine-Olefin Compounds.

    Science.gov (United States)

    Li, Shi-Xia; Ma, Yan-Na; Yang, Shang-Dong

    2017-04-07

    An effective synthesis of chiral atropoisomeric biaryl phosphine-olefin compounds via palladium-catalyzed enantioselective C-H olefination has been developed for the first time. The reactions are operationally simple, tolerate wide functional groups, and have a good ee value. Notably, P(O)R 2 not only acts as the directing group to direct C-H activation in order to make a useful ligand but also serves to facilitate composition of the product in a useful manner in this transformation.

  19. Electronic structure of C r2AlC as observed by angle-resolved photoemission spectroscopy

    Science.gov (United States)

    Ito, Takahiro; Pinek, Damir; Fujita, Taishi; Nakatake, Masashi; Ideta, Shin-ichiro; Tanaka, Kiyohisa; Ouisse, Thierry

    2017-11-01

    We investigate the electronic band structure and Fermi surfaces (FSs) of C r2AlC single crystals with angle-resolved photoemission spectroscopy. We evidence hole bands centered around the M points and electron bands centered around the Γ point in reciprocal space. Electron and hole bands exhibit an open, tubular structure along the c axis, confirming the quasi-two-dimensional character of this highly anisotropic, nanolamellar compound. Dependence of the photoionization cross sections on beam light polarization and orientation allows us to assess the orbital character of each observed band locally. Despite some differences, density functional theory calculations show a good agreement with experiment.

  20. New anisotropic rare earth fluorides BaR2F8(R=Y,Dy-Lu): growth and characterization

    International Nuclear Information System (INIS)

    Kaminskii, A.A.; Butashin, A.V.; Sulyanov, S.N.; Bagayev, S.N.; Eichler, H.J.; Findeisen, J.; Liu, B.; Taeuber, U.; Peuser, P.

    1998-01-01

    Polymorphism of BaR 2 F 8 compounds is analyzed, and some peculiarities of the crystal growth from the melt are discussed. We report on the orthorhombic BaLu 2 F 8 crystal with ordered structure, a new crystalline material for generating Ln 3+ activator ions. Spectroscopic and laser characteristics of Nd 3+ - and Er 3+ -doped BaLu 2 F 8 samples are discussed as representative examples. Besides, we pay special attention to monoclinic BaY 2 F 8 :Er 3+ crystals, as active media for highly efficient CW 3 μm laser-diode pumped lasers. (orig.)

  1. Effects of the mGluR2/3 agonist LY379268 on ketamine-evoked behaviours and neurochemical changes in the dentate gyrus of the rat

    NARCIS (Netherlands)

    Imre, Gabor; Salomons, Amber; Jongsma, Minke; Fokkema, Dirk S.; Den Boer, Johan A.; Ter Horst, Gert J.

    One of the functions of group 11 metabotropic glutamate receptors (mGluR2/3) is to modulate glutamate release. Thus, targeting mGluR2/3s might be a novel treatment for several psychiatric disorders associated with inappropriate glutamatergic neurotransmission, such as schizophrenia. In an effort to

  2. r2VIM: A new variable selection method for random forests in genome-wide association studies.

    Science.gov (United States)

    Szymczak, Silke; Holzinger, Emily; Dasgupta, Abhijit; Malley, James D; Molloy, Anne M; Mills, James L; Brody, Lawrence C; Stambolian, Dwight; Bailey-Wilson, Joan E

    2016-01-01

    Machine learning methods and in particular random forests (RFs) are a promising alternative to standard single SNP analyses in genome-wide association studies (GWAS). RFs provide variable importance measures (VIMs) to rank SNPs according to their predictive power. However, in contrast to the established genome-wide significance threshold, no clear criteria exist to determine how many SNPs should be selected for downstream analyses. We propose a new variable selection approach, recurrent relative variable importance measure (r2VIM). Importance values are calculated relative to an observed minimal importance score for several runs of RF and only SNPs with large relative VIMs in all of the runs are selected as important. Evaluations on simulated GWAS data show that the new method controls the number of false-positives under the null hypothesis. Under a simple alternative hypothesis with several independent main effects it is only slightly less powerful than logistic regression. In an experimental GWAS data set, the same strong signal is identified while the approach selects none of the SNPs in an underpowered GWAS. The novel variable selection method r2VIM is a promising extension to standard RF for objectively selecting relevant SNPs in GWAS while controlling the number of false-positive results.

  3. Toxic mechanisms of 3-monochloropropane-1,2-diol on progesterone production in R2C rat leydig cells.

    Science.gov (United States)

    Sun, Jianxia; Bai, Shun; Bai, Weibin; Zou, Feiyan; Zhang, Lei; Su, Zhijian; Zhang, Qihao; Ou, Shiyi; Huang, Yadong

    2013-10-16

    3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been shown to impede the male reproductive function. However, its mechanism of action remains to be elucidated. In this study, the effects of 3-MCPD on progesterone production were investigated using R2C Leydig cells. 3-MCPD caused concentration-dependent inhibition of cell viability at the IC25, IC50, and IC75 levels of 1.027, 1.802, and 3.160 mM, respectively. Single cell gel/comet assay and atomic force microscopy assay showed that 3-MCPD significantly induced early apoptosis. In addition, 3-MCPD significantly reduced progesterone production by reducing the expression of cytochrome P450 side-chain cleavage enzyme, steroidogenic acute regulatory protein, and 3β-hydroxysteroid dehydrogenase in R2C cells. The change in steroidogenic acute regulatory protein expression was highly consistent with progesterone production. Furthermore, the mitochondrial membrane potential and cAMP significantly decreased.

  4. Composition and crystallization kinetics of R2O-Al2O3-SiO2 glass-ceramics

    International Nuclear Information System (INIS)

    Xiong, Dehua; Cheng, Jinshu; Li, Hong

    2010-01-01

    The crystallization behavior and microstructure of R 2 O-Al 2 O 3 -SiO 2 (R means K, Na and Li) glass were investigated by means of differential scanning calorimeter (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The crystallization kinetic parameters including the crystallization apparent activation energy (E a ), the Avrami parameter (n), glass transition temperature (T g ) and the activity energy of glass transition (E t ) were also measured with different methods. The results have shown that: the DSC traces of composition A parent glass have two different precipitation crystallization peaks corresponding to E a1 (A) = 151.4 kJ/mol (Li 2 SiO 3 ) and E a2 (A) = 623.1 kJ/mol (Li 2 Si 2 O 5 ), the average value of n = 1.70 (Li 2 Si 2 O 5 ) for the surface crystallization and E t (A) = 202.8 kJ/mol. And E a (B) = 50.7 kJ/mol (Li 2 SiO 3 ), the average value of n = 3.89 (Li 2 SiO 3 ) for the bulk crystallization and E t (B) = 220.4 kJ/mol for the composition B parent glass. Because of the content of R 2 O is bigger than composition A, composition B parent glass has a lower E a , T g and a larger n, E t .

  5. Identification and Characterization of the Diverse Stress-Responsive R2R3-RMYB Transcription Factor from Hibiscus sabdariffa L.

    Science.gov (United States)

    Mohamed, Bahaeldeen Babikar; Aftab, Beenish; Sarwar, Muhammad Bilal; Ahmad, Zarnab; Hassan, Sameera; Husnain, Tayyab

    2017-01-01

    Various regulatory proteins play a fundamental role to manage the healthy plant growth under stress conditions. Differential display reverse transcriptase PCR and random amplification of cDNA ends (RACE) was used to explore the osmotic stress-responsive transcripts. We identified and characterized the salt stress-responsive R2R3 type RMYB transcription factor from Hibiscus sabdariffa which has an open reading frame of 690 bp, encoding 229 long chain amino acids. In silico analysis confirmed the conserved R2 and R3 domain as well as an NLS-1 localization site. The deduced amino acids of RMYB shared 83, 81, 80, 79, 72, 71, and 66% homology with Arabidopsis thaliana, Glycine max, Oryza sativa, Zea maize, Malus domestica, Populus tremula × Populus alba, and Medicago sativa specific MYB family, respectively. We observed the gene upregulation in stem, leaf, and root tissue in response to abiotic stress. Furthermore, RMYB gene was cloned into plant expression vector under CaMV35S promoter and transformed to Gossypium hirsutum: a local cotton cultivar. Overexpression of RMYB was observed in transgenic plants under abiotic stresses which further suggests its regulatory role in response to stressful conditions. The RMYB transcription factor-overexpressing in transgenic cotton plants may be used as potential agent for the development of stress tolerant crop cultivars. PMID:29181384

  6. Dispersion interactions between neighboring Bi atoms in (BiH3 )2 and Te(BiR2 )2.

    Science.gov (United States)

    Haack, Rebekka; Schulz, Stephan; Jansen, Georg

    2018-03-13

    Triggered by the observation of a short Bi⋯Bi distance and a BiTeBi bond angle of only 86.6° in the crystal structure of bis(diethylbismuthanyl)tellurane quantum chemical computations on interactions between neighboring Bi atoms in Te(BiR 2 ) 2 molecules (R = H, Me, Et) and in (BiH 3 ) 2 were undertaken. Bi⋯Bi distances atoms were found to significantly shorten upon inclusion of the d shells of the heavy metal atoms into the electron correlation treatment, and it was confirmed that interaction energies from spin component-scaled second-order Møller-Plesset theory (SCS-MP2) agree well with coupled-cluster singles and doubles theory including perturbative triples (CCSD(T)). Density functional theory-based symmetry-adapted perturbation theory (DFT-SAPT) was used to study the anisotropy of the interplay of dispersion attraction and steric repulsion between the Bi atoms. Finally, geometries and relative stabilities of syn-syn and syn-anti conformers of Te(BiR 2 ) 2 (R = H, Me, Et) and interconversion barriers between them were computed. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  7. Solid-solution stability and preferential site-occupancy in (R-R')2Fe14B compounds

    Science.gov (United States)

    Colin, C. V.; Ito, M.; Yano, M.; Dempsey, N. M.; Suard, E.; Givord, D.

    2016-06-01

    The rare-earth (R) uniaxial anisotropy of R2Fe14B compounds with magnetic R atoms (e.g., Nd or Pr) is at the origin of the exceptional hard magnetic properties achieved in magnets based on these compounds. The uniaxial anisotropy found in Ce2Fe14B is attributed mainly to the magnetism of Fe. Ce is the most abundant R element and there has been much recent effort to fabricate magnets in which Ce is partially substituted for Nd. In the present neutron study of (R1-xCex)2Fe14B (R = La or Nd), Ce is found to enter the R2Fe14B phase over the entire composition range. The crystallographic parameters decrease with increasing Ce content and the Ce atoms preferentially occupy the smaller 4f sites. It is concluded that Ce in these (RR')2Fe14B compounds essentially maintains the intermediate valence character found in Ce2Fe14B. It is proposed that, in this intermediate valence state, Ce weakly contributes to uniaxial anisotropy, thus making a link with the fact that significant coercivity is preserved in Ce-substituted NdFeB magnets.

  8. Electrically tunable transport and high-frequency dynamics in antiferromagnetic S r3I r2O7

    Science.gov (United States)

    Seinige, Heidi; Williamson, Morgan; Shen, Shida; Wang, Cheng; Cao, Gang; Zhou, Jianshi; Goodenough, John B.; Tsoi, Maxim

    2016-12-01

    We report dc and high-frequency transport properties of antiferromagnetic S r3I r2O7 . Temperature-dependent resistivity measurements show that the activation energy of this material can be tuned by an applied dc electrical bias. The latter allows for continuous variations in the sample resistivity of as much as 50% followed by a reversible resistive switching at higher biases. Such a switching is of high interest for antiferromagnetic applications in high-speed memory devices. Interestingly, we found the switching behavior to be strongly affected by a high-frequency (microwave) current applied to the sample. The microwaves at 3-7 GHz suppress the dc switching and produce resonancelike features that we tentatively associated with the dissipationless magnonics recently predicted to occur in antiferromagnetic insulators subject to ac electric fields. We have characterized the effects of microwave irradiation on electronic transport in S r3I r2O7 as a function of microwave frequency and power, strength and direction of external magnetic field, strength and polarity of applied dc bias, and temperature. Our observations support the potential of antiferromagnetic materials for high-speed/high-frequency spintronic applications.

  9. DEVELOPMENT OF CONTROL SYSTEM FOR PROGRESS OF CONSTRUCTION AND INSTALLATION WORKS BASED ON INTEGRATED APPLICATION OF Primavera P6 Professional R8.3.2 AND ArchiCAD 17.0.0 SOFTWARE PRODUCTS

    Directory of Open Access Journals (Sweden)

    V. P. Grakhov

    2017-01-01

    Full Text Available The paper considers application and development of information technologies while carrying out project management in construction. Organizational and technological support of works throughout its life cycle exerts an influence on quality and efficiency of successful implementation of the construction project. In order to achieve the project goal it is necessary perfectly to organize and plan works, distribute roles and responsibilities of the project participants, regulate composition and content of the project documentation. While analyzing technical and economic indices of construction organization activity and management systems operating in these organizations, conclusion has been made that market experience in functioning of operational management systems has not been adequately applied in practice of domestic construction organizations. Thus, introduction of integrated management systems for quality, costs, time parameters pertaining to project construction, their resource support will contribute to improvement of economic situation of construction organizations. The solution consists in application of up-to-date information technologies, maximum implementation of computer systems and programs in the sphere of production, creation of application software. It has been shown that it is necessary to develop a software model that provides a possibility comprehensively to apply information technology tools for monitoring progress of construction and installation works, systematization of information technology application that allow to control key parameters of construction and installation works, improvement of system for providing actual information in project implementation process. An example of complex application of software products Primavera P6 Professional R8.3.2 and ArchiCAD 17.0.0 is given in the paper.

  10. Effects of Plant Growth Regulators (PGRs)Sprayed at R5 on the Amino Acid Components in Soybean Seeds%R5期喷施植物生长调节剂对不同品质类型大豆籽粒氨基酸组分的影响

    Institute of Scientific and Technical Information of China (English)

    宋柏权; 赵黎明; 林思宇; 冯乃杰; 杨骥; 李建英; 郑殿峰

    2012-01-01

    In field trail, three plant growth regulators( PGRs) of SOD simulations( SODM ) ,Choline chloride( Cc) and diethyl aminoethyl hexanoate( DTA-6) were sprayed on soybeans with different quality types at R5,and the amino acid components of soybean seeds were determined after harvest. SODM , Cc and DTA-6 all reduced total amino acids content for three soybean types, the decreasing amplitude was the smallest (0.50% -1.03 % ) in high protein cultivar Heinong 35 , while was the largest in high protein and high oil cultivar Kennong 4. The three PGRs changed the ratio of different amino acids for three quality type soybeans,and all improved the contents of alanine,valine,isoleucine in high protein cultivar Heinong 35.%在大田条件下,于R5期对不同品质类型大豆品种叶片喷施SOD摸拟物(SODM)、氯化胆碱(Choline chloride,Cc)和2-N,N-二乙氨基乙基己酸酯(Diethyl aminoethyl hexanoate,DTA-6)3种植物生长调节剂,成熟收获后测定籽粒中氨基酸组分含量.结果表明:SODM、Cc、DTA-6均降低了不同品种类型大豆的氨基酸总量,其中高蛋白品种黑农35氨基酸总量降幅(0.50% ~ 1.03%)最小,而双高品种垦农4号氨基酸总量降幅(2.53% ~4.67%)最大.SODM、Cc、DTA-6对不同品质类型大豆氨基酸组分比例均有影响,三者均提高了高蛋白品种黑农35的丙氨酸、缬氨酸和异亮氨酸含量.

  11. 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. Structure-activity relationships and identification of potent and selective iGluR5 modulators

    DEFF Research Database (Denmark)

    Butini, Stefania; Pickering, Darryl S; Morelli, Elena

    2008-01-01

    (S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist. Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit iGluR5. Derivatives 5 and 7, with their unique pharmacolog...

  12. Large-scale synthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate by a stereoselective carbonyl reductase with high substrate concentration and product yield.

    Science.gov (United States)

    Liu, Zhi-Qiang; Hu, Zhong-Liang; Zhang, Xiao-Jian; Tang, Xiao-Ling; Cheng, Feng; Xue, Ya-Ping; Wang, Ya-Jun; Wu, Lin; Yao, Dan-Kai; Zhou, Yi-Teng; Zheng, Yu-Guo

    2017-05-01

    To biosynthesize the (3R,5S)-CDHH in an industrial scale, a newly synthesized stereoselective short chain carbonyl reductase (SCR) was successfully cloned and expressed in Escherichia coli. The fermentation of recombinant E. coli harboring SCR was carried out in 500 L and 5000 L fermenters, with biomass and specific activity of 9.7 g DCW/L, 15749.95 U/g DCW, and 10.97 g DCW/L, 19210.12 U/g DCW, respectively. The recombinant SCR was successfully applied for efficient production of (3R,5S)-CDHH. The scale-up synthesis of (3R,5S)-CDHH was performed in 5000 L bioreactor with 400 g/L of (S)-CHOH at 30°C, resulting in a space-time yield of 13.7 mM/h/g DCW, which was the highest ever reported. After isolation and purification, the yield and d.e. of (3R,5S)-CDHH reached 97.5% and 99.5%, respectively. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:612-620, 2017. © 2017 American Institute of Chemical Engineers.

  13. Localization of mGluR5, GABAB, GABAA, and cannabinoid receptors on the vago-vagal reflex pathway responsible for transient lower esophageal sphincter relaxation in humans: an immunohistochemical study

    NARCIS (Netherlands)

    Rohof, W. O.; Aronica, E.; Beaumont, H.; Troost, D.; Boeckxstaens, G. E.

    2012-01-01

    Background Transient lower esophageal sphincter relaxations (TLESRs) are the predominant mechanisms underlying gastro-esophageal reflux. TLESRs are mediated by a vago-vagal reflex, which can be blocked by interaction with metabotropic Glutamate Receptor 5 (mGluR5), ?-aminobutyric acid type B

  14. Initial mass function in R-associations CMaR1, Mon R1 and Mon R2 from radiodata

    International Nuclear Information System (INIS)

    Pyatunina, T.B.

    1985-01-01

    Results of search for compact radiosources in R-associations CMa R1 and Mon R1 carried out with the radiotelescope RATAN-600 at the 7.6-cm wavelength are given. The number of sources found in the association Mon R1 is approximately equal to the expected number of background extragalactic radiosources. In the association CMa R1 seven radiosources of small angular diameter with the flux greater than 30 mJy are found, two of which probably are background sources. A comparison of optical and radiodata on the association CMa R1 and previously published data on the association Mon R2 make it possible to estimate the initial mass function for associations under study: xi(M) infinity Msup(-2.7+-0.7) for stars with M approximately 10Msub(Sun)

  15. Synthesis and structural and electrical characterization of new materials Bi3R2FeTi3O15

    International Nuclear Information System (INIS)

    Gil Novoa, O.D.; Landínez Téllez, D.A.; Roa-Rojas, J.

    2012-01-01

    In this work we report the synthesis of polycrystalline samples of Bi 5 FeTi 3 O 15 and Bi 3 R 2 FeTi 3 O 15 new compounds with R=Nd, Sm, Gd, Dy, Ho and Yb. The materials were synthesized by the standard solid state reaction recipe from high purity (99.99%) powders. The structural characteristics of materials were analyzed by X-ray diffraction experiments. Rietveld refinement by the GSAS code was performed, taking the input data from the ICSD 74037 database. Results reveal that materials crystallized in orthorhombic single-phase structures and space group Fmm2. Measurements of polarization as a function of applied electric field were carried out using a Radiant Technology polarimeter. We determine the occurrence of hysteretic behaviors, which are characteristic of ferroelectric materials. The main values of remnant and coercive applied fields were observed for substitutions with Yb and Nd, which have the main atomic radii.

  16. Magnetic moment and magnetocrystalline anisotropy of 3d-ion subsystem in R2T14B

    International Nuclear Information System (INIS)

    Bartashevich, M.I.; Kudrevatykh, N.V.; Andreev, A.V.; Rejmer, V.A.

    1990-01-01

    The effect of substituting cobalt for iron on the magnetic moment, magneto-crystalline anisotropy and thermal expansion of R 2 (Fe 1-x Co x ) 14 B single crystals (R=Y, Gd, 0≤x≤0.3) is investigated. The uniaxial magnetic anisotropy constant K 1 for the 3d-subsystem passes through a maximum at T=4.2 K with increasing Co concentration. For T c the temperature dependence of K 1 does not possess a positive slope. The magnetic moment of the 3d-subsystem at 4.2 K does not exhibit the maximum at intermediate concentrations observed for most R(Fe, Co)-intermetallics. An explanation is presented of the changes in the magnetic properties. It is shown that the variation of the interatomic distances on thermal expansion should not affect the magnitude of the anisotropy constant of the 3d- and R-subsystems

  17. Strong CO+ and {{\\rm{N}}}_{2}^{+} Emission in Comet C/2016 R2 (Pan-STARRS)

    Science.gov (United States)

    Cochran, Anita L.; McKay, Adam J.

    2018-02-01

    We report on imaging and spectroscopic observations of comet C/2016 R2 (Pan-STARRS) obtained with the 0.8 m and 2.7 m telescopes of McDonald Observatory in 2017 November and December, respectively. The comet was at a heliocentric distance greater than 3 au during both sets of observations. The images showed a well-developed tail with properties that suggested it was an ion tail. The spectra confirmed that we were observing well-developed bands of CO+ and {{{N}}}2+. The {{{N}}}2+ detection was unequivocally cometary and was one of the strongest bands of {{{N}}}2+ detected in a comet spectrum. We derived the ratio of these two ions and from that we were able to derive that N2/CO = 0.15. This is the highest such ratio reported for a comet. This Letter includes data taken at The McDonald Observatory of The University of Texas at Austin.

  18. Ising versus XY anisotropy in frustrated R(2)Ti(2)O(7) compounds as "Seen" by Polarized Neutrons.

    Science.gov (United States)

    Cao, H; Gukasov, A; Mirebeau, I; Bonville, P; Decorse, C; Dhalenne, G

    2009-07-31

    We studied the field induced magnetic order in R(2)Ti(2)O(7) pyrochlore compounds with either uniaxial (R=Ho, Tb) or planar (R=Er, Yb) anisotropy, by polarized neutron diffraction. The determination of the local susceptibility tensor {chi(parallel to),chi(perpendicular)} provides a universal description of the field induced structures in the paramagnetic phase (2-270 K), whatever the field value (1-7 T) and direction. Comparison of the thermal variations of chi(parallel to) and chi(perpendicular) with calculations using the rare earth crystal field shows that exchange and dipolar interactions must be taken into account. We determine the molecular field tensor in each case and show that it can be strongly anisotropic.

  19. Thermodynamics of R-(+)-2-(4-Hydroxyphenoxy)propanoic Acid Dissolution in Methanol, Ethanol, and Methanol-Ethanol Mixture

    Science.gov (United States)

    Liu, Wei; Ma, Jinju; Yao, Xinding; Fang, Ruina; Cheng, Liang

    2018-05-01

    The solubilities of R-(+)-2-(4-hydroxyphenoxy)propanoic acid (D-HPPA) in methanol, ethanol and various methanol-ethanol mixtures are determined in the temperature range from 273.15 to 323.15 K at atmospheric pressure using a laser detecting system. The solubilities of D-HPPA increase with increasing mole fraction of ethanol in the methanol-ethanol mixtures. Experimental data were correlated with Buchowski-Ksiazczak λ h equation and modified Apelblat equation; the first one gives better approximation for the experimental results. The enthalpy, entropy and Gibbs free energy of D-HPPA dissolution in methanol, ethanol and methanol-ethanol mixtures were also calculated from the solubility data.

  20. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

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    Nan Hua

    Full Text Available Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs. In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.

  1. HF-EPR, Raman, UV/VIS light spectroscopic, and DFT studies of the ribonucleotide reductase R2 tyrosyl radical from Epstein-Barr virus.

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    Ane B Tomter

    Full Text Available Epstein-Barr virus (EBV belongs to the gamma subfamily of herpes viruses, among the most common pathogenic viruses in humans worldwide. The viral ribonucleotide reductase small subunit (RNR R2 is involved in the biosynthesis of nucleotides, the DNA precursors necessary for viral replication, and is an important drug target for EBV. RNR R2 generates a stable tyrosyl radical required for enzymatic turnover. Here, the electronic and magnetic properties of the tyrosyl radical in EBV R2 have been determined by X-band and high-field/high-frequency electron paramagnetic resonance (EPR spectroscopy recorded at cryogenic temperatures. The radical exhibits an unusually low g₁-tensor component at 2.0080, indicative of a positive charge in the vicinity of the radical. Consistent with these EPR results a relatively high C-O stretching frequency associated with the phenoxyl radical (at 1508 cm⁻¹ is observed with resonance Raman spectroscopy. In contrast to mouse R2, EBV R2 does not show a deuterium shift in the resonance Raman spectra. Thus, the presence of a water molecule as a hydrogen bond donor moiety could not be identified unequivocally. Theoretical simulations showed that a water molecule placed at a distance of 2.6 Å from the tyrosyl-oxygen does not result in a detectable deuterium shift in the calculated Raman spectra. UV/VIS light spectroscopic studies with metal chelators and tyrosyl radical scavengers are consistent with a more accessible dimetal binding/radical site and a lower affinity for Fe²⁺ in EBV R2 than in Escherichia coli R2. Comparison with previous studies of RNR R2s from mouse, bacteria, and herpes viruses, demonstrates that finely tuned electronic properties of the radical exist within the same RNR R2 Ia class.

  2. Expression of the sweetpotato R2R3-type IbMYB1a gene induces anthocyanin accumulation in Arabidopsis.

    Science.gov (United States)

    Chu, Hyosub; Jeong, Jae Cheol; Kim, Wook-Jin; Chung, Dong Min; Jeon, Hyo Kon; Ahn, Young Ock; Kim, Sun Ha; Lee, Haeng-Soon; Kwak, Sang-Soo; Kim, Cha Young

    2013-06-01

    R2R3-type MYB transcription factors (TFs) play important roles in transcriptional regulation of anthocyanins. The R2R3-type IbMYB1 is known to be a key regulator of anthocyanin biosynthesis in the storage roots of sweetpotato. We previously showed that transient expression of IbMYB1a led to anthocyanin pigmentation in tobacco leaves. In this article, we generated transgenic Arabidopsis plants expressing the IbMYB1a gene under the control of CaMV 35S promoter, and the sweetpotato SPO and SWPA2 promoters. Overexpression of IbMYBa in transgenic Arabidopsis produced strong anthocyanin pigmentation in seedlings and generated a deep purple color in leaves, stems and seeds. Reverse transcription-polymerase chain reaction analysis showed that IbMYB1a expression induced upregulation of several structural genes in the anthocyanin biosynthetic pathway, including 4CL, CHI, F3'H, DFR, AGT, AAT and GST. Furthermore, overexpression of IbMYB1a led to enhanced expression of the AtTT8 (bHLH) and PAP1/AtMYB75 genes. high-performance liquid chromatography analysis revealed that IbMYB1a expression led to the production of cyanidin as a major core molecule of anthocyanidins in Arabidopsis, as occurs in the purple leaves of sweetpotato (cv. Sinzami). This result shows that the IbMYB1a TF is sufficient to induce anthocyanin accumulation in seedlings, leaves, stems and seeds of Arabidopsis plants. Copyright © Physiologia Plantarum 2012.

  3. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae.

    Science.gov (United States)

    Lin-Wang, Kui; Bolitho, Karen; Grafton, Karryn; Kortstee, Anne; Karunairetnam, Sakuntala; McGhie, Tony K; Espley, Richard V; Hellens, Roger P; Allan, Andrew C

    2010-03-21

    The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all the commercially important rosaceous species. We use gene specific primers to show that the three MYB activators of apple anthocyanin (MYB10/MYB1/MYBA) are likely alleles of each other. MYB transcription factors, with high sequence identity to the apple gene were isolated from across the rosaceous family (e.g. apples, pears, plums, cherries, peaches, raspberries, rose, strawberry). Key identifying amino acid residues were found in both the DNA-binding and C-terminal domains of these MYBs. The expression of these MYB10 genes correlates with fruit and flower anthocyanin levels. Their function was tested in tobacco and strawberry. In tobacco, these MYBs were shown to induce the anthocyanin pathway when co-expressed with bHLHs, while over-expression of strawberry and apple genes in the crop of origin elevates anthocyanins. This family-wide study of rosaceous R2R3 MYBs provides insight into the evolution of this plant trait. It has implications for the development of new coloured fruit and flowers, as well as aiding the understanding of temporal-spatial colour change.

  4. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae

    Directory of Open Access Journals (Sweden)

    McGhie Tony K

    2010-03-01

    Full Text Available Abstract Background The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the gene determining fruit flesh and foliage anthocyanin has been termed MYB10. In order to further understand tissue-specific anthocyanin regulation we have isolated orthologous MYB genes from all the commercially important rosaceous species. Results We use gene specific primers to show that the three MYB activators of apple anthocyanin (MYB10/MYB1/MYBA are likely alleles of each other. MYB transcription factors, with high sequence identity to the apple gene were isolated from across the rosaceous family (e.g. apples, pears, plums, cherries, peaches, raspberries, rose, strawberry. Key identifying amino acid residues were found in both the DNA-binding and C-terminal domains of these MYBs. The expression of these MYB10 genes correlates with fruit and flower anthocyanin levels. Their function was tested in tobacco and strawberry. In tobacco, these MYBs were shown to induce the anthocyanin pathway when co-expressed with bHLHs, while over-expression of strawberry and apple genes in the crop of origin elevates anthocyanins. Conclusions This family-wide study of rosaceous R2R3 MYBs provides insight into the evolution of this plant trait. It has implications for the development of new coloured fruit and flowers, as well as aiding the understanding of temporal-spatial colour change.

  5. Interactions between the R2R3-MYB transcription factor, AtMYB61, and target DNA binding sites.

    Directory of Open Access Journals (Sweden)

    Michael B Prouse

    Full Text Available Despite the prominent roles played by R2R3-MYB transcription factors in the regulation of plant gene expression, little is known about the details of how these proteins interact with their DNA targets. For example, while Arabidopsis thaliana R2R3-MYB protein AtMYB61 is known to alter transcript abundance of a specific set of target genes, little is known about the specific DNA sequences to which AtMYB61 binds. To address this gap in knowledge, DNA sequences bound by AtMYB61 were identified using cyclic amplification and selection of targets (CASTing. The DNA targets identified using this approach corresponded to AC elements, sequences enriched in adenosine and cytosine nucleotides. The preferred target sequence that bound with the greatest affinity to AtMYB61 recombinant protein was ACCTAC, the AC-I element. Mutational analyses based on the AC-I element showed that ACC nucleotides in the AC-I element served as the core recognition motif, critical for AtMYB61 binding. Molecular modelling predicted interactions between AtMYB61 amino acid residues and corresponding nucleotides in the DNA targets. The affinity between AtMYB61 and specific target DNA sequences did not correlate with AtMYB61-driven transcriptional activation with each of the target sequences. CASTing-selected motifs were found in the regulatory regions of genes previously shown to be regulated by AtMYB61. Taken together, these findings are consistent with the hypothesis that AtMYB61 regulates transcription from specific cis-acting AC elements in vivo. The results shed light on the specifics of DNA binding by an important family of plant-specific transcriptional regulators.

  6. Overview of the ISS Radiation Environment Observed during the ESA EXPOSE-R2 Mission in 2014-2016

    Science.gov (United States)

    Dachev, T. P.; Bankov, N. G.; Tomov, B. T.; Matviichuk, Yu. N.; Dimitrov, Pl. G.; Häder, D.-P.; Horneck, G.

    2017-11-01

    The radiation risk radiometer-dosimeter (R3D)-R2 solid-state detector performed radiation measurements at the European Space Agency EXPOSE-R2 platform outside of the Russian "Zvezda" module at the International Space Station (ISS) from 24 October 2014 to 11 January 2016. The ISS orbital parameters were average altitude of 415 km and 51.6° inclination. We developed special software and used experimentally obtained formulas to determine the radiation flux-to-dose ratio from the R3DR2 Liulin-type deposited-energy spectrometer. We provide for the first time simultaneous, long-term estimates of radiation dose external to the ISS for four source categories: (i) galactic cosmic ray particles and their secondary products; (ii) protons in the South Atlantic Anomaly region of the inner radiation belt (IRB); (iii) relativistic electrons and/or bremsstrahlung in the outer radiation belt (ORB); and (iv) solar energetic particle (SEP) events. The latter category is new in this study. Additionally, in this study, secondary particles (SP) resulting from energetic particle interaction with the detector and nearby materials are identified. These are observed continuously at high latitudes. The detected SPs are identified using the same sorting requirements as SEP protons. The IRB protons provide the highest consistent hourly dose, while the ORB electrons and SEPs provide the most extreme hourly doses. SEPs were observed 11 times during the study interval. The R3DR2 data support calculation of average equivalent doses. The 30 day and 1 year average equivalent doses are much smaller than the skin and eyes doses recommendations by the National Council on Radiation Protection (Report 132), which provides radiation protection guidance for Low Earth Orbit.

  7. Origin of inflation in CFT driven cosmology. R2-gravity and non-minimally coupled inflaton models

    International Nuclear Information System (INIS)

    Barvinsky, A.O.; Kamenshchik, A.Yu.; Nesterov, D.V.

    2015-01-01

    We present a detailed derivation of the recently suggested new type of hill-top inflation [arXiv:1509.07270] originating from the microcanonical density matrix initial conditions in cosmology driven by conformal field theory (CFT). The cosmological instantons of topology S 1 x S 3 , which set up these initial conditions, have the shape of a garland with multiple periodic oscillations of the scale factor of the spatial S 3 -section. They describe underbarrier oscillations of the inflaton and scale factor in the vicinity of the inflaton potential maximum, which gives a sufficient amount of inflation required by the known CMB data. We build the approximation of two coupled harmonic oscillators for these garland instantons and show that they can generate inflation consistent with the parameters of the CMB primordial power spectrum in the non-minimal Higgs inflation model and in R 2 gravity. In particular, the instanton solutions provide smallness of inflationary slow-roll parameters ε and η < 0 and their relation ε ∝ η 2 characteristic of these two models. We present the mechanism of formation of hill-like inflaton potentials, which is based on logarithmic loop corrections to the asymptotically shift-invariant tree-level potentials of these models in the Einstein frame. We also discuss the role of R 2 -gravity as an indispensable finite renormalization tool in the CFT driven cosmology, which guarantees the nondynamical (ghost free) nature of its scale factor and special properties of its cosmological garland-type instantons. Finally, as a solution to the problem of hierarchy between the Planckian scale and the inflation scale we discuss the concept of a hidden sector of conformal higher spin fields. (orig.)

  8. DHEAS increases levels of GluR2/3 and GluR2, AMPA receptor subunits, in C57BL/6 mice hippocampus El DHEAS incrementa la expresión de GluR2/3 y GLUR2 del receptor AMPA en el hipocampo de ratones C57/BL6

    Directory of Open Access Journals (Sweden)

    Diego Sepúlveda Falla

    2010-05-01

    Full Text Available

    Dehydroepiandrosterone sulfate (DHEA-S is a neurosteroid that has effects such as neuromodulator of synaptic transmission and neuroprotection. The specific signaling pathways for these effects are not elucidated yet. Given that, some neurosteroids act through the activation of ionotropic glutamate receptors, therefore the effect of DHEA-S on the subunits GluR2  and GluR3 of the AMPA receptor was evaluated.  Either DHEA-S or a control substance was administered to C57/BL6 mice. Subunit expression of the AMPA receptor was analyzed by Western blotting.

     

     

    Results show that long-term DHEA-S administration to C57/BL6 mice, increases the protein levels of the subunits GluR2 and GluR2/3 of the AMPA receptors located in the hippocampus.

  9. Homoeologous Recombination of the V1r1-V1r2 Gene Cluster of Pheromone Receptors in an Allotetraploid Lineage of Teleosts

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    Lei Zhong

    2017-11-01

    Full Text Available In contrast to other olfactory receptor families that exhibit frequent lineage-specific expansions, the vomeronasal type 1 receptor (V1R family exhibits a canonical six-member repertoire in teleosts. V1r1 and V1r2 are present in no more than one copy in all examined teleosts, including salmons, which are ancient polyploids, implying strict evolutionary constraints. However, recent polyploids have not been examined. Here, we identified a young allotetraploid lineage of weatherfishes and investigated their V1r1-V1r2 cluster. We found a novel pattern that the parental V1r1-V1r2 clusters had recombined in the tetraploid genome and that the recombinant was nearly fixed in the tetraploid population. Subsequent analyses suggested strong selective pressure, for both a new combination of paralogs and homogeneity among gene duplicates, acting on the V1r1-V1r2 pair.

  10. Relocation of a rust resistance gene R 2 and its marker-assisted gene pyramiding in confection sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Qi, L L; Ma, G J; Long, Y M; Hulke, B S; Gong, L; Markell, S G

    2015-03-01

    The rust resistance gene R 2 was reassigned to linkage group 14 of the sunflower genome. DNA markers linked to R 2 were identified and used for marker-assisted gene pyramiding in a confection type genetic background. Due to the frequent evolution of new pathogen races, sunflower rust is a recurring threat to sunflower production worldwide. The inbred line Morden Cross 29 (MC29) carries the rust resistance gene, R 2 , conferring resistance to numerous races of rust fungus in the US, Canada, and Australia, and can be used as a broad-spectrum resistance resource. Based on phenotypic assessments and SSR marker analyses on the 117 F2 individuals derived from a cross of HA 89 with MC29 (USDA), R 2 was mapped to linkage group (LG) 14 of the sunflower, and not to the previously reported location on LG9. The closest SSR marker HT567 was located at 4.3 cM distal to R 2 . Furthermore, 36 selected SNP markers from LG14 were used to saturate the R 2 region. Two SNP markers, NSA_002316 and SFW01272, flanked R 2 at a genetic distance of 2.8 and 1.8 cM, respectively. Of the three closely linked markers, SFW00211 amplified an allele specific for the presence of R 2 in a marker validation set of 46 breeding lines, and SFW01272 was also shown to be diagnostic for R 2 . These newly developed markers, together with the previously identified markers linked to the gene R 13a , were used to screen 524 F2 individuals from a cross of a confection R 2 line and HA-R6 carrying R 13a . Eleven homozygous double-resistant F2 plants with the gene combination of R 2 and R 13a were obtained. This double-resistant line will be extremely useful in confection sunflower, where few rust R genes are available, risking evolution of new virulence phenotypes and further disease epidemics.

  11. Comparison of Deferasirox and deferoxamine treatment in iron-overloaded patients: liver iron concentration determined by quantitative MRI-R_2"*

    International Nuclear Information System (INIS)

    Peng Peng; Long Liling; Huang Zhongkui; Zhang Ling; Feng Xiao; Li Xiaohui; Yang Gaohui

    2013-01-01

    Objective: To explore the value of MRI-R_2"* and to compare clinical effect of two iron chelators (Deferasirox and deferoxamine) in iron-overloaded patients. Methods: By completely randomized balanced design, 24 iron-overloaded patients were randomly divided into 2 groups, which consisted of 12 patients treated with Deferasirox and 12 patients treated with deferoxamine. The planned Deferasirox dose was 40 mg · kg"-"1 · d"-"1, and the deferoxamine dose was no less than 50 mg · kg"-"1 · d"-"1. All patients underwent quantitative MRI at the time points of the primary screening, 6 months and 12 months. Pair Wilcoxon rank sum test was used to compare the differences of liver R_2"* values of the 2 groups at various time points respectively. Wilcoxon rank sum test was used to compare the differences of change rate of liver R_2"* values between the two groups at the time point of 6 months, 12 months, respectively. Results: Deferasirox group's liver R_2"* values of primary screening, 6 months and 12 months were 1081, 889 and 712 Hz, while deferoxamine group's liver R_2"* values were 1042, 838 and 488 Hz. There was no statistically significant difference between liver R_2"* values of two groups at primary screening (Z = -0.029, P > 0.05). The change rate of liver R_2"* of Deferasirox group at 12 month was -32%, while it was -58% for the deferoxamine group, and there was statistically significant difference between the two groups (Z = -3.060, P < 0.01). The change rate of serum ferritin of Deferasirox group at 12 month was -15%, while it was -55% for the deferoxamine group, and there was statistically significant difference between the two groups (Z = -2.945, P < 0.01). Conclusion: By using MRI-R_2"*, it suggest that both Deferasirox and deferoxamine can effectively remove liver iron and deferoxamine is superior to Deferasirox. (authors)

  12. Research on the Solid State Fermentation of Jerusalem Artichoke Pomace for Producing R,R-2,3-Butanediol by Paenibacillus polymyxa ZJ-9.

    Science.gov (United States)

    Cao, Can; Zhang, Li; Gao, Jian; Xu, Hong; Xue, Feng; Huang, Weiwei; Li, Yan

    2017-06-01

    R,R-2,3-butanediol (R,R-2,3-BD) was produced by Paenibacillus polymyxa ZJ-9, which was capable of utilizing inulin without previous hydrolysis. The Jerusalem artichoke pomace (JAP) derived from the conversion of Jerusalem artichoke powder into inulin extract, which was usually used for biorefinery by submerged fermentation (SMF), was utilized in solid state fermentation (SSF) to produce R,R-2,3-BD. In this study, the fermentation parameters of SSF were optimized and determined in flasks. A novel bioreactor was designed and assembled for the laboratory scale-up of SSF, with a maximum yield of R,R-2,3-BD (67.90 g/kg (JAP)). This result is a 36.3% improvement compared with the flasks. Based on the same bath of Jerusalem artichoke powder, the total output of R,R-2,3-BD increased by 38.8% for the SSF of JAP combined with the SMF of inulin extraction. Overall, the utilization of JAP for R,R-2,3-BD production was beneficial to the comprehensive utilization of Jerusalem artichoke tuber.

  13. Tissue Destruction in Bullous Pemphigoid Can Be Complement Independent and May Be Mitigated by C5aR2

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    Christian M. Karsten

    2018-03-01

    Full Text Available Bullous pemphigoid (BP, the most frequent autoimmune bullous disorder, is a paradigmatic autoantibody-mediated disease associated with autoantibodies against BP180 (type XVII collagen, Col17. Several animal models have been developed that reflect important clinical and immunological features of human BP. Complement activation has been described as a prerequisite for blister formation, however, the recent finding that skin lesions can be induced by anti-Col17 F(ab′2 fragments indicates complement-independent mechanisms to contribute to blister formation in BP. Here, C5−/− mice injected with anti-Col17 IgG showed a reduction of skin lesions by about 50% associated with significantly less skin-infiltrating neutrophils compared to wild-type mice. Reduction of skin lesions and neutrophil infiltration was seen independently of the employed anti-Col17 IgG dose. Further, C5ar1−/− mice were protected from disease development, whereas the extent of skin lesions was increased in C5ar2−/− animals. Pharmacological inhibition of C5a receptor 1 (C5aR1 by PMX53 led to reduced disease activity when applied in a prophylactic setting. In contrast, PMX-53 treatment had no effect when first skin lesions had already developed. While C5aR1 was critically involved in neutrophil migration in vitro, its role for Col17-anti-Col17 IgG immune complex-mediated release of reactive oxygen species from neutrophils was less pronounced. Our data demonstrate that complement-dependent and -independent mechanisms coexist in anti-Col17-autoantibody-mediated tissue destruction. C5aR1 and C5aR2 seem to play opposing roles in this process with C5aR1 exerting its primary effect in recruiting inflammatory cells to the skin during the early phase of the disease. Further studies are required to fully understand the role of C5aR2 in autoantibody-mediated skin inflammation.

  14. An R2R3-MYB gene, LeAN2, positively regulated the thermo-tolerance in transgenic tomato.

    Science.gov (United States)

    Meng, Xia; Wang, Jie-Ru; Wang, Guo-Dong; Liang, Xiao-Qing; Li, Xiao-Dong; Meng, Qing-Wei

    2015-03-01

    LeAN2 is an anthocyanin-associated R2R3-MYB transcription factor, but little is known about its function in imparting thermo-tolerance to higher plants. To examine the function of LeAN2 in the regulation of heat stress in tomato, LeAN2 was isolated and transgenic tomato plants were obtained. Overexpression of LeAN2 under the control of the CaMV35S promoter in tomato induced the up-regulation of several structural genes in the anthocyanin biosynthetic pathway as well as anthocyanin accumulation in transgenic tomato plants. Transgenic tomato plants showed enhanced tolerance to heat stress by maintaining higher fresh weight (FW), net photosynthetic rate (Pn) and maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm) compared with wild-type (WT) plants. Furthermore, transgenic plants showed higher non-enzymatic antioxidant activity, lower levels of reactive oxygen species (ROS), and higher contents of D1 protein than that in WT plants under heat stress. These results indicate that LeAN2 had an important function in heat stress resistance. Copyright © 2014 Elsevier GmbH. All rights reserved.

  15. Research-to-operations (R2O) for the Space Environmental Effects Fusion System (SEEFS) system-impact products

    Science.gov (United States)

    Quigley, Stephen

    The Space Vehicles Directorate of the Air Force Research Laboratory (AFRL/RVBX) and the Space Environment Branch of the Space and Missile Systems Center (SMC SLG/WMLE) have combined efforts to design, develop, test, implement, and validate numerical and graphical products for Air Force Space Command's (AFSPC) Space Environmental Effects Fusion System (SEEFS). These products are generated to analyze, specify, and forecast the effects of the near-earth space environment on Department of Defense weapons, navigation, communications, and surveillance systems. Jointly developed projects that have been completed as prototypes and are undergoing development for real-time operations include a SEEFS architecture and database, five system-impact products, and a high-level decision aid product. This first round of SEEFS products includes the Solar Radio Burst Effects (SoRBE) on radar and satellite communications, Radar Auroral Clutter (RAC), Scintillation Effects on radar and satellite communications (RadScint and SatScint), and Satellite Surface and Deep Charge/Discharge (Char/D) products. This presentation will provide overviews of the current system impact products, along with plans and potentials for future products expected for the SEEFS program. The overviews will include information on applicable research-to-operations (R2O) issues, to include input data coverage and quality control, output confidence levels, modeling standards, and validation efforts.

  16. An R2R3-type MYB transcription factor, GmMYB29, regulates isoflavone biosynthesis in soybean.

    Directory of Open Access Journals (Sweden)

    Shanshan Chu

    2017-05-01

    Full Text Available Isoflavones comprise a group of secondary metabolites produced almost exclusively by plants in the legume family, including soybean [Glycine max (L. Merr.]. They play vital roles in plant defense and have many beneficial effects on human health. Isoflavone content is a complex quantitative trait controlled by multiple genes, and the genetic mechanisms underlying isoflavone biosynthesis remain largely unknown. Via a genome-wide association study (GWAS, we identified 28 single nucleotide polymorphisms (SNPs that are significantly associated with isoflavone concentrations in soybean. One of these 28 SNPs was located in the 5'-untranslated region (5'-UTR of an R2R3-type MYB transcription factor, GmMYB29, and this gene was thus selected as a candidate gene for further analyses. A subcellular localization study confirmed that GmMYB29 was located in the nucleus. Transient reporter gene assays demonstrated that GmMYB29 activated the IFS2 (isoflavone synthase 2 and CHS8 (chalcone synthase 8 gene promoters. Overexpression and RNAi-mediated silencing of GmMYB29 in soybean hairy roots resulted in increased and decreased isoflavone content, respectively. Moreover, a candidate-gene association analysis revealed that 11 natural GmMYB29 polymorphisms were significantly associated with isoflavone contents, and regulation of GmMYB29 expression could partially contribute to the observed phenotypic variation. Taken together, these results provide important genetic insights into the molecular mechanisms underlying isoflavone biosynthesis in soybean.

  17. Transforming an EPA QA/R-2 quality management plan into an ISO 9002 quality management system.

    Science.gov (United States)

    Kell, R A; Hedin, C M; Kassakhian, G H; Reynolds, E S

    2001-01-01

    The Environmental Protection Agency's (EPA) Office of Emergency and Remedial Response (OERR) requires environmental data of known quality to support Superfund hazardous waste site projects. The Quality Assurance Technical Support (QATS) Program is operated by Shaw Environmental and Infrastructure, Inc. to provide EPA's Analytical Operations Center (AOC) with performance evaluation samples, reference materials, on-site laboratory auditing capabilities, data audits (including electronic media data audits), methods development, and other support services. The new QATS contract awarded in November 2000 required that the QATS Program become ISO 9000 certified. In a first for an EPA contractor, the QATS staff and management successfully transformed EPA's QA/R-2 type Quality Management Plan into a Quality Management System (QMS) that complies with the requirements of the internationally recognized ISO 9002 standard and achieved certification in the United States, Canada, and throughout Europe. The presentation describes how quality system elements of ISO 9002 were implemented on an already existing quality system. The psychological and organizational challenges of the culture change in QATS' day-to-day operations will be discussed for the benefit of other ISO 9000 aspirants.

  18. A chimeric repressor of petunia PH4 R2R3-MYB family transcription factor generates margined flowers in torenia.

    Science.gov (United States)

    Kasajima, Ichiro; Sasaki, Katsutomo

    2016-05-03

    The development of new phenotypes is key to the commercial development of the main floricultural species and cultivars. Important new phenotypes include features such as multiple-flowers, color variations, increased flower size, new petal shapes, variegation and distinctive petal margin colourations. Although their commercial use is not yet common, the transgenic technologies provide a potentially rapid means of generating interesting new phenotypes. In this report, we construct 5 vectors which we expected to change the color of the flower anthocyanins, from purple to blue, regulating vacuolar pH. When these constructs were transformed into purple torenia, we unexpectedly recovered some genotypes having slightly margined petals. These transgenic lines expressed a chimeric repressor of the petunia PhPH4 gene under the control of Cauliflower mosaic virus 35 S RNA promoter. PhPH4 is an R2R3-type MYB transcription factor. The transgenic lines lacked pigmentation in the petal margin cells both on the adaxial and abaxial surfaces. Expressions of Flavanone 3-hydroxylase (F3H), Flavonoid 3'-hydroxylase (F3'H) and Flavonoid 3'5'-hydroxylase (F3'5'H) genes were reduced in the margins of these transgenic lines, suggesting an inhibitory effect of PhPH4 repressor on anthocyanin synthesis.

  19. 78 FR 56921 - South Bay Salt Pond Restoration Project, Phase 2 (Ponds R3, R4, R5, S5, A1, A2W, A8, A8S, A19...

    Science.gov (United States)

    2013-09-16

    ...-F2013227943] South Bay Salt Pond Restoration Project, Phase 2 (Ponds R3, R4, R5, S5, A1, A2W, A8, A8S, A19... South Bay Salt Pond Restoration Project and consists of restoring and enhancing over 2,000 acres of... Pollution Control Plant located at 700 Los Esteros Road, San Jose, California. The details of the public...

  20. Synthesis of carbon-14 labelled cis-malonato [(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II) (SKI 2053R)

    International Nuclear Information System (INIS)

    Kim, Dae-Kee; Kim, Youngseok; Rim, Jonggill; Kim, Ganghyeok; Gam, Jongsik; Song, Sungkun; Yoo, Kwanghee; Kim, Key H.

    1994-01-01

    The synthesis of 14 C-labelled cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e]platinum(II) from [1,4- 14 C] D-tartaric acid is described. The overall radiochemical yield of the product in a eight-step sequence was 23.8% and radiochemical purity was 98.5%. (author)

  1. Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

    Science.gov (United States)

    Zhang, Yu-Dong; Wu, Chen-Jiang; Wang, Qing; Zhang, Jing; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin

    2015-08-01

    The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC). Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions. Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

  2. A constitutively expressed pair of rpoE2-chrR2 in Azospirillum brasilense Sp7 is required for survival under antibiotic and oxidative stress.

    Science.gov (United States)

    Gupta, Namrata; Kumar, Santosh; Mishra, Mukti Nath; Tripathi, Anil Kumar

    2013-02-01

    Extracytoplasmic function (ECF) sigma factors (σ(E)) are known to bring about changes in gene expression to enable bacteria to adapt to different stresses. The Azospirillum brasilense Sp245 genome harbours nine genes encoding σ(E), of which two are adjacent to the genes encoding ChrR-type zinc-binding anti-sigma (ZAS) factors. We describe here the role and regulation of a new pair of rpoE-chrR, which was found in the genome of A. brasilense Sp7 in addition to the previously described rpoE-chrR pair (designated rpoE1-chrR1). The rpoE2-chrR2 pair is also cotranscribed, and their products show protein-protein interaction. The -10 and -35 promoter elements of rpoE2-chrR2 and rpoE1-chrR1 were similar but not identical. Unlike the promoter of rpoE1-chrR1, the rpoE2-chrR2 promoter was neither autoregulated nor induced by oxidative stress. Inactivation of chrR2 or overexpression of rpoE2 in A. brasilense Sp7 resulted in an overproduction of carotenoids. It also conferred resistance to oxidative stresses and antibiotics. By controlling the synthesis of carotenoids, initiation and elongation of translation, protein folding and purine biosynthesis, RpoE2 seems to play a crucial role in preventing and repairing the cellular damage caused by oxidative stress. Lack of autoregulation and constitutive expression of rpoE2-chrR2 suggest that RpoE2-ChrR2 may provide a rapid mechanism to cope with oxidative stress, wherein singlet oxygen ((1)O(2))-mediated dissociation of the RpoE2-ChrR2 complex might release RpoE2 to drive the expression of its target genes.

  3. Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS facilitates surface expression of GluR2-containing AMPA receptors.

    Directory of Open Access Journals (Sweden)

    Hyunjeong Yang

    Full Text Available Some ubiquitin-like (UBL domain-containing proteins are known to play roles in receptor trafficking. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs undergo constitutive cycling between the intracellular compartment and the cell surface in the central nervous system. However, the function of UBL domain-containing proteins in the recycling of the AMPARs to the synaptic surface has not yet been reported.Here, we report that the Transmembrane and ubiquitin-like domain-containing 1 (Tmub1 protein, formerly known as the Hepatocyte Odd Protein Shuttling (HOPS protein, which is abundantly expressed in the brain and which exists in a synaptosomal membrane fraction, facilitates the recycling of the AMPAR subunit GluR2 to the cell surface. Neurons transfected with Tmub1/HOPS-RNAi plasmids showed a significant reduction in the AMPAR current as compared to their control neurons. Consistently, the synaptic surface expression of GluR2, but not of GluR1, was significantly decreased in the neurons transfected with the Tmub1/HOPS-RNAi and increased in the neurons overexpressing EGFP-Tmub1/HOPS. The altered surface expression of GluR2 was speculated to be due to the altered surface-recycling of the internalized GluR2 in our recycling assay. Eventually, we found that GluR2 and glutamate receptor interacting protein (GRIP were coimmunoprecipitated by the anti-Tmub1/HOPS antibody from the mouse brain. Taken together, these observations show that the Tmub1/HOPS plays a role in regulating basal synaptic transmission; it contributes to maintain the synaptic surface number of the GluR2-containing AMPARs by facilitating the recycling of GluR2 to the plasma membrane.

  4. Coordinated regulation of anthocyanin biosynthesis in Chinese bayberry (Myrica rubra) fruit by a R2R3 MYB transcription factor.

    Science.gov (United States)

    Niu, Shan-Shan; Xu, Chang-Jie; Zhang, Wang-Shu; Zhang, Bo; Li, Xian; Lin-Wang, Kui; Ferguson, Ian B; Allan, Andrew C; Chen, Kun-Song

    2010-03-01

    Chinese bayberry (Myrica rubra) is a fruit crop with cultivars producing fruit ranging from white (Shuijing, SJ) to red (Dongkui, DK) and dark red-purple (Biqi, BQ), as a result of different levels of anthocyanin accumulation. Genes encoding the anthocyanin biosynthesis enzymes chalcone synthase, chalcone isomerase, flavanone 3-hydroxylase (F3H), flavonoid 3'-hydroxylase (F3'H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS) and UDPglucose: flavonoid 3-O-glucosyltransferase (UFGT), as well as MrMYB1, a R2R3 MYB transcription factor homologous to known activators of anthocyanin biosynthesis, were isolated from ripe fruit of BQ. Differences in mRNA abundance of MrF3H, MrF3'H, MrDFR1, MrANS and MrUFGT were highly correlated with differential accumulation of anthocyanins between cultivars, suggesting coordinated regulation by transcription factors. The transcript level of MrMYB1 was strongly associated with the anthocyanin content in ripe fruit of the three cultivars, as well as different anthocyanin containing tissues of BQ fruit. Fruit bagging strongly inhibited anthocyanin accumulation in fruit as well as the expression of all anthocyanin biosynthetic genes and MrMYB1. Overexpression of MrMYB1 stimulated both anthocyanin accumulation and activated an Arabidopsis-DFR promoter in tobacco (Nicotiana tabacum). MrMYB1d, an allele with a 1 bp deletion at nucleotide 30 of coding sequence, was observed in SJ and DK fruit, suggesting that a nonsense mutation of the MYB1 protein may be responsible for no or low expression of MYB1 in the white and red fruit. These results show that coordinated expression of multiple biosynthetic genes is involved in anthocyanin accumulation in Chinese bayberry fruit, and this is regulated by MrMYB1.

  5. Anthocyanin biosynthesis in pears is regulated by a R2R3-MYB transcription factor PyMYB10.

    Science.gov (United States)

    Feng, Shouqian; Wang, Yanling; Yang, Song; Xu, Yuting; Chen, Xuesen

    2010-06-01

    Skin color is an important factor in pear breeding programs. The degree of red coloration is determined by the content and composition of anthocyanins. In plants, many MYB transcriptional factors are involved in regulating anthocyanin biosynthesis. In this study, a R2R3-MYB transcription factor gene, PyMYB10, was isolated from Asian pear (Pyrus pyrifolia) cv. 'Aoguan'. Sequence analysis suggested that the PyMYB10 gene was an ortholog of MdMYB10 gene, which regulates anthocyanin biosynthesis in red fleshed apple (Malus x domestica) cv. 'Red Field'. PyMYB10 was identified at the genomic level and had three exons, with its upstream sequence containing core sequences of cis-acting regulatory elements involved in light responsiveness. Fruit bagging showed that light could induce expression of PyMYB10 and anthocyanin biosynthesis. Quantitative real-time PCR revealed that PyMYB10 was predominantly expressed in pear skins, buds, and young leaves, and the level of transcription in buds was higher than in skin and young leaves. In ripening fruits, the transcription of PyMYB10 in the skin was positively correlated with genes in the anthocyanin pathway and with anthocyanin biosynthesis. In addition, the transcription of PyMYB10 and genes of anthocyanin biosynthesis were more abundant in red-skinned pear cultivars compared to blushed cultivars. Transgenic Arabidopsis plants overexpressing PyMYB10 exhibited ectopic pigmentation in immature seeds. The study suggested that PyMYB10 plays a role in regulating anthocyanin biosynthesis and the overexpression of PyMYB10 was sufficient to induce anthocyanin accumulation.

  6. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).

    Science.gov (United States)

    Jochems, Caroline; Tritsch, Sarah R; Pellom, Samuel Troy; Su, Zhen; Soon-Shiong, Patrick; Wong, Hing C; Gulley, James L; Schlom, Jeffrey

    2017-09-26

    M7824 (MSB0011359C) is a novel first-in-class bifunctional fusion protein consisting of a fully human IgG1 anti-PD-L1 monoclonal antibody (with structural similarities to avelumab) linked to the extracellular domain of two TGFβ receptor 2 (TGFβR2) molecules serving as a TGFβ Trap. Avelumab has demonstrated clinical activity in a range of human cancers and has been approved by the Food and Drug Administration for the therapy of Merkel cell and bladder carcinomas. Preclinical studies have shown this anti-PD-L1 is capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). In the studies reported here, it is shown that M7824 is also capable of mediating ADCC of a wide range of human carcinoma cells in vitro , employing natural killer (NK) cells as effectors, albeit not as potent as anti-PD-L1 employing some tumor cells as targets. The addition of the IL-15 superagonist fusion protein complex ALT-803 enhanced the ADCC capacity of both anti-PD-L1 and M7824, and to levels that both agents now demonstrated similar levels of ADCC of tumor cells. TGFβ is a known immunosuppressive entity. Studies reported here show TGFβ1 induced reduction of several NK activation markers as well as reduction of endogenous NK lytic activity and NK-mediated ADCC of tumor cells. These phenomena could be reduced or mitigated, however, by M7824, but not by anti-PD-L1. M7824, but not anti-PD-L1, was also shown to reduce the immunosuppressive activity of regulatory T cells on human CD4 + T-cell proliferation. These studies thus demonstrate the dual functionalities of M7824 and provide the rationale for its further clinical development.

  7. Magnetostructural coupling behavior at the ferromagnetic transition in double-perovskite S r2FeMo O6

    Science.gov (United States)

    Yang, Dexin; Harrison, Richard J.; Schiemer, Jason A.; Lampronti, Giulio I.; Liu, Xueyin; Zhang, Fenghua; Ding, Hao; Liu, Yan'gai; Carpenter, Michael A.

    2016-01-01

    The ordered double-perovskite S r2FeMo O6 (SFMO) possesses remarkable room-temperature low-field colossal magnetoresistivity and transport properties which are related, at least in part, to combined structural and magnetic instabilities that are responsible for a cubic-tetragonal phase transition near 420 K. A formal strain analysis combined with measurements of elastic properties from resonant ultrasound spectroscopy reveal a system with weak biquadratic coupling between two order parameters belonging to Γ4+ and m Γ4+ of parent space group F m 3 ¯m . The observed softening of the shear modulus by ˜50% is due to the classical effects of strain/order parameter coupling at an improper ferroelastic (Γ4+) transition which is second order in character, while the ferromagnetic order parameter (m Γ4+ ) couples only with volume strain. The influence of a third order parameter, for ordering of Fe and Mo on crystallographic B sites, is to change the strength of coupling between the Γ4+ order parameter and the tetragonal shear strain due to the influence of changes in local strain heterogeneity at a unit cell scale. High anelastic loss below the transition point reveals the presence of mobile ferroelastic twin walls which become pinned by oxygen vacancies in a temperature interval near 340 K. The twin walls must be both ferroelastic and ferromagnetic, but due to the weak coupling between the magnetic and structural order parameters it should be possible to pull them apart with a weak magnetic field. These insights into the role of strain coupling and relaxational effects in a system with only weak coupling between three order parameters allow rationalization and prediction of how static and dynamic properties of the material might be tuned in thin film form by choice of strain contrast with a substrate.

  8. Can multi-slice or navigator-gated R2* MRI replace single-slice breath-hold acquisition for hepatic iron quantification?

    International Nuclear Information System (INIS)

    Loeffler, Ralf B.; McCarville, M.B.; Song, Ruitian; Hillenbrand, Claudia M.; Wagstaff, Anne W.; Smeltzer, Matthew P.; Krafft, Axel J.; Hankins, Jane S.

    2017-01-01

    Liver R2* values calculated from multi-gradient echo (mGRE) magnetic resonance images (MRI) are strongly correlated with hepatic iron concentration (HIC) as shown in several independently derived biopsy calibration studies. These calibrations were established for axial single-slice breath-hold imaging at the location of the portal vein. Scanning in multi-slice mode makes the exam more efficient, since whole-liver coverage can be achieved with two breath-holds and the optimal slice can be selected afterward. Navigator echoes remove the need for breath-holds and allow use in sedated patients. To evaluate if the existing biopsy calibrations can be applied to multi-slice and navigator-controlled mGRE imaging in children with hepatic iron overload, by testing if there is a bias-free correlation between single-slice R2* and multi-slice or multi-slice navigator controlled R2*. This study included MRI data from 71 patients with transfusional iron overload, who received an MRI exam to estimate HIC using gradient echo sequences. Patient scans contained 2 or 3 of the following imaging methods used for analysis: single-slice images (n = 71), multi-slice images (n = 69) and navigator-controlled images (n = 17). Small and large blood corrected region of interests were selected on axial images of the liver to obtain R2* values for all data sets. Bland-Altman and linear regression analysis were used to compare R2* values from single-slice images to those of multi-slice images and navigator-controlled images. Bland-Altman analysis showed that all imaging method comparisons were strongly associated with each other and had high correlation coefficients (0.98 ≤ r ≤ 1.00) with P-values ≤0.0001. Linear regression yielded slopes that were close to 1. We found that navigator-gated or breath-held multi-slice R2* MRI for HIC determination measures R2* values comparable to the biopsy-validated single-slice, single breath-hold scan. We conclude that these three R2* methods can be

  9. Can multi-slice or navigator-gated R2* MRI replace single-slice breath-hold acquisition for hepatic iron quantification?

    Energy Technology Data Exchange (ETDEWEB)

    Loeffler, Ralf B.; McCarville, M.B.; Song, Ruitian; Hillenbrand, Claudia M. [St. Jude Children' s Research Hospital, Diagnostic Imaging, Memphis, TN (United States); Wagstaff, Anne W. [St. Jude Children' s Research Hospital, Diagnostic Imaging, Memphis, TN (United States); Rhodes College, Memphis, TN (United States); University of Alabama at Birmingham School of Medicine, Birmingham, AL (United States); Smeltzer, Matthew P. [St. Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); University of Memphis, Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, Memphis, TN (United States); Krafft, Axel J. [St. Jude Children' s Research Hospital, Diagnostic Imaging, Memphis, TN (United States); University Hospital Center Freiburg, Department of Radiology, Freiburg (Germany); Hankins, Jane S. [St. Jude Children' s Research Hospital, Department of Hematology, Memphis, TN (United States)

    2017-01-15

    Liver R2* values calculated from multi-gradient echo (mGRE) magnetic resonance images (MRI) are strongly correlated with hepatic iron concentration (HIC) as shown in several independently derived biopsy calibration studies. These calibrations were established for axial single-slice breath-hold imaging at the location of the portal vein. Scanning in multi-slice mode makes the exam more efficient, since whole-liver coverage can be achieved with two breath-holds and the optimal slice can be selected afterward. Navigator echoes remove the need for breath-holds and allow use in sedated patients. To evaluate if the existing biopsy calibrations can be applied to multi-slice and navigator-controlled mGRE imaging in children with hepatic iron overload, by testing if there is a bias-free correlation between single-slice R2* and multi-slice or multi-slice navigator controlled R2*. This study included MRI data from 71 patients with transfusional iron overload, who received an MRI exam to estimate HIC using gradient echo sequences. Patient scans contained 2 or 3 of the following imaging methods used for analysis: single-slice images (n = 71), multi-slice images (n = 69) and navigator-controlled images (n = 17). Small and large blood corrected region of interests were selected on axial images of the liver to obtain R2* values for all data sets. Bland-Altman and linear regression analysis were used to compare R2* values from single-slice images to those of multi-slice images and navigator-controlled images. Bland-Altman analysis showed that all imaging method comparisons were strongly associated with each other and had high correlation coefficients (0.98 ≤ r ≤ 1.00) with P-values ≤0.0001. Linear regression yielded slopes that were close to 1. We found that navigator-gated or breath-held multi-slice R2* MRI for HIC determination measures R2* values comparable to the biopsy-validated single-slice, single breath-hold scan. We conclude that these three R2* methods can be

  10. Synthesis of (R)-5-(Di[2,3-3H2]propylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one-([3H]U-86170) and (R)-5-([2,3-3H2]propylamino)-5,6-dihydro-4H-imidazo(4,5,1-ij) quinolin-2(1H)-one ([3H]U-91356)

    International Nuclear Information System (INIS)

    Moon, M.W.; Hsi, R.S.P.

    1992-01-01

    (R)-5-(diallylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one (12b) was prepared in 9% overall yield from 3-aminoquinoline. Reaction of 12b in ethyl acetate with tritium gas in presence of a 5% platinum on carbon catalyst afforded a mixture of (R)-5-(di[2,3- 3 H 2 ]propylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2(1H)-one ([ 3 H]U-86170, 69 Ci/mmol) and (R)-5-([2,3- 3 H 2 ]-propylamino)5,6-dihydro-4H-imidazo-[4,5,1-ij]quinolin-2(1H)-one ( [ 3 H]U-91356, 34 Ci/mmol) which was separated by preparative reverse-phase chromatography. U-86170 and U-91356 are potent dopamine D2 agonists. The labelled compounds are useful for drug disposition studies. [ 3 H]U-86170 is also useful as a dopamine D2 agonist radioligand for receptor binding studies. (author)

  11. High-resolution structural and functional assessments of cerebral microvasculature using 3D Gas ΔR2*-mMRA.

    Science.gov (United States)

    Huang, Chien-Hsiang; Chen, Chiao-Chi V; Siow, Tiing-Yee; Hsu, Sheng-Hsiou S; Hsu, Yi-Hua; Jaw, Fu-Shan; Chang, Chen

    2013-01-01

    The ability to evaluate the cerebral microvascular structure and function is crucial for investigating pathological processes in brain disorders. Previous angiographic methods based on blood oxygen level-dependent (BOLD) contrast offer appropriate visualization of the cerebral vasculature, but these methods remain to be optimized in order to extract more comprehensive information. This study aimed to integrate the advantages of BOLD MRI in both structural and functional vascular assessments. The BOLD contrast was manipulated by a carbogen challenge, and signal changes in gradient-echo images were computed to generate ΔR2* maps. Simultaneously, a functional index representing the regional cerebral blood volume was derived by normalizing the ΔR2* values of a given region to those of vein-filled voxels of the sinus. This method is named 3D gas ΔR2*-mMRA (microscopic MRA). The advantages of using 3D gas ΔR2*-mMRA to observe the microvasculature include the ability to distinguish air-tissue interfaces, a high vessel-to-tissue contrast, and not being affected by damage to the blood-brain barrier. A stroke model was used to demonstrate the ability of 3D gas ΔR2*-mMRA to provide information about poststroke revascularization at 3 days after reperfusion. However, this technique has some limitations that cannot be overcome and hence should be considered when it is applied, such as magnifying vessel sizes and predominantly revealing venous vessels.

  12. CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.

    Science.gov (United States)

    Horejsí, Zuzana; Takai, Hiroyuki; Adelman, Carrie A; Collis, Spencer J; Flynn, Helen; Maslen, Sarah; Skehel, J Mark; de Lange, Titia; Boulton, Simon J

    2010-09-24

    TEL2 interacts with and is essential for the stability of all phosphatidylinositol 3-kinase-related kinases (PIKKs), but its mechanism of action remains unclear. Here, we show that TEL2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (CK2). Proteomic analyses establish that the CK2 phosphosite of TEL2 confers binding to the R2TP/prefoldin-like complex, which possesses chaperon/prefoldin activities required during protein complex assembly. The PIH1D1 subunit of the R2TP complex binds directly to the CK2 phosphosite of TEL2 in vitro and is required for the TEL2-R2TP/prefoldin-like complex interaction in vivo. Although the CK2 phosphosite mutant of TEL2 retains association with the PIKKs and HSP90 in cells, failure to interact with the R2TP/prefoldin-like complex results in instability of the PIKKs, principally mTOR and SMG1. We propose that TEL2 acts as a scaffold to coordinate the activities of R2TP/prefoldin-like and HSP90 chaperone complexes during the assembly of the PIKKs. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Optimization of Xylanase Production through Response Surface Methodology by Fusarium sp. BVKT R2 Isolated from forest soil and its applications in saccharification

    Directory of Open Access Journals (Sweden)

    Ramanjaneyulu Golla

    2016-09-01

    Full Text Available AbstractXylanses are hydrolytic enzymes with wide applications in several industries like biofuels, paper and pulp, deinking, food and feed. The present study was aimed at hitting at high yield xylanase producing fungi from natural resources. Two highest xylanase producing fungal isolates - Q12 and L1were picked from collection of 450 fungal cultures for the utilization of xylan. These fungal isolates - Q12 and L1 were identified basing on ITS gene sequencing analysis as Fusarium sp. BVKT R2 (KT119615 and Fusarium strain BRR R6 (KT119619, respectively with construction of phylogenetic trees. Fusarium sp. BVKT R2 was further optimized for maximum xylanase production and the interaction effects between variables on production of xylanase were studied through response surface methodology. The optimal conditions for maximal production of xylanase were sorbitol 1.5%, yeast extract 1.5%, pH of 5.0, Temperature of 32.5ºC, and agitation of 175 rpm. Under optimal conditions, the yields of xylanase production by Fusarium sp. BVKT R2 was as high as 4560 U/ml in SmF. Incubation of different lignocellulosic biomasses with crude enzyme of Fusarium sp. BVKT R2 at 37°C for 72 h could achieve about 45% saccharification. The results suggest that Fusarium sp. BVKT R2 has potential applications in saccharification process of biomass.Key words: Fusarium sp., Optimization, Response Surface Methodology, Saccharification, Submerged fermentation, Xylanase

  14. Dynamic Changes in Striatal mGluR1 But Not mGluR5 during Pathological Progression of Parkinson's Disease in Human Alpha-Synuclein A53T Transgenic Rats: A Multi-PET Imaging Study.

    Science.gov (United States)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Furutsuka, Kenji; Nengaki, Nobuki; Shimoda, Yoko; Shiomi, Satoshi; Takei, Makoto; Hashimoto, Hiroki; Yui, Joji; Wakizaka, Hidekatsu; Hatori, Akiko; Xie, Lin; Kumata, Katsushi; Zhang, Ming-Rong

    2016-01-13

    Parkinson's disease (PD) is a prevalent degenerative disorder affecting the CNS that is primarily characterized by resting tremor and movement deficits. Group I metabotropic glutamate receptor subtypes 1 and 5 (mGluR1 and mGluR5, respectively) are important targets for investigation in several CNS disorders. In the present study, we investigated the in vivo roles of mGluR1 and mGluR5 in chronic PD pathology by performing longitudinal positron emission tomography (PET) imaging in A53T transgenic (A53T-Tg) rats expressing an abnormal human α-synuclein (ASN) gene. A53T-Tg rats showed a dramatic decline in general motor activities with age, along with abnormal ASN aggregation and striatal neuron degeneration. In longitudinal PET imaging, striatal nondisplaceable binding potential (BPND) values for [(11)C]ITDM (N-[4-[6-(isopropylamino) pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[(11)C]methylbenzamide), a selective PET ligand for mGluR1, temporarily increased before PD symptom onset and dramatically decreased afterward with age. However, striatal BPND values for (E)-[(11)C]ABP688 [3-(6-methylpyridin-2-ylethynyl)-cyclohex-2-enone-(E)-O-[(11)C]methyloxime], a specific PET ligand for mGluR5, remained constant during experimental terms. The dynamic changes in striatal mGluR1 BPND values also showed a high correlation in pathological decreases in general motor activities. Furthermore, declines in mGluR1 BPND values were correlated with decreases in BPND values for [(18)F]FE-PE2I [(E)-N-(3-iodoprop-2E-enyl)-2β-carbo-[(18)F]fluoroethoxy-3β-(4-methylphenyl) nortropane], a specific PET ligand for the dopamine transporter, a biomarker for dopaminergic neurons. In conclusion, our results have demonstrated for the first time that dynamic changes occur in mGluR1, but not mGluR5, that accompany pathological progression in a PD animal model. Synaptic signaling by glutamate, the principal excitatory neurotransmitter in the brain, is modulated by group I metabotropic glutamate

  15. High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7T.

    Science.gov (United States)

    Betts, Matthew J; Acosta-Cabronero, Julio; Cardenas-Blanco, Arturo; Nestor, Peter J; Düzel, Emrah

    2016-09-01

    Quantitative susceptibility mapping (QSM) has recently emerged as a novel magnetic resonance imaging (MRI) method to detect non-haem iron deposition, calcifications, demyelination and vascular lesions in the brain. It has been suggested that QSM is more sensitive than the more conventional quantifiable MRI measure, namely the transverse relaxation rate, R2*. Here, we conducted the first high-resolution, whole-brain, simultaneously acquired, comparative study of the two techniques using 7Tesla MRI. We asked which of the two techniques would be more sensitive to explore global differences in tissue composition in elderly adults relative to young subjects. Both QSM and R2* revealed strong age-related differences in subcortical regions, hippocampus and cortical grey matter, particularly in superior frontal regions, motor/premotor cortices, insula and cerebellar regions. Within the basal ganglia system-but also hippocampus and cerebellar dentate nucleus-, QSM was largely in agreement with R2* with the exception of the globus pallidus. QSM, however, provided superior anatomical contrast and revealed age-related differences in the thalamus and in white matter, which were otherwise largely undetected by R2* measurements. In contrast, in occipital cortex, age-related differences were much greater with R2* compared to QSM. The present study, therefore, demonstrated that in vivo QSM using ultra-high field MRI provides a novel means to characterise age-related differences in the human brain, but also combining QSM and R2* using multi-gradient recalled echo imaging can potentially provide a more complete picture of mineralisation, demyelination and/or vascular alterations in aging and disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. MCSA Windows Server 2012 R2 complete study guide exams 70-410, 70-411, 70-412, and 70-417

    CERN Document Server

    Panek, William

    2014-01-01

    Prepare for the MCSA Windows Server 2012 R2 Exams Microsoft's new version of the MCSA certification for WindowsServer 2012 R2 requires passing three exams (or one Upgrade exam ifyou have your MCSA or MCITP in Windows Server 2008). Thisvalue-priced study guide includes more than 1,000 pages of qualityexam-prep content, covering 100% of the objective domains of allthree exams (as well as the Upgrade exam, 70-417). In addition, you get access to an interactive practice testenvironment with more than 500 questions, electronic flashcards,and videos showing how to perform the more difficult tasks.

  17. Survival of the lichen model system Circinaria gyrosa before flight to the ISS (EXPOSE R2 mission)

    Science.gov (United States)

    De la Torre Noetzel, Rosa

    Abstract Space Verification Tests (SVT) are necessary for selection of the most promising biological organisms for flight experiments in Low Earth Orbit or other space destinations: Simulation of sample assembly, exposure to expected space parameters and sample disassembly are significantly advanced by such tests, will be performed with this tests, allowing post-analysis of the exposed biological material and thus a deeper understanding of the individual and synergistic effects of space. In this work we present the results obtained with the lichen species Circinaria gyrosa after the SVT 2 run-2 tests concerning the EXPOSE-R2 Mission Preflight Test Program, performed at the planetary and space simulation facilities at DLR (Deutsches Zentrum für Luft- und Raumfahrt, Cologne, Germany) [1], from October 2013 to January 2014. This vagrant lichen species was collected at the steppic highlands of Central Spain and defined as “astrobiological model system” due to previous test at space missions (BIOPAN-6, Foton M-3) [2, 3], Therefore, C. gyrosa is part of the BIOMEX experiment (Biology and Mars Experiment, ESA) [4] which will be exposed from July 2014 to January 2016 on board of EXPOSE R2 on the International Space Station. C. gyrosa was exposed at DLR to simulated space- and Mars parameters: a) space vacuum 10-5 Pa, space UV-radiation (200-400 nm, fluence of 12 months mission = 5 x 105 kJm-2) and temperature fluctuations (-25 ºC to 10 ºC); b); Mars Simulated CO2 atmosphere, Mars pressure of 103 Pa, Mars UV-radiation (200-400 nm), and temperature fluctuations (-25 ºC to 10 ºC). In line with the lichen's well studied adaptations to harsh environmental conditions [5, 6] we observed a high recovery- and resistance capacity of C. gyrosa which was demonstrated after a 72 hours re-activation process of in the UV-Radiation and Bioclimatology Laboratories of INTA (Atmospheric Research and Instrumentation, Dept. Earth Observation). These results confirm the high survival

  18. mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant delayed matching/non-matching-to-sample task

    Science.gov (United States)

    LaCrosse, Amber L.; Burrows, Brian T.; Angulo, Rachel M.; Conrad, Phoebe R.; Himes, Sarah M.; Mathews, Nordia; Wegner, Scott A.; Taylor, Sara B.; Olive, M. Foster

    2014-01-01

    Rationale Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert pro-cognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. Objectives To determine the ability of the mGluR5 PAM 3-cyano-N-1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the NMDA receptor antagonist MK-801. Methods Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS→DMS or DMS→DNMS). In Experiment 1, rats were treated daily prior to each session with either vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. Results In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle+MK−801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801, and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning and no other group differences were observed. Conclusions MK-801 induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in initial task learning or when treatment was initiated following task reversal. PMID:24973895

  19. Structural basis for site-specific reading of unmodified R2 of histone H3 tail by UHRF1 PHD finger

    Institute of Scientific and Technical Information of China (English)

    Chengkun Wang; Jie Shen; Zhongzheng Yang; Ping Chen; Bin Zhao; Wei Hu; Wenxian Lan

    2011-01-01

    Dear Editor,We report two NMR complex structures of PHDUHRF1 binding to unmodified or K9 trimethylated histone tails,which clarify a controversy regarding how the binding of UHRF1 to H3 tails is mediated.Based on our structures,H3R2,not H3K9,mediates PHD binding.

  20. Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer.

    Science.gov (United States)

    Wang, Qi; Li, Juanjuan; Wu, Wei; Shen, Ruizhe; Jiang, He; Qian, Yuting; Tang, Yanping; Bai, Tingting; Wu, Sheng; Wei, Lumin; Zang, Yi; Zhang, Ji; Wang, Lifu

    2016-03-08

    The importance of Pituitary homeobox 2 (Pitx2) in malignancy remains enigmatic, and Pitx2 has not been previously implicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed gene expression profiling of human PDAC tissues and identified Pitx2 as a promising candidate. Pitx2 expression was decreased from 2.6- to 19-fold in human PDAC tissues from microarray units. Immunochemistry staining showed that Pitx2 expression was moderate to intense in normal pancreatic and pancreatic intraepithelial neoplastic lesions, whereas low in human PDAC tissues. The Pitx2 levels correlated with overall patient survival post-operatively in PDAC. Induction of Pitx2 expression partly inhibited the malignant phenotype of PDAC cells. Interestingly, low Pitx2 expression was correlated with Smad4 mutant inactivation, but not with Pitx2 DNA-methylation. Furthermore, Smad4 protein bound to Pitx2 promoter and stimulated Pitx2 expression in PDAC. In addition, Pitx2 protein bound to the promoter of the protein phosphatase 2A regulatory subunit B55α (PPP2R2A) and upregulated PPP2R2A expression, which may activate dephosphorylation of Akt in PDAC. These findings provide new mechanistic insights into Pitx2 as a tumor suppressor in the downstream of Smad4. And Pitx2 protein promotes PPP2R2A expression which may inhibit Akt pathway. Therefore, we propose that the Smad4-Pitx2-PPP2R2A axis, a new signaling pathway, suppresses the pancreatic carcinogenesis.

  1. Calculations of the magnetic properties of R2M14B intermetallic compounds (R=rare earth, M=Fe, Co)

    International Nuclear Information System (INIS)

    Ito, Masaaki; Yano, Masao; Dempsey, Nora M.; Givord, Dominique

    2016-01-01

    The hard magnetic properties of “R–M–B” (R=rare earth, M=mainly Fe) magnets derive from the specific intrinsic magnetic properties encountered in Fe-rich R 2 M 14 B compounds. Exchange interactions are dominated by the 3d elements, Fe and Co, and may be modeled at the macroscopic scale with good accuracy. Based on classical formulae that relate the anisotropy coefficients to the crystalline electric field parameters and exchange interactions, a simple numerical approach is used to derive the temperature dependence of anisotropy in various R 2 Fe 14 B compounds (R=Pr, Nd, Dy). Remarkably, a unique set of crystal field parameters give fair agreement with the experimentally measured properties of all compounds. This implies reciprocally that the properties of compounds that incorporate a mixture of different rare-earth elements may be predicted accurately. This is of special interest for material optimization that often involves the partial replacement of Nd with another R element and also the substitution of Co for Fe. - Highlights: • Anisotropy constants derived from CEF parameters of R 2 M 14 B compounds (M=Fe, Co). • Anisotropy constants of all R 2 Fe 14 B compounds using unique set of CEF parameters. • Moment non-collinearity in magnetization processes under B app along hard axis.

  2. Purification, crystallization and preliminary X-ray diffraction analysis of the IL-20-IL-20R1-IL-20R2 complex

    Energy Technology Data Exchange (ETDEWEB)

    Logsdon, Naomi J.; Allen, Christopher E.; Rajashankar, Kanagalaghatta R.; Walter, Mark R. (Cornell); (UAB)

    2012-02-08

    Interleukin-20 (IL-20) is an IL-10-family cytokine that regulates innate and adaptive immunity in skin and other tissues. In addition to protecting the host from various external pathogens, dysregulated IL-20 signaling has been shown to contribute to the pathogenesis of human psoriasis. IL-20 signals through two cell-surface receptor heterodimers, IL-20R1-IL-20R2 and IL-22R1-IL-20R2. In this report, crystals of the IL-20-IL-20R1-IL-20R2 ternary complex have been grown from polyethylene glycol solutions. The crystals belonged to space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = 111, c = 135 {angstrom}, and diffracted X-rays to 3 {angstrom} resolution. The crystallographic asymmetric unit contains one IL-20-IL-20R1-IL-20R2 complex, corresponding to a solvent content of approximately 54%.

  3. A concise route to branched erythrono-gamma-lactones. Synthesis of the leaf-closing substance potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate

    DEFF Research Database (Denmark)

    Pedersen, Daniel Sejer; Robinson, Tony V; Taylor, Dennis K

    2009-01-01

    -94% yield), including the natural plant lactone (+/-)-2-C-d-methylerythrono-1,4-lactone 1. The latter compound was treated with aqueous potassium hydroxide to afford potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate 2, which is a leaf-closing substance of Leucaena leucocephalam....

  4. SYNTHESIS OF ENANTIOMERICALLY PURE (R)-2-SULFANYLPROPANOIC AND (S)-2-SULFANYLPROPANOIC ACIDS (THIOLACTIC ACID) FROM ETHYL (S)-LACTATE USING PIG-LIVER ESTERASE

    NARCIS (Netherlands)

    HOF, RP; KELLOGG, RM

    1995-01-01

    The methanesulfonates of optically pure ethyl (S)-lactate or ethyl (R)-2-chloropropanoate 5, obtained with inversion of configuration from ethyl (S)-lactate on treatment with SOCl2, can be substituted by caesium thiolates with inversion of configuration to yield (R) and (S) ethyl

  5. The Implementation of the Responsibility to Protect (R2P) Norms by the African Standby Force in Sub-Saharan Africa

    Science.gov (United States)

    2017-06-09

    Security Council to intervene in situations where genocide, war crimes, and crimes against humanity are occurring to protect civilians. In this regard...Republic of the Congo PSC Peace and Security Council R2P Responsibility to Protect REC Regional Economic Communities SADC Southern Africa...Development Community SADCBRIG Southern Africa Development Community Standby Brigade UN United Nations UNSC United Nations Security Council x

  6. Fasting induces IL-1 resistance and free fatty acid-mediated up-regulation of IL-1R2 and IL-1RA

    Directory of Open Access Journals (Sweden)

    jenifer j joesting

    2014-07-01

    Full Text Available Objective: Weight loss is a near societal obsession and many diet programs use significant calorie restriction (CR including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 hr fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 hrs. Expression of the endogenous IL-1 antagonists IL-1 receptor type 2 (IL-1R2 and IL-1 receptor antagonist (IL-1RA were determined as were sickness behaviors before and after IL-1 administration.Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver and IL-1RA (68-fold in liver. Fasted mice were protected from IL-1-induced weight loss, hypoglycemia, loss of locomotor and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1 on IL-1R2 gene expression in adipose tissue and liver (2.6-fold and 1.6-fold, respectively. Fasting not only increased IL-1RA and IL-1R2 protein 2.5-fold and 3.2-fold, respectively, in liver; but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14-fold and 11-fold, respectively. Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.

  7. Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.

    Science.gov (United States)

    Barker, Jacqueline M; Lench, Daniel H; Chandler, L Judson

    2016-01-01

    Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior. In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior. Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session. Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior. Together

  8. Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.

    Science.gov (United States)

    Qiu, Weihua; Zhou, Bingsen; Darwish, Dana; Shao, Jimin; Yen, Yun

    2006-02-10

    Ribonucleotide reductase (RR) is a highly regulated enzyme in the deoxyribonucleotide synthesis pathway. RR is responsible for the de novo conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. Besides two subunits, hRRM1 and hRRM2, p53R2 is a newly identified member of RR family that is induced by ultraviolet light in a p53-dependent manner. To understand the molecular interaction of RR subunits, we employed a eukaryotic expression system to express and purify all three subunits. After in vitro reconstitution, the results of [(3)H]CDP reduction assay showed that both eukaryotic recombinant hRRM2 and p53R2 proteins could interact with hRRM1 to form functional RR holoenzyme. The reconstituted RR activity was time-dependent and the reaction rate reached the plateau phase after 40min incubation. No matter the concentration, RR holoenzyme reconstituted from p53R2 and hRRM1 could only achieve about 40-75% kinetic activity of that from hRRM2 and hRRM1. The synthetic C-terminal heptapeptide competition assays confirmed that hRRM2 and p53R2 share the same binding site on hRRM1, but the binding site on hRRM1 demonstrated higher affinity for hRRM2 than for p53R2. In allosteric regulation assay, the effect of activation or inhibition of hRRM1 with ATP or dATP suggested that these effectors could regulate RR activity independent of different RR small subunits. Taken together, the eukaryotic expression system RR holoenzyme will provide a very useful tool to understand the molecular mechanisms of RR activity and the interactions of its subunits.

  9. Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts.

    Science.gov (United States)

    Gao, Lu; Tao, Yi; Hu, Tianxiao; Liu, Weina; Xu, Chen; Liu, Jie; You, Xingji; Gu, Hang; Ni, Xin

    2012-10-01

    CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E(2)) and progesterone (P(4)) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E(2), whereas increased P(4) production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E(2) but increased P(4) production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E(2) production and an increase in P(4) production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E(2) production but not decreased P(4) production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E(2) and P(4) production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E(2) production and decreased P(4) production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.

  10. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

    International Nuclear Information System (INIS)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-01-01

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca 2+ permeability, we investigated whether Ca 2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca 2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  11. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

    Science.gov (United States)

    Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

    2009-10-15

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  12. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    International Nuclear Information System (INIS)

    Golubovskaya, Vita M; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G

    2013-01-01

    Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site. By different assays in isogenic HCT116p53 + / + and HCT116 p53 - / - cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53 + / + but not in HCT116 p53 - / - xenografts in vivo. In addition, R2 sensitized HCT116p53 + / + cells to doxorubicin and 5-fluorouracil. Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches

  13. Analysis of the DNA-Binding Activities of the Arabidopsis R2R3-MYB Transcription Factor Family by One-Hybrid Experiments in Yeast.

    Directory of Open Access Journals (Sweden)

    Zsolt Kelemen

    Full Text Available The control of growth and development of all living organisms is a complex and dynamic process that requires the harmonious expression of numerous genes. Gene expression is mainly controlled by the activity of sequence-specific DNA binding proteins called transcription factors (TFs. Amongst the various classes of eukaryotic TFs, the MYB superfamily is one of the largest and most diverse, and it has considerably expanded in the plant kingdom. R2R3-MYBs have been extensively studied over the last 15 years. However, DNA-binding specificity has been characterized for only a small subset of these proteins. Therefore, one of the remaining challenges is the exhaustive characterization of the DNA-binding specificity of all R2R3-MYB proteins. In this study, we have developed a library of Arabidopsis thaliana R2R3-MYB open reading frames, whose DNA-binding activities were assayed in vivo (yeast one-hybrid experiments with a pool of selected cis-regulatory elements. Altogether 1904 interactions were assayed leading to the discovery of specific patterns of interactions between the various R2R3-MYB subgroups and their DNA target sequences and to the identification of key features that govern these interactions. The present work provides a comprehensive in vivo analysis of R2R3-MYB binding activities that should help in predicting new DNA motifs and identifying new putative target genes for each member of this very large family of TFs. In a broader perspective, the generated data will help to better understand how TF interact with their target DNA sequences.

  14. Usefulness of R2* maps generated by iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation sequence for cerebral artery dissection

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Ayumi; Shinohara, Yuki; Fujii, Shinya; Miyoshi, Fuminori; Kuya, Keita; Ogawa, Toshihide [Tottori University, Division of Radiology, Department of Pathophysiological, and Therapeutic Science, Faculty of Medicine, Yonago (Japan); Yamashita, Eijiro [Tottori University Hospital, Division of Clinical Radiology, Yonago (Japan)

    2015-09-15

    Acute intramural hematoma resulting from cerebral artery dissection is usually visualized as a region of intermediate signal intensity on T1-weighted images (WI). This often causes problems with distinguishing acute atheromatous lesions from surrounding parenchyma and dissection. The present study aimed to determine whether or not R2* maps generated by the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation sequence (IDEAL IQ) can distinguish cerebral artery dissection more effectively than three-dimensional variable refocusing flip angle TSE T1WI (T1-CUBE) and T2*WI. We reviewed data from nine patients with arterial dissection who were assessed by MR images including R2* maps, T2*WI, T1-CUBE, and 3D time-of-flight (TOF)-MRA. We visually assessed intramural hematomas in each patient as positive (clearly visible susceptibility effect reflecting intramural hematoma as hyperintensity on R2* map and hypointensity on T2*WI), negative (absent intramural hematoma), equivocal (difficult to distinguish between intramural hematoma and other paramagnetic substances such as veins, vessel wall calcification, or hemorrhage) and not evaluable (difficult to determine intramural hematoma due to susceptibility artifacts arising from skull base). Eight of nine patients were assessed during the acute phase. Lesions in all eight patients were positive for intramural hematoma corresponding to dissection sites on R2* maps, while two lesions were positive on T2*WI and three lesions showed high-intensity on T1-CUBE reflected intramural hematoma during the acute phase. R2* maps generated using IDEAL IQ can detect acute intramural hematoma associated with cerebral artery dissection more effectively than T2*WI and earlier than T1-CUBE. (orig.)

  15. Conifer R2R3-MYB transcription factors: sequence analyses and gene expression in wood-forming tissues of white spruce (Picea glauca

    Directory of Open Access Journals (Sweden)

    Grima-Pettenati Jacqueline

    2007-03-01

    Full Text Available Abstract Background Several members of the R2R3-MYB family of transcription factors act as regulators of lignin and phenylpropanoid metabolism during wood formation in angiosperm and gymnosperm plants. The angiosperm Arabidopsis has over one hundred R2R3-MYBs genes; however, only a few members of this family have been discovered in gymnosperms. Results We isolated and characterised full-length cDNAs encoding R2R3-MYB genes from the gymnosperms white spruce, Picea glauca (13 sequences, and loblolly pine, Pinus taeda L. (five sequences. Sequence similarities and phylogenetic analyses placed the spruce and pine sequences in diverse subgroups of the large R2R3-MYB family, although several of the sequences clustered closely together. We searched the highly variable C-terminal region of diverse plant MYBs for conserved amino acid sequences and identified 20 motifs in the spruce MYBs, nine of which have not previously been reported and three of which are specific to conifers. The number and length of the introns in spruce MYB genes varied significantly, but their positions were well conserved relative to angiosperm MYB genes. Quantitative RTPCR of MYB genes transcript abundance in root and stem tissues revealed diverse expression patterns; three MYB genes were preferentially expressed in secondary xylem, whereas others were preferentially expressed in phloem or were ubiquitous. The MYB genes expressed in xylem, and three others, were up-regulated in the compression wood of leaning trees within 76 hours of induction. Conclusion Our survey of 18 conifer R2R3-MYB genes clearly showed a gene family structure similar to that of Arabidopsis. Three of the sequences are likely to play a role in lignin metabolism and/or wood formation in gymnosperm trees, including a close homolog of the loblolly pine PtMYB4, shown to regulate lignin biosynthesis in transgenic tobacco.

  16. The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue

    DEFF Research Database (Denmark)

    Clausen, Rasmus Prætorius; Naur, Peter; Kristensen, Anders Skov

    2009-01-01

    The design, synthesis, and pharmacological characterization of a highly potent and selective glutamate GluR5 agonist is reported. (S)-2-Amino-3-((RS)-3-hydroxy-8-methyl-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (5) is the 8-methyl analogue of (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H......-cyclohepta[d]isoxazol-4-yl)propionic acid ((S)-4-AHCP, 4). Compound 5 displays an improved selectivity profile compared to 4. A versatile stereoselective synthetic route for this class of compounds is presented along with the characterization of the binding affinity of 5 to ionotropic glutamate receptors (i......GluRs). Functional characterization of 5 at cloned iGluRs using a calcium imaging assay and voltage-clamp recordings show a different activation of GluR5 compared to (S)-glutamic acid (Glu), kainic acid (KA, 1), and (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl)propionic acid ((S)-ATPA, 3) as previously...

  17. High-pressure synthesis and characterization of the effective pseudospin S =1 /2 XY pyrochlores R2P t2O7 (R =Er ,Yb )

    Science.gov (United States)

    Cai, Y. Q.; Cui, Q.; Li, X.; Dun, Z. L.; Ma, J.; dela Cruz, C.; Jiao, Y. Y.; Liao, J.; Sun, P. J.; Li, Y. Q.; Zhou, J. S.; Goodenough, J. B.; Zhou, H. D.; Cheng, J.-G.

    2016-01-01

    We report on the high-pressure syntheses and detailed characterizations of two effective pseudospin S =1 /2 XY pyrochlores E r2P t2O7 and Y b2P t2O7 via x-ray/neutron powder diffraction, dc and ac magnetic susceptibility, and specific-heat measurements down to 70 mK. We found that both compounds undergo long-range magnetic transitions at TN ,C≈0.3 K , which are ascribed to an antiferromagnetic- and ferromagnetic-type order for E r2P t2O7 and Y b2P t2O7 , respectively, based on the field dependence of their transition temperatures as well as the systematic comparisons with other similar pyrochlores R2B2O7 (R =Er ,Yb ;B =Sn ,Ti ,Ge ). The observed TN of E r2P t2O7 is much lower than that expected from the relationship of TN versus the ionic radius of B4 + derived from the series of E r2B2O7 , while the TC of Y b2P t2O7 is the highest among the series of ferromagnetic compounds Y b2B2O7 (B =Sn ,Pt ,Ti ). Given the monotonic variation of the lattice constant as a function of the B -cation size across these two series of R2B2O7 (R =Er ,Yb ), the observed anomalous values of TN ,C in the Pt-based XY pyrochlores imply that another important factor beyond the nearest-neighbor R -R distance is playing a role. In light of the anisotropic exchange interactions Jex={Jz z,J±,J±±,Jz ± } for the S =1 /2 XY pyrochlores, we have rationalized these observations by considering a weakened (enhanced) antiferromagnetic planar J± (ferromagnetic Ising-like Jz z) due to strong Pt 5 d -O 2 p hybridization within the plane perpendicular to the local [111] direction.

  18. The structure of a mixed GluR2 ligand-binding core dimer in complex with (S)-glutamate and the antagonist (S)-NS1209

    DEFF Research Database (Denmark)

    Kasper, Christina; Pickering, Darryl S; Mirza, Osman

    2006-01-01

    domains has been observed. (S)-NS1209 adopts a novel binding mode, including hydrogen bonding to Tyr450 and Gly451 of D1. Parts of (S)-NS1209 occupy new areas of the GluR2 ligand-binding cleft, and bind near residues that are not conserved among receptor subtypes. The affinities of (RS)-NS1209 at the Glu....... The thermodynamics of binding of the antagonists (S)-NS1209, DNQX and (S)-ATPO to the GluR2 ligand-binding core have been determined by displacement isothermal titration calorimetry. The displacement of (S)-glutamate by all antagonists was shown to be driven by enthalpy....

  19. Synthesis, characterization and crystal structure of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid

    Science.gov (United States)

    Muche, Simon; Müller, Matthias; Hołyńska, Małgorzata

    2018-03-01

    The condensation reaction of ortho-vanillin and L-cysteine leads to formation of a racemic mixture of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid and not, as reported in the available literature, to a Schiff base. The racemic mixture was fully characterized by 1D and 2D NMR techniques, ESI-MS and X-ray diffraction. Addition of ZnCl2 led to formation of crystals in form of colorless needles, suitable for X-ray diffraction studies. The measured crystals were identified as the diastereomer (2R,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid 1. The bulk material is racemic. Thiazolidine exists as zwitterion in solid state, as indicated by the crystal structure.

  20. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study.

    Science.gov (United States)

    Mirzaa, Ghayda M; Conti, Valerio; Timms, Andrew E; Smyser, Christopher D; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B; Guerrini, Renzo

    2015-12-01

    Bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, cognitive impairment, and epilepsy. The causes of BPP are heterogeneous, but only a few genetic causes have been reported. The aim of this study was to identify additional genetic causes of BPP and characterise their frequency in this population. Children (aged ≤18 years) with polymicrogyria were enrolled into our research programme from July, 1980, to October, 2015, at two centres (Florence, Italy, and Seattle, WA, USA). We obtained samples (blood and saliva) throughout this period at both centres and did whole-exome sequencing on DNA from eight trios (two parents and one affected child) with BPP in 2014. After the identification of mosaic PIK3R2 mutations in two of these eight children, we performed targeted screening of PIK3R2 by two methods in a cohort of 118 children with BPP. First, we performed targeted sequencing of the entire PIK3R2 gene by single molecule molecular inversion probes (smMIPs) on 38 patients with BPP with normal to large head size. Second, we did amplicon sequencing of the recurrent PIK3R2 mutation (Gly373Arg) in 80 children with various types of polymicrogyria including BPP. One additional patient had clinical whole-exome sequencing done independently, and was included in this study because of the phenotypic similarity to our cohort. We identified a mosaic mutation (Gly373Arg) in a regulatory subunit of the PI3K-AKT-mTOR pathway, PIK3R2, in two children with BPP. Of the 38 patients with BPP and normal to large head size who underwent targeted next-generation sequencing by smMIPs, we identified constitutional and mosaic PIK3R2 mutations in 17 additional children. In parallel, one patient had the recurrent PIK3R2 mutation identified by clinical whole-exome sequencing. Seven of these 20 patients had BPP alone, and 13 had BPP in association with features of the

  1. Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis.

    Science.gov (United States)

    Wang, Yongwei; Du, Yali; Liu, Gang; Guo, Shanshan; Hou, Bo; Jiang, Xianyong; Han, Bing; Chang, Yanzhong; Nie, Guangjun

    2017-04-01

    Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups. In the current work, we describe eight Chinese cases of hereditary hemochromatosis. Gene sequencing results revealed eight mutations (five novel mutations) in HFE, HFE2, TfR2, and SLC40A1 genes in these Chinese HH patients. In addition, we used Polymorphism Phenotyping v2 (Polyphen), Sorting Intolerant From Tolerant (SIFT), and a sequence alignment program to predict the molecular consequences of missense mutations.

  2. Reactivity-worth estimates of the OSMOSE samples in the MINERVE reactor R1-MOX, R2-UO2 and MORGANE/R configurations.

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Z.; Klann, R. T.; Nuclear Engineering Division

    2007-08-03

    An initial series of calculations of the reactivity-worth of the OSMOSE samples in the MINERVE reactor with the R2-UO2 and MORGANE/R core configuration were completed. The calculation model was generated using the lattice physics code DRAGON. In addition, an initial comparison of calculated values to experimental measurements was performed based on preliminary results for the R1-MOX configuration.

  3. Biocatalytic Asymmetric Synthesis of (1R, 2S)-N-Boc-vinyl-ACCA Ethyl Ester with a Newly Isolated Sphingomonas aquatilis.

    Science.gov (United States)

    Zhu, Shaozhou; Shi, Ying; Zhang, Xinyu; Zheng, Guojun

    2018-02-01

    1-amino cyclopropane-1-carboxylic acid (ACCA) and its derivatives are essential pharmacophoric unit that widely used in drug research and development. Specifically, (1R, 2S)-N-Boc-vinyl-ACCA ethyl ester (vinyl-ACCA) is a key chiral intermediate in the synthesis of highly potent hepatitis C virus (HCV) NS3/4A protease inhibitors such as asunaprevir and simeprevir. Developing strategies for the asymmetric synthesis of vinyl-ACCA is thus extremely high demand. In this study, 378 bacterial strains were isolated from soil samples using N-Boc-vinyl-ACCA ethyl ester as the sole carbon source and were screened for esterase activity. Fourteen of which worked effectively for the asymmetric synthesis of (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester. The strain CY-2, identified as Sphingomonas aquatilis, which showed the highest stability and enantioselectivity was selected as whole cell biocatalyst for further study. A systematic study of all factors influencing the enzymatic hydrolysis was performed. Under optimized conditions, resolution of rac-vinyl-ACCA to (1R, 2S)-N-Boc-1-vinyl ACCA ethyl ester with 88.2% ee and 62.4% conversion (E = 9) was achieved. Besides, S. aquatilis was also used to transform other 10 different substrates. Notably, it was found that 7 of them could be stereoselectively hydrolyzed, especially for (1R,2S)-1-amino-vinyl-ACCA ethyl ester hydrochloride (99.6% ee, E>200). Our investigations provide a new efficient whole cell biocatalyst for resolution of ACCA and might be developed for industry application.

  4. Elimination Reactions of (E)-2,4,6-Trinitrobenzaldehyde O-benzoyloximes Promoted by R2NH in MeCN. Change of Reaction Mechanism

    International Nuclear Information System (INIS)

    Cho, Bong Rae; Pyun, Sang Yong

    2010-01-01

    We have studied the nitrile-forming elimination reactions from 1 promoted by R 2 NH in MeCN. The reaction proceeded by (E1cb) irr mechanism. Change of the β-aryl group from 2,4-dinitrophenyl to a more strongly electron-withdrawing 2,4,6-trinitrophenyl increased the reaction rate by 470-fold, shifted the transition state toward more reactant-like, and changed the reaction mechanism from E2 to (E1cb) irr . To the best of our knowledge, this is the first example of nitrile-forming elimination reaction that proceeds by the (E1cb) irr mechanism in MeCN. Noteworthy is the carbanion stabilizing ability of the 2,4,6-trinitrophenyl group in aprotic solvent. Nitrile-forming elimination reactions of (E)-benzaldoxime derivatives have been extensively investigated under various conditions. The reactions proceeded by the E2 mechanism in MeCN despite the fact that the reactants have syn stereochemistry, poor leaving, and sp 2 hybridized β-carbon atom, all of which favor E1cb- or E1cb-like transition state. Moreover, the transition state structures were relatively insensitive to the variation of the reactant structures. The results have been attributed to the poor anion solvating ability of MeCN, which favors E2 transition state with maximum charge dispersal. For eliminations from strongly activated (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC(O)C 6 H 4 X, a change in the reaction mechanism from E2 to (E1cb) irr was observed as the base-solvent was changed from R 2 NH in MeCN to R 2 NH/R 2 NH 2 + in 70 mol % MeCN(aq). A combination of a strong electron-withdrawing β-aryl group and anion-solvating protic solvent was required for the mechanistic change

  5. Involvement of microRNA miR-2b-3p in regulation of metabolic resistance to insecticides in Plutella xylostella.

    Science.gov (United States)

    Etebari, K; Afrad, M H; Tang, B; Silva, R; Furlong, M J; Asgari, S

    2018-03-24

    The diamondback moth, Plutella xylostella, has developed extremely high levels of resistance to chlorantraniliprole and other classes of insecticides in the field. As microRNAs (miRNAs) play important roles in various biological processes through gene regulation, we examined the miRNA profile of P. xylostella in response to chlorantraniliprole exposure. RNA sequencing analysis showed that insecticide treatment caused significant changes in the abundance of some miRNAs. Increasing exposure time and insecticide concentration induced more dysregulated miRNAs in P. xylostella larvae. We also screened potential target genes for some of the differentially expressed miRNAs (such as miR-2b-3p, miR-14b-5p and let-7-5p), which may play important roles in insecticide resistance development. Exposure of P. xylostella larvae to chlorantraniliprole caused considerable overexpression in the transcript levels of potential target genes cytochrome P450 9f2 (CYP9F2) and 307a1 (CYP307a1). Application of miR-2b-3p and miR-14b-5p mimics significantly suppressed the relative transcript levels of CYP9F2 and CYP307a1, respectively, in a P. xylostella cell line. Furthermore, enrichment of P. xylostella diet with miR-2b-3p mimics significantly increased mortality in deltamethrin-resistant larvae when exposed to deltamethrin. The results suggest that miR-2b-3p may suppress CYP9F2 transcript levels in P. xylostella and consequently inhibit larval detoxification pathways. The findings provide an insight into possible role of miRNAs in regulation of metabolic resistance of insects to insecticides. © 2018 The Royal Entomological Society.

  6. Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA

    DEFF Research Database (Denmark)

    Lunn, Marie-Louise; Hogner, Anders; Stensbøl, Tine B

    2003-01-01

    Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety...

  7. Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

    Science.gov (United States)

    Smith, Kimberly R; Spector, Alan C

    2017-10-01

    Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1 ) detectable when both receptor subunits are absent and 2 ) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose. Copyright © 2017 the American Physiological Society.

  8. Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

    Directory of Open Access Journals (Sweden)

    Omar Ramos-Lopez

    2016-02-01

    Full Text Available Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG. This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively. Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively. In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG.

  9. Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [{sup 11}C]ABP688 PET

    Energy Technology Data Exchange (ETDEWEB)

    DuBois, Jonathan M.; Porras-Betancourt, Manuel; Massarweh, Gassan; Soucy, Jean-Paul; Kobayashi, Eliane [McGill University, Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec (Canada); Rousset, Olivier G. [Johns Hopkins University, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Rowley, Jared [McGill University, Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, Montreal (Canada); Reader, Andrew J. [McGill University, PET Unit, McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal (Canada); King' s College London, St. Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Labbe, Aurelie [McGill University, Department of Epidemiology, Biostatistics and Occupational health, Montreal (Canada); Douglas Mental Health University Institute / Douglas Institut Universitaire en Sante Mentale, Department of Psychiatry, Montreal (Canada); Rosa-Neto, Pedro [McGill University, Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec (Canada); McGill University, Translational Neuroimaging Laboratory, McGill Center for Studies in Aging, Douglas Mental Health University Institute, Montreal (Canada)

    2016-01-15

    Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [{sup 11}C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [{sup 11}C]ABP688 binding potential (BP{sub ND}) and the existence of age/sex effects in healthy individuals. Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [{sup 11}C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BP{sub ND} was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere. We found the highest [{sup 11}C]ABP688 BP{sub ND} in the lateral prefrontal and anterior cingulate cortices. The lowest [{sup 11}C]ABP688 BP{sub ND} was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [{sup 11}C]ABP688 BP{sub ND} without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction. The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span. (orig.)

  10. Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [11C]ABP688 PET

    International Nuclear Information System (INIS)

    DuBois, Jonathan M.; Porras-Betancourt, Manuel; Massarweh, Gassan; Soucy, Jean-Paul; Kobayashi, Eliane; Rousset, Olivier G.; Rowley, Jared; Reader, Andrew J.; Labbe, Aurelie; Rosa-Neto, Pedro

    2016-01-01

    Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [ 11 C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [ 11 C]ABP688 binding potential (BP ND ) and the existence of age/sex effects in healthy individuals. Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [ 11 C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BP ND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere. We found the highest [ 11 C]ABP688 BP ND in the lateral prefrontal and anterior cingulate cortices. The lowest [ 11 C]ABP688 BP ND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [ 11 C]ABP688 BP ND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction. The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span. (orig.)

  11. Ectopic Overexpression of a Novel R2R3-MYB, NtMYB2 from Chinese Narcissus Represses Anthocyanin Biosynthesis in Tobacco

    Directory of Open Access Journals (Sweden)

    Muhammad Anwar

    2018-03-01

    Full Text Available R2R3 MYB transcription factors play key functions in the regulation of secondary metabolites. In the present study, a R2R3 MYB transcriptional factor NtMYB2 was identified from Chinese narcissus (Narcissus tazetta L. var. Chinensis Roem and functionally characterized. NtMYB2 belongs to subgroup 4 of the R2R3 MYB transcription factor family that are related to repressor MYBs involved in the regulation of anthocyanin and flavonoids. Transient expression confirmed that NtMYB2 strongly reduced the red pigmentation induced by MYB- anthocyanin activators in agro-infiltrated tobacco leaves. Ectopic expression of NtMYB2 in tobacco significantly reduced the pigmentation and altered the floral phenotypes in transgenic tobacco flowers. Gene expression analysis suggested that NtMYB2 repressed the transcript levels of structural genes involved in anthocyanin biosynthesis pathway, especially the UFGT gene. NtMYB2 gene is expressed in all examined narcissus tissues; the levels of transcription in petals and corona is higher than other tissues and the transcription level at the bud stage was highest. These results show that NtMYB2 is involved in the regulation of anthocyanin biosynthesis pathway and may act as a repressor by down regulating the transcripts of key enzyme genes in Chinese narcissus.

  12. Ectopic Overexpression of a Novel R2R3-MYB, NtMYB2 from Chinese Narcissus Represses Anthocyanin Biosynthesis in Tobacco.

    Science.gov (United States)

    Anwar, Muhammad; Wang, Guiqing; Wu, Jiacheng; Waheed, Saquib; Allan, Andrew C; Zeng, Lihui

    2018-03-28

    R2R3 MYB transcription factors play key functions in the regulation of secondary metabolites. In the present study, a R2R3 MYB transcriptional factor NtMYB2 was identified from Chinese narcissus ( Narcissus tazetta L. var. Chinensis Roem) and functionally characterized. NtMYB2 belongs to subgroup 4 of the R2R3 MYB transcription factor family that are related to repressor MYBs involved in the regulation of anthocyanin and flavonoids. Transient expression confirmed that NtMYB2 strongly reduced the red pigmentation induced by MYB- anthocyanin activators in agro-infiltrated tobacco leaves. Ectopic expression of NtMYB2 in tobacco significantly reduced the pigmentation and altered the floral phenotypes in transgenic tobacco flowers. Gene expression analysis suggested that NtMYB2 repressed the transcript levels of structural genes involved in anthocyanin biosynthesis pathway, especially the UFGT gene. NtMYB2 gene is expressed in all examined narcissus tissues; the levels of transcription in petals and corona is higher than other tissues and the transcription level at the bud stage was highest. These results show that NtMYB2 is involved in the regulation of anthocyanin biosynthesis pathway and may act as a repressor by down regulating the transcripts of key enzyme genes in Chinese narcissus.

  13. Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.

    Science.gov (United States)

    Hata, Shuko; Ise, Kazue; Azmahani, Abdullah; Konosu-Fukaya, Sachiko; McNamara, Keely May; Fujishima, Fumiyoshi; Shimada, Keiji; Mitsuzuka, Koji; Arai, Yoichi; Sasano, Hironobu; Nakamura, Yasuhiro

    2017-12-01

    Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The coefficient of determination R2 and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded.

    Science.gov (United States)

    Nakagawa, Shinichi; Johnson, Paul C D; Schielzeth, Holger

    2017-09-01

    The coefficient of determination R 2 quantifies the proportion of variance explained by a statistical model and is an important summary statistic of biological interest. However, estimating R 2 for generalized linear mixed models (GLMMs) remains challenging. We have previously introduced a version of R 2 that we called [Formula: see text] for Poisson and binomial GLMMs, but not for other distributional families. Similarly, we earlier discussed how to estimate intra-class correlation coefficients (ICCs) using Poisson and binomial GLMMs. In this paper, we generalize our methods to all other non-Gaussian distributions, in particular to negative binomial and gamma distributions that are commonly used for modelling biological data. While expanding our approach, we highlight two useful concepts for biologists, Jensen's inequality and the delta method, both of which help us in understanding the properties of GLMMs. Jensen's inequality has important implications for biologically meaningful interpretation of GLMMs, whereas the delta method allows a general derivation of variance associated with non-Gaussian distributions. We also discuss some special considerations for binomial GLMMs with binary or proportion data. We illustrate the implementation of our extension by worked examples from the field of ecology and evolution in the R environment. However, our method can be used across disciplines and regardless of statistical environments. © 2017 The Author(s).

  15. Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

    Science.gov (United States)

    Huong, Nguyen Thi Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

    2005-08-01

    Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

  16. Production of R,R-2,3-butanediol of ultra-high optical purity from Paenibacillus polymyxa ZJ-9 using homologous recombination.

    Science.gov (United States)

    Zhang, Li; Cao, Can; Jiang, Ruifan; Xu, Hong; Xue, Feng; Huang, Weiwei; Ni, Hao; Gao, Jian

    2018-08-01

    The present study describes the use of metabolic engineering to achieve the production of R,R-2,3-butanediol (R,R-2,3-BD) of ultra-high optical purity (>99.99%). To this end, the diacetyl reductase (DAR) gene (dud A) of Paenibacillus polymyxa ZJ-9 was knocked out via homologous recombination between the genome and the previously constructed targeting vector pRN5101-L'C in a process based on homologous single-crossover. PCR verification confirmed the successful isolation of the dud A gene disruption mutant P. polymyxa ZJ-9-△dud A. Moreover, fermentation results indicated that the optical purity of R,R-2,3-BD increased from about 98% to over 99.99%, with a titer of 21.62 g/L in Erlenmeyer flasks. The latter was further increased to 25.88 g/L by fed-batch fermentation in a 5-L bioreactor. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Method of forming an oxide superconducting thin film having an R1A2C3 crystalline phase over an R2A1C1 crystalline phase

    International Nuclear Information System (INIS)

    Lelental, M.; Romanofsky, H.J.

    1992-01-01

    This patent describes a process which comprises forming a mixed rare earth alkaline earth copper oxide layer on a substrate and converting the mixed rare earth alkaline earth copper oxide layer to an electrically conductive layer. It comprises crystalline R 1 A 2 C 3 oxide phase by heating in the presence of oxygen, wherein rare earth and R is in each instance chosen from among yttrium, lanthanum, samarium, europium, gadolinium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium and alkaline earth and A is in each instance chosen from among calcium, strontium and barium, characterized in that a crystalline R 2 A 1 C 1 oxide phase is first formed as a layer on the substrate and the crystalline R 1 A 2 C 3 oxide phase is formed over the crystalline R 2 A 1 C 1 oxide phase by coating a mixed rare earth alkaline earth copper oxide on the crystalline R 2 A 1 C 1 oxide phase and heating the mixed rare earth alkaline earth copper oxide to a temperature of at least 1000 degrees C

  18. A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

    Science.gov (United States)

    Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

    2015-12-28

    Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Complete Calibration of the Color-Redshift Relation (C3R2): A Critical Foundation for Weak Lensing Cosmology with Euclid and WFIRST

    Science.gov (United States)

    Masters, Daniel C.; Stern, Daniel; Cohen, Judy; Capak, Peter

    2018-01-01

    A primary objective of both WFIRST and Euclid is to provide a 3D map of the distribution of matter across a significant fraction of the universe from the weak lensing shear field. Doing so will require accurate redshifts to the billions of galaxies that comprise the weak lensing samples of these surveys; achieving the required accuracy is a “tall pole” challenge for both missions. Here we present the ongoing Complete Calibration of the Color-Redshift Relation (C3R2) survey, designed specifically to calibrate the empirical galaxy color-redshift relation to Euclid depth. C3R2 is an ambitious Keck spectroscopy program, with a survey design based on a machine learning technique that allows us to optimally select the most important galaxies to sample the full range of galaxy colors. C3R2 is a multi-center program with time from all the primary Keck partners (Caltech, UC, Hawaii, and NASA), with a total of 34.5 Keck nights allocated to this project. Data Release 1, including 1283 high-confidence spectroscopic redshifts, is published as Masters, Stern, Cohen, Capak, et al. (2017), and we are currently completing Data Release 2, which will include >2000 additional high-confidence spectroscopic redshifts (Masters et al., in prep.). We will discuss current results and prospects for the survey going forward.

  20. Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children.

    Science.gov (United States)

    Melo, Silvia V; Agnes, Grasiela; Vitolo, Márcia R; Mattevi, Vanessa S; Campagnolo, Paula D B; Almeida, Silvana

    2017-01-01

    Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood.

  1. Advanced chronic kidney disease in non-valvular atrial fibrillation: extending the utility of R2CHADS2 to patients with advanced renal failure.

    Science.gov (United States)

    Bautista, Josef; Bella, Archie; Chaudhari, Ashok; Pekler, Gerald; Sapra, Katherine J; Carbajal, Roger; Baumstein, Donald

    2015-04-01

    The R2CHADS2 is a new prediction rule for stroke risk in atrial fibrillation (AF) patients wherein R stands for renal risk. However, it was created from a cohort that excluded patients with advanced renal failure (defined as glomerular filtration rate of advanced renal failure and aims to compare its predictive power against the currently used CHADS and CHA2DS2VaSc. This retrospective cohort study analyzed the 1-year risk for stroke of the 524 patients with AF at Metropolitan Hospital Center. AUC and C statistics were calculated using three groups: (i) the entire cohort including patients with advanced renal failure, (ii) a cohort excluding patients with advanced renal failure and (iii) all patients with GFR statistic was highest in R2CHADS compared with CHADS or CHADSVASC in group 1 (0.718 versus 0.605 versus 0.602) and in group 2 (0.724 versus 0.584 versus 0.579). However, there was no statistically significant difference in group 3 (0.631 versus 0.629 versus 0.623). Our study supports the utility of R2CHADS2 as a clinical prediction rule for stroke risk in patients with advanced renal failure.

  2. Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

    Science.gov (United States)

    Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

    2001-09-01

    1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

  3. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

    Science.gov (United States)

    Zhang, Junfeng; Zhang, Zongqi; Zhang, David Y; Zhu, Jianbing; Zhang, Tiantian; Wang, Changqian

    2013-01-01

    Endothelial progenitor cells (EPCs) are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126) in the endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGFβ1). EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL) for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2) was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126) was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin) and to maintain the mRNA expression of progenitor cell markers (CD34, CD133). In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

  4. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

    Directory of Open Access Journals (Sweden)

    Junfeng Zhang

    Full Text Available AIMS: Endothelial progenitor cells (EPCs are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126 in the endothelial-to-mesenchymal transition (EndMT induced by transforming growth factor beta 1 (TGFβ1. METHODS AND RESULTS: EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2 was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126 was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin and to maintain the mRNA expression of progenitor cell markers (CD34, CD133. In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. CONCLUSIONS: These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

  5. Decreased Renal Function Is Associated with Elevated CHA2DS2VASC and R2CHADS2 Scores in Non-Valvular Atrial Fibrillation Patients Presenting with Stroke.

    Science.gov (United States)

    Vindhyal, Mohinder; Vindhyal, Shravani R; Haneke, Travis; Ndunda, Paul M; Eid, Freidy; Kallail, K James

    2017-12-11

    Introduction Atrial fibrillation (AF), the most common cardiac arrhythmia, affects approximately 2.3 million patients in the United States, costing around $26 billion. Atrial fibrillation is associated with a two- to seven-fold increased risk of stroke, one of the most serious complications. Chronic kidney disease affects approximately 13% of the US population and has been associated with higher rates of AF than the general population. In patients with chronic kidney disease (CKD), the risk of stroke increases as the glomerular filtration rate (GFR) decreases, especially in CKD stages three and four. Several risks stratification scores such as CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, stroke), CHA2DS2VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex), and R2CHADS2 (renal failure, congestive heart failure, age, diabetes, stroke) scores are used for stroke risk assessment in patients with non-valvular atrial fibrillation (NVAF). This study investigates the association between renal functions and risk stratification scoring systems in patients with non-valvular AF presenting with stroke. Methods Using the convenience sampling method, 171 subjects were selected from the eligible population (n = 386). A Pearson product-moment correlation coefficient was calculated to determine the association between the GFR and each of the CHA2DS2VASc and R2CHADS2 scores. In addition, a Pearson product-moment correlation coefficient was calculated to determine the association between the CHA2DS2VASc and R2CHADS2 scores. Results The selected population represented 44.3% of the eligible subjects. Of these, 88% were Caucasian, 60% were female, and the mean age was 78 years. The mean CHA2DS2VASc score was six (range 2-9). The mean eGFR was 69.77 (range 6-108). Both the mode and the median CHA2DS2VASc score was four (range 2-8). A weak, but significant, negative correlation was found between renal

  6. TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill

    International Nuclear Information System (INIS)

    Mohr, Andrea; Yu, Rui; Zwacka, Ralf M.

    2015-01-01

    TRAIL is a potent and specific inducer of apoptosis in tumour cells and therefore is a possible new cancer treatment. It triggers apoptosis by binding to its cognate, death-inducing receptors, TRAIL-R1 and TRAIL-R2. In order to increase its activity, receptor-specific ligands and agonistic antibodies have been developed and some cancer types, including pancreatic cancer, have been reported to respond preferentially to TRAIL-R1 triggering. The aim of the present study was to examine an array of TRAIL-receptor specific variants on a number of pancreatic cancer cells and test the generality of the concept of TRAIL-R1 preference in these cells. TRAIL-R1 and TRAIL-R2 specific sTRAIL variants were designed and tested on a number of pancreatic cancer cells for their TRAIL-receptor preference. These sTRAIL variants were produced in HEK293 cells and were secreted into the medium. After having measured and normalised the different sTRAIL variant concentrations, they were applied to pancreatic and control cancer cells. Twenty-four hours later apoptosis was measured by DNA hypodiploidy assays. Furthermore, the specificities of the sTRAIL variants were validated in HCT116 cells that were silenced either for TRAIL-R1 or TRAIL-R2. Our results show that some pancreatic cancer cells use TRAIL-R1 to induce cell death, whereas other pancreatic carcinoma cells such as AsPC-1 and BxPC-3 cells trigger apoptosis via TRAIL-R2. This observation extended to cells that were naturally TRAIL-resistant and had to be sensitised by silencing of XIAP (Panc1 cells). The measurement of TRAIL-receptor expression by FACS revealed no correlation between receptor preferences and the relative levels of TRAIL-R1 and TRAIL-R2 on the cellular surface. These results demonstrate that TRAIL-receptor preferences in pancreatic cancer cells are variable and that predictions according to cancer type are difficult and that determining factors to inform the optimal TRAIL-based treatments still have to be identified

  7. Characterization of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next generation sequencing study

    Science.gov (United States)

    Mirzaa, Ghayda; Conti, Valerio; Timms, Andrew E.; Smyser, Christopher D.; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B.; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B.; Guerrini, Renzo

    2015-01-01

    SUMMARY Background Bilateral perisylvian polymicrogyria (BPP), the most common form of regional polymicrogyria, causes the congenital bilateral perisylvian syndrome, featuring oromotor dysfunction, cognitive impairment and epilepsy. BPP is etiologically heterogeneous, but only a few genetic causes have been reported. The aim of this study was to identify additional genetic etiologies of BPP and delineate their frequency in this patient population. Methods We performed child-parent (trio)-based whole exome sequencing (WES) on eight children with BPP. Following the identification of mosaic PIK3R2 mutations in two of these eight children, we performed targeted screening of PIK3R2 in a cohort of 118 children with BPP who were ascertained from 1980 until 2015 using two methods. First, we performed targeted sequencing of the entire PIK3R2 gene by single molecule molecular inversion probes (smMIPs) on 38 patients with BPP with normal-large head size. Second, we performed amplicon sequencing of the recurrent PIK3R2 mutation (p.Gly373Arg) on 80 children with various types of polymicrogyria including BPP. One additional patient underwent clinical WES independently, and was included in this study given the phenotypic similarity to our cohort. All patients included in this study were children (BPP. Of the 38 patients with BPP and normal-large head size who underwent targeted next generation sequencing by smMIPs, we identified constitutional and mosaic PIK3R2 mutations in 17 additional children. In parallel, one patient was found to have the recurrent PIK3R2 mutation by clinical WES. Seven patients had BPP alone, and 13 had BPP in association with features of the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH). Nineteen patients had the same mutation (Gly373Arg), and one had a nearby missense mutation (p.Lys376Glu). Across the entire cohort, mutations were constitutional in 12 and mosaic in eight patients. Among mosaic patients, we observed substantial

  8. Evaluation of ERA-Interim, MERRA, NCEP-DOE R2 and CFSR Reanalysis precipitation Data using Gauge Observation over Ethiopia for a period of 33 years

    Directory of Open Access Journals (Sweden)

    Tewodros Woldemariam Tesfaye

    2017-09-01

    Full Text Available The vital demand of reliable climatic and hydrologic data of fine spatial and temporal resolution triggered the employment of reanalysis datasets as a surrogate in most of the hydrological modelling exercises. This study examines the performance of four widely used reanalysis datasets: ERA-Interim, NCEP-DOE R2, MERRA and CFSR, in reproducing the spatio-temporal characteristics of observed daily precipitation of different stations spread across Ethiopia, East Africa. The appropriateness of relying on reanalysis datasets for hydrologic modelling, climate change impact assessment and regional modelling studies is assessed using various statistical and non-parametric techniques. ERA-Interim is found to exhibit higher correlation and least root mean square error values with observed daily rainfall, which is followed by CFSR and MERRA in most of the stations. The variability of daily precipitation is better captured by ERA, CFSR and MERRA, while NCEP-DOE R2 overestimated the spread of the precipitation data. While ERA overestimates the probability of moderate rainfall, it is seemingly better in capturing the probability of low rainfall. CFSR captures the overall distribution reasonable well. NCEP-DOE R2 appears to be outperforming others in capturing the probabilities of higher magnitude rainfall. Climatological seasonal cycle and the characteristics of wet and dry spells are compared further, where ERA seemingly replicates the pattern more effectively. However, observed rainfall exhibits higher frequency of short wet spells when compared to that of any reanalysis datasets. MERRA relatively underperforms in simulating the wet spell characteristics of observed daily rainfall. CFSR overestimates the mean wet spell length and mean dry spell length. Spatial trend analysis indicates that the northern and central western Ethiopia show increasing trends, whereas the Central and Eastern Ethiopia as well as the Southern Ethiopia stations show either no trend

  9. miR2Pathway: A Novel Analytical Method to Discover MicroRNA-mediated Dysregulated Pathways Involved in Hepatocellular Carcinoma.

    Science.gov (United States)

    Li, Chaoxing; Dinu, Valentin

    2018-03-22

    MicroRNAs (miRNAs) are small, non-coding RNAs involved in the regulation of gene expression at a post-transcriptional level. Recent studies have shown miRNAs as key regulators of a variety of biological processes, such as proliferation, differentiation, apoptosis, metabolism, etc. Aberrantly expressed miRNAs influence individual gene expression level, but rewired miRNA-mRNA connections can influence the activity of biological pathways. Here, we define rewired miRNA-mRNA connections as the differential (rewiring) effects on the activity of biological pathways between hepatocellular carcinoma (HCC) and normal phenotypes. Our work presented here uses a PageRank-based approach to measure the degree of miRNA-mediated dysregulation of biological pathways between HCC and normal samples based on rewired miRNA-mRNA connections. In our study, we regard the degree of miRNA-mediated dysregulation of biological pathways as disease risk of biological pathways. Therefore, we propose a new method, miR2Pathway, to measure and rank the degree of miRNA-mediated dysregulation of biological pathways by measuring the total differential influence of miRNAs on the activity of pathways between HCC and normal states. miR2Pathway proposed here systematically shows the first evidence for a mechanism of biological pathways being dysregulated by rewired miRNA-mRNA connections, and provides new insight into exploring mechanisms behind HCC. Thus, miR2Pathway is a novel method to identify and rank miRNA-dysregulated pathways in HCC. Copyright © 2018. Published by Elsevier Inc.

  10. Disruptive chemical doping in a ferritin-based iron oxide nanoparticle to decrease r2 and enhance detection with T1-weighted MRI.

    Science.gov (United States)

    Clavijo Jordan, M Veronica; Beeman, Scott C; Baldelomar, Edwin J; Bennett, Kevin M

    2014-01-01

    Inorganic doping was used to create flexible, paramagnetic nanoparticle contrast agents for in vivo molecular magnetic resonance imaging (MRI) with low transverse relaxivity (r2). Most nanoparticle contrast agents formed from superparamagnetic metal oxides are developed with high r2. While sensitive, they can have limited in vivo detection due to a number of constraints with T2 or T2*-weighted imaging. T1-weighted imaging is often preferred for molecular MRI, but most T1-shortening agents are small chelates with low metal payload or are nanoparticles that also shorten T2 and limit the range of concentrations detectable with T1-weighting. Here we used tungsten and iron deposition to form doped iron oxide crystals inside the apoferritin cavity to form a WFe nanoparticle with a disordered crystal and un-coupled atomic magnetic moments. The atomic magnetic moments were thus localized, resulting in a principally paramagnetic nanoparticle. The WFe nanoparticles had no coercivity or saturation magnetization at 5 K and sweeping up to ± 20,000 Oe, while native ferritin had a coercivity of 3000 Oe and saturation at ± 20,000 Oe. This tungsten-iron crystal paramagnetism resulted in an increased WFe particle longitudinal relaxivity (r1) of 4870 mm(-1) s(-1) and a reduced transverse relaxivity (r2) of 9076 mm(-1) s(-1) compared with native ferritin. The accumulation of the particles was detected with T1-weighted MRI in concentrations from 20 to 400 nm in vivo, both injected in the rat brain and targeted to the rat kidney glomerulus. The WFe apoferritin nanoparticles were not cytotoxic up to 700 nm particle concentrations, making them potentially important for targeted molecular MRI. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

    Science.gov (United States)

    Chen, Yung-Che; Chen, Ting-Wen; Su, Mao-Chang; Chen, Chung-Jen; Chen, Kuang-Den; Liou, Chia-Wei; Tang, Petrus; Wang, Ting-Ya; Chang, Jen-Chieh; Wang, Chin-Chou; Lin, Hsin-Ching; Chin, Chien-Hung; Huang, Kuo-Tung; Lin, Meng-Chih; Hsiao, Chang-Chun

    2016-04-01

    We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB). Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS. IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA. A commentary on this article appears in this issue on page 723. © 2016

  12. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

    Science.gov (United States)

    Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

    2015-09-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. Copyright © 2015 the American Physiological Society.

  13. Synthesis of 2-(2-R1-Hydrazino-5-(R2-benzyl-2-thiazolines on the Basis of Meerweins Arylation Products of Allyl Isothiocyanate

    Directory of Open Access Journals (Sweden)

    Mykola I. Ganushchak

    2003-02-01

    Full Text Available 3-Aryl-2-chloropropylisothiocyanates (1 are formed by interaction of arenediazonium chlorides with allyl isothiocyanate. Adducts 1 react with monoacylhydrazines to form 1-acyl-4-(3-aryl-2-chloropropylthiosemicarbazides (2a–d. Thiosemicarbazides 2a–d in the presence of bases selectively transform into 2-(2-R1-hydrazino-5-(R2-benzyl-2-thiazolines (3a–d.

  14. Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones

    Czech Academy of Sciences Publication Activity Database

    Malinová, Anna; Cvačková, Zuzana; Matějů, Daniel; Hořejší, Zuzana; Abeza, C.; Vandermoere, F.; Bertrand, E.; Staněk, David; Verheggen, C.

    2017-01-01

    Roč. 216, č. 6 (2017), s. 1579-1596 ISSN 0021-9525 R&D Projects: GA ČR GPP301/12/P425; GA ČR GA15-00790S; GA ČR(CZ) GA14-34264S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : dominant retinitis-pigmentosa * splicing factor prp8 * rna-polymerase-ii * structural basis * spliceosomal snrnps * coiled bodies * cajal bodies * r2tp complex * mutations * biogenesis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 7.955, year: 2016

  15. A R2R3-MYB transcription factor regulates the flavonol biosynthetic pathway in a traditional Chinese medicinal plant, Epimedium sagittatum

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    2016-07-01

    Full Text Available Flavonols as plant secondary metabolites with vital roles in plant development and defense against UV light, have been demonstrated to be the main bioactive components in the genus Epimedium plants, several species of which are used as materials for Herba Epimedii, an important traditional Chinese medicine. The flavonol biosynthetic pathway genes had been already isolated from E. sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis has not been functionally characterized so far in Epimedium plants. In this study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1 involved in regulation of the flavonol biosynthetic pathway from E. sagittatum. Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB family which contains the flavonol-specific MYB regulators identified to date. Transient reporter assay showed that EsMYBF1 strongly activated the promoters of EsF3H (flavanone 3-hydroxylase and EsFLS (flavonol synthase, but not the promoters of EsDFRs (dihydroflavonol 4-reductase and EsANS (anthocyanidin synthase in transiently transformed Nicotiana benthamiana leaves. Both yeast two-hybrid assay and transient reporter assay validated EsMYBF1 to be independent of EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol content and the decreased anthocyanin content in flowers. Correspondingly, the structural genes involved in flavonol synthesis were upregulated in the EsMYBF1 overexpression lines, including NtCHS (chalcone synthase, NtCHI (chalcone isomerase, NtF3H and NtFLS, whereas the late biosynthetic genes of the anthocyanin pathway (NtDFR and NtANS were remarkably downregulated, compared to the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB regulator, and involved in regulation of the biosynthesis of the flavonol-derived bioactive components in E

  16. The MMP inhibitor (R)-2-(N-benzyl-4-(2-[18F]fluoroethoxy)phenylsulphonamido) -N-hydroxy-3-methylbutanamide: Improved precursor synthesis and fully automated radiosynthesis

    International Nuclear Information System (INIS)

    Wagner, Stefan; Faust, Andreas; Breyholz, Hans-Joerg; Schober, Otmar; Schaefers, Michael; Kopka, Klaus

    2011-01-01

    Summary: The CGS 25966 derivative (R)-2-(N-Benzyl-4-(2-[ 18 F]fluoroethoxy)phenyl-sulphonamido) -N-hydroxy-3-methylbutanamide [ 18 F]9 represents a very potent radiolabelled matrix metalloproteinase inhibitor. For first human PET studies it is mandatory to have a fully automated radiosynthesis and a straightforward precursor synthesis available. The realisation of both requirements is reported herein. In particular, the corresponding precursor 8 was obtained in a reliable 7 step synthesis with an overall chemical yield of 2.3%. Furthermore, the target compound [ 18 F]9 was prepared with a radiochemical yield of 14.8±3.9% (not corrected for decay).

  17. Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

    Science.gov (United States)

    Lee, Hyosung; Park, Ki Duk; Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Wilson, Sarah M; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R; Khanna, Rajesh; Kohn, Harold

    2014-07-24

    We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

  18. Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGF-R2

    Energy Technology Data Exchange (ETDEWEB)

    Gheorghescu, Anna Kaskova [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); Tywoniuk, Bartlomiej [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Duess, Johannes [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); National Children' s Research Centre, Our Lady' s Children' s Hospital, Crumlin, Dublin 12 (Ireland); Buchete, Nicolae-Viorel, E-mail: buchete@ucd.ie [School of Physics, University College Dublin, Belfield, Dublin 4 (Ireland); Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Thompson, Jennifer, E-mail: jennifer.thompson@ucd.ie [School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland)

    2015-11-15

    Cadmium (Cd) has several industrial applications, and is found in tobacco products, a notable source of human exposure. Vascular endothelial cells are key targets of Cd toxicity. Here, we aim to quantify the alteration to vascular branching pattern following Cd exposure in the chick extra-embryonic membrane (EEM) using fractal analysis, and explore molecular cues to angiogenesis such as VEGF-A and VEGF-R2 expression following Cd treatment. Chicken embryos were incubated for 60 h to Hamburger–Hamilton developmental stage 16–17, then explanted and treated with 50 μL of 50 μmol cadmium acetate (CdAc) or an equivalent volume of equimolar sodium acetate (NaAc). Images of embryos and their area vasculosa (AV) were captured and analyzed at 4 different time points (4, 8, 24 and 48 h) following treatment. Vascular branching in the AV was quantified using its fractal dimension (D{sub f}), estimated using a box counting method. Gallinaceous VEGF ELISA was used to measure the VEGF-A concentration in the EEM following treatment, with determination of the relative expression of VEGF-A and VEGF-R2 using quantitative real-time RT-PCR. Vascular branching increased monotonically in the control group at all time points. The anti-angiogenic effect of Cd exposure on the AV was reflected by a significant reduction in D{sub f} when compared with controls. D{sub f} was more markedly reduced in cultures with abnormal embryos. The expression of VEGF-A protein, and VEGF-A and VEGF-R2 mRNA were reduced in Cd-exposed EEMs. Both molecules contribute to growth, vessel sprouting and branching processes, which supports our findings using fractal analysis. - Highlights: • The chick area vasculosa was undersized in embryos exposed to 50 μM cadmium acetate. • Fractal dimension was reduced in the AV after Cd exposure, indicating decreased branching. • VEGF-A protein was decreased in Cd-treated extraembryonic membranes. • VEGF-A and VEGF-R2 mRNA was decreased in Cd-treated extraembryonic

  19. Purification and characterization of an anti-Prelog alcohol dehydrogenase from Oenococcus oeni that reduces 2-octanone to (R)-2-octanol.

    Science.gov (United States)

    Meng, Fantao; Xu, Yan

    2010-04-01

    An anti-Prelog alcohol dehydrogenase from Oenococcus oeni that reduces 2-octanone to (R)-2-octanol was purified by 26-fold to homogeneity. The enzyme had a homodimeric structure consisting of 49 kDa subunits, required NADPH, but not NADH, as a cofactor and was a Zn-independent short-chain dehydrogenase. Aliphatic methyl ketones (chain length > or =6 carbon atoms) and aromatic methyl ketones were the preferred substrates for the enzyme, the best being 2-octanone. Maximum enzyme activity with 2-octanone was at 45 degrees C and at pH 8.0.

  20. Preparation of the metabotropic glutamate receptor 5 (mGluR5) PET tracer [18F]FPEB for human use: An automated radiosynthesis and a novel one-pot synthesis of its radiolabeling precursor

    International Nuclear Information System (INIS)

    Lim, Keunpoong; Labaree, David; Li, Songye; Huang, Yiyun

    2014-01-01

    The radiotracer 3-[ 18 F]fluoro-5-(2-pyridinylethynyl)benzonitrile, or [ 18 F]FPEB, is a promising PET imaging agent for the metabotropic glutamate subtype 5 receptor (mGluR5). In an effort to develop a routine production method of this radiotracer for use in clinical research we adapted its radiosynthesis to an automated chemistry module. In the meanwhile, we also developed a simplified “one-pot” method for the preparation of the nitrobenzonitrile radiolabeling precursor for [ 18 F]FPEB and its reference standard to replace the existing multi-step synthetic approach. - Highlights: • Radiosynthesis of [ 18 F]FPEB was performed in a Tracerlab FX-FN automated module. • The radiolabeling precursor was prepared from a “one-pot” Suzuki coupling method. • Total synthesis time from EOB to a final injectable dose was about 90 min. • The procedure was applied in the routine preparation of [ 18 F]FPEB for human use

  1. Environmental enrichment improves learning and memory and long-term potentiation in young adult rats through a mechanism requiring mGluR5 signaling and sustained activation of p70s6k.

    Science.gov (United States)

    Hullinger, Rikki; O'Riordan, Kenneth; Burger, Corinna

    2015-11-01

    Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    Directory of Open Access Journals (Sweden)

    Chenggu Cai

    Full Text Available Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2 and Tas1r3 (taste receptor type 1 member 3. Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  3. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    Science.gov (United States)

    Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

    2016-01-01

    Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  4. A multi-site controlled trial of the R&R2MHP cognitive skills program for mentally disordered female offenders.

    Science.gov (United States)

    Jotangia, Amit; Rees-Jones, Angharad; Gudjonsson, Gisli H; Young, Susan

    2015-05-01

    This study aimed to evaluate the acceptability and efficacy of delivering the Reasoning and Rehabilitation Mental Health Program (R&R2MHP) to female mentally disordered offenders detained in medium and low secure hospital settings. Group treatment participants (N = 18) and control participants receiving treatment as usual (N = 20) completed self-report measures pre- and post-group. An informant measure of ward behavior was also completed by staff. Violent attitudes and locus of control were assessed at 3-month follow-up. Program completion was excellent (89%). A conservative intention-to-treat analysis found significant treatment effects post-group for positive problem-solving orientation, rational problem-solving style, and locus of control (medium-large effect), but no treatment effect for violent attitudes, anger, and ward behavior. At follow-up, a large treatment effect was found for locus of control. Ad hoc per protocol analyses found a large treatment effect for ward behavior. The findings provide preliminary support for the feasibility and utility of delivering R&R2MHP to females in secure psychiatric settings. © The Author(s) 2013.

  5. A non-randomised controlled trial of the R&R2MHP cognitive skills program in high risk male offenders with severe mental illness.

    Science.gov (United States)

    C-Y Yip, Vivienne; Gudjonsson, Gisli H; Perkins, Derek; Doidge, Amie; Hopkin, Gareth; Young, Susan

    2013-10-18

    The growing popularity of offending behavior programs has led to the interest of whether such programs are effective with mentally disordered offenders. This study aimed to evaluate the effectiveness of the Reasoning and Rehabilitation program adapted for offenders with severe mental illness (R&R2 MHP). A sample of 59 adult high risk males detained in a high secure hospital completed questionnaires at baseline and post treatment to assess violent attitudes, anger, coping processes and social problem-solving. An informant measure of social and psychological functioning, including disruptive behavior, was completed by staff at the same time. The data of 30 patients who participated in the group condition were compared using intention to treat analysis with 29 controls who received treatment as usual. 80% of group participants completed the program. In contrast to controls, significant medium-large treatment effects were found at outcome on self-reported measures of violent attitudes, social problem-solving and coping processes. Improvements were endorsed by informant ratings of disruptive behavior, social and psychological functioning. The R&R2MHP had a comparatively low dropout rate and was effective in a sample of high risk mentally disordered offenders requiring detention in high security. Future research should use a randomized controlled design. Current Controlled Trials ACTRN12613000216718.

  6. Optimization method to branch-and-bound large SBO state spaces under dynamic probabilistic risk assessment via use of LENDIT scales and S2R2 sets

    International Nuclear Information System (INIS)

    Nielsen, Joseph; Tokuhiro, Akira; Khatry, Jivan; Hiromoto, Robert

    2014-01-01

    Traditional probabilistic risk assessment (PRA) methods have been developed to evaluate risk associated with complex systems; however, PRA methods lack the capability to evaluate complex dynamic systems. In these systems, time and energy scales associated with transient events may vary as a function of transition times and energies to arrive at a different physical state. Dynamic PRA (DPRA) methods provide a more rigorous analysis of complex dynamic systems. Unfortunately DPRA methods introduce issues associated with combinatorial explosion of states. In order to address this combinatorial complexity, a branch-and-bound optimization technique is applied to the DPRA formalism to control the combinatorial state explosion. In addition, a new characteristic scaling metric (LENDIT – length, energy, number, distribution, information and time) is proposed as linear constraints that are used to guide the branch-and-bound algorithm to limit the number of possible states to be analyzed. The LENDIT characterization is divided into four groups or sets – 'state, system, resource and response' (S2R2) – describing reactor operations (normal and off-normal). In this paper we introduce the branch-and-bound DPRA approach and the application of LENDIT scales and S2R2 sets to a station blackout (SBO) transient. (author)

  7. Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information.

    Science.gov (United States)

    Szabó, György; Túrós, György I; Kolok, Sándor; Vastag, Mónika; Sánta, Zsuzsanna; Dékány, Miklós; Lévay, György I; Greiner, István; Natsumi, Minami; Tatsuya, Watanabe; Keserű, György M

    2018-03-14

    Metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs) have been implicated as potential pharmacotherapy for psychiatric conditions. Screening our corporate compound deck, we identified a benzotriazole fragment (4) that was rapidly optimized to a potent and metabolically stable early lead (16). The highly lipophilic character of 16, together with its limited solubility, permeability, and high protein binding, however, did not allow reaching of the proof of concept in vivo. Since further attempts on the optimization of druglike properties were unsuccessful, the original hit 4 has been revisited and was optimized following the principles of fragment based drug discovery (FBDD). Lacking structural information on the receptor-ligand complex, we implemented a group efficiency (GE) based strategy and identified a new fragment like lead (60) with more balanced profile. Significant improvement achieved on the druglike properties nominated the compound for in vivo proof of concept studies that revealed the chemotype being a promising PAM lead targeting mGluR2 receptors.

  8. Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2*-relaxometry and chemical shift-based sequences

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, B.; Rauch, S.; Schocke, M.; Jaschke, W.; Kremser, C. [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Zoller, H. [Medical University of Innsbruck, Department of Internal Medicine, Innsbruck (Austria); Kannengiesser, S. [Siemens AG, Healthcare Sector, MR Applications Development, Erlangen (Germany); Zhong, X. [Siemens Healthcare, MR R and D Collaborations, Atlanta, GA (United States); Reiter, G. [Siemens AG, Healthcare Sector, MR R and D Collaborations, Graz (Austria)

    2015-05-01

    To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixo