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Sample records for r2 r6 r4

  1. Pappas' scheme of correlating R6 and R4 co-ordinate transformations

    Teli, M.T.

    1984-01-01

    Pappas has suggested that R 4 co-ordinates can be connected with those in the R 6 by taking t'sub(x)=t'sub(y)=t'sub(z)=t'. Such connection is here obtained by introducing the scaling of space-time co-ordinates xsub(i), tsub(i) in all the frames by the corresponding factor c/c'sub(i) and have shown that taking of t'sub(x)=t'sub(y)=t'sub(z)=t' for this purpose is not necessary. The scaling factors get ignored after the connection

  2. Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

    Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.

    2006-01-01

    The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglut......The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S...

  3. Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for activity toward monoamine transporters.

    Kharkar, Prashant S; Batman, Angela M; Zhen, Juan; Beardsley, Patrick M; Reith, Maarten E A; Dutta, Aloke K

    2009-07-01

    A novel series of optically active molecules based on a 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol template were developed. Depending on stereochemistry, the compounds exhibit various degrees of affinity for three dopamine, serotonin, and norepinephrine transporters. These molecules have the potential for treating several neurological disorders such as drug abuse, depression, and attention deficit hyperactivity disorder.Herein we describe the synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol-based dihydroxy compounds in which the hydroxy groups are located on both the piperidine ring and the N-phenylethyl side chain. In vitro uptake inhibition data of these molecules indicate high affinity for the dopamine transporter (DAT) in addition to moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9 b and 9 d exhibit affinities for all three monoamine transporters, with highest potency at DAT and NET, and moderate potency at the serotonin transporter (SERT) (K(i): 2.29, 78.4, and 155 nM for 9 b and 1.55, 14.1, and 259 nM for 9 d, respectively). Selected compounds 9 a, 9 d, and 9 d' were tested for their locomotor activity effects in mice and for their ability to occasion the cocaine-discriminative stimulus in rats. These test compounds generally exhibit a much longer duration of action than cocaine for elevating locomotor activity, and completely generalize the cocaine-discriminative stimulus in a dose-dependent manner.

  4. Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for monoamine transporters

    Kharkar, Prashant S.; Batman, Angela M.; Zhen, Juan; Beardsley, Patrick M.; Reith, Maarten E. A.

    2012-01-01

    In this report we describe synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol based dihydroxy compounds where the hydroxy groups are located both on the piperidine ring and also on the N-phenylethyl side chain exo-cyclically. In vitro uptake inhibition data indicates high affinity of these molecules for the dopamine transporter (DAT) in addition to their moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9b and 9d exhibited affinities for all three monoamine transporters with highest potency at DAT and NET and moderate potency at the serotonin transporter (SERT) (Ki 2.29, 78.4 and 155 nM for 9b and 1.55, 14.1 and 259 nM for 9d, respectively). Selected compounds, 9a, 9d and 9d’ were tested for their locomotor activity effects in mice, and for their ability to occasion the cocaine discriminative stimulus in rats. These test compounds generally exhibited a much longer duration of action than cocaine for elevating locomotor activity, and dose-dependently completely generalized the cocaine discriminative stimulus. PMID:19449323

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

    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.

  6. SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

    Gougat, Jean; Ferrari, Bernard; Sarran, Lionel; Planchenault, Claudine; Poncelet, Martine; Maruani, Jeanne; Alonso, Richard; Cudennec, Annie; Croci, Tiziano; Guagnini, Fabio; Urban-Szabo, Katalin; Martinolle, Jean-Pierre; Soubrié, Philippe; Finance, Olivier; Le Fur, Gérard

    2004-05-01

    The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.

  7. Functional characterisation of homomeric ionotropic glutamate receptors GluR1-GluR6 in a fluorescence-based high throughput screening assay

    Strange, Mette; Bräuner-Osborne, Hans; Jensen, Anders A.

    2006-01-01

    We have constructed stable HEK293 cell lines expressing the rat ionotropic glutamate receptor subtypes GluR1(i), GluR2Q(i), GluR3(i), GluR4(i), GluR5Q and GluR6Q and characterised the pharmacological profiles of the six homomeric receptors in a fluorescence-based high throughput screening assay...... assay reported to date. We propose that high throughput screening of compound libraries at the six GluR-HEK293 cell lines could be helpful in the search for structurally and pharmacologically novel ligands acting at the receptors....

  8. R2 Cognitive Computing

    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...

  9. Multi-instantons in R4 and Minimal Surfaces in R2,1

    Tekin, Bayram

    2000-01-01

    It is known that self-duality equations for multi-instantons on a line in four dimensions are equivalent to minimal surface equations in three dimensional Minkowski space. We extend this equivalence beyond the equations of motion and show that topological number, instanton moduli space and anti-self-dual solutions have representations in terms of minimal surfaces. The issue of topological charge is quite subtle because the surfaces that appear are non-compact. This minimal surface/instanton correspondence allows us to define a metric on the configuration space of the gauge fields. We obtain the minimal surface representation of an instanton with arbitrary charge. The trivial vacuum and the BPST instanton as minimal surfaces are worked out in detail. BPS monopoles and the geodesics are also discussed. (author)

  10. R4SA for Controlling Robots

    Aghazarian, Hrand

    2009-01-01

    The R4SA GUI mentioned in the immediately preceding article is a userfriendly interface for controlling one or more robot(s). This GUI makes it possible to perform meaningful real-time field experiments and research in robotics at an unmatched level of fidelity, within minutes of setup. It provides such powerful graphing modes as that of a digitizing oscilloscope that displays up to 250 variables at rates between 1 and 200 Hz. This GUI can be configured as multiple intuitive interfaces for acquisition of data, command, and control to enable rapid testing of subsystems or an entire robot system while simultaneously performing analysis of data. The R4SA software establishes an intuitive component-based design environment that can be easily reconfigured for any robotic platform by creating or editing setup configuration files. The R4SA GUI enables event-driven and conditional sequencing similar to those of Mars Exploration Rover (MER) operations. It has been certified as part of the MER ground support equipment and, therefore, is allowed to be utilized in conjunction with MER flight hardware. The R4SA GUI could also be adapted to use in embedded computing systems, other than that of the MER, for commanding and real-time analysis of data.

  11. (1R,4R,6S,7R-5,5-Dibromo-1,4,8,8-tetramethyltricyclo[5.4.1.04,6]dodecan-12-one

    Mohamed Zaki

    2014-05-01

    Full Text Available The title compound, C16H24Br2O, was synthesized from the reaction of β-himachalene (3,5,5,9-tetramethyl-2,4a,5,6,7,8-hexahydro-1H-benzocycloheptene, which was isolated from Atlas cedar (Cedrus atlantica. The asymmetric unit contains two independent molecules with similar conformations. Each molecule is built up from two fused seven-membered rings and an additional three-membered ring. In both molecules, one of the seven-membered rings has a chair conformation, whereas the other displays a screw-boat conformation.

  12. Theory and verification manual for BARC-R6 software

    Rastogi, Rohit; Bhasin, Vivek; Vaze, K.K.; Kushwaha, H.S.

    2001-01-01

    This report presents the technical description of the BARC-R6 computer code that has been developed in Reactor Safety Division, BARC. The program has been designed to run on Windows95 based PCs. The R6 method is a tool, which can perform analysis considering fracture and plastic instability together as failure criteria. The R6 method for analyzing flawed components requires construction of number of graphs. The results of study are arrived at by analyzing these graphs. BARC- R6 is designed with a highly intuitive graphical user interface for input as well as output. This report presents the implementation details of the program. The current version has provision for any flaw orientation and type in pipes and elbows. This program will be highly useful for fracture assessment and Leak Before Break (LBB) qualification for Nuclear Power Plant (NPP) piping. The complete PHT piping of any typical NPP can be assessed with in a very short time. It is capable of handling Option-1 and Option-2 Failure Assessment Line (FAL) for both Category-1 and Category-3 type analysis. It has provision for exhaustive sensitivity analyses for judging the significance of margins with respect to variation in material properties, crack sizes etc. The report is divided into 6 sections. The first section introduces the document. The details offer method are presented in the second section. This is followed by the technical description of the program. The fourth section lists many benchmark problems solved to highlight its usage and validation. These benchmark problems cover the wide range of cases encountered in the practical situations. The user manual is provided in the fifth section. The sixth section contains the references used in this report. This is followed by an appendix containing the co-relations for stress intensity factor and limit loads, used in the BARC-R6 code. (author)

  13. R6 assessment of IPIRG-2 programme experiments

    Sharples, J.K.; France, C.C.; Budden, P.J.

    1999-01-01

    The International Piping Integrity Research Group (IPIRG) Programme was an international group programme managed by the US Nuclear Regulatory Commission (US NRC) and was aimed at developing a better understanding of the fracture behaviour of pressurised nuclear plant piping The second stage IPIRG experiments (IPIRG-2) included the development of data for the verification of fracture analyses for cracked pipes and fittings subjected to dynamic and/or cyclic load histories. This paper describes the results of work undertaken on analysing selected IPIRG-2 experiments using the UK R6 fracture assessment methodology. The level of conservatism of the R6 methodology is presented by comparing predicted applied bending moments at initiation and instability with the experimentally determined values. (author)

  14. Verification of failure avoidance concepts in R6 Rev3

    Milne, I.; Knee, N.

    1988-09-01

    The first part of this Report outlines how recent developments in fracture mechanics have led to a more accurate interpretation of the two-criteria approach to defect assessment. The implementation of these developments into Revision 3 of the Central Electricity Generating Board code of practice for the assessment of the defect tolerance of structures (R6) is described. One of the key elements of the revised version is the recommendation that the failure assessment line should be derived from the actual tensile stress/strain properties of the material. The second part of the Report addresses the validation of the method, which is a crucial step on the way to obtaining acceptance of R6 by, in particular, the regulatory bodies. The range of structures used to validate the procedure is illustrated by two examples. The use of conservative data and assumptions is fundamental to the R6 philosophy, which means that the procedure should not be used as a predictive tool. In the second example the importance of making these conservative assumptions is clearly illustrated. (author)

  15. The Group 2 Metabotropic Glutamate Receptor Agonist LY379268 Rescues Neuronal, Neurochemical and Motor Abnormalities in R6/2 Huntington’s Disease Mice

    Reiner, A.; Lafferty, D.C.; Wang, H.B.; Del Mar, N.; Deng, Y.P.

    2012-01-01

    Excitotoxic injury to striatum by dysfunctional cortical input or aberrant glutamate uptake may contribute to Huntington’s Disease (HD) pathogenesis. Since corticostriatal terminals possess mGluR2/3 autoreceptors, whose activation dampens glutamate release, we tested the ability of the mGluR2/3 agonist LY379268 to improve the phenotype in R6/2 HD mice with 120–125 CAG repeats. Daily subcutaneous injection of a maximum tolerated dose (MTD) of LY379268 (20mg/kg) had no evident adverse effects in WT mice, and diverse benefits in R6/2 mice, both in a cohort of mice tested behaviorally until the end of R6/2 lifespan and in a cohort sacrificed at 10 weeks of age for blinded histological analysis. MTD LY379268 yielded a significant 11% increase in R6/2 survival, an improvement on rotarod, normalization and/or improvement in locomotor parameters measured in open field (activity, speed, acceleration, endurance, and gait), a rescue of a 15–20% cortical and striatal neuron loss, normalization of SP striatal neuron neurochemistry, and to a lesser extent enkephalinergic striatal neuron neurochemistry. Deficits were greater in male than female R6/2 mice, and drug benefit tended to be greater in males. The improvements in SP striatal neurons, which facilitate movement, are consistent with the improved movement in LY379268-treated R6/2 mice. Our data indicate that mGluR2/3 agonists may be particularly useful for ameliorating the morphological, neurochemical and motor defects observed in HD. PMID:22472187

  16. D6R4 amplitudes in various dimensions

    Pioline, Boris

    2015-01-01

    Four-graviton couplings in the low energy effective action of type II string vacua compactified on tori are strongly constrained by supersymmetry and U-duality. While the R 4 and D 4 R 4 couplings are known exactly in terms of Langlands-Eisenstein series of the U-duality group, the D 6 R 4 couplings are not nearly as well understood. Exploiting the coincidence of the U-duality group in D=6 with the T-duality group in D=5, we propose an exact formula for the D 6 R 4 couplings in type II string theory compactified on T 4 , in terms of a genus-two modular integral plus a suitable Eisenstein series. The same modular integral computes the two-loop correction to D 6 R 4 in 5 dimensions, but here provides the non-perturbative completion of the known perturbative terms in D=6. This proposal hinges on a systematic re-analysis of the weak coupling and large radius of the D 6 R 4 in all dimensions D≥3, which fills in some gaps and resolves some inconsistencies in earlier studies.

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

    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)

  18. Mastering Microsoft Windows Server 2008 R2

    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

  19. The Monoceros R2 Molecular Cloud

    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.

  20. Windows Server 2012 R2 administrator cookbook

    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.

  1. Studsvik's R2 reactor - Review of activities

    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)

  2. s-wave scattering for deep potentials with attractive tails falling off faster than -1/r2

    Mueller, Tim-Oliver; Kaiser, Alexander; Friedrich, Harald

    2011-01-01

    For potentials with attractive tails, as occur in typical atomic interactions, we present a simple formula for the s-wave phase shift δ 0 . It exposes a universal dependence of δ 0 (E) on the potential tail and the influence of effects specific to a given potential, which enter via the scattering length a, or equivalently, the noninteger part Δ th of the threshold quantum number n th . The formula accurately reproduces δ 0 (E) from threshold up to the semiclassical regime, far beyond the validity of the effective-range expansion. We derive the tail functions occurring in the formula for δ 0 (E) and demonstrate the validity of the formula for attractive potential tails proportional to 1/r 6 or to 1/r 4 , and also for a mixed potential tail consisting of a 1/r 4 term together with a non-negligible 1/r 6 contribution.

  3. R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD)

    Cervenakova, L.; Brown, P.; Nagle, J. [and others

    1994-09-01

    There are conflicting reports on the association of deletions in the PRNP gene on chromosome 20 with CJD, a rapidly progressive fatal spongiform encephalopathy. We accumulated data suggesting that a deletion of R3-R4 type (parts of the third and fourth repeats are deleted from the area of four repeating 24 bp sequences in the 5{prime} region of the gene) is causing CJD. Screening of 129 unaffected control individuals demonstrated presence of a deletion of R2 type in four (1.55% of the studied chromosomes), but none of them had the R3-R4 type. Of 181 screened patients with spongiform encephalopathies, two had a deletion of R3-R4 type with no other mutations in the coding sequence. Both patients had a classical rapidly progressive dementing disease and diffuse spongiform degeneration, and both cases were apparently sporadic. The same R3-R4 type of deletion was detected in three additional neuropathologically confirmed spongiform encephalopathy patients, of which two had other known pathogenic mutations in the PRNP gene: at codon 178 on the methionine allele exhibiting the phenotype of fatal familial insomnia, and codon 200 causing CJD with severe dementia; the third was a patient with iatrogenic CJD who developed the disease after treatment with growth hormone extracted from cadaveric human pituitary glands. In all cases the deletion coincided with a variant sequence at position 129 coding for methionine.

  4. Mastering Windows Server 2012 R2

    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

  5. R2 inflation in anisotropic universes

    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

  6. (1R,2R,3R,4S,5S-3-Methyl-8-oxabicyclo[3.2.1]oct-6-ene-2,4-diyl diacetate

    Viktor A. Tafeenko

    2011-08-01

    Full Text Available The molecule of the title compound, C12H16O5, has crystallographically imposed mirror symmetry with the mirror plane passing through the endocyclic O atom and the mid-point of the double bond. In the crystal, molecules are linked by C—H...O hydrogen bonds, forming chains running along the a axis.

  7. Group IB Organometallic Chemistry XIX.Synthesis and characterization of mixed-organocopper cluster compounds R4R'2Cu6 containing aryl and acetylide ligands.

    Koten, G. van; Hoedt, R.W.M. ten; Noltes, J.G.

    1977-01-01

    Mixed-organocopper cluster compounds Ar4Cu6(CCR)2 (Ar = 2-Me2NC6H4, R = phenyl, 4-tolyl, 2,4-xylyl or mesityl) have been prepared in high yield by the ligand-substitution reaction of Ar4Cu6Br2 with two equivalents of LiCCR. Ar4Cu6(CCC6H4CH3-4)2 has also been prepared via the aryl¡ªarylacetylide

  8. Developments in UK defect assessment procedures R6 revision 4 and BS7910

    Sharples, J.K.; Ainsworth, R.A.; Budden, P.J.

    2003-01-01

    The R6 defect assessment procedures have been developed over many years by the UK nuclear power generation industry. The procedures are updated on a regular basis, taking into account the information resulting from the R6 development programme and other available information worldwide. A major revision, Revision 4, of the R6 procedures was released in 2000. Just prior to that release, in 1999, the British Standards flaw assessment procedure BS7910 was issued and combined and updated the previous published documents PD6493 and PD6539, for components operating at temperatures where creep was negligible and important, respectively. BS79l0 is also under constant development. This paper provides a brief overview of the BS7910 and R6 Revision 4 procedures and describes updates to the respective documents since they were first issued. Some ongoing developments which will lead to future revisions to the documents are also described. (author)

  9. Elastic-plastic fracture analysis of carbon steel piping using the latest CEGB R6 approach

    Kanno, S.; Hasegawa, K.; Shimizu, T.; Kobayashi, H.

    1991-01-01

    The elastic-plastic fracture of carbon steel piping having various pipe diameters and circumferential crack angles and subjected to a bending moment is analyzed using the latest United Kingdom Central Electricity Generating Board R6 approach. The elastic-plastic fracture criterion must be applied instead of the plastic collapse criterion with increase of the pipe diameter and the crack angle. A simplified elastic-plastic fracture analysis procedure based on the R6 approach is proposed. (author)

  10. R2 dark energy in the laboratory

    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.

  11. R4 terms in supergravities via T -duality constraint

    Razaghian, Hamid; Garousi, Mohammad R.

    2018-05-01

    It has been speculated in the literature that the effective actions of string theories at any order of α' should be invariant under the Buscher rules plus their higher covariant-derivative corrections. This may be used as a constraint to find effective actions at any order of α', in particular, the metric, the B -field, and the dilaton couplings in supergravities at order α'3 up to an overall factor. For the simple case of zero B -field and diagonal metric in which we have done the calculations explicitly, we have found that the constraint fixes almost all of the seven independent Riemann curvature couplings. There is only one term which is not fixed, because when metric is diagonal, the reduction of two R4 terms becomes identical. The Riemann curvature couplings that the T -duality constraint produces for both type II and heterotic theories are fully consistent with the existing couplings in the literature which have been found by the S-matrix and by the sigma-model approaches.

  12. Pseudo-simple heteroclinic cycles in R4

    Chossat, Pascal; Lohse, Alexander; Podvigina, Olga

    2018-06-01

    We study pseudo-simple heteroclinic cycles for a Γ-equivariant system in R4 with finite Γ ⊂ O(4) , and their nearby dynamics. In particular, in a first step towards a full classification - analogous to that which exists already for the class of simple cycles - we identify all finite subgroups of O(4) admitting pseudo-simple cycles. To this end we introduce a constructive method to build equivariant dynamical systems possessing a robust heteroclinic cycle. Extending a previous study we also investigate the existence of periodic orbits close to a pseudo-simple cycle, which depends on the symmetry groups of equilibria in the cycle. Moreover, we identify subgroups Γ ⊂ O(4) , Γ ⊄ SO(4) , admitting fragmentarily asymptotically stable pseudo-simple heteroclinic cycles. (It has been previously shown that for Γ ⊂ SO(4) pseudo-simple cycles generically are completely unstable.) Finally, we study a generalized heteroclinic cycle, which involves a pseudo-simple cycle as a subset.

  13. R.4. Innovative concept for plutonium finishing facility

    Bertolotti, G.; Laguerie, I.V. de; Richter, R.; Gillet, B.

    1998-01-01

    After complete shutdown of the units of the previous UP2 plant, the new R4 facility will ensure the purification of Plutonium of the UP2-800 plant for the whole range of fuel to be reprocessed in the years to come. This facility features four main units: - Purification of plutonium nitrate; - Conversion into plutonium oxide; - PuO 2 conditioning into cans; Acid recovery. An extensive R and D program resulted in significant innovations. From a technological aspect the centrifugal extractor and the sub-critical tube bundle tank contributed to the reduction of the building dimensions. The extensive use of on-line analyses enables a more efficient follow-up of the process while minimizing the effluent production. On the other hand, the organization of the building which consists in grouping the rooms presenting the same risk of dispersal of nuclear materials also contributed to reduce the active zone volume. This facility, as any other facilities on the LA HAGUE site, will be remotely operated. (author)

  14. Surface-enhanced resonance Raman scattering spectroscopy of single R6G molecules

    Zhou Zeng-Hui; Liu Li; Wang Gui-Ying; Xu Zhi-Zhan

    2006-01-01

    Surface-enhanced resonance Raman scattering (SERRS) of Rhodamine 6G (R6G) adsorbed on colloidal silver clusters has been studied. Based on the great enhancement of the Raman signal and the quench of the fluorescence, the SERRS spectra of R6G were recorded for the samples of dye colloidal solution with different concentrations. Spectral inhomogeneity behaviours from single molecules in the dried sample films were observed with complementary evidences, such as spectral polarization, spectral diffusion, intensity fluctuation of vibrational lines and even "breathing" of the molecules. Sequential spectra observed from a liquid sample with an average of 0.3 dye molecules in the probed volume exhibited the expected Poisson distribution for actually measuring 0, 1 or 2 molecules. Difference between the SERRS spectra of R6G excited by linearly and circularly polarized light were experimentally measured.

  15. Ionic fluids with r-6 pair interactions have power-law electrostatic screening

    Kjellander, Roland; Forsberg, Bjoern

    2005-01-01

    The decay behaviour of radial distribution functions for large distances r is investigated for classical Coulomb fluids where the ions interact with an r -6 potential (e.g. a dispersion interaction) in addition to the Coulombic and the short-range repulsive potentials (e.g. a hard core). The pair distributions and the density-density (NN), charge-density (QN) and charge-charge (QQ) correlation functions are investigated analytically and by Monte Carlo simulations. It is found that the NN correlation function ultimately decays like r -6 for large r, just as it does for fluids of electroneutral particles interacting with an r -6 potential. The prefactor is proportional to the squared compressibility in both cases. The QN correlations decay in general like r -8 and the QQ correlations like r -10 in the ionic fluid. The average charge density around an ion decays generally like r -8 and the average electrostatic potential like r -6 . This behaviour is in stark contrast to the decay behaviour for classical Coulomb fluids in the absence of the r -6 potential, where all these functions decay exponentially for large r. The power-law decays are, however, the same as for quantum Coulomb fluids. This indicates that the inclusion of the dispersion interaction as an effective r -6 interaction potential in classical systems yields the same decay behaviour for the pair correlations as in quantum ionic systems. An exceptional case is the completely symmetric binary electrolyte for which only the NN correlation has a power-law decay but not the QQ correlations. These features are shown by an analysis of the bridge function

  16. (1R,3R,4R,6S-4-(7-Methoxy-2-oxo-2H-chromen-6-yl-1-methyl-3,6-dioxabicyclo[3.1.0]hexan-2-yl acetate

    Wong Phakhodee

    2012-12-01

    Full Text Available In the title compound, C17H16O7, which was isolated from the leaves of Micromelum integerrimum, the furan ring adopts an envelope conformation with the O atom as the flap. An intramolecular C—H...O hydrogen bond occurs. The carbonyl O atom is disordered in a 0.57 (8:0.43 (8 ratio. In the crystal, molecules are linked by weak C—H...O hydrogen bonds into a C(10 chain along [010].

  17. Adaptation to experimental jet-lag in R6/2 mice despite circadian dysrhythmia.

    Nigel I Wood

    Full Text Available The R6/2 transgenic mouse model of Huntington's disease (HD shows a disintegration of circadian rhythms that can be delayed by pharmacological and non-pharmacological means. Since the molecular machinery underlying the circadian clocks is intact, albeit progressively dysfunctional, we wondered if light phase shifts could modulate the deterioration in daily rhythms in R6/2 mice. Mice were subjected to four x 4 hour advances in light onset. R6/2 mice adapted to phase advances, although angles of entrainment increased with age. A second cohort was subjected to a jet-lag paradigm (6 hour delay or advance in light onset, then reversal after 2 weeks. R6/2 mice adapted to the original shift, but could not adjust accurately to the reversal. Interestingly, phase shifts ameliorated the circadian rhythm breakdown seen in R6/2 mice under normal LD conditions. Our previous finding that the circadian period (tau of 16 week old R6/2 mice shortens to approximately 23 hours may explain how they adapt to phase advances and maintain regular circadian rhythms. We tested this using a 23 hour period light/dark cycle. R6/2 mice entrained to this cycle, but onsets of activity continued to advance, and circadian rhythms still disintegrated. Therefore, the beneficial effects of phase-shifting are not due solely to the light cycle being closer to the tau of the mice. Our data show that R6/2 mice can adapt to changes in the LD schedule, even beyond the age when their circadian rhythms would normally disintegrate. Nevertheless, they show abnormal responses to changes in light cycles. These might be caused by a shortened tau, impaired photic re-synchronization, impaired light detection and/or reduced masking by evening light. If similar abnormalities are present in HD patients, they may suffer exaggerated jet-lag. Since the underlying molecular clock mechanism remains intact, light may be a useful treatment for circadian dysfunction in HD.

  18. Center type performance of differentiable vector fields in R2

    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)

  19. Altered dopamine and serotonin metabolism in motorically asymptomatic R6/2 mice.

    Fanny Mochel

    Full Text Available The pattern of cerebral dopamine (DA abnormalities in Huntington disease (HD is complex, as reflected by the variable clinical benefit of both DA antagonists and agonists in treating HD symptoms. In addition, little is known about serotonin metabolism despite the early occurrence of anxiety and depression in HD. Post-mortem enzymatic changes are likely to interfere with the in vivo profile of biogenic amines. Hence, in order to reliably characterize the regional and chronological profile of brain neurotransmitters in a HD mouse model, we used a microwave fixation system that preserves in vivo concentrations of dopaminergic and serotoninergic amines. DA was decreased in the striatum of R6/2 mice at 8 and 12 weeks of age while DA metabolites, 3-methoxytyramine and homovanillic acid, were already significantly reduced in 4-week-old motorically asymptomatic R6/2 mice. In the striatum, hippocampus and frontal cortex of 4, 8 and 12-week-old R6/2 mice, serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly decreased in association with a decreased turnover of serotonin. In addition, automated high-resolution behavioural analyses displayed stress-like behaviours such as jumping and grooming and altered spatial learning in R6/2 mice at age 4 and 6 weeks respectively. Therefore, we describe the earliest alterations of DA and serotonin metabolism in a HD murine model. Our findings likely underpin the neuropsychological symptoms at time of disease onset in HD.

  20. Unraveling the symmetry ambiguity in a hexamer: Calculation of the R6 human insulin structure

    O'Donoghue, Sean I.; Chang Xiaoqing; Abseher, Roger; Nilges, Michael; Led, Jens J.

    2000-01-01

    Crystallographic and NMR studies of insulin have revealed a highly flexible molecule with a range of different aggregation and structural states; the importance of these states for the function of the hormone is still unclear. To address this question, we have studied the solution structure of the insulin R 6 symmetric hexamer using NMR spectroscopy. Structure determination of symmetric oligomers by NMR is complicated due to 'symmetry ambiguity' between intra- and intermonomer NOEs, and between different classes of intermonomer NOEs. Hence, to date, only two symmetric tetramers and one symmetric pentamer (VTB, B subunit of verotoxin) have been solved by NMR; there has been no other symmetric hexamer or higher-order oligomer. Recently, we reported a solution structure for R 6 insulin hexamer. However, in that study, a crystal structure was used as a reference to resolve ambiguities caused by the threefold symmetry; the same method was used in solving VTB. Here, we have successfully recalculated R 6 insulin using the symmetry-ADR method, a computational strategy in which ambiguities are resolved using the NMR data alone. Thus the obtained structure is a refinement of the previous R 6 solution structure. Correlated motions in the final structural ensemble were analysed using a recently developed principal component method; this suggests the presence of two major conformational substates. The study demonstrates that the solution structure of higher-order symmetric oligomers can be determined unambiguously from NMR data alone, using the symmetry-ADR method. This success bodes well for future NMR studies of higher-order symmetric oligomers. The correlated motions observed in the structural ensemble suggest a new insight into the mechanism of phenol exchange and the T 6 ↔ R 6 transition of insulin in solution

  1. Multicenter R2* mapping in the healthy brain

    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...

  2. Partial synthesis of (3R,6'R)-alpha-cryptoxanthin and (3R)-beta-cryptoxanthin from (3R,3'R,6'R)-lutein.

    Khachik, Frederick; Chang, An-Ni; Gana, Audry; Mazzola, Eugene

    2007-02-01

    (3R,3'R,6'R)-Lutein (1), (3R,3'R)-zeaxanthin (2), (3R,6'R)-alpha-cryptoxanthin (3), and (3R)-beta-cryptoxanthin (4) are among dietary hydroxycarotenoids that have been identified in human serum, milk, and ocular tissues. While 1 containing 6% of 2 is commercially available, industrial production of optically active 3 and 4 has not yet been accomplished. Several processes have been developed that transform 1 into 3, 4, and minor quantities of (3R,5'RS,6'R)-3',4'-didehydro-5',6'-dihydro-beta,beta-caroten-3-ol (5) (a regioisomer of 3). In one process, lutein (1) was cleanly deoxygenated to 3 in the presence of trifluoroacetic acid (TFA) and Me3N.BH3 in CH2Cl2 at ambient temperature in nearly 90% yield. Reaction of lutein (1) with a Lewis acid (AlCl3, ZnBr2, ZnI2) and a hydride donor (Me3N.BH3, Na[BH3(OCOCF3)], NaCNBH3) in solvents such as CH2Cl2, THF, and TBME produced similar results. In a two-step process, high-temperature acid-catalyzed dehydration of 1 (propanol/water/acid, 90 degrees C) gave a mixture of anhydroluteins 6, 7, and 8 in 86% yield. In the second step, these dehydration products underwent ionic hydrogenation with TFA/Me3N.BH3 in CH2Cl2 to afford a mixture of 3 and 4 in nearly 80% yield that contained only 1% of 5.

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

    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

  4. Mainstream Smoke Chemistry and in Vitro and In Vivo Toxicity of the Reference Cigarettes 3R4F and 2R4F

    Roemer E

    2014-12-01

    Full Text Available A new reference cigarette, the 3R4F, has been developed to replace the depleting supply of the 2R4F cigarette. The present study was designed to compare mainstream smoke chemistry and toxicity of the two reference cigarettes under the International Organization for Standardization (ISO machine smoking conditions, and to further compare mainstream smoke chemistry and toxicological activity of the 3R4F cigarette by two different smoking regimens, i.e., the machine smoking conditions specified by ISO and the Health Canada intensive (HCI smoking conditions.

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

    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.

  6. Loss of Hda activity stimulates replication initiation from I-box, but not R4 mutant origins in Escherichia coli.

    Riber, Leise; Fujimitsu, Kazuyuki; Katayama, Tsutomu; Løbner-Olesen, Anders

    2009-01-01

    Initiation of chromosome replication in Escherichia coli is limited by the initiator protein DnaA associated with ATP. Within the replication origin, binding sites for DnaA associated with ATP or ADP (R boxes) and the DnaA(ATP) specific sites (I-boxes, tau-boxes and 6-mer sites) are found. We analysed chromosome replication of cells carrying mutations in conserved regions of oriC. Cells carrying mutations in DnaA-boxes I2, I3, R2, R3 and R5 as well as FIS and IHF binding sites resembled wild-type cells with respect to origin concentration. Initiation of replication in these mutants occurred in synchrony or with slight asynchrony only. Furthermore, lack of Hda stimulated initiation in all these mutants. The DnaA(ATP) containing complex that leads to initiation can therefore be formed in the absence of several of the origin DnaA binding sites including both DnaA(ATP) specific I-boxes. However, competition between I-box mutant and wild-type origins, revealed a positive role of I-boxes on initiation. On the other hand, mutations affecting DnaA-box R4 were found to be compromised for initiation and could not be augmented by an increase in cellular DnaA(ATP)/DnaA(ADP) ratio. Compared with the sites tested here, R4 therefore seems to contribute to initiation most critically.

  7. 26 CFR 1.414(r)-6 - Qualified separate line of business-administrative scrutiny requirement-individual determinations.

    2010-04-01

    ...-administrative scrutiny requirement-individual determinations. 1.414(r)-6 Section 1.414(r)-6 Internal Revenue... Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(r)-6 Qualified separate line of business... determined under § 1.414(r)-3) that does not satisfy any of the safe harbors in § 1.414(r)-5 for a testing...

  8. Glutamate Receptors GluR1 and GluR4 in the Hamster Superior Colliculus: Distribution and Co-localization with Calcium-Binding Proteins and GABA

    Choi, Jae-Sik; Lee, Jea-Young; Jeon, Chang-Jin

    2009-01-01

    We investigated the distributions of AMPA glutamate receptor subtypes GluR1 and GluR4 in the hamster superior colliculus (SC) with antibody immunocytochemistry and the effect of enucleation on these distributions. We compared these labelings to those of GluR2/3 in our previous report (Park et al., 2004, Neurosci Res., 49:139–155) and calcium-binding proteins calbindin D28K, calretinin, parvalbumin, and GABA. Anti-GluR1-immunoreactive (IR) cells were scattered throughout the SC. By contrast, anti-GluR4-IR cells formed distinct clusters within the lower lateral stratum griseum intermediale (SGI) and lateral stratum album intermediale (SAI). The GluR1- and GluR4-IR neurons varied in size and morphology. The average diameter of the GluR1-IR cells was 13.00 µm, while the GluR4-IR cells was 20.00 µm. The large majority of IR neurons were round or oval cells, but they also included stellate, vertical fusiform and horizontal cells. Monocular enucleation appeared to have no effect on the GluR1 and GluR4 immunoreactivity. Some GluR1-IR cells expressed calbindin D28K (9.50%), calretinin (6.59%), parvalbumin (2.53%), and GABA (20.54%). By contrast, no GluR4-IR cells expressed calcium-binding proteins or GABA. Although the function of the AMPA receptor subunits in SC is not yet clear, the distinct segregation of the GluR subunits, its differential colocalization with calcium-binding proteins and GABA, and differential responses to enucleation suggest the functional diversity of the receptor subunits in visuo-motor integration in the SC

  9. Multiple Copies of a Simple MYB-Binding Site Confers Trans-regulation by Specific Flavonoid-Related R2R3 MYBs in Diverse Species

    Cyril Brendolise

    2017-10-01

    Full Text Available In apple, the MYB transcription factor MYB10 controls the accumulation of anthocyanins. MYB10 is able to auto-activate its expression by binding its own promoter at a specific motif, the R1 motif. In some apple accessions a natural mutation, termed R6, has more copies of this motif within the MYB10 promoter resulting in stronger auto-activation and elevated anthocyanins. Here we show that other anthocyanin-related MYBs selected from apple, pear, strawberry, petunia, kiwifruit and Arabidopsis are able to activate promoters containing the R6 motif. To examine the specificity of this motif, members of the R2R3 MYB family were screened against a promoter harboring the R6 mutation. Only MYBs from subgroups 5 and 6 activate expression by binding the R6 motif, with these MYBs sharing conserved residues in their R2R3 DNA binding domains. Insertion of the apple R6 motif into orthologous promoters of MYB10 in pear (PcMYB10 and Arabidopsis (AtMY75 elevated anthocyanin levels. Introduction of the R6 motif into the promoter region of an anthocyanin biosynthetic enzyme F3′5′H of kiwifruit imparts regulation by MYB10. This results in elevated levels of delphinidin in both tobacco and kiwifruit. Finally, an R6 motif inserted into the promoter the vitamin C biosynthesis gene GDP-L-Gal phosphorylase increases vitamin C content in a MYB10-dependent manner. This motif therefore provides a tool to re-engineer novel MYB-regulated responses in plants.

  10. R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

    Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

    2012-05-09

    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

  11. Qualification of PHT piping of Indian 500 MW PHWR for LBB, using R-6 method

    Rastogi, Rohit; Bhasin, V.; Kushwaha, H.S.

    1997-01-01

    This document discusses the qualification of straight pipe portion of the primary heat transport (PHT) piping of Indian 500 MWe pressurised heavy water reactor (PHWR) for leak before break (LBB). The evaluation is done using R-6 [1] method. The results presented here are: the safety margins which exist on straight pipe components of main PHT piping of 500 MWe, under leakage size crack (LSC) and design basis accident loads; the sensitivity of safety margins with respect to different analysis parameters and the qualification of PHT piping for LBB based on criterion given by NUREG-1061 [2] and TECDOC-774 [3]. (author)

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

    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)

  13. R6 validation exercise: through thickness residual stress measurements on an experiment test vessel ring

    Mitchell, D.H.

    1988-06-01

    A series of bursting tests on thick-walled pressure vessels has been carried out as part of a validation exercise for the CEGB R6 failure assessment procedure. The objective of these tests was the examination of the behaviour of typical PWR primary vessel material subject to residual stresses in addition to primary loading with particular reference to the R6 assessment procedure. To this end, a semi-elliptic part-through defect was sited in the vessel longitudinal seam, which was a submerged arc weld in the non stress-relieved condition; it was then pressure tested to failure. Prior to the final assembly of this vessel, a ring of material was cut from it to act as a test-piece on which a residual stress survey could be made. Surface measurements using the centre-hole technique were made by CERL personnel, and this has been followed by two through- thickness measurements at BNL using the deep-hole technique. This paper describes these deep-hole measurements and presents the results from them. (author)

  14. PARP-1 Inhibition Is Neuroprotective in the R6/2 Mouse Model of Huntington's Disease.

    Antonella Cardinale

    Full Text Available Poly (ADP-ribose polymerase 1 (PARP-1 is a nuclear enzyme that is involved in physiological processes as DNA repair, genomic stability, and apoptosis. Moreover, published studies demonstrated that PARP-1 mediates necrotic cell death in response to excessive DNA damage under certain pathological conditions. In Huntington's disease brains, PARP immunoreactivity was described in neurons and in glial cells, thereby suggesting the involvement of apoptosis in HD. In this study, we sought to determine if the PARP-1 inhibitor exerts a neuroprotective effect in R6/2 mutant mice, which recapitulates, in many aspects, human HD. Transgenic mice were treated with the PARP-1 inhibitor INO-1001 mg/Kg daily starting from 4 weeks of age. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that INO 1001-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as striatal atrophy, morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. INO-1001 was effective in significantly increasing activated CREB and BDNF in the striatal spiny neurons, which might account for the beneficial effects observed in this model. Our findings show that PARP-1 inhibition could be considered as a valid therapeutic approach for HD.

  15. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2

    Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne

    2015-01-01

    of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood...

  16. Comparison of R6 and A16 J estimation methods under combined mechanical and thermal loads with FE results

    Nam, Hyun-Suk; Oh, Chang-Young; Kim, Yun-Jae; Jerng, Dong Wook; Ainsworth, Robert A.; Budden, Peter J.; Marie, Stéphane

    2015-01-01

    This paper compares elastic–plastic values of J calculated using the methods in the UK R6 and the French A16 fitness-for-service procedures with FE results for a vessel with a circumferential surface crack under axial tension and a radial thermal gradient. In the FE analyses, the relative magnitudes and loading sequence of mechanical and thermal loads are systematically varied, together with the material strain hardening exponent. Fully circumferential and semi-elliptical surface crack with two relative crack depths are considered. It is found that the R6 estimates are overall accurate but can be non-conservative at large L_r. The A16 estimates are more conservative than the R6 estimates at small L_r but are conservative even at large L_r. Possible sources of conservatism and non-conservatism in R6 and A16 are discussed. - Highlights: • Accuracy of existing J estimation methods for combined mechanical and thermal loading are compared with FE results. • The methods in the UK R6 and the French A16 procedures are considered. • The R6 estimates are overall accurate but can be non-conservative at large L_r. • The A16 estimates are more conservative than the R6 estimates at small L_r but are conservative even at large L_r. • Possible sources of conservatism and non-conservatism in R6 and A16 are discussed.

  17. Distribution and characterization of Podosphaera macularis virulent on hop cultivars possessing R6-based resistance to powdery mildew

    In 2012, an epidemic of powdery mildew occurred in Washington and Idaho on previously resistant cultivars whose resistance was putatively based on the gene designated R6. In 2013, isolates capable of causing severe disease on cultivars with R6-based resistance were confirmed in Oregon and became wid...

  18. The interaction between AMPKβ2 and the PP1-targeting subunit R6 is dynamically regulated by intracellular glycogen content.

    Oligschlaeger, Yvonne; Miglianico, Marie; Dahlmans, Vivian; Rubio-Villena, Carla; Chanda, Dipanjan; Garcia-Gimeno, Maria Adelaida; Coumans, Will A; Liu, Yilin; Voncken, J Willem; Luiken, Joost J F P; Glatz, Jan F C; Sanz, Pascual; Neumann, Dietbert

    2016-04-01

    AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKβ at Thr-148, which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKβ1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase type 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK. In the present study, we further investigated the interaction of R6 with AMPKβ and the possible dependency on Thr-148 phosphorylation status. Yeast two-hybrid (Y2H) analyses and co-immunoprecipitation (IP) of the overexpressed proteins in human embryonic kidney (HEK) 293T) cells revealed that both AMPKβ1 and AMPK-β2 wild-type (WT) isoforms bind to R6. The AMPKβ-R6 interaction was stronger with the muscle-specific AMPKβ2-WT and required association with the substrate-binding motif of R6. When HEK293T cells or C2C12 myotubes were cultured in high-glucose medium, AMPKβ2-WT and R6 weakly interacted. In contrast, glycogen depletion significantly enhanced this protein interaction. Mutation of AMPKβ2 Thr-148 prevented the interaction with R6 irrespective of the intracellular glycogen content. Treatment with the AMPK activator oligomycin enhanced the AMPKβ2-R6 interaction in conjunction with increased Thr-148 phosphorylation in cells grown in low-glucose medium. These data are in accordance with R6 binding directly to AMPKβ2 when both proteins detach from the diminishing glycogen particle, which is simultaneous with increased AMPKβ2 Thr-148 autophosphorylation. Such a model points to a possible control of AMPK by PP1-R6 upon glycogen depletion in muscle. © 2016 Authors; published by Portland Press Limited.

  19. Some remarks on the space R2(E

    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.

  20. Practical applications of the R6 leak-before-break procedure

    Bouchard, P.J.

    1997-01-01

    A forthcoming revision to the R6 Leak-before-Break Assessment Procedure is briefly described. Practical application of the LbB concepts to safety-critical nuclear plant is illustrated by examples covering both low temperature and high temperature (>450 degrees C) operating regimes. The examples highlight a number of issues which can make the development of a satisfactory LbB case problematic: for example, coping with highly loaded components, methodology assumptions and the definition of margins, the effect of crack closure owing to weld residual stresses, complex thermal stress fields or primary bending fields, the treatment of locally high stresses at crack intersections with free surfaces, the choice of local limit load solution when predicting ligament breakthrough, and the scope of calculations required to support even a simplified LbB case for high temperature steam pipe-work systems

  1. Practical applications of the R6 leak-before-break procedure

    Bouchard, P.J.

    1997-04-01

    A forthcoming revision to the R6 Leak-before-Break Assessment Procedure is briefly described. Practical application of the LbB concepts to safety-critical nuclear plant is illustrated by examples covering both low temperature and high temperature (>450{degrees}C) operating regimes. The examples highlight a number of issues which can make the development of a satisfactory LbB case problematic: for example, coping with highly loaded components, methodology assumptions and the definition of margins, the effect of crack closure owing to weld residual stresses, complex thermal stress fields or primary bending fields, the treatment of locally high stresses at crack intersections with free surfaces, the choice of local limit load solution when predicting ligament breakthrough, and the scope of calculations required to support even a simplified LbB case for high temperature steam pipe-work systems.

  2. Probabilistic fracture failure analysis of nuclear piping containing defects using R6 method

    Lin, Y.C.; Xie, Y.J.; Wang, X.H.

    2004-01-01

    Failure analysis of in-service nuclear piping containing defects is an important subject in the nuclear power plants. Considering the uncertainties in various internal operating loadings and external forces, including earthquake and wind, flaw sizes, material fracture toughness and flow stress, this paper presents a probabilistic assessment methodology for in-service nuclear piping containing defects, which is especially designed for programming. A general sampling computation method of the stress intensity factor (SIF), in the form of the relationship between the SIF and the axial force, bending moment and torsion, is adopted in the probabilistic assessment methodology. This relationship has been successfully used in developing the software, Safety Assessment System of In-service Pressure Piping Containing Flaws (SAPP-2003), based on a well-known engineering safety assessment procedure R6. A numerical example is given to show the application of the SAPP-2003 software. The failure probabilities of each defect and the whole piping can be obtained by this software

  3. Dynamics, integrability and topology for some classes of Kolmogorov Hamiltonian systems in R+4

    Llibre, Jaume; Xiao, Dongmei

    2017-02-01

    In this paper we first give the sufficient and necessary conditions in order that two classes of polynomial Kolmogorov systems in R+4 are Hamiltonian systems. Then we study the integrability of these Hamiltonian systems in the Liouville sense. Finally, we investigate the global dynamics of the completely integrable Lotka-Volterra Hamiltonian systems in R+4. As an application of the invariant subsets of these systems, we obtain topological classifications of the 3-submanifolds in R+4 defined by the hypersurfaces axy + bzw + cx2 y + dxy2 + ez2 w + fzw2 = h, where a , b , c , d , e , f , w and h are real constants.

  4. Microsoft System Center 2012 R2 Operations Manager cookbook

    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.

  5. Spectral sum rule for time delay in R2

    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

  6. 海马神经元中TAT-GluR6-9c-dansyl小肽的荧光观察%Delivery of GluR6-9c into hippocampal neurons by TAT transduction domain

    纵艳艳; 裴冬生; 孙亚峰; 张光毅

    2005-01-01

    目的研究TAT-GluR6-9c-dansyl荧光小肽是否可以进入细胞内部.方法在培养的海马神经元中加入TAT-GluR6-9c-dansyl荧光小肽和对照肽TAT38-48-dansyl.结果用10 μmol/L TAT-GluR6-9c-dansyl处理的海马神经元在荧光显微镜下可以观到绿色荧光的出现,而对照肽TAT38-48-dansyl无荧光出现.结论 TAT-GluR6-9c-dansyl荧光小肽可以进入细胞.

  7. The two ∇6R4 type invariants and their higher order generalisation

    Bossard, Guillaume; Verschinin, Valentin

    2015-01-01

    We show that there are two distinct classes of ∇ 6 R 4 type supersymmetry invariants in maximal supergravity. The second class includes a coupling in F 2 ∇ 4 R 4 that generalises to 1/8 BPS protected F 2k ∇ 4 R 4 couplings. We work out the supersymmetry constraints on the corresponding threshold functions, and argue that the functions in the second class satisfy to homogeneous differential equations for arbitrary k≥1, such that the corresponding exact threshold functions in type II string theory should be proportional to Eisenstein series, which we identify. This analysis explains in particular that the exact ∇ 6 R 4 threshold function is the sum of an Eisenstein function and a solution to an inhomogeneous Poisson equation in string theory.

  8. Metabotropic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease

    Levey, Allan

    2001-01-01

    ...) as a novel target for the treatment of PD. We have localized mGluR4 in basal ganglia structures, and explored its role in mediating the electrophysiological effects of glutamate in rat brain slices...

  9. Oracle JDeveloper 11gR2 Cookbook

    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

  10. Posttreatment with group II metabotropic glutamate receptor agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate is only weakly effective on seizures in immature rats

    Folbergrová, Jaroslava; Druga, Rastislav; Tsenov, Grygoriy; Haugvicová, Renata; Otáhal, Jakub

    2009-01-01

    Roč. 1273, - (2009), s. 144-154 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR GA309/08/0292; GA ČR(CZ) GA304/07/1137 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : DL-homocysteic acid-induced seizures * posttreatment with 2R * 4R-APDC * partial protection Subject RIV: FH - Neuro logy Impact factor: 2.463, year: 2009

  11. Matching the $D^{6}R^{4}$ interaction at two-loops

    D'Hoker, Eric; Pioline, Boris; Russo, Rodolfo

    2015-01-01

    The coefficient of the $D^6 {\\cal R}^4$ interaction in the low energy expansion of the two-loop four-graviton amplitude in type II superstring theory is known to be proportional to the integral of the Zhang-Kawazumi (ZK) invariant over the moduli space of genus-two Riemann surfaces. We demonstrate that the ZK invariant is an eigenfunction with eigenvalue 5 of the Laplace-Beltrami operator in the interior of moduli space. Exploiting this result, we evaluate the integral of the ZK invariant explicitly, finding agreement with the value of the two-loop $D^6 {\\cal R}^4$ interaction predicted on the basis of S-duality and supersymmetry. A review of the current understanding of the $D^{2p} {\\cal R}^4$ interactions in type II superstring theory compactified on a torus $T^d$ with $p \\leq 3$ and $d \\leq 4$ is included.

  12. GluR2 ligand-binding core complexes

    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...

  13. Equipment for thermal neutron flux measurements in reactor R2

    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.

  14. Microsoft System Center Data Protection Manager 2012 R2 cookbook

    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.

  15. R2E – identifying problems, mitigating risks

    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...

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

    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.

  17. 26 CFR 1.414(r)-4 - Qualified separate line of business-fifty-employee and notice requirements.

    2010-04-01

    ...-employee and notice requirements. 1.414(r)-4 Section 1.414(r)-4 Internal Revenue INTERNAL REVENUE SERVICE... Bonus Plans, Etc. § 1.414(r)-4 Qualified separate line of business—fifty-employee and notice... business (as determined under § 1.414(r)-3) satisfies the 50-employee and notice requirements of § 1.414(r...

  18. Mitochondrial cristae remodelling is associated with disrupted OPA1 oligomerisation in the Huntington's disease R6/2 fragment model.

    Hering, Tanja; Kojer, Kerstin; Birth, Nathalie; Hallitsch, Jaqueline; Taanman, Jan-Willem; Orth, Michael

    2017-02-01

    There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals. Mitochondrial morphology was determined using electron microscopy, and transcript and protein levels of factors that play a key role in fission and fusion, including DRP1, mitofusin 1 and 2, mitofilin and OPA1, and cytochrome c and caspase 3 were assessed by RT-qPCR and immunoblotting. OPA1 oligomerisation was evaluated using blue native gels. In striatum and cortex of R6/2 mice, mitochondrial cristae morphology was abnormal. Mitofilin and the overall levels of the fission and fusion factors were unaffected; however, OPA1 oligomerisation was abnormal in striatum and cortex of R6/2 mice. Mitochondrial and cytoplasmic cytochrome c levels were similar in R6/2 and wild-type mice with no significant increase of activated caspase 3. Our results indicate that the integrity of the mitochondrial cristae is compromised in striatum and cortex of the R6/2 mice and that this is most likely caused by impaired OPA1 oligomerisation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Characterization of somatostatin receptors and associated signaling pathways in pancreas of R6/2 transgenic mice.

    Somvanshi, Rishi K; Jhajj, Amrit; Heer, Michael; Kumar, Ujendra

    2018-02-01

    The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (β), glucagon (α) and somatostatin (δ) producing cells in the pancreatic islets of 11weeks old R6/2 Huntington's Disease transgenic (HD tg) and age-matched wild type (wt) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptophysin (SYP) in addition to signal transduction pathways associated with diabetes. In R6/2 mice, islets are relatively smaller in size, exhibit enhanced expression and nuclear inclusion of mHtt along with the loss of insulin, glucagon and somatostatin expression. In comparison to wt, R6/2 mice display enhanced mRNA for all SSTRs except SSTR2. In the pancreatic lysate, SSTR1, 4 and 5 immunoreactivity decreases whereas SSTR3 immunoreactivity increases with no discernible changes in SSTR2 immunoreactivity. Furthermore, at the cellular level, R6/2 mice exhibit a receptor specific distributional pattern of SSTRs like immunoreactivity and colocalization with β, α and δ cells. While GAD expression is increased, TH and SYP immunoreactivity was decreased in R6/2 mice, anticipating a cross-talk between the CNS and pancreas in diabetes pathophysiology. We also dissected out the changes in signaling pathway and found decreased activation and expression of PKA, AKT, ERK1/2 and STAT3 in R6/2 mice pancreas. These findings suggest that the impaired organization of SSTRs within islets may lead to perturbed hormonal regulation and signaling. These interconnected complex events might shed new light on the pathogenesis of diabetes in neurodegenerative diseases and the role of SSTRs in potential therapeutic intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2.

    Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne; Josefsen, Knud

    2015-04-20

    Huntington's disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood glucose levels during prolonged fasting compared to wild type animals.

  1. Investigating the role of (2S,4R)-4-hydroxyproline in elastin model peptides

    Bochicchio, Brigida; Laurita, Alessandro; Heinz, Andrea

    2013-01-01

    Post-translational modifications play a key role in defining the biological functions of proteins. Among them, the hydroxylation of proline producing the (2S,4R)-4-hydroxyproline (Hyp) is one of the most frequent modifications observed in vertebrates, being particularly abundant in the proteins o...

  2. Shadow corrosion evaluation in the Studsvik R2 reactor

    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)

  3. System Center 2012 R2 Virtual Machine Manager cookbook

    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.

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

    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)

  5. C2R2: Training Students To Build Coastal Resilience

    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.

  6. Genome Sequences of the Oxytetracycline Production Strain Streptomyces rimosus R6-500 and Two Mutants with Chromosomal Rearrangements

    Baranasic, Damir

    2014-07-17

    The genome sequence of Streptomyces rimosus R6-500, an industrially improved strain which produces high titers of the important antibiotic oxytetracycline, is reported, as well as the genome sequences of two derivatives arising due to the genetic instability of the strain.

  7. Genome Sequences of the Oxytetracycline Production Strain Streptomyces rimosus R6-500 and Two Mutants with Chromosomal Rearrangements

    Baranasic, Damir; Zucko, Jurica; Nair, Mridul; Pain, Arnab; Long, Paul F.; Hranueli, Daslav; Cullum, John; Starcevic, Antonio

    2014-01-01

    The genome sequence of Streptomyces rimosus R6-500, an industrially improved strain which produces high titers of the important antibiotic oxytetracycline, is reported, as well as the genome sequences of two derivatives arising due to the genetic instability of the strain.

  8. Combining regio- and enantioselectivity of lipases for the preparation of (R)-4-chloro-2-butanol.

    Méndez, Jonh J; Oromi, Mireia; Cervero, Maria; Balcells, Mercè; Torres, Mercè; Canela, Ramon

    2007-01-01

    Preparation of 98% ee (R)-4-chloro-2-butanol was carried out by the enzymatic hydrolysis of chlorohydrin esters, using fungal resting cells and commercial enzymes. Hydrolyzes were carried out using lipases from Candida antarctica (Novozym 435), C. rugosa, Rhizomucor miehei (Lipozyme IM), Burkolia cepacia, and resting cells of Rhizopus oryzae and Aspergillus flavus. The influence of the enzyme, the solvent, the temperature, and the alkyl chain length on the selectivity of hydrolyzes of isomeric mixtures of chlorohydrin esters is described. Regioselectivity was higher than 95% for some of the tested lipases. Novozym 435 allowed preparation of the (R)-4-chloro-2-butanol after 15 min of reaction at 30-40 degrees C. (c) 2006 Wiley-Liss, Inc.

  9. On a supersymmetric completion of the R4 term in IIB supergravity

    Haro, Sebastian de; Sinkovics, Annamaria; Skenderis, Kostas

    2003-01-01

    We analyze the possibility of constructing a supersymmetric invariant that contains the R 4 term among its components as a superpotential term in type IIB on-shell superspace. We consider a scalar superpotential, i.e. an arbitrary holomorphic function of a chiral scalar superfield. In general, type IIB superspace does not allow for the existence of chiral superfields, but the obstruction vanishes for a specific superfield, the dilaton superfield. This superfield contains all fields of type IIB supergravity among its components, and its existence is implied by the solution of the Bianchi identities. The construction requires the existence of an appropriate chiral measure, and we find an obstruction to the existence of such a measure. The obstruction is closely related to the obstruction for the existence of chiral superfields and is non-linear in the fields. These results imply that the type IIB superinvariant related to the R 4 term is not associated with a scalar chiral superpotential

  10. Optimization of Xylanase Production through Response Surface Methodology by Fusarium sp. BVKT R2 Isolated from forest soil and its applications in saccharification

    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

  11. JESS-D-16-00510 R4.pdf | forthcoming | jess | Volumes | public ...

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00510 R4.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 ...

  12. JESS-D-16-00247 R4.pdf | forthcoming | jess | Volumes | public ...

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00247 R4.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 ...

  13. JESS-D-16-00096 R4.pdf | forthcoming | jess | Volumes | public ...

    Home; public; Volumes; jess; forthcoming; JESS-D-16-00096 R4.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. SU(2) Yang-Mills solitons in R2 gravity

    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.

  15. R2 effect-size measures for mediation analysis

    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

  16. R2 effect-size measures for mediation analysis.

    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.

  17. Robotic Range Clearance Competition (R2C2)

    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

  18. R2 cosmology: Inflation without a phase transition

    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

  19. Foundations of SQL Server 2008 R2 Business Intelligence

    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

  20. Relocation of a rust resistance gene R 2 and its marker-assisted gene pyramiding in confection sunflower (Helianthus annuus L.).

    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.

  1. Amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole

    Saidov, D.K.; Rakhmonov, R.O.; Khodzhiboev, Yu.; Kukaniev, M.A.; Bandaev, S.

    2015-01-01

    Present article is devoted to amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole. The reaction of new modifications of derivatives of imidazo-[2.1-B]-1.3.4-thiadiazoles-2-bromine-6-p-bromophenyl and 2-alkyl alkylene sulfonyl-6-phenyl imidazo--[2.1-B]-1.3.4-thiadiazole on Mannich with secondary and heterocyclic amines was studied.

  2. Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington?s Disease Mouse Model R6/2

    Nielsen, Signe Marie Borch; Hasholt, Lis; N?rrem?lle, Anne; Josefsen, Knud

    2015-01-01

    Huntington?s disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indic...

  3. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  4. R2E strategy and activities during LS1

    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)

  5. Renormalization group procedure for potential −g/r2

    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.

  6. 6. Investigation of R2M17 compounds

    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

  7. A New Very-High-Efficiency R4 Converter for High-Power Fuel Cell Applications

    Nymand, Morten; Andersen, Michael Andreas E.

    2009-01-01

    of fullbridge switching stages and power transformers, operate in parallel on primary side and in series on secondary side. Current sharing is guaranteed by series connection of transformer secondary windings and three small cascaded current balancing transformers on primary side. The detailed design of a 10 k......W prototype converter is presented. Input voltage range is 30-60 V and output voltage is 800 V. Test results, including voltage- and current waveforms and efficiency measurements, are presented. A record high converter efficiency of 98.2 % is achieved. The proposed R4 boost converter thus constitutes a low...

  8. Determinants of internal medicine residents' choice in the canadian R4 Fellowship Match: A qualitative study

    Kassam Narmin

    2011-06-01

    Full Text Available Abstract Background There is currently a discrepancy between Internal Medicine residents' decisions in the Canadian subspecialty fellowship match (known as the R4 match and societal need. Some studies have been published examining factors that influence career choices. However, these were either demographic factors or factors pre-determined by the authors' opinion as possibly being important to incorporate into a survey. Methods A qualitative study was undertaken to identify factors that determine the residents choice in the subspecialty (R4 fellowship match using focus group discussions involving third and fourth year internal medicine residents Results Based on content analysis of the discussion data, we identified five themes: 1 Practice environment including acuity of practice, ability to do procedures, lifestyle, job prospects and income 2 Exposure in rotations and to role models 3 Interest in subspecialty's patient population and common diseases 4 Prestige and respect of subspecialty 5 Fellowship training environment including fellowship program resources and length of training Conclusions There are a variety of factors that contribute to Internal Medicine residents' fellowship choice in Canada, many of which have been identified in previous survey studies. However, we found additional factors such as the resources available in a fellowship program, the prestige and respect of a subspecialty/career, and the recent trend towards a two-year General Internal Medicine fellowship in our country.

  9. (3R*,6R*,4′S*,8′R*,3′′R*,6′′R*-3,3′′-Diisopropyl-6,6′′-dimethyl-2′,6′-diphenyldispiro[cyclohexane-1,4′-(3,7-dioxa-2,6-diazabicyclo[3.3.0]octane-8′,1′′-cyclohexane]-2,2′′-dione

    Abdeslam Ansari

    2013-07-01

    Full Text Available The two oxazolidine rings (A and B of the title compound, C34H44N2O4, display roughly half-chair conformations, which could be described as twisted on the C—O bond. Together, the fused oxazolidine rings have a butterfly shape, with the H atoms attached to the ring junction C atoms in a cis orientation. The cyclohexane rings of both p-menthone fragments display chair conformations. The absolute configuration could not be determined from the X-ray diffraction data, but the relative configuration of the stereocentres could be deduced.

  10. Regulation of Rac1 GTPase activity by quinine through G-protein and bitter taste receptor T2R4.

    Sidhu, Crystal; Jaggupilli, Appalaraju; Chelikani, Prashen; Bhullar, Rajinder P

    2017-02-01

    Rac1 belongs to the Rho family of small GTPases and regulates actin cytoskeleton reorganization. T2R4 is a bitter taste receptor belonging to the G protein-coupled receptor family of proteins. In addition to mediating bitter taste perception from the tongue, T2R4s are found in extra-oral tissues, e.g., nasal epithelium, airways, brain, testis suggesting a much broader physiological function for these receptors. Anti-malarial drug and a bitter tasting compound, quinine, is a known agonist for T2R4, whereas BCML (Nα,Nα-Bis(carboxymethyl)-L-lysine) acts as an inverse agonist. Using western blot and Ca ++ mobilization assays, the effects of quinine on Rac1 activity in HEK293T cells stably expressing T2R4/Gα 16/44 , T2R4, or Gα 16/44 and transiently transfected with HA-Rac1 were investigated. Quinine treatment caused a significant reduction in the amount of active Rac1, whereas in the presence of BCML, quinine failed to cause any significant change in active Rac1. No significant change in Rac1 activity was observed in BAPTA-AM plus quinine-treated Gα 16/44 cells, suggesting possibility of a pathway in addition to the canonical Ca ++ -dependent pathway. A noticeable role for Gα 16/44 independent of T2R4 is observed in quinine-mediated Rac1 inactivation. Further, a significant difference in quinine-induced Ca ++ response in T2R4/Gα 16/44 or T2R4 cells was observed validating the partial role of calcium and importance of Gα 16/44 . This study is the first to show an inhibitory downstream action of a T2R4 agonist on Rac1 function. Further investigation will help in better understanding the downstream signal transduction network of T2R4 and its extra-oral physiological roles.

  11. Microstructure in Zircaloy Creep Tested in the R2 Reactor

    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

  12. Metabolism of Lutein and Zeaxanthin in Rhesus Monkeys: Identification of (3R,6′R)- and (3R,6′S)-3′-Dehydro-lutein as Common Metabolites and Comparison to Humans

    Albert, Gesa I.; Hoeller, Ulrich; Schierle, Joseph; Neuringer, Martha; Johnson, Elizabeth J.; Schalch, Wolfgang

    2012-01-01

    Lutein and zeaxanthin are xanthophylls that can be found highly concentrated in the macula of the retina. They are thought to protect the macula through their role as blue-light filters and because of their antioxidant and singlet oxygen quenching properties. Examination of metabolites unique to lutein and zeaxanthin such as 3′-dehydro-lutein, and of their stereochemistry may provide insight to the mechanism by which they are formed and by which they exert protection. To evaluate the formation of such metabolites, eleven monkeys were raised on a xanthophyll-free diet, and supplemented with pure lutein or pure zeaxanthin (2.2 mg/kg body weight/d). The period of supplementation ranged between 12 to 92 weeks. At study start and throughout the study, serum samples were taken and analyzed for xanthophylls using different HPLC systems. Xanthophyll metabolites were identified using UV/VIS and HR-MS detection. Lutein and zeaxanthin metabolites were found in detectable amounts with 3′-dehydro-lutein being a common metabolite of both. Using chiral-phase HPLC, two diastereomers, (3R,6′R)-3′-dehydro-lutein and (3R,6′S)-3′-dehydro-lutein, were identified and shown to be present in nearly equimolar amounts. A pathway for their formation from either lutein or zeaxanthin is proposed. These finding were comparable to results obtained with human plasma. PMID:18582588

  13. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

  14. DYSFUNCTIONAL KYNURENINE PATHWAY METABOLISM IN THE R6/2 MOUSE MODEL OF HUNTINGTON’S DISEASE

    Sathyasaikumar, Korrapati V.; Stachowski, Erin K.; Amori, Laura; Guidetti, Paolo; Muchowski, Paul J.; Schwarcz, Robert

    2013-01-01

    Elevated concentrations of neurotoxic metabolites of the kynurenine pathway (KP) of tryptophan degradation may play a causative role in Huntington’s disease (HD). The brain levels of one of these compounds, 3-hydroxykynurenine (3-HK), are increased in both HD and several mouse models of the disease. In the present study, we examined this impairment in greater detail using the R6/2 mouse, a well-established animal model of HD. Initially, mutant and age-matched wild-type mice received an intrastriatal injection of 3H-tryptophan to assess the acute, local de novo production of kynurenine, the immediate bioprecursor of 3-HK, in vivo. No effect of genotype was observed between 4 and 12 weeks of age. In contrast, intrastriatally applied 3H-kynurenine resulted in significantly increased neosynthesis of 3H-3-HK, but not other tritiated KP metabolites, in the R6/2 striatum. Subsequent ex vivo studies in striatal, cortical and cerebellar tissue revealed substantial increases in the activity of the biosynthetic enzyme of 3-HK, kynurenine 3-monooxygenase (KMO) and significant reductions in the activity of its degradative enzyme, kynureninase, in HD mice starting at 4 weeks of age. Decreased kynureninase activity was most evident in the cortex and preceded the increase in KMO activity. The activity of other KP enzymes showed no consistent brain abnormalities in the mutant mice. These findings suggest that impairments in its immediate metabolic enzymes jointly account for the abnormally high brain levels of 3-HK in the R6/2 model of HD. PMID:20236387

  15. Detection of early behavioral markers of Huntington's disease in R6/2 mice employing an automated social home cage

    Rudenko, Olga; Tkach, Vadim; Berezin, Vladimir

    2009-01-01

    developed behavior screening system, the IntelliCage, allows automated testing of mouse behavior in the home cage employing individual recognition of animals living in social groups. The present study validates the ability of the IntelliCage system to detect behavioral and cognitive dysfunction in R6/2 mice......Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder, for which no known cure or effective treatment exists. To facilitate the search for new potential treatments of HD, an automated system for analyzing the behavior of transgenic HD mice is urgently needed. A recently...

  16. Seizures induced in immature rats by homocysteic acid and the associated brain damage are prevented by group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate.

    Folbergrová, Jaroslava; Druga, Rastislav; Otáhal, Jakub; Haugvicová, Renata; Mares, Pavel; Kubová, Hana

    2005-04-01

    The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.

  17. The R + var-epsilon R2 cosmology

    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

  18. Scalaron from R2-gravity as a heavy field

    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.

  19. Synthesis, characterization and crystal structure of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid

    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. On R4 threshold corrections in type IIB string theory and (p,q)-string instantons

    Kiritsis, E.; Pioline, B.

    1997-01-01

    We obtain the exact non-perturbative thresholds of R 4 terms in type IIB string theory compactified to eight and seven dimensions. These thresholds are given by the perturbative tree-level and one-loop results together with the contribution of the D-instantons and of the (p,q)-string instantons. The invariance under U-duality is made manifest by rewriting the sum as a non-holomorphic-invariant modular function of the corresponding discrete U-duality group. In the eight-dimensional case, the threshold is the sum of an order-1 Eisenstein series for SL(2,Z) and an order-3/2 Eisenstein series for SL(3,Z). The seven-dimensional result is given by the order-3/2 Eisenstein series for SL(5,Z). We also conjecture formulae for the non-perturbative thresholds in lower-dimensional compactifications and discuss the relation with M-theory. (orig.)

  1. Global, decaying solutions of a focusing energy-critical heat equation in R4

    Gustafson, Stephen; Roxanas, Dimitrios

    2018-05-01

    We study solutions of the focusing energy-critical nonlinear heat equation ut = Δu - | u|2 u in R4. We show that solutions emanating from initial data with energy and H˙1-norm below those of the stationary solution W are global and decay to zero, via the "concentration-compactness plus rigidity" strategy of Kenig-Merle [33,34]. First, global such solutions are shown to dissipate to zero, using a refinement of the small data theory and the L2-dissipation relation. Finite-time blow-up is then ruled out using the backwards-uniqueness of Escauriaza-Seregin-Sverak [17,18] in an argument similar to that of Kenig-Koch [32] for the Navier-Stokes equations.

  2. 2C-R4WM Spectroscopy of Jet Cooled NO_3

    Fukushima, Masaru; Ishiwata, Takashi; Hirota, Eizi

    2016-06-01

    We have generated NO_3 from pyrolysis of N_2O_5 following supersonic free jet expansion, and carried out two color resonant four wave mixing ( 2C-R4WM ) spectroscopy of the tilde{B} ^2E' - tilde{X} ^2A_2' electronic transition. One laser was fixed to pump NO_3 to a ro-vibronic level of the tilde{B} state, and the other laser ( probe ) was scanned across two levels of the tilde{X} ^2A_2' state lying at 1051 and 1492 cm-1, the ν_1 (a_1') and ν_3 (e') fundamentals, respectively. The 2C-R4WM spectra have unexpected back-ground signal of NO_3 ( stray signal due to experimental set-up is also detected ) similar to laser induced fluorescence ( LIF ) excitation spectrum of the 0-0 band, although the back-ground signal was not expected in considering the 2C-R4WM scheme. Despite the back-ground interference, we have observed two peaks at 1051.61 and 1055.29 cm-1 in the ν_1 region of the spectrum, and the frequencies agree with the two bands, 1051.2 and 1055.3 cm-1, of our relatively higher resolution dispersed fluorescence spectrum, the former of which has been assigned to the ν_1 fundamental. Band width of both peaks, ˜ 0.2 cm-1, is broader than twice the experimental spectral-resolution, 0.04 cm-1 ( because this experiment is double resonance spectroscopy ), and the 1051.61 cm-1 peak is attributed to a Q branch band head ( a line-like Q branch ) of the ν_1 fundamental. The other branches are suspected to be hidden in noise of the back-ground signal. The 1055.29 cm-1 peak is also attributed to a Q band head. The tilde{B} ^2E'1/2 ( J' = 3/2, K' = 1 ) - tilde{X} ^2A_2' ( N'' = 1, K'' = 0 ) ro-vibronic transition was used as the pump transition. The dump ( probe ) transition to both a_1' and e' vibronic levels are then allowed as perpendicular transition. Accordingly, it cannot be determined from present results whether the 1055.29 cm-1 band is attributed to a_1' or e' (ν_3), unfortunately. The 2C-R4WM spectrum of the 1492 cm-1 band region shows one Q head at 1499.79 cm

  3. Seasonal snow of arctic Alaska R4D investigations. Final report

    Benson, C.S.

    1993-02-01

    Seasonal snow is present on the Arctic Slope of Alaska for nine months each year. Its presence or absence determines whether 80% of the solar radiation is reflected or absorbed, respectively. Although life on the Arctic Slope is adapted to, and in some cases dependent upon seasonal snow, little is known about it from a scientific point of view. Its quantity has been grossly underestimated, and knowledge of its distribution and the extent of wind transport and redistribution is very limited. This research project dealt with the amount, regional distribution and physical properties of wind blown snow and its biological role in the R4D area of the Arctic Slope. Physical processes which operate within the snow that were studied included the flux of heat and vapor and the fractionation of stable isotopes through it during fall and winter, and the complex heat and mass transfer within the snow and between snow, its substrate and the overlying atmosphere during the melt period.

  4. Formation of non-equilibrium structures in R6M5 steel under strong pulse beams action

    Rusin, Yu.G.; Plotnikov, S.V.

    2001-01-01

    Formation of non-equilibrium structures in R6M5 steel surface layer in the supply state under irradiation by strong pulse beams (SPB) is examined. Cylindric samples with diameter 10 mm and height 15 mm of R6M5 fast-cutting steel with following content (weight %): 0.85% C, 0.4% Mn, 0.5% Si, 4.0 Cr; 2.1% V; 5.3% Mo, 6.0% W; 0.4% Ni, Fe (the rest) were examined. Irradiation by SPB was conducted on the 'TEMP' modified accelerator operating in a technological regime with carbon beams parameters: energy from 0.3 up o 0.4 MeV, beam density in an impulse from 20 to 250 A/cm 2 , pulse duration from 60 tp 100 ns. The beam consists of 70 % carbon ions and 30 % hydrogen ions. Phase identification and its structural phase analysis have been studied on the DRON-3 X-ray diffractometer of common assignment. Topography of metallographic specimen surface has been examined on the REM-200 scanning electron microscope. Doping elements redistribution and phases quantitative characteristics after SPB action were studied with help of the X-ray spectral microanalysis (XRSA) on the MS-46 Camebax microanalyzer. Character of doping elements redistribution in the alloy (XRSA data) show its appreciably redistribution, moreover in the melted zone the increased content of molybdenum, tungsten, vanadium is observing, and in the zone of thermal action its increase relatively to matrix values

  5. Systemic delivery of recombinant brain derived neurotrophic factor (BDNF in the R6/2 mouse model of Huntington's disease.

    Carmela Giampà

    Full Text Available Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model.

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

    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

  7. Comparison of COD, R6, and J-contour integral methods of defect assessment, modified to give critical flaw sizes

    Burdekin, F.M.; Turner, C.E.

    1982-01-01

    A comparative study of the application of different elastic-plastic fracture mechanics methods to the calculation of critical defect sizes in pressure vessels showed widely varying results. The present authors have investigated in detail the reasons for the variations resulting from the use of the CEGB R6, COD design curve, and J-design curve methods to the particular pressure vessel problems. To obtain reasonable agreement between the three methods for the calculation of critical flaw sizes in high stress gradient situations, the published COD method in PD6493 has to be modified to remove its inherent safety factor, and to allow for stress gradients, and a consistent treatment for gross yielding/collapse has to be adopted for all three methods. (author)

  8. Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of Huntington's disease.

    Ivan Rattray

    Full Text Available Huntington's disease (HD is caused by the expansion of a CAG repeat in the huntingtin (HTT gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI, as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear.

  9. Systems of transversal sections near critical energy levels of hamiltonian systems in $Mathbb{R}^{4}$

    de, Naiara V

    2018-01-01

    In this article the authors study Hamiltonian flows associated to smooth functions H:\\mathbb R^4 \\to \\mathbb R restricted to energy levels close to critical levels. They assume the existence of a saddle-center equilibrium point p_c in the zero energy level H^{-1}(0). The Hamiltonian function near p_c is assumed to satisfy Moser's normal form and p_c is assumed to lie in a strictly convex singular subset S_0 of H^{-1}(0). Then for all E \\gt 0 small, the energy level H^{-1}(E) contains a subset S_E near S_0, diffeomorphic to the closed 3-ball, which admits a system of transversal sections \\mathcal F_E, called a 2-3 foliation. \\mathcal F_E is a singular foliation of S_E and contains two periodic orbits P_2,E\\subset \\partial S_E and P_3,E\\subset S_E\\setminus \\partial S_E as binding orbits. P_2,E is the Lyapunoff orbit lying in the center manifold of p_c, has Conley-Zehnder index 2 and spans two rigid planes in \\partial S_E. P_3,E has Conley-Zehnder index 3 and spans a one parameter family of planes in S_E \\setmin...

  10. Enhanced bioreduction synthesis of ethyl (R)-4-chloro-3-hydroybutanoate by alkalic salt pretreatment.

    Chong, Ganggang; Di, Junhua; Ma, Cuiluan; Wang, Dajing; Wang, Chu; Wang, Lingling; Zhang, Pengqi; Zhu, Jun; He, Yucai

    2018-08-01

    In this study, biomass-hydrolysate was used for enhancing the bioreduction of ethyl 4-chloro-3-oxobutanoate (COBE). Firstly, dilute alkalic salt pretreatment was attempted to pretreat bamboo shoot shell (BSS). It was found that enzymatic in situ hydrolysis of 20-50 g/L BSS pretreated with dilute alkalic salts (0.4% Na 2 CO 3 , 0.032% Na 2 S) at 7.5% sulfidity by autoclaving at 110 °C for 40 min gave sugar yields at 59.9%-73.5%. Moreover, linear relationships were corrected on solid recovery-total delignification-sugar yield. In BSS-hydrolysates, xylose and glucose could promote the reductase activity of recombinant E. coli CCZU-A13. Compared with glucose, hydrolysate could increase the reductase activity by 1.35-folds. Furthermore, the cyclohexane-hydrolysate (10:90, v/v) biphasic media containing ethylene diamine tetraacetic acid (EDTA, 40 mM) and l-glutamine (150 mM) was built for the effective biosynthesis of ethyl (R)-4-chloro-3-hydroxybutanoate [(R)-CHBE] (94.6% yield) from 500 mM COBE. In conclusion, this strategy has high potential for the effective biosynthesis of (R)-CHBE (>99% e.e.). Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    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.

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

    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.

  13. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

    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.

  14. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

    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.

  15. Failure to launch: the self-regulating Md-MYB10 R6 gene from apple is active in flowers but not leaves of Petunia.

    Boase, Murray R; Brendolise, Cyril; Wang, Lei; Ngo, Hahn; Espley, Richard V; Hellens, Roger P; Schwinn, Kathy E; Davies, Kevin M; Albert, Nick W

    2015-10-01

    The Md - MYB10 R6 gene from apple is capable of self-regulating in heterologous host species and enhancing anthocyanin pigmentation, but the activity of MYB10 is dependent on endogenous protein partners. Coloured foliage due to anthocyanin pigments (bronze/red/black) is an attractive trait that is often lacking in many bedding, ornamental and horticultural plants. Apples (Malus × domestica) containing an allelic variant of the anthocyanin regulator, Md-MYB10 R6 , are highly pigmented throughout the plant, due to autoregulation by MYB10 upon its own promoter. We investigated whether Md-MYB10 R6 from apple is capable of functioning within the heterologous host Petunia hybrida to generate plants with novel pigmentation patterns. The Md-MYB10 R6 transgene (MYB10-R6 pro :MYB10:MYB10 term ) activated anthocyanin synthesis when transiently expressed in Antirrhinum rosea (dorsea) petals and petunia leaf discs. Stable transgenic petunias containing Md-MYB10 R6 lacked foliar pigmentation but had coloured flowers, complementing the an2 phenotype of 'Mitchell' petunia. The absence of foliar pigmentation was due to the failure of the Md-MYB10 R6 gene to self-activate in vegetative tissues, suggesting that additional protein partners are required for Md-MYB10 to activate target genes in this heterologous system. In petunia flowers, where endogenous components including MYB-bHLH-WDR (MBW) proteins were present, expression of the Md-MYB10 R6 promoter was initiated, allowing auto-regulation to occur and activating anthocyanin production. Md-MYB10 is capable of operating within the petunia MBW gene regulation network that controls the expression of the anthocyanin biosynthesis genes, AN1 (bHLH) and MYBx (R3-MYB repressor) in petals.

  16. Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington's disease.

    Hamilton, James; Pellman, Jessica J; Brustovetsky, Tatiana; Harris, Robert A; Brustovetsky, Nickolay

    2016-07-01

    Alterations in oxidative metabolism and defects in mitochondrial Ca 2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca 2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca 2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca 2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca 2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca 2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca 2+ Overall, our data argue against respiratory deficiency and impaired Ca 2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    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.)

  18. Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

    Jack C. Reidling

    2018-01-01

    Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

  19. Alteration of rare-earth-metal cluster iodides R(R6I12Z) through cation substitution

    Jensen, E.A.; Corbett, J.D.

    2003-01-01

    Four examples of (A x R 1-x )R 6 I 12 Z phases further illustrate the flexibility of the rhombohedral R 7 X 12 Z structure to substitution of heterocations for the isolated R III atoms without destruction of the structure. The examples with R=La, Pr, Z=Fe, Co, Ir, and stoichiometric amounts of A=Na or Ca were prepared by traditional high temperature techniques and characterized by single crystal and Guinier powder X-ray diffraction techniques. Product compositions refined in the parent space group R3-bar from reactions of stoichiometry AR 6 I 12 Z were (Na 0.90 Pr 0.10 )Pr 6 I 12 Ir, (Na 0.954 La 0.046 )La 6 I 12 Fe, and (Ca 0.801 La 0.199 )La 6 I 12 Co. More general characteristics of and trends in the family of R 7 X 12 Z structures are also considered, including distortions of the ideal motif as a function of extremes in the components

  20. Impact of personal goals on the internal medicine R4 subspecialty match: a Q methodology study.

    Daniels, Vijay J; Kassam, Narmin

    2013-12-21

    There has been a decline in interest in general internal medicine that has resulted in a discrepancy between internal medicine residents' choice in the R4 subspecialty match and societal need. Few studies have focused on the relative importance of personal goals and their impact on residents' choice. The purpose of this study was to assess if internal medicine residents can be grouped based on their personal goals and how each group prioritizes these goals compared to each other. A secondary objective was to explore whether we could predict a resident's desired subspecialty choice based on their constellation of personal goals. We used Q methodology to examine how postgraduate year 1-3 internal medicine residents could be grouped based on their rankings of 36 statements (derived from our previous qualitative study). Using each groups' defining and distinguishing statements, we predicted their subspecialties of interest. We also collected the residents' first choice in the subspecialty match and used a kappa test to compare our predicted subspecialty group to the residents' self-reported first choice. Fifty-nine internal medicine residents at the University of Alberta participated between 2009 and 2010 with 46 Q sorts suitable for analysis. The residents loaded onto four factors (groups) based on how they ranked statements. Our prediction of each groups' desired subspecialties with their defining and/or distinguishing statements are as follows: group 1 - general internal medicine (variety in practice); group 2 - gastroenterology, nephrology, and respirology (higher income); group 3 - cardiology and critical care (procedural, willing to entertain longer training); group 4 - rest of subspecialties (non-procedural, focused practice, and valuing more time for personal life). There was moderate agreement (kappa = 0.57) between our predicted desired subspecialty group and residents' self-reported first choice (p internal medicine subspecialty. The key goals that define

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

    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.

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

    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.

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

    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.

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

    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…

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

    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.

  6. Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington's Disease: A Targeted GC-MS/MS Sterol Analysis.

    Kreilaus, Fabian; Spiro, Adena S; Hannan, Anthony J; Garner, Brett; Jenner, Andrew M

    2015-01-01

    Cholesterol has essential functions in neurological processes that require tight regulation of synthesis and metabolism. Perturbed cholesterol homeostasis has been demonstrated in Huntington's disease, however the exact role of these changes in disease pathogenesis is not fully understood. This study aimed to comprehensively examine changes in cholesterol biosynthetic precursors, metabolites and oxidation products in the striatum and cortex of the R6/1 transgenic mouse model of Huntington's disease. We also aimed to characterise the progression of the physical phenotype in these mice. GC-MS/MS was used to quantify a broad range of sterols in the striatum and cortex of R6/1 and wild type mice at 6, 12, 20, 24 and 28 weeks of age. Motor dysfunction was assessed over 28 weeks using the RotaRod and the hind-paw clasping tests. 24(S)-Hydroxycholesterol and 27-hydroxycholesterol were the major cholesterol metabolites that significantly changed in R6/1 mice. These changes were specifically localised to the striatum and were detected at the end stages of the disease. Cholesterol synthetic precursors (lathosterol and lanosterol) were significantly reduced in the cortex and striatum by 6 weeks of age, prior to the onset of motor dysfunction, as well as the cognitive and affective abnormalities previously reported. Elevated levels of desmosterol, a substrate of delta(24)-sterol reductase (DHCR24), were also detected in R6/1 mice at the end time-point. Female R6/1 mice exhibited a milder weight loss and hind paw clasping phenotype compared to male R6/1 mice, however, no difference in the brain sterol profile was detected between sexes. Several steps in cholesterol biosynthetic and metabolic pathways are differentially altered in the R6/1 mouse brain as the disease progresses and this is most severe in the striatum. This provides further insights into early molecular mediators of HD onset and disease progression and identifies candidate molecular targets for novel therapeutic

  7. Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington's disease by the induction of BDNF-dependent synaptic plasticity.

    Anglada-Huguet, Marta; Vidal-Sancho, Laura; Giralt, Albert; García-Díaz Barriga, Gerardo; Xifró, Xavier; Alberch, Jordi

    2016-11-01

    Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation. However, this role was not explored in neurodegenerative diseases. Here, we investigated the capacity of PGE2 EP2 receptor to promote synaptic plasticity and memory improvements in a model of HD, the R6/1 mice, by administration of the agonist misoprostol. We found that misoprostol increases dendritic branching in cultured hippocampal neurons in a brain-derived neurotrophic factor (BDNF)-dependent manner. Then, we implanted an osmotic mini-pump system to chronically administrate misoprostol to R6/1 mice from 14 to 18weeks of age. We observed that misoprostol treatment ameliorates the R6/1 long-term memory deficits as analyzed by the T-maze spontaneous alternation task and the novel object recognition test. Importantly, administration of misoprostol promoted the expression of hippocampal BDNF. Moreover, the treatment with misoprostol in R6/1 mice blocked the reduction in the number of PSD-95 and VGluT-1 positive particles observed in hippocampus of vehicle-R6/1 mice. In addition, we observed an increase of cAMP levels in the dentate ` of WT and R6/1 mice treated with misoprostol. Accordingly, we showed a reduction in the number of mutant huntingtin nuclear inclusions in the dentate gyrus of R6/1 mice. Altogether, these results suggest a putative therapeutic effect of PGE2 EP2 receptor in reducing cognitive deficits in HD. Copyright © 2016. Published by Elsevier Inc.

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

    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

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

    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...

  10. On $R^4$ terms and MHV amplitudes in N = 5,6 supergravity vacua of Type II superstrings

    Bianchi, Massimo

    2011-01-01

    We compute one-loop threshold corrections to $R^4$ terms in N= 5,6 supergravity vacua of Type II superstrings. We then discuss non-perturbative corrections generated by asymmetric D-brane instantons. Finally we derive generating functions for MHV amplitudes at tree level in N = 5, 6 supergravities.

  11. Dimensionality and R4P: A Health Equity Framework for Research Planning and Evaluation in African American Populations.

    Hogan, Vijaya; Rowley, Diane L; White, Stephanie Baker; Faustin, Yanica

    2018-02-01

    Introduction Existing health disparities frameworks do not adequately incorporate unique interacting contributing factors leading to health inequities among African Americans, resulting in public health stakeholders' inability to translate these frameworks into practice. Methods We developed dimensionality and R4P to integrate multiple theoretical perspectives into a framework of action to eliminate health inequities experienced by African Americans. Results The dimensional framework incorporates Critical Race Theory and intersectionality, and includes dimensions of time-past, present and future. Dimensionality captures the complex linear and non-linear array of influences that cause health inequities, but these pathways do not lend themselves to approaches to developing empirically derived programs, policies and interventions to promote health equity. R4P provides a framework for addressing the scope of actions needed. The five components of R4P are (1) Remove, (2) Repair, (3) Remediate, (4) Restructure and (5) Provide. Conclusion R4P is designed to translate complex causality into a public health equity planning, assessment, evaluation and research tool.

  12. Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP

    Mathiesen, Jesper Mosolff; Svendsen, Nannette; Bräuner-Osborne, Hans

    2003-01-01

    We have identified 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893) and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP) as positive allosteric modulators for the hmGluR4. SIB-1893 and MPEP enhanced the potency and efficacy of L-2-amino-4-phophonobutyrate (L-AP4) in guanosine 5'-O-(3-[(35)S...

  13. Zwaar gehavend wrak voor de kust van Kuinre : Definitief onderzoek van scheepswrak op kavel R 4 in de Noordoostpolder

    van Holk, André; van Popta, Yftinus; Spiekhout, Adriana; Blok, K.; Verweij, J.P.F.

    2012-01-01

    In the autumn of 2004 a large quantity of wooden material was brough to the surface due to ploughing. This was located in lot R4 in the Noordoostpolder (province of Flevoland). After inspection the construction elements were identified as part of a ship. In order to prevent it from being destroyed

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

    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

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

    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.

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

    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.

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

    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...

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

    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.

  19. Insight into a conformation of the PNA-PNA duplex with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones

    Maitarad, Amphawan; Poomsuk, Nattawee; Vilaivan, Chotima; Vilaivan, Tirayut; Siriwong, Khatcharin

    2018-04-01

    Suitable conformations for peptide nucleic acid (PNA) self-hybrids with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones (namely, acpcPNA and epi-acpcPNA, respectively) were investigated based on molecular dynamics simulations. The results revealed that hybridization of the acpcPNA was observed only in the parallel direction, with a conformation close to the P-type structure. In contrast, self-hybrids of the epi-acpcPNA were formed in the antiparallel and parallel directions; the antiparallel duplex adopted the B-form conformation, and the parallel duplex was between B- and P-forms. The calculated binding energies and the experimental data indicate that the antiparallel epi-acpcPNA self-hybrid was more stable than the parallel duplex.

  20. Synthesis and in vivo evaluation of [O-methyl-11C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT2A receptor PET ligand

    Kumar, J.S. Dileep; Prabhakaran, Jaya; Erlandsson, Kjell; Majo, Vattoly J.; Simpson, Norman R.; Pratap, Mali; Heertum, Ronald L. van; Mann, J. John; Parsey, Ramin V.

    2006-01-01

    The serotonin 2A (5-HT 2A ) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT 2A antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K i =0.79 nM) 5HT 2A antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [ 11 C]methyltriflate in order to determine the suitability of [ 11 C]MPM to quantify 5-HT 2A in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40±5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [ 11 C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT 2A receptors. The time-activity curves for the high-binding regions peaked at ∼45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT 2A receptors but also 38% blocking in cerebellum, which has a low 5-HT 2A receptor concentration. Although [ 11 C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT 2A receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT 2A receptors with PET

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

    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.)

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

    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.

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

    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.

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

    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.

  5. 26 CFR 31.3306(r)(2)-1 - Treatment of amounts deferred under certain nonqualified deferred compensation plans.

    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...

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

    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

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

    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

  8. Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.

    Shirayama, Yukihiko; Hashimoto, Kenji

    2018-01-01

    (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  9. SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease.

    Michal Mielcarek

    Full Text Available Huntington's disease (HD is a progressive neurological disorder for which there are no disease-modifying treatments. Transcriptional dysregulation is a major molecular feature of HD, which significantly contributes to disease progression. Therefore, the development of histone deacetylase (HDAC inhibitors as therapeutics for HD has been energetically pursued. Suberoylanilide hydroxamic acid (SAHA - a class I HDAC as well an HDAC6 inhibitor, improved motor impairment in the R6/2 mouse model of HD. Recently it has been found that SAHA can also promote the degradation of HDAC4 and possibly other class IIa HDACs at the protein level in various cancer cell lines. To elucidate whether SAHA is a potent modifier of HDAC protein levels in vivo, we performed two independent mouse trials. Both WT and R6/2 mice were chronically treated with SAHA and vehicle. We found that prolonged SAHA treatment causes the degradation of HDAC4 in cortex and brain stem, but not hippocampus, without affecting its transcript levels in vivo. Similarly, SAHA also decreased HDAC2 levels without modifying the expression of its mRNA. Consistent with our previous data, SAHA treatment diminishes Hdac7 transcript levels in both wild type and R6/2 brains and unexpectedly was found to decrease Hdac11 in R6/2 but not wild type. We investigated the effects of SAHA administration on well-characterised molecular readouts of disease progression. We found that SAHA reduces SDS-insoluble aggregate load in the cortex and brain stem but not in the hippocampus of the R6/2 brains, and that this was accompanied by restoration of Bdnf cortical transcript levels.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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

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

    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.)

  20. A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function.

    Peachey, Neal S; Hasan, Nazarul; FitzMaurice, Bernard; Burrill, Samantha; Pangeni, Gobinda; Karst, Son Yong; Reinholdt, Laura; Berry, Melissa L; Strobel, Marge; Gregg, Ronald G; McCall, Maureen A; Chang, Bo

    2017-08-01

    GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6 nob8 mouse has a reduced-amplitude b-wave component of the ERG, which reflects light-evoked DBC activity. Sequencing identified a missense mutation that converts a highly conserved methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent with prior studies of Grm6 mutant mice, the laminar size and structure in the Grm6 nob8 retina were comparable to control. The Grm6 nob8 phenotype is distinguished from other Grm6 mutants that carry a null allele by a reduced but not absent ERG b-wave, decreased but present expression of mGluR6 at DBC dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a reduced but not absent b-wave, there were a subset of retinal ganglion cells whose responses to light onset have times to peak within the range of those in control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is trafficked less than control. However, the mGluR6 that is localized to the DBC dendritic tips is able to initiate DBC signal transduction. The Grm6 nob8 mouse extends the Grm6 allelic series and will be useful for elucidating the role of mGluR6 in DBC signal transduction and in human disease. NEW & NOTEWORTHY This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a distinct phenotype from that seen in other Grm6 mouse models.

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

    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.

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

    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.

  3. The moduli space of two U(1) instantons on noncommutative $R^4$ and $R^3\\times S^1$

    Lee, Kimyeong; Tong, David; Yi, Sangheon

    2000-01-01

    We employ the ADHM method to derive the moduli space of two instantons in U(1) gauge theory on a noncommutative space. We show by an explicit hyperK\\"ahler quotient construction that the relative metric of the moduli space of two instantons on $R^4$ is the Eguchi-Hanson metric and find a unique threshold bound state. For two instantons on $R^3\\times S^1$, otherwise known as calorons, we give the asymptotic metric and conjecture a completion. We further discuss the relationship of caloron modu...

  4. Assessment of CATHARE2 V1.5qR6 using the experimental data of BETHSY natural circulation tests

    Huang Yanping; Jia Dounan

    2003-01-01

    The assessment of CATHARE2 V1.5qR6 is carried out against the experimental data of BETHSY natural circulation test-4. 1a-TC. Results show that the experimental process under single phase natural circulation can be predicted very well by CATHARE2 V1.5qR6, the primary mass inventory at the transition points from single phase natural circulation to two-phase natural circulation and from two-phase natural circulation to reflux condensation mode are also predicted correctly. The predicted results for thermohydraulic parameters of two-phase natural circulation and reflux condensation mode are not so good. Generally speaking, the prediction capability of CATHARE2 V1.5 for strong and two-phase flow process should be improved further in future

  5. Environmental and nutritional factors that affect growth and metabolism of the pneumococcal serotype 2 strain D39 and its nonencapsulated derivative strain R6.

    Sandra M Carvalho

    Full Text Available Links between carbohydrate metabolism and virulence in Streptococcus pneumoniae have been recurrently established. To investigate these links further we developed a chemically defined medium (CDM and standardized growth conditions that allowed for high growth yields of the related pneumococcal strains D39 and R6. The utilization of the defined medium enabled the evaluation of different environmental and nutritional factors on growth and fermentation patterns under controlled conditions of pH, temperature and gas atmosphere. The same growth conditions impacted differently on the nonencapsulated R6, and its encapsulated progenitor D39. A semi-aerobic atmosphere and a raised concentration of uracil, a fundamental component of the D39 capsule, improved considerably D39 growth rate and biomass. In contrast, in strain R6, the growth rate was enhanced by strictly anaerobic conditions and uracil had no effect on biomass. In the presence of oxygen, the difference in the growth rates was mainly attributed to a lower activity of pyruvate oxidase in strain D39. Our data indicate an intricate connection between capsule production in strain D39 and uracil availability. In this study, we have also successfully applied the in vivo NMR technique to study sugar metabolism in S. pneumoniae R6. Glucose consumption, end-products formation and evolution of intracellular metabolite pools were monitored online by (13C-NMR. Additionally, the pools of NTP and inorganic phosphate were followed by (31P-NMR after a pulse of glucose. These results represent the first metabolic profiling data obtained non-invasively for S. pneumoniae, and pave the way to a better understanding of regulation of central metabolism.

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

    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.)

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

    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.

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

    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)

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

    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 $displaystyle C = int_{(0,1]}int_{mathbb{R}^2}hbox{e}^{-eta ru(y - gamma r|y|^2}hbox{d} yP(hbox{d}r$

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

    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

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

    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.

  12. R2d2 Drives Selfish Sweeps in the House Mouse.

    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.

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

    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.

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

    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.

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

    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

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

    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

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

    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

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

    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.

  19. Microsoft® Office Communications Server 2007 R2 Resource Kit

    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

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

    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

  1. Thermal expansion and spontaneous magnetostriction of R2Co7 intermetallic compounds

    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

  2. The tensor hypercontracted parametric reduced density matrix algorithm: coupled-cluster accuracy with O(r(4)) scaling.

    Shenvi, Neil; van Aggelen, Helen; Yang, Yang; Yang, Weitao; Schwerdtfeger, Christine; Mazziotti, David

    2013-08-07

    Tensor hypercontraction is a method that allows the representation of a high-rank tensor as a product of lower-rank tensors. In this paper, we show how tensor hypercontraction can be applied to both the electron repulsion integral tensor and the two-particle excitation amplitudes used in the parametric 2-electron reduced density matrix (p2RDM) algorithm. Because only O(r) auxiliary functions are needed in both of these approximations, our overall algorithm can be shown to scale as O(r(4)), where r is the number of single-particle basis functions. We apply our algorithm to several small molecules, hydrogen chains, and alkanes to demonstrate its low formal scaling and practical utility. Provided we use enough auxiliary functions, we obtain accuracy similar to that of the standard p2RDM algorithm, somewhere between that of CCSD and CCSD(T).

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

    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

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

    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.

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

    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.

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

    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

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

    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

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

    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...

  9. (2S,4R-2-[(1R-1-(4-Bromophenyl-2-nitroethyl]-4-ethylcyclohexanone

    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.

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

    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.

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

    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

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

    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

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

    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)

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

    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

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

  3. (1R,6R,13R,18R-(Z,Z-1,18-Bis[(4R-2,2-dimethyl-1,3-dioxolan-4-yl]-3,16-dimethylene-8,20-diazadispiro[5.6.5.6]tetracosa-7,19-diene

    Stéphanie M. Guéret

    2010-07-01

    Full Text Available The crystal structure of the title compound, C34H54N2O4, has been solved in order to prove the relative and absolute chirality of the newly-formed stereocentres which were established using an asymmetric Diels–Alder reaction at an earlier stage in the synthesis. This unprecedented stable dialdimine contains a 14-membered ring and was obtained as the minor diastereoisomer in the Diels–Alder reaction. The absolute stereochemistry of the stereocentres of the acetal functionality was known to be R based on the use of a chiral (R-trisubstituted dienophile derived from enantiopure (S-glyceraldehyde. The assignment of the configuration in the dienophile and the title di-aldimine differs from (S-glyceraldehyde due to a change in the priority order of the substituents. The crystal structure establishes the presence of six stereocentres all attributed to be R. The 14-membered ring contains two aldimine bonds [C—N = 1.258 (2 and 1.259 (2 Å]. It adopts a similar conformation to that proposed for trans–trans-cyclotetradeca-1,8-dienes.

  4. Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease.

    Anna Bobrowska

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6 in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD.

  5. The structures of T6, T3R3 and R6 bovine insulin: combining X-ray diffraction and absorption spectroscopy

    Frankær, Christian Grundahl; Knudsen, Marianne Vad; Noren, Katarina

    2012-01-01

    The crystal structures of three conformations, T6, T3R3 and R6, of bovine insulin were solved at 1.40, 1.30 and 1.80 Å resolution, respectively. All conformations crystallized in space group R3. In contrast to the T6 and T3R3 structures, different conformations of the N-terminal B-chain residue Phe......B1 were observed in the R6 insulin structure, resulting in an eightfold doubling of the unit-cell volume upon cooling. The zinc coordination in each conformation was studied by X-ray absorption spectroscopy (XAS), including both EXAFS and XANES. Zinc adopts a tetrahedral coordination in all R3 sites...... molecules, as well as in other high-resolution insulin structures. As the radiation dose for XRD experiments is two orders of magnitude higher compared with that of XAS experiments, the single crystals were exposed to a higher degree of radiation damage that affected the zinc coordination in the T3 sites...

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

    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

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

    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

  8. 4-bit digital to analog converter using R-2R ladder and binary weighted resistors

    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%.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    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 ...

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    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/

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

    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

  5. Effects of attenuation and scatter corrections in cat brain PET images using microPET R4 scanner

    Kim, Jin Su; Lee, Jae Sung; Lee, Jong Jin

    2006-01-01

    The aim of this study was to examine the effects of attenuation correction (AC) and scatter correction (SC) on the quantification of PET count rates. To assess the effects of AC and SC, 18 F-FDG PET images of phantom and cat brain were acquired using microPET R4 scanner. Thirty-minute transmission images using 68 Ge source and emission images after injection of FDG were acquired. PET images were reconstructed using. 2D OSEM. AC and SC were applied. Regional count rates were measured using ROls drawn on cerebral cortex including frontal, parietal, and latral temporal lobes and deep gray matter including head of caudate nucleus, putamen and thalamus for pre- and post-AC and SC images. The count rates were then normalized with the injected dose per body weight. To assess the effects of AC, count ratio of 'deep gray matter/cerebral cortex' was calculated. To assess the effects of SC, ROls were also drawn on the gray matter (GM) and white matter (WM), and contrast between them ((GM-WM)/GM) was measured. After the AC, count ratio of 'deep gray matter/cerebral cortex' was increased by 17±7%. After the SC, contrast was also increased by 12±3%. Relative count of deep gray matter and contrast between gray and white matters were increased after AC and SC, suggesting that the AC would be critical for the quantitative analysis of cat brain PET data

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

    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

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

    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.

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

    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)

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

    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.

  10. Magnetic phase transitions in R2Fe17 compounds under pressure

    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

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

    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

  12. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

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

    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.

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

    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.

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

    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

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

    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

  17. Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

    Liliana B Menalled

    2010-03-01

    Full Text Available Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

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

    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.

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

    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.

  20. Antioxidant activity of salts of 2-(5-R-4-amino-1,2,4-triazole-3-ylthioacetic acid

    Ye. S. Pruglo

    2017-12-01

    Full Text Available Antioxidants are chemical structures that prevent the oxidation of other chemicals. They protect key cell components by neutralizing the harmful effect of free radicals which are natural products of cell metabolism. Oxidative stress leads to serious cell damage which results in various human diseases such as Alzheimer's disease, Parkinson's disease, atherosclerosis, cancer, arthritis, neurodegenerative disorders etc. The deficiency of antioxidants in food also leads to oxidative stress, which indicates a lack of antioxidant substances consumed by humans. Therefore, the search of substances that could not only prevent but also increase the resistance of the human body to active forms of oxygen or nitrogen and interfere with the processes of oxidative stress is an important task of medicine and pharmacy. The purpose of this work was to study the antioxidant activity (AOA of salts of 2-(5-R-4-R-4H-1,2,4-triazole-3-ylthioacetic acids with non-enzymatic initiation of free radical oxidation and to establish laws concerning chemical structure and biological effects of the studied substances. Materials and methods. Original derivatives of 1,2,4-triazole were used in the series of screening studies. The antioxidant activity of the compounds in vitro was determined according to the methodical recommendations of the State Pharmacological Center MoH Ukraine using the method of non-enzymatic initiation of lipid peroxide oxidation. Results. Dimethylammonium salt of 2-(4-amino-5-(2-bromophenyl-1,2,4-triazole-3-ylthioacetic acid (3c possessed with a high AOA which reduced the content of TBK-AP by 54,95% ( р˂0,001. Derivatives of 4-amino-1,2,4-triazole had the most distinct AOA containing С5 carbon atoms 2-bromophenyl substituent. Thus, methylammonium salt 3b reduced the TBK-AP content by 80,31 (p˂0,001 which exceeds the reference ascorbic acid by 45,05% and the prototype thiotriazoline by 36,64%. Considering the data of experimental studies it was found

  1. Thermodynamics of gravitational clustering phenomena: N-body self-gravitating gas on the sphere {{{S}}^{3}}\\subset {{{R}}^{4}}

    Tello-Ortiz, F.; Velazquez, L.

    2016-10-01

    This work is devoted to the thermodynamics of gravitational clustering, a collective phenomenon with a great relevance in the N-body cosmological problem. We study a classical self-gravitating gas of identical non-relativistic particles defined on the sphere {{{S}}3}\\subset {{{R}}4} by considering gravitational interaction that corresponds to this geometric space. The analysis is performed within microcanonical description of an isolated Hamiltonian system by combining continuum approximation and the steepest descend method. According to numerical solution of resulting equations, the gravitational clustering can be associated with two microcanonical phase transitions. A first phase transition with a continuous character is associated with breakdown of SO(4) symmetry of this model. The second one is the gravitational collapse, whose continuous or discontinuous character crucially depends on the regularization of short-range divergence of gravitation potential. We also derive the thermodynamic limit of this model system, the astrophysical counterpart of the Gibbs-Duhem relation, the order parameters that characterize its phase transitions and the equation of state. Other interesting behavior is the existence of states with negative heat capacities, which appear when the effects of gravitation turn dominant for energies sufficiently low. Finally, we comment on the relevance of some of these results in the study of astrophysical and cosmological situations. Special interest deserves the gravitational modification of the equation of state due to the local inhomogeneities of matter distribution. Although this feature is systematically neglected in studies about universe expansion, the same one is able to mimic an effect that is attributed to the dark energy: a negative pressure.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.)

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

    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%.

  8. R2WinBUGS: A Package for Running WinBUGS from R

    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.

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

    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)

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

    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.

  11. Site-specific magnetic anisotropies in R2Fe14B systems

    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.

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

    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....

  13. Degradation and stability of R2R manufactured polymer solar cells

    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...

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

    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

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

    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

  16. Biotransformation of (-)-(1R,4S)-Menthone and (+)-(1S,4R)-Menthone by the Common Cutworm Spodoptera litura Larvae.

    Marumoto, Shinsuke; Okuno, Yoshiharu; Hagiwara, Yuki; Miyazawa, Mitsuo

    2017-08-01

    Using biotransformation as a biocatalytic process has the advantage of being able to proceed under mild conditions and with high regio- and enantioselectivity. This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)-(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)-(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,3S,4S)-7-hydroxyneomenthol (1-2) and (-)-(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2 generated three enantiomers of the above metabolites, designated as 2-1 to 2-3, respectively. The C-9 position of (-)-menthone and (+)-menthone was oxidized to carboxylic acid by S. litura, which is a metabolic pathway not observed in any other example of biocatalysis.

  17. 75 FR 3471 - International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the...

    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...

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

    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.

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

    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)

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

    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

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

    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...

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

    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.

  3. Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

    Dryja, Thaddeus P.; McGee, Terri L.; Berson, Eliot L.; Fishman, Gerald A.; Sandberg, Michael A.; Alexander, Kenneth R.; Derlacki, Deborah J.; Rajagopalan, Aruna S.

    2005-01-01

    We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. PMID:15781871

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

    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

  5. User's guide to FBASE: Relational database software for managing R1/R4 (Northern/Intermountain Regions) fish habitat inventory data

    Sherry P. Wollrab

    1999-01-01

    FBASE is a microcomputer relational database package that handles data collected using the R1/R4 Fish and Fish Habitat Standard Inventory Procedures (Overton and others 1997). FBASE contains standard data entry screens, data validations for quality control, data maintenance features, and summary report options. This program also prepares data for importation into an...

  6. Crystal structure of (1R,4R-tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.2]octane-5-carboxylate

    Suvratha Krishnamurthy

    2015-07-01

    Full Text Available In the title compound, C11H17NO4, commonly known as N-tert-butoxycarbonyl-5-hydroxy-d-pipecolic acid lactone, the absolute configuration is (1R,4R due to the enantiomeric purity of the starting material which remains unchanged during the course of the reaction. In the crystal there no intermolecular hydrogen bonds.

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

    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.

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

    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.)

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

    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

  10. Micro-heterogeneities in R2O-RO-B2O3

    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.)

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

    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.

  12. Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenylmethyl-4R-4H-1,2,4-triazole-3-ylthioacetic acids and its salts

    A. M. Rud

    2018-02-01

    Full Text Available Today’s a creation of new domestic medicines is very important problem for pharmacy and medicine. Therefore, it is relevant to synthesize new domestic biologically active compounds. It is known that a large number of new 3-thio and 4-amino derivatives on the basis of 1,2,4-triazole have recently been synthesized, among which compounds with high pharmacological activity have been found. Based on the experience of previous studies and with the aim of creating new original drugs, our goal was to synthesize 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids series and to obtain salts on its basis, which have high indicators of pharmacological activity based on the literature data. The goal of the work is a targeted synthesis of potential low-toxic and highly effective compounds with a wide spectrum of pharmacological activity among 5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-thione derivatives, confirmation of their individuality and structure, as well as the study of physical-chemical properties, for the further pharmacological screening. Materials and methods. 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids were prepared by heating 5- (hydroxy(phenylmethyl-4-R-4H-1,2,4-triazol-3-thiones with chloroacetic acid. Subsequently, the synthesized thioacetic acids were subject for modification. Salts of 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids were obtained by reacting thioacetic acids with equivalents of sodium or potassium hydroxides. To obtain Iron(II, Copper(II or Zinc(II salts, half-molar amounts of the appropriate sulfates were added to the obtained solutions. Salts of 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids with organic bases were obtained by the reaction of acids with piperidine or morpholine in ethanol medium. Results. During the synthetic studies, 13 previously undescribed new compounds were obtained. The individuality of 2-((5-(hydroxy

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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)

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

    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

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

    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."

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

    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

  5. 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

    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

  6. Effect of gamma radiation of 60Co in the variability of chinese bean [Vigna unguiculata (l.) Walpers] en R4M4

    Salmeron E, J.; Bueno J, J.E.; Valencia E, F.; Cervantes S, T.; Cruz T, E. De la

    2007-01-01

    Selection of plants of Chinese bean coming from seed irradiated with gammas of 60 Co in the generation R 4 M 4 (fourth recurrent irradiation, fourth segregate generation) were carried out, taking as selection approaches the plant architecture, the numbers of sheaths for plant, sheath longitude, position of the sheaths, grain size and resistance to plagues and illnesses. 17 lines were selected for grain and 3 lines with fodder characteristics of black grain color were also obtained. (Author)

  7. Selective and interactive effects of D2 receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

    Isherwood, Sarah N; Robbins, Trevor W; Nicholson, Janet R; Dalley, Jeffrey W; Pekcec, Anton

    2017-09-01

    Metabotropic glutamate receptor 4 (mGluR4) and dopamine D 2 receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D 2 receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the D 2 receptor antagonist eticlopride, on two distinct forms of impulsivity. Rats were trained on the five-choice serial reaction time task (5-CSRTT) of sustained visual attention and segregated according to low, mid, and high levels of motor impulsivity (LI, MI and HI, respectively), with unscreened rats used as an additional control group. A separate group of rats was trained on a delay discounting task (DDT) to assess choice impulsivity. Systemic administration of Cpd11 dose-dependently increased motor impulsivity and impaired attentional accuracy on the 5-CSRTT in all groups tested. Eticlopride selectively attenuated the increase in impulsivity induced by Cpd11, but not the accompanying attentional impairment, at doses that had no significant effect on behavioural performance when administered alone. Cpd11 also decreased choice impulsivity on the DDT (i.e. increased preference for the large, delayed reward) and decreased locomotor activity. These findings demonstrate that mGluR4s, in conjunction with D 2 receptors, affect motor- and choice-based measures of impulsivity, and therefore may be novel targets to modulate impulsive behaviour associated with a number of neuropsychiatric syndromes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Synthesis, NMR spectral and antimicrobial studies of some [N-methyl-3t-alkyl-2r,6c-diarylpiperidin-4-ylidine]-5‧-methylthiazolidine-4-ones

    Prakash, S. M.; Pandiarajan, K.; Kumar, S.

    2013-06-01

    Four new [N-methyl-3t-alkyl-2r,6c-diaryl-4-ylidine]-5'-methylthiozolidin-4-ones 9-12 have been synthesized by the condensation of N-methyl-3t-alkyl-2r,6c-diarylpiperidin-4-one thiosemicarbazones with ethyl 2-bromopropionate. These compounds have been characterized using FT-IR, 1H NMR, 13C NMR spectral techniques. HOMOCOSY, HSQC and HMBC spectral study have been done for [N-methyl-3,3-dimethyl-2r,6c-bis(p-methoxyphenyl)piperidin-4-ylidine]-5'-methylthiazolidine-4-one (12). Two geometrical isomers are formed in this reaction. In all these compounds piperidin rings adopt chair conformation. The rotation of the aryl group at C-2 is rather slow in 10-12. Antimicrobial activities have also been studied for 9-12. These compounds are active against all the tested bacterial and fungal strains.

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

    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.

  10. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

    Lin CL

    2015-07-01

    Full Text Available Ching-Lung Lin,1 Sheue-Er Wang,2 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Soeurs de Saint Paul de Chartres Medical Corporate Body, Taoyuan City, 3Brion Research Institute of Taiwan, New Taipei City, Taiwan Abstract: Cardiac failure is often observed in aging patients with Huntington’s disease (HD. However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01. Cardiac expressions of superoxide dismutase 2 (SOD2 and B-cell lymphoma 2 (Bcl-2 in aging R6/2 HD mice were significantly lower than their WT (P<0.01, but cardiac expressions of tumor necrosis factor alpha (TNF-α, neurotrophin-3 (3-NT, 4-hydroxynonenal (4-HNE, Bcl-2-associated X protein (Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05. Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05. Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01, but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly

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

    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

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

    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

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

    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.

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

    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

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

    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

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

    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.

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

    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.

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

    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

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

    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

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

    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

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

    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

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

    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

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

    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

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

    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...

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

    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

  6. 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.

    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.

  7. New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylates

    Liliana Azotla-Cruz

    2017-01-01

    Full Text Available According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N-alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K2CO3 system the reaction of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N-substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (1Н and 13С spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N-benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N-methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

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

    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)

    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

    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).

    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

    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)

    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

    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)

    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

    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.

    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.

    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. The delta-opioid receptor agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] synergistically enhances the locomotor-activating effects of some psychomotor stimulants, but not direct dopamine agonists, in rats.

    Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

    2008-02-01

    The nonpeptidic delta-opioid agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] produces many stimulant-like behavioral effects in rodents and monkeys, such as locomotor stimulation, generalization to cocaine in discrimination procedures, and antiparkinsonian effects. Tolerance to the locomotor-stimulating effects of SNC80 develops after a single administration of SNC80 in rats; it is not known whether cross-tolerance develops to the effects of other stimulant compounds. In the initial studies to determine whether SNC80 produced cross-tolerance to other stimulant compounds, it was discovered that amphetamine-stimulated locomotor activity was greatly enhanced in SNC80-pretreated rats. This study evaluated acute cross-tolerance between delta-opioid agonists and other locomotor-stimulating drugs. Locomotor activity was measured in male Sprague-Dawley rats implanted with radiotransmitters, and activity levels were recorded in the home cage environment. Three-hour SNC80 pretreatment produced tolerance to further delta-opioid receptor stimulation but also augmented greatly amphetamine-stimulated locomotor activity in a dose-dependent manner. Pretreatments with other delta-opioid agonists, (+)BW373U86 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide] and oxymorphindole (17-methyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2',3'-indolomorphinan), also modified amphetamine-induced activity levels. SNC80 pretreatment enhanced the stimulatory effects of the dopamine/norepinephrine transporter ligands cocaine and nomifensine (1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinanmine maleate salt), but not the direct dopamine receptor agonists SKF81297 [R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] and quinpirole [trans-(-)-(4alphaR)-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline

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

    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.)

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

    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.

    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.

    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.

    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. AdS and stabilized extra dimensions in multi-dimensional gravitational models with nonlinear scalar curvature terms R-1 and R4

    Guenther, Uwe; Zhuk, Alexander; Bezerra, Valdir B; Romero, Carlos

    2005-01-01

    We study multi-dimensional gravitational models with scalar curvature nonlinearities of types R -1 and R 4 . It is assumed that the corresponding higher dimensional spacetime manifolds undergo a spontaneous compactification to manifolds with a warped product structure. Special attention has been paid to the stability of the extra-dimensional factor spaces. It is shown that for certain parameter regions the systems allow for a freezing stabilization of these spaces. In particular, we find for the R -1 model that configurations with stabilized extra dimensions do not provide a late-time acceleration (they are AdS), whereas the solution branch which allows for accelerated expansion (the dS branch) is incompatible with stabilized factor spaces. In the case of the R 4 model, we obtain that the stability region in parameter space depends on the total dimension D = dim(M) of the higher dimensional spacetime M. For D > 8 the stability region consists of a single (absolutely stable) sector which is shielded from a conformal singularity (and an antigravity sector beyond it) by a potential barrier of infinite height and width. This sector is smoothly connected with the stability region of a curvature-linear model. For D 4 model

  6. Synthesis, physical-chemical properties of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acid esters

    V. M. Odyntsova

    2017-04-01

    Full Text Available The nitrogen-containing heterocyclic systems from the class of 1,2,4-triazole derivatives, which exhibit wide range of actions, occupy special place among the variety of heterocyclic compounds. Derived biologically active substances are actively introduced into practice as new original and effective drugs. We were interested in esters of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids, which exhibit high biological activity and can be intermediates for the synthesis of amides, hydrazides, ylidenderivatives of corresponding acids. The aim of this work is the synthesis of new esters of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids and the establishment of their physical-chemical properties. Materials and methods. Melting point was determined by open capillary method on the device OptiMelt MPA100. The elemental composition of the synthesized compounds was determined on the universal analyzer ElementarVario ЕL cube (CHNS (standard – sulfanilamide. 1H NMR spectra were recorded on spectrometer Varian Mercury VX-200 (1H, 200 MHz in the solvent dimethyl sulfoxide-d6 (tetramethylsilane internal standard and decoded using a program ADVASP(tm Analyzer program (Umatek International Inc.. Chromato-mass-spectral studies were performed on hazarding chromatograph Agilent 1260 Infinity HPLC equipped with mass spectrometer Agilent 6120 (ionization electro-spray (ESI. The results and discussion. Synthesis of 11 new compounds, namely esters of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids was carried out by two methods. According to the A method the alkylation of previously synthesized 3-(adamantan-1-yl-1H-1,2,4-triazole-5-thiol was performed with the use of corresponding methyl ester of 2-chloroacetic acid and the presence of equivalent amount of sodium hydroxide. The B method involves the etherification of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acid with the use of methyl, ethyl, i

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

    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

  8. Enantioselective synthesis of (+-polyzonimine, defensive monoterpene alkaloid produced by a milliped Polyzonium rosalbum, and determination of its S absolute configuration by Its conversion to (4S,5R,6S-(+-nitropolyzonamine

    Takagi Yasuyo

    2000-01-01

    Full Text Available Asymmetric Michael addition of the enamine derived from 2,2-dimethylcyclopentanecarbox-aldehyde and (S-prolinol methyl ether to nitroethylene afforded the adduct of 75-76% ee, which finally yielded enantiomerically pure (+-polyzonimine, a nitrogen-containing spirocyclic compound isolated from the defensive glands of a milliped, Polyzonium rosalbum. By converting (+-polyzonimine into (4S,5R,6S-(+-nitropolyzonamine, the hitherto uncertain absolute configuration of the former was established as S.

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

    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

    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

    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)

    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

    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.

    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)

    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

    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

    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. Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents.

    Abes, Saïd; Moulton, Hong M; Clair, Philippe; Prevot, Paul; Youngblood, Derek S; Wu, Rebecca P; Iversen, Patrick L; Lebleu, Bernard

    2006-12-01

    The efficient and non-toxic nuclear delivery of steric-block oligonucleotides (ON) is a prerequisite for therapeutic strategies involving splice correction or exon skipping. Cationic cell penetrating peptides (CPPs) have given rise to much interest for the intracellular delivery of biomolecules, but their efficiency in promoting cytoplasmic or nuclear delivery of oligonucleotides has been hampered by endocytic sequestration and subsequent degradation of most internalized material in endocytic compartments. In the present study, we compared the splice correction activity of three different CPPs conjugated to PMO(705), a steric-block ON targeted against the mutated splicing site of human beta-globin pre-mRNA in the HeLa pLuc705 splice correction model. In contrast to Tat48-60 (Tat) and oligoarginine (R(9)F(2)) PMO(705) conjugates, the 6-aminohexanoic-spaced oligoarginine (R-Ahx-R)(4)-PMO(705) conjugate was able to promote an efficient splice correction in the absence of endosomolytic agents. Our mechanistic investigations about its uptake mechanisms lead to the conclusion that these three vectors are internalized using the same endocytic route involving proteoglycans, but that the (R-Ahx-R)(4)-PMO(705) conjugate has the unique ability to escape from lysosomial fate and to access to the nuclear compartment. This vector, which has displays an extremely low cytotoxicity, the ability to function without chloroquine adjunction and in the presence of serum proteins. It thus offers a promising lead for the development of vectors able to enhance the delivery of therapeutic steric-block ON in clinically relevant models.

  19. Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins.

    Chen, Buxin; Siderovski, David P; Neubig, Richard R; Lawson, Mark A; Trejo, Joann

    2014-01-17

    The G protein-coupled protease-activated receptor 1 (PAR1) is irreversibly proteolytically activated by thrombin. Hence, the precise regulation of PAR1 signaling is important for proper cellular responses. In addition to desensitization, internalization and lysosomal sorting of activated PAR1 are critical for the termination of signaling. Unlike most G protein-coupled receptors, PAR1 internalization is mediated by the clathrin adaptor protein complex 2 (AP-2) and epsin-1, rather than β-arrestins. However, the function of AP-2 and epsin-1 in the regulation of PAR1 signaling is not known. Here, we report that AP-2, and not epsin-1, regulates activated PAR1-stimulated phosphoinositide hydrolysis via two different mechanisms that involve, in part, a subset of R4 subfamily of "regulator of G protein signaling" (RGS) proteins. A significantly greater increase in activated PAR1 signaling was observed in cells depleted of AP-2 using siRNA or in cells expressing a PAR1 (420)AKKAA(424) mutant with defective AP-2 binding. This effect was attributed to AP-2 modulation of PAR1 surface expression and efficiency of G protein coupling. We further found that ectopic expression of R4 subfamily members RGS2, RGS3, RGS4, and RGS5 reduced activated PAR1 wild-type signaling, whereas signaling by the PAR1 AKKAA mutant was minimally affected. Intriguingly, siRNA-mediated depletion analysis revealed a function for RGS5 in the regulation of signaling by the PAR1 wild type but not the AKKAA mutant. Moreover, activation of the PAR1 wild type, and not the AKKAA mutant, induced Gαq association with RGS3 via an AP-2-dependent mechanism. Thus, AP-2 regulates activated PAR1 signaling by altering receptor surface expression and through recruitment of RGS proteins.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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

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

    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

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

    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.

  8. ß-Adrenergic Stimulation Increases RyR2 Activity via Intracellular Ca2+ and Mg2+ Regulation

    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

  9. ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.

    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.

  10. Functional Characterization of Cotton GaMYB62L, a Novel R2R3 TF in Transgenic Arabidopsis.

    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.

  11. REDESIGN OF OUTER HOOD PANEL OF ESEMKA R2 CAR TO IMPROVE PEDESTRIAN PROTECTION USING FINITE ELEMENT MODELING

    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.

  12. Multiple R2R3-MYB transcription factors involved in the regulation of anthocyanin accumulation in peach flower

    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.

  13. Transfer of deuterium from [1R-2H]- and [1S-2H] ethanol to reduced metabolites formed in vivo

    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

  14. Smooth manifolds for certain dynamical systems and periodic solitons for nonlinear Klein-Gordon equations on R2

    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

  15. Final report on the IAEA research contracts No. 1194/RB, 1194/R1/RB and 1194/R2/RB

    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)

  16. P(O)R2-Directed Enantioselective C-H Olefination toward Chiral Atropoisomeric Phosphine-Olefin Compounds.

    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.

  17. Electronic structure of C r2AlC as observed by angle-resolved photoemission spectroscopy

    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.

  18. New anisotropic rare earth fluorides BaR2F8(R=Y,Dy-Lu): growth and characterization

    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.)

  19. Synthesis and in vivo evaluation of [O-methyl-{sup 11}C](2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine as a 5-HT{sub 2A} receptor PET ligand

    Kumar, J.S. Dileep [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: dk2038@columbia.edu; Prabhakaran, Jaya [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Erlandsson, Kjell [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Majo, Vattoly J. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Simpson, Norman R. [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Pratap, Mali [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Heertum, Ronald L. van [Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Mann, J. John [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Dept. of Radiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Parsey, Ramin V. [Dept. of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)]|[Div. of Brain Imaging, Dept. of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-05-15

    The serotonin{sub 2A} (5-HT{sub 2A}) receptor is implicated in the pathophysiology of schizophrenia and mood disorders, and in vivo studies of this receptor would be of value in studying the pathophysiology of these disorders and in measuring the relationship of clinical response to receptor occupancy for 5-HT{sub 2A} antagonists such as atypical antipsychotics. Therefore, (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-methoxy)-phenyl]ethyl] phenoxy]ethyl-1-methylpyrrolidine (MPM) (13), a selective and high-affinity (K {sub i}=0.79 nM) 5HT{sub 2A} antagonist, has been radiolabeled with carbon-11 by O-methylation of the corresponding desmethyl analogue (2R,4R)-4-hydroxy-2-[2-[2-[2-(3-hydroxy)phenyl]ethyl]phenoxy] ethyl-1-methylpyrrolidine (12) with [{sup 11}C]methyltriflate in order to determine the suitability of [{sup 11}C]MPM to quantify 5-HT{sub 2A} in living brain using PET. Desmethyl-MPM 12 and standard MPM were prepared, starting from 3-hydroxymethylphenol (2), in excellent yield. The yield obtained for radiolabeling was 40{+-}5% (EOB), and the total synthesis time was 30 min at EOS. PET studies with [{sup 11}C]MPM in baboon showed a distribution in the brain consistent with the known distribution of 5-HT{sub 2A} receptors. The time-activity curves for the high-binding regions peaked at {approx}45 min after injection. Blocking studies with M100907 demonstrated not only 38-57% blocking of tracer binding in brain regions known to have 5-HT{sub 2A} receptors but also 38% blocking in cerebellum, which has a low 5-HT{sub 2A} receptor concentration. Although [{sup 11}C]MPM exhibits appropriate kinetics in baboon for imaging 5-HT{sub 2A} receptors, its specific binding in cerebellum and higher proportion of nonspecific binding limit its usefulness for the in vivo quantification of 5-HT{sub 2A} receptors with PET.

  20. Automated synthesis of ["1"8F](2S,4R)-4-fluoroglutamine on a GE TRACERlab™ FX-N Pro module

    Zhang, Xiang; Basuli, Falguni; Shi, Zhen-Dan; Xu, Biying; Blackman, Burchelle; Choyke, Peter L.; Swenson, Rolf E.

    2016-01-01

    Glutamine (Gln) and its analogues may serve as imaging agents for tumor diagnosis using positron emission tomography (PET), especially for tumors with negative ["1"8F]FDG scan. We report the first automated synthesis of ["1"8F](2S,4R)-4-fluoroglutamine (["1"8F]FGln) on a GE TRACERlab™ FX-N Pro module. ["1"8F]FGln was obtained in 80±3 min with a radiochemical yield of 21±3% (n=5, uncorrected). The radiochemical purity was >98%, and optical purity 90±5%. The synthesis is highly reproducible with good chemical purity, radiochemical yield, and is suitable for translation to cGMP production. - Highlights: • The radiosynthesis of ["1"8F]fluoroglutamine was optimized with improved yield and purity. • Fully automated synthesis was established on a GE TRACERlab™ FX-N Pro module. • Radiochemical yield of 21±3% (uncorrected, n=5) was obtained with good reproducibility. • The automation could be easily adapted to cGMP production for routine clinical use.

  1. Effects of the mGluR2/3 agonist LY379268 on ketamine-evoked behaviours and neurochemical changes in the dentate gyrus of the rat

    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.

    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.

    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

    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.

    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.

    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

    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

    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. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  10. In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine.

    Dunphy, Mark P S; Harding, James J; Venneti, Sriram; Zhang, Hanwen; Burnazi, Eva M; Bromberg, Jacqueline; Omuro, Antonio M; Hsieh, James J; Mellinghoff, Ingo K; Staton, Kevin; Pressl, Christina; Beattie, Bradley J; Zanzonico, Pat B; Gerecitano, John F; Kelsen, David P; Weber, Wolfgang; Lyashchenko, Serge K; Kung, Hank F; Lewis, Jason S

    2018-05-01

    Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07). Patients experienced no adverse effects. Conclusion Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. © RSNA, 2018 Online

  11. Initial mass function in R-associations CMaR1, Mon R1 and Mon R2 from radiodata

    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)

  12. Synthesis and structural and electrical characterization of new materials Bi3R2FeTi3O15

    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.

  13. Magnetic moment and magnetocrystalline anisotropy of 3d-ion subsystem in R2T14B

    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

  14. Strong CO+ and {{\\rm{N}}}_{2}^{+} Emission in Comet C/2016 R2 (Pan-STARRS)

    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.

  15. Ising versus XY anisotropy in frustrated R(2)Ti(2)O(7) compounds as "Seen" by Polarized Neutrons.

    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.

  16. Thermodynamics of R-(+)-2-(4-Hydroxyphenoxy)propanoic Acid Dissolution in Methanol, Ethanol, and Methanol-Ethanol Mixture

    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.

  17. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

    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.

  18. HF-EPR, Raman, UV/VIS light spectroscopic, and DFT studies of the ribonucleotide reductase R2 tyrosyl radical from Epstein-Barr virus.

    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.

  19. Expression of the sweetpotato R2R3-type IbMYB1a gene induces anthocyanin accumulation in Arabidopsis.

    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.

  20. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae.

    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.

  1. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae

    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.

  2. Interactions between the R2R3-MYB transcription factor, AtMYB61, and target DNA binding sites.

    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.

  3. Overview of the ISS Radiation Environment Observed during the ESA EXPOSE-R2 Mission in 2014-2016

    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.

  4. Origin of inflation in CFT driven cosmology. R2-gravity and non-minimally coupled inflaton models

    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.)

  5. Charge disproportionation of mixed-valent Cr triggered by Bi lone-pair effect in the A -site-ordered perovskite BiC u3C r4O12

    Etter, Martin; Isobe, Masahiko; Sakurai, Hiroya; Yaresko, Alexander; Dinnebier, Robert E.; Takagi, Hidenori

    2018-05-01

    A new A -site-ordered perovskite BiC u3C r4O12 is synthesized under a high pressure of 7.7 GPa. A phase transition from a paramagnetic metal to a ferrimagnetic metal is observed at Tc=190 K accompanied with a structural change from cubic to monoclinic. Structural analysis of the low-temperature monoclinic phase reveals that this transition represents a charge disproportionation of C r3.75 + into C r4 + and C r3.5 + . We argue that the asymmetric displacement of Bi caused by a lone-pair effect triggers the formation of a dimeric Cr4+2O5 unit and leads to an ordering of C r4 + and C r3.5 + below the transition.

  6. 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

    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.

  7. Homoeologous Recombination of the V1r1-V1r2 Gene Cluster of Pheromone Receptors in an Allotetraploid Lineage of Teleosts

    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.

  8. Comparison of Deferasirox and deferoxamine treatment in iron-overloaded patients: liver iron concentration determined by quantitative MRI-R_2"*

    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)

  9. Research on the Solid State Fermentation of Jerusalem Artichoke Pomace for Producing R,R-2,3-Butanediol by Paenibacillus polymyxa ZJ-9.

    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.

  10. Tissue Destruction in Bullous Pemphigoid Can Be Complement Independent and May Be Mitigated by C5aR2

    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.

  11. Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

    Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

    2001-07-20

    The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

  12. An R2R3-MYB gene, LeAN2, positively regulated the thermo-tolerance in transgenic tomato.

    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.

  13. Research-to-operations (R2O) for the Space Environmental Effects Fusion System (SEEFS) system-impact products

    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.

  14. An R2R3-type MYB transcription factor, GmMYB29, regulates isoflavone biosynthesis in soybean.

    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.

  15. Transforming an EPA QA/R-2 quality management plan into an ISO 9002 quality management system.

    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.

  16. A chimeric repressor of petunia PH4 R2R3-MYB family transcription factor generates margined flowers in torenia.

    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.

  17. Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

    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.

  18. A constitutively expressed pair of rpoE2-chrR2 in Azospirillum brasilense Sp7 is required for survival under antibiotic and oxidative stress.

    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.

  19. Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS facilitates surface expression of GluR2-containing AMPA receptors.

    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.

  20. Coordinated regulation of anthocyanin biosynthesis in Chinese bayberry (Myrica rubra) fruit by a R2R3 MYB transcription factor.

    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.

  1. Anthocyanin biosynthesis in pears is regulated by a R2R3-MYB transcription factor PyMYB10.

    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.

  2. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).

    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.

  3. Magnetostructural coupling behavior at the ferromagnetic transition in double-perovskite S r2FeMo O6

    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.

  4. Can multi-slice or navigator-gated R2* MRI replace single-slice breath-hold acquisition for hepatic iron quantification?

    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

  5. Can multi-slice or navigator-gated R2* MRI replace single-slice breath-hold acquisition for hepatic iron quantification?

    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

  6. High-resolution structural and functional assessments of cerebral microvasculature using 3D Gas ΔR2*-mMRA.

    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.

  7. CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.

    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.

  8. An efficient conversion of (3R,3'R,6'R)-lutein to (3R,3'S,6'R)-lutein (3'-epilutein) and (3R,3'R)-zeaxanthin.

    Khachik, Frederick

    2003-01-01

    Two dietary carotenoids, (3R,3'R,6'R)-lutein (1) and (3R,3'R)-zeaxanthin (2), and their metabolite (3R,3'S,6'R)-lutein (3'-epilutein) (3) accumulate in human serum, milk, and ocular tissues. There is increasing evidence that compounds 1 and 2 play an important role in the prevention of age-related macular degeneration. Therefore, the availability of these carotenoids for metabolic studies and clinical trials is essential. Compound 1 is isolated from extracts of marigold flowers (Tagete erecta) and is commercially available, whereas 2 is only accessible by a lengthy total synthesis, and a viable method for synthesis of 3 has not yet been developed. This report describes an efficient conversion of technical grade 1 to 2 via 3. Acid-catalyzed epimerization of 1 yields an equimolar mixture of diastereomers 1 and 3. The mixture was separated by enzyme-mediated acylation with lipase AK from Pseudomonas fluorescens that preferentially esterified 3 and after alkaline hydrolysis yielded this carotenoid in 90% diastereomeric excess (de). Compound 3 was also separated from 1 in 56-88% de by solvent extraction and low-temperature crystallization, Soxhlet extraction, or supercritical fluid extraction. Base-catalyzed isomerization of 3 gave 2 in excellent yield, providing a convenient alternative to the total synthesis of this important dietary carotenoid.

  9. High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7T.

    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.

  10. MCSA Windows Server 2012 R2 complete study guide exams 70-410, 70-411, 70-412, and 70-417

    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.

  11. Survival of the lichen model system Circinaria gyrosa before flight to the ISS (EXPOSE R2 mission)

    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

  12. 78 FR 56921 - South Bay Salt Pond Restoration Project, Phase 2 (Ponds R3, R4, R5, S5, A1, A2W, A8, A8S, A19...

    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...

  13. Synthesis of carbon-14 labelled cis-malonato [(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II) (SKI 2053R)

    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)

  14. Análisis de incertidumbre en calibración de medidores de presión según DKD-R 6-1. Cinco métodos de cálculo

    Luis Pablo Constantino

    2014-12-01

    Full Text Available Este trabajo presenta un estudio de las contribuciones de incertidumbre e incertidumbre expandida que tienen lugar en la calibración de un medidor digital de presión por comparación directa con una balanza de presión. Se discute la ecuación propuesta por la guía DKD-R 6-1 para la estimación de incertidumbre, según plataforma GUM y Monte Carlo, proponiendo un modelo alternativo. Se determinan las diferencias que existen en las incertidumbres resultantes obtenidas  según estos métodos y en qué forma los distintos componentes del modelo influyen en estas diferencias, según la magnitud de su incertidumbre estándar y la distribución de probabilidad (DDP asociada que se le asigna.El desarrollo se realiza según el método GUM utilizando la metodología analítica. Adicionalmente  se repite el ejercicio en forma comparativa utilizando cuatro diferentes herramientas de cálculo. Dos de estas herramientas están basadas en aproximaciones numéricas del método clásico: software GUM Workbench © y método numérico de Kragten. Las otras dos son consistentes con el suplemento 1 de la Guía de la Expresión de la Incertidumbre de Medida según el método de Monte Carlo (MCM. en un caso el lenguaje R y por otra parte MCM Alchimia, aplicación desarrollada por uno de los autores.  

  15. Structural basis for site-specific reading of unmodified R2 of histone H3 tail by UHRF1 PHD finger

    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.

  16. Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer.

    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.

  17. Calculations of the magnetic properties of R2M14B intermetallic compounds (R=rare earth, M=Fe, Co)

    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.

  18. Purification, crystallization and preliminary X-ray diffraction analysis of the IL-20-IL-20R1-IL-20R2 complex

    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%.

  19. A concise route to branched erythrono-gamma-lactones. Synthesis of the leaf-closing substance potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate

    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....

  20. SYNTHESIS OF ENANTIOMERICALLY PURE (R)-2-SULFANYLPROPANOIC AND (S)-2-SULFANYLPROPANOIC ACIDS (THIOLACTIC ACID) FROM ETHYL (S)-LACTATE USING PIG-LIVER ESTERASE

    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

  1. The Implementation of the Responsibility to Protect (R2P) Norms by the African Standby Force in Sub-Saharan Africa

    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

  2. Fasting induces IL-1 resistance and free fatty acid-mediated up-regulation of IL-1R2 and IL-1RA

    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.

  3. Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.

    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

  4. Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.

    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.

  5. Regulation of estradiol and progesterone production by CRH-R1 and -R2 is through divergent signaling pathways in cultured human placental trophoblasts.

    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.

  6. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    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

  7. Analysis of the DNA-Binding Activities of the Arabidopsis R2R3-MYB Transcription Factor Family by One-Hybrid Experiments in Yeast.

    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.

  8. 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

    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.)

  9. Conifer R2R3-MYB transcription factors: sequence analyses and gene expression in wood-forming tissues of white spruce (Picea glauca

    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.

  10. High-pressure synthesis and characterization of the effective pseudospin S =1 /2 XY pyrochlores R2P t2O7 (R =Er ,Yb )

    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.

  11. Producción de ácido indol-3-acético por Pseudomonas veronii R4 y formación de raíces en hojas de vid “Thompson seedless” in vitro

    Maria Peñafiel Jaramillo; Alexandra Elizabeth Barrera Álvarez; Emma Danielly Torres Navarrete; Hayron Fabricio Canchignia Martínez; Humberto Prieto-Encalada; Jaime Morante Carriel

    2016-01-01

    Rizobacterias con actividad antagonista son empleadas a problemas patológicos y promueven el desarrollo de tejido radicular de especies vegetales El objetivo del estudio fue evaluar la capacidad en síntesis de ácido indol-3-acetico (AIA) y la formación de raíces en hojas de vid “Thompson Seedless”, por el empleo de Pseudomonas veronii R4 in vitro. La bacteria, fue incubada en medio mínimo M9 y se verificó la producción de AIA a 24, 48 y 72 h de muestreo, los sobrenadantes fueron analizandos p...

  12. The structure of a mixed GluR2 ligand-binding core dimer in complex with (S)-glutamate and the antagonist (S)-NS1209

    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....

  13. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study.

    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

  14. Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis.

    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.

  15. Reactivity-worth estimates of the OSMOSE samples in the MINERVE reactor R1-MOX, R2-UO2 and MORGANE/R configurations.

    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.

  16. Biocatalytic Asymmetric Synthesis of (1R, 2S)-N-Boc-vinyl-ACCA Ethyl Ester with a Newly Isolated Sphingomonas aquatilis.

    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.

  17. Elimination Reactions of (E)-2,4,6-Trinitrobenzaldehyde O-benzoyloximes Promoted by R2NH in MeCN. Change of Reaction Mechanism

    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

  18. Involvement of microRNA miR-2b-3p in regulation of metabolic resistance to insecticides in Plutella xylostella.

    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.

  19. Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA

    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...

  20. Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

    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.

  1. Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

    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.

  2. Ectopic Overexpression of a Novel R2R3-MYB, NtMYB2 from Chinese Narcissus Represses Anthocyanin Biosynthesis in Tobacco

    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.

  3. Ectopic Overexpression of a Novel R2R3-MYB, NtMYB2 from Chinese Narcissus Represses Anthocyanin Biosynthesis in Tobacco.

    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.

  4. Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.

    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.

  5. The coefficient of determination R2 and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded.

    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).

  6. Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

    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.

  7. Production of R,R-2,3-butanediol of ultra-high optical purity from Paenibacillus polymyxa ZJ-9 using homologous recombination.

    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.

  8. Method of forming an oxide superconducting thin film having an R1A2C3 crystalline phase over an R2A1C1 crystalline phase

    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

  9. A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

    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.

  10. Complete Calibration of the Color-Redshift Relation (C3R2): A Critical Foundation for Weak Lensing Cosmology with Euclid and WFIRST

    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.

  11. Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children.

    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.

  12. Advanced chronic kidney disease in non-valvular atrial fibrillation: extending the utility of R2CHADS2 to patients with advanced renal failure.

    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.

  13. 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.

    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.

  14. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

    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.

  15. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

    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.

  16. Decreased Renal Function Is Associated with Elevated CHA2DS2VASC and R2CHADS2 Scores in Non-Valvular Atrial Fibrillation Patients Presenting with Stroke.

    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

  17. TRAIL-receptor preferences in pancreatic cancer cells revisited: Both TRAIL-R1 and TRAIL-R2 have a licence to kill

    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

  18. Characterization of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next generation sequencing study

    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

  19. Evaluation of ERA-Interim, MERRA, NCEP-DOE R2 and CFSR Reanalysis precipitation Data using Gauge Observation over Ethiopia for a period of 33 years

    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

  20. miR2Pathway: A Novel Analytical Method to Discover MicroRNA-mediated Dysregulated Pathways Involved in Hepatocellular Carcinoma.

    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.